Alterations to Melanocortinergic, GABAergic and Cannabinoid Neurotransmission Associated with Olanzapine-Induced Weight Gain

Background/Aim: Second generation antipsychotics (SGAs) are used to treat schizophrenia but can cause serious metabolic side-effects, such as obesity and diabetes. This study examined the effects of low to high doses of olanzapine on appetite/ metabolic regulatory signals in the hypothalamus and brainstem to elucidate the mechanisms underlying olanzapineinduced obesity. Methodology/Results: Levels of pro-opiomelanocortin (POMC), neuropeptide Y (NPY) and glutamic acid decarboxylase (GAD65, enzyme for GABA synthesis) mRNA expression, and cannabinoid CB1 receptor (CB1R) binding density (using [ 3 H]SR-141716A) were examined in the arcuate nucleus (Arc) and dorsal vagal complex (DVC) of female Sprague Dawley rats following 0.25, 0.5, 1.0 or 2.0 mg/kg olanzapine or vehicle (36/day, 14-days). Consistent with its weight gain liability, olanzapine significantly decreased anorexigenic POMC and increased orexigenic NPY mRNA expression in a dose-sensitive manner in the Arc. GAD65 mRNA expression increased and CB1R binding density decreased in the Arc and DVC. Alterations to neurotransmission signals in the brain significantly correlated with body weight and adiposity. The minimum dosage threshold required to induce weight gain in the rat was 0.5 mg/kg olanzapine. Conclusions: Olanzapine-induced weight gain is associated with reduced appetite-inhibiting POMC and increased NPY. This study also supports a role for the CB1R and GABA in the mechanisms underlying weight gain side-effects, possibly b

What works for whom in the management of diabetes in people living with dementia: a realist review

Background Dementia and diabetes mellitus are common long-term conditions and co-exist in a large number of older people. People living with dementia (PLWD) may be less able to manage their diabetes, putting them at increased risk of complications such as hypoglycaemia. The aim of this review was to identify key mechanisms within different interventions that are likely to improve diabetes outcomes in PLWD. Methods This is a realist review involving scoping of the literature and stakeholder interviews to develop theoretical explanations of how interventions might work, systematic searches of the evidence to test and develop the theories and their validation with a purposive sample of stakeholders. Twenty-six stakeholders — user/patient representatives, dementia care providers, clinicians specialising in diabetes or dementia and researchers — took part in interviews, and 24 participated in a consensus conference. Results We included 89 papers. Ten focused on PLWD and diabetes, and the remainder related to people with either dementia, diabetes or other long-term conditions. We identified six context-mechanism-outcome configurations which provide an explanatory account of how interventions might work to improve the management of diabetes in PLWD. This includes embedding positive attitudes towards PLWD, person-centred approaches to care planning, developing skills to provide tailored and flexible care, regular contact, family engagement and usability of assistive devices. An overarching contingency emerged concerning the synergy between an intervention strategy, the dementia trajectory and social and environmental factors, especially family involvement. Conclusions Evidence highlighted the need for personalised care, continuity and family-centred approaches, although there was limited evidence that this happens routinely. This review suggests there is a need for a flexible service model that prioritises quality of life, independence and patient and carer priorities. Future research on the management of diabetes in older people with complex health needs, including those with dementia, needs to look at how organisational structures and workforce development can be better aligned to their needs. Trial registration PROSPERO, CRD42015020625. Registered on 18 May 2015

Linking Patterns in Endocrine-Disrupting Compounds to Storm Discharge and Yoy Smb Health in the Upper Juniata River Watershed

Population declines and disease incidence in smallmouth bass (Micropterus dolomieu) in the Susquehanna River basin have been linked to endocrine-disrupting compounds (EDCs) as a likely causative agent. Nothing is known about this link in the upper Juniat

Temporal and spatial variation in endocrine disrupting compounds and young-of-theyear smallmouth bass health in the upper Juniata River system

