Sunday, July 30, 2017
This review explores the current evidence on benefits and harms of therapeutic interventions in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and makes recommendations. CFS/ME is a complex, multi-system, chronic medical condition whose pathophysiology remains unknown. No established diagnostic tests exist nor are any FDA-approved drugs available for treatment. Because of the range of symptoms of CFS/ME, treatment approaches vary widely. Studies undertaken have heterogeneous designs and are limited by sample size, length of follow-up, applicability and methodological quality. The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. Similarly, adaptive pacing appears to offer some benefits, but the results are debatable: so is the use of nutritional supplements, which may be of value to CFS/ME patients with biochemically proven deficiencies. To summarize, the recommended treatment strategies should include proper administration of nutritional supplements in CFS/ME patients with demonstrated deficiencies and personalized pacing programs to relieve symptoms and improve performance of daily activities, but a larger randomized controlled trial (RCT) evaluation is required to confirm these preliminary observations. At present, no firm conclusions can be drawn because the few RCTs undertaken to date have been small-scale, with a high risk of bias, and have used different case definitions. Further, RCTs are now urgently needed with rigorous experimental designs and appropriate data analysis, focusing particularly on the comparison of outcomes measures according to clinical presentation, patient characteristics, case criteria and degree of disability (i.e. severely ill ME cases or bedridden).
The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is a recently identified condition in which the exposure to an adjuvant leads to an aberrant autoimmune response. We aimed to summarize the results obtained from the ASIA syndrome registry up to December 2016, in a descriptive analysis of 300 cases of ASIA syndrome, with a focus on the adjuvants, the clinical manifestations, and the relationship with other autoimmune diseases. A Web-based registry, based on a multicenter international study, collected clinical and laboratory data in a form of a questionnaire applied to patients with ASIA syndrome. Experts in the disease validated all cases independently. A comparison study regarding type of adjuvants and differences in clinical and laboratory findings was performed. Three hundred patients were analyzed. The mean age at disease onset was 37 years, and the mean duration of time latency between adjuvant stimuli and development of autoimmune conditions was 16.8 months, ranging between 3 days to 5 years. Arthralgia, myalgia, and chronic fatigue were the most frequently reported symptoms. Eighty-nine percent of patients were also diagnosed with another defined rheumatic/autoimmune condition. The most frequent autoimmune disease related to ASIA syndrome was undifferentiated connective tissue disease (UCTD). ASIA syndrome is associated with a high incidence of UCTD and positive anti-nuclear antibodies (ANA) test. Clinical and laboratory features differ from the type of adjuvant used. These findings may contribute to an increased awareness of ASIA syndrome and help physicians to identify patients at a greater risk of autoimmune diseases following the exposure to vaccines and other adjuvants. The ASIA syndrome registry provides a useful tool to systematize this rare condition.
"I was completely revitalised," says Karen. "Suddenly, I could be sociable again. I would go to work, go home, eat dinner and feel restless."
Karen (not her real name) experienced this relief from chronic fatigue syndrome while taking a drug that is usually used to treat the blood cancer lymphoma and rheumatoid arthritis (see "Karen's experience", below).
She was one of 18 people with CFS who reported improvements after taking rituximab as part of a small trial in Bergen, Norway. The results could lead to new treatments for the condition, which can leave people exhausted and housebound.
Finding a cause for CFS has been difficult. Four years ago, claims that a mouse virus was to blame proved to be unfounded, and some have suggested the disease is psychosomatic.
The latest study implicates the immune system, at least in some cases. Rituximab wipes out most of the body's B-cells, which are the white blood cells that make antibodies.
Øystein Fluge and Olav Mella of the Haukeland University Hospital in Bergen noticed its effect on CFS symptoms in 2004, when they used the drug to treat lymphoma in a person who happened to also have CFS.
Several months later, the person's CFS symptoms had disappeared. A small, one-year trial in 2011 found that two-thirds of those who received rituximab experienced relief, compared with none of the control group.
