SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease defined by a progressive decline in lung function due to scarring and accumulation of extracellular matrix (ECM) proteins. The SOCS (Suppressor Of Cytokine Signaling) domain is a 40 amino acid conserved domain known to form a functional ubiquitin ligase complex targeting the Von Hippel Lindau (VHL) protein for proteasomal degradation. Here we show that the SOCS conserved domain operates as a molecular tool, to disrupt collagen and fibronectin fibrils in the ECM associated with fibrotic lung myofibroblasts.

Association of SARS-CoV-2 Infection during pregnancy with placental weight and histopathologic lesions.

Introduction: The reported gross and histopathologic changes in the placenta associated with SARS-CoV-2 infection are heterogeneous. We sought to summarize placental histopathologic findings from pregnancies affected by SARS-CoV-2 infection according to timing of infection and symptom severity.

Methods: We conducted a retrospective cohort study of patients with SARS-CoV-2 infection during pregnancy who had deliveries at Mayo Clinic, Rochester, Minnesota, from April 2020 through June 2021.

Concordance and test-retest consistency of sleep biomarker-based neurodegenerative disorder profiling.

Biomarkers that aid in early detection of neurodegeneration are needed to enable early symptomatic treatment and enable identification of people who may benefit from neuroprotective interventions. Increasing evidence suggests that sleep biomarkers may be useful, given the bi-directional relationship between sleep and neurodegeneration and the prominence of sleep disturbances and altered sleep architectural characteristics in several neurodegenerative disorders. This study aimed to demonstrate that sleep can accurately characterize specific neurodegenerative disorders (NDD).

Disorder within order: identification of the disordered loop of STAS domain as the inhibitory domain in SLC26A9 chloride channel.

The chloride transporter-channel SLC26A9 is mediated by a reciprocal regulatory mechanism through the interaction between its cytoplasmic STAS domain and the R domain of CFTR. In vertebrate Slc26a9s, the STAS domain structures are interrupted by a disordered loop which is conserved in mammals but is variable in non-mammals. Despite the numerous studies involving the STAS domains in SLC26 proteins, the role of the disordered loop region has not been identified.

Novel Perspectives Focused on the Relationship Between Herpesvirus Encephalitis and Anti-GFAP-Antibody-Positive Astrocytopathy.

Virus encephalitis (VE), recognized as one of the common kinds of central nervous system (CNS) diseases after virus infection, has a surprising correlation with autoimmune encephalitis (AE) when autoimmune antibodies emerge in cerebrospinal fluid (CSF) or serum. Herpes simplex virus and Epstein-Barr virus are the most critical agents worldwide. By molecular mimicry, herpes viruses can invade the brain directly or indirectly.

The eSAH score: a simple practical predictive model for SAH mortality and outcomes.

We developed a simple quantifiable scoring system that predicts aneurysmal subarachnoid hemorrhage (aSAH) mortality, delayed cerebral ischemia (DCI), and modified Rankin scale (mRS) outcomes using readily available SAH admission data with SAH volume (SAHV) measured on computed tomography (CT). We retrospectively analyzed a cohort of 277 patients with aSAH admitted at our Comprehensive Stroke Center at Mayo Clinic in Jacksonville, Florida, between January 5, 2012, and February 24, 2022. We developed a mathematical radiographic model SAHV that measures basal cisternal SAH blood volume using a derivation of the ABC/2 ellipsoid formula (A = width/thickness, B = length, C = vertical extension) on noncontrast CT, which we previously demonstrated is comparable to pixel-based manual segmentation on noncontrast CT.

The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis.

Serine 31 is a phospho-site unique to the histone H3.3 variant; mitotic phospho-Ser31 is restricted to pericentromeric heterochromatin, and disruption of phospho-Ser31 results in chromosome segregation defects and loss of p53-dependant G cell-cycle arrest. Ser31 is proximal to the H3.

DNA aptamers that modulate biological activity of model neurons.

There is an urgent need for agents that promote health and regeneration of cells and tissues, specifically to treat diseases of the aging nervous system. Age-associated nervous system degeneration and various diseases are driven by many different biochemical stresses, often making it difficult to target any one disease cause. Our laboratory has previously identified DNA aptamers with apparent regenerative properties in murine models of multiple sclerosis by selecting aptamers that bind oligodendrocyte membrane preparations.

Similar deficiencies, different outcomes: succinate dehydrogenase loss in adrenal medulla vs. fibroblast cell culture models of paraganglioma.

