Emerging targets of α-synuclein spreading in α-synucleinopathies: a review of mechanistic pathways and interventions.

α-Synucleinopathies constitute a spectrum of neurodegenerative disorders, including Parkinson's disease (PD), Lewy body dementia (LBD), Multiple System Atrophy (MSA), and Alzheimer's disease concurrent with LBD (AD-LBD). These disorders are unified by a pathological hallmark: aberrant misfolding and accumulation of α-synuclein (α-syn). This review delves into the pivotal role of α-syn, the key agent in α-synucleinopathy pathophysiology, and provides a survey of potential therapeutics that target cell-to-cell spread of pathologic α-syn.

Efficacy of repetitive transcranial magnetic stimulation for phantom limb pain- a meta analysis of randomized controlled trials.

Introduction: Phantom limb pain (PLP) is a neuropathic syndrome experienced by the majority of amputees. Various treatment options are available for amputees suffering from PLP including pharmacological, psychological and neuromodulation techniques. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that has proven its efficacy in alleviating PLP.

Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson's disease.

The pathogenesis of Lewy body diseases (LBDs), including Parkinson's disease (PD), involves α-synuclein (α-Syn) aggregation that originates in peripheral organs and spreads to the brain. PD incidence is increased in individuals with chronic renal failure, but the underlying mechanisms remain unknown. Here we observed α-Syn deposits in the kidneys of patients with LBDs and in the kidney and central nervous system of individuals with end-stage renal disease without documented LBDs.

Digital Disputes: Minimizing Legal Vulnerability in the Information Age.

Background: This project aims to provide guidance for surgeons' online interactions by reviewing key legal decisions.

Methods: The Nexis Uni database was queried to search for state and federal case law and law journal articles. Search terms were "social media" AND (facial w/s plastic!) and internet AND advice AND "plastic surgery.

Salt-in-presalt electrolyte solutions for high-potential non-aqueous sodium metal batteries.

Room-temperature non-aqueous sodium metal batteries are viable candidates for cost-effective and safe electrochemical energy storage. However, they show low specific energy and poor cycle life as the use of conventional organic-based non-aqueous electrolyte solutions enables the formation of interphases that cannot prevent degradations at the positive and negative electrodes. Here, to promote the formation of inorganic NaF-rich interphases on both negative and positive electrodes, we propose the salt-in-presalt (SIPS) electrolyte formulation strategy.

The global air pollution and undernutrition among children under five.

Malnutrition and PM pollution remain a pressing global public health concern, especially to vulnerable populations like children under five years old. This study aimed to investigate the correlation between undernutrition in children under five years old and air pollution (exposure to PM) on a global scale. This ecological study evaluated the correlation between undernutrition (wasting and stunting) and air pollution in 123 countries.

Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis.

Background And Objective: Selection of patients harboring mutations in homologous recombination repair (HRR) genes for treatment with a PARP inhibitor (PARPi) is challenging in metastatic castration-resistant prostate cancer (mCRPC). To gain further insight, we quantitatively assessed the differential efficacy of PARPi therapy among patients with mCRPC and different HRR gene mutations.

Methods: This living meta-analysis (LMA) was conducted using the Living Interactive Evidence synthesis framework.

Should digoxin immune fab be administered based solely on reported ingested amount in acute digoxin poisoning?

Acute digoxin poisoning is increasingly uncommon in emergency medicine. Furthermore, controversy exists regarding indications for antidotal digoxin immune fab in acute poisoning. In healthy adults, the fab prescribing information recommends administration based on "known consumption of fatal doses of digoxin: ≥10mg," while many emergency medicine textbooks suggest fab administration be driven by clinical features or potassium concentration.

Risk of bias assessment tools often addressed items not related to risk of bias and used numerical scores.

Objective: We aimed to determine whether the existing risk of bias assessment tools addressed constructs other than risk of bias or internal validity, and whether they used numerical scores to express quality, which is discouraged and may be a misleading approach.

Methods: We searched Ovid MEDLINE and Embase to identify quality appraisal tools across all disciplines in human health research. Tools designed specifically to evaluate reporting quality were excluded.

The Role of Sex and Gender in Acute Kidney Injury - Consensus Statements from the 33 Acute Disease Quality Initiative.

Sex differences exist in acute kidney injury (AKI), and the role that sex and gender play along the AKI care continuum remains unclear. The 33 Acute Disease Quality Initiative meeting evaluated available data on the role of sex and gender in AKI and identified knowledge gaps. Data from experimental models, pathophysiology, epidemiology, clinical care, gender, social determinants of health, education, and advocacy were reviewed.

Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.

Background: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2·4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA.

Integration of 168,000 samples reveals global patterns of the human gut microbiome.

The factors shaping human microbiome variation are a major focus of biomedical research. While other fields have used large sequencing compendia to extract insights requiring otherwise impractical sample sizes, the microbiome field has lacked a comparably sized resource for the 16S rRNA gene amplicon sequencing commonly used to quantify microbiome composition. To address this gap, we processed 168,464 publicly available human gut microbiome samples with a uniform pipeline.