The latest study, involving 29 people with CFS, shows that repeated rituximab infusions can keep symptoms at bay for years.
"Eleven of the 18 responders were still in remission three years after beginning the treatment, and some have now had no symptoms for five years," says Fluge. "Suddenly, their limbs started to work again and their hands were no longer cold or sweaty."
"I am very intrigued by the rituximab story," says Nancy Klimas, an authority on CFS at Nova Southeastern University in Fort Lauderdale, Florida. "It's particularly exciting when people seem to have experienced very long periods of remission, and even speak of recovery," she says.
On Wednesday, EWG released its groundbreaking National Tap Water Database – a project two years in the making that allows nearly every American to punch in their zipcode to find out exactly what's in their local drinking water and how it can affect their health. The information in the database goes far beyond anything utilities or the Environmental Protection Agency provides. EWG found a number of contaminants, that while regulated under the Safe Drinking Water Act, are often found at levels that many scientists believe pose health risks.
"Americans deserve the fullest picture possible of what's in their tap water," said EWG President Ken Cook. "But they won't get that information from the government or, in many cases, from their utilities. The only place they'll find that is EWG's drinking water report."
The database provides real solutions to Americans concerned about their water quality. First and foremost, it provides advice on choosing the right water filter so they can take matters into their own hands and remove contaminants. Filtering tap water is not only cheaper than bottled water – it's far better for the environment, too.
Men are suffering a sharp decline in fertility because of the prevalence of every-day plastics, say scientists.
And Niels Jørgensen, associate professor at Rigshospital, Copenhagen, has told the European Society for Human Reproduction and Embryology's conference in Lisbon that only one in four men have "good" sperm.
According to The Times, phthalates, chemicals that are found in shower curtains, car dashboards and cleaning materials, "can be breathed in, consumed or absorbed through the skin of pregnant women, inhibiting testosterone production in male foetuses, leading to sons with low sperm counts".
Jørgensen said that society should be "very worried" by these studies, and advised women to try to avoid cosmetics.
Friday, July 28, 2017
Walnut consumption may increase the amount of beneficial bacteria in the gut, according to a recent animal study published in The Journal of Nutritional Biochemistry.
At the end of 10 weeks, rats fed a diet containing ground walnuts showed an increase in beneficial bacteria types including, Lactobacillus, Roseburia, and Ruminococcaceae.
Rats in the walnut diet group also showed greater gut bacteria diversity than those consuming the walnut-free control diet.
"The diet groups had distinct microbial communities with animals consuming walnuts displaying significantly greater species diversity," concluded the researchers from Louisiana State University.
The finding is also important because the ability to positively influence gut bacteria composition with foods like walnuts may eventually lead to better health outcomes.
"Gut health is an emerging research area, but we are seeing that greater bacterial diversity may be associated with better health outcomes, whereas low diversity has been linked to conditions such as obesity and inflammatory bowel disease," said lead researcher professor Lauri Byerley.
LONDON — England is in the midst of a unique national experiment, the world's most ambitious effort to treat depression, anxiety and other common mental illnesses.
The rapidly growing initiative, which has gotten little publicity outside the country, offers virtually open-ended talk therapy free of charge at clinics throughout the country: in remote farming villages, industrial suburbs, isolated immigrant communities and high-end enclaves. The goal is to eventually create a system of primary care for mental health not just for England but for all of Britain.
At a time when many nations are debating large-scale reforms to mental health care, researchers and policy makers are looking hard at England's experience, sizing up both its popularity and its limitations. Mental health care systems vary widely across the Western world, but none have gone nearly so far to provide open-ended access to talk therapies backed by hard evidence. Experts say the English program is the first broad real-world test of treatments that have been studied mostly in carefully controlled lab conditions.
