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A fourth wave of the opioid epidemic is coming, a national expert on drug buy caduet online without prescription use and policy said during a virtual panel discussion this week hosted by the Berkshire County, Massachusetts, District Attorney’s Office and the Berkshire Opioid Addiction Prevention Collaborative.Dr. Daniel Ciccarone, a professor of family and community medicine at the University of California, San Francisco (UCSF) School of Medicine, said the next wave in the country’s opioid health emergency will focus on stimulants like methamphetamine and cocaine, and drug combinations where stimulants are used in conjunction with opioids.“The use of methamphetamines is back and it’s back big time,” said Ciccarone, whose most recent research has focused on heroin use.Previously, officials had said there were three buy caduet online without prescription waves of the opioid epidemic – the first being prescription pills, the second being heroin, and the third being synthetic drugs, like fentanyl.Now, Ciccarone said, what federal law enforcement and medical experts are seeing is an increase in the use of stimulants, especially methamphetamines.The increase in deaths due to stimulants may be attributed to a number of causes. The increase in supply, both imported and domestically produced, as well as the increase of the drugs’ potency.“Meth’s purity and potency has gone up to historical levels,” he said. €œAs of 2018, we’ve reached unseen heights of 97 percent buy caduet online without prescription potency and 97 percent purity. In a prohibitionist world, we should not be seeing such high quality.

This is almost pharmaceutical quality.”Additionally, buy caduet online without prescription law enforcement and public health experts like Ciccarone are seeing an increase in the co-use of stimulants with opioids, he said. Speedballs, cocaine mixed with heroin, and goofballs, methamphetamines used with heroin or fentanyl, are becoming more common from the Midwest into Appalachia and up through New England, he said.Federal law enforcement officials are recommending local communities prepare for the oncoming rise in illegal drugs coming into their communities.“Some people will use them both at the same time, but some may use them in some combination regularly,” he said. €œThey may use meth in the morning to go to work, and use heroin at night to come down.”The co-use, he said, was an organic response buy caduet online without prescription to the fentanyl overdose epidemic.“Some of the things that we heard … is that meth is popularly construed as helping to decrease heroin and fentanyl use. Helping with heroin withdraw symptoms and helping with heroin overdoses,” he said. €œWe debated this for many years that people were using stimulants to reverse overdoses – we’re hearing it again.”“Supply is up, purity is up, price buy caduet online without prescription is down,” he said.

€œWe know from economics that when drug patterns go in that direction, use is going up.”Ciccarone said that there should not be deaths because of stimulants, but that heroin/fentanyl is the deadly element in the equation.His recommendations to communities were not to panic, but to lower the stigma surrounding drug use in order to affect change. Additionally, he said, buy caduet online without prescription policies should focus on reduction. supply reduction, buy caduet online without prescription demand reduction and harm reduction. But not focus on only one single drug.Additionally, he said that by addressing issues within communities and by healing communities socially, economically and spiritually, communities can begin to reduce demand.“We’ve got to fix the cracks in our society, because drugs fall into the cracks,” he said.Shutterstock U.S. Rep.

Annie Kuster (D-NH) recently held two virtual roundtables addressing how COVID-19 has affected New Hampshire’s healthcare industry.“The health and economic crisis caused by COVID-19 has created significant challenges for Granite State healthcare, mental health, and substance use treatment providers — at the same time, we are seeing increases in substance abuse and mental illness across New Hampshire,” Kuster said. €œFrom the transition to telehealth care and cancellations of elective procedures to a lack of personal protective equipment and increasing health needs of our communities – providers have overcome a multitude of obstacles due to COVID-19 in recent months. I was glad to hear from these hard-working Granite Staters, whose insights will continue to guide my work in Congress as we respond to this pandemic. I’m committed to ensuring that communities across New Hampshire can safely access the care and treatment they deserve.”The first roundtable addressed substance-use disorder (SUD) and mental health.The second virtual roundtable was an opportunity for health care providers to speak about their workplace challenges during the pandemic. Kuster is the founder and co-chairwoman of the Bipartisan Opioid Task Force, which held a virtual discussion in June on the opioid crisis and the pandemic.Shutterstock Opioid prescription rates for outpatient knee surgery vary nationwide, according to a study recently published in BMJ Open.

€œWe found massive levels of variation in the proportion of patients who are prescribed opioids between states, even after adjusting for nuances of the procedure and differences in patient characteristics,” said Dr. M. Kit Delgado, the study’s senior author and an assistant professor of Emergency Medicine and Epidemiology in the Perelman School of Medicine at the University of Pennsylvania. €œWe’ve also seen that the average number of pills prescribed was extremely high for outpatient procedures of this type, particularly for patients who had not been taking opioids prior to surgery.”Researchers examined insurance claims for nearly 100,000 patients who had arthroscopic knee surgery between 2015 and 2019 and had not used any opioid prescriptions in the six months before the surgery.Within three days of a procedure, 72 percent of patients filled an opioid prescription. High prescription rates were found in the Midwest and the Rocky Mountain regions.

The coasts had lower rates.Nationwide, the average prescription strength was equivalent to 250 milligrams of morphine over five days. This is the threshold for increased risk of opioid overdose death, according to the Centers for Disease Control and Prevention.Shutterstock U.S. Secretary of Labor Eugene Scalia awarded nearly $20 million to four states significantly impacted by the opioid crisis, the Department of Labor announced Thursday. The Florida Department of Economic Opportunity, the Maryland Department of Labor, the Ohio Department of Job and Family Services, and the Wisconsin Department of Workforce Development were awarded the money as part of the DOL’s “Support to Communities. Fostering Opioid Recovery through Workforce Development” created after the passage of the SUPPORT for Patients and Communities Act of 2018.

The money will be used to retrain workers in areas with high rates of substance use disorders. At a press conference in Piketon, Ohio, Scalia said the DOL had awarded Ohio’s Department of Job and Family Services $5 million to help communities in southern Ohio combat the opioid crisis in that area. €œToday’s funding represents this Administration’s continued commitment to serving those most in need,” said Assistant Secretary for Employment and Training John Pallasch. €œThe U.S. Department of Labor is taking a strong stand to support individuals and communities impacted by the crisis.”Grantees will use the funds to collaborate with community partners, such as employers, local workforce development boards, treatment and recovery centers, law enforcement officials, faith-based community organizations, and others, to address the economic effects of substance misuse, opioid use, addiction, and overdose..

A fourth wave of the opioid epidemic is coming, a national expert on drug use and policy said during https://www.cityreal.lv/can-i-get-caduet-over-the-counter/ a virtual panel discussion this week hosted by the Berkshire County, Massachusetts, District Attorney’s Office and the Berkshire Opioid cheap caduet online canada Addiction Prevention Collaborative.Dr. Daniel Ciccarone, a professor of family and community medicine at the University of California, San Francisco (UCSF) School of Medicine, said the next wave in the country’s opioid health emergency will focus on stimulants like methamphetamine and cocaine, and drug combinations where stimulants are used in conjunction with opioids.“The use of methamphetamines is back and it’s back cheap caduet online canada big time,” said Ciccarone, whose most recent research has focused on heroin use.Previously, officials had said there were three waves of the opioid epidemic – the first being prescription pills, the second being heroin, and the third being synthetic drugs, like fentanyl.Now, Ciccarone said, what federal law enforcement and medical experts are seeing is an increase in the use of stimulants, especially methamphetamines.The increase in deaths due to stimulants may be attributed to a number of causes. The increase in supply, both imported and domestically produced, as well as the increase of the drugs’ potency.“Meth’s purity and potency has gone up to historical levels,” he said.

€œAs of 2018, we’ve reached unseen heights of 97 percent potency and 97 percent purity cheap caduet online canada. In a prohibitionist world, we should not be seeing such high quality. This is almost pharmaceutical quality.”Additionally, law enforcement and public health experts cheap caduet online canada like Ciccarone are seeing an increase in the co-use of stimulants with opioids, he said.

Speedballs, cocaine mixed with heroin, and goofballs, methamphetamines used with heroin or fentanyl, are becoming more common from the Midwest into Appalachia and up through New England, he said.Federal law enforcement officials are recommending local communities prepare for the oncoming rise in illegal drugs coming into their communities.“Some people will use them both at the same time, but some may use them in some combination regularly,” he said. €œThey may use meth in the morning to go to work, and use heroin at night to come down.”The co-use, he said, was an organic response to the fentanyl overdose epidemic.“Some of the things that we heard … cheap caduet online canada is that meth is popularly construed as helping to decrease heroin and fentanyl use. Helping with heroin withdraw symptoms and helping with heroin overdoses,” he said.

€œWe debated this cheap caduet online canada for many years that people were using stimulants to reverse overdoses – we’re hearing it again.”“Supply is up, purity is up, price is down,” he said. €œWe know from economics that when drug patterns go in that direction, use is going up.”Ciccarone said that there should not be deaths because of stimulants, but that heroin/fentanyl is the deadly element in the equation.His recommendations to communities were not to panic, but to lower the stigma surrounding drug use in order to affect change. Additionally, he said, policies should focus on cheap caduet online canada reduction.

supply cheap caduet online canada reduction, demand reduction and harm reduction. But not focus on only one single drug.Additionally, he said that by addressing issues within communities and by healing communities socially, economically and spiritually, communities can begin to reduce demand.“We’ve got to fix the cracks in our society, because drugs fall into the cracks,” he said.Shutterstock U.S. Rep.

Annie Kuster (D-NH) recently held two virtual roundtables addressing how COVID-19 has affected New Hampshire’s healthcare industry.“The health and economic crisis caused by COVID-19 has created significant challenges for Granite State healthcare, mental health, and substance use treatment providers — at the same time, we are seeing increases in substance abuse and mental illness across New Hampshire,” Kuster said. €œFrom the transition to telehealth care and cancellations of elective procedures to a lack of personal protective equipment and increasing health needs of our communities – providers have overcome a multitude of obstacles due to COVID-19 in recent months. I was where to get caduet glad to hear from these hard-working Granite Staters, whose insights will continue to guide my work in Congress as we respond to this pandemic.

I’m committed to ensuring that communities across New Hampshire can safely access the care and treatment they deserve.”The first roundtable addressed substance-use disorder (SUD) and mental health.The second virtual roundtable was an opportunity for health care providers to speak about their workplace challenges during the pandemic. Kuster is the founder and co-chairwoman of the Bipartisan Opioid Task Force, which held a virtual discussion in June on the opioid crisis and the pandemic.Shutterstock Opioid prescription rates for outpatient knee surgery vary nationwide, according to a study recently published in BMJ Open. €œWe found massive levels of variation in the proportion of patients who are prescribed opioids between states, even after adjusting for nuances of the procedure and differences in patient characteristics,” said Dr.

M. Kit Delgado, the study’s senior author and an assistant professor of Emergency Medicine and Epidemiology in the Perelman School of Medicine at the University of Pennsylvania. €œWe’ve also seen that the average number of pills prescribed was extremely high for outpatient procedures of this type, particularly for patients who had not been taking opioids prior to surgery.”Researchers examined insurance claims for nearly 100,000 patients who had arthroscopic knee surgery between 2015 and 2019 and had not used any opioid prescriptions in the six months before the surgery.Within three days of a procedure, 72 percent of patients filled an opioid prescription.

High prescription rates were found in the Midwest and the Rocky Mountain regions. The coasts had lower rates.Nationwide, the average prescription strength was equivalent to 250 milligrams of morphine over five days. This is the threshold for increased risk of opioid overdose death, according to the Centers for Disease Control and Prevention.Shutterstock U.S.

Secretary of Labor Eugene Scalia awarded nearly $20 million to four states significantly impacted by the opioid crisis, the Department of Labor announced Thursday. The Florida Department of Economic Opportunity, the Maryland Department of Labor, the Ohio Department of Job and Family Services, and the Wisconsin Department of Workforce Development were awarded the money as part of the DOL’s “Support to Communities. Fostering Opioid Recovery through Workforce Development” created after the passage of the SUPPORT for Patients and Communities Act of 2018.

The money will be used to retrain workers in areas with high rates of substance use disorders. At a press conference in Piketon, Ohio, Scalia said the DOL had awarded Ohio’s Department of Job and Family Services $5 million to help communities in southern Ohio combat the opioid crisis in that area. €œToday’s funding represents this Administration’s continued commitment to serving those most in need,” said Assistant Secretary for Employment and Training John Pallasch.

€œThe U.S. Department of Labor is taking a strong stand to support individuals and communities impacted by the crisis.”Grantees will use the funds to collaborate with community partners, such as employers, local workforce development boards, treatment and recovery centers, law enforcement officials, faith-based community organizations, and others, to address the economic effects of substance misuse, opioid use, addiction, and overdose..

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Section 1 how much caduet cost. Identifying Stress &. Trauma1.1 Sussing Out Stress by Hermann Englert 1.2 Treating a Toxin to how much caduet cost Learning by Clancy Blair 1.3 The Trauma after the Storm by Anna Harwood Section 2. Effects on the Body &.

Immune System 2.1 The Danger of Stress by Melinda Wenner 2.2 Fact or Fiction?. Stress Causes Gray Hair by how much caduet cost Coco Ballantyne 2.3 Female Stress. A Faster, Stronger Response by Debra A. Bangasser 2.4 Fight or Flight May Be in Our Bones by Diana Kwon Section 3.

Effects on the how much caduet cost Mind &. Brain 3.1 This Is Your Brain in Meltdown by Amy Arnsten, Carolyn M. Mazure &. Rajita Sinha how much caduet cost 3.2 Strain on the Brain by Brian Mossop 3.3 Why Can't Christine Blasey Ford Remember How She Got Home?.

by Jim Hopper 3.4 Language Patterns Reveal Body’s Hidden Response to Stress by Jo Marchant Section 4. Burnout 4.1 Why Aren’t We Talking About Burnout?. by Krystal D'Costa 4.2 how much caduet cost Conquering Burnout by Michael P. Leiter &.

Christina Maslach 4.3 Frontline Trauma by Jillian Mock Section 5. Stress Management 5.1 Fight the Frazzled Mind by Robert Epstein 5.2 How I Broke the Cycle of Stress by Ashten Duncan 5.3 The Essence of Optimism by Elaine Fox 5.4 Changing Our how much caduet cost DNA through Mind Control?. by Bret Stetka 5.5 Mind of the Meditator by Matthieu Ricard, Antoine Lutz &. Richard J.

