Putative PINK1/Parkin activators lower the threshold for mitophagy by sensitizing cells to mitochondrial stress.

The PINK1/Parkin pathway targets damaged mitochondria for degradation via mitophagy. Genetic evidence implicates impaired mitophagy in Parkinson's disease, making its pharmacological enhancement a promising therapeutic strategy. Here, we characterize two mitophagy activators: a novel Parkin activator, FB231, and the reported PINK1 activator MTK458.

Geographic Variation in the Utilization of Cancer Care From Subspecialized Medical Oncologists in the United States, 2008 to 2020.

Background: The growing complexity of cancer care may be driving an increase in subspecialized medical oncologists who focus on treating specific cancer types. However, little is known about trends in subspecialization among oncologists and differences in utilization of subspecialists.

Objective: To quantify trends in oncologist subspecialization and assess differences in utilization of subspecialized cancer care in the United States.

A protocol for pre-treatment testing for antibodies to galactose-alpha-1,3-galactose to mitigate the risk of cetuximab hypersensitivity reactions - a retrospective cohort review.

Purpose: Cetuximab improves survival in KRAS wildtype metastatic colorectal cancer. However, high rates of hypersensitivity reactions (HSRs) limit its use, with HSR rates up to 10-20 %. A major driver of cetuximab HSR is from pre-formed IgE antibody response to galactose-1,3-alpha-galactose (alpha-gal).

Time-lapse imaging systems for embryo incubation and assessment to improve reproductive outcomes in women undergoing in vitro fertilisation: study protocol for an individual participant data meta-analysis of randomised controlled trials.

Introduction: Time-lapse imaging (TLI) systems for embryo incubation and assessment are hypothesised to improve the success rates of in vitro fertilisation (IVF) treatment by providing undisturbed culture conditions for embryos and/or providing more information on embryo development (morphokinetic parameters) to improve predictive accuracy for embryo selection. Despite numerous aggregate meta-analyses showing uncertainty of benefit, IVF clinics globally continue to invest significant resources into this technology with little translation of evidence into guidelines or policy frameworks. This may be attributed to heterogeneity in participant populations and/or variations in the use of TLI, as highlighted in the aggregate meta-analyses.

LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes.

Protein misfolding is a contributor to the development of type 2 diabetes (T2D), but the specific role of impaired proteostasis is unclear. Here we show a robust accumulation of misfolded proteins in the mitochondria of human pancreatic islets from patients with T2D and elucidate its impact on β cell viability through the mitochondrial matrix protease LONP1. Quantitative proteomics studies of protein aggregates reveal that islets from donors with T2D have a signature resembling mitochondrial rather than endoplasmic reticulum protein misfolding.

Feasibility of Conservative Management for Intraperitoneal Bladder Perforation: A Single-Institution Case Series.

: Bladder injuries are broadly classified based on anatomical location into two main categories: extraperitoneal and intraperitoneal. Traditionally, clinicians manage most extraperitoneal bladder ruptures conservatively with catheter drainage, while intraperitoneal ruptures are surgically repaired. This study aims to evaluate the feasibility of conservative management of intraperitoneal bladder rupture in the largest series to date.

Oncogenic Activity and Sorafenib Sensitivity of p.S214C Mutation in Lung Cancer.

: RAF pathway aberrations are one of the hallmarks of lung cancer. Sorafenib is a multi-kinase inhibitor targeting the RAF pathway and is FDA-approved for several cancers, yet its efficacy in lung cancer is controversial. Previous clinical research showed that a p.

Effect of simvastatin on postoperative complications in patients undergoing one-lung ventilation during surgery: the Prevention HARP-2 randomised controlled trial.

Rationale: Surgeries that require one-lung ventilation have high rates of postoperative cardiopulmonary complications with associated morbidity and mortality. Statins may limit inflammation involved in the development of these complications.

Objectives: We tested the hypothesis that perioperative simvastatin use reduces postoperative cardiopulmonary complications, compared with placebo, in surgery requiring one-lung ventilation.