Wednesday, July 26, 2017
Promotion of influenza vaccines is one of the most visible and aggressive public health policies today. Twenty years ago, in 1990, 32 million doses of influenza vaccine were available in the United States. Today around 135 million doses of influenza vaccine annually enter the US market, with vaccinations administered in drug stores, supermarkets—even some drive-throughs. This enormous growth has not been fueled by popular demand but instead by a public health campaign that delivers a straightforward, who-in-their-right-mind-could-possibly-disagree message: influenza is a serious disease, we are all at risk of complications from influenza, the flu shot is virtually risk free, and vaccination saves lives. Through this lens, the lack of influenza vaccine availability for all 315 million US citizens seems to border on the unethical. Yet across the country, mandatory influenza vaccination policies have cropped up, particularly in healthcare facilities,1 precisely because not everyone wants the vaccination, and compulsion appears the only way to achieve high vaccination rates.2 Closer examination of influenza vaccine policies shows that although proponents employ the rhetoric of science, the studies underlying the policy are often of low quality, and do not substantiate officials' claims. The vaccine might be less beneficial and less safe than has been claimed, and the threat of influenza appears overstated.
A study by University of Florida Health researchers published recently in the Journal of Pain Research provides a possible explanation for that atypical exhaustion, supporting a hypothesis that the bodies of those with chronic fatigue inappropriately magnify minute muscle byproducts caused by exertion.
"People with chronic fatigue are essentially sensing muscle metabolites while they are not doing anything, and they're not supposed to be," said Roland Staud, M.D., a professor of rheumatology and clinical immunology in the UF College of Medicine and the study's lead author. "Generally speaking, when we're at rest, we don't feel our muscles."
Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes
We therefore investigated the compound with the highest overlap, SFN, in greater detail. SFN is a naturally occurring isothiocyanate found in cruciferous vegetables such as broccoli. It activates nuclear factor erythroid 2–related factor 2 (NRF2) by modifying the conformation of Kelch-like ECH-associated protein 1 (KEAP1) cytoplasmic chaperone, thus releasing NRF2 for translocation to the nucleus and transcriptional activation of genes with the antioxidant response element (ARE) in their promoters (23). Although SFN uptake into cells leads to an initial burst of reactive oxygen species, it then rapidly activates the KEAP1-NRF2-ARE system to induce antioxidant enzymes and increase cellular glutathione for an overall antioxidative effect (24). As an inducer of endogenous antioxidants, SFN has been extensively studied for its protective effects in different experimental models associated with oxidative stress and chemoprotection (25), inflammatory disorders (26), and fatty liver disease (27, 28). To date, SFN has not been implicated for the treatment of exaggerated hepatic glucose production in T2D.
Friday, July 21, 2017
The use of positive airway pressure (PAP) to treat sleep apnea does not reduce the risk of cardiovascular events and death, a new analysis suggests.
In a meta-analysis of 10 randomized clinical trials comprising more than 7000 patients, PAP was not associated with a reduction in major adverse cardiovascular events (MACE), cardiovascular death, all-cause death, stroke, or heart failure compared with no or sham treatment.
"While sleep apnea is clearly associated in observational studies with risks of cardiovascular disease, it doesn't seem as if those risks can be reversed by treating people with PAP," coauthor Dr Bruce Neal, the George Institute for Global Health, University of New South Wales, Sydney, Australia, said in an interview.
"Whether that's because our treatment method with PAP isn't very good or whether the association that we see in the observational studies is being driven by something else isn't really clear to us," Neal said.
The results were published online July 11, 2017 in JAMA.
Thursday, July 20, 2017
More than one third of global dementia cases may be preventable by addressing nine lifestyle factors that affect an individual's risk, according to the findings of a new comprehensive report from The Lancet Commission on Dementia Prevention, Intervention, and Care.
The report, presented today at the Alzheimer's Association International Conference (AAIC) 2017 and simultaneously published in The Lancet, was compiled by 24 international experts in the field of dementia who reviewed the available literature in the field and conducted a new meta-analysis that included some risk factors not considered in previous similar analyses.
They found that nine lifestyle factors are responsible for 35% of dementia burden. These factors include not completing secondary education in early life; hypertension; obesity and hearing loss in midlife; and smoking, depression, physical inactivity, social isolation, and diabetes in later life.