Davidson Section how much caduet cost 6. Resilience. Aftermath 6.1 Ready for Anything by Steven M. Southwick & how much caduet cost.

Dennis S. Charney 6.2 The Neuroscience of True Grit by Gary Stix 6.3 The Coronavirus and Post-Traumatic Growth by Steve Taylor 6.4 COVID-19. The Biggest Psychological Experiment by Lydia DenworthIn response how much caduet cost to the COVID-19 pandemic, members of the Rapid Deployment Vaccine Collaborative (or RaDVaC)—a group composed of scientists and their friends or colleagues—have been self-administering an untested vaccine for SARS-CoV-2 (the virus that causes COVID-19). The RaDVaC scientists describe their project as aiming “to reduce risk of harm from SARS-CoV-2, minimally until there is at least one effective commercial vaccine widely available.” Although the project’s white paper includes includes terms and conditions designed to shield the authors from liability, RaDVaC’s self-experimentation raises important legal and ethical questions.

Self-experimentation has a fascinating history. In the early 1900s, Walter Reed conducted experiments in Cuba deliberately how much caduet cost exposing individuals to yellow fever that included members of the study team as participants. These led to significant public health benefits in confirming that yellow fever was transmitted by mosquitoes, but also resulted in the deaths of several participants. Some Nobel Prize–winning work by scientists was based on self-experimentation that initially was seen as crazy.

For instance, in how much caduet cost 1984, Barry Marshall swallowed bacteria to prove that they caused gastritis and peptic ulcers. Many cardiac procedures are based on a 1929 experiment by a German doctor who inserted a catheter into his own heart. Perhaps surprisingly, how much caduet cost self-experimentation was once considered an ethical safeguard. The Nuremberg Code, established in response to grossly unethical experiments during World War II, permitted higher risk research if investigators also volunteered to participate, as they had in the earlier yellow fever studies.

However, the idea that self-experimentation can justify higher research risks was abandoned in later codes of ethics. Not only is self-experimentation legally and ethically complex, but protections like independent review and informed consent, which are now required by research regulations, may how much caduet cost be a better way to protect research participants. Existing regulations for research were not designed to address self-experimentation. Laws governing research typically define research as an activity designed to produce generalizable knowledge, which does not cover experimentation that is badly designed, unlikely to produce useful data, and merely aiming to protect a small group of people.

In addition, the how much caduet cost U.S. Common Rule governs federally funded research, and RaDVaC is not using any federal funding. However, Harvard is covered by a “federalwide assurance” under which the institution has agreed that all research it conducts will abide by the regulations (regardless of funding source). If studies of immune responses involving self-experimentation are planned in George Church’s laboratory at Harvard, as has been reported, this undoubtedly requires approval by an Institutional Review Board, which would provide some oversight of how much caduet cost this self-experimentation.

If results are to be published in a peer-reviewed journal, moreover, most, if not all, journals would require assurance of regulatory review and oversight. The U.S. Food and Drug Administration has similar power to regulate research, and, how much caduet cost perhaps more relevant for our purposes, “drugs” (including human biological materials and biologics)—even if they are not distributed for profit. The RaDVaC project uses biological materials—more specifically, small chains of amino acids from key SARS-CoV-2 proteins—and therefore may fall under the FDA’s jurisdiction.

While the FDA has not traditionally exercised this authority to regulate the analogous practice of small scale, do-it-yourself biohacking, it retains the power to do so in the future. Finally, if people were harmed by taking this vaccine, they could also how much caduet cost sue RaDVaC, but the disclaimers in the white paper are carefully designed to avoid liability. Even if the law doesn’t adequately address this behavior, it may be ethically problematic—including because it could be a waste of scientific expertise and research effort. If RaDVaC intends to produce generalizable knowledge about this vaccine, unsystematic self-experimentation is unlikely to produce useful information.

For example, self-experimentation can lead to biased results if researchers overestimate the chance that the vaccine works, or fail to report side how much caduet cost effects. Randomized controlled trials, by contrast, are typically designed with researchers being blinded to who receives the intervention or the placebo. Beyond self-experimentation, friends, staff members, and family members of the scientists involved are taking this vaccine based on these expert’s recommendations, which could lead to two potential misconceptions. First, people taking the vaccine might overestimate the how much caduet cost likelihood that they are protected from SARS-CoV-2 and change their behavior.

If some individuals falsely believe they are protected, they might engage in riskier behavior that could cause harm to themselves and others. A second misconception is the idea that this is research that could benefit others. The same data analyst seemed to believe this when he added “my continued existence through this pandemic will be a useful data set.” Yet the RaDVaC project could not produce useful data in the same way as standard, well-designed vaccine trials, for example, because it is unclear whether individuals receiving the vaccine are thoroughly evaluated or monitored, how much caduet cost and there does not appear to be a control group. Even if everyone involved with this project fully understands what they are getting into, however, there are also questions about expertise and privilege.

Senior scientists benefit from many layers of privilege. Investment in their education, expertise in specialized areas, how much caduet cost and access to information or materials. Arguably, these privileges come with a responsibility to use expertise for the benefit of society. If the RaDVaC vaccine is how much caduet cost potentially beneficial, then it is tragic not to test it in a rigorously designed study.

Indeed, uncontrolled self-experimentation is part of a larger problem in the COVID-19 pandemic. Panic about the virus has led to the widespread use of interventions outside of well-designed clinical trials. Without such trials, we remain in how much caduet cost the dark about which interventions offer net benefits or net harms. Insofar as the scientists involved have expertise in vaccine research, they should either reform the RaDVaC project or lend their expertise to serious projects.

On the other hand, if scientists don’t have relevant expertise, their overconfidence at their ability to work outside of their wheelhouse may be harmful. Earlier this week, Steven Salzberg, a how much caduet cost computational biologist, called for experimental COVID-19 vaccines to be rolled out before the results of phase III testing. An op-ed denouncing his misinformed view was published the next day, and Salzberg reversed his position immediately. Similarly, some of the named members of the RaDVaC project have expertise in genetics, neuroscience, and anti-aging research.

Their time might be better spent on projects in these fields, which will still be important when this how much caduet cost pandemic is finally over. Rather than trying everything but the kitchen sink against COVID-19, it would be wiser to focus our collective efforts on prioritizing the most promising interventions and testing them in rigorous research, as has been done for some treatments for COVID-19. RaDVaC’s scientists should be encouraged to collaborate on systematic COVID-19 vaccine testing if they have relevant expertise, and to do other valuable things with their time if not.Not far from the famously multihued architecture of Bilbao in northern Spain, an underground world boasts its own vibrant display of color. The stalagmites and stalactites of Goikoetxe Cave are not just the usual white how much caduet cost.

Many range from honey to deep red. New research shows that these formations, known generally as speleothems, get their red color from organic compounds leached from soil and transported by water. Scientists suggest, in an article published online in April in Quaternary how much caduet cost International, that Goikoetxe Cave's speleothems record environmental conditions such as rainfall.The wildfire season is off to a roaring start. The hot summer is worsening drought and drying out vegetation—an unfortunately ideal environment for wildfires to rage.

But that’s just one consequence of global warming. It’s also leading to how much caduet cost flooding, torrential rainstorms and heat-related deaths. In fact, the climate crisis has led to a widespread public health crisis. And as an ear, nose and throat physician, I see the effects more and more often.

I vividly remember a patient who came in late for her appointment during a July how much caduet cost heat wave. When I walked in, she said, “I’m so sorry I’m late, I was up all night walking my grandbaby around the train station.” Without air conditioning at home, the child was sweating through her clothes in the heat of the night, putting her at risk for dehydration. July 2019 was the hottest July on record. September 2019 was the hottest on how much caduet cost record.

January 2020 was the hottest on record. May 2020 was the hottest on record. This is how much caduet cost not a coincidence. It is a pattern.

Carbon dioxide, an important greenhouse gas contributing to global warming, has increased by 9 percent since 2005 and by 31 percent since 1950. A U.N how much caduet cost. Intergovernmental Panel on Climate Change special report pointed out that the world has already warmed about one degree Celsius from pre-industrial levels. It stressed the urgency to act to limit warming to 1.5 degrees, and that a two-degree increase will lead to how much caduet cost unprecedented extreme heat, water scarcity and food shortages around the globe.

Heat affects every part of our body. It can lead to heat exhaustion, heat stroke, anxiety, impaired cognitive function and even premature death from heart and lung disease. Across the country, the health concerns how much caduet cost of the climate crisis are increasingly being recognized, pushing thousands of medical providers—doctors, nurses, pharmacists, therapists, medical students—to become advocates for change. In my own practice, I explain to patients how the climate crisis affects their health.

For example, apart from contributing to global warming, rising carbon dioxide levels increase the amount of pollen that plants produce as a consequence of higher rates of photosynthesis. This rise in pollen levels can lead to worsening allergy symptoms. Another example is fine particulate matter (known as PM2.5) associated with air pollution, much of it linked to the burning of fossil fuels that help drive the warming. When we breathe in these particles, they travel down the airway and settle in the tiny air sacs called alveoli of the lungs, causing inflammation and potentially worsening asthma symptoms.

The explanations are simple, but the health risks are widespread and complex. Ground-level ozone pollution, which is worse in hotter weather, can also harm people with asthma and other respiratory diseases. And that harm falls disproportionately on the poor. Wealthier people living in North America have a per capita carbon footprint that is 25 percent higher than those of lower-income residents, with some affluent suburbs producing emissions 15 times higher than nearby neighborhoods.

These carbon emissions contribute to global warming, and the subsequent health consequences are felt far beyond the neighborhood that produces them. Older adults, children, low-income communities and communities of color are less resilient on average to the health impacts of climate change. The climate crisis is thus leading to a disproportionate public health crisis—and worse, it is a threat multiplier. At a time when many Americans are economically challenged, continued heat waves and the higher energy bills they trigger threaten access to water and energy security.

The economic benefits of a low-carbon economy are clear. Estimates suggest that without climate investments, the United States will face economic damage from climate change equivalent to 1–3 percent of GDP per year by 2100. The majority of Americans think global warming is happening. The climate crisis has unfairly been labeled as political, when in fact, people recognize that something needs to be done about it.

Even for those who are seemingly unaffected, there is increasing global recognition that the safeguards of living in a protected community and affording expert medical care will eventually fail if global warming continues unchecked. Unfortunately, there will be no vaccine in six months or a year for the climate crisis. The only treatment is collective climate action in the present. Climate action is required of our elected leaders, and we must mandate it of ourselves.

It can be as simple as educating family and friends, while making sustainable shopping and traveling choices. It includes eating less meat, unplugging electronics and raising a voice against the fossil fuel industry. With a rise in demand for absentee ballots for the election this November, it is crucial to request mail-in ballots right away to make sure our voices are heard. The United States is the second largest emitter of greenhouse gases, and we must vote for green policy.

Legislative action and policy change work, as evidenced by the Clean Air Act and its subsequent amendments, which are projected to save 230,000 lives in 2020. The climate crisis is a public health issue, and we must start healing the planet in order to heal each other. Fighting against the climate crisis is one of the most patriotic things we can do right now. It will protect our health and the health of our neighbors across the country and the globe, and will allow all of us to live on this planet, the only home we have..

Section 1 cheap caduet online canada. Identifying Stress &. Trauma1.1 Sussing Out Stress by Hermann Englert 1.2 Treating a Toxin to Learning cheap caduet online canada by Clancy Blair 1.3 The Trauma after the Storm by Anna Harwood Section 2. Effects on the Body &.

Immune System 2.1 The Danger of Stress by Melinda Wenner 2.2 Fact or Fiction?. Stress cheap caduet online canada Causes Gray Hair by Coco Ballantyne 2.3 Female Stress. A Faster, Stronger Response by Debra A. Bangasser 2.4 Fight or Flight May Be in Our Bones by Diana Kwon Section 3.

Effects on the cheap caduet online canada Mind &. Brain 3.1 This Is Your Brain in Meltdown by Amy Arnsten, Carolyn M. Mazure &. Rajita Sinha 3.2 Strain on the Brain by Brian Mossop 3.3 Why Can't Christine Blasey Ford Remember How She Got Home? cheap caduet online canada.

by Jim Hopper 3.4 Language Patterns Reveal Body’s Hidden Response to Stress by Jo Marchant Section 4. Burnout 4.1 Why Aren’t We Talking About Burnout?. by Krystal cheap caduet online canada D'Costa 4.2 Conquering Burnout by Michael P. Leiter &.

Christina Maslach 4.3 Frontline Trauma by Jillian Mock Section 5. Stress Management 5.1 Fight the Frazzled Mind by Robert Epstein 5.2 How I Broke the Cycle of Stress by Ashten Duncan cheap caduet online canada 5.3 The Essence of Optimism by Elaine Fox 5.4 Changing Our DNA through Mind Control?. by Bret Stetka 5.5 Mind of the Meditator by Matthieu Ricard, Antoine Lutz &. Richard J.

Davidson Section cheap caduet online canada 6. Resilience. Aftermath 6.1 Ready for Anything by Steven M. Southwick & cheap caduet online canada.

Dennis S. Charney 6.2 The Neuroscience of True Grit by Gary Stix 6.3 The Coronavirus and Post-Traumatic Growth by Steve Taylor 6.4 COVID-19. The Biggest Psychological Experiment by Lydia DenworthIn response to the COVID-19 pandemic, members of the Rapid Deployment Vaccine Collaborative (or RaDVaC)—a group composed of scientists cheap caduet online canada and their friends or colleagues—have been self-administering an untested vaccine for SARS-CoV-2 (the virus that causes COVID-19). The RaDVaC scientists describe their project as aiming “to reduce risk of harm from SARS-CoV-2, minimally until there is at least one effective commercial vaccine widely available.” Although the project’s white paper includes includes terms and conditions designed to shield the authors from liability, RaDVaC’s self-experimentation raises important legal and ethical questions.

Self-experimentation has a fascinating history. In the early 1900s, Walter Reed conducted experiments in Cuba deliberately exposing individuals to yellow fever that included members of the study team as cheap caduet online canada participants. These led to significant public health benefits in confirming that yellow fever was transmitted by mosquitoes, but also resulted in the deaths of several participants. Some Nobel Prize–winning work by scientists was based on self-experimentation that initially was seen as crazy.

For instance, in 1984, Barry Marshall swallowed bacteria to prove that they caused gastritis cheap caduet online canada and peptic ulcers. Many cardiac procedures are based on a 1929 experiment by a German doctor who inserted a catheter into his own heart. Perhaps surprisingly, self-experimentation was cheap caduet online canada once considered an ethical safeguard. The Nuremberg Code, established in response to grossly unethical experiments during World War II, permitted higher risk research if investigators also volunteered to participate, as they had in the earlier yellow fever studies.

