OBJECTIVES:We sought to investigate roles that Merck&Co Inc played in state human papillomavirus (HPV) immunization policymaking, to elicit key stakeholders' perceptions of the appropriateness of these activities, and to explore implications for relationships between health policymakers and industry.

METHODS:We used a series of state case studies combining data from key informant interviews with analysis of media reports and archival materials. We interviewed 73 key informants in 6 states that were actively engaged in HPV vaccine policy deliberations.

RESULTS:Merck promoted school-entry mandate legislation by serving as an information resource, lobbying legislators, drafting legislation, mobilizing female legislators and physician organizations, conducting consumer marketing campaigns, and filling gaps in access to the vaccine. Legislators relied heavily on Merck for scientific information. Most stakeholders found lobbying by vaccine manufacturers acceptable in principle, but perceived that Merck had acted too aggressively and nontransparently in this case.

CONCLUSIONS:Although policymakers acknowledge the utility of manufacturers' involvement in vaccination policymaking, industry lobbying that is overly aggressive, not fully transparent, or not divorced from financial contributions to lawmakers risks undermining the prospects for legislation to foster uptake of new vaccines.

Cannabidiol (CBD) represents a new promising drug due to a wide spectrum of pharmacological actions. In order to relate CBD clinical efficacy to its pharmacological mechanisms of action, we performed a bibliographic search on PUBMED about all clinical studies investigating the use of CBD as a treatment of psychiatric symptoms. Findings to date suggest that (a) CBD may exert antipsychotic effects in schizophrenia mainly through facilitation of endocannabinoid signalling and cannabinoid receptor type 1 antagonism; (b) CBD administration may exhibit acute anxiolytic effects in patients with generalised social anxiety disorder through modification of cerebral blood flow in specific brain sites and serotonin 1A receptor agonism; (c) CBD may reduce withdrawal symptoms and cannabis/tobacco dependence through modulation of endocannabinoid, serotoninergic and glutamatergic systems; (d) the preclinical pro-cognitive effects of CBD still lack significant results in psychiatric disorders. In conclusion, current evidences suggest that CBD has the ability to reduce psychotic, anxiety and withdrawal symptoms by means of several hypothesised pharmacological properties. However, further studies should include larger randomised controlled samples and investigate the impact of CBD on biological measures in order to correlate CBD's clinical effects to potential modifications of neurotransmitters signalling and structural and functional cerebral changes.

With increasing age, the immune system undergoes a remodeling process, termed immunosenescence, which is accompanied by considerable shifts in leukocyte subpopulations and a decline in various immune cell functions. Clinically, immunosenescence is characterized by increased susceptibility to infections, a more frequent reactivation of latent viruses, decreased vaccine efficacy, and an increased prevalence of autoimmunity and cancer. Physiologically, the immune system has some adaptive strategies to cope with aging, while in some settings, maladaptive responses aggravate the speed of aging and morbidity. While a lack of physical activity, decreased muscle mass, and poor nutritional status facilitate immunosenescence and inflammaging, lifestyle factors such as exercise and dietary habits affect immune aging positively. This review will discuss the relevance and mechanisms of immunoprotection through physical activity and specific exercise interventions. In the second part, we will focus on the effect of dietary interventions through the supplementation of the essential amino acid tryptophan,-3 polyunsaturated fatty acids, and probiotics (with a special focus on the kynurenine pathway).

Major depressive disorder (MDD), schizophrenia (SCH), Alzheimer's disease (AD), and Parkinson's disease (PD) are devastating neurological disorders, which increasingly contribute to global morbidity and mortality. Although the pathogenic mechanisms of these conditions are quite diverse, chronic neuroinflammation is one underlying feature shared by all these diseases. Even though the specific root causes of these diseases remain to be identified, evidence indicates that the observed neuroinflammation is initiated by unique pathological features associated with each specific disease. If the initial acute inflammation is not resolved, a chronic neuroinflammatory state develops and ultimately contributes to disease progression. Chronic neuroinflammation is characterized by adverse and non-specific activation of glial cells, which can lead to collateral damage of nearby neurons and other glia. This misdirected neuroinflammatory response is hypothesized to contribute to neuropathology in MDD, SCH, AD, and PD. Physical activity (PA), which is critical for maintenance of whole body and brain health, may also beneficially modify neuroimmune responses. Since PA has neuroimmune-modifying properties, and the common underlying feature of MDD, SCH, AD, and PD is chronic neuroinflammation, we hypothesize that PA could minimize brain diseases by modifying glia-mediated neuroinflammation. This review highlights current evidence supporting the disease-altering potential of PA and exercise through modifications of neuroimmune responses, specifically in MDD, SCH, AD and PD.

