Small Number Of Human Studies Research Articles

A review of the safety of linezolid during pregnancy, a potential alternative syphilis treatment.

With growing maternal and congenital syphilis epidemics and shortages of benzathine penicillin, alternative syphilis treatments are needed. Linezolid has shown efficacy against syphilis in animal models. This review found no teratogenic effects. Some adverse effects were seen in animals, but none were reported in a small number of human studies.

Food abundance in men before puberty predicts a range of cancers in grandsons

Nutritional conditions early in human life may influence phenotypic characteristics in later generations. A male-line transgenerational pathway, triggered by the early environment, has been postulated with support from animal and a small number of human studies. Here we analyse individuals born in Uppsala Sweden 1915–29 with linked data from their children and parents, which enables us to explore the hypothesis that pre-pubertal food abundance may trigger a transgenerational effect on cancer events. We used cancer registry and cause-of-death data to analyse 3422 cancer events in grandchildren (G2) by grandparental (G0) food access. We show that variation in harvests and food access in G0 predicts cancer occurrence in G2 in a specific way: abundance among paternal grandfathers, but not any other grandparent, predicts cancer occurrence in grandsons but not in granddaughters. This male-line response is observed for several groups of cancers, suggesting a general susceptibility, possibly acquired in early embryonic development. We observed no transgenerational influence in the middle generation.

Environmental Exposures and Seizures Treated by Illinois Emergency Medical Services and Hospitals.

Up to 10% of the population will have at least one seizure in their lifetime, with young children and elderly having the highest risk (WHO 2019). Human epidemiological studies and controlled animal studies have shown that exposure to common environmental pollutants, including carbon monoxide, lead, and nitrogen dioxide may lead to neurotoxicity and alter human susceptibility to seizures. While the biomechanism causing altered human seizure susceptibility is not entirely clear, air pollution has been shown to increase oxidative stress and neuroinflammation in humans and animals. The small number of human studies have included populations exposed to high levels of ambient air pollution, but the results have been inconsistent in regard to an increase in seizure occurrence and sudden deaths among people with epilepsy. There remains no reported data on the presence and strength of an association between chronic low-level environmental exposures to common air pollutants and seizure risk. Using medical billing records from Illinois hospitals and emergency medical services data on ambulance runs from 2011-2019, we evaluated the association between point sources of pollution mixtures (Toxic Release Inventory sites, Superfund sites, highways) and ZIP code level seizure rates.

Longitudinal Change in Cortisol Levels Across the Adult Life Span.

Cortisol is a key stress hormone implicated in the pathogenesis of many age-related diseases. Longitudinal information on cortisol exposure has been restricted to animal models and a small number of human studies. The purpose of the present study was to quantify longitudinal change in cortisol across the adult life span. We conducted a prospective longitudinal study of 24-hour urinary free cortisol excretion from ages 20 to 90 years and older. Participants were 1,814 men and women from the Baltimore Longitudinal Study of Aging who provided a total of 5,527 urine specimens for analysis. The average duration of longitudinal follow-up was 6.6 years. The primary outcome measure was 24-hour urinary free cortisol to creatinine ratio (UFC/Cr) as determined by liquid chromatography/mass spectrometry. UFC/Cr follows a U-shaped pattern across the life span with decreases in UFC/Cr in the 20s and 30s, relative stability in the 40s and 50s, and increases thereafter. This pattern of change was robust with respect to adjustment for several potential confounding factors. Age-related changes in cortisol exposure raise important questions about the potential protective or exacerbating role of cortisol exposure in predicting medical, physiological, and behavioral outcomes.

Paternal grandfather\u2019s access to food predicts all-cause and cancer mortality in grandsons

Studies of animals and plants suggest that nutritional conditions in one generation may affect phenotypic characteristics in subsequent generations. A small number of human studies claim to show that pre-pubertal nutritional experience trigger a sex-specific transgenerational response along the male line. A single historical dataset, the Överkalix cohorts in northern Sweden, is often quoted as evidence. To test this hypothesis on an almost 40 times larger dataset we collect harvest data during the pre-pubertal period of grandparents (G0, n = 9,039) to examine its potential association with mortality in children (G1, n = 7,280) and grandchildren (G2, n = 11,561) in the Uppsala Multigeneration Study. We find support for the main Överkalix finding: paternal grandfather’s food access in pre-puberty predicts his male, but not female, grandchildren’s all-cause mortality. In our study, cancer mortality contributes strongly to this pattern. We are unable to reproduce previous results for diabetes and cardiovascular mortality.

Nutraceuticals and skin appearance: Is there any evidence to support this growing trend?