Heterozygosity for loss-of-function alleles of the genes encoding the four subunits of succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD), as well as the SDHAF2 assembly factor predispose affected individuals to pheochromocytoma and paraganglioma (PPGL), two rare neuroendocrine tumors that arise from neural crest-derived paraganglia. Tumorigenesis results from loss of the remaining functional SDHx gene copy, leading to a cell with no functional SDH and a defective tricarboxylic acid (TCA) cycle. It is believed that the subsequent accumulation of succinate competitively inhibits multiple dioxygenase enzymes that normally suppress hypoxic signaling and demethylate histones and DNA, ultimately leading to increased expression of genes involved in angiogenesis and cell proliferation.

Expert Perspective: Management of Relapses in Giant Cell Arteritis.

Giant cell arteritis (GCA) is a relapsing large-vessel vasculitis with risk of serious ischemic manifestations including vision loss and vascular damage in the form of large-artery stenosis, aneurysms and dissections. Approximately 50% of patients treated with glucocorticoid (GC) monotherapy and 30% of patients receiving adjunctive therapy with tocilizumab experience disease relapses, often during the first 2 years after diagnosis. Although most relapses in GCA do not involve life- or organ-threatening presentations and can be controlled successfully, frequent relapses may lead to increased use of GC and consequent treatment-related morbidity, in addition to risk of further vascular damage.

Physiological shedding and C-terminal proteolytic processing of TMEM106B.

Genetic variants in TMEM106B, coding for a transmembrane protein of unknown function, have been identified as critical genetic modulators in various neurodegenerative diseases with a strong effect in patients with frontotemporal degeneration. The luminal domain of TMEM106B can form amyloid-like fibrils upon proteolysis. Whether this luminal domain is generated under physiological conditions and which protease(s) are involved in shedding remain unclear.

Cell-free DNA methylation-based inflammation score as a marker for hepatocellular carcinoma among people living with HIV.

Background: People living with the human immunodeficiency virus (HIV) are at a greater risk of developing hepatocellular carcinoma (HCC), potentially due to the stimulation of inflammation by HIV infection. Inflammation-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (cfDNA), may serve as promising minimally invasive biomarkers that can inform diagnosis of HCC.

Methods: Using data from 249 individuals with HIV (114 individuals with normal liver conditions, 69 with fibrosis, 30 with cirrhosis, and 36 with HCC), we constructed a cfDNA methylation-based inflammation score (inflammation-DNAm score) based on 54 CpGs previously associated with circulating C-reactive protein concentrations.

Radiotherapy-resistant prostate cancer cells escape immune checkpoint blockade through the senescence-related ataxia telangiectasia and Rad3-related protein.

Background: The majority of patients with prostate cancer (PCa) exhibit intrinsic resistance to immune checkpoint blockade (ICB) following radiotherapy (RT). This resistance is generally attributed to the limited antigen presentation of heterogeneous cells within tumors. Here, we aimed to isolate and characterize these diverse subgroups of tumor post-RT to understand the molecular mechanisms of their resistance to ICB.

The Right Ventricle and Exercise Capacity in Adults with Repaired Tetralogy of Fallot: Passive Bystander or Active Participant?

Exercise intolerance is a hallmark symptom in adults with repaired tetralogy of Fallot (TOF). This may be attributed to the disease-related impairment in RV systolic function, augmentation in right ventricular (RV) load, and their combined effect on altering left ventricular (LV) hemodynamics. To further elucidate these mechanisms, we examined oxygen uptake (VO) by indirect-calorimetry and cardiac hemodynamics by echocardiography in 34 TOF (48 ± 14 yrs) and 29 healthy controls (41 ± 15 yrs), at rest and during exercise.

At the Scrub Sink: Evaluation of Ureteric Patency During Cystoscopy.

At the scrub sink, we discussed the best ways to evaluate for ureteric patency during cystoscopy. For decades, surgeons have been using intravenous indigo carmine for evaluating ureteric patency. Ten years ago, a shortage of indigo carmine halted production.

Supporting Patient Involvement in U.S. Medical Education Through Changes in Accreditation.

For over half of a century, there have been calls for greater patient and community involvement in U.S. medical education.

ChatGPT and frequently asked patient questions for upper eyelid blepharoplasty surgery.

Purpose: Online health information seekers may access information produced by artificial intelligence language models such as ChatGPT (OpenAI). The medical field may pose a significant challenge for incorporating these applications given the training and experience needed to master clinical reasoning. The objective was to evaluate the performance of ChatGPT responses compared to human oculofacial plastic surgeon (OPS) responses to FAQs about an upper eyelid blepharoplasty procedure.