Monday, July 17, 2017
Widely used heartburn drugs are associated with increased risk of death, and the longer a person uses the drugs, the greater the risk, new research suggests.
Proton pump inhibitors or PPIs, have been tied to a wide range of side effects including fractures, dementia, heart disease, pneumonia and kidney disease, the study's senior author Dr. Ziyad Al-Aly of Washington University School of Medicine in St. Louis told Reuters Health in a telephone interview.
"We took it a bit further and asked is this class associated with a higher risk of death, and the answer is yes," he said.
Researchers believe they have uncovered a key piece of the puzzle in the connection between diet and dementia.
They linked a specific dietary pattern to blood markers of inflammation. In addition, they showed that in elderly adults who followed such a dietary pattern, brain gray matter volume was less, and they had worse visuospatial cognitive function.
"We found that people who consume less omega 3, less calcium, vitamin E, vitamin D, and vitamin B5 and B2 have more inflammatory biomarkers," study investigator Yian Gu, PhD, Columbia University and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, New York City, told Medscape Medical News.
An inflammatory dietary pattern, said Dr Gu, "is bad for both the brain and cognition."
The study was presented here at the Alzheimer's Association International Conference (AAIC) 2017.
Saturday, July 15, 2017
Scientists have identified a pair of markers—readily detectable in patients' blood using an enzyme-linked immunosorbent assay (ELISA)—that can accurately identify those with early-stage pancreatic ductal adenocarcinoma (PDAC), according to a report published yesterday in Science (July 12).
The mortality rate for pancreatic cancer is staggeringly high—a 7 percent 5-year survival rate, according to an estimate from the American Cancer Society—and it's expected to rank second on the list of top causes of cancer death within the next three years, write the authors in their report.
Doctors are typically only able to detect this cancer "after it causes pronounced symptoms, when it has advanced far enough to be lethal," lead author Kenneth Zaret of the Perelman School of Medicine at the University of Pennsylvania tells UPI.
The researchers sought to find markers that could catch patients with the disease before it progressed into later stages. In a prior study, they modeled the advance of this disease by manipulating human PDAC cells into a pluripotent state, hypothesizing that they "might undergo early stages of cancer," the authors write in their report. They investigated the types of proteins secreted by these cells, and in the current study they looked for some of these proteins in the blood of patients with PDAC.
One protein, thrombospondin-2, was elevated in patients with PDAC. When combined with the already-identified cancer marker CA19-9, the researchers were even better at detecting these patients and discriminating between cancer stage. For instance, in a sample of 537 people, including PDAC patients, participants with other pancreatic disorders, and healthy individuals, the researchers demonstrated that thrombospondin-2 together with CA19-9 could pick out PDAC patients with 98 percent specificity and 87 percent sensitivity.
The vaccine was about 42 percent effective in preventing illness severe enough to send a patient to the doctor's office. But it was essentially ineffective protecting some age groups. That includes people 65 and older — the group that's hardest hit by flu, suffering the most deaths and hospitalizations.
The flu season that just ended was a long one that peaked in February and was considered moderately severe. But the flu-related hospitalization rate for older adults was the highest it's been since the severe 2014-2015 flu season.
Like that season, last winter was dominated by a kind of flu — Type A H3N2 — that tends to cause more deaths and serious illnesses than other seasonal flu viruses.
In four of the last seven flu seasons, flu vaccine was essentially ineffective in seniors, past studies suggest. The worst performances tend to be in H3N2-dominant seasons.
Health officials say flu vaccine still protects many people. And even if fares poorly against the dominant virus, it can do a good job against other circulating flu strains.
"While it is clear we need better flu vaccines, it's important that we not lose sight of the important benefits of vaccination with currently available vaccines," said Jill Ferdinands, a flu epidemiologist at the Centers for Disease Control and Prevention, in a statement.
The CDC calculates vaccine effectiveness from a sample of flu tests done on patients in five states.
