Revealing the reaction path of UVC bond rupture in cyclic disulfides with ultrafast x-ray scattering.

Disulfide bonds are ubiquitous molecular motifs that influence the tertiary structure and biological functions of many proteins. Yet, it is well known that the disulfide bond is photolabile when exposed to ultraviolet C (UVC) radiation. The deep-UV-induced S─S bond fragmentation kinetics on very fast timescales are especially pivotal to fully understand the photostability and photodamage repair mechanisms in proteins.

Closing the Gap: Digital Innovations to Address Hypertension Disparities.

Purpose Of Review: Significant inequities persist in hypertension detection and control, with minoritized populations disproportionately experiencing organ damage and premature death due to uncontrolled hypertension. Remote blood pressure monitoring combined with telehealth visits (RBPM) is proving to be an effective strategy for controlling hypertension. Yet there are challenges related to technology adoption, patient engagement and social determinants of health (SDoH), contributing to disparities in patient outcomes.

Diagnostic value of CT scans in pediatric patients with acute non-traumatic altered mental status: a systematic review and meta-analysis.

Background: Computed tomography (CT) scans are widely used for evaluating children with acute atraumatic altered mental status (AMS) despite concerns about radiation exposure and limited diagnostic yield. This study aims to assess the efficacy of CT scans in this population and provide evidence-based recommendations.

Methods: A systematic review was conducted according to PRISMA guidelines.

Content Validity of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.

Methods: Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA.

A STING-CASM-GABARAP pathway activates LRRK2 at lysosomes.

Mutations that increase LRRK2 kinase activity have been linked to Parkinson's disease and Crohn's disease. LRRK2 is also activated by lysosome damage. However, the endogenous cellular mechanisms that control LRRK2 kinase activity are not well understood.

Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.

IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.

Trends in Osteoporosis Drug Therapy Receipt Among Commercial and Medicare Advantage Enrollees in the United States, 2011-2022.

Context: A national assessment of osteoporosis drug therapy (ODT) use can inform the extent of underdiagnosis and undertreatment of osteoporosis.

Objective: The aim was to describe trends in ODT use by age, sex, fragility fracture, and documented osteoporosis.

Methods: This was a retrospective analysis of patient-quarter observations for adults aged ≥50 years with commercial or Medicare Advantage health insurance in the OptumLabs Data Warehouse between 2011 and 2022.

Intranasal Calcitriol Accelerates Improvement of Sinonasal Inflammation and Olfactory Impairment in Mice After Cessation of Chronic Cigarette-Smoke Exposure.

Rationale: Smoking has been shown to be associated with circulating deficiencies in 25(OH)D3 and reduced sinonasal tissue levels of the active form of vitamin D, 1,25(OH)2D3. Given vitamin D's ability to reduce inflammation, we sought to examine if intranasal (IN) delivery of calcitriol [clinical analog of 1,25(OH)2D3] could reduce inflammation and improve disease severity in a murine model of chronic cigarette smoke-induced sinonasal inflammation (CS-SI).

Methods: Mice were exposed to CS 5 h/day, 5 days/week for 9 months, and then began IN calcitriol three times per week for 4 weeks.

Assessment of clinical characteristics and mortality in patients hospitalized with SARS-CoV-2 from January 2022 to November 2022, when Omicron variants were predominant in the United States.

Objective: To describe the demographic/clinical characteristics, treatment patterns, and mortality among patients hospitalized with COVID-19 during Omicron predominance by immunocompromised and high-risk status.

Methods: Retrospective observational study of patients hospitalized with COVID-19 between January 1, 2022 and November 30, 2022, using data from the Optum de-identified Clinformatics® Data Mart Database. Patient demographic/clinical characteristics, treatments, mortality and costs, were assessed, during the emergence of BA.

Investigating Postoperative Urinary Retention: Risk Factors and Postsurgical Outcomes in Total Joint Arthroplasty.

Background: Postoperative urinary retention (POUR), a known complication following total joint arthroplasty (TJA), remains inconsistent in its diagnostic criteria, prevalence, and risk factors. This study aims to quantify POUR rates, identify risk factors, and assess complications associated with catheterization in TJA.

Methods: A single-center cohort undergoing TJA between January 2015 and December 2022 was retrospectively reviewed.

Development of a latency model for HIV-1 subtype C and the impact of long terminal repeat element genetic variation on latency reversal.

Sub-Saharan Africa accounts for almost 70 % of people living with HIV (PLWH) worldwide, with the greatest numbers centred in South Africa where 98 % of infections are caused by subtype C (HIV-1C). However, HIV-1 subtype B (HIV-1B), prevalent in Europe and North America, has been the focus of most cure research and testing despite making up only 12 % of HIV-1 infections globally. Development of latency models for non-subtype B viruses is a necessary step to address this disproportionate focus.

The impact of highly effective modulator therapy on sinusitis and dysosmia in young children with cystic fibrosis: a prospective study protocol.