Risk of carcinomas among children and adolescents with birth defects.

Background: Birth defects are associated with childhood cancer, but little is known regarding pediatric carcinomas, a group of especially rare tumors.

Methods: We used Cox proportional hazards regression to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for any carcinoma, as well as thyroid, hepatocellular, and renal carcinoma specifically, up to 18 years of age among children with major, non-syndromic anomalies or chromosomal/genetic syndromes, relative to unaffected children.

Results: Our registry-linkage study included nine states and 21,933,476 children between 1990 and 2018: 641,827 with non-syndromic anomalies, and 49,619 with syndromes.

The interplay between chromatin remodeling and DNA double-strand break repair: Implications for cancer biology and therapeutics.

Proper chromatin remodeling is crucial for many cellular physiological processes, including the repair of DNA double-strand break (DSB). While the mechanism of DSB repair is well understood, the connection between chromatin remodeling and DSB repair remains incompletely elucidated. In this review, we aim to highlight recent studies demonstrating the close relationship between chromatin remodeling and DSB repair.

Informing ICU Digital Twins: Dynamic Assessment of Cardiorespiratory Failure Trajectories in Patients with Sepsis.

Understanding clinical trajectories of sepsis patients is crucial for prognostication, resource planning, and to inform digital twin models of critical illness. This study aims to identify common clinical trajectories based on dynamic assessment of cardiorespiratory support using a validated electronic health record data that covers retrospective cohort of 19,177 patients with sepsis admitted to ICUs of Mayo Clinic Hospitals over eight-year period. Patient trajectories were modeled from ICU admission up to 14 days using an unsupervised machine learning two-stage clustering method based on cardiorespiratory support in ICU and hospital discharge status.

CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells.

Localized prostate cancer can be cured by radiation or surgery, but advanced prostate cancer continues to be a clinical challenge. Altered alternative polyadenylation occurs in numerous cancers and can downregulate tumor-suppressor genes and upregulate oncogenes. We found that the cleavage and polyadenylation specificity factor (CPSF) complex factor CPSF1 is upregulated in patients with advanced prostate cancer, with high CPSF1 expression correlating with worse progression-free survival.

Short-term outcomes of low anterior resection with and without ileostomy for low, mid and upper rectal cancers.

Although the addition of an ileostomy to low anterior resection (LAR) may often be considered preventative of anastomotic leakage (AL), evidence that clearly demonstrates such benefit is lacking. This study aimed to identify the impact of adding an ileostomy upon AL and organ-space surgical site infection (SSI) rates in patients with lower, middle, or upper rectal cancer. This case-control study included rectal cancer patients who had undergone elective LAR in the American College of Surgeons-National Surgical Quality Improvement Program dataset between 2016 and 2022.

Effect of antiplatelet and anticoagulant medications on implant survival: a long-term retrospective cohort study.

Purpose: This large-scale retrospective study aimed to examine the long-term effect of antiplatelet and anticoagulant medications intake on dental implant treatment outcome.

Materials And Methods: This study retrospectively examined data from patients who underwent dental implant procedures at several university dental clinics within the BigMouth network between 2011 and 2022. Patients' characteristics including age, gender, ethnicity, race, tobacco use, systemic medical conditions and intake of antiplatelets and anticoagulants were analyzed.

ACTB::ZMIZ2-rearranged adnexal carcinoma: a second case.

A case of cutaneous adnexal neoplasm with unusual squamoid morphology and harboring an in frame ACTB::ZMIZ2 fusion transcript was recently described. Herein, we report a second case of adnexal carcinoma harboring similar morphology and an identical in frame ACTB::ZMIZ2 fusion transcript. This 2.

Hypopituitarism Screening in Patients with Traumatic Brain Injury in the Primary Care Setting at the Minneapolis Veterans Affairs Health Care System.

Introduction: Traumatic brain injury (TBI) is a significant health issue among veterans and poses a substantial risk for pituitary injury. Consensus guidelines recommend that patients who have sustained a TBI should undergo a baseline pituitary hormonal evaluation after the primary brain insult. Patients with abnormal screening test results or with symptoms of hypopituitarism should be referred to endocrinology for a full assessment.

A nuanced scrutiny of the segmental renal artery spectral Doppler in "Pickering" the right diagnosis.

Approximately 5-10% of patients with hypertension have secondary hypertension. We describe a case of secondary hypertension from bilateral renal artery stenosis (RAS): "Pickering syndrome." This is a case of hypertension secondary to bilateral RAS which provides an opportunity to review secondary hypertension with a specific focus on RAS, in terms of when to consider work up, causes of secondary hypertension, diagnostic testing, and treatment.

Comprehensive Assessment of the Risk of Symptomatic Embolism in Patients With Infective Endocarditis.

Background: Echocardiographic evaluation of vegetations is crucial in infective endocarditis (IE). Although several studies have noted a link between larger vegetations and an increased risk of embolization, a more comprehensive evaluation of vegetation characteristics in a contemporary cohort has not been conducted. Our study aimed to define the short-term risk of symptomatic embolization in patients with IE.