Clinical Trials 101

December 30, 2016

The following are a series of Frequently Asked Questions (FAQ) pertaining to clinical trials, and what the process entails:

What is a clinical trial?

Clinical trials are well-designed studies that collect information about new treatments for diseases and disorders. Most of the time, this means medications, but clinical trials can also test other things, such as stem cell therapies, surgical techniques, tests for diagnosis, medical devices, as well as others. In particular, clinical trials focus on administering an experimental therapy in humans, as opposed to animals, which are conducted first in the lab (known as “pre-clinical research”).

Why do we need clinical trials?

Clinical trials are needed for medical treatments to be approved by government organizations, such as the US Food and Drug Administration (FDA). Without clinical trials, doctors and other prescribing healthcare providers (such as nurse practitioners or physician’s assistants) cannot prescribe medications or recommend other medical treatments. These studies are needed to understand two important types of information 1) that the treatment is effective (also called efficacious), ie, that it really works and 2) that the treatment is safe for use in humans.

In addition to helping patients by making the best possible treatments available, clinical trials also advance scientific understanding of a disease or disorder.

How do clinical trials work?

Usually, effectiveness is compared versus a placebo (sugar pill with no medication in it), or another type of comparison. Another type of medication comparison that is common is a different drug, already approved for use. A comparison is needed to understand that the medication works and also to see if the medication is safe. Researchers will design the clinical trial for a specific period of time, during which the people participating will either get the treatment, or the comparison treatment. Typically a study is done “double-blind,” which means that neither the researchers giving the treatments nor the participants know who is getting which treatment. This prevents “bias,” which means expectations that could influence the outcome of the study.

Researchers giving the treatment will have a code that is later “unblinded” so they find out what treatment they were giving. The researchers also record measurements while the participants are receiving the treatment. These measurements can be for different things, such as to determine if the treatment is working, to assess safety and side-effects. Other measurements might include blood levels of the medications. If someone participates in a clinical trial, they will be informed about the measurements that will be taken before the trial starts. An “Informed Consent” document tells participants about the trial.

What kind of clinical trials are there?

The type of trial that most people read about and consider enrolling in is called an interventional trial. This tests treatments that are not yet approved for use. Prevention trials are designed to stop medical conditions from occurring. Observational trials are used to look at health issues in large groups of people, and do not involve treatment. Diagnostic and screening trials are intended to detect and diagnose medical problems.

What are the phases of clinical trials?

Developing a new medical treatment takes many years. The process is intended to best treat medical conditions without harming people. Before a medical treatment can even be tested in people, animal testing is absolutely required. As mentioned above, this phase is called pre-clinical testing. Animal testing is governed by three principals: 1) to reduce the use of animals to the minimum but still collect data indicating that the treatment is safe and effective in people, 2) minimize animal suffering and assure animal welfare as much as possible, 3) replace animal experiments with other alternatives when possible.

Phase I testing is the first step in humans. The purpose is to determine safety and to evaluate side effects. Phase I studies also test how the drug is absorbed, distributed and eliminated from the body. Often people who do not have the disease (healthy individuals) participate in Phase I. The number of people involved at this stage is usually small.

Phase II trials are sometimes divided into Phase IIA and Phase IIB. Sometimes these two sub-phases are combined. Phase II trials further assess dosing and are designed to determine the best drug dose to use and how much of a dose is safe. Phase II studies can also measure efficacy and safety testing in small numbers of participants. Often a treatment must pass Phase II in order to proceed to Phase III.

Most reports of medical treatment studies focus on Phase III trials. These are the large trials that are required for a drug or other treatment to receive approval for use. The purpose of this phase is to test efficacy and safety as well as to monitor for side effects. The main drug effects are often called the primary efficacy endpoints. Other measurements may be called the secondary endpoints.

Sometimes researchers conduct Phase IV trials, after a drug has been approved. These trials collect additional information about the drug or treatment.

Why participate in a clinical trial?

There are several reasons to participate in a clinical trial. One is to get access to a treatment that is not otherwise available. The treatment may be better than others available for the condition. A risk however, could be that the treatment is not better or even has side effects. Treatments in clinical trials are typically free to the participants.

Clinical trials also help to advance science and to generally help other people with the medical condition being studied. They may help with making a new treatment available, but could also improve the general understanding of the disease.

