Prithviraj Rajebhosale
Oct 23, 2024; 44:e0063242024-e0063242024
Cellular

The GluN3A subunit of N-methyl-D-aspartate receptors (NMDARs) plays an established role in synapse development, but its contribution to neural circuits in the adult brain is less clear. Recent work has demonstrated that in select cell populations, GluN3A assembles with GluN1 to form GluN1/GluN3A receptors that are insensitive to glutamate and instead serve as functional excitatory glycine receptors (eGlyRs). Our understanding of these eGlyRs, and how they contribute to intrinsic excitability and synaptic communication within relevant networks of the developing and the mature brain, is only beginning to be uncovered. Here, using male and female mice, we demonstrate that GluN3A subunits are enriched in the adult ventral hippocampus (VH), where they localize to synaptic and extrasynaptic sites and can assemble as functional eGlyRs on CA1 pyramidal cells. GluN3A expression was barely detectable in the adult dorsal hippocampus (DH). We also observed a high GluN2B content in the adult VH, characterized by slow NMDAR current decay kinetics and a high sensitivity to the GluN2B-containing NMDAR antagonist ifenprodil. Interestingly, the GluN2B enrichment in the adult VH was dependent on GluN3A as GluN3A deletion accelerated NMDAR decay and reduced ifenprodil sensitivity in the VH, suggesting that GluN3A expression can regulate the balance of conventional NMDAR subunit composition at synaptic sites. Lastly, we found that GluN3A knock-out also enhanced both NMDAR-dependent calcium influx and NMDAR-dependent long-term potentiation in the VH. Together, these data reveal a novel role for GluN3A and eGlyRs in the control of ventral hippocampal circuits in the mature brain.

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by -secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V₃₂₁L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back signaling and was previously found to be associated with psychosis (Walss-Bass et al., 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back signaling in the dentate gyrus (DG) of male and female mice. The V₃₂₁L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V₃₂₁L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V₃₂₁L DG. These genes coordinated a larger network with other dysregulated genes. Weighted gene correlation network analysis and protein interaction network analyses revealed striking similarity between DG transcriptomes of V₃₂₁L mouse and humans with SCZ.

The brain diagram, called a connectome, could revolutionize researchers' understanding of the human brain, which has many parallels with a fruit fly's

Teachers, administrators, and school support staff must understand their own social-emotional abilities before they can impart those skills to students, according to new research.

The film follows three Indianapolis adults as they seek to overcome obstacles on the path to earning an educational credential that they missed earlier.

Poor sleep is linked to cardiometabolic disease, depression and anxiety, among other concerns. Sleep disturbances can begin in childhood, but insomnia symptoms in children aren’t always taken seriously — and how childhood symptoms develop into a persisting disorder remains elusive. Learn more from Julio Fernandez-Mendoza, professor at the College of Medicine, in the next Virtual Speaker Series from the Penn State Alumni Association from noon to 1 p.m. ET on Oct. 18. 

Loneliness and cognitive performance were related in the short term for older adults, according to a new study from researchers in the Penn State College of Health and Human Development.

"My biggest honour in my journey as Food Pharmer is when Sudha Murthy Ma'am contacted me," content creator Revant Himatsingka said.

Sponsors in the Child and Adult Care Food Program (CACFP) can receive reimbursement for meals served in compliance with program regulations at qualifying child care centers, adult day care centers, emergency shelters, family day care homes and afterschool programs. Sponsors may be reimbursed for up to two meals and one snack per participant each day. Participant eligibility is tied to income eligibility guidelines that are adjusted annually by the USDA.

In 2021, anonymous reports helped protect 2,184 vulnerable adults from potential abuse; new hotline makes reporting neglect, abuse and exploitation easy and confidential   NEWARK (Nov. 30, 2022) – The Delaware Division of Services for Aging and Adults with Physical Disabilities (DSAAPD) today announced the launch of the new Adult Protective Services (APS) hotline – 888-APS-4302. With one simple […]

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Bronchiectasis is a chronic lung condition which is characterised by recurrent chest infections, chronic sputum production and cough, and limited exercise tolerance. While bronchiectasis may be caused by various aetiologies, these features are shared by most patients with bronchiectasis regardless of the cause. This review consolidates the existing evidence on patient-managed interventions for adults with bronchiectasis, while also outlining areas for future research. Airway clearance techniques and hyperosmolar agents are key components of the bronchiectasis management and consistently recommended for clinical implementation. Questions around their prescription, such as optimal sequence of delivery, are still to be answered. Pulmonary rehabilitation and exercise are also recommended for patients with bronchiectasis. Relatively strong evidence underpins this recommendation during a clinically stable stage of the disease, although the role of pulmonary rehabilitation following an exacerbation is still unclear. Additionally, self-management programmes feature prominently in bronchiectasis treatment, yet the lack of consensus regarding their definition and outcomes presents hurdles to establishing a cohesive evidence base. Moreover, cough, a cardinal symptom of bronchiectasis, warrants closer examination. Although managing cough in bronchiectasis may initially appear risky, further research is necessary to ascertain whether strategies employed in other respiratory conditions can be safely and effectively adapted to bronchiectasis, particularly through identifying patient responder populations and criteria where cough may not enhance airway clearance efficacy and its control is needed. Overall, there is a growing recognition of the importance of patient-managed interventions in the bronchiectasis management. Efforts to improve research methodologies and increase research funding are needed to further advance our understanding of these interventions, and their role in optimising patient care and outcomes.