However, the idea that self-experimentation can justify higher research risks was abandoned in later codes of ethics. Not only is self-experimentation legally and ethically complex, but protections like independent review and informed consent, which are now required by research regulations, may be a better way to protect cheap caduet online canada research participants. Existing regulations for research were not designed to address self-experimentation. Laws governing research typically define research as an activity designed to produce generalizable knowledge, which does not cover experimentation that is badly designed, unlikely to produce useful data, and merely aiming to protect a small group of people.

In addition, cheap caduet online canada the U.S. Common Rule governs federally funded research, and RaDVaC is not using any federal funding. However, Harvard is covered by a “federalwide assurance” under which the institution has agreed that all research it conducts will abide by the regulations (regardless of funding source). If studies of immune responses involving self-experimentation are planned cheap caduet online canada in George Church’s laboratory at Harvard, as has been reported, this undoubtedly requires approval by an Institutional Review Board, which would provide some oversight of this self-experimentation.

If results are to be published in a peer-reviewed journal, moreover, most, if not all, journals would require assurance of regulatory review and oversight. The U.S. Food and Drug Administration has similar power to regulate research, and, perhaps more relevant for our purposes, “drugs” (including human biological materials and biologics)—even if they are not distributed for profit cheap caduet online canada. The RaDVaC project uses biological materials—more specifically, small chains of amino acids from key SARS-CoV-2 proteins—and therefore may fall under the FDA’s jurisdiction.

While the FDA has not traditionally exercised this authority to regulate the analogous practice of small scale, do-it-yourself biohacking, it retains the power to do so in the future. Finally, if people were harmed by taking this cheap caduet online canada vaccine, they could also sue RaDVaC, but the disclaimers in the white paper are carefully designed to avoid liability. Even if the law doesn’t adequately address this behavior, it may be ethically problematic—including because it could be a waste of scientific expertise and research effort. If RaDVaC intends to produce generalizable knowledge about this vaccine, unsystematic self-experimentation is unlikely to produce useful information.

For example, self-experimentation can lead to biased results if researchers overestimate cheap caduet online canada the chance that the vaccine works, or fail to report side effects. Randomized controlled trials, by contrast, are typically designed with researchers being blinded to who receives the intervention or the placebo. Beyond self-experimentation, friends, staff members, and family members of the scientists involved are taking this vaccine based on these expert’s recommendations, which could lead to two potential misconceptions. First, people taking the vaccine might overestimate the likelihood cheap caduet online canada that they are protected from SARS-CoV-2 and change their behavior.

If some individuals falsely believe they are protected, they might engage in riskier behavior that could cause harm to themselves and others. A second misconception is the idea that this is research that could benefit others. The same data analyst seemed to believe this when he added “my continued existence through this pandemic will be a cheap caduet online canada useful data set.” Yet the RaDVaC project could not produce useful data in the same way as standard, well-designed vaccine trials, for example, because it is unclear whether individuals receiving the vaccine are thoroughly evaluated or monitored, and there does not appear to be a control group. Even if everyone involved with this project fully understands what they are getting into, however, there are also questions about expertise and privilege.

Senior scientists benefit from many layers of privilege. Investment in their education, expertise in cheap caduet online canada specialized areas, and access to information or materials. Arguably, these privileges come with a responsibility to use expertise for the benefit of society. If the RaDVaC vaccine is potentially beneficial, then it is tragic not to test cheap caduet online canada it in a rigorously designed study.

Indeed, uncontrolled self-experimentation is part of a larger problem in the COVID-19 pandemic. Panic about the virus has led to the widespread use of interventions outside of well-designed clinical trials. Without such trials, we remain in the dark about which interventions cheap caduet online canada offer net benefits or net harms. Insofar as the scientists involved have expertise in vaccine research, they should either reform the RaDVaC project or lend their expertise to serious projects.

On the other hand, if scientists don’t have relevant expertise, their overconfidence at their ability to work outside of their wheelhouse may be harmful. Earlier this cheap caduet online canada week, Steven Salzberg, a computational biologist, called for experimental COVID-19 vaccines to be rolled out before the results of phase III testing. An op-ed denouncing his misinformed view was published the next day, and Salzberg reversed his position immediately. Similarly, some of the named members of the RaDVaC project have expertise in genetics, neuroscience, and anti-aging research.

Their time might be better spent on projects in these fields, which will still be important when this pandemic is finally over cheap caduet online canada. Rather than trying everything but the kitchen sink against COVID-19, it would be wiser to focus our collective efforts on prioritizing the most promising interventions and testing them in rigorous research, as has been done for some treatments for COVID-19. RaDVaC’s scientists should be encouraged to collaborate on systematic COVID-19 vaccine testing if they have relevant expertise, and to do other valuable things with their time if not.Not far from the famously multihued architecture of Bilbao in northern Spain, an underground world boasts its own vibrant display of color. The stalagmites and cheap caduet online canada stalactites of Goikoetxe Cave are not just the usual white.

Many range from honey to deep red. New research shows that these formations, known generally as speleothems, get their red color from organic compounds leached from soil and transported by water. Scientists suggest, in an article published online in April in Quaternary International, that Goikoetxe Cave's speleothems record environmental conditions such as rainfall.The wildfire season is off to cheap caduet online canada a roaring start. The hot summer is worsening drought and drying out vegetation—an unfortunately ideal environment for wildfires to rage.

But that’s just one consequence of global warming. It’s also leading to flooding, torrential rainstorms cheap caduet online canada and heat-related deaths. In fact, the climate crisis has led to a widespread public health crisis. And as an ear, nose and throat physician, I see the effects more and more often.

I vividly remember a patient who cheap caduet online canada came in late for her appointment during a July heat wave. When I walked in, she said, “I’m so sorry I’m late, I was up all night walking my grandbaby around the train station.” Without air conditioning at home, the child was sweating through her clothes in the heat of the night, putting her at risk for dehydration. July 2019 was the hottest July on record. September 2019 cheap caduet online canada was the hottest on record.

January 2020 was the hottest on record. May 2020 was the hottest on record. This is not cheap caduet online canada a coincidence. It is a pattern.

Carbon dioxide, an important greenhouse gas contributing to global warming, has increased by 9 percent since 2005 and by 31 percent since 1950. A U.N cheap caduet online canada. Intergovernmental Panel on Climate Change special report pointed out that the world has already warmed about one degree Celsius from pre-industrial levels. It stressed the urgency to act to limit cheap caduet online canada warming to 1.5 degrees, and that a two-degree increase will lead to unprecedented extreme heat, water scarcity and food shortages around the globe.

Heat affects every part of our body. It can lead to heat exhaustion, heat stroke, anxiety, impaired cognitive function and even premature death from heart and lung disease. Across the country, the health concerns of the climate crisis are increasingly being recognized, pushing thousands of medical providers—doctors, nurses, pharmacists, therapists, cheap caduet online canada medical students—to become advocates for change. In my own practice, I explain to patients how the climate crisis affects their health.

For example, apart from contributing to global warming, rising carbon dioxide levels increase the amount of pollen that plants produce as a consequence of higher rates of photosynthesis. This rise in pollen levels can lead to worsening allergy symptoms cheap caduet online canada. Another example is fine particulate matter (known as PM2.5) associated with air pollution, much of it linked to the burning of fossil fuels that help drive the warming. When we breathe in these particles, they travel down the airway and settle in the tiny air sacs called alveoli of the lungs, causing inflammation and potentially worsening asthma symptoms.

The explanations are simple, but the health risks are widespread and cheap caduet online canada complex. Ground-level ozone pollution, which is worse in hotter weather, can also harm people with asthma and other respiratory diseases. And that harm falls disproportionately on the poor. Wealthier people living in North America have a per capita carbon footprint that is 25 percent higher than those of lower-income residents, with some cheap caduet online canada affluent suburbs producing emissions 15 times higher than nearby neighborhoods.

These carbon emissions contribute to global warming, and the subsequent health consequences are felt far beyond the neighborhood that produces them. Older adults, children, low-income communities and communities of color are less resilient on average to the health impacts of climate change. The climate crisis is cheap caduet online canada thus leading to a disproportionate public health crisis—and worse, it is a threat multiplier. At a time when many Americans are economically challenged, continued heat waves and the higher energy bills they trigger threaten access to water and energy security.

The economic benefits of a low-carbon economy are clear. Estimates suggest that without climate investments, the United States will face economic damage from climate change equivalent to 1–3 percent cheap caduet online canada of GDP per year by 2100. The majority of Americans think global warming is happening. The climate crisis has unfairly been labeled as political, when in fact, people recognize that something needs to be done about it.

Even for those who are seemingly unaffected, there is increasing global recognition that the safeguards of cheap caduet online canada living in a protected community and affording expert medical care will eventually fail if global warming continues unchecked. Unfortunately, there will be no vaccine in six months or a year for the climate crisis. The only treatment is collective climate action in the present. Climate action is required of our elected leaders, and we cheap caduet online canada must mandate it of ourselves.

It can be as simple as educating family and friends, while making sustainable shopping and traveling choices. It includes eating less meat, unplugging electronics and raising a voice against the fossil fuel industry. With a rise in demand for absentee ballots for the election this November, it is crucial to request mail-in ballots right away to make sure our voices are heard. The United States is the second largest emitter of greenhouse gases, and we must vote for green policy.

Legislative action and policy change work, as evidenced by the Clean Air Act and its subsequent amendments, which are projected to save 230,000 lives in 2020. The climate crisis is a public health issue, and we must start healing the planet in order to heal each other. Fighting against the climate crisis is one of the most patriotic things we can do right now. It will protect our health and the health of our neighbors across the country and the globe, and will allow all of us to live on this planet, the only home we have..

Caduet 5 20mg

This story appeared in the November 2020 issue as "Bacteria and the Brain." Subscribe to Discover magazine for more stories like this.It’s not always easy to convince caduet 5 20mg people that the human gut is a sublime and wondrous place worthy of special attention. Sarkis Mazmanian discovered that soon after arriving at Caltech for his first faculty job 14 years ago, when he explained to a local artist what he had in mind for the walls outside his new office.The resulting mural greets visitors to the Mazmanian Lab today. A vaguely psychedelic, 40-foot-long, tube-shaped colon that’s pink, purple and red caduet 5 20mg snakes down the hallway. In a panel next to it, fluorescent yellow and green bacteria explode out of a deeply inflamed section of the intestinal tract, like radioactive lava from outer space.The mural is modest compared with what the scientist has been working on since. Over the last decade or so, Mazmanian has been a leading proponent of the idea that the flora of the human caduet 5 20mg digestive tract has a far more powerful effect on the human body and mind than we thought — a scientific effort that earned him a $500,000 MacArthur Fellowship “Genius Grant” in 2012.

Since then, Mazmanian and a small but growing cadre of fellow microbiologists have amassed a tantalizing body of evidence on the microbiome’s role in all kinds of brain disorders, including schizophrenia, Alzheimer’s disease, Parkinson’s disease and depression.But the results they’ve seen in autism could, in the end, prove the most transformative. Autism affects about 1 in 59 children in the U.S., and involves profound social withdrawal, communication problems, and sometimes anxiety and aggression. The causes caduet 5 20mg of the brain disorder have remained speculative. Now, Mazmanian and other researchers are finding that autism may be inextricably linked to — or even caused by — irregularities in the gut microbiome.A Biology StoryAt 47, Mazmanian — with his shaved head, flannel shirt and skinny jeans — resembles a young, urban hipster on his way to write at the local café. Originally, literary caduet 5 20mg life was his plan.

Born in Lebanon to two Armenian refugees, neither of whom had more than a first-grade education, Mazmanian landed in the class of an energetic high school English teacher in California’s San Fernando Valley, where his family first settled. The teacher recognized his gift for language and encouraged him to pursue a career in literature. Mazmanian enrolled at UCLA in 1990, planning to major in English.Everything changed when he took his first caduet 5 20mg biology class. Hunched over his new, thick textbook in the library, reading about basic biological concepts like photosynthesis, Mazmanian felt a vast new world opening up to him.Sarkis Mazmanian, shown in front of a mural that celebrates the human gut, is part of a group of microbiologists researching the effects of the digestive tract on a range of disorders. (Credit.

Caltech)“For the first time in my life, I wanted to turn the page and see where the story was going to go,” he says. €œI think I decided that minute to become a scientist.”Mazmanian was most fascinated by the idea that tiny organisms, invisible to the naked eye, could function as powerful, self-contained machines — powerful enough to take over and destroy the human body. After graduating with a degree in microbiology, Mazmanian joined a UCLA infectious diseases lab and began studying bacteria that cause staph infections.As his dissertation defense approached, Mazmanian read a one-page commentary penned by a prominent microbiologist, highlighting the fact that our intestines are teeming with hundreds, if not thousands, of different species of bacteria. But it was still largely unknown what they are and how they affect the human body.When Mazmanian dug further, he found that no one had yet answered what seemed to him to be the most obvious question. Why would the human immune system, designed to attack and destroy foreign invaders, allow hundreds of species of bacteria to live and thrive in our guts unmolested?.

To him, the bacteria’s survival implied that we had evolved to coexist with them. And if that were so, he reasoned, there must be some benefit to both the microbes and the human body — a symbiotic relationship. But what was it?. Gut InvadersMazmanian set out to study the link between gut microbes and the immune system. As a postdoctoral researcher, he joined the lab of Harvard University infectious disease specialist Dennis Kasper.To start, Mazmanian examined how the immune systems of germ-free mice — lab mice completely protected, starting at birth, from all microbes — differed from those of mice with either few or normal levels of microbes.

He expected this initial census would be just a first step in a long and arduous quest for scientific pay dirt. But when he went to examine a printout of his results in the lab, he realized immediately he might already be onto something big. The germ-free mice had a 30 to 40 percent reduction in a specific type of immune cell known as helper T-cells.This colorized close-up of a mouse’s gut reveals the tight relationship between the gut microbe Bacteroides fragilis (red) and the epithelial surface of the colon (blue). (Credit. Caltech)Since helper T-cells play a key role in coordinating attacks against invading pathogens, the finding suggested that the immune systems of the germ-free mice were far less robust than those found in peers with normal levels of microbes.“That was exciting, right?.

