Methamphetamine Effects on Adolescent Brain Development in Both Sexes

Vulnerability to drug addiction in adolescents (ADOLs) may lead to faster rates of addiction and higher rates of relapse. The brain is developing in adolescence, including the prefrontal cortex (PFC) and the nucleus accumbens (NAc), which are regions involved in self-control and reward systems, respectively. Further, females, both human and rat models, often exhibit faster rates of addiction than males. Research from this lab has found previously that adult rats of both sexes exposed to amphetamine during ADOL had reduced expression of dopamine D1 receptors (D1R) in the medial PFC but no change in the NAc. The purpose of this current study is to determine how age and sex influence methamphetamine’s (METH) effects on the brain and behavio

Gaps in Treatment and Surveillance: Head and Neck Cancer Care in a Safety-Net Hospital.

Objective:Treatment delays and suboptimal adherence to posttreatment surveillance may adversely affect head and neck cancer (HNC) outcomes. Such challenges can be exacerbated in safety-net settings that struggle with limited resources and serve a disproportionate number of patients vulnerable to gaps in care. This study aims to characterize treatment delays and adherence with posttreatment surveillance in HNC care at an urban tertiary care public hospital in San Francisco. Study Design:Retrospective chart review. Setting:Urban tertiary care public hospital in San Francisco. Subjects and Methods:We identified all cases of HNC diagnosed from 2008 to 2010 through the electronic medical record. We abstracted data, including patient characteristics, disease characteristics, pathology and radiology findings, treatment details, posttreatment follow-up, and clinical outcomes. Results:We included 64 patients. Median time from diagnosis to treatment initiation (DTI) was 57 days for all patients, 54 days for patients undergoing surgery only, 49 days for patients undergoing surgery followed by adjuvant radiation ± chemotherapy, 65 days for patients undergoing definitive radiation ± chemotherapy, and 29 days for patients undergoing neoadjuvant chemotherapy followed by radiation or chemoradiation. Overall, 69% of patients completed recommended treatment. Forty-two of 61 (69%) patients demonstrated adherence to posttreatment visits in year 1; this fell to 14 out of 30 patients (47%) by year 5. Conclusion:DTI was persistently prolonged in this study compared with prior studies in other public hospital settings. Adherence to posttreatment surveillance was suboptimal and continued to decline as the surveillance period progressed

Speed School Programme in Ethiopia. Tracking the progress of Speed School students 2011-2017

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Treadmill exercise has minimal impact on obesogenic diet-related gut microbiome changes but alters adipose and hypothalamic gene expression in rats

Exercise has been extensively utilised as an effective therapy for overweight- and obesity-associated changes that are linked to health complications. Several preclinical rodent studies have shown that treadmill exercise alongside an unhealthy diet improves metabolic health and microbiome composition. Furthermore, chronic exercise has been shown to alter hypothalamic and adipose tissue gene expression in diet-induced obesity. However, limited work has investigated whether treadmill exercise commenced following exposure to an obesogenic diet is sufficient to alter microbiome composition and metabolic health. To address this gap in the literature, we fed rats a high-fat/high-sugar western-style cafeteria diet and assessed the effects of 4 weeks of treadmill exercise on adiposity, diet-induced gut dysbiosis, as well as hypothalamic and retroperitoneal white adipose tissue gene expression. Forty-eight male Sprague-Dawley rats were allocated to either regular chow or cafeteria diet and after 3 weeks half the rats on each diet were exposed to moderate treadmill exercise for 4 weeks while the remainder were exposed to a stationary treadmill. Microbial species diversity was uniquely reduced in exercising chow-fed rats, while microbiome composition was only changed by cafeteria diet. Despite limited effects of exercise on overall microbiome composition, exercise increased inferred microbial functions involved in metabolism, reduced fat mass, and altered adipose and hypothalamic gene expression. After controlling for diet and exercise, adipose Il6 expression and liver triglyceride concentrations were significantly associated with global microbiome composition. Moderate treadmill exercise induced subtle microbiome composition changes in chow-fed rats but did not overcome the microbiome changes induced by prolonged exposure to cafeteria diet. Predicted metabolic function of the gut microbiome was increased by exercise. The effects of exercise on the microbiome may be modulated by obesity severity. Future work should investigate whether exercise in combination with microbiome-modifying interventions can synergistically reduce diet- and obesity-associated comorbidities

Non-REM sleep with hypertonia in Parkinsonian Spectrum Disorders: A pilot investigation.