Vaccines against some other infectious diseases are not considered successful unless they are at least 90 percent effective. But flu is particularly challenging. Over the last ten winters, overall flu vaccine effectiveness has averaged about 46 percent.
Last winter's vaccine did well in protecting young children, about 60 percent effective. And it did OK in older children and in adults ages 50 to 64. But it had no clear effect in adults 18 to 49, or among the oldest adults.
Results were presented at a meeting in Atlanta of the Advisory Committee on Immunization Practices, which provides vaccine advice to the CDC.
Wednesday, July 12, 2017
The family of a Missouri woman who died from a rare tick-borne illness is speaking out about the dangers of the virus, which has only been confirmed in a handful of patients since it was discovered in 2014. Tamela Wilson, who died June 23 of complications stemming from Bourbon virus, had worked at Meramec State Park in Sullivan, and removed two ticks from her body a few weeks prior to falling ill, The St. Louis Post-Dispatch reported.
The 58-year-old woman's stepmother, Kathy Potter, said doctors didn't know to test for the disease, and diagnosed her with a urinary tract infection before sending her home with antibiotics.
Some epidemiologic studies of nutrition focus on dietary patterns rather than single nutrients or foods to evaluate the association between diet and health outcomes.1 Accumulated evidence supports an association between healthy dietary patterns and a decreased risk of death.2-11 Results from recent studies suggest that improved diet quality, as assessed by means of the Alternate Healthy Eating Index–2010 score,12 the Alternate Mediterranean Diet score,10,13 and the Dietary Approaches to Stop Hypertension (DASH) diet score,14 was associated with reductions of 8% to 22% in the risk of death from any cause15,16 and reductions of 19% to 28% in the risk of death from cardiovascular disease and 11% to 23% in the risk of death from cancer.2-4,17
Given such consistent evidence, the 2015 Dietary Guidelines for Americans recommended the Alternate Healthy Eating Index, the Alternate Mediterranean Diet, and DASH as practical, understandable, and actionable diet plans for the public.18 Such guidelines are important in the United States and globally because unhealthy diets have been ranked as a major factor contributing to death and health complications.19 Evaluation of changes in diet quality over time in relation to the subsequent risk of death would be important. Here, we evaluated the association between 12-year changes (from 1986 through 1998) in the three diet-quality scores noted above and the subsequent risk of total and cause-specific death from 1998 through 2010 among participants in the Nurses' Health Study and the Health Professionals Follow-up Study. We also examined short-term changes (baseline to 8-year follow-up, 1986–1994) and long-term changes (baseline to 16-year follow-up, 1986–2002) in diet quality in relation to total and cause-specific mortality.
Monday, July 10, 2017
Paradoxes concerning CVD abound. Food scientists hotly dispute whether a plant-based diet or an omnivorous diet is optimal for the prevention of CVD . Cardiologists debate whether the vulnerable plaque hypothesis to explain coronary artery disease (CAD) events, a foundational basis of lipid-lowering treatment, should be abandoned . A recent trial showed that evacetrapib, a drug that lowers low-density lipoprotein (LDL) cholesterol, had no effect on the CVD outcomes, bringing into question the mechanism of the benefit of statins in reducing CVD events . Counterintuitively, while the incidences of obesity and diabetes (i.e. risk factors for CVD) have risen during recent decades in Western countries, deaths attributed to CVD have fallen markedly .
Globally, about 30% of all deaths are due to CVD. About 38% of people in high-income countries die of CVD compared to 28% in low and middle-income countries . However, CVD death rates among young people (< age 65) are higher in low and middle-income countries because of the shorter average lifespan. Nearly 80% of deaths in high-income countries occur among those over the age of 60 compared to 42% in low and middle-income countries . These and the other CVD paradoxes call for new hypotheses that better explain the diverse and puzzling data. This paper will present data that supports the hypothesis that vitamin K2 (menaquinones: MK-4–MK-13) plays a central role in CVD etiology, epidemiology, and pathogenesis.