€ Mazmanian recalls. €œObviously I repeated it and tested it in a number of different ways. Then I asked the next question. €˜Can I restore the [immune] function in an adult animal?. €™â€‰â€Mazmanian colonized the guts of the immunocompromised, germ-free mice with microbes from standard lab mice.

After receiving the fecal transplant, their T-cell counts shot up. Within a month, their numbers were identical to mice raised outside the germ-free bubble.Resolving to identify the microorganisms causing this transformation, Mazmanian resorted to trial and error. One by one, he added strains of bacteria found in the guts of mice to the guts of germ-free mice.He got nowhere with the first five or six species he examined. Then, simply because it was convenient, he decided to test one more that was readily available in his lab. Mazmanian’s adviser, Kasper, had been studying a gut microbe called Bacteroides fragilis.

When Mazmanian implanted one of Kasper’s specimens into the gut of his germ-free mice, the results were dramatic. The T-cell numbers spiked to normal. Eventually, Mazmanian demonstrated he could reproduce this effect simply by adding a single molecule that these bacteria produce, called polysaccharide A, to their guts.“There was no logic in the choice whatsoever,” Mazmanian recalls. €œ[B. Fragilis] was available, it came from the gut.” In other words, he got lucky.Mazmanian dug deeper and discovered that the biggest impact B.

Fragilis had was on the population of a subtype of helper T-cells called regulatory, or suppressor, T-cells. These cells play a key role in preventing the immune system from attacking its host body, protecting against autoimmune or inflammatory diseases. It was the first time any scientist had demonstrated that a single compound from a single microbe could reverse a specific problem with the immune system.To Mazmanian, the finding, published in 2005 in the journal Cell, alluded to new approaches to treating a wide array of autoimmune, inflammatory and allergic disorders. What if it were possible to help a faulty immune system by tweaking a patient’s microbiome?. It was with this exploration in mind that he arrived in Pasadena in 2006 to set up his lab at Caltech.A Convenient CollaborationA few years later, Mazmanian was having lunch on campus with neuroscientist and colleague Paul Patterson.

Patterson had been preoccupied with a mystery that had, for years, confounded those studying autism in humans. When pregnant mothers have a severe infection in the second trimester, their babies are much more likely to develop autism.As Mazmanian tells it, Patterson was a man of few words, and at lunch Mazmanian was “going on and on” about his own work.“You know,” Patterson interjected thoughtfully, “I think kids with autism have GI issues.”Patterson recalled reading that something like 60 percent of children with autism had some form of clinical GI problem, such as bloating, constipation, flatulence or diarrhea. Was it possible, he wondered, that there was a microbiome connection?. As they talked, Mazmanian’s excitement grew.A few years earlier, Patterson had discovered that when he exposed pregnant mice to pathogens like the influenza virus, they gave birth to pups that grew up more likely to be startled by loud noises, to shy away from social contact and to groom themselves repetitively — symptoms that resemble those of autism. Patterson was in the process of comparing the brains of these autism-mimicking mice with their neurotypical cousins to see if he could detect any differences that might explain how the maternal immune system was somehow interfering with the pups’ brain development.Mazmanian had a suggestion.

The next time Patterson sacrificed one of his autistic mice to study their brains, what if he set the intestines aside for his colleague down the hall?. When the guts arrived in Mazmanian’s lab, he found that the intestines of the neurotypical mice looked normal. But the guts of the autism-mimicking offspring were almost uniformly inflamed. Could it be that the microbiome was the cause of this inflammation?. And could that, in turn, be somehow connected to the behavioral symptoms?.

Throughout the winter and spring of 2012, Mazmanian and Patterson continued their conversation. Mazmanian found distinct differences in the microbiomes of the mice. And, they noticed, the mice with the features of autism had leaky gut syndrome, an increased permeability of the gut lining that can allow pathogens and allergens to leach out. This condition had also been reported in children with autism.So Mazmanian and Patterson turned their attention outside the gut. They took blood samples to see if any gut microbes, or the compounds they produce, were circulating in the rest of the body.

They homed in on one molecule in particular, called 4-ethylphenyl sulfate, which was roughly 45 times as abundant in the mice that had symptoms of autism. And it looked familiar. Structurally, it was almost identical to a molecule recently found to be significantly elevated in human children with autism.It was enough to take the next step. Every day for three weeks, Mazmanian injected the molecule, harvested from the mice with autism-like symptoms, directly into the bloodstream of 5-week-old normal lab mice (the age at which the autistic mice normally developed leaky gut). Then Mazmanian and his team gave them a series of behavioral tests.

The mice were far more easily startled and were less comfortable in large empty spaces than their untreated peers, indications of an increase in anxiety-related behaviors commonly seen in the mice with autism-like symptoms. The researchers published their results in Cell in 2013.Though surprising, the data made sense in some ways. Many drug companies rely on small-molecule drugs that can be taken orally, but still manage to cross the blood-brain barrier and affect behavior. It seemed entirely possible that small molecules, created by bacteria in the gut, could enter the bloodstream and reach the brain. And they don’t even have to leak out of the gut to do so.Of Mice and MenPatterson died in 2014, at age 70, just six months after the publication of the duo’s groundbreaking Cell paper.

Around the same time, a series of parallel experiments in a clinic hundreds of miles away was already paving the way forward. While Patterson and Mazmanian had been working in mice, Rosa Krajmalnik-Brown, a microbiologist at Arizona State University, had teamed up with Jim Adams, who directs the university’s autism and Asperger’s research program, to study humans.The researchers were conducting a detailed analysis of the microbiome of human autism patients and found that the bacteria were far less diverse in the children with autism. Notably, several important species involved in the digestion of carbohydrates were severely depleted.Krajmalnik-Brown and Adams launched a preliminary trial to test the effects of fecal transplants on 18 children between the ages of 7 and 16 with severe autism, who also had severe GI issues. The researchers administered powerful antibiotics to kill off the microbiomes of the children and followed them with a bowel cleanse. They then replaced the microbes with transplanted flora taken from the guts of healthy neurotypical adult volunteers.The results were better than anyone could have expected.

The procedure resulted in a large reduction in GI symptoms and increased the diversity of bacteria in the children’s guts. But more significantly, their neurological symptoms were reduced. At the onset of the study in 2017, an independent evaluator found 83 percent of participants had severe autism. Two years after the initial trial, only 17 percent were rated as severely autistic. And 44 percent were no longer on the autism scale.“[My child] did a complete 180,” says Dana Woods, whose then-7-year-old son Ethan enrolled in the initial study five years ago.

€œHis ability to communicate is so much different now. He’s just so much more present. He’s so much more aware. He’s no longer in occupational therapy. He’s no longer in speech therapy.

After the study, he tested two points away from a neurotypical child.”In their first report on the trial in 2017, the team highlighted a number of distinct changes in the microbiome after the transplants, in particular a surge in the populations of three types of bacteria. Among them was a four-fold increase in Bifidobacterium, a probiotic organism that seems to play a key role in the maintenance of a healthy gut.But figuring out what was happening on a cellular level — to really look inside some guts — would require another vehicle. The ASU team needed Mazmanian’s mice.“At the end of the day, what we care about is healing people and how the microbiome affects people,” explains Krajmalnik-Brown. €œThat’s why we work with people. But with mice you can do things that are more mechanistic.”The Great Mouse Detective(Credit.

Caltech)Together, Krajmalnik-Brown, Mazmanian and their collaborators would uncover some tantalizing new insights that go a long way to solving the mystery. In May 2019, the team published another high-profile paper in Cell, after they transplanted stool samples from Krajmalnik-Brown’s severely autistic patients into the guts of Mazmanian’s germ-free mice. The offspring of these mice showed the autism-like symptoms, such as repetitive and compulsive behavior.This time, the team dug even deeper into the biochemical processes playing out in the brain, looking not just at behavior but at the chemicals involved in creating it. The mice that developed autism-like behaviors had measurably lower levels of two substances called taurine and 5-aminovaleric acid (5AV). When they dug into the literature, the team learned that these two substances are known to mimic activity of a key signaling agent in the brain called gamma-aminobutyric acid (GABA) — a neurotransmitter that other studies have found is deficient in the brains of children with autism.What’s more, some have speculated that the tendency of children with autism to experience sensory overstimulation may stem from the inability to tamp down overexcited neurons.

A lack of GABA could lead to just that.The scientists next orally administered high levels of taurine and 5AV to pregnant mice with the autistic children’s microbiomes. When their pups were born, the researchers continued to feed the young the substances until they reached adulthood. Compared with untreated animals, the second-generation mice had significantly fewer behavioral symptoms. Taurine reduced repetitive behavior, as measured by marble burying, increased the level of social interaction, and relieved anxiety. Mice administered 5AV were more active and social.“We healed humans with behavioral problems,” says Krajmalnik-Brown.

€œ[And we] transferred some of those deficits and behaviors to mice — basically the opposite. It’s huge.”Mazmanian hopes to take the next step in the months ahead.“I can flip a switch, turn on a light, I know that switch turns on that light. I don’t know the circuit, I don’t know where the wire is,” Mazmanian says. €œExactly how that’s happening … we just don’t understand that.”This most recent study, by itself, hardly proves that dysregulated microbiomes cause the brain disorder — a point that plenty of other scientists skeptical of Mazmanian’s work are happy to make.“The paper made a big splash, but trying to model psychiatric-related human conditions in mice, in my view, is a little bit of a stretch,” says Sangram Sisodia, a neurobiologist at the University of Chicago who studies the microbiome. €œA mouse with autism?.

€Nor was that the only criticism. Several researchers have suggested that the group didn’t give proper attention to one of their tests ­— one whose results conflicted with their thesis ­— while others found flaws in the statistical methods they used to assess their results. Mazmanian downplays these criticisms, but agrees the work is not yet conclusive.Meanwhile, the ASU trial has also engendered skepticism, mainly due to its tiny sample size, the lack of a control group and the methods by which the children were assessed for autism severity. Krajmalnik-Brown and Adams say they stand by their results, but agree more research is needed. In recent months, they have launched two new studies that will address these issues.Adams insists the work is already changing lives.

€œWe followed up with every one of our 18 participants,” he says, referring to the children who received fecal transplants. €œSure enough, we found that most of the GI benefits had remained. And family after family said their child just slowly, steadily continued making more improvement.” They published the update in Scientific Reports in spring 2019.“I’m not ready to say the case is closed,” says Mazmanian. €œHealthy skepticism is a good thing. I believe the preclinical data, I believe the mouse data.

But there’s a lot of studies that still need to be done.” A Healthy Gut, A New OutlookEthan Woods had GI issues and symptoms of autism until researchers introduced new microbes to his gut. His mother says the treatment changed everything. (Credit. Dana Woods)Prior to his fecal transplant at age 7, Ethan Woods suffered from chronic and severe diarrhea, constipation and cramping, symptoms so extreme that to his mother, Dana, he sounded like “a bit like a woman in labor when he was trying to have a bowel movement.” “It was just awful watching your child go through this,” she says, explaining that when she enrolled her autistic son in the Arizona State study, her “only goal was to fix his gut.”Remarkably, Ethan’s agony began to disappear just a few weeks into the trial. But that was not the most dramatic difference.

Before the transplant, Ethan’s speech was drawn out and slow, his language skills rudimentary. He seemed to live in his own bubble. He had frequent outbursts. For as long as Dana could remember, her mornings with Ethan had been marked by arguing, fighting, pushing and anger. But then one morning, something shocking happened.“He woke me up one morning with his face right in my face with this big smile and he said, ‘Morning, Mom!.

€™â€‰â€ she recalls. €œAnd he was just excited and happy and ready to go about his day with this big smile. It choked me up to the point where I teared up because I had never experienced a happy kid in the morning.”Later, Ethan carried over an iPad and opened an app with a talking cat that repeats back the words children speak aloud. He played back a video recording of himself from just a few weeks earlier.“[He] looks me in the eye and says, ‘Mom, why did I talk like that?. What is wrong with me?.

€™ And as soon as he did that, I caught my breath. I had to compose myself and say, ‘I don’t know. But do you feel better?. Do you feel different?. Why do you think?.

€™â€‰â€Ethan’s communication skills had already begun to improve. Within a year of the study, his speech therapist graduated him from speech therapy because he had met all his goals.“He went from one end of the rainbow all the way to the other end of the rainbow,” she says. €œPrior to the study, I was very afraid. My biggest fear was ‘how is he going to navigate the world when I’m not here?. €™ And I think I have a lot of hope now that he is going to be OK now on his own.”There’s something strange about the female orgasm, something that scientists have been unable to explain.

Biological functions are normally discussed in terms of evolutionary pressure, or reproductive advantage. If a biological trait improves your chances of having more offspring, then it’s more likely to stick around in your species. The male orgasm makes perfect sense — ejaculate contains the genetic material that’s necessary for making babies. But the female orgasm has been harder to nail down. Fertilization doesn’t depend on it, and “fun” isn’t exactly in the pantheon of evolutionary explanations.Researchers that study how the female orgasm relates to reproductive success have two main options — either ask people invasive questions about their most personal moments, or to find a way to stick probes in or on them during said moments.

Neither of these approaches have resulted in the kind of “wet lab” research that’s the gold standard for biological understanding.What we do know, despite widespread cultural discomfort with talking openly about sex and pleasure, is that there appears to be significant sexual dysfunction in American society. Back in 2014, researchers from the Kinsey Institute, the preeminent U.S. Academy for the study of sex and relationships, said as much. In a survey of nearly 3,000 people, they found that men, straight or gay, orgasmed 85 percent of the time during consensual sexual encounters. Lesbian women orgasmed less often, 75 percent of the time, while straight women fared worst with just a 60 percent chance of orgasm.

Other studies have shown that something like 10-15 percent of women experience lifelong anorgasmia, meaning they’ve never experienced orgasm. A further 40 percent of women report some kind of inability to reach orgasm in the past year.The orgasm gap is hard to explain. Some think that it comes down to straight men’s finesse, or lack thereof, citing the difference between straight and lesbian satisfaction. Indeed, it makes sense that knowing your way around the territory would help. But for many couples this isn’t a helpful revelation, since the emotional maturity necessary to teach sexual dexterity is often out of reach.

Shortcut to SatisfactionLuckily, we live in an era of Silicon Valley disruption, which has even started lapping at the shores of sex research. Technologist Liz Klinger is at the forefront of this transition. She and her team have built a platform that lets people become citizen scientists of sex —without ever having to get out from between the sheets.About a decade ago, Klinger’s company, Lioness, released what they billed as the first “smart vibrator,” a sex toy that could actually learn about you. The final product was a far cry from the first prototype, which was much more laboratory object than sex toy.The “test device was this whole mess of wires, with a hard connection. We had to physically send it to our beta testers, who used it and sent it back,” recalls Klinger.