Sometimes there are other incentives to participating in a clinical trial. Participants may receive some reimbursement or they may receive additional benefits, such as counseling or educational materials. These benefits are detailed in any documentation that the participants are given before the trial starts.

How is privacy protected in a clinical trial?

People who participate in a clinical trial are anonymous except to the professionals conducting the trial. These professionals are not allowed to reveal the identity of people participating in the trial to anyone who is not involved in the study.

Personal information that is collected during the trial has to be protected, for example, in locked file drawers or in password protected computers.

Any reports that are made available to the public about the data collected in a clinical trial cannot have any information that identifies the people participating.

Can participants leave a clinical trial once it has started?

It is the right of the participant to leave a clinical trial for any reason at any time. If a participant is receiving a treatment, it is important to consult with a physician to make sure that it is safe to stop the treatment or to help taper off the treatment or replace it with a different treatment.

What happens when the trial ends?

After the trial ends, the investigators will begin to analyze the data that has been collected during the trial. They will write up reports about what they have found and submit them to a treatment approving agency, such as the FDA. The agency will make decisions about whether the treatment will move further into other trials, or whether it will be approved.

The study researchers may also write reports about what they have found in the trial that are made available to the public. These reports could be published as presentations at medical conferences, or as scientific papers in medical journals. Often a drug company will issue press releases on their web site, describing where the data has been presented.

Do participants still get treatment after the trial ends?

After the trial ends, treatment may end, or participants may be offered continued treatment. This is frequently referred to as an “open label extension.” Participants who have received placebo are sometimes able to get the treatment at the end of a study as well. To understand what happens after the trial ends, it is important to speak with the individuals conducting the trial to see if the option exists to continue the treatment after the trial has ended. Participants should also review any documentation describing the trial, such as the Informed Consent documentation. A doctor could also make a decision to continue the participant on the treatment (if it is available) or a similar treatment.

Can someone get a medication that has not gone through a clinical trial?

All medications must go through clinical trials to be used in patients. It is possible for physicians and other prescribing healthcare providers to prescribe a medication that has gone through clinical trials for a different use. This is called “off-label use.” It means that the treatment went through a clinical trial, usually for a similar condition. Using a medication off-label is based on the clinical judgement of the person prescribing the medication.

If a drug works, why can’t we just start giving it to people right away?

It is important to make sure that a drug is more effective than existing treatments, actually works in a disease and that it is safe. Decisions to give drugs or other medical treatments have to come from scientific data, not just the opinion of a healthcare provider, patient or other individual. Clinical trials help to assure all of these things.

Isn’t there a way to get treatments for serious medical conditions approved for use faster?

The FDA does have what is called a Fast Track Designation, which helps to make drugs available faster if they are used for a life-threatening condition or if they can help fulfill an unmet medical need. A drug company developing the treatment needs to request Fast Track Designation. This can be done at any time during the treatment development process. After a drug company requests Fast Track Designation, the FDA has 60 days to make a decision.

How can someone participate in a clinical trial?

Companies developing treatments often have contact information available on their websites that interested participants use to find out how to be included in a trial. The medical centers conducting the trials may also have contact information. Trials conducted in the United States are registered with Clinicaltrials.gov, and individuals responsible for enrolling trials will have their contact information listed there. CenterWatch is another site that helps connect people with clinical trials.

https://parkinsonsnewstoday.com/clinical-trials-101/

Can Drinking Tea Help Fight Cancer, Parkinson's and Diabetes?

December 29, 2016

Can drinking tea help fight some types of cancer, Parkinson's disease and Type 2 diabetes, or even improve your mood?

"It probably doesn't live up to the hype of being a miracle cure, but it is beneficial, especially if you drink it simply, without adding sugar, cream or milk, which adds lots of calories," says Kathleen Zelman, director of nutrition at WebMD and a registered dietitian in Atlanta. While not a silver bullet against any malady, research is promising that tea can help protect us from serious diseases while improving our overall health, Zelman says.