Vitamin K comprises a family of fat-soluble, structurally-similar compounds that function as enzymatic co-factors in the cross-linking of γ-carboxyl with ε-amino side chains in vitamin K-dependent proteins. Vitamin K-dependent proteins include not only blood coagulation proteins manufactured in the liver but also components of many extrahepatic tissues including arterial vessels and bones. Vitamin K1 (phylloquinone) comes primarily from green leafy vegetables. Vitamin K2 molecules are designated as MK-4–MK-13 according to the lengths of their isoprenyl side chains attached to a 2-methyl-1,4-naphthoquinone ring. Some vitamin K2 comes from dietary animal products without bacterial action (MK-4). Other vitamin K2 originates from bacterial action in animal and human guts and from bacterial action in fermenting plants and dairy products (MK-5–MK-13) . In conjunction with vitamin D, vitamin K2 regulates the deposition of calcium, so bones and teeth receive calcium while blood vessels such as coronary arteries do not .
Animal trials and human observational studies have demonstrated that vitamin K2 deficiency (dietary deficiency or vitamin K inhibition by warfarin) contributes to CVD by stiffening and calcifying coronary arteries and other vessels . An eight-year-long observational study involving 4,807 men and women aged 55 years and older in Rotterdam, Netherlands found that people in the lowest tertile of intake (vitamin K2 < 21.6 µg/day) had 27% more CVD mortality than people in the mid tertile (vitamin K2 = 21.6–32.7 µg/day) and 57% more than those in the upper tertile (vitamin K2 > 32.7 µg/day) . As per the Multi-Ethnic Study of Atherosclerosis (MESA) in the United States, CVD incidence over 11 years of observation increased progressively as vitamin K2-dependent protein activity decreased, with event rates of 5.9 and 11.7 per 1000 person-years in the highest and lowest quartiles, respectively .
Biometric markers such as BMI, FBS, hemoglobin A1c, SBP, and serum cholesterol/HDL-cholesterol ratio (TC/HDL) have been correlated with CVD events in developed countries . Socioeconomic risk factors such as dropping out of school, poverty, and certain occupations have also been correlated with CVD . It has been found that nutritional and other stresses on infants and young children are associated with higher CVD death rates later in life. Study of infants in utero during the influenza pandemic of 1918  and during the Dutch famine of 1944  showed that these individuals suffered increased rates of CVD deaths in later life. Early childhood mortality (age 0–5 years) provides a reasonable index of fetal, infant, and early childhood distress (FICD) that might correlate with mortality from CVD in early adult life and middle age.
This study will use multiple regression analysis of female and male cohort data worldwide to relate early death from CVD (dependent variable) with major CVD risk factors (independent variables) to determine the attributable risks for each of these factors. For conditions associated with CVD (i.e. obesity, diabetes, hypertension, and increased TC/HDL), similar multiple regression analysis-derived formulae will be used to determine the attributable risks.
Higher coffee intake is linked to significantly lower risk for death, two large studies confirm. The benefit was found in diverse European populations, as well as across different racial/ethnic groups, researchers report in articles published online today in Annals of Internal Medicine.
Because coffee is one of the most popular drinks in the United States and worldwide, the public health effect of coffee intake could be substantial, even if the effect on an individual is small.
Despite mounting evidence for the health and mortality benefits of coffee consumption, the relationship between coffee intake and mortality in different European populations in which coffee preparation methods vary has been unclear. Similarly, data on coffee drinking among nonwhite populations were lacking.
The two new studies address those gaps.
In EPIC (European Prospective Investigation into Cancer and Nutrition), a large, prospective cohort study, Marc J. Gunter, PhD, from the International Agency for Research on Cancer, Lyon, France, and colleagues examined the association of coffee intake with all-cause and cause-speciﬁc mortality among 451,743 participants (130,662 men and 321,081 women) in 10 European countries.
"[O]ur results suggest that higher levels of coffee drinking are associated with lower risk for death from various causes, specifically digestive and circulatory diseases," the authors write.