The researchers would download the data collected by the toy’s four sensors — temperature, motion, acceleration and pressure — and compile it into a chart that represented arousal and orgasm, as told through the story of pelvic-floor muscle contractions.It was an immediate success for sex partners who needed ways to talk about pleasure in a more objective way. Klinger recalled that when she got the first beta-test couple on the phone, “the wife was like ‘holy crap, we finally were able to talk about these things that I’ve had a lot of trouble talking about.’ It turned out that she wanted more foreplay, and he didn’t know quite that that meant. He’d spend more time, but it just didn’t match up, you know?. € With the company’s signature offering in hand — a chart of sexual arousal over time — Klinger found that couples could have a conversation “without the subtext of ‘oh, you’re not good enough, or I don’t like you enough,’ on the husband’s part and ‘I’m so tired of talking about this’ on the wife’s part,” she says. The chart “can change people’s perceptions of their own experiences, and how they talk about them with others.”Doing the Deed — For ScienceThis spring, the company has launched a research platform dubbed Lioness 2.0 — a new optional service that, unsurprisingly, their data-obsessed users have greeted with open arms.

Now, instead of simply using the toy to understand themselves better, Lioness owners can opt in to the kinds of hands-on studies that are necessary for a deeper understanding of sex and pleasure. So far, the company is working with Nigeria’s Society for Family Health to study how pleasure changes with menopause across age, race and orientation, as well as with the U.S.’s Center for Genital Health and Education to explore the role of pelvic floor muscles in orgasm.Pani Farvid, a professor of applied psychology at The New School in New York City, has some reservations about the platform. €œI really like what they’re trying to do, but there could be more added to make it a bit more comprehensive. My concern is that there's a misconception that sex is just about the orgasm, that it’s just physiological and that pleasure just has to do with the genitals.” From where she’s sitting, “that’s a very mechanical view of sexuality.” If the Lioness is helping to equalize the orgasm gap, or helping people understand their bodies better, “I think that's great,” says Farvid. €œBut as a critical sexologist, I'm interested in delving deeper into what these practices mean.” If sex is hyper-focused on orgasm, to exclusion of everything else, she cautions that these norms “have real-life negative impacts on people's sex lives and their sense of themselves.”At this point, knee-deep in an era of data collection that was once the sole purview of white-coat-wearing scientists, it’s old news that we need to be careful with what our technology is doing to us.

No tool can serve as a cure-all, even if it comes loaded with a neat app and some space-age sensors. What it can offer, though, is the opportunity to start a conversation, and the chance to take a long, honest look at something about yourself — whether it’s the number of steps you take every day, or the way you want to be touched.Wondering how to keep your glasses from fogging up when your mask is on?. Look no further. If we've learned one thing throughout the COVID-19 pandemic, it's the importance of wearing a mask. Countless studies have shown over the past eight months that wearing a protective barrier over your nose and mouth — whether it's a standard-issue surgical mask or an N95 respirator — can significantly decrease the odds of catching and transmitting disease.

What's more, some research shows that masking up can reduce the severity of an infection if a masked person does contract COVID-19. But while masks are potentially lifesaving, they can be uncomfortable, often changing your breathing patterns and fogging up your glasses when breath escapes through the top of the mask. Among people who choose not to wear a mask to prevent the spread of COVID-19, many cite discomfort as a key reason why.Wesley Wilson, a tumor immunologist in Pennsylvania, knows how annoying it can be when your glasses are fogging up. He says fogging is “definitely a problem” among his hospital colleagues, who need to wear protective goggles and surgical masks while on the job. Fortunately, they've also picked up a few helpful hacks for keeping their vision clear while wearing a mask with glasses.#1.

Use Tape“If you have to keep your mask on for hours, tape works like a charm,” Wilson says. This especially applies to healthcare professionals in his practice who are required to keep their masks on at all times, except during lunch. €œIf you're putting on your mask and taking it off a lot, tape probably isn't practical — but two small pieces of tape on the cheeks keep the mask fitted closer to your face, and the hot air out of your glasses,” he says.#2. Fit the Mask to Your FaceWhile some air leakage is to be expected, wearing a mask that fits securely to your face will prevent glass fogging and filter the virus more effectively since less air is coming in or out. Find surgical masks or N95s that come with a nose bridge, a small, flexible piece of metal or plastic that allows the mask to more closely fit the contours of your face.

Nose bridges can be sewn inside masks or affixed to the front.Read More. Why It Feels Like You Can't Breathe Inside Your Face Mask#3. Adjust Your MaskAccording to the American Academy of Ophthalmology, a minor adjustment in how you wear your mask could be enough to prevent fog as well. Simply pull the mask over your nose and rest your glasses on top of your face mask. As long as the mask is fitted close to your face, this should prevent hot air from slipping out.#4.

Spray Your GlassesA former ice hockey player, Wilson says the protective visor under his helmet would often fog with hot air while he was on the ice during games. Like an ocean diver, he would use de-misting solution or a defogging spray (such as this one) to keep his visor free of fog. The same concept applies to eyeglass fog caused by masking, he says. €œYou can either buy a spray or you can make your own with either shaving cream or soap and water,” says Wilson. €œWiping some shaving cream on your glasses and then wiping it off will coat them with a similar surface-tension altering compound that prevents fog.”With the COVID-19 pandemic showing no signs of stopping, there’s a lot of responsibility on people to wear face masks while out in public.

But even if you do wear a mask, you might not be wearing it properly.   According to CDC guidelines, face masks are meant to cover both the nose and the mouth and fit securely under the chin. While most people who mask-up do wear them correctly, that’s not always the case. Some people prefer to wear their masks pulled down so it only covers their mouth, leaving their nose exposed. But this can defeat a key purpose of wearing a mask. Research from several scientists have demonstrated that the nose is highly vulnerable to COVID-19 infection.  Wearing a mask helps slow the spread of COVID-19 by preventing the transmission of droplets and aerosols that are produced when a person breathes, talks, coughs or sneezes.

The CDC says this is a primary way the virus spreads. Nasal Negligence     In April, an international team of researchers determined that the nose is a key entry point for SARS-CoV-2, the virus that causes COVID-19. Their work, which was published in the journal Nature Medicine, explained that nasal cells in particular contain high levels of the proteins that SARS-CoV-2 attaches to in order to enter the body. The proteins are called ACE2 and TMPRSS2. €¯â€¯â€¯â€¯â€¯â€¯â€¯ To track down the protein pathways for the virus, the researchers examined tissue samples from donors that included lung, eye, nasal, intestinal, heart, kidney and liver cells.

Waradon Sungnak, an immunologist at the Wellcome Sanger Institute and the lead author of the study, explained that the researchers examined the nose cells somewhat as an afterthought, and did not anticipate them to be so important. Because the nose is a main pathway for the virus, Sungnak says it's a possible explanation for why COVID-19 spread so efficiently early in the pandemic.  “The expression of these viral entry factors are high in the nose,” Sungnak says. €œSo, it’s a very easy place for the virus to get in and then once it gets in, a place to replicate. So if there’s any way for you to block that from happening, I think it’s worth it. So, for me, it doesn’t really make sense if you’re putting on a mask, to not be putting a barrier on the nose.” COVID-19 Gateway  Another study, published in Cell in July, pointed to the importance of protecting the nose.

A team tracked how the coronavirus entered the lungs and where the initial site of infection was. The researchers mapped surface receptors in the airways to determine which areas contained the most ACE2 proteins. They determined that the highest concentrations of these proteins are located in are in the nose, instead of the deep lungs as they had anticipated. After exposing tissue samples to SARS-CoV-2, the team determined that the nose was the most fertile infection point of the entire respiratory system. Read next.

Why It Feels Like You Can't Breathe Inside Your Face Mask — and What to Do About ItStudy author Richard Boucher, a pulmonary researcher at the University of North Carolina in Chapel Hill, says that the findings are consistent with the way the nose is used by the body as a filtration device, to both draw in and trap viruses. While in the nose, the viruses can be “micro-aspirated,” or breathed into the lungs through tiny droplets of body fluids. Once in the lungs, the virus replicates itself using the cells there. Boucher says micro-aspiration is more common among older people and those with medical conditions. As a result, these populations are more likely to have viruses like COVID-19 impact their lower respiratory system, which includes airways and lungs.

Younger or healthier people, in contrast, are more likely to have the virus remain in their nasal passages, which means they'll experience milder symptoms such as runny noses or sneezing. Boucher says it’s clear that protecting the nose is extremely important to protecting the lungs and respiratory tract from COVID-19. Based on the findings of his study, wearing a mask underneath the nose is completely ineffective in protecting someone’s respiratory system.    “It may in fact be bad because it gives you a false sense of protection,” Boucher says. €œYou may go into circumstances that are not so wise, but you think you’re protected so you’ll take the risk. So, in one sense it’s the worst of all worlds.

It’s ineffective, but it may deceive you into thinking you’re protected.” .

This story appeared in the November 2020 issue as "Bacteria and the Brain." Subscribe to Discover magazine for more stories like this.It’s not cheap caduet online canada always easy to convince people that the human gut is a sublime and wondrous place worthy of special attention. Sarkis Mazmanian discovered that soon after arriving at Caltech for his first faculty job 14 years ago, when he explained to a local artist what he had in mind for the walls outside his new office.The resulting mural greets visitors to the Mazmanian Lab today. A vaguely psychedelic, 40-foot-long, tube-shaped colon that’s cheap caduet online canada pink, purple and red snakes down the hallway. In a panel next to it, fluorescent yellow and green bacteria explode out of a deeply inflamed section of the intestinal tract, like radioactive lava from outer space.The mural is modest compared with what the scientist has been working on since.

Over the last decade or so, Mazmanian has been a leading proponent of the idea that the flora of the human digestive tract has a far more powerful effect on the human body and cheap caduet online canada mind than we thought — a scientific effort that earned him a $500,000 MacArthur Fellowship “Genius Grant” in 2012. Since then, Mazmanian and a small but growing cadre of fellow microbiologists have amassed a tantalizing body of evidence on the microbiome’s role in all kinds of brain disorders, including schizophrenia, Alzheimer’s disease, Parkinson’s disease and depression.But the results they’ve seen in autism could, in the end, prove the most transformative. Autism affects about 1 in 59 children in the U.S., and involves profound social withdrawal, communication problems, and sometimes anxiety and aggression. The causes of the brain disorder have remained cheap caduet online canada speculative.

Now, Mazmanian and other researchers are finding that autism may be inextricably linked to — or even caused by — irregularities in the gut microbiome.A Biology StoryAt 47, Mazmanian — with his shaved head, flannel shirt and skinny jeans — resembles a young, urban hipster on his way to write at the local café. Originally, literary cheap caduet online canada life was his plan. Born in Lebanon to two Armenian refugees, neither of whom had more than a first-grade education, Mazmanian landed in the class of an energetic high school English teacher in California’s San Fernando Valley, where his family first settled. The teacher recognized his gift for language and encouraged him to pursue a career in literature.

Mazmanian enrolled at UCLA cheap caduet online canada in 1990, planning to major in English.Everything changed when he took his first biology class. Hunched over his new, thick textbook in the library, reading about basic biological concepts like photosynthesis, Mazmanian felt a vast new world opening up to him.Sarkis Mazmanian, shown in front of a mural that celebrates the human gut, is part of a group of microbiologists researching the effects of the digestive tract on a range of disorders. (Credit. Caltech)“For the first time in my life, I wanted to turn the page and see where the story was going to go,” he says.

€œI think I decided that minute to become a scientist.”Mazmanian was most fascinated by the idea that tiny organisms, invisible to the naked eye, could function as powerful, self-contained machines — powerful enough to take over and destroy the human body. After graduating with a degree in microbiology, Mazmanian joined a UCLA infectious diseases lab and began studying bacteria that cause staph infections.As his dissertation defense approached, Mazmanian read a one-page commentary penned by a prominent microbiologist, highlighting the fact that our intestines are teeming with hundreds, if not thousands, of different species of bacteria. But it was still largely unknown what they are and how they affect the human body.When Mazmanian dug further, he found that no one had yet answered what seemed to him to be the most obvious question. Why would the human immune system, designed to attack and destroy foreign invaders, allow hundreds of species of bacteria to live and thrive in our guts unmolested?.

To him, the bacteria’s survival implied that we had evolved to coexist with them. And if that were so, he reasoned, there must be some benefit to both the microbes and the human body — a symbiotic relationship. But what was it?. Gut InvadersMazmanian set out to study the link between gut microbes and the immune system.

As a postdoctoral researcher, he joined the lab of Harvard University infectious disease specialist Dennis Kasper.To start, Mazmanian examined how the immune systems of germ-free mice — lab mice completely protected, starting at birth, from all microbes — differed from those of mice with either few or normal levels of microbes. He expected this initial census would be just a first step in a long and arduous quest for scientific pay dirt. But when he went to examine a printout of his results in the lab, he realized immediately he might already be onto something big. The germ-free mice had a 30 to 40 percent reduction in a specific type of immune cell known as helper T-cells.This colorized close-up of a mouse’s gut reveals the tight relationship between the gut microbe Bacteroides fragilis (red) and the epithelial surface of the colon (blue).

(Credit. Caltech)Since helper T-cells play a key role in coordinating attacks against invading pathogens, the finding suggested that the immune systems of the germ-free mice were far less robust than those found in peers with normal levels of microbes.“That was exciting, right?. € Mazmanian recalls. €œObviously I repeated it and tested it in a number of different ways.

Then I asked the next question. €˜Can I restore the [immune] function in an adult animal?. €™â€‰â€Mazmanian colonized the guts of the immunocompromised, germ-free mice with microbes from standard lab mice. After receiving the fecal transplant, their T-cell counts shot up.

Within a month, their numbers were identical to mice raised outside the germ-free bubble.Resolving to identify the microorganisms causing this transformation, Mazmanian resorted to trial and error. One by one, he added strains of bacteria found in the guts of mice to the guts of germ-free mice.He got nowhere with the first five or six species he examined. Then, simply because it was convenient, he decided to test one more that was readily available in his lab. Mazmanian’s adviser, Kasper, had been studying a gut microbe called Bacteroides fragilis.

