Nitrous Oxide activates layer 5 prefrontal neurons via SK2 channel inhibition for antidepressant effect.

Nitrous oxide (NO) induces rapid and durable antidepressant effects. The cellular and circuit mechanisms mediating this process are not known. Here we find that a single dose of inhaled NO induces rapid and specific activation of layer V (L5) pyramidal neurons in the cingulate cortex of rodents exposed to chronic stress conditions.

Scaling cervical cancer screening in Mozambique: analysis of loop electrosurgical excision procedure (LEEP) specimens.

Objectives: As cervical cancer screening programs are implemented and expanded, an increasing number of women require loop electrosurgical excision procedure (LEEP) for treatment of pre-invasive cervical disease. Our objective was to describe the pathological results of LEEP specimens performed as part of the MULHER study and identify factors associated with positive LEEP margins.

Methods: The MULHER study enrolled 9014 women who underwent HPV testing followed by visual assessment for treatment (VAT) using visual inspection with acetic acid (VIA) and thermal ablation for those with positive results.

Propofol binds and inhibits skeletal muscle ryanodine receptor 1.

Background: As the primary Ca release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, triggering agents including halogenated volatile anaesthetics bias RyR1 to an open state resulting in uncontrolled Ca release, increased sarcomere tension, and heat production. Propofol does not trigger MH and is commonly used for patients at risk of MH.

Difficult to treat Pseudomonas: successful salvage therapy with cefepime-zidebactam.

Carbapenem-resistant Pseudomonas aeruginosa (CRPa) infection is extremely challenging to manage. Cefepime-zidebactam is a novel combination that can be considered for salvage therapy when no other antimicrobials are susceptible. A 15-y-old boy presented with 56% thermal burns, followed by skin and soft tissue infection, secondary bacteraemia, complicated parapneumonic effusion and endophthalmitis due to CRPa, which was not susceptible to any of the routinely available antibiotics.

Barriers to the introduction of novel advanced targeted treatments for Australian dermatology patients: Are skin diseases symptomatic of a systemic healthcare problem?

The aim of this article is to provide education to clinicians about certain barriers restricting the use of advanced targeted treatments in Australian health care. For illustrative purposes, the article focuses on dermatological conditions, but the content is relevant to all specialties that treat inflammatory and chronic diseases. Barriers to care discussed result in a lower than necessary standard of care for patients in Australia despite important advancements in medicine.

Critical assessment of variant prioritization methods for rare disease diagnosis within the rare genomes project.

Background: A major obstacle faced by families with rare diseases is obtaining a genetic diagnosis. The average "diagnostic odyssey" lasts over five years and causal variants are identified in under 50%, even when capturing variants genome-wide. To aid in the interpretation and prioritization of the vast number of variants detected, computational methods are proliferating.

Primary Cutaneous Melanoma-Management in 2024.

: Maximizing survival for patients with primary cutaneous melanomas (melanomas) depends on an early diagnosis and appropriate management. Several new drugs have been shown to improve survival in high-risk melanoma patients. Despite well-documented guidelines, many patients do not receive optimal management, particularly when considering patient age.

Supercharged coiled-coil protein with N-terminal decahistidine tag boosts siRNA complexation and delivery efficiency of a lipoproteoplex.

Short interfering RNA (siRNA) therapeutics have soared in popularity due to their highly selective and potent targeting of faulty genes, providing a non-palliative approach to address diseases. Despite their potential, effective transfection of siRNA into cells requires the assistance of an accompanying vector. Vectors constructed from non-viral materials, while offering safer and non-cytotoxic profiles, often grapple with lackluster loading and delivery efficiencies, necessitating substantial milligram quantities of expensive siRNA to confer the desired downstream effects.

The blobulator: a webtool for identification and visual exploration of hydrophobic modularity in protein sequences.

Motivation: Clusters of hydrophobic residues are known to promote structured protein stability and drive protein aggregation. Recent work has shown that identifying contiguous hydrophobic residue clusters (termed "blobs") has proven useful in both intrinsically disordered protein (IDP) simulation and human genome studies. However, a graphical interface was unavailable.

Propofol directly binds and inhibits skeletal muscle ryanodine receptor 1 (RyR1).

As the primary Ca release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in the type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, exposure to triggering drugs such as the halogenated volatile anesthetics biases RyR1 to an open state, resulting in uncontrolled Ca release, sarcomere tension and heat production. Restoration of Ca into the SR also consumes ATP, generating a further untenable metabolic load.

