Medial hypothalamic MC3R signalling regulates energy rheostasis in adult mice.

Although mammals resist both acute weight loss and weight gain, the neural circuitry mediating bi-directional defense against weight change is incompletely understood. Global constitutive deletion of the melanocortin-3-receptor (MC3R) impairs the behavioural response to both anorexic and orexigenic stimuli, with MC3R knockout mice demonstrating increased weight gain following anabolic challenges and increased weight loss following anorexic challenges (i.e.

Machine-guided design of cell-type-targeting cis-regulatory elements.

Cis-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing and stimulus responses, which collectively define the thousands of unique cell types in the body. While there is great potential for strategically incorporating CREs in therapeutic or biotechnology applications that require tissue specificity, there is no guarantee that an optimal CRE for these intended purposes has arisen naturally. Here we present a platform to engineer and validate synthetic CREs capable of driving gene expression with programmed cell-type specificity.

Reproducible lung protective effects of a TGFβR1/ALK5 inhibitor in a bleomycin-induced and spirometry-confirmed model of IPF in male mice.

This study comprehensively validated the bleomycin (BLEO) induced mouse model of IPF for utility in preclinical drug discovery. To this end, the model was rigorously evaluated for reproducible phenotype and TGFβ-directed treatment outcomes. Lung disease was profiled longitudinally in male C57BL6/JRJ mice receiving a single intratracheal instillation of BLEO (n = 10-12 per group).

A single-cell transcriptomic map of the developing Atoh1 lineage identifies neural fate decisions and neuronal diversity in the hindbrain.

Proneural transcription factors establish molecular cascades to orchestrate neuronal diversity. One such transcription factor, Atonal homolog 1 (Atoh1), gives rise to cerebellar excitatory neurons and over 30 distinct nuclei in the brainstem critical for hearing, breathing, and balance. Although Atoh1 lineage neurons have been qualitatively described, the transcriptional programs that drive their fate decisions and the full extent of their diversity remain unknown.

Children's confidence on mathematical equivalence and fraction problems.

Metacognition is how people think about their own thinking, and it includes children's confidence in their problem-solving solutions. We assessed children's metacognition in two areas of mathematics that are often plagued by misconceptions and often studied separately-mathematical equivalence (e.g.

Successful Management of Cherubism Patient With Staged Bone Grafting and Fat Grafting.

Cherubism is a rare hereditary dysplasia of the craniofacial skeleton with unpredictable course and controversial management. The authors report a case managed at the onset with limited mandibular resection and primary autogenous bone grafting, as well as staged secondary fat grafting for contour definition. Over 5 years, the patient demonstrated no recurrence of deformity except for mild hypoplasia, which was improved with fat grafting.

Neuroanatomical dissection of the MC3R circuitry regulating energy rheostasis.

Although mammals resist both acute weight loss and weight gain, the neural circuitry mediating bi-directional defense against weight change is incompletely understood. Global constitutive deletion of the melanocortin-3-receptor (MC3R) impairs the behavioral response to both anorexic and orexigenic stimuli, with MC3R knockout mice demonstrating increased weight gain following anabolic challenges and increased weight loss following anorexic challenges (i.e.

Optimizing the measurement of sample entropy in resting-state fMRI data.

Introduction: The complexity of brain signals may hold clues to understand brain-based disorders. Sample entropy, an index that captures the predictability of a signal, is a promising tool to measure signal complexity. However, measurement of sample entropy from fMRI signals has its challenges, and numerous questions regarding preprocessing and parameter selection require research to advance the potential impact of this method.

Recombinant Full-length Plasmodium falciparum Circumsporozoite Protein-Based Vaccine Adjuvanted With Glucopyranosyl Lipid A-Liposome Quillaja saponaria 21: Results of Phase 1 Testing With Malaria Challenge.

Background: Malaria is preventable yet causes >600 000 deaths annually. RTS,S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication.

Methods: We conducted an open-label, dose escalation phase 1 study of a full-length recombinant circumsporozoite protein vaccine (rCSP) administered with adjuvant glucopyranosyl lipid A-liposome Quillaja saponaria 21 formulation (GLA-LSQ) on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naive adults.

Interpersonal communication, cultural norms, and community perceptions associated with care-seeking for fever among children under age five in Magoé district, Mozambique.

Background: Malaria is endemic throughout Mozambique, contributing significantly to the country's burden of disease. Prompt and effective treatment for fevers in children can limit the mortality and morbidity impacts of the disease but many children in the country are not taken for formal care when ill. Using an ideational model of behaviour, this study assesses the magnitude of the relationships for potential drivers of care-seeking, including interpersonal communication, malaria messaging, and knowledge and attitudes about malaria, with actual care-seeking behaviours for under-five children with fever in Magoé district, Mozambique.

Machine-guided design of synthetic cell type-specific -regulatory elements.