When Mazmanian implanted one of Kasper’s specimens into the gut of his germ-free mice, the results were dramatic. The T-cell numbers spiked to normal. Eventually, Mazmanian demonstrated he could reproduce this effect simply by adding a single molecule that these bacteria produce, called polysaccharide A, to their guts.“There was no logic in the choice whatsoever,” Mazmanian recalls. €œ[B.

Fragilis] was available, it came from the gut.” In other words, he got lucky.Mazmanian dug deeper and discovered that the biggest impact B. Fragilis had was on the population of a subtype of helper T-cells called regulatory, or suppressor, T-cells. These cells play a key role in preventing the immune system from attacking its host body, protecting against autoimmune or inflammatory diseases. It was the first time any scientist had demonstrated that a single compound from a single microbe could reverse a specific problem with the immune system.To Mazmanian, the finding, published in 2005 in the journal Cell, alluded to new approaches to treating a wide array of autoimmune, inflammatory and allergic disorders.

What if it were possible to help a faulty immune system by tweaking a patient’s microbiome?. It was with this exploration in mind that he arrived in Pasadena in 2006 to set up his lab at Caltech.A Convenient CollaborationA few years later, Mazmanian was having lunch on campus with neuroscientist and colleague Paul Patterson. Patterson had been preoccupied with a mystery that had, for years, confounded those studying autism in humans. When pregnant mothers have a severe infection in the second trimester, their babies are much more likely to develop autism.As Mazmanian tells it, Patterson was a man of few words, and at lunch Mazmanian was “going on and on” about his own work.“You know,” Patterson interjected thoughtfully, “I think kids with autism have GI issues.”Patterson recalled reading that something like 60 percent of children with autism had some form of clinical GI problem, such as bloating, constipation, flatulence or diarrhea.

Was it possible, he wondered, that there was a microbiome connection?. As they talked, Mazmanian’s excitement grew.A few years earlier, Patterson had discovered that when he exposed pregnant mice to pathogens like the influenza virus, they gave birth to pups that grew up more likely to be startled by loud noises, to shy away from social contact and to groom themselves repetitively — symptoms that resemble those of autism. Patterson was in the process of comparing the brains of these autism-mimicking mice with their neurotypical cousins to see if he could detect any differences that might explain how the maternal immune system was somehow interfering with the pups’ brain development.Mazmanian had a suggestion. The next time Patterson sacrificed one of his autistic mice to study their brains, what if he set the intestines aside for his colleague down the hall?.

When the guts arrived in Mazmanian’s lab, he found that the intestines of the neurotypical mice looked normal. But the guts of the autism-mimicking offspring were almost uniformly inflamed. Could it be that the microbiome was the cause of this inflammation?. And could that, in turn, be somehow connected to the behavioral symptoms?.

Throughout the winter and spring of 2012, Mazmanian and Patterson continued their conversation. Mazmanian found distinct differences in the microbiomes of the mice. And, they noticed, the mice with the features of autism had leaky gut syndrome, an increased permeability of the gut lining that can allow pathogens and allergens to leach out. This condition had also been reported in children with autism.So Mazmanian and Patterson turned their attention outside the gut.

They took blood samples to see if any gut microbes, or the compounds they produce, were circulating in the rest of the body. They homed in on one molecule in particular, called 4-ethylphenyl sulfate, which was roughly 45 times as abundant in the mice that had symptoms of autism. And it looked familiar. Structurally, it was almost identical to a molecule recently found to be significantly elevated in human children with autism.It was enough to take the next step.

Every day for three weeks, Mazmanian injected the molecule, harvested from the mice with autism-like symptoms, directly into the bloodstream of 5-week-old normal lab mice (the age at which the autistic mice normally developed leaky gut). Then Mazmanian and his team gave them a series of behavioral tests. The mice were far more easily startled and were less comfortable in large empty spaces than their untreated peers, indications of an increase in anxiety-related behaviors commonly seen in the mice with autism-like symptoms. The researchers published their results in Cell in 2013.Though surprising, the data made sense in some ways.

Many drug companies rely on small-molecule drugs that can be taken orally, but still manage to cross the blood-brain barrier and affect behavior. It seemed entirely possible that small molecules, created by bacteria in the gut, could enter the bloodstream and reach the brain. And they don’t even have to leak out of the gut to do so.Of Mice and MenPatterson died in 2014, at age 70, just six months after the publication of the duo’s groundbreaking Cell paper. Around the same time, a series of parallel experiments in a clinic hundreds of miles away was already paving the way forward.

While Patterson and Mazmanian had been working in mice, Rosa Krajmalnik-Brown, a microbiologist at Arizona State University, had teamed up with Jim Adams, who directs the university’s autism and Asperger’s research program, to study humans.The researchers were conducting a detailed analysis of the microbiome of human autism patients and found that the bacteria were far less diverse in the children with autism. Notably, several important species involved in the digestion of carbohydrates were severely depleted.Krajmalnik-Brown and Adams launched a preliminary trial to test the effects of fecal transplants on 18 children between the ages of 7 and 16 with severe autism, who also had severe GI issues. The researchers administered powerful antibiotics to kill off the microbiomes of the children and followed them with a bowel cleanse. They then replaced the microbes with transplanted flora taken from the guts of healthy neurotypical adult volunteers.The results were better than anyone could have expected.

The procedure resulted in a large reduction in GI symptoms and increased the diversity of bacteria in the children’s guts. But more significantly, their neurological symptoms were reduced. At the onset of the study in 2017, an independent evaluator found 83 percent of participants had severe autism. Two years after the initial trial, only 17 percent were rated as severely autistic.

And 44 percent were no longer on the autism scale.“[My child] did a complete 180,” says Dana Woods, whose then-7-year-old son Ethan enrolled in the initial study five years ago. €œHis ability to communicate is so much different now. He’s just so much more present. He’s so much more aware.

He’s no longer in occupational therapy. He’s no longer in speech therapy. After the study, he tested two points away from a neurotypical child.”In their first report on the trial in 2017, the team highlighted a number of distinct changes in the microbiome after the transplants, in particular a surge in the populations of three types of bacteria. Among them was a four-fold increase in Bifidobacterium, a probiotic organism that seems to play a key role in the maintenance of a healthy gut.But figuring out what was happening on a cellular level — to really look inside some guts — would require another vehicle.

The ASU team needed Mazmanian’s mice.“At the end of the day, what we care about is healing people and how the microbiome affects people,” explains Krajmalnik-Brown. €œThat’s why we work with people. But with mice you can do things that are more mechanistic.”The Great Mouse Detective(Credit. Caltech)Together, Krajmalnik-Brown, Mazmanian and their collaborators would uncover some tantalizing new insights that go a long way to solving the mystery.

In May 2019, the team published another high-profile paper in Cell, after they transplanted stool samples from Krajmalnik-Brown’s severely autistic patients into the guts of Mazmanian’s germ-free mice. The offspring of these mice showed the autism-like symptoms, such as repetitive and compulsive behavior.This time, the team dug even deeper into the biochemical processes playing out in the brain, looking not just at behavior but at the chemicals involved in creating it. The mice that developed autism-like behaviors had measurably lower levels of two substances called taurine and 5-aminovaleric acid (5AV). When they dug into the literature, the team learned that these two substances are known to mimic activity of a key signaling agent in the brain called gamma-aminobutyric acid (GABA) — a neurotransmitter that other studies have found is deficient in the brains of children with autism.What’s more, some have speculated that the tendency of children with autism to experience sensory overstimulation may stem from the inability to tamp down overexcited neurons.

A lack of GABA could lead to just that.The scientists next orally administered high levels of taurine and 5AV to pregnant mice with the autistic children’s microbiomes. When their pups were born, the researchers continued to feed the young the substances until they reached adulthood. Compared with untreated animals, the second-generation mice had significantly fewer behavioral symptoms. Taurine reduced repetitive behavior, as measured by marble burying, increased the level of social interaction, and relieved anxiety.

Mice administered 5AV were more active and social.“We healed humans with behavioral problems,” says Krajmalnik-Brown. €œ[And we] transferred some of those deficits and behaviors to mice — basically the opposite. It’s huge.”Mazmanian hopes to take the next step in the months ahead.“I can flip a switch, turn on a light, I know that switch turns on that light. I don’t know the circuit, I don’t know where the wire is,” Mazmanian says.

€œExactly how that’s happening … we just don’t understand that.”This most recent study, by itself, hardly proves that dysregulated microbiomes cause the brain disorder — a point that plenty of other scientists skeptical of Mazmanian’s work are happy to make.“The paper made a big splash, but trying to model psychiatric-related human conditions in mice, in my view, is a little bit of a stretch,” says Sangram Sisodia, a neurobiologist at the University of Chicago who studies the microbiome. €œA mouse with autism?. €Nor was that the only criticism. Several researchers have suggested that the group didn’t give proper attention to one of their tests ­— one whose results conflicted with their thesis ­— while others found flaws in the statistical methods they used to assess their results.

Mazmanian downplays these criticisms, but agrees the work is not yet conclusive.Meanwhile, the ASU trial has also engendered skepticism, mainly due to its tiny sample size, the lack of a control group and the methods by which the children were assessed for autism severity. Krajmalnik-Brown and Adams say they stand by their results, but agree more research is needed. In recent months, they have launched two new studies that will address these issues.Adams insists the work is already changing lives. €œWe followed up with every one of our 18 participants,” he says, referring to the children who received fecal transplants.

€œSure enough, we found that most of the GI benefits had remained. And family after family said their child just slowly, steadily continued making more improvement.” They published the update in Scientific Reports in spring 2019.“I’m not ready to say the case is closed,” says Mazmanian. €œHealthy skepticism is a good thing. I believe the preclinical data, I believe the mouse data.

But there’s a lot of studies that still need to be done.” A Healthy Gut, A New OutlookEthan Woods had GI issues and symptoms of autism until researchers introduced new microbes to his gut. His mother says the treatment changed everything. (Credit. Dana Woods)Prior to his fecal transplant at age 7, Ethan Woods suffered from chronic and severe diarrhea, constipation and cramping, symptoms so extreme that to his mother, Dana, he sounded like “a bit like a woman in labor when he was trying to have a bowel movement.” “It was just awful watching your child go through this,” she says, explaining that when she enrolled her autistic son in the Arizona State study, her “only goal was to fix his gut.”Remarkably, Ethan’s agony began to disappear just a few weeks into the trial.

But that was not the most dramatic difference. Before the transplant, Ethan’s speech was drawn out and slow, his language skills rudimentary. He seemed to live in his own bubble. He had frequent outbursts.

For as long as Dana could remember, her mornings with Ethan had been marked by arguing, fighting, pushing and anger. But then one morning, something shocking happened.“He woke me up one morning with his face right in my face with this big smile and he said, ‘Morning, Mom!. €™â€‰â€ she recalls. €œAnd he was just excited and happy and ready to go about his day with this big smile.

It choked me up to the point where I teared up because I had never experienced a happy kid in the morning.”Later, Ethan carried over an iPad and opened an app with a talking cat that repeats back the words children speak aloud. He played back a video recording of himself from just a few weeks earlier.“[He] looks me in the eye and says, ‘Mom, why did I talk like that?. What is wrong with me?. €™ And as soon as he did that, I caught my breath.

I had to compose myself and say, ‘I don’t know. But do you feel better?. Do you feel different?. Why do you think?.

€™â€‰â€Ethan’s communication skills had already begun to improve. Within a year of the study, his speech therapist graduated him from speech therapy because he had met all his goals.“He went from one end of the rainbow all the way to the other end of the rainbow,” she says. €œPrior to the study, I was very afraid. My biggest fear was ‘how is he going to navigate the world when I’m not here?.

€™ And I think I have a lot of hope now that he is going to be OK now on his own.”There’s something strange about the female orgasm, something that scientists have been unable to explain. Biological functions are normally discussed in terms of evolutionary pressure, or reproductive advantage. If a biological trait improves your chances of having more offspring, then it’s more likely to stick around in your species. The male orgasm makes perfect sense — ejaculate contains the genetic material that’s necessary for making babies.

But the female orgasm has been harder to nail down. Fertilization doesn’t depend on it, and “fun” isn’t exactly in the pantheon of evolutionary explanations.Researchers that study how the female orgasm relates to reproductive success have two main options — either ask people invasive questions about their most personal moments, or to find a way to stick probes in or on them during said moments. Neither of these approaches have resulted in the kind of “wet lab” research that’s the gold standard for biological understanding.What we do know, despite widespread cultural discomfort with talking openly about sex and pleasure, is that there appears to be significant sexual dysfunction in American society. Back in 2014, researchers from the Kinsey Institute, the preeminent U.S.

Academy for the study of sex and relationships, said as much. In a survey of nearly 3,000 people, they found that men, straight or gay, orgasmed 85 percent of the time during consensual sexual encounters. Lesbian women orgasmed less often, 75 percent of the time, while straight women fared worst with just a 60 percent chance of orgasm. Other studies have shown that something like 10-15 percent of women experience lifelong anorgasmia, meaning they’ve never experienced orgasm.

A further 40 percent of women report some kind of inability to reach orgasm in the past year.The orgasm gap is hard to explain. Some think that it comes down to straight men’s finesse, or lack thereof, citing the difference between straight and lesbian satisfaction. Indeed, it makes sense that knowing your way around the territory would help. But for many couples this isn’t a helpful revelation, since the emotional maturity necessary to teach sexual dexterity is often out of reach.

Shortcut to SatisfactionLuckily, we live in an era of Silicon Valley disruption, which has even started lapping at the shores of sex research. Technologist Liz Klinger is at the forefront of this transition. She and her team have built a platform that lets people become citizen scientists of sex —without ever having to get out from between the sheets.About a decade ago, Klinger’s company, Lioness, released what they billed as the first “smart vibrator,” a sex toy that could actually learn about you. The final product was a far cry from the first prototype, which was much more laboratory object than sex toy.The “test device was this whole mess of wires, with a hard connection.

We had to physically send it to our beta testers, who used it and sent it back,” recalls Klinger. The researchers would download the data collected by the toy’s four sensors — temperature, motion, acceleration and pressure — and compile it into a chart that represented arousal and orgasm, as told through the story of pelvic-floor muscle contractions.It was an immediate success for sex partners who needed ways to talk about pleasure in a more objective way. Klinger recalled that when she got the first beta-test couple on the phone, “the wife was like ‘holy crap, we finally were able to talk about these things that I’ve had a lot of trouble talking about.’ It turned out that she wanted more foreplay, and he didn’t know quite that that meant. He’d spend more time, but it just didn’t match up, you know?.