Physical limitations, depression and anxiety are prevalent among older adults. Mild to moderate exercise can promote physical and psychological health and reduce the risk of chronic diseases. Qigong, a type of Chinese traditional medicine exercise, has demonstrated beneficial effects on physical ability and mental health in adults with chronic conditions. The purpose of this review was to systematically assess the effects of Qigong exercise on physical and psychological health outcomes in older adults. A total of 1282 older adults aged 62 to 83 years with depressive symptoms, frailty or chronic medical illnesses were included in this review. The meta-analysis showed that Qigong exercise resulted in significantly improved physical ability compared with active control or usual care (standardized mean difference [SMD]  1.00 and 1.20, respectively). The pooled effects of studies with thrice weekly Qigong sessions had the greatest effect () on physical ability in older adults. Lower quality studies demonstrated larger effect sizes than those of higher quality. Although Qigong exercise showed favorable effects on depression, balance and functioning, the overall effects did not reach statistical significance. No significant adverse events were reported. The findings suggest that the Qigong exercise may be an option for older adults to improve physical ability, functional ability, balance and to lessen depression and anxiety. However, the number of RCTs that enroll older adults is limited. More methodologically sound RCTs are needed to confirm the efficacy of Qigong exercise on physical and psychological health in older adults with chronic illnesses.

As one of the most serious complications of diabetes, diabetic cardiomyopathy (DCM) imposes a huge burden on individuals and society, and represents a major public health problem. It has long been recognized that physical exercise has important health benefits for patients with type 2 diabetes, and regular physical exercise can delay or prevent the complications of diabetes. Current studies show that physical exercise has been regarded as an importantly non-pharmacological treatment for diabetes and DCM, with high efficacy and low adverse events. It can inhibit the pathological processes of myocardial apoptosis, myocardial fibrosis, and myocardial microvascular diseases through improving myocardial metabolism, enhancing the regulation of Ca, and protecting the function of mitochondria. Eventually, it can alleviate the occurrence and development of diabetic complications. Describing the mechanisms of physical exercise on DCM may provide a new theory for alleviating, or even reversing the development of DCM, and prevent it from developing to heart failure.

Major depressive disorder (MDD) is a prevalent psychiatric disorder associated with varied prognosis, chronic course, and duration of illness with reduced quality of life. One factor that significantly contributes to the relevant disease burden of MDD is the heterogeneous treatment response patients experience with current treatment options. A variety of experimental protocols in humans and animals have highlighted that inflammation and neuroinflammation are relevant biological factors that interact with external stimuli and neurophysiological mechanisms, and can trigger MDD. It is well established that exercise is efficacious in treating mild to moderate depression with response rates comparable to mainstream therapies such as antidepressant medication and cognitive behavioral therapy. Several studies have shown that physical exercise is beneficial for a range of chronic diseases. Indeed, physical exercise can promote molecular changes that swerve a chronic pro-inflammatory state to an anti-inflammatory state in both periphery and central nervous system. The changes caused by physical exercise include an increase in PGC1α gene expression, a transcriptional co-activator involved in reducing the synthesis and releasing of pro-inflammatory cytokines, and an increase in anti-inflammatory cytokines. PGC1α changes the metabolism of kynurenine towards, and, in turn, it reduces glutamatergic neurotoxicity. Moreover, somestudies have shown that physical exercise promotes alterations in the circuitry of monoaminergic neurotransmission, at least in some aspects, through the effects on the release of proinflammatory cytokines. This review will highlight the effects of physical exercise as therapy and its relation withthe biological mechanisms involved in the pathophysiology of MDD, with particular emphasis in the interactions among physical exercise, hypothalamic-pituitary-adrenal (HPA) axis, neuroinflammation, and with the neurotransmitters underlying the main brain circuits involved in the MDD.