Background:

The COVID-19 pandemic social distancing requirements encouraged patients to avoid public spaces including in-office health care visits. Ambulatory-care-sensitive conditions (ACSCs) represent conditions that can be managed with quality primary care and when access is limited, these conditions can lead to avoidable emergency department (ED) visits.

The management of chylothorax remains challenging given the limited evidence and significant heterogeneity in practice. In addition, there are no practical guidelines on the optimal approach to manage this complex condition. We convened an international group of 27 experts from 20 institutions across five countries and four specialties (pulmonary, interventional radiology, thoracic surgery and nutrition) with experience and expertise in managing adult patients with chylothorax. We performed a literature and internet search for reports addressing seven clinically relevant PICO (Patient, Intervention, Comparison and Outcome) questions pertaining to the management of adult patients with chylothorax. This consensus statement, consisting of best practice statements based on expert consensus addressing these seven PICO questions, was formulated by a systematic and rigorous process involving the evaluation of published evidence, augmented with provider experience. Panel members participated in the development of the final best practice statements using the modified Delphi technique. Our consensus statement aims to offer guidance in clinical decision making when managing patients with chylothorax while also identifying gaps in knowledge and informing future research.

ABSTRACTIntroduction: Nigeria has the highest number of children who have not received any vaccines in Africa. The training-of-trainers (TOT) model used to train program managers (PMs) and health care workers (HCWs) is ineffective for adult learning and limits immunization programs’ success. We incorporated adult learning principles (ALPs) in designing and delivering TOT for immunization PMs and HCWs to use data to engage communities for tailored immunization strategies.Methods: Our study was implemented in 3 local government areas (LGAs) of the Federal Capital Territory, Nigeria. A training curriculum was developed, integrating ALPs and technical and operational content based on best practices in delivering immunization training and the training needs assessment findings. State PMs (n=10), LGA PMs (n=30), and HCWs (n=42) were trained on the human-centered design for tailoring immunization programs (HCD-TIP) approaches using ALPs. We used interviews and surveys with purposively and conveniently sampled PMs and HCWs, respectively, and observations to assess participants’ satisfaction, knowledge and competence, behavior changes, and results. The interviews were analyzed thematically, and surveys were statistically.Results: There was a high level of satisfaction with the training among LGA PMs (100%), state PMs (91%), and HCWs (85%), with significant knowledge and competence improvements post-training (P<.001). The trained participants conducted 2 HCD sessions with 24 undervaccinated communities and co-designed 24 prototype solutions for testing. Results showed increased coverage of the pentavalent vaccine first dose (54%) and third dose (188%) across 12 participating communities. Improved community colaboration, communication skills, and data-driven approaches were the most cited behavior changes in practice.Conclusion: The application of ALPs in training, use of HCD-TIP approaches and tools, and supportive supervision enhanced PMs’ and HCWs’ capacity for tailored interventions. Countries should consider adopting a holistic approach that focuses on using these approaches in immunization programs to strengthen the health system for equitable vaccine coverage.

BACKGROUND AND PURPOSE:

World Health Organization (WHO) grade 2 and 3 diffuse gliomas account for approximately 5% of primary brain tumors. They are invasive and infiltrative tumors and have considerable morbidity, causing progressive neurologic deterioration. The mean survival time is <10 years from diagnosis. Surgical debulking represents first-line management. The extent of resection is associated with progression-free and overall survival. Radiologic assessment of the extent of resection is challenging. This can be underestimated on early postoperative MRI, meaning that accurate assessment may be achieved only on delayed follow-up imaging. We hypothesized that DWI may help facilitate more reliable estimates of the extent of resection on early postoperative MRI. This study aimed to assess the utility of DWI in early postoperative MRI to evaluate the extent of resection.