AbstractThe rise of the nutraceutical market, specifically oral nutrition supplements claiming to improve skin appearance, is striking. This paper aims to examine the published scientific evidence for beneficial effects of nutraceuticals on skin appearance. An overview of skin physiology and intrinsic and extrinsic ageing is provided which underlies the potential physiological processes nutraceuticals purport to counter. Common ingredients used are explored. Some of these (vitamins A, C, B2, B3, B7, copper, iodine, zinc) have authorised skin‐related health claims, but many do not. Current evidence for those without existing authorised claims (e.g. green tea extract, pomegranate extract, carotenoids, evening primrose oil, borage oil, fish oil, collagen and co‐enzyme Q10) is reviewed, focussing primarily on evidence from randomised controlled trials where available, in relation to skin parameters including wrinkles and hydration. Issues of safety are also considered, and the postulated mechanisms for some emerging ingredients, such as cocoa flavanols and probiotics, are explored. Evidence from high quality human trials demonstrating clear benefit is required by regulatory authorities in order for foods and nutrition supplements to carry a health or beauty claim. To date, the evidence for many ingredients in relation to skin appearance is limited, not sufficiently robust and/or inconsistent. Although there are a small number of human studies suggesting a potential benefit and some plausible biological mechanisms, much of the evidence to date comes from animal and in vitro studies. There are simply not enough good quality randomised controlled trials in this area to draw firm conclusions about the benefit of nutraceuticals to skin appearance.

The effect of exercise on non-exercise physical activity and sedentary behavior in adults.

It is widely assumed that structured exercise causes an additive increase in physical activity energy expenditure (PAEE) and total daily energy expenditure (TDEE). However, the common observation that exercise often leads to a less than expected decrease in body weight, without changes in energy intake, suggests that some compensatory behavioral adaptations occur. A small number of human studies have shown that adoption of structured exercise can lead to decreases in PAEE, which is often interpreted as a decrease in physical activity (PA) behavior. An even smaller number of studies have objectively measured PA, and with inconsistent results. In animals, high levels of imposed PA induce compensatory changes in some components of TDEE. Recent human cohort studies also provide evidence that in those at the highest levels of PA, TDEE is similar when compared to less physically active groups. The objective of this review is to summarize the effects of structured exercise training on PA, sedentary behavior, PAEE and TDEE. Using models from ecological studies in animals and observational data in humans, an alternative model of TDEE in humans is proposed. This model may serve as a framework to investigate the complex and dynamic regulation of human energy budgets.

Potential Strategies to Address the Major Clinical Barriers Facing Stem Cell Regenerative Therapy for Cardiovascular Disease

ImportanceAlthough progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical implementation still exist.ObjectivesTo summarize the current barriers to the clinical implementation of stem cell therapy in patients with cardiovascular disease and to discuss potential strategies to overcome them.Evidence ReviewInformation for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 25, 2016. Ten randomized clinical trials and 8 systematic reviews were included.FindingsOne of the major clinical barriers facing the routine implementation of stem cell therapy in patients with cardiovascular disease is the limited and inconsistent benefit observed thus far. Reasons for this finding are unclear but may be owing to poor cell retention and survival, as suggested by numerous preclinical studies and a small number of human studies incorporating imaging to determine cell fate. Additional studies in humans using imaging to determine cell fate are needed to understand how these factors contribute to the limited efficacy of stem cell therapy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: coadministration of immunosuppressive and prosurvival agents, delivery of cardioprotective factors packaged in exosomes rather than the cells themselves, and use of tissue-engineering strategies to provide structural support for cells. If larger grafts are achieved using these strategies, it will be imperative to carefully monitor for the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity.Conclusions and RelevanceDespite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical barriers outlined herein before the next wave of large clinical trials is under way.

Melatonin, Autophagy and Intestinal Bowel Disease

The intestinal epithelium forms a barrier against the intestinal contents and the wider environment, allowing entry of selected molecules for nutrition and programming of the mucosal immune system, but excluding toxins and most microorganisms. Many receptors and signalling pathways are coupled and implicated in the epithelial control and significant advances have been achieved in the understanding of the pathogenesis of inflammatory bowel disease (IBD) and in the introduction of biologics. However, not all of the patients respond and many lose their response. Data from experimental studies have documented that the pineal secretory product melatonin exerts important inmunoregulatory and antiinflammatory effects in different models of colitis. These actions have been associated to a variety of mechanisms, such as reduction of T cells number, modulation of macrophage activity, suppression of NFκB activity, inhibition of cell adhesion molecules and proinflammatory cytokines , suppression of COX-2 and iNOS levels and the consequent synthesis of PGE2 and NO, reduction of matrix metalloproteinase (MMP) -2 and -9 activity, and modulation of apoptosis. In addition, the beneficial effects of melatonin in IBD are related to its scavenger effect on free radicals and the activation of several antioxidant enzymes. However, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. There is a considerable bulk of information supporting the connection between autophagy and human diseases, including IBD, and although autophagy is actually considered more a pro-survival than a pro-death pathway, these two features of its action are relevant in human diseases, having therapeutic potential for both activators and inhibitors of autophagy. Some of the opposite effects than have been reported for melatonin in IBD could be related to the duality of its effects on autophagy, which itself can be beneficial or detrimental. In this review, new data for melatonin in IBD are discussed, trying to provide recent information of different molecular mechanism including the role of the autophagy regulation.