Here's what the research says about how consuming tea may help fight some maladies:

Cancer 

Studies have not conclusively shown that drinking tea will prevent you from getting cancer or by itself defeat cancer, but it could help fight cancer cells. Green tea in particular is considered effective in fighting cancer cells because it contains high levels of polyphenols, antioxidants found in the Camellia sinensis plants used to make many teas, such as the green, black and white varieties. Antioxidants -- chemicals that neutralize free radicals, preventing them from causing damage -- help prevent the types of free radical damage that are associated with cancer development. "There's some promising lab studies and population-based studies suggesting tea can help fight cancer, but more clinical studies are needed," says Chris D'Adamo, director of research at the Center for Integrative Medicine at the University of Maryland.

In a 2014 study, researchers from Penn State University's Center for Plant and Mushroom Foods for Health found that drinking green tea could help kill the cells that cause oral cancer. And a 2015 study published in the journal PLOS One found that a constituent of ginger that's produced when the ginger root is dried or cooked was effective in killing breast cancer cells without harming noncancerous ones. The ginger product was more effective in fighting cancer cells than Taxol, an anti-cancer drug, the study said. While the findings don't suggest ginger can help prevent or cure cancer, researchers found the results encouraging.

Parkinson's Disease

If you want to delay the onset of Parkinson's disease symptoms, tea might be an ally. Research published in 2014 in the journal Frontiers in Aging Neuroscience suggests both green and black tea could slow the effects of the progressive movement disorder. The analysis showed that drinking more than three cups of tea daily was associated with delaying the onset of Parkinson's symptoms by more than seven years in 278 people.

Type 2 Diabetes

People with diabetes have to be careful about what they consume, but they might be better off ignoring inhibitions when it comes to green tea. A study published in 2013 in the Diabetes and Metabolism Journal found that Japanese people who consumed six cups of green tea daily were 33 percent less likely to develop Type 2 diabetes than those who drank less than one cup of green tea a week. Antioxidants in green tea may help reduce glucose levels by blocking normal glucose uptake into the body's tissues.

Depression

Drinking tea won't cure depression, but it might reduce your risk of becoming depressed. Research published in 2015 in the Australian and New Zealand Journal of Psychiatry found that drinking three cups of tea daily decreased the risk of depression by 37 percent. Researchers analyzed the findings of 11 studies that included more than 22,800 participants.

The aromas of some teas can help people feel better, says Dr. Kelly Kasper, an associate professor of obstetrics and gynecology at Indiana University Health. Kasper says she recommends tea to her patients because it can have a calming effect, which can help improve one's mood.

Respiratory Conditions 

Many tea makers claim on their packaging that their product helps with breathing. Tea can't cure asthma or other respiratory ailments, like bronchitis, but it can help mitigate the symptoms of these conditions, says Dr. Patrick Fratellone, a cardiologist and integrative physician in New York City. Some teas, such as nettle tea -- which comes from a plant grown in temperate regions worldwide that has small, hollow, needle-like hairs on its stems and leaves -- have anti-inflammatory properties, which can help fight allergies that damage the lungs, he adds. "If you add a slice of lemon or lime to your tea, it will boost the drink's anti-inflammatory qualities, which will make it more effective in fighting respiratory ailments and boosting your immune system," Fratellone says.

Digestive Disorders

Herbal teas, such as chamomile, peppermint, ginger and fennel varieties, can help ease the digestive tract and soothe an upset stomach, Zelman says. "The main benefit to these teas is how they make you feel, rather than treating any conditions," she says. "When your stomach doesn't feel well, herbal teas are highly recommended because they are so easy to digest. They're not magical, but they are soothing." During her time as a pediatric dietitian, Zelman recommended tea for young children who had trouble digesting foods and beverages.

Some herbal teas are nervines -- herbal products that are often thought to help calm a person's digestive tract and produce other health benefits. Fratellone, for instance, says teas that are nervines, such as chamomile and lemon balm, "improve digestion, which helps maintain a healthy body."

Finding the Right Tea for You

If you aren't a regular tea drinker and want to give it a try, here are three strategies experts recommend:

Try a variety of teas. There are hundreds of teas on the market, and if you try different flavors, you're more likely to find one you like, Zelman says. "It doesn't matter how good something is for you; if you don't like it, you won't consume it," she says. If you prefer caffeine-free teas, Zelman suggests trying flavored herbal teas, which are made from bark, leaves, flowers, buds and fruits. "I think mint herbal tea is just amazing, and the flavor is really satisfying," she says. "Wrapping your hands around a warm cup of herbal tea is really soothing to me."