€ With the company’s signature offering in hand — a chart of sexual arousal over time — Klinger found that couples could have a conversation “without the subtext of ‘oh, you’re not good enough, or I don’t like you enough,’ on the husband’s part and ‘I’m so tired of talking about this’ on the wife’s part,” she says. The chart “can change people’s perceptions of their own experiences, and how they talk about them with others.”Doing the Deed — For ScienceThis spring, the company has launched a research platform dubbed Lioness 2.0 — a new optional service that, unsurprisingly, their data-obsessed users have greeted with open arms. Now, instead of simply using the toy to understand themselves better, Lioness owners can opt in to the kinds of hands-on studies that are necessary for a deeper understanding of sex and pleasure. So far, the company is working with Nigeria’s Society for Family Health to study how pleasure changes with menopause across age, race and orientation, as well as with the U.S.’s Center for Genital Health and Education to explore the role of pelvic floor muscles in orgasm.Pani Farvid, a professor of applied psychology at The New School in New York City, has some reservations about the platform.

€œI really like what they’re trying to do, but there could be more added to make it a bit more comprehensive. My concern is that there's a misconception that sex is just about the orgasm, that it’s just physiological and that pleasure just has to do with the genitals.” From where she’s sitting, “that’s a very mechanical view of sexuality.” If the Lioness is helping to equalize the orgasm gap, or helping people understand their bodies better, “I think that's great,” says Farvid. €œBut as a critical sexologist, I'm interested in delving deeper into what these practices mean.” If sex is hyper-focused on orgasm, to exclusion of everything else, she cautions that these norms “have real-life negative impacts on people's sex lives and their sense of themselves.”At this point, knee-deep in an era of data collection that was once the sole purview of white-coat-wearing scientists, it’s old news that we need to be careful with what our technology is doing to us. No tool can serve as a cure-all, even if it comes loaded with a neat app and some space-age sensors.

What it can offer, though, is the opportunity to start a conversation, and the chance to take a long, honest look at something about yourself — whether it’s the number of steps you take every day, or the way you want to be touched.Wondering how to keep your glasses from fogging up when your mask is on?. Look no further. If we've learned one thing throughout the COVID-19 pandemic, it's the importance of wearing a mask. Countless studies have shown over the past eight months that wearing a protective barrier over your nose and mouth — whether it's a standard-issue surgical mask or an N95 respirator — can significantly decrease the odds of catching and transmitting disease.

What's more, some research shows that masking up can reduce the severity of an infection if a masked person does contract COVID-19. But while masks are potentially lifesaving, they can be uncomfortable, often changing your breathing patterns and fogging up your glasses when breath escapes through the top of the mask. Among people who choose not to wear a mask to prevent the spread of COVID-19, many cite discomfort as a key reason why.Wesley Wilson, a tumor immunologist in Pennsylvania, knows how annoying it can be when your glasses are fogging up. He says fogging is “definitely a problem” among his hospital colleagues, who need to wear protective goggles and surgical masks while on the job.

Fortunately, they've also picked up a few helpful hacks for keeping their vision clear while wearing a mask with glasses.#1. Use Tape“If you have to keep your mask on for hours, tape works like a charm,” Wilson says. This especially applies to healthcare professionals in his practice who are required to keep their masks on at all times, except during lunch. €œIf you're putting on your mask and taking it off a lot, tape probably isn't practical — but two small pieces of tape on the cheeks keep the mask fitted closer to your face, and the hot air out of your glasses,” he says.#2.

Fit the Mask to Your FaceWhile some air leakage is to be expected, wearing a mask that fits securely to your face will prevent glass fogging and filter the virus more effectively since less air is coming in or out. Find surgical masks or N95s that come with a nose bridge, a small, flexible piece of metal or plastic that allows the mask to more closely fit the contours of your face. Nose bridges can be sewn inside masks or affixed to the front.Read More. Why It Feels Like You Can't Breathe Inside Your Face Mask#3.

Adjust Your MaskAccording to the American Academy of Ophthalmology, a minor adjustment in how you wear your mask could be enough to prevent fog as well. Simply pull the mask over your nose and rest your glasses on top of your face mask. As long as the mask is fitted close to your face, this should prevent hot air from slipping out.#4. Spray Your GlassesA former ice hockey player, Wilson says the protective visor under his helmet would often fog with hot air while he was on the ice during games.

Like an ocean diver, he would use de-misting solution or a defogging spray (such as this one) to keep his visor free of fog. The same concept applies to eyeglass fog caused by masking, he says. €œYou can either buy a spray or you can make your own with either shaving cream or soap and water,” says Wilson. €œWiping some shaving cream on your glasses and then wiping it off will coat them with a similar surface-tension altering compound that prevents fog.”With the COVID-19 pandemic showing no signs of stopping, there’s a lot of responsibility on people to wear face masks while out in public.

But even if you do wear a mask, you might not be wearing it properly.   According to CDC guidelines, face masks are meant to cover both the nose and the mouth and fit securely under the chin. While most people who mask-up do wear them correctly, that’s not always the case. Some people prefer to wear their masks pulled down so it only covers their mouth, leaving their nose exposed. But this can defeat a key purpose of wearing a mask.

Research from several scientists have demonstrated that the nose is highly vulnerable to COVID-19 infection.  Wearing a mask helps slow the spread of COVID-19 by preventing the transmission of droplets and aerosols that are produced when a person breathes, talks, coughs or sneezes. The CDC says this is a primary way the virus spreads. Nasal Negligence     In April, an international team of researchers determined that the nose is a key entry point for SARS-CoV-2, the virus that causes COVID-19. Their work, which was published in the journal Nature Medicine, explained that nasal cells in particular contain high levels of the proteins that SARS-CoV-2 attaches to in order to enter the body.

The proteins are called ACE2 and TMPRSS2. €¯â€¯â€¯â€¯â€¯â€¯â€¯ To track down the protein pathways for the virus, the researchers examined tissue samples from donors that included lung, eye, nasal, intestinal, heart, kidney and liver cells. Waradon Sungnak, an immunologist at the Wellcome Sanger Institute and the lead author of the study, explained that the researchers examined the nose cells somewhat as an afterthought, and did not anticipate them to be so important. Because the nose is a main pathway for the virus, Sungnak says it's a possible explanation for why COVID-19 spread so efficiently early in the pandemic.  “The expression of these viral entry factors are high in the nose,” Sungnak says.

€œSo, it’s a very easy place for the virus to get in and then once it gets in, a place to replicate. So if there’s any way for you to block that from happening, I think it’s worth it. So, for me, it doesn’t really make sense if you’re putting on a mask, to not be putting a barrier on the nose.” COVID-19 Gateway  Another study, published in Cell in July, pointed to the importance of protecting the nose. A team tracked how the coronavirus entered the lungs and where the initial site of infection was.

The researchers mapped surface receptors in the airways to determine which areas contained the most ACE2 proteins. They determined that the highest concentrations of these proteins are located in are in the nose, instead of the deep lungs as they had anticipated. After exposing tissue samples to SARS-CoV-2, the team determined that the nose was the most fertile infection point of the entire respiratory system. Read next.

Why It Feels Like You Can't Breathe Inside Your Face Mask — and What to Do About ItStudy author Richard Boucher, a pulmonary researcher at the University of North Carolina in Chapel Hill, says that the findings are consistent with the way the nose is used by the body as a filtration device, to both draw in and trap viruses. While in the nose, the viruses can be “micro-aspirated,” or breathed into the lungs through tiny droplets of body fluids. Once in the lungs, the virus replicates itself using the cells there. Boucher says micro-aspiration is more common among older people and those with medical conditions.

As a result, these populations are more likely to have viruses like COVID-19 impact their lower respiratory system, which includes airways and lungs. Younger or healthier people, in contrast, are more likely to have the virus remain in their nasal passages, which means they'll experience milder symptoms such as runny noses or sneezing. Boucher says it’s clear that protecting the nose is extremely important to protecting the lungs and respiratory tract from COVID-19. Based on the findings of his study, wearing a mask underneath the nose is completely ineffective in protecting someone’s respiratory system.    “It may in fact be bad because it gives you a false sense of protection,” Boucher says.

€œYou may go into circumstances that are not so wise, but you think you’re protected so you’ll take the risk. So, in one sense it’s the worst of all worlds. It’s ineffective, but it may deceive you into thinking you’re protected.” .

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Imagine being infected https://www.cityreal.lv/how-much-does-generic-caduet-cost/ with a deadly virus that buy caduet usa makes you impervious to pain. By the buy caduet usa time you realize you are infected, it’s already too late. You have spread it far and wide. Recent findings in my lab suggest buy caduet usa that this scenario may be one reason that people infected with SARS-CoV-2, the virus causing COVID-19, may be spreading the disease without knowing it.Most accounts to date have focused on how the virus invades cells via the ACE2 protein on the surface of many cells.

But recent studies, which have not yet been peer-reviewed, suggest there is another route to infecting the cell that enables it to infect the nervous system. This led my research group to uncover a link buy caduet usa between a particular cellular protein and pain – an interaction that is disrupted by the coronavirus. Our research has now been peer-reviewed and will be published in the journal PAIN.I am a scientist who studies how proteins on cells trigger pain signals that are transmitted through the body to the brain. When these proteins are active, the nerve cells are talking to buy caduet usa each other.

This conversation occurs at deafening levels in chronic pain. So by studying what causes the excitability of nerve cells to change, we can begin to unravel buy caduet usa how chronic pain becomes established. This also allows us to design ways to mute this conversation to blunt or stop chronic pain.My laboratory has a longstanding interest in designing nonopioid-based alternatives for pain management.Linking SARS-CoV-2 and painYou might be wondering how my lab began to probe the connection between SARS-CoV-2 and pain. We were inspired by two preliminary reports that appeared on the preprint server BioRxiv that showed that the infamous spike proteins on the surface of the SARS-CoV-2 virus bound to a protein called buy caduet usa neuropilin-1.

This means that the virus can also use this protein to invade nerve cells as well as through the ACE2 protein.For the past year, some six months before the pandemic took hold, my colleagues and I had been studying the role of neuropilin-1 in the context of pain perception. Because neuropilin-1, like the ACE2 receptor, allowed spike to enter the cells, we wondered if this alternate gateway buy caduet usa could also be related to pain.Under normal circumstances, the neuropilin-1 protein controls the growth of blood vessels, and as well as the growth and survival of neurons.However, when neuropilin-1 binds to a naturally occurring protein called called Vascular endothelial growth factor A (VEGF-A), this triggers pain signals. This signal is transmitted via the spinal cord into higher brain centers to cause the sensation we all know as pain.Staring at this jigsaw puzzle – neuropilin-1 and VEGF-A and neuropilin and spike – we wondered if there was a link between spike and pain.Previous research has shown a link between VEGF-A and pain. For people with osteoarthritis, for instance, studies have shown that increased activity of the VEGF gene in fluids lubricating joints, like the knee, is associated with higher pain scores.Although activity of the neuropilin-1 gene is higher in biological samples from COVID-19 patients compared to healthy controls and activity of the neuropilin-1 gene is increased in pain-sensing neurons in an animal model of chronic pain, the role of neuropilin-1 in pain has never been explored until now.In in vitro studies done in my lab using nerve cells, we showed that when spike binds to neuropilin-1 it decreases pain signaling, which suggests that in a living animal it would also have a pain-dulling effect.When the buy caduet usa spike protein binds to the neuropilin-1 protein, it blocks the VEGF-A protein from binding and thus hijack’s a cell’s pain circuitry.

This binding suppresses the excitability of pain neurons, how much does caduet cost per pill leading to lower sensitivity to pain.Crystal structure of neuropilin-1 b1 domain (white surface with binding site in red) showing binding of VEGF-A (left), spike protein (middle), and the neuropilin-1 inhibitor EG00229 (right). (Credit. Dr. Samantha Perez-Miller, CC BY-SA)From the COVID-19 fog a new pain target emergesIf our finding that the new coronavirus is attacking cells through a protein associated with pain and disabling the protein can be confirmed in humans, it may provide a new pathway for drug development to treat COVID-19.A small molecule, called EG00229, targeting neuropilin-1 had been reported in a 2018 study.

This molecule binds to the same region of the neuropilin-1 protein as the viral spike protein and VEGF-A. So I and my colleagues asked if this molecule was able to block pain. It did, during pain simulations in rats. Our data reaffirmed the notion of neuropilin-1 as a new player in pain signaling.There is precedence for targeting the neuropilin-1 protein for cancer treatment.

For example, a Phase 1a clinical trial of an antibody called MNRP1685A (known under the product name Vesencumab) that recognizes and binds to neuropilin-1 and blocks VEGF-binding. This was mostly well tolerated in cancer patients, but it caused pain rather than blocking it.Our studies identify a different approach because we targeted blocking the pain-triggering VEGF-A protein, which then resulted in pain relief. So our preclinical work described here provides a rationale for targeting the VEGF-A/NRP-1 pro-pain signaling system in future clinical trials.Analysis of the structure of the neuropilin-1 receptor protein may allow design of drugs targeting this critical site which also controls axon growth, cell survival – in addition to pain relief.For instance, these neuropilin-1 receptor targeted drugs could potentially block viral infection. The testing of several candidate compounds, some of them on the FDA’s generally regarded as safe list, is currently underway by my group.Sneaky virus, fooling people into believing that they do not have COVID-19.

But, ironically, it may be gifting us with the knowledge of a new protein, critical for pain. Two roads emerge in the forest ahead. (1) block neuropilin-1 to limit SARS-CoV-2 entry, and (2) block neuropilin-1 to block pain.Rajesh Khanna is a Professor of Pharmacology, University of Arizona. This article originally appeared on The Conversation under a Creative Commons license.

Imagine being infected with a deadly virus that makes you impervious to cheap caduet online canada pain. By the cheap caduet online canada time you realize you are infected, it’s already too late. You have spread it far and wide.

Recent findings in my lab suggest that this scenario may be one reason that people infected with SARS-CoV-2, the virus causing COVID-19, may be spreading the disease without knowing it.Most accounts to date have focused on how cheap caduet online canada the virus invades cells via the ACE2 protein on the surface of many cells. But recent studies, which have not yet been peer-reviewed, suggest there is another route to infecting the cell that enables it to infect the nervous system. This led my research group to uncover a link between a particular cellular protein and pain – cheap caduet online canada an interaction that is disrupted by the coronavirus.