Identifying the white matter pathways involved in multiple sclerosis-related tremor using diffusion tensor imaging.

Background: Tremor affects up to 45% of patients with Multiple Sclerosis (PwMS). Current understanding is based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology.

Objective: To characterize the brain white matter (WM) correlates of MS-related tremor using diffusion tensor imaging (DTI).

Association of the COVID-19 Pandemic on Treatment Times for ST-Elevation Myocardial Infarction: Observations from the Los Angeles County Regional System.

Previous studies have documented longer treatment times and worse outcomes for patients with ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) during the COVID-19 pandemic. The objective of the present study was to evaluate the impact of the COVID-19 pandemic on treatment times and outcomes for patients with STEMI who underwent primary PCI within a regional system of care. This was a retrospective study using data from the Los Angeles County Emergency Medical Services Agency.

In Vivo and In Vitro Characterization of the Recently Emergent PRRSV 1-4-4 L1C Variant (L1C.5) in Comparison with Other PRRSV-2 Lineage 1 Isolates.

The recently emerged PRRSV 1-4-4 L1C variant (L1C.5) was in vivo and in vitro characterized in this study in comparison with three other contemporary 1-4-4 isolates (L1C.1, L1A, and L1H) and one 1-7-4 L1A isolate.

Reversible platypnoea-orthodeoxia syndrome.

Platypnoea-orthodeoxia syndrome is characterised by dyspnoea and oxygen desaturation in the upright position usually caused by an extracardiac shunt and less often due to dynamic factors that accentuate an intracardiac right-to-left shunt. In our patient, the collapse of lower lobe of left lung secondary to bronchial stenosis due to endobronchial tuberculosis and resultant mediastinal shift was the factor that led to an otherwise unrecognised intracardiac right-to-left shunt leading to platypnoea-orthodeoxia. We postulate that there would have been an increased stretching and widening of a patent foramen ovale in the upright position due to gravity resulting in an increased shunt despite normal intracardiac pressures.

The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique.

Objective: To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally.

Methods: Women aged 30-49 years were prospectively enrolled and offered primary HPV testing using either self-collected or provider-collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation.

Constructing Nucleic Acid Delivering Lipoproteoplexes from Coiled-Coil Supercharged Protein and Cationic Liposomes.

The safe and efficient delivery of nucleic acids is crucial for both clinical applications of gene therapy and pre-clinical laboratory research. Such delivery strategies rely on vectors to condense nucleic acid payloads and escort them into the cell without being degraded in the extracellular environment; however, the construction and utilization of these vectors can be difficult and time-consuming. Here, we detail the steps involved in the rapid, laboratory-scale production and assessment of a versatile, nucleic acid delivery vehicle, known as the lipoproteoplex.

Urinary incontinence prevalence and factors associated with patients talking with doctors about urine control.

Objectives: Patient perceptions of their doctors may influence talking to them about urinary incontinence (UI). We estimated prevalence of UI among Medicare beneficiaries and assessed association between beneficiaries' demographic and clinical characteristics and whether they spoke to their doctor about UI and association between beneficiaries' perceptions of their doctor and whether they spoke to their doctor about UI.

Methods: This study was approved by the Purdue University Institutional Review Board (IRB) and determined exempt, category 4 (protocol number 1907022503, approval on August 5th, 2019).

Probing the Conformational Space of the Cannabinoid Receptor 2 and a Systematic Investigation of DNP-Enhanced MAS NMR Spectroscopy of Proteins in Detergent Micelles.

Tremendous progress has been made in determining the structures of G-protein coupled receptors (GPCR) and their complexes in recent years. However, understanding activation and signaling in GPCRs is still challenging due to the role of protein dynamics in these processes. Here, we show how dynamic nuclear polarization (DNP)-enhanced magic angle spinning nuclear magnetic resonance in combination with a unique pair labeling approach can be used to study the conformational ensemble at specific sites of the cannabinoid receptor 2.

Adherence to and persistence with adjuvant hormone therapy, healthcare utilization, and healthcare costs among older women with breast cancer: A population-based longitudinal cohort study.

Introduction: To assess associations between adherence to and persistence with adjuvant hormone therapy, healthcare utilization, and healthcare costs among older women with breast cancer.

Materials And Methods: This study was a population-based longitudinal cohort study using the Surveillance, Epidemiology, and End Results (SEER) registry linked with Medicare claims. This study included older women diagnosed with stage I-III hormone receptor-positive breast cancer from 2009 through 2017.