Synephrine Inhibits Oxidative Stress and HO-Induced Premature Senescence.

Synephrine, a protoalkaloid found in Citrus aurantium (CA) peels, exerts lipolytic, anti-inflammatory, and vasoconstrictive effects; however, its antioxidant activity remains unclear. In this study, electron spin resonance spectroscopy revealed that synephrine scavenged both hydroxyl and superoxide anion radicals. Several external stimuli, such as HO, X-rays, and ultraviolet (UV) radiation, cause stress-induced premature senescence (SIPS).

Clinicopathologic characteristics of ductal carcinoma in situ and risk of subsequent invasive breast cancer: a multicenter, population-based cohort study.

Purpose: To study the association between clinicopathologic characteristics of ductal carcinoma in situ (DCIS) and risk of subsequent invasive breast cancer (IBC).

Methods: We conducted a case-control study nested in a multicenter, population-based cohort of 8175 women aged ≥ 18 years with DCIS diagnosed between 1987 and 2016 and followed for a median duration of 83 months. Cases (n = 497) were women with a first diagnosis of DCIS who developed a subsequent IBC ≥ 6 months later; controls (2/case; n = 959) were matched to cases on age at and calendar year of DCIS diagnosis.

Multi-Institutional Analysis of Pancreatoduodenectomy for Nonfamilial Periampullary Adenoma: A Novel Risk Score to Guide Shared Decision-Making.

Introduction: Pancreatoduodenectomy (PD) may occasionally be indicated for complete removal of periampullary (duodenal and ampullary) adenomas (PAs). As compared with malignant indications, PD for benign or pre-malignant disease is often associated with increased morbidity. While the Spigelman classification assesses malignancy risk for familial adenomatous polyposis (FAP)-related duodenal adenomas, no malignancy risk score (MRS) exists for non-FAP related PAs.

"She tells me the HIV is eating my brains": barriers and facilitators to antiretroviral therapy adherence among Eswatini adolescents living with HIV.

Despite the successful rollout of antiretroviral therapy (ART) and positive ART outcomes in the Kingdom of Eswatini, adolescents still present poor ART outcomes including low viral load suppression and suboptimal ART adherence. The aim of the study was to explore the perceptions of adolescents living with HIV (ALHIV) on the barriers and facilitators to ART adherence in Eswatini. We conducted a qualitative study using in-depth interviews among 29 ALHIV and on ART in Eswatini in December 2023.

An orally available P1'-5-fluorinated M inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier.

We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.

Consortium-driven rapid software validation for Research Electronic Data Capture (REDCap).

There is a growing trend for studies run by academic and nonprofit organizations to have regulatory submission requirements. As a result, there is greater reliance on REDCap, an electronic data capture (EDC) widely used by researchers in these organizations. This paper discusses the development and implementation of the Rapid Validation Process (RVP) developed by the REDCap Consortium, aimed at enhancing regulatory compliance and operational efficiency in response to the dynamic demands of modern clinical research.

Evaluating the association of genotype and cognitive resilience in SuperAgers.

Importance: "SuperAgers" are oldest-old adults (ages 80+) whose memory performance resembles that of adults in their 50s to mid-60s. Factors underlying their exemplary memory are underexplored in large, racially diverse cohorts.

Objective: To determine the frequency of genotypes in non-Hispanic Black and non-Hispanic White SuperAgers compared to middle-aged (ages 50-64), old (ages 65-79), and oldest-old (ages 80+) controls and Alzheimer's disease (AD) dementia cases.

Predilection for Perplexion: Preoperative microstructural damage is linked to postoperative delirium.

Postoperative delirium is the most common postsurgical complication in older adults and is associated with an increased risk of long-term cognitive decline and Alzheimer's disease (AD) and related dementias (ADRD). However, the neurological basis of this increased risk-whether postoperative delirium unmasks latent preoperative pathology or leads to AD-relevant pathology after perioperative brain injury-remains unclear. Recent advancements in neuroimaging techniques now enable the detection of subtle brain features or damage that may underlie clinical symptoms.