-regulatory elements (CREs) control gene expression, orchestrating tissue identity, developmental timing, and stimulus responses, which collectively define the thousands of unique cell types in the body. While there is great potential for strategically incorporating CREs in therapeutic or biotechnology applications that require tissue specificity, there is no guarantee that an optimal CRE for an intended purpose has arisen naturally through evolution. Here, we present a platform to engineer and validate synthetic CREs capable of driving gene expression with programmed cell type specificity.

Paraventricular Thalamic Circuits Link Energy Homeostasis with Anxiety-Related Behavior.

The hypothalamic melanocortin system is critically involved in sensing stored energy and communicating this information throughout the brain, including to brain regions controlling motivation and emotion. This system consists of first-order agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) neurons located in the hypothalamic arcuate nucleus and downstream neurons containing the melanocortin-3 () and melanocortin-4 receptor (). Although extensive work has characterized the function of downstream neurons, the identity and function of -containing neurons are poorly understood.

drives the heterogeneity of the pontine nuclei neurons and promotes their differentiation.

Pontine nuclei (PN) neurons mediate the communication between the cerebral cortex andthe cerebellum to refine skilled motor functions. Prior studies showed that PN neurons fall into two subtypes based on their anatomic location and region-specific connectivity, but the extent of their heterogeneity and its molecular drivers remain unknown. encodes a transcription factor that is expressed in the PN precursors.

Malaria-Related Psychosocial Factors, Past Antenatal Care-Seeking Behaviors, and Future Antenatal Care-Seeking Intentions by Maternal Age in Malawi and Democratic Republic of the Congo.

Young women in sub-Saharan Africa are a group at increased risk for malaria in pregnancy. Early antenatal care (ANC) seeking makes it more likely that women will receive the recommended doses of intermittent preventive treatment of malaria in pregnancy. This study used data from national Malaria Behavior Surveys conducted in Malawi and the Democratic Republic of the Congo (DRC) in 2021 to explore the association between intention to attend ANC in the first trimester for a future pregnancy (early ANC intention) and psychosocial factors among women aged 15-49 years.

Establishment of Restraint Stress-induced Anorexia and Social Isolation-induced Anorexia Mouse Models.

Anorexia nervosa (AN) is a devastating neuropsychiatric disease with a prevalence rate of approximately 0.3%-1% among women and morbidity and mortality rates among the highest of all neuropsychiatric disorders. The disease etiology is complex but primarily characterized by reduced food intake and body weight, and intense anxiety and fear associated with gaining weight.

Ideational factors and their association with insecticide treated net use in Magoe District, Mozambique.

Background: Insecticide treated bed nets (ITN) are considered a core malaria vector control tool by the WHO and are the main contributor to the large decline in malaria burden in sub-Saharan Africa over the past 20 years, but they are less effective if they are not broadly and regularly used. ITN use may depend on factors including temperature, relative humidity, mosquito density, seasonality, as well as ideational or psychosocial factors including perceptions of nets and perceptions of net use behaviours.

Methods: A cross-sectional household survey was conducted as part of a planned randomized controlled trial in Magoe District, Mozambique.

Histopathologic Features of Breast Tissue From Transgender Men and Their Associations With Androgen Therapy.

Objectives: To assess the histopathologic features of breast tissue of transgender men (TM) undergoing gender-affirming bilateral mastectomies in relation to androgen therapy (AT).

Methods: We reviewed 374 transgender bilateral mastectomy cases from 2017 to 2020. Of these, 314 (84.

Evaluation of a Geographic Screening Protocol for Chronic Parasitic Infections Before Kidney Transplant: An Institutional Experience in Minnesota.

Pretransplant recommendations advise risk-based screening for strongyloidiasis, schistosomiasis, and Chagas disease. We evaluated the implementation of a chronic parasite screening protocol at a health system in a nonendemic region serving a large foreign-born population. Candidates listed for kidney transplant at Hennepin Healthcare (Minneapolis, MN) between 2010 and 2020 were included.

Development and Validation of a Measure to Assess Readiness to Advance Health and Equity: The Assessment for Advancing Community Transformation (AACT).

Multi-sector partnerships are core in efforts to improve population health but are often not as fully developed or positioned to advance health and equity in their communities as believed to be. Therefore, measuring the collaborations multi-sector partnerships undertake is important to document the inputs, processes, and outcomes that evolve as they work together towards achieving their goals, which ultimately creates a greater sense of shared accountability. In this study we present the development and validation of the Assessment for Advancing Community Transformation (AACT), a new tool designed to measure readiness to advance health and health equity.

Young children interpret number gestures differently than nonsymbolic sets.

Researchers have long been interested in the origins of humans' understanding of symbolic number, focusing primarily on how children learn the meanings of number words (e.g., "one", "two", etc.

Hospital pharmacy acquisition of nonstocked antimicrobials-current processes and areas for improvement.

Background: The delivery of prompt and appropriate antimicrobial therapy for life-threatening infections is an important antimicrobial stewardship measure and a priority for hospitals.

Objectives: To better understand U.S.