Female specific interactions of serotonin and testosterone in the rostral ventromedial medulla after activity-induced muscle pain.

Classical preclinical studies show that serotonin (5-HT) injected into the rostral ventromedial medulla (RVM) produces analgesia that is blocked by 5-HT2 receptor antagonists. One key modulator of 5-HT activity is the serotonin transporter (SERT) which reduces serotonergic signaling through reuptake into the presynaptic terminal. In the activity-induced muscle pain model, females show widespread pain and increased SERT expression in the RVM whereas males show localized pain and no changes in SERT expression.

The Role of Acid-Sensing Ion Channel 1A (ASIC1A) in the Behavioral and Synaptic Effects of Oxycodone and Other Opioids.

Opioid-seeking behaviors depend on glutamatergic plasticity in the nucleus accumbens core (NAcc). Here we investigated whether the behavioral and synaptic effects of opioids are influenced by acid-sensing ion channel 1A (ASIC1A). We tested the effects of ASIC1A on responses to several opioids and found that mice had elevated behavioral responses to acute opioid administration as well as opioid seeking behavior in conditioned place preference (CPP).

Molecular Modeling and In Vitro Functional Analysis of the RGS12 PDZ Domain Variant Associated with High-Penetrance Familial Bipolar Disorder.

Bipolar disorder's etiology involves genetics, environmental factors, and gene-environment interactions, underlying its heterogeneous nature and treatment complexity. In 2020, Forstner and colleagues catalogued 378 sequence variants co-segregating with familial bipolar disorder. A notable candidate was an R59Q missense mutation in the PDZ (PSD-95/Dlg1/ZO-1) domain of RGS12.

The Influence of Dopaminergic Medication on Regularity and Determinism of Gait and Balance in Parkinson's Disease: A Pilot Analysis.

: Understanding how dual-tasking and Parkinson's disease medication affect gait and balance regularity can provide valuable insights to patients, caregivers, and clinicians regarding frailty and fall risk. However, dual-task gait and balance studies in PD most often only employ linear measures to describe movement regularity. Some have used nonlinear techniques to analyze PD performances, but only in the on-medication state.

Shear stress-stimulated AMPK couples endothelial cell mechanics, metabolism and vasodilation.

Endothelial cells respond to mechanical force by stimulating cellular signaling, but how these pathways are linked to elevations in cell metabolism and whether metabolism supports the mechanical response remains poorly understood. Here, we show that the application of force to endothelial cells stimulates VE-cadherin to activate liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. VE-cadherin-stimulated AMPK increases eNOS (also known as NOS3) activity and localization to the plasma membrane, reinforcement of the actin cytoskeleton and cadherin adhesion complex, and glucose uptake.

Surgical Management of Neuroendocrine Tumor Liver Metastases.

Patients with neuroendocrine tumor liver metastases (NETLMs) may develop carcinoid syndrome, carcinoid heart disease, or other symptoms from overproduction of hormones. Hepatic resection and cytoreduction is the most direct treatment of NETLMs in eligible patients, and cytoreduction improves symptoms, may reduce the sequelae of carcinoid syndrome, and extends survival. Parenchymal-sparing procedures, such as ablation and enucleation, should be considered during cytoreduction to maximize treatment of multifocal tumors while preserving healthy liver tissue.

AptamerRunner: An accessible aptamer structure prediction and clustering algorithm for visualization of selected aptamers.

Aptamers are short single-stranded DNA or RNA molecules with high affinity and specificity for targets and are generated using the iterative systematic evolution of ligands by exponential enrichment (SELEX) process. Next-generation sequencing (NGS) revolutionized aptamer selections by allowing a more comprehensive analysis of SELEX-enriched aptamers as compared to Sanger sequencing. The current challenge with aptamer NGS datasets is identifying a diverse cohort of candidate aptamers with the highest likelihood of successful experimental validation.

Treatment of Short Stature in Aggrecan-deficient Patients With Recombinant Human GH: 3-year Response.

Context: Patients with aggrecan (ACAN) deficiency present with dominantly inherited short stature, as well as early-onset joint disease.

Objective: The objective of this study was to evaluate the efficacy and safety of recombinant human GH (rhGH) on linear growth in ACAN-deficient children.

Methods: Open-label, single-arm, prospective study over 3 years recruiting 10 treatment-naïve patients with heterozygous mutations in , age ≥2 years, prepubertal, and normal IGF-I concentration.

Pembrolizumab-induced cytokine release syndrome with severe encephalopathy in the setting of clear cell vaginal carcinoma: A case report.