Backbone and Sidechain H, N and C Resonance Assignments of a Multidrug Efflux Membrane Protein using Solution and Solid-State NMR.

EmrE is a bacterial membrane-embedded multidrug transporter that functions as an asymmetric homodimer. EmrE is implicated in antibiotic resistance, but is now known to confer either resistance or susceptibility depending on the identity of the small molecule substrate. Here, we report both solution- and solid-state NMR assignments of S64V-EmrE at pH 5.

A post-assembly conformational change makes the SARS-CoV-2 polymerase elongation-competent.

Coronaviruses (CoV) encode sixteen non-structural proteins (nsps), most of which form the replication-transcription complex (RTC). The RTC contains a core composed of one nsp12 RNA-dependent RNA polymerase (RdRp), two nsp8s and one nsp7. The core RTC recruits other nsps to synthesize all viral RNAs within the infected cell.

#natural, #vegan, #healing: A Content Analysis of Health Content Among Instagram Posts Focused on Cannabis Edibles.

Background: Despite limited scientific evidence, public perceptions of cannabis as health enhancing are significant. As food products, cannabis edibles (edibles), may also leverage food-related associations that convey health. Social media is a prominent and influential source of largely unregulated cannabis information and a potential place to correct misinformation.

Factors Associated with Persisting Post-Concussion Symptoms Among Collegiate Athletes and Military Cadets: Findings from the NCAA-DoD CARE Consortium.

Background: Persisting post-concussion symptoms (PPCS) is a condition characterized by prolonged recovery from a mild traumatic brain injury (mTBI) and compromised quality of life. Previous literature, on the basis of small sample sizes, concludes that there are several risk factors for the development of PPCS.

Objective: We seek to identify protective and risk factors for developing slow recovery or persisting post-concussion symptoms (PPCS) by analyzing medical history, contact sport level, setting, and the Sport Concussion Assessment Tool (SCAT) and Brief Symptom Inventory (BSI-18) assessments at baseline and post-injury.

Assessment and treatment considerations for patients with colorectal liver metastases: AHPBA consensus guideline and update for surgeons.

Background: Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM).

Bridging the Last Mile: The Critical Role of Local Civil Society in Advancing Equity and Inclusion for Neglected Tropical Diseases.

Neglected tropical diseases (NTDs) disproportionately affect vulnerable populations, exacerbating existing inequities in health, gender, and socioeconomic status. Civil society organizations (CSOs) play a vital but often undervalued role in addressing these inequities by engaging with communities and fostering accountability of NTD programs and governments while ensuring transparency in their own operations and responsiveness to community needs. Drawing lessons from the HIV/AIDS and leprosy responses, this paper argues that CSOs are indispensable for sustainable and inclusive NTD programming.

Advancing precision psychiatry and targeted treatments: Insights from immunopsychiatry.

Despite tremendous advancements in neuroscience, there has been limited impact on patient care. Current psychiatric treatments are largely non-specific, and drug development is hindered by outdated, overinclusive diagnostic categories and a "one-size-fits-all" approach. Additionally, mechanisms underlying psychiatric illnesses and their treatments with conventional medications remain poorly understood.

Water insecurity is associated with sugar-sweetened beverage consumption in a small-scale population in Lowland Bolivia experiencing lifestyle changes.

Background: Emerging evidence indicates water insecurity (WI) is detrimental to nutritional outcomes and dietary choices.

Objective: This study measured WI experiences alongside market and traditional sugar-sweetened beverage (SSB) consumption in a small-scale society experiencing early stages of the nutrition transition (i.e.

MAPPING THE CEREBROSPINAL FLUID PROTEOME IN BIPOLAR DISORDER.

Background: Bipolar disorder (BD) is a severe psychiatric condition with unclear etiology and no established biomarkers. Here, we aimed to characterize the cerebrospinal fluid (CSF) proteome in euthymic BD individuals to identify potential protein biomarkers.

Methods: We employed nano-flow liquid chromatography coupled to high-resolution mass spectrometry to quantify over 2,000 CSF proteins in 374 individuals from two independent clinical cohorts (n=164+89 and 66+55 cases and controls, respectively).