Over a 2-year time frame in summer 2016 and 2017, we quantified the dynamics of endocrine disrupting compounds (EDCs) in the upper Juniata River system. EDCs have been implicated as a likely cause of declines in recruitment and thus adult smallmouth bass (SMB) populations in the lower Juniata and Susquehanna Rivers since 2005. We studied the mainstem of the upper Juniata River (near Mapleton), and 5 other major tributaries in the drainage system. Specifically, we quantified EDC levels (estradiol equivalents, EEQ in ng/L) across a range of flow types at 9 different sites and subsequently looked at how these hydrologic conditions (e.g., peak storm flows vs. ascending flow, vs. base flows, etc.) and landscape characteristics among sites may explain the variation in EDCs. In addition, we measured EDC levels along a continuum of the Juniata River downstream of a waste water treatment plant to quantify decay patterns once entering water. Finally, at each site we collected information on young-of-the-year (YOY) SMB condition and diet. We used non-lethal gastric lavage techniques to extract diet contents and sacrificed a subset of individuals to estimate efficiency. EDC concentrations varied widely within sites at the same time, within sites at different times, among sites, and between years, but levels thus far in our surveys have not surpassed 1 ng/L, a threshold considered to be a concern for fish health. Initial analyses indicate that river discharge and flow characteristics related to storm runoff cannot explain variation in EDCs, nor have we identified landscape characteristics at 2 spatial scales that can explain variation. Thus far, we could not detect a trend in EDC concentrations downstream of the waste water treatment plant. In 2016, YOY SMB were numerous and were in excellent health, but were nearly absence during the same time in 2017. Most individuals contained at least some prey items, which on average consisted of about half aquatic prey and half terrestrial or neustonic prey. Rusty crayfish diet lacked resemblance to diet in YOY SMB. After gastric lavage, only a few fish were found to have some stomach contents remaining when dissected in the lab. Furthermore, nearly all YOY SMB fully recovered from field lavage experiences. Our study has identified levels of EDCs in the upper Juniata River systems that should be considered important for addressing ecological health in the broader Susquehanna River basin. Advancing our understanding of the dynamics of these emerging contaminants and their potential effects on smallmouth bass will require tracking and measuring specific compounds. We found gastric lavage to be a safe and effective technique to study YOY SMB feeding ecology without having to kill numerous individuals of this popular gamefish

Variability in Endocrine-Disrupting Compounds in the Upper Juniata River System

Population declines and disease incidence in smallmouth bass (Micropterus dolomieu) in the Susquehanna River basin have been linked to endocrine-disrupting compounds (EDCs) as a likely causative agent. Nothing is known about EDC dynamics in the upper Juniata River basin, and specifically how EDC patterns may vary with hydrologic conditions and landscape characteristics. We sampled water in the mainstem of the Juniata River and at 5 major tributaries across a range of discharges (e.g., peak storm flows, descending flows, base flows, etc.) and landscape characteristics over a 2-year time frame during the summers of 2016 and 2017. Samples were analyzed for EDCs measured as total estradiol equivalents (EEQ, ng/L). We also collected information on pH, dissolved oxygen, temperature, specific conductance, and total dissolved solids during each sampling event to identify possible connections between hydrologic conditions and variation in EDC concentrations. We found extremely high spatial and temporal variation in EDCs concentrations. Concentrations varied highly within sites at the same time, within sites at different times, among sites, and between years, but levels thus far have not surpassed the 1 ng/L threshold considered to be a concern for fish health. Thus far, we could not detect a trend in EDC concentrations along a continuum of the Juniata River downstream of the waste water treatment plant. Additionally, our current analyses cannot link variation in EDC concentrations to discharge, simple water quality measurements, or landuse/landcover at 2 spatial scales, but early indications suggest that EDCs are present in quantities that should be considered important for addressing ecological health in the broader Susquehanna River basin

Diet of Young-Of-The-Year Smallmouth Bass in the Upper Juniata River System

The decline of young-of-the-year (YOY) smallmouth bass (SMB, Micropterus dolomieu) recruitment and adult densities in the Susquehanna River basin since 2005 raises concern for the health and well being of the fishery. Our study focused on understanding the feeding ecology of YOY SMB in the upper Juniata River watershed, a major tributary to the Susquehanna River. We studied the mainstem of the upper Juniata River, and the major tributaries forming and joining the river. We sampled the YOY smallmouth bass for a two-year period during the summer of 2016 and 2017. Our specific objectives were to 1) characterize the diet of SMB and a potential invasive competitor, the rusty crayfish (Orconectes rusticus), 2) document the physical condition and external health of individuals, and 3) evaluate the effectiveness of gastric lavage to extract diet contents at an early life history stage. A subset of individuals was sacrificed to check lavage efficiency and these individuals were also sent to be examined for histopathological anomalies that may result from pharmaceutical contamination (i.e., endocrine disrupting compounds) that is considered to be a likely cause of SMB decline. We also quantified habitat conditions using rapid visual techniques and ecological health of each site following the protocols for the Pennsylvania Index of Biotic Integrity for wadeable freestone streams. PA IBI scores (range 34 – 67) and habitat conditions (range 46 – 70%) were rather poor in both years. In summer (July and August) 2016, YOY SMB were numerous and were in excellent health, but were nearly absence during the same time in 2017. Few external anomalies consisted of parasites only. Most individuals were full of prey items, which on average consisted of about half aquatic prey and half terrestrial or neustonic prey. Rusty crayfish diet contents lacked any resemblance to diet contents in YOY SMB. Gastric lavage techniques were effective at removing gut contents and only a few individuals were found to have stomach contents remaining when dissected in the lab. Furthermore, nearly all YOY SMB fully recovered from field lavage experiences. Only 2 individuals died, and this was likely due to extreme river surface water temperatures (89 F) at the time of sampling. Thus, gastric lavage is a safe and effective technique to study YOY SMB feeding ecology and important links between recruitment, diet, and food quality without having to kill numerous fish