Background: Chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) are prevalent disease complications in people with cystic fibrosis. These understudied comorbidities significantly impact quality of life. The impact of highly effective modulator therapy (HEMT) in young children with cystic fibrosis (YCwCF) on these disease complications is unknown.

Personal light treatment devices: a countermeasure to improve sleep, fatigue, and circadian misalignment in an operational setting.

Carefully timed light exposure is a promising countermeasure to overcome the negative sleep and circadian implications of shift work. However, many lighting interventions are static and applied at the group level (e.g.

Bayesian modeling framework for optimizing pre-hospital stroke triage decisions.

Ischemic stroke is responsible for significant morbidity and mortality in the United States and worldwide. Stroke treatment optimization requires emergency medical personnel to make rapid triage decisions concerning destination hospitals that may differ in their ability to provide highly time-sensitive pharmaceutical and surgical interventions. These decisions are particularly crucial in rural areas, where transport decisions can have a large impact on treatment times - often involving a trade-off between delay in pharmaceutical therapy or a delay in endovascular thrombectomy.

Impact of antiparasitic therapy on cardiovascular outcomes in chronic Chagas disease. A systematic review and meta-analysis.

Background: Endemic in more than 20 countries, Chagas disease affects 6.3 million people worldwide, leading to 28,000 new infections and 7700 deaths each year. Previous meta-analyses on antiparasitic treatment need updates to encompass recent studies and to assess key clinically meaningful endpoints.

Stress reactivity moderates the association between early experiences of unpredictability and emotional problems in adolescents.

Researchers have documented that exposure to different kinds of psychosocial stressors can lead to emotional difficulties and, further, that heightened reactivity to stress can moderate these associations. Recently, investigators have distinguished among threat, deprivation, and unpredictability as different dimensions of early life stress (ELS). It is not clear, however, whether reactivity in specific stress response systems functions as a diathesis to lead to emotional difficulties following exposure to these dimensions of ELS.

In vivo calcium imaging reveals directional sensitivity of C-low threshold mechanoreceptors.

C-low threshold mechanoreceptors (C-LTMRs) in animals (termed C-tactile (CT) fibres in humans) are a subgroup of C-fibre primary afferents, which innervate hairy skin and respond to low-threshold punctate indentations and brush stimuli. These afferents respond to gentle touch stimuli and are implicated in mediating pleasant/affective touch. These afferents have traditionally been studied using low-throughput, technically challenging approaches, including microneurography in humans and teased fibre electrophysiology in other mammals.

SenPred: a single-cell RNA sequencing-based machine learning pipeline to classify deeply senescent dermal fibroblast cells for the detection of an in vivo senescent cell burden.

Background: Senescence classification is an acknowledged challenge within the field, as markers are cell-type and context dependent. Currently, multiple morphological and immunofluorescence markers are required. However, emerging scRNA-seq datasets have enabled an increased understanding of senescent cell heterogeneity.

Factors Associated With Prolonged Venous Transit in Large Vessel Occlusion Acute Ischemic Strokes.

Background And Purpose: Prolonged venous transit (PVT), derived from computed tomography perfusion (CTP) time-to-maximum (T) maps, reflects compromised venous outflow (VO) in acute ischemic stroke due to large vessel occlusion (AIS-LVO). Poor VO is associated with worse clinical outcomes, but pre-treatment markers predictive of PVT are not well described.

Methods: We conducted a retrospective analysis of 189 patients with anterior circulation AIS-LVO who underwent baseline CT evaluation, including non-contrast CT, CT angiography, and CTP.

Diagnostic models to differentiate Takotsubo syndrome from acute coronary syndrome: A systematic review and meta-analysis.

Aims: Differentiation between patients with Takotsubo syndrome and acute coronary syndrome (ACS) remains a challenge. We performed a systematic review to identify and evaluate diagnostic predictive models to distinguish both conditions.

Methods And Results: We performed an electronic search in PubMed, EMBASE, and Scopus until January 2024.

Recruitment and Retention of Direct Care Workers During the COVID-19 Pandemic: Challenges and Opportunities.

The COVID-19 pandemic exacerbated the challenges of home- and community-based service (HCBS) providers in recruiting and retaining direct care workers (DCWs). One of the largest and fastest-growing occupations in the U.S.

In vitro NIH3T3 mouse embryonic fibroblast cell model does not predict AAV2 or AAVdj-mediated cell transformation.

One of the potential risk factors of recombinant adeno-associated virus (rAAV)-based gene therapy is insertional mutagenesis, which has been associated with the development of hepatocellular carcinoma (HCC) in rAAV-treated neonatal mice. The objective of this study was to investigate if well-established in vitro cell transformation assays (CTA) in mouse cell lines can detect AAV2 or AAVdj-mediated cell transformation. Since AAV integration at the Rian locus in neonatal mice has been implicated in AAV-mediated HCC, an rAAV vector specifically targeting the mouse Rian locus and an additional rAAV vector previously shown to cause HCC in neonatal mice were both tested for the induction of cell transformation in NIH3T3 cells.