Emerging evidence highlights the substantial role of the kynurenine pathway in various physiological systems and pathological conditions. Physical exercise has been shown to impact the kynurenine pathway in response to both single (acute) and multiple (chronic) exercise training stimuli. In this perspective article, we briefly outline the current knowledge concerning exercise-induced modulations of the kynurenine pathway and discuss underlying mechanisms. Furthermore, we expose the potential involvement of exercise-induced kynurenine pathway modulations on energy homeostasis (eg, through de novo synthesis of NAD) and finally suggest how these modulations may contribute to exercise-induced benefits in the prevention and treatment of chronic diseases.

QUESTION:Does physical exercise training improve physical function and quality of life in people with cognitive impairment and dementia? Which training protocols improve physical function and quality of life? How do cognitive impairment and other patient characteristics influence the outcomes of exercise training?

DESIGN:Systematic review with meta-analysis of randomised trials.

PARTICIPANTS:People with mild cognitive impairment or dementia as the primary diagnosis.

INTERVENTION:Physical exercise.

OUTCOME MEASURES:Strength, flexibility, gait, balance, mobility, walking endurance, dual-task ability, activities of daily living, quality of life, and falls.

RESULTS:Forty-three clinical trials (n=3988) were included. According to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system, the meta-analyses revealed strong evidence in support of using supervised exercise training to improve the results of 30-second sit-to-stand test (MD 2.1 repetitions, 95% CI 0.3 to 3.9), step length (MD 5cm, 95% CI 2 to 8), Berg Balance Scale (MD 3.6 points, 95% CI 0.3 to 7.0), functional reach (3.9cm, 95% CI 2.2 to 5.5), Timed Up and Go test (-1second, 95% CI -2 to 0), walking speed (0.13m/s, 95% CI 0.03 to 0.24), and 6-minute walk test (50m, 95% CI 18 to 81) in individuals with mild cognitive impairment or dementia. Weak evidence supported the use of exercise in improving flexibility and Barthel Index performance. Weak evidence suggested that non-specific exercise did not improve dual-tasking ability or activity level. Strong evidence indicated that exercise did not improve quality of life in this population. The effect of exercise on falls remained inconclusive. Poorer physical function was a determinant of better response to exercise training, but cognitive performance did not have an impact.

CONCLUSION:People with various levels of cognitive impairment can benefit from supervised multi-modal exercise for about 60minutes a day, 2 to 3days a week to improve physical function. [Lam FMH , Huang MZ, Liao LR, Chung RCK, Kwok TCY, Pang MYC (2018) Physical exercise improves strength, balance, mobility, and endurance in people with cognitive impairment and dementia: a systematic review. Journal of Physiotherapy XX: XX-XX].

A growing body of literature indicates a potential role for physical exercise in the treatment of attention deficit hyperactivity disorder (ADHD). Suggested effects include the reduction of ADHD core symptoms as well as improvements in executive functions. In the current review, we provide a short overview on the neurophysiological mechanisms assumed to underlie the beneficial effects of exercise. Further, we review the current evidence from experimental studies regarding both acute exercise and long-term interventions in ADHD. While the positive effects observed after acute aerobic exercise are promising, very few well-designed long-term intervention studies have been conducted yet. Moreover, although exercise effects have not yet been studied in borderline personality disorder (BPD), in the end of this paper we derive hypotheses why exercise could also be beneficial for this patient population.

Accumulating evidence indicates that exercise can enhance brain function and attenuate neurodegeneration. Besides improving neuroplasticity by altering the synaptic structure and function in various brain regions, exercise also modulates multiple systems that are known to regulate neuroinflammation and glial activation. Activated microglia and several pro-inflammatory cytokines play active roles in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The purpose of this review is to highlight the impacts of exercise on microglial activation. Possible mechanisms involved in exercise-modulated microglial activation are also discussed. Undoubtedly, more studies are needed in order to disclose the detailed mechanisms, but this approach offers therapeutic potential for improving the brain health of millions of aging people where pharmacological intervention has failed.