INTRODUCTION: From an ongoing multicenter effort toward differentiation of Parkinsonian spectrum disorders (PSD) from other types of neurodegenerative disorders, the sleep biomarker non-rapid-eye-movement sleep with hypertonia (NRH) emerged. METHODS: This study included in the PSD group patients with dementia with Lewy bodies/Parkinson disease dementia (DLB/PDD = 16), Parkinson disease (PD = 16), and progressive supranuclear palsy (PSP = 13). The non-PSD group included patients with Alzheimer disease dementia (AD = 24), mild cognitive impairment (MCI = 35), and a control group with normal cognition (CG = 61). In-home, multi-night Sleep Profiler studies were conducted in all participants. Automated algorithms detected NRH, characterized by elevated frontopolar electromyographic power. Between-group differences in NRH were evaluated using Logistic regression, Mann-Whitney U and Chi-squared tests. RESULTS: NRH was greater in the PSD group compared to non-PSD (13.9 ± 11.0% vs. 3.1 ± 4.7%, P < 0.0001). The threshold NRH≥5% provided the optimal between-group differentiation (AUC = 0.78, P < 0.001). NRH was independently associated with the PSD group after controlling for age, sex, and SSRI/SNRI use (P < 0.0001). The frequencies of abnormal NRH by subgroup were PSP = 92%, DLB/PDD = 81%, PD = 56%, MCI = 26%, AD = 17%, and CG = 16%. The odds of abnormal NRH in each PSD subgroup ranged from 3.7 to 61.2 compared to each non-PSD subgroup. The night-to-night and test-retest intraclass correlations were excellent (0.78 and 0.84, both P < 0.0001). CONCLUSIONS: In this pilot study, NRH appeared to be a novel candidate sleep biomarker for PSD-related neurodegeneration. Future studies in larger cohorts are needed to confirm these findings, understand the etiology of NRH magnitude/duration, and determine whether it is an independent prodromal marker for specific neurodegenerative pathologies

REST Regulates Distinct Transcriptional Networks in Embryonic and Neural Stem Cells

The maintenance of pluripotency and specification of cellular lineages during embryonic development are controlled by transcriptional regulatory networks, which coordinate specific sets of genes through both activation and repression. The transcriptional repressor RE1-silencing transcription factor (REST) plays important but distinct regulatory roles in embryonic (ESC) and neural (NSC) stem cells. We investigated how these distinct biological roles are effected at a genomic level. We present integrated, comparative genome- and transcriptome-wide analyses of transcriptional networks governed by REST in mouse ESC and NSC. The REST recruitment profile has dual components: a developmentally independent core that is common to ESC, NSC, and differentiated cells; and a large, ESC-specific set of target genes. In ESC, the REST regulatory network is highly integrated into that of pluripotency factors Oct4-Sox2-Nanog. We propose that an extensive, pluripotency-specific recruitment profile lends REST a key role in the maintenance of the ESC phenotype

What influences people’s responses to public health messages for managing risks and preventing infectious diseases? A rapid systematic review of the evidence and recommendations

Background: Individual behaviour changes, such as hand hygiene and physical distancing, are required on a population scale to reduce transmission of infectious diseases such as COVID-19. However, little is known about effective methods of communicating risk reducing information, and how populations might respond. Objective: To synthesise evidence relating to what (1) characterises effective public health messages for managing risk and preventing infectious disease and (2) influences people’s responses to messages. Design: A rapid systematic review was conducted. Protocol is published on Prospero CRD42020188704. Data sources: Electronic databases were searched: Ovid Medline, Ovid PsycINFO and Healthevidence. org, and grey literature (PsyarXiv, OSF Preprints) up to May 2020. Study selection: All study designs that (1) evaluated public health messaging interventions targeted at adults and (2) concerned a communicable disease spread via primary route of transmission of respiratory and/or touch were included. Outcomes included preventative behaviours, perceptions/awareness and intentions. Non-English language papers were excluded. Synthesis: Due to high heterogeneity studies were synthesised narratively focusing on determinants of intentions in the absence of measured adherence/ preventative behaviours. Themes were developed independently by two researchers and discussed within team to reach consensus. Recommendations were translated from narrative synthesis to provide evidence-based methods in providing effective messaging. Results: Sixty-eight eligible papers were identified. Characteristics of effective messaging include delivery by credible sources, community engagement, increasing awareness/knowledge, mapping to stage of epidemic/ pandemic. To influence intent effectively, public health messages need to be acceptable, increase understanding/perceptions of health threat and perceived susceptibility. Discussion: There are four key recommendations: (1) engage communities in development of messaging, (2) address uncertainty immediately and with transparency, (3) focus on unifying messages from sources and (4) frame messages aimed at increasing understanding, social responsibility and personal control. Embedding principles of behavioural science into public health messaging is an important step towards more effective health-risk communication during epidemics/pandemics

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447