Buy organic. Fratellone recommends trying to buy organic teas because they're cultivated from pesticide-free plants that were typically produced with clean, toxin-free water.

Be careful about buying teas from countries like China and Nigeria, where tea might be cultivated in soil that contains potentially toxic heavy metals and other inorganic materials. The packaging on organic teas typically says where a tea was cultivated, Fratellone says. He recommends checking ConsumerLab.com, a website that publishes recalls and consumer warnings about teas worldwide.

Follow your nose. Many organic food stores have a wide variety of teas, and some shops sell just tea. Smell different types to see which ones appeal to you, Kasper advises. "If you like the way it smells, you will probably like the way it tastes," Kasper says.

Ruben Castaneda is a Health & Wellness reporter at U.S. News. He previously covered the crime beat in Washington, D.C. and state and federal courts in suburban Maryland, and he's the author of the book "S Street Rising: Crack, Murder and Redemption in D.C." You can follow him on Twitter, connect with him at LinkedIn or email him at rcastaneda@usnews.com.

http://sports.yahoo.com/news/drinking-tea-help-fight-cancer-parkinsons-diabetes-174837107.html

Famous Paintings By Artists Who Had Alzheimer’s and Parkinson’s May Reveal Clues To Diagnosis

December 29, 2016

GUY GILLETTE VIA GETTY IMAGES

Painters’ brushstrokes could provide subtle clues to Alzheimer’s and Parkinson’syears before the diseases are diagnosed, according to analysis of some of the world’s most famous art.

Experts identified gradual changes in the painting styles of Salvador Dali, Norval Morrisseau, James Brooks and other artists known to have suffered from the degenerative illnesses.

The groundbreaking study could lead to a new avenue of research for scientists searching for ways to diagnose brain diseases in their earliest stages, the Press Association reported.

esearchers at Maynooth University in Ireland and the University of Liverpool digitally transformed 2,092 paintings by seven artists into black and white in an attempt to reveal clues to the diseases.

Professor Ronan Reilly, from the Department of Computer Science at Maynooth University in Ireland, ran tests similar to those which search for repeating patterns in snowflakes.

“Identifying changes in someone’s behaviour that can predict clinical diagnoses years later is very challenging; however, this data suggests that it could be possible to identify changes in the structure of a painting many years before the diagnosis of a neurological disorder,” he said.

Works by Dali, Morrisseau, Brooks and other artists who suffered from Parkinson’s or Alzheimer’s was compared to paintings by Picasso, Marc Chagall and Claudo Monet, who did not.

Artists who aged without brain disease did not simplify the patterns and structures they used, according to the study, which was published in the Neurospychology journal. 

Dr Alex Forsythe, from the University of Liverpool’s School of Psychology, said: “Art has long been embraced by psychologists as an effective method of improving the quality of life for those persons living with cognitive disorders.

“We have built on this tradition by unpicking artists’ ‘handwriting’ through the analysis of their individual connection with the brush and paint.

“This process offers the potential for the detection of emerging neurological problems.”

Video: http://www.huffingtonpost.co.uk/entry/scientists-find-subtle-clues-to-alzheimers-in-famous-artists-work_uk_5864d055e4b0f24da6e8446e?ir=UK&utm_hp_ref=uk

Gut microorganisms affect our physiology

December 29, 2016

Credit: CC0 Public Domain

Researchers have found evidence that could shed new light on the complex community of trillions of microorganisms living in all our guts, and how they interact with our bodies.

Scientists at the University of Exeter Medical School and University of Zaragoza in Spain studied a protein known as TLR2, a critical detector of the microbiotafound in the intestine. They found that it regulates levels of serotonin - a neurotransmitter which carries messages to the brain, and is also found in the gut, where it regulates our bowel routines.

The research, carried out in cell cultures and verified in mice, provides strong evidence that microbiota can interfere with human physiology by modulating the serotonin transporter activity. Serotonin transporter is a target for numerous diseases and it seems that microbiota living in our guts is able to interfere with this transporter, controlling our serotonin levels.

The finding, published in PLOS ONE, comes as scientists across the world are working to understand the complicated interactions between the "invisible world" of the microbiota in our bodies and the impact they have on our health and even our moods. Recently, scientists in California found evidence that the bacteria in the gut play a role in causing Parkinson's Disease.