BackgroundAttention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, for which there are effective pharmacological treatments that improve symptoms and reduce complications. Guidelines published by the National Institute for Health and Care Excellence recommend that primary care practitioners prescribe medication for adult ADHD under shared-care agreements with Adult Mental Health Services (AMHS). However, provision remains uneven, with some practitioners reporting a lack of support.AimThis study aimed to describe elements of support, and their availability/use, in primary care prescribing for adult ADHD medication in England to improve access for this underserved population and inform service improvement.Design and settingCross-sectional surveys were used to elicit data from commissioners, health professionals (HPs), and people with lived experience of ADHD (LE) across England about elements supporting pharmacological treatment of ADHD in primary care.MethodThree interlinked cross-sectional surveys were used to ask every integrated care board in England (commissioners), along with convenience samples of HPs and LEs, about prescribing rates, AMHS availability, wait times, and shared-care agreement protocols/policies for the pharmacological treatment of ADHD in primary care. Descriptive analyses, percentages, and confidence intervals were used to summarise responses by stakeholder group. Variations in reported provision and practice were explored and displayed visually using mapping software.ResultsData from 782 responders (42 commissioners, 331 HPs, 409 LEs) revealed differences in reported provision by stakeholder group, including for prescribing (95% of HPs versus 64% of LEs). In all, >40% of responders reported extended AMHS wait times of ≥2 years. There was some variability by NHS region – for example, London had the lowest reported extended wait time (25%), while East of England had the highest (55%).ConclusionElements supporting appropriate shared-care prescribing of ADHD medication via primary care are not universally available in England. Coordinated approaches are needed to address these gaps.

BackgroundCOVID-19 pandemic restrictions may have influenced behaviours related to weight.AimTo describe patterns of weight change among adults living in England with type 2 diabetes (T2D) and/or hypertension during the pandemic.Design and settingAn observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP.MethodClinical and sociodemographic characteristics associated with rapid weight gain (>0.5 kg/m2/year) were investigated using multivariable logistic regression.ResultsData were extracted on adults with T2D (n = 1 231 455, 43.9% female, and 76.0% White British) or hypertension (n = 3 558 405, 49.7% female, and 84.3% White British). Adults with T2D lost weight overall (median δ = −0.1 kg/m2/year [interquartile range {IQR} −0.7–0.4]). However, rapid weight gain was common (20.7%) and associated with the following: sex (male versus female: adjusted odds ratio [aOR] 0.78 [95% confidence interval {CI} = 0.77 to 0.79]); age (older age reduced odds, for example, aged 60–69 years versus 18–29 years: aOR 0.66 [95% CI = 0.61 to 0.71]); deprivation (least deprived Index of Multiple Deprivation [IMD] quintile versus most deprived IMD quintile: aOR 0.87 [95% CI = 0.85 to 0.89]); White ethnicity (Black versus White: aOR 0.95 [95% CI = 0.92 to 0.98]); mental health conditions (for example, depression: aOR 1.13 [95% CI = 1.12 to 1.15]); and diabetes treatment (non-insulin treatment versus no pharmacological treatment: aOR 0.68 [95% CI = 0.67 to 0.69]). Adults with hypertension maintained stable weight overall (median δ = 0.0 kg/m2/year [IQR −0.6–0.5]); however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D.ConclusionAmong adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common among females, younger adults, those living in more deprived areas, and those with mental health conditions.

BackgroundIncident benzodiazepine prescriptions in primary care for anxiety decreased between 2003 and 2018. However, from 2008, incident prescribing of benzodiazepines for anxiety increased among those aged 18–34 years. There are increasing concerns around prescribing of benzodiazepines. Further, although guidelines state benzodiazepines should only be prescribed short term, in 2017, 44% of incident prescriptions were prescribed for longer than the recommended duration of 2–4 weeks.AimTo understand when and why GPs prescribe benzodiazepines for anxiety in young adults.Design and settingA qualitative study was undertaken using in-depth interviews with 17 GPs from 10 general practices in South West England.MethodInterviews were conducted by telephone or videocall. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and data analysed using reflexive thematic analysis.ResultsGPs described caution in prescribing benzodiazepines for anxiety in young adults, but thought they had an important role in acute situations. GPs described caution in prescribing duration, but some thought longer-term prescriptions could be appropriate. In light of these views, some GPs questioned whether primary care needs to revisit how clinicians are using benzodiazepines. GPs perceived that some young adults requested benzodiazepines and suggested this might be because they wanted quick symptom relief. GPs noted that refusing to prescribe felt uncomfortable and that the number of young adults presenting to general practice, already dependent on benzodiazepines, had increased.ConclusionPatient-driven factors for prescribing benzodiazepines suggest there are current unmet treatment needs among young adults with anxiety. Given increases in prescribing in this age group, it may be timely to revisit the role of benzodiazepines in the management of people with anxiety in primary care.

The type 2 diabetes mellitus drug semaglutide is effective for weight loss in non-diabetic overweight or obese adults, when taken alongside a reduced-calorie diet and exercise, researchers have found.