Regular exercise has systemic beneficial effects, including the promotion of brain function. The adaptive response to regular exercise involves the up-regulation of the enzymatic antioxidant system and modulation of oxidative damage. Reactive oxygen species (ROS) are important regulators of cell signaling. Exercise, via intensity-dependent modulation of metabolism and/or directly activated ROS generating enzymes, regulates the cellular redox state of the brain. ROS are also involved in the self-renewal and differentiation of neuronal stem cells and the exercise-mediated neurogenesis could be partly associated with ROS production. Exercise has strong effects on the immune system and readily alters the production of cytokines. Certain cytokines, especially IL-6, IL-1, TNF-α, IL-18 and IFN gamma, are actively involved in the modulation of synaptic plasticity and neurogenesis. Cytokines can also contribute to ROS production. ROS-mediated alteration of lipids, protein, and DNA could directly affect brain function, while exercise modulates the accumulation of oxidativedamage. Oxidative alteration of macromolecules can activate signaling processes, membrane remodeling, and gene transcription. The well known neuroprotective effects of exercise are partly due to redox-associated adaptation.

WHAT IS KNOWN AND OBJECTIVE:Antiepileptic drugs often produce serious adverse effects, and many patients do not respond to them properly. Phytocannabinoids produce anticonvulsant effects in preclinical and preliminary human studies, and appear to produce fewer adverse effects than available antiepileptic drugs. The present review summarizes studies on the anticonvulsant properties of phytocannabinoids.

METHODS:Literature search using the PubMed database to identify studies on phytocannabinoids and epilepsy.

RESULTS AND DISCUSSION:Preclinical studies suggest that phytocannabinoids, especially cannabidiol and cannabidivarin, have potent anticonvulsant effects which are mediated by the endocannabinoid system. Human studies are limited in number and quality, but suggest that cannabidiol has anticonvulsant effects in adult and infantile epilepsy and is well tolerated after prolonged administration.

WHAT IS NEW AND CONCLUSION:Phytocannabinoids produce anticonvulsant effects through the endocannabinoid system, with few adverse effects. Cannabidiol and cannabidivarin should be tested in randomized, controlled clinical trials, especially in infantile epileptic syndromes.

PURPOSE OF REVIEW:Plant-based diets have been used with growing popularity for the treatment of a wide range of lifestyle-related diseases, including diabetes, hypertension, and obesity. With the reinvigoration of the conservative and dietary management of chronic kidney disease (CKD) and the use of low protein diets for secondary prevention of CKD to delay or prevent dialysis therapy, there is an increasing interest in the potential role of plant-based diets for these patients.

RECENT FINDINGS:Recently, a body of evidence related to the role of plant-based diet in preventing CKD has reemerged. Several observational studies have shown that red and processed meat have been associated with increased risk of CKD as well as faster progressing in those with preexisting CKD. In several substitution analyses, replacement of one serving of red and/or processed meat has been linked with sizable reductions in CKD risk as primary prevention. Although limited, experimental trials for the treatment of metabolic acidosis in CKD with fruits and vegetables show outcomes comparable to oral bicarbonate. The use of plant-based diets in CKD may have other benefits in the areas of hypertension, weight, hyperphosphatemia, reductions in hyperfiltration, and, possibly, mortality. The risk of potassium overload from plant-based diets appears overstated, mostly opinion-based, and not supported the evidence. Plant-based diets are generally well tolerated and provide adequate protein intake, including essential amino acids as long as the is correctly implemented.

SUMMARY:Plant-based diets should be recommended for both primary and secondary prevention of CKD. Concerns of hyperkalemia and protein inadequacy related to plant-based diets may be outdated and unsupported by the current body of literature. Healthcare providers in general medicine and nephrology can consider plant-based diets as an important tool for prevention and management of CKD.

Obesity affects over one-third of Americans and increases the risk of cardiovascular disease and type II diabetes. Interventional trials have consistently demonstrated that consumption of plant-based diets reduces body fat in overweight and obese subjects, even when controlling for energy intake. Nonetheless, the mechanisms underlying this effect have not been well-defined. This review discusses six major dietary mechanisms that may lead to reduced body fat. These include (1) reduced caloric density, (2) improved gut microbiota symbiosis, (3) increased insulin sensitivity, (4) reduced trimethylamine-N-oxide (TMAO), (5) activation of peroxisome proliferator-activated receptors (PPARs), and (6) over-expression of mitochondrial uncoupling proteins. Collectively, these factors improve satiety and increase energy expenditure leading to reduced body weight.