Understanding the physical health associations of intra-individual variability in life satisfaction among older adults.

It is well established that inter-individual differences in life satisfaction positively predict health, but it is less clear how intra-individual variability in life satisfaction across time could influence health, particularly across individuals with different satisfaction levels. To address this gap, we analysed a large panel dataset from a national sample of 8,674 older adults, aged 50-70 (M = 59, SD = 5.42) in Singapore who completed surveys over 53 consecutive months.

[F]FMISO PET in metastatic neuroendocrine tumours: a pilot study.

Objectives: The phenomenon of peripheral [Ga]DOTATATE avidity without central avidity (which we have termed a "DONUT") has been observed in neuroendocrine neoplasm (NEN) lesions. There has been speculation as to whether this is due to hypoxia, de-differentiated disease or other causes. The presence of hypoxia may have prognostic and therapeutic implications, and was evaluated in these lesions using the PET hypoxia imaging biomarker [F]FMISO.

Out-of-pocket medical costs in relation to resection of colorectal liver metastases in the Australian healthcare system.

Purpose: The cost of treating colorectal liver metastases (CRLM) places a financial burden on the healthcare system; however, there is limited research on the out-of-pocket (OOP) costs to patients. This study aimed to assess the direct medical OOP costs on patients who undergo liver resection for CRLM and evaluate their financial worry, stress, and difficulty.

Methods: This was a retrospective cohort analysis of the OOP costs for patients who underwent potentially curative resection of CRLM in Sydney, Australia, between 2010 and June 2021.

Unified Classification of the Type III Secreted Effectors of Bacterial Plant Pathogens to Advance Phytopathology Research.

Many diverse bacterial phytopathogens deploy type III secreted effectors (T3SEs) to promote virulence by interrupting host immunity and other critical plant processes. However, the virulence of T3SEs has been countered on the host side through the evolution of a multitude of resistance genes (R-genes) capable of recognizing the presence of T3SEs and eliciting a response termed effector triggered immunity (ETI). This dynamic sets up an evolutionary arms race that has led to enormous diversification of both bacterial T3SEs and plant R-genes.

Transcranial Photobiomodulation Improves Cognitive Function, Post-Concussion, and PTSD Symptoms in Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) occurs in millions of people globally each year, with mild TBI (mTBI) representing over 90% of cases. Despite the common assumption of full recovery, significant disturbances persist in many patients with mTBI, including cognitive deficit, headache, dizziness, sleep problems, and symptoms of post-traumatic stress disorder (PTSD). Given that effective treatment is still scarce, the present study investigated the efficacy of transcranial photobiomodulation (tPBM) as an intervention for improving these sequelae in patients with mTBI.

[F]FDG Metabolic Tumor Volume as a Prognostic Marker in Neuroendocrine Neoplasm: A Multicenter Study.

[F]FDG PET/CT avidity predicts higher-grade disease and worse prognosis in patients with metastatic neuroendocrine neoplasm. However, there is less evidence regarding the role of [F]FDG-avid tumor volume in predicting prognosis. We planned to determine whether metabolic tumor volume (MTV) on [F]FDG PET/CT predicts prognosis in patients with advanced gastroenteropancreatic neuroendocrine neoplasm (GEPNEN).

The Therapeutic Potential of EGCG and Pro-EGCG in Mitigating Ovarian Hyperstimulation Syndrome: Unraveling the Modulatory Mechanism through the VEGF Pathway.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication of controlled ovarian hyperstimulation (COH) during fertilization (IVF) treatment, characterized by increased capillary permeability. Vascular endothelial growth factor (VEGF) is a key mediator in OHSS, with serum VEGF levels correlating with its severity. In this study, we investigated the therapeutic potential of (-)-epigallocatechin-3-gallate (EGCG) and its derivative, Pro-EGCG, in mitigating OHSS.