Sunday, July 9, 2017
But the mantra that moderate drinking is good for the heart has never been put to a rigorous scientific test, and new research has linked even modest alcohol consumption to increases in breast cancer and changes in the brain. That has not stopped the alcoholic beverage industry from promoting the alcohol-is-good-for-you message by supporting scientific meetings and nurturing budding researchers in the field.
Now the National Institutes of Health is starting a $100 million clinical trial to test for the first time whether a drink a day really does prevent heart attacks. And guess who is picking up most of the tab?
Five companies that are among the world's largest alcoholic beverage manufacturers — Anheuser-Busch InBev, Heineken, Diageo, Pernod Ricard and Carlsberg — have so far pledged $67.7 million to a foundation that raises money for the National Institutes of Health, said Margaret Murray, the director of the Global Alcohol Research Program at the National Institute on Alcohol Abuse and Alcoholism, which will oversee the study.
The decision to let the alcohol industry pay the bulk of the cost has raised concern among researchers who track influence-peddling in science.
"Research shows that industry-sponsored research almost invariably favors the interests of the industry sponsor, even when investigators believe they are immune from such influence," said Marion Nestle, a professor of nutrition and food studies at New York University who is the author of several books on the topic, including "Food Politics: How the Food Industry Influences Nutrition and Health."
Sevin = 1-naphthyl methylcarbamate
The nightly release of melatonin from the pineal gland is regulated by biological clocks in the suprachiasmatic nucleus (SCN) of the hypothalamus and transmits signals to the brain and peripheral target tissues through activation of the G-protein coupled melatonin receptors MT1 and/or MT2.1–3 Rhythmicity of pineal melatonin synthesis from serotonin is tightly orchestrated by N-acetyltransferase (AA-NAT) and hydroxyindole-o-methyltransferase (HIOMT) both of which have peak enzymatic activities during the night.4–6 Activation of melatonin receptors play a pivotal role in modulating the phase and amplitude of circadian rhythms phase and amplitude through the body.1,7,8 Circadian rhythm misalignment is implicated in various conditions such as jet lag, delayed sleep phase syndrome (DSPS), advanced sleep phase syndrome (ASPS), and seasonal affective disorders (SAD).9 Activation of melatonin receptors inhibit cyclic adenosine monophosphate (cAMP) formation,10–13 regulate phosphorylation of the cAMP responsive element-binding protein (CREB),14 protein kinase activities,15,16 and ion fluxes.12,17 In essence, the melatonin receptor system regulates a wide-array of cellular signaling events essential to maintain rhythmicity and homeostatic balance of various regulatory processes.3,18 Aberrant melatonin receptor activation, sensitivity, and trafficking are linked to pathological conditions including cancer,19 diabetes,2,20 and cardiovascular disease.21
Exposure to chemicals that are structurally similar to melatonin can significantly alter this balance and could result in alteration of melatonin mediated signaling3 and potentially other conditions that impact human health. In the present study, innovative combinations of computational tools for chemical clustering of large data sets of environmental chemicals were employed in tandem with predictive three-dimensional models in an attempt to identify new-class of environmental neuroendocrine disruptors targeting melatonin receptors. Briefly, environmental chemicals that could potentially interact with melatonin receptors based on their structural similarity were identified using an integrated pharmacoinformatics screen from a comprehensive Chem2Risk knowledge-base. Molecular docking of select environmental modulators established novel bimolecular interactions of carbamate insecticides carbaryl and carbofuran with the MT1 and MT2 melatonin receptors in silico. Furthermore, the current study investigated ligand affinity, selectivity, and apparent intrinsic efficacy of selected environmental disruptors on hMT1 and hMT2 melatonin receptors in vitro.
