Pharmacologically increasing cGMP improves proteostasis and reduces neuropathy in mouse models of CMT1.

Increasing cyclic GMP activates 26S proteasomes via phosphorylation by Protein Kinase G and stimulates the intracellular degradation of misfolded proteins. Therefore, agents that raise cGMP may be useful therapeutics against neurodegenerative diseases and other diseases in which protein degradation is reduced and misfolded proteins accumulate, including Charcot Marie Tooth 1A and 1B peripheral neuropathies, for which there are no treatments. Here we increased cGMP in the S63del mouse model of CMT1B by treating for three weeks with either the phosphodiesterase 5 inhibitor tadalafil, or the brain-penetrant soluble guanylyl cyclase stimulator CYR119.

The Role of Sleep in Links Between Daily Interpersonal Stress and Internalizing and Externalizing Symptoms During Middle Childhood.

Background: Interpersonal stress has been consistently linked with poorer adjustment, and healthy sleep may play a promotive or protective role in this relation. However, little is known regarding such associations among children. The current study examined longitudinal associations between daily interpersonal stress, sleep, and internalizing/externalizing symptoms during middle childhood.

Enhancing Hospital Reimbursement Through a Pediatric Surgery Resident Orientation Program: A Focus on Accurate Diagnosis Code Documentation for Acute Appendicitis.

Background: The usage of specific ICD-10 diagnosis codes significantly influences hospital reimbursement compared to non-specific codes. This study hypothesized that a formal orientation program for pediatric surgery residents would enhance the selection of accurate and specific diagnosis codes for acute appendicitis such as K35.30 for "Acute appendicitis with localized peritonitis" rather than K35.

Lightweight medical image segmentation network with multi-scale feature-guided fusion.

In the field of computer-aided medical diagnosis, it is crucial to adapt medical image segmentation to limited computing resources. There is tremendous value in developing accurate, real-time vision processing models that require minimal computational resources. When building lightweight models, there is always a trade-off between computational cost and segmentation performance.

Effects of acute smoking abstinence among people with schizophrenia: A systematic review and meta-analysis of laboratory studies.

Background: Smoking rates in schizophrenia are exceptionally high; however, cessation rates remain low with limited research on effective interventions. A critical component of intervention development is identifying the effects of abstinence that are most salient and therefore may contribute to lapse and relapse.

Objectives: We conducted a systematic review and meta-analysis of controlled laboratory studies investigating acute smoking abstinence effects among people with schizophrenia and schizoaffective disorder.

Dietary eggs, egg nutrients, polygenic score for body mass index, "Western pattern" diet, and weight change, a prospective analysis in the Women's health initiative.

Background & Aims: Eggs contain nutrients which could help enrich the diets of postmenopausal women. Egg consumption and elevated body weight have been associated with elevated risk of serious chronic disease. It is possible that elevated body weight mediates between egg consumption and serious chronic disease.

Differing Transcriptomic Responses in High Titer versus Low Titer Mosquitoes after Oral Infection with Sindbis Virus.

Oral infection of mosquitoes by arboviruses often results in a large degree of variation in the amount of infectious virus between individual mosquitoes, even when the mosquitoes are from inbred laboratory strains. This variability in arbovirus load has been shown to affect virus transmissibility. Previously, our group described population genetic and specific infectivity differences between the virus populations found in high and low titer mosquitoes that had been orally infected with Sindbis virus (SINV).

Subcellular Drug Distribution: Exploring Organelle-Specific Characteristics for Enhanced Therapeutic Efficacy.

The efficacy and potential toxicity of drug treatments depends on the drug concentration at its site of action, intricately linked to its distribution within diverse organelles of mammalian cells. These organelles, including the nucleus, endosome, lysosome, mitochondria, endoplasmic reticulum, Golgi apparatus, lipid droplets, exosomes, and membrane-less structures, create distinct sub-compartments within the cell, each with unique biological features. Certain structures within these sub-compartments possess the ability to selectively accumulate or exclude drugs based on their physicochemical attributes, directly impacting drug efficacy.