The mitophagy receptors BNIP3 and NIX mediate tight attachment and expansion of the isolation membrane to mitochondria.

BNIP3 and NIX are the main receptors for mitophagy, but their mechanisms of action remain elusive. Here, we used correlative light EM (CLEM) and electron tomography to reveal the tight attachment of isolation membranes (IMs) to mitochondrial protrusions, often connected with ER via thin tubular and/or linear structures. In BNIP3/NIX-double knockout (DKO) HeLa cells, the ULK1 complex and nascent IM formed on mitochondria, but the IM did not expand.

Challenging arterial patterns of renal and testicular arteries in a human cadaver: clinical significance and embryological bases revisited.

Typically, a kidney gets its arterial supply from a single renal artery, and the testicular arteries originate from the anterolateral surface of the abdominal aorta. The present case describes a variation in the origin of the testicular artery, which originates from a right accessory renal artery. We observed two renal arteries with the inferior vena cava sandwiched in between.

Response to: Evaluating time-lapse imaging systems for embryo incubation and selection in ART: a critical review of a randomized controlled trial.

The concerns raised by the authors of this commentary are largely addressed in the paper and the requested information is available in the supplementary materials and the published trial protocol referenced in the paper. We have further detailed some information to address their concerns. The planned effect size was based on the results reported by the largest randomized controlled trial at the start of our trial and supported by peer review and patient and clinician input.

Renal mucinous cystadenoma in the context of lynch syndrome and colonic neuroendocrine neoplasm: a case report.

Renal mucinous cystadenoma (RMC) is an exceptionally rare finding with a poorly understood pathogenesis. Links between RMC and other malignancies are not well described, nor are there known associations with familial cancer disorders. We present the first case of RMC associated with Lynch syndrome (LS) and neuroendocrine neoplasm.

Modeling Incremental Benefit of Medication Reconciliation on ICU Outcomes.

Background: Medication errors such as medication discrepancies can occur in patients who are hospitalized and may result in adverse drug events (ADEs). Pharmacist-led medication reconciliation (MR) is an intervention that can be used to address medication discrepancies. Estimating the impact of MR in a medical setting is challenging to do experimentally.

Lung Cancer Surveillance for Patients With Head and Neck Cancer.

Importance: Patients with head and neck squamous cell cancer (HNSCC) are at a greater risk of developing pulmonary metastases and/or second primary lung cancer. However, it remains uncertain whether lung screening in these patients, when the initial staging studies are negative, confers any survival benefit.

Objective: To evaluate long-term cancer survival outcomes in patients with HNSCC undergoing chest radiography vs low-dose computed tomography screening for pulmonary metastasis and/or second primary lung cancer.

A Conceptual Model of Refugee Family Dynamics: A Study with Sri Lankan Tamils.

Sri Lankan Tamil refugees have endured over four decades of protracted displacement in southern India. This paper synthesizes findings from four studies conducted between 2005 and 2018 among refugees residing in the Gummidipoondi and Trichy refugee camps in the state of Tamil Nadu, India. Framed by a Community Based Participatory Research, in collaboration with the Organization for Eelam Refugee Rehabilitation (OfERR) and Community Advisory Board, these studies aimed to investigate the challenges related to migration stressors, mental health, family dynamics, and resource utilization of the Sri Lankan refugees living in India.

Dual regulation of mitochondrial fusion by Parkin-PINK1 and OMA1.

Mitochondrial stress pathways protect mitochondrial health from cellular insults. However, their role under physiological conditions is largely unknown. Here, using 18 single, double and triple whole-body and tissue-specific knockout and mutant mice, along with systematic mitochondrial morphology analysis, untargeted metabolomics and RNA sequencing, we discovered that the synergy between two stress-responsive systems-the ubiquitin E3 ligase Parkin and the metalloprotease OMA1-safeguards mitochondrial structure and genome by mitochondrial fusion, mediated by the outer membrane GTPase MFN1 and the inner membrane GTPase OPA1.