Agricultural use of carbamates as insecticides is due to their strong yet reversible inhibitory effect on acetylcholinesterase.22 Occupational exposure to carbamates has been reported to be associated with psychological distress and depression among agricultural workers.23,24 There is also a positive correlation between carbamate exposure and the risk of developing diabetes and metabolic syndrome.25 Carbaryl produces behavioral changes in rodents such as tremor26 and hypothermia.27 Furthermore, a recent study reports age-specific sensitivity to carbaryl in Brown-Norway rats indicative of age-related changes in metabolism. Even low-dose (3 mg/kg) carbaryl treatment exhibits these age-specific differences in both biochemical and behavioral experiments.28 While some of these effects were attributed to cholinesterase inhibition and neurotoxicity at higher doses, persistent exposure to lower doses of insecticides including carbamates in both occupational and nonoccupational environment was associated with increased risk of various disease conditions including diabetes, cancer, and depression.24,25 Center for Disease Control (CDC) reports that in addition to the dermal routes (the most common route of exposure), several classes of insecticides including the carbamates that are used in spray formulations can reach the brain and other target tissues via inhalation, circumventing liver metabolism (CDC ToxGuide, 2003) and repeated exposure to these chemicals (as in occupational exposure) tend to render higher concentrations of insecticides in target tissues. It is imperative to find alternative targets and mechanisms through which carbamates and other insecticides render such a wide range of biochemical and behavioral effects.
Friday, July 7, 2017
However, recent developments have shaken consumers' trust in the USDA Organic label. Aurora, a top dairy producer in the country, was found ducking organic standards, selling conventional milk under the guise of organic.
The Aurora scandal exposed glaring gaps in organic inspections. Some inspections are scheduled in advance, giving a businesses time for a cover-up, and certifiers don't always inspect at crucial times during the season. USDA inspection at Aurora, for example, happened during winter months—though peak grazing season happens in summer. That way, inspectors didn't catch that operators weren't grazing their 15,000 head of dairy cows on grass as organic standards required.
Meanwhile, imported chemically-treated corn and soybeans were deliberately mislabeled organic to boost profits, when they entered the United States, further shaking consumer faith in the certified label.
Thursday, July 6, 2017
Sunday, July 2, 2017
Those of us who have participated in science know that 9 of every 10 experiments are failures. Now imagine that the last 50 years has been a grand clinical research experiment, with the American population as unwitting participants, conducted by 10 principal investigators—Coca-Cola, Pepsico, Kraft, Unilever, General Mills, Nestlé, Mars, Kellogg, Proctor & Gamble, and Johnson & Johnson. In 1965, these corporations posed the hypothesis that processed food is better than real food. To determine if the experiment was a success or a failure, we have to examine the outcome variables. In this case, there are 4: food consumption, health/disease, environment, and cash flow, divided into companies, consumers, and society.
The review article by Heymsfield and Wadden (Jan. 19 issue)1 is valuable with respect to the clinical management of obesity, but information about the contribution of mitochondrial genes to obesity is not included. Mitochondrial dysfunction is associated with an accumulation of fat that can occur during aging and in patients with obesity, the metabolic syndrome, or diabetes mellitus.2
Zheng et al.3 found that obese participants with a high metabolic syndrome score have increased DNA methylation in the mitochondrial genes MT-CO1 and MT-ND6 and in the mitochondrion-related nuclear gene PPARGC1A. Flaquer et al.4 conducted a study using samples obtained from 6528 participants in the KORA (Cooperative Health Research in the Region of Augsburg) studies and found that two mitochondrial single-nucleotide polymorphisms (SNPs) located in the cytochrome c oxidase subunit genes (MT-CO1 and MT-CO3) and three mitochondrial SNPs located in the NADH dehydrogenase subunit genes (MT-ND1, MT-ND2, and MT-ND4L) were significantly associated with a higher body-mass index (BMI). Latorre-Pellicer et al.5 systematically characterized conplastic mice (mice in which the nuclear genome of one mouse is backcrossed into the cytoplasm of another, so that the nuclear genes and mitochondrial genes are from different parents) throughout their lifespan. They found that the mitochondrial DNA haplotype profoundly influences mitochondrial proteostasis and generation of reactive oxygen species, insulin signaling, telomere shortening, the development of obesity, and mitochondrial dysfunction. These findings highlight the importance of the contribution of mitochondrial genetic variants to the risk of a high BMI.