The research, carried out in cell cultures and verified in mice, provides strong evidence that microbiota can interfere with human physiology by modulating the serotonin transporter activity. Serotonin transporter is a target for numerous diseases and it seems that microbiota living in our guts is able to interfere with this transporter, controlling our serotonin levels. NeuroscienceNews image is for illustrative purposes only from
http://neurosciencenews.com/physiology-gut-microorganism-5831/

It may also help explain how the microbiota in our guts affect our physiology. Inflammatory bowel disease is thought to be triggered when TLR2 is not functioning properly, but so far, the mechanisms behind this have not been fully understood. This study aimed to further this understanding, and was supported the Foundation for the Study of Inflammatory Bowel Diseases in Aragón (ARAINF), in Spain.

Dr Eva Latorre, a postdoctoral researcher at the University of Exeter Medical School, said the new finding helped to further understanding in a fast-growing research area. She said: "This paper has concluded that the protein TLR2 alters the availability of serotonin, which is important in a range of conditions from depression to inflammatory bowel disease. It is early days in this research though. We need to understand much more about the relationship between the microbiota in our guts and how they interact, before we can hope to harness effective new treatments."

The research team examined human cells in a model of the intestine in the laboratory, looking at how they express proteins and RNA - activities which regulate how they behave. They found that TLR2 controls serotonin transporter - obtaining the same result in studies on mice.

Principal investigator of this study, Professor José E Mesonero, at the University of Zaragoza, said: "This paper opens our minds about the complex universe of this forgotten organ: the microbiome. We have concluded that TLR2 not only can detect microbiota, but also modulate serotonin transport, one of the crucial mechanism in neurological and inflammatory diseases. Much has to be yet studied, but this work can improve our understanding about the connection between gut and brain thought microbiota."

The paper, called 'Intestinal serotonin transporter inhibition by Toll-like receptor 2 activation. A feedback modulation', is published in PLOS ONE, by Eva Latorre, Elena Layunta, Laura Grasa, Marta Castro, Julián Pardo, Fernando Gomollón, Ana I. Alcalde and José E. Mesonero.

 Explore further: Researchers visualize brain's serotonin pump, provide blueprint for new, more effective SSRIs

Journal reference: PLoS ONE

Provided by: University of Exeter

http://medicalxpress.com/news/2016-12-gut-microorganisms-affect-physiology.html

Inactivity in obese mice linked to a decreased motivation to move

December 29, 2016

Obese mouse and healthy weight mouse. Credit: Alexxai Kravitz

Starting a regular program at the gym is a common New Year's resolution, but it's one that most people are unable to stick with for very long. Now a study done in mice is providing clues about one of the reasons why it may be hard for so many people to stick with an exercise program. The investigators found that in obese mice, physical inactivity results from altered dopamine receptors rather than excess body weight. The report appears in Cell Metabolism on December 29.

"We know that physical activity is linked to overall good health, but not much is known about why people or animals with obesity are less active," says the study's senior author Alexxai V. Kravitz, an investigator in the Diabetes, Endocrinology, and Obesity Branch at the National Institute of Diabetes and Digestive and Kidney Diseases—part of the National Institutes of Health. "There's a common belief that obese animals don't move as much because carrying extra body weight is physically disabling. But our findings suggest that assumption doesn't explain the whole story."

Kravitz has a background in studying Parkinson's disease, and when he began conducting obesity research a few years ago, he was struck by similarities in behavior between obese mice and Parkinsonian mice. Based on that observation, he hypothesized that the reason the mice were inactive was due to dysfunction in their dopamine systems.

"Other studies have connected dopamine signaling defects to obesity, but most of them have looked at reward processing—how animals feel when they eat different foods," Kravitz says. "We looked at something simpler: dopamine is critical for movement, and obesity is associated with a lack of movement. Can problems with dopamine signaling alone explain the inactivity?"

Obese mouse and healthy weight mouse. Credit: Alexxai Kravitz

In the study, mice were fed either a standard or a high-fat diet for 18 weeks. Beginning in the second week, the mice on the unhealthy diet had higher body weight. By the fourth week, these mice spent less time moving and got around much more slowly when they did move. Surprisingly, the mice on high-fat diet moved less before they gained the majority of the weight, suggesting that the excess weight alone was not responsible for the reduced movements.

