Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.     

Health Behavior Correlates of Depression in a Sample of High School Students

Frequency of symptoms of depression and selected health-related practices and events were measured in a sample of 219 high school students. Students reported numerous symptoms of depression. Relative proportions of boys and girls reporting symptoms of depression were not significantly different. However, girls reported experiencing more severe depression than their male counterparts. Depression correlated significantly with several of the 22 health practices and states of affect examined. Both the determinants and manifestations of depression in adolescent cohorts require in-depth investigation. Possible implications for school health personnel are discussed.     

Pain in individuals with RASopathies: Prevalence and clinical characterization in a sample of 80 affected patients

Pain in individuals with RASopathies is a neglected topic in literature. In this article, we assessed prevalence and profile of pain in a sample of 80 individuals affected by RASopathies. The study sample included individuals with Noonan syndrome (N = 42), Costello syndrome (N = 17), and cardio‐facio‐cutaneous syndrome (N = 21). A set of standardized questionnaires and scales were administered (VAS/numeric scale, r‐FLACC, Wang‐Baker scale, NPSI, BPI, NCCPC‐R) to detect and characterize acute and chronic pain and to study the influence of pain on quality of life (PEDs‐QL, SF‐36) and sleeping patterns (SDSC); revision of past medical history and multisystemic evaluation was provided. Available clinical data were correlated to the presence of pain. High prevalence of acute (44%) and chronic (61%) pain was documented in the examined sample. Due to age and intellectual disability, acute pain was localized in 18/35 individuals and chronic pain in 33/49. Muscle‐skeletal and abdominal pain was more frequently reported. The intensity of acute and chronic pain interfered with daily activities in 1/3 of the sample. Pain negatively impacted on QoL and sleeping patterns. This work documents that pain is highly prevalent in RASopathies. Future studies including subjective and objective measures of pain are required to discriminate a somatosensory abnormality from an abnormal elaboration of painful stimuli at a central level.     

Evaluating the psychometric properties of the EQ-5D-5L and SF-6D among patients with haemophilia

The European Journal of Health Economics - The aim of this study was to evaluate the psychometric properties of the EQ-5D-5L and SF-6D, and to compare their performance among patients living with...     

Subacute and acute fasciolosis in sheep in southern Brazil

Eight outbreaks of acute and subacute fasciolosis are reported in sheep in the municipality of Santa Vitória do Palmar, southern Brazil, in areas used for irrigated rice cultivation, which are subject to frequent flooding. Two outbreaks occurred mid-winter during July and August, and six occurred during spring and early summer. Morbidity ranged from 3 to 66.7 %, and mortality ranged from 3 to 50 %. Clinical signs included weight loss, mucosal pallor, apathy, depression, muscle tremors, and drooling; these were followed by death within approximately 24 h. Some sheep were found dead. Gross lesions were characterized by an irregular liver capsule with fibrin deposition and hemorrhages. The liver parenchyma contained hemorrhagic tracts or irregular clear areas alternated with dark hemorrhagic areas. Histologically, hemorrhagic dark red tracts of necrotic liver parenchyma and an inflammatory infiltrate were noted; these lesions coincided with the presence of immature flukes. Langhans-type giant cells, fibrous tissue, and bile duct cell proliferation were observed in subacute cases. Chronic fasciolosis is a well-known disease to farmers in southern Brazil; nevertheless, acute and subacute fasciolosis, which are more difficult to diagnose and treat, may cause important economic losses. Efficient control of fasciolosis requires integration of measures to treat infections in the definitive host, to reduce the population of snails of the genus Lymnaea, and to avoid contact between the parasite and host by appropriate pasture management.     

Early Impacts of a Healthy Food Distribution Program on the Availability and Price of Fresh Fruits and Vegetables in Small Retail Venues in Los Angeles

Healthy food distribution programs that allow small retailers to purchase fresh fruits and vegetables at wholesale prices may increase the profitability of selling produce. While promising, little is known about how these programs affect the availability of fresh fruits and vegetables in underserved communities. This study examined the impacts of a healthy food distribution program in Los Angeles County over its first year of operation (August 2015–2016). Assessment methods included: (1) a brief survey examining the characteristics, purchasing habits, and attitudes of stores entering the program; (2) longitudinal tracking of sales data examining changes in the volume and variety of fruits and vegetables distributed through the program; and (3) the collection of comparison price data from wholesale market databases and local grocery stores. Seventeen stores participated in the program over the study period. One-fourth of survey respondents reported no recent experience selling produce. Analysis of sales data showed that, on average, the total volume of produce distributed through the program increased by six pounds per week over the study period (95% confidence limit: 4.50, 7.50); trends varied by store and produce type. Produce prices offered through the program approximated those at wholesale markets, and were lower than prices at full-service grocers. Results suggest that healthy food distribution programs may reduce certain supply-side barriers to offering fresh produce in small retail venues. While promising, more work is needed to understand the impacts of such programs on in-store environments and consumer behaviors.     

Cannabis and symptoms of PMS and PMDD

Cannabis has been found to alleviate a wide array of medical symptoms, including those that overlap with physical and emotional symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD), including insomnia, irritability, depression, and joint pain. Little work has addressed the use of cannabis as a treatment for PMS or PMDD or the role of women’s cannabis treatment expectancies as a predictor of consumption. Women who reported having experienced PMS and PMDD and endorsed lifetime cannabis use (N?=?145), completed an online survey assessing their frequency of cannabis use, PMS/PMDD symptoms, expectancies of cannabis-induced relief from symptoms, as well as cannabis-related problems. Women were found to hold meaningful expectancies that cannabis would treat all PMS/PMDD symptoms, except for overeating/food cravings. Cannabis treatment expectancies were positively associated with PMS/PMDD symptoms and with monthly cannabis use, and were negatively associated with cannabis-related problems. Research should further examine the relationship of cannabis treatment expectancies with individuals’ cannabis use, as findings indicate the potential for these expectancies to serve a punitive or protective role in the development of cannabis-related problems. Increased research on how cannabis might ameliorate symptoms of PMS and PMDD could help establish an alternative treatment plan that offers relief with fewer negative side effects.