Beneficial effects of cannabidiol (CBD) have been described for a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood. Similar to clinical antidepressant or atypical antipsychotic drugs, recent findings clearly indicate that CBD, either acutely or repeatedly administered, induces plastic changes. For example, CBD attenuates the decrease in hippocampal neurogenesis and dendrite spines density induced by chronic stress and prevents microglia activation and the decrease in the number of parvalbumin-positive GABA neurons in a pharmacological model of schizophrenia. More recently, it was found that CBD modulates cell fate regulatory pathways such as autophagy and others critical pathways for neuronal survival in neurodegenerative experimental models, suggesting the potential benefit of CBD treatment for psychiatric/cognitive symptoms associated with neurodegeneration. These changes and their possible association with CBD beneficial effects in psychiatric disorders are reviewed here.

More than 6 million Americans have heart failure (HF) and more than 500,000 are diagnosed each year. In addition to its many adverse medical consequences, HF is also a significant risk factor for neurological disorders like Alzheimer's disease and associated with cognitive impairment long prior to the onset of these conditions. Converging bodies of literature suggest cognitive dysfunction in HF may be at least partially modifiable. One key mechanism for cognitive improvement is improved cerebral blood flow, which may be possible with exercise in patients with HF. This brief review provides a model for the likely neurocognitive benefits of exercise in HF and encourages further work in this area.

Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder of the autonomic nervous system in which a change from the supine position to an upright position causes an abnormally large increase in heart rate or tachycardia (30 bpm within 10 min of standing or head-up tilt). This response is accompanied by a decrease in blood flow to the brain and hence a spectrum of symptoms associated with cerebral hypoperfusion. Many of these POTS-related symptoms are also observed in chronic anxiety and panic disorders, and therefore POTS is frequently under- and misdiagnosed.

ETHNOPHARMACOLOGICAL RELEVANCE: Inonotus obliquus (Chaga mushroom), one of the widely known medicinal mushrooms, has been used to treat various cancers in Russia and most of Baltic countries for many centuries. AIM OF THE STUDY: To examine the anti-proliferative effects of Inonotus obliquus extract on melanoma B16-F10 cells. Furthermore, to assess the anti-tumor effect of Inonotus obliquus extract in vivo in Balb/c mice. MATERIALS AND METHODS: The water extract of Inonotus obliquus was studied for anti-proliferative effects on the growth and morphology of B16-F10 melanoma cells and for anti-tumor effect using in vivo in Balb/c mice. RESULTS: Inonotus obliquus extract not only inhibited the growth of B16-F10 cells by causing cell cycle arrest at G(0)/G(1) phase and apoptosis, but also induced cell differentiation. These effects were associated with the down-regulation of pRb, p53 and p27 expression levels, and further showed that Inonotus obliquus extract resulted in a G(0)/G(1) cell cycle arrest with reduction of cyclin E/D1 and Cdk 2/4 expression levels. Furthermore, the anti-tumor effect of Inonotus obliquus extract was assessed in vivo in Balb/c mice. Intraperitoneal administration of Inonotus obliquus extract significantly inhibited the growth of tumor mass in B16-F10 cells implanted mice, resulting in a 3-fold (relative to the positive control, (*)p<0.05) inhibit at dose of 20mg/kg/day for 10 days. CONCLUSION: This study showed that the water extract of Inonotus obliquus mushroom exhibited a potential anticancer activity against B16-F10 melanoma cells in vitro and in vivo through the inhibition of proliferation and induction of differentiation and apoptosis of cancer cells.

This article provides an overview of the current literature relating to the efficacy of dietary nitrate (NO) ingestion in altering aspects of cardiovascular and metabolic health and exercise capacity in healthy and diseased individuals. The consumption of NO-rich vegetables, such as spinach and beetroot, have been variously shown to promote nitric oxide bioavailability, reduce systemic blood pressure, enhance tissue blood flow, modulate muscle Outilisation and improve exercise tolerance both in normoxia and in hypoxia, as is commonly observed in a number of disease states. NOingestion may, therefore, act as a natural means for augmenting performance and attenuating complications associated with limited Oavailability or transport, hypertension and the metabolic syndrome. Recent studies indicate that dietary NOmight also augment intrinsic skeletal muscle contractility and improve the speed and power of muscle contraction. Moreover, several investigations suggest that NOsupplementation may improve aspects of cognitive performance both at rest and during exercise. Collectively, these observations position NOas more than a putative ergogenic aid and suggest that increasing natural dietary NOintake may act as a prophylactic in countering the predations of senescence and certain cardiovascular-metabolic diseases.