The investigators looked at six different components in the dopamine signaling pathway and found that the obese, inactive mice had deficits in the D2 dopamine receptor. "There are probably other factors involved as well, but the deficit in D2 is sufficient to explain the lack of activity," says Danielle Friend, first author and former NIDDK postdoctoral fellow.

The team also studied the connection between inactivity and weight gain, to determine if it was causative. By studying lean mice that were engineered to have the same defect in the D2 receptor, they found that those mice did not gain weight more readily on a high-fat diet, despite their lack of inactivity, suggesting that weight gain was compounded once the mice start moving less.

"In many cases, willpower is invoked as a way to modify behavior," Kravitz says. "But if we don't understand the underlying physical basis for that behavior, it's difficult to say that willpower alone can solve it."

He adds that if we begin to decipher the physiological causes for why people with obesity are less active, it may also help reduce some of the stigma that they face. Future research will focus on how unhealthy eating affects dopamine signaling. The researchers also plan to look at how quickly the mice recover to normal activity levels once they begin eating a healthy diet and losing weight.

More information: Cell Metabolism, Friend et al: "Basal ganglia dysfunction contributes to physical inactivity in obesity" http://www.cell.com/cell-metabolism/fulltext/S1550-4131(16)30596-4 , DOI: 10.1016/j.cmet.2016.12.001

Journal reference: Cell Metabolism

Provided by: Cell Press 

http://medicalxpress.com/news/2016-12-inactivity-obese-mice-linked-decreased.html

Can paint strokes help identify Alzheimer's?

December 29, 2016

A new University of Liverpool study published today in Neuropsychology shows that it may be possible to detect neurodegenerative disorders in artists before they are diagnosed.

Psychologist Dr Alex Forsythe from the University's School of Psychology and her team, working with Dr Tamsin Williams of Tees, Esk, and Wear Valleys NHS Trust, Vale of York and Maynooth University, Ireland, examined 2092 paintings from the careers of seven famous artists who experienced both normal ageing and neurodegenerative disorders.

Of the seven, two had suffered from Parkinson's disease (Salvador Dali and Norval Morrisseau), two had suffered from Alzheimer's disease (James Brooks and Willem De Kooning) and three had no recorded neurodegenerative disorders (Marc Chagall, Pablo Picasso and Claude Monet).

Fractal analyses

The brushstrokes of each of the paintings were analysed using a method of applying non-traditional mathematics to patterns known as 'Fractal' analyses to identify complex geometric patterns.

Fractals are mathematical characterisations of self-repeating patterns often described as the 'fingerprints of nature'. They can be found in natural phenomena such as clouds, snowflakes, trees, rivers, and mountains. This method has also been used to determine the authenticity of major works of art.

Although painters work within a different style or genre, the fractal dimension in which they operate should remain comparable.

Patterns of change

The results were examined to see if the variations in an artist's unique 'fractals' in their work over their career were due to them just increasing in age or because of ongoing cognitive deterioration.

The study showed clear patterns of change in the fractal dimension of the paintings differentiated artists who suffered neurological deterioration from those aging normally.

Dr Alex Forsythe, said: "Art has long been embraced by psychologists an effective method of improving the quality of life for those persons living with cognitive disorders.

"We have built on this tradition by unpicking artists 'handwriting' through the analysis of their individual connection with the brush and paint. This process offers the potential for the detection of emerging neurological problems.

"We hope that our innovation may open up new research directions that will help to diagnose neurological disease in the early stages"

Journal reference: Neuropsychology

Provided by: University of Liverpool

http://medicalxpress.com/news/2016-12-alzheimer_1.html

‘Latest Spoke in the Wheel’ Drives Brain-Mapping Advances

NEUROSCIENCE NEWSDECEMBER 28, 2016

Summary: Super resolution microscopy may help to provide a better understanding of the structure and functions of the brain.

Source: SPIE.

Producing nanoscale maps of protein organization on cell surfaces or within organelles is another exciting prospect in super-resolution microscopy. NeuroscienceNews image is for illustrative purposes only.