Maternal Smoking During Pregnancy and Offspring Brain Structure and Function: Review and Agenda for Future Research

Maternal smoking during pregnancy (MSDP) has been associated with long-term neurobehavioral and cognitive deficits in offspring. Animal models demonstrate alterations in brain structure and function following prenatal nicotine exposure. However, few studies have assessed the relationship between MSDP and brain development in humans. Therefore, the aims of this review are (a) to synthesize findings from the small number of human studies investigating effects of MSDP on offspring brain development and (b) to outline an agenda for future research in this nascent area. We searched MEDLINE and Psychinfo databases for human studies of MSDP and offspring brain structure and/or function. Eleven studies meeting our search criteria were identified; 6 studies investigated effects of MSDP on brain structure; 5 examined effects on brain function. Across studies, MSDP was associated with decreased volume/thickness of the cerebellum and corpus callosum, increased auditory brainstem responses, and lack of coordination across brain regions during information and auditory processing. Results from the small number of human studies revealed effects of MSDP on brain structure and function, highlighting potential neural pathways linking MSDP and offspring neurobehavioral and cognitive deficits. Given the limited amount of research in this area, we propose an agenda for future research. Gold standard studies would utilize longitudinal designs, integrated biological and maternal report measures of MSDP, and repeated measures of brain structure/function and neurobehavioral deficits across key developmental periods.

Distribution, function and physiological role of melatonin in the lower gut.

Melatonin is a hormone with endocrine, paracrine and autocrine actions. It is involved in the regulation of multiple functions, including the control of the gastrointestinal (GI) system under physiological and pathophysiological conditions. Since the gut contains at least 400 times more melatonin than the pineal gland, a review of the functional importance of melatonin in the gut seems useful, especially in the context of recent clinical trials. Melatonin exerts its physiological effects through specific membrane receptors, named melatonin-1 receptor (MT1), MT2 and MT3. These receptors can be found in the gut and their involvement in the regulation of GI motility, inflammation and pain has been reported in numerous basic and clinical studies. Stable levels of melatonin in the lower gut that are unchanged following a pinealectomy suggest local synthesis and, furthermore, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.

Mycoprotein and health

SummaryMycoprotein is a high protein, high fibre, low fat food ingredient derived from fermentation of the filamentous fungus Fusarium venenatum. Interest in the putative role of mycoprotein in lowering blood cholesterol concentrations, reducing energy intakes and controlling blood sugar levels has generated a small number of human studies investigating the effects of mycoprotein on cholesterol reduction, satiety and insulinaemia/glycaemia.In today's ‘obesogenic’ environment, in which there is an abundance of foods high in fat and/or sugar available to consumers, there is growing interest in foods that are both nutritious and satiating, but that are of low‐energy density, and are low in saturates, salt and sugar. Mycoprotein has a favourable fatty acid profile (being relatively low in saturates), a fibre content that is comparable with other vegetarian protein sources, and a naturally low sodium content. Mycoprotein is a good source of zinc and selenium but the levels of iron and vitamin B12 in mycoprotein are low in comparison to red meat.A small number of studies investigating the cholesterol‐lowering effects of mycoprotein have been carried out among normo‐ and hypercholesterolaemic adults. The published studies to date have a number of limitations (including small sample sizes and short study durations), but overall the studies report statistically significant reductions in total cholesterol amongst hypercholesterolaemic subjects (in the order of 4–14%). These results look promising in terms of the ability of mycoprotein to contribute modest but meaningful effects on blood cholesterol concentrations, as part of a varied and balanced diet. However, the exact amount of mycoprotein that would need to be consumed in free‐living populations to have meaningful effects on cholesterol is a candidate for further confirmatory research.A number of studies have investigated the effects of mycoprotein in comparison with other protein sources on satiety. Several studies suggest that the effects of mycoprotein on satiety are greater than an equivalent amount of chicken but it is unclear what mechanism underlies this. The studies conducted so far are relatively small, and carried out under controlled conditions, so it is difficult to extrapolate the results to larger free‐living populations.The promotion of mycoprotein could potentially be useful, alongside other strategies, in the management of obesity and type 2 diabetes, as it appears to show beneficial effects on glycaemia and insulinaemia in the small number of studies where this has been investigated. More research is needed to better understand the mechanism of action whereby mycoprotein influences glycaemia and insulinaemia, and whether there is any dose‐dependent effect.This paper reviews the published evidence for mycoprotein and the topics above, draws interim conclusions about the role of mycoprotein in human health and identifies areas for future research.