Reduced UPF1 levels in senescence impair nonsense-mediated mRNA decay.

Cells regulate gene expression through various RNA regulatory mechanisms, and this regulation often becomes less efficient with age, contributing to accelerated aging and various age-related diseases. Nonsense-mediated mRNA decay (NMD), a well-characterized RNA surveillance mechanism, degrades aberrant mRNAs with premature termination codons (PTCs) to prevent the synthesis of truncated proteins. While the role of NMD in cancer and developmental and genetic diseases is well documented, its implications in human aging remain largely unexplored.

Novel synaptic markers predict early tau pathology and cognitive deficit in an asymptomatic population at risk of Alzheimer's disease.

Cognitive dysfunction in Alzheimer's disease (AD) correlates closely with pathology in the neuronal microtubule-associated protein tau. Tau pathology may spread via neural synapses. In a population of cognitively unimpaired elderly at elevated risk of AD, we investigated four cerebrospinal (CSF) markers of synaptic dysfunction and degeneration.

Identification of MORF4L1 as an endogenous substrate of CRBN and its potential role as a therapeutic target in cancer.

The ubiquitin-proteasome system (UPS) is essential for cellular homeostasis, regulating the degradation of proteins involved in key processes such as cell cycle, apoptosis, and DNA repair. Dysregulation of the UPS is implicated in hepatocellular carcinoma (HCC), contributing to tumor progression and therapeutic resistance. The cereblon (CRBN) E3 ubiquitin ligase complex is a crucial component of the UPS, particularly in modulating protein degradation in response to small-molecule modulators like thalidomide.

A case study on postoperative radiation therapy of the big toe.

Sweat gland cancers, particularly eccrine sweat gland carcinomas, are rare and challenging to treat due to their aggressive nature and inconspicuous clinical presentation. Aggressive digital papillary adenocarcinoma, a rare subtype, frequently presents with delays in diagnosis, increasing the risk of metastasis and recurrence. Surgical excision remains the standard treatment, but the role of postoperative radiation therapy is not well-established due to the paucity of data.

Rates of Return to Sexual Activity Are High In Patients Undergoing Hip Arthroscopy And Occurs Within Six Weeks Postoperatively In Most Patients: A Systematic Review.

Purpose: To provide an aggregate review of literature on 1) outcomes related to the quality of intercourse (frequency, postoperative pain during intercourse, postoperative sexual dysfunction) after hip arthroscopy and 2) patient-reported outcomes regarding postoperative sexual function after hip arthroscopy.

Methods: This systematic review followed The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Cochrane Controlled Register of Trials (CENTRAL), and Scopus were queried in March 2024.

Changes in Contraceptive Method Use, Access, and Experiences of Care During a Statewide Contraceptive Initiative.

Objective: To examine changes in contraceptive use, access, and care experiences during a statewide contraceptive access initiative, Delaware Contraceptive Access Now.

Study Design: We used responses from the Delaware/Maryland Survey of Women at the early wave (11/2016-3/2017) and late wave (2/2021-10/2021). Our cross-sectional sample included 6,467 respondents at risk of unintended pregnancy.

Fine-tuning of gene expression through the Mettl3-Mettl14-Dnmt1 axis controls ESC differentiation.

The marking of DNA, histones, and RNA is central to gene expression regulation in development and disease. Recent evidence links N6-methyladenosine (mA), installed on RNA by the METTL3-METTL14 methyltransferase complex, to histone modifications, but the link between mA and DNA methylation remains scarcely explored. This study shows that METTL3-METTL14 recruits the DNA methyltransferase DNMT1 to chromatin for gene-body methylation.

A study of internal structure validity for the American board of surgery in training examination.

Background: As principles of competency-based medical education are implemented into graduate medical education [GME] programs, it is imperative that the assessments employed are reliable and valid. Internal structure is a core component of validity evidence that has been under studied. In this study, we examined elements of the internal structure for the American Board of Surgery In-Training Examination [ABSITE].