•Pembrolizumab is increasingly used in the treatment of gynecologic cancers and has a half-life of 26 days.•Cytokine release syndrome with severe encephalopathy is a rare immune-mediated adverse effect.•Supportive care remains an important part of treatment of immune-mediated toxicity.

Laboratory Informatics Approaches to Improving Care for Gender- Diverse Patients.

Improving care for gender-diverse (GD) patients necessitates developing informatics tools and approaches to support optimal laboratory testing. This requires increased functionality and standardization of laboratory information system/electronic health record and data collection processes. Data tailored to accommodate immediate clinical care and clinical decision support (CDS) also have an impact on interoperability and downstream data needs for patients.

p66shc deficiency attenuates high glucose-induced autophagy dysfunction in Schwann cells.

Schwann cells are the most abundant cells in the peripheral nervous system, maintaining the development, function and regeneration of peripheral nerves. Defects in these Schwann cells injury response potentially contribute to the pathogenesis of diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus. The protein p66shc is essential in regulating oxidative stress responses, autophagy induction and cell survival, and is also vital in the development of DPN.

Muscle inflammation is regulated by NF-κB from multiple cells to control distinct states of wasting in cancer cachexia.

Although cancer cachexia is classically characterized as a systemic inflammatory disorder, emerging evidence indicates that weight loss also associates with local tissue inflammation. We queried the regulation of this inflammation and its causality to cachexia by exploring skeletal muscle, whose atrophy strongly associates with poor outcomes. Using multiple mouse models and patient samples, we show that cachectic muscle is marked by enhanced innate immunity.

Lasers efficacy in pain management after primary and secondary endodontic treatment: a systematic review and meta-analysis of randomized clinical trials.

Postoperative pain is a common concern following root canal treatments (RCT), impacting both patients and oral health practitioners. This systematic review and meta-analysis aimed to evaluate the effectiveness of laser treatment modalities in reducing postoperative pain compared to conventional methods after primary and secondary RCT in permanent mature teeth. A search of three electronic databases (PubMed, ScienceDirect, and The Cochrane Library) was conducted, using a broad range of keywords and terms.

Design and Implementation of a Computer-Controlled Hybrid Oscillatory Ventilator.

During mechanical ventilation, lung function and gas exchange in structurally heterogeneous lungs may be improved when volume oscillations at the airway opening are applied at multiple frequencies simultaneously, a technique referred to as multifrequency oscillatory ventilation (MFOV). This is in contrast to conventional high-frequency oscillatory ventilation (HFOV), for which oscillatory volumes are applied at a single frequency. In the present study, as a means of fully realizing the potential of MFOV, we designed and tested a computer-controlled hybrid oscillatory ventilator capable of generating the flows, tidal volumes, and airway pressures required for MFOV, HFOV, conventional mechanical ventilation (CMV), as well as oscillometric measurements of respiratory impedance.

Identification of SLC35A1 as an essential host factor for the transduction of multi-serotype recombinant adeno-associated virus (AAV) vectors.

We conducted a genome-wide CRISPR/Cas9 screen in suspension 293-F cells transduced with rAAV5. The highly selected genes revealed after two rounds of screens included the previously reported , , and , along with a cluster of genes involved in glycan biogenesis, Golgi apparatus localization and endoplasmic reticulum penetration. In this report, we focused on solute carrier family 35 member A1 (), a Golgi apparatus-localized cytidine 5'-monophosphate-sialic acid (CMP-SIA) transporter.

Collaborative Filtering for the Imputation of Patient Reported Outcomes.

This study addresses the prevalent issue of missing data in patient-reported outcome datasets, particularly focusing on head and neck cancer patient symptom ratings sourced from the MD Anderson Symptom Inventory. Given that many data mining and machine learning algorithms necessitate complete datasets, the accurate imputation of missing data as an initial step becomes crucial. In this study we propose, for the first time, the use of collaborative filtering for imputing missing head and neck cancer patient symptom ratings.

A conceptual model for assessing the risk of unidentified pain.

Untreated or undertreated pain is well established as a significant problem, but unidentified pain is a distinct construct that still needs to be clearly modeled or fully described. This paper aims to develop a conceptual model of unidentified pain in humans with the goal of future development of an unidentified pain risk tool. A multi-phase process was employed consisting sequentially of 1) brainstorming followed by consensus building, 2) peer-review and publication of an integrative theoretical review protocol for "unidentified pain," 3) conduct of the integrative review, and 4) a repeated brainstorming session to identify areas of risk for unidentified pain to produce a conceptual model.