Ampakines and the threefold path to cognitive enhancement

Ampakines are the first peripherally administered drugs that increase excitatory monosynaptic responses in the brain. Because of this effect, the compounds improve communication in complex networks, potently facilitate long-term potentiation (LTP) and induce the expression of neurotrophic factors. Ampakines are effective in animal models of neuropsychiatric disorders and have produced positive results in a small number of human studies. Neurobiological considerations and modeling studies suggest that the drugs, in addition to their effects on disturbed behavior, will alter the encoding and organization of information in normal brains. Results from physiological and behavioral studies accord with this prediction. Building on these findings, this article considers how the threefold effects of ampakines will modify, and enhance, cognition.

The periodontal-systemic connection: implications for treatment of patients with osteoporosis and periodontal disease.

Osteoporosis and osteopenia may influence periodontal disease and tooth loss. Medications such as hormone replacement therapy and nutritional supplements that are used to prevent or treat osteoporosis have been evaluated for beneficial effects on oral health in a small number of human studies. Hormone replacement therapy (HRT), which slows the rate of bone loss at skeletal sites such as the hip and spine, also appears to reduce the rate of alveolar bone loss in postmenopausal women. HRT use is consistently associated with greater tooth retention and a reduced likelihood of edentulism in studies of elderly women. The number of studies on the effects of calcium or vitamin D intake on oral outcomes is limited, but suggest that higher intake levels are associated with reduced prevalence of clinical attachment loss and lower risk of tooth loss. Data from a prospective study of oral health in men show a similar association between higher calcium intake and reduced alveolar bone loss. The number of teeth with progression of alveolar bone loss over a 7-year period was significantly lower among men whose calcium intake was at least 1,000 mg per day, compared to men with a calcium intake below this level. Future studies should confirm these findings and evaluate the oral effects of new medications for osteoporosis. If confirmed, the implications for dental professionals may include an expanded array of medications for the treatment of periodontal disease and a greater emphasis on nutrition education for patients.

Platelets and restenosis

Restenosis is currently the major limitation of percutaneous transluminal coronary angioplasty (PTCA). Factors such as elastic recoil, migration of vascular smooth muscle cells from media to intima, neointimal proliferation and vascular remodeling underly the restenotic process. Presently there is no effective therapy available for restenosis. The role of platelets in the development of thrombosis and abrupt closure after PTCA is well recognized. However, the effects of platelets in PTCA extend well beyond the early phase. Although antiplatelet agents such as glycoprotein IIb/IIIa antagonists have been reported to reduce target vessel revascularization, major unresolved controversies still exist. This report reviews the potential role of platelets in restenosis. Various drugs, successfully tested in experimental studies and in a small number of human studies, that inhibit the effect of platelets on the restenotic process are also reviewed.

Dietary interventions affecting chylomicron and chylomicron remnant clearance

Interest in effects of diet on postprandial lipoproteins has increased in recent years as a result of accumulating evidence for adverse cardiovascular consequences of elevated concentrations of triglyceride rich lipoproteins. Particular attention has been given to ability of different fatty acids to modulate postprandial lipoprotein responses because of evidence for both harmful and protective cardiovascular properties of the saturated, monounsaturated and ω-6 and ω-3 polyunsaturated fatty acid (PUFA) classes. Evidence for direct atherogenic properties of chylomicron remnants has led to attempts to monitor effects of diet specifically on this lipoprotein class. Limitations in the methods employed to measure chylomicron remnants and the small number of human studies which have evaluated effects of meal, and background diet, fatty acid composition, makes it difficult to draw definitive conclusions at the present time. However consideration of data from both animal and human studies tends to support the conclusion that diets, and meals, rich in PUFA (particularly long chain ω-3 PUFA), result in attenuated postprandial responses of the intestinally-derived lipoproteins. Attenuated responses to high PUFA meals appear to be due to greater rates of clearance and greater activation of lipoprotein lipase (LPL). Attenuated responses to high PUFA background diets may be due to adaptive changes involving both accelerated rates of clearance in peripheral tissues and liver, as well as decreased output of the competitor for chylomicron clearance, very low density lipoprotein (VLDL).