Advances in microscopy techniques have often triggered important discoveries in the field of neuroscience, enabling vital insights in understanding the brain and promising new treatments for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. A special section on “Super-resolution Microscopy of Neural Structure and Function” in the current issue of the journal Neurophotonics, published by SPIE, the international society for optics and photonics, details this work in reports on ground-breaking new research and reviews.

Starting with the Golgi technique at the end of the 19th century, to electron microscopy in the 1950s, to fluorescent confocal and two-photon microscopy at the close of the 20th century, microscopy techniques have driven important breakthroughs in neuroscience, note guest editors Valentin Nägerl and Jean-Baptiste Sibarita of the Université de Bordeaux and the CNRS in their editorial for the special section.

“By providing higher spatial and temporal resolutions, as well as more contrast and specificity, these ground-breaking techniques have greatly informed our view of how the brain works,” the editors write.

Super-resolution fluorescence microscopy “is the latest spoke in the revolutionary wheel,” the guest editors note. “Recognized with the Nobel Prize in chemistry in 2014 for overcoming the diffraction barrier of light microscopy, it unlocks a new potential to upend biological research at the molecular level. Ten years after their development in a handful of laboratories, super-resolution microscopy techniques have caught on like wildfire and are now routinely used in a large number of biology labs.”

While super-resolution microscopy is a relative recent addition to the arsenal of tools available for neuroscientific research, said Neurophotonics editor-in-chief David Boas of Massachusetts General Hospital, Harvard Medical School, “the breadth of impactful applications is growing rapidly. This special section provides a snapshot of this growth with a collection of exciting papers illustrating the breadth of applications.”

Articles in the section, many of them accessible via open access, help validate and assess new techniques by comparing them with more established approaches. Among them:

In “Filling the gap: adding super-resolution to array tomography for correlated ultrastructural and molecular identification of electrical synapses at the C. elegans connectome,” Sebastian Matthias Markert of the University of Würzburg and co-authors describe a new method to correlate molecular information with ultrastructural context. Their aim is to allow researchers to dissect the molecular underpinnings of the ultrastructural organization and function of electrical synapses precisely and confidently.

Producing nanoscale maps of protein organization on cell surfaces or within organelles is another exciting prospect in super-resolution microscopy. In “Counting numbers of synaptic proteins: absolute quantification and single molecule imaging techniques,” Angela Patrizio and Christian Specht of École Normale Supérieure describe how single-molecule-based microscopy techniques offer unparalleled opportunities to study protein content and dynamics in key functional compartments.

An early hallmark of neurodegenerative diseases such as Alzheimer’s and Parkinson’s is the misfolding and self-aggregation of proteins into amyloid structures that are believed to wreak havoc on neurons and synapses. In “Probing amyloid protein aggregation with optical super-resolution methods: from the test tube to models of disease”, Clemens Kaminski and Gabriele Kaminski Schierle of the University of Cambridge explain the potential of new optical super-resolution techniques to provide insight on the molecular mechanism of the pathogenic self-assembly process in vitro and inside cells.

Launched in 2014, Neurophotonics is published digitally in the SPIE Digital Library and in print. The journal covers advances in optical technology applicable to the study of the brain and their impact on basic and clinical neuroscience applications.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Amy Nelson – SPIE 

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: Full open access research for “Filling the gap: adding super-resolution to array tomography for correlated ultrastructural and molecular identification of electrical synapses at the C. elegans connectome” by Sebastian Matthias Markert, Sebastian Britz, Sven Proppert, Marietta Lang, Daniel Witvliet, Ben Mulcahy, Markus Sauer, Mei Zhen, Jean-Louis Bessereau, Christian Stigloherin Neurophotonics. Published online October 2016 doi:10.1117/1.NPh.3.4.041802

Abstract

Filling the gap: adding super-resolution to array tomography for correlated ultrastructural and molecular identification of electrical synapses at the C. elegans connectome

Correlating molecular labeling at the ultrastructural level with high confidence remains challenging. Array tomography (AT) allows for a combination of fluorescence and electron microscopy (EM) to visualize subcellular protein localization on serial EM sections. Here, we describe an application for AT that combines near-native tissue preservation via high-pressure freezing and freeze substitution with super-resolution light microscopy and high-resolution scanning electron microscopy (SEM) analysis on the same section. We established protocols that combine SEM with structured illumination microscopy (SIM) and direct stochastic optical reconstruction microscopy (