A Synergistic Overview between Microfluidics and Numerical Research for Vascular Flow and Pathological Investigations.

Vascular diseases are widespread, and sometimes such life-threatening medical disorders cause abnormal blood flow, blood particle damage, changes to flow dynamics, restricted blood flow, and other adverse effects. The study of vascular flow is crucial in clinical practice because it can shed light on the causes of stenosis, aneurysm, blood cancer, and many other such diseases, and guide the development of novel treatments and interventions. Microfluidics and computational fluid dynamics (CFDs) are two of the most promising new tools for investigating these phenomena.

Revisiting One of the Oldest Orphanages, Asylums, and Indigenous Residential Boarding Schools: The Thomas Indian School at Seneca Nation.

For Indigenous populations, one of the most recognized acts of historical trauma has come from boarding schools. These institutions were established by federal and state governments to forcibly assimilate Indigenous children into foreign cultures through spiritual, physical, and sexual abuse and through the destruction of critical connections to land, family, and tribal community. This literature review focuses on the impact of one of the oldest orphanages, asylums, and Indigenous residential boarding schools in the United States.

Effect of sintering cycle on the strength and translucency of multilayered zirconia.

Purpose: A newly introduced sintering protocol promises to offer higher translucency while not significantly compromising the flexural strength of the material. However, the effect of the novel sintering protocol has not been thoroughly validated. The purpose of this study was to measure and compare the effect of two sintering protocols on the translucency and flexural strength of two multilayered zirconia materials.

Switch-like Gene Expression Modulates Disease Susceptibility.

A fundamental challenge in biomedicine is understanding the mechanisms predisposing individuals to disease. While previous research has suggested that switch-like gene expression is crucial in driving biological variation and disease susceptibility, a systematic analysis across multiple tissues is still lacking. By analyzing transcriptomes from 943 individuals across 27 tissues, we identified 1,013 switch-like genes.

Synthesis of Hydrazonyl Sultones via Phosphine-Mediated Cyclodehydration of Vicinal Sulfo-acyl Hydrazides.

We report a phosphine-mediated cyclodehydration procedure for the facile synthesis of -aryl/alkyl-substituted hydrazonyl sultones, a class of bioorthogonal reagents, from the readily prepared vicinal sulfo-acyl hydrazides in moderate to good yields. The aqueous stability and bioorthogonal reactivity of these hydrazonyl sultones toward bicyclo[6.1.

Prenatal Tobacco Exposure and Behavioral Disorders in Children and Adolescents: Systematic Review and Meta-Analysis.

Prenatal tobacco exposure has been implicated in increased risk of the development of behavioral disorders in children and adolescents. The purpose of the current study was to systematically examine the association between prenatal tobacco exposure and diagnoses of Attention Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder in childhood and adolescence. We searched Medline, Psychinfo, ERIC, Proquest, Academic Search Complete, PsychArticles, Psychology and Behavioral Sciences Collection, Web of Science, CINAHL Plus, and Google Scholar databases through October 2022.

Leveraging bifactor modeling to test prospective direct and indirect effects of adolescent alcohol use and externalizing symptoms on the development of task-general executive functioning.

Adolescence is a period of substantial maturation in brain regions underlying Executive Functioning (EF). Adolescence is also associated with initiation and escalation of Alcohol Use (AU), and adolescent AU has been proposed to produce physiological and neurobiological events that derail healthy EF development. However, support has been mixed, which may be due to (1) failure to consider co-occurring externalizing symptoms (including other drug use) and poor social adaptation, and (2) heterogeneity and psychometric limitations in EF measures.

Poly(lactic-co-glycolic acid) nanoparticle fabrication, functionalization, and biological considerations for drug delivery.

Nanoparticles can be used for drug delivery and consist of many sizes and chemical compositions. They can accommodate a diverse population of drugs and can be made to target specific areas of the body. Fabrication methods generally follow either top-down or bottom-up manufacturing techniques, which have differing production controls, which determine nanoparticle characteristics including but not limited to size and encapsulation efficiency.