Our research has now been peer-reviewed and will be published in the journal PAIN.I am a scientist who studies how proteins on cells trigger pain signals that are transmitted through the body to the brain. When these cheap caduet online canada proteins are active, the nerve cells are talking to each other. This conversation occurs at deafening levels in chronic pain.

So by studying what causes the cheap caduet online canada excitability of nerve cells to change, we can begin to unravel how chronic pain becomes established. This also allows us to design ways to mute this conversation to blunt or stop chronic pain.My laboratory has a longstanding interest in designing nonopioid-based alternatives for pain management.Linking SARS-CoV-2 and painYou might be wondering how my lab began to probe the connection between SARS-CoV-2 and pain. We were inspired by two preliminary reports that appeared on the preprint server BioRxiv that showed that the infamous spike proteins on the cheap caduet online canada surface of the SARS-CoV-2 virus bound to a protein called neuropilin-1.

This means that the virus can also use this protein to invade nerve cells as well as through the ACE2 protein.For the past year, some six months before the pandemic took hold, my colleagues and I had been studying the role of neuropilin-1 in the context of pain perception. Because neuropilin-1, cheap caduet online canada like the ACE2 receptor, allowed spike to enter the cells, we wondered if this alternate gateway could also be related to pain.Under normal circumstances, the neuropilin-1 protein controls the growth of blood vessels, and as well as the growth and survival of neurons.However, when neuropilin-1 binds to a naturally occurring protein called called Vascular endothelial growth factor A (VEGF-A), this triggers pain signals. This signal is transmitted via the spinal cord into higher brain centers to cause the sensation we all know as pain.Staring at this jigsaw puzzle – neuropilin-1 and VEGF-A and neuropilin and spike – we wondered if there was a link between spike and pain.Previous research has shown a link between VEGF-A and pain.

For people with osteoarthritis, for instance, studies have shown that increased activity of the VEGF gene in fluids lubricating joints, like the knee, is associated with higher pain scores.Although activity of the neuropilin-1 gene is higher in biological samples from COVID-19 patients compared to healthy controls and activity of the neuropilin-1 gene is increased in pain-sensing neurons in an animal model of chronic pain, the role of neuropilin-1 in pain has never been explored until now.In in vitro studies cheap caduet online canada done in my lab using nerve cells, we showed that when spike binds to neuropilin-1 it decreases pain signaling, which suggests that in a living animal it would also have a pain-dulling effect.When the spike protein binds to the neuropilin-1 protein, it blocks the VEGF-A protein from binding and thus hijack’s a cell’s pain circuitry. This binding suppresses the excitability of pain neurons, leading to lower sensitivity to pain.Crystal structure of neuropilin-1 b1 domain (white surface with binding site in red) showing binding of VEGF-A (left), spike protein (middle), and the neuropilin-1 inhibitor EG00229 (right). (Credit.

Dr. Samantha Perez-Miller, CC BY-SA)From the COVID-19 fog a new pain target emergesIf our finding that the new coronavirus is attacking cells through a protein associated with pain and disabling the protein can be confirmed in humans, it may provide a new pathway for drug development to treat COVID-19.A small molecule, called EG00229, targeting neuropilin-1 had been reported in a 2018 study. This molecule binds to the same region of the neuropilin-1 protein as the viral spike protein and VEGF-A.

So I and my colleagues asked if this molecule was able to block pain. It did, during pain simulations in rats. Our data reaffirmed the notion of neuropilin-1 as a new player in pain signaling.There is precedence for targeting the neuropilin-1 protein for cancer treatment.

For example, a Phase 1a clinical trial of an antibody called MNRP1685A (known under the product name Vesencumab) that recognizes and binds to neuropilin-1 and blocks VEGF-binding. This was mostly well tolerated in cancer patients, but it caused pain rather than blocking it.Our studies identify a different approach because we targeted blocking the pain-triggering VEGF-A protein, which then resulted in pain relief. So our preclinical work described here provides a rationale for targeting the VEGF-A/NRP-1 pro-pain signaling system in future clinical trials.Analysis of the structure of the neuropilin-1 receptor protein may allow design of drugs targeting this critical site which also controls axon growth, cell survival – in addition to pain relief.For instance, these neuropilin-1 receptor targeted drugs could potentially block viral infection.

The testing of several candidate compounds, some of them on the FDA’s generally regarded as safe list, is currently underway by my group.Sneaky virus, fooling people into believing that they do not have COVID-19. But, ironically, it may be gifting us with the knowledge of a new protein, critical for pain. Two roads emerge in the forest ahead.

(1) block neuropilin-1 to limit SARS-CoV-2 entry, and (2) block neuropilin-1 to block pain.Rajesh Khanna is a Professor of Pharmacology, University of Arizona. This article originally appeared on The Conversation under a Creative Commons license. Read the original here..

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€‹â€‹NSW has reported two new cases of locally transmitted caduet COVID-19 in the 24 hours to 8pm last night.Three cases in overseas travellers in hotel quarantine were also diagnosed, bringing the total number of cases in NSW to 4,158. Confirmed cases (including interstate residents caduet in NSW health care facilities) 4,158 Deaths (in NSW from confirmed cases)​ 55 Total tests carried out 2,917,454 There were 7,401 tests reported to 8pm last night, compared with 6,952 in the previous 24 hours.Anyone with symptoms of a cold should assume it’s COVID-19 until proven otherwise by a test. Get tested on the day you get those symptoms – don’t wait to see if they go away. Of the new cases to 8pm last night caduet.

Three were acquired overseas and are now in hotel quarantine Two were locally acquired, both linked to known cases and clusters One locally acquired case is a household contact of a previously confirmed case linked to the Liverpool private clinic cluster, which now has a total of 12 cases. The other locally acquired case caduet is a close contact of a confirmed case linked to someone who attended the childcare centre at Oran Park.NSW Health is treating 64 COVID-19 cases, with one patient in intensive care. This patient does not require ventilation. Ninety-four per cent of cases being treated by NSW Health are in non-acute, out-of-hospital care.NSW is at a critical point, and the only way to find undiagnosed cases and prevent further caduet transmission is to increase testing.NSW Health particularly thanks the Oran Park community for its brilliant response to our calls for increased testing.

From 1 August to 10 October 2020, the average number of COVID-19 tests conducted each week among residents of Oran Park was 227, but during the week ending 17 October 2020, the number of tests increased almost four-fold to 895.However, increases in surrounding suburbs were far more modest and NSW Health continues to appeal to the community in South Western Sydney to come forward for testing right away if anyone has even the mildest of symptoms like a runny nose or scratchy throat, cough, fever or other symptoms that could be COVID-19. This is also particularly important in Western Sydney and South Eastern Sydney, where there have also been locally transmitted cases recently.There are caduet more than 300 COVID-19 testing locations across NSW. To find your nearest clinic visit COVID-19 testing clinics or contact your GP.COVID-19 is still likely circulating in the community and we must all be vigilant. To help caduet stop the spread of COVID-19.

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NSW is at a critical point, and the only way to find new cases and prevent further transmission is to increase testing.NSW Health is appealing to the community to come forward for testing right away if anyone has even the mildest of symptoms like a runny nose or scratchy throat, cough, fever or other symptoms that could be COVID-19. This is particularly important in caduet South Western Sydney, Western Sydney and South Eastern Sydney where there have been recent locally transmitted cases.Everyone plays an important role in helping to contain the pandemic by getting tested quickly and following social distancing rules. Get tested on the day you get symptoms – don’t wait to see if they go away. Assume it’s COVID-19 until proven otherwise by a test, and remember there is no limit on how many tests you can have.Testing is quick, free, and easy and most caduet people receive their test result within 24 hours.

If you have even the mildest of symptoms like a runny nose or scratchy throat, cough, fever or other symptoms that could be COVID-19, please come forward for testing right away. There are more than 300 COVID-19 testing locations caduet across NSW. To find your nearest clinic visit COVID-19 testing clinics or contact your GP.NSW Health is treating 69 COVID-19 cases, with one patient in intensive care. This patient does not require caduet ventilation.

Ninety-six per cent of cases being treated by NSW Health are in non-acute, out-of-hospital care.COVID-19 is still likely circulating in the community and we must all be vigilant. To help stop the caduet spread of COVID-19. If you are unwell, get tested and isolate right away – don’t delay. Wash your caduet hands regularly.

Take hand sanitiser with you when you go out. Keep your caduet distance. Leave 1.5 metres between yourself and others. Wear a mask when using public transport, caduet rideshares and taxis, and in shops, places of worship and other places where you can’t physically distance.

When taking taxis or rideshares, commuters should also sit in the back.Locations linked to known cases, advice on testing and isolation, and areas identified for increased testing can be at NSW Government - Latest news and updates.Confirmed cases to date Overseas​ 2,215 Interstate acquired 91 Loca​lly acquired – contact of a confirmed case and/or in a known cluster 1,452 Locally acquired – contact not identified 395 Under investigation 0 Counts reported for a particular day may vary over time with ongoing enhanced surveillance activities.Returned travellers in hotel quarantine to date Symptomati​c travellers tested 5,954 Found positive 138 Asymptomatic travellers sc​reened at day 2 36,037 Found positive 179 Asymptomatic travellers screened at day 10 48,458 Found positive 129.

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The other locally acquired case is a close contact of a confirmed case linked to someone who attended the childcare centre at Oran Park.NSW Health is treating cheap caduet online canada 64 COVID-19 cases, with one patient in intensive care. This patient does not require ventilation. Ninety-four per cent of cases being treated by NSW Health are in non-acute, cheap caduet online canada out-of-hospital care.NSW is at a critical point, and the only way to find undiagnosed cases and prevent further transmission is to increase testing.NSW Health particularly thanks the Oran Park community for its brilliant response to our calls for increased testing. From 1 August to 10 October 2020, the average number of COVID-19 tests conducted each week among residents of Oran Park was 227, but during the week ending 17 October 2020, the number of tests increased almost four-fold to 895.However, increases in surrounding suburbs were far more modest and NSW Health continues to appeal to the community in South Western Sydney to come forward for testing right away if anyone has even the mildest of symptoms like a runny nose or scratchy throat, cough, fever or other symptoms that could be COVID-19. This is also particularly important in Western Sydney and South Eastern Sydney, where there have also been locally transmitted cheap caduet online canada cases recently.There are more than 300 COVID-19 testing locations across NSW.

To find your nearest clinic visit COVID-19 testing clinics or contact your GP.COVID-19 is still likely circulating in the community and we must all be vigilant. To help cheap caduet online canada stop the spread of COVID-19. If you are unwell, get tested and isolate right away – don’t delay.Wash your hands regularly. Take hand cheap caduet online canada sanitiser with you when you go out.Keep your distance. Leave 1.5 metres between yourself and others.

Wear a mask when using public transport, rideshares and taxis, and in shops, cheap caduet online canada places of worship and other places where you can’t physically distance. When taking taxis or rideshares, commuters should also sit in the back. Confirmed cases to date Overseas​ 2,218 Interstate acquired 91 Loca​lly acquired – contact of a confirmed case and/or in a known cluster 1,455 Locally acquired – contact not identified 394 Under investigation 0 Counts reported for a particular day may vary over time with ongoing enhanced surveillance activities.Returned travellers in hotel quarantine to date Symptomati​c travellers tested 5,970 Found positive 138 Asymptomatic travellers sc​reened at day 2 36,406 Found positive 181 Asymptomatic travellers screened at day 10 48,768 cheap caduet online canada Found positive 129 ​​​NSW has reported no new cases of locally transmitted COVID-19 in the 24 hours to 8pm last night. The last time there were no new locally transmitted cases in NSW was the 24 hours to 6 October.Four cases in overseas travellers in hotel quarantine were diagnosed, bringing the total number of cases in NSW to 4,153. Confirmed cases (including interstate residents in NSW health care facilities) 4,153 Deaths (in NSW from confirmed cases)​ 55 Total tests carried out 2,910,053 There were 6,952 tests reported cheap caduet online canada to 8pm last night, compared with 12,985 in the previous 24 hours.Testing numbers have dropped recently, which is a concern.

NSW is at a critical point, and the only way to find new cases and prevent further transmission is to increase testing.NSW Health is appealing to the community to come forward for testing right away if anyone has even the mildest of symptoms like a runny nose or scratchy throat, cough, fever or other symptoms that could be COVID-19. This is particularly important in South Western Sydney, Western Sydney and South Eastern Sydney where there have been recent locally transmitted cases.Everyone plays an important role in helping to contain the pandemic cheap caduet online canada by getting tested quickly and following social distancing rules. Get tested on the day you get symptoms – don’t wait to see if they go away. Assume it’s COVID-19 until cheap caduet online canada proven otherwise by a test, and remember there is no limit on how many tests you can have.Testing is quick, free, and easy and most people receive their test result within 24 hours. If you have even the mildest of symptoms like a runny nose or scratchy throat, cough, fever or other symptoms that could be COVID-19, please come forward for testing right away.

There are more than 300 COVID-19 cheap caduet online canada testing locations across NSW. To find your nearest clinic visit COVID-19 testing clinics or contact your GP.NSW Health is treating 69 COVID-19 cases, with one patient in intensive care. This patient does not cheap caduet online canada require ventilation. Ninety-six per cent of cases being treated by NSW Health are in non-acute, out-of-hospital care.COVID-19 is still likely circulating in the community and we must all be vigilant. To help stop the cheap caduet online canada spread of COVID-19.

If you are unwell, get tested and isolate right away – don’t delay. Wash your cheap caduet online canada hands regularly. Take hand sanitiser with you when you go out. Keep your cheap caduet online canada distance. Leave 1.5 metres between yourself and others.

Wear a mask when using public transport, rideshares and taxis, and in shops, places of worship and other places where you can’t physically distance cheap caduet online canada. When taking taxis or rideshares, commuters should also sit in the back.Locations linked to known cases, advice on testing and isolation, and areas identified for increased testing can be at NSW Government - Latest news and updates.Confirmed cases to date Overseas​ 2,215 Interstate acquired 91 Loca​lly acquired – contact of a confirmed case and/or in a known cluster 1,452 Locally acquired – contact not identified 395 Under investigation 0 Counts reported for a particular day may vary over time with ongoing enhanced surveillance activities.Returned travellers in hotel quarantine to date Symptomati​c travellers tested 5,954 Found positive 138 Asymptomatic travellers sc​reened at day 2 36,037 Found positive 179 Asymptomatic travellers screened at day 10 48,458 Found positive 129.


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