“Filling the gap: adding super-resolution to array tomography for correlated ultrastructural and molecular identification of electrical synapses at the C. elegans connectome” by Sebastian Matthias Markert, Sebastian Britz, Sven Proppert, Marietta Lang, Daniel Witvliet, Ben Mulcahy, Markus Sauer, Mei Zhen, Jean-Louis Bessereau, Christian Stigloherin Neurophotonics. Published online October 2016 doi:10.1117/1.NPh.3.4.041802

http://neurosciencenews.com/brain-mapping-neuroscience-5822/

EPA Amends Proposed Regulation Of Syngenta Ingredient In Response To Public Comments

December 28, 2016  Elizabeth Balboa , Benzinga Staff Writer 

The Environmental Protection Agency is acting to mitigate health risks of paraquat dichloride — an herbicide commonly used in Syngenta AG (ADR) 

 products — in response to fatalities from chemical ingestion and extended exposure.

Paraquat Dichloride: More Than Just A Plant Killer

An EPA-led analysis of incidents also identified a potential link between the chemical and Parkinson’s disease, which is consistent with other recent studies.

Paraquat, an occasional suicide agent with no known antidote, is highly toxic, with one sip proving fatal. It is also corrosive, and dermal exposure has led to skin grafts and, in some cases, death.

Still, the EPA recorded an average use of 4 million pounds of the chemical over 7 million acres of U.S. crops between 2011 and 2013. Now, the agency is acting — as it has multiple times since the 1980s — to reduce the herbicide’s health effects.

It’s not the first to react to paraquat’s reported risks.

Prior to the EPA investigation, the California Department of Pesticide Regulations prioritized paraquat for risk assessment in response to occupational exposure in 2014.

Global Efforts

Thirty-two (32) countries — and the European Union — have entirely banned use of the chemical, and Canada issued a number of safety regulations in 2015. These included concentration reduction, provision of training for applicators and modification of packaging and labels to distinguish the chemical as hazardous.

EPA's Proposed Measures

Apart from concentration alterations, the EPA’s latest recommended measures resemble those effected by Canada. Additional steps include restricted distribution to certified applicators and containment of the chemical in closed-system packaging. Requirements of hose-like appendages to transfer the chemical are intended to limit skin contact and accidental ingestion.

The EPA is giving paraquat manufacturers until September 2018 to alter packaging labels and September 2020 to implement closed-system packaging.

What Changed?

The initially proposed steps released in March suggested the prohibition of hand-held distribution equipment to decrease dermal exposure, but the decision released in December excludes this measure. The EPA changed its ruling after numerous stakeholders — including Syngenta and the U.S. Department of Agriculture — asserted the necessity of handheld application during public comment in the spring. The agency is instead requiring paraquat to contain a dye to aid in early leak detection.

The EPA initially anticipated a shift from paraquat use inspired by the now-eschewed measure.

“Prohibition of hand-held equipment may cause growers to change to an alternative chemical, or mixtures of chemicals, to achieve similar weed control,” the March memorandum noted.

Many stakeholders protested this measure during public comment on the grounds of the inefficacy of paraquat alternatives.

Syngenta and others raised issue with additional elements of the initial risk mitigation approach — including label safety language delineating risk of injury through eye exposure and risk of poisoning through skin contact. The company also rejected the EPA’s acknowledged link between paraquat and Parkinson’s.

Meanwhile, other commentators demanded more stringent regulations limiting the chemical’s use. Both the Pesticide Action Network and Center for Biological Diversity requested a ban similar to that enforced throughout Europe.

CBD questioned the ecological risks of paraquat on endangered species and their habitats, and the EPA noted ongoing assessments of the potential threat.

Despite protests of varying degrees from both sides of the issue, the agency reported that paraquat manufacturers seemed prepared to comply with final regulations voluntarily.

The EPA is still in the process of re-evaluating paraquat for the pesticide’s scheduled registration review. A final decision weighing the advantages and disadvantages of continued use will be issued in 2018.

Syngenta was not available to comment for this report.

https://www.benzinga.com/news/16/12/8847130/epa-amends-proposed-regulation-of-syngenta-ingredient-in-response-to-public-comme