Tail Anchored protein insertion mediated by CAML and TRC40 links to neuromuscular function in mice.

Motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) and progressive bulbar palsy, involve loss of muscle control resulting from death of motor neurons. Although the exact pathogenesis of these syndromes remains elusive, many are caused by genetically inherited mutations. Thus, it is valuable to identify additional genes that can impact motor neuron survival and function.

Bone Enzyme-Responsive Biodegradable Poly(propylene fumarate) and Polycaprolactone Polyphosphoester Dendrimer Cross-Linked via Click Chemistry for Bone Tissue Engineering.

Traditional polymer systems often rely on toxic initiators or catalysts for cross-linking, posing significant safety risks. For bone tissue engineering, another issue is that the scaffolds often take a longer time to degrade, inconsistent with bone formation pace. Here, we developed an enzyme-responsive biodegradable poly(propylene fumarate) (PPF) and polycaprolactone (PCL) polyphosphoester (PPE) dendrimer cross-linked utilizing click chemistry (EnzDeg-click-PFCLPE scaffold) for enhanced biocompatibility and degradation.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

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.

Focal choroidal excavation (FCE)-related choroidal neovascular membrane (CNV) in a child.

Purpose: To report the rare clinical, optical coherence tomography (OCT), and OCT-angiography findings of a visually significant choroidal neovascular membrane (CNV) in the setting of focal choroidal excavation (FCE) in a child.

Methods: Case report and literature review.

Results: A 9-year-old girl with FCE-related central CNV based on clinical findings and multimodal imaging.

Trustworthiness of a machine learning early warning model in medical and surgical inpatients.

Objectives: In the general hospital wards, machine learning (ML)-based early warning systems (EWSs) can identify patients at risk of deterioration to facilitate rescue interventions. We assess subpopulation performance of a ML-based EWS on medical and surgical adult patients admitted to general hospital wards.

Materials And Methods: We assessed the scores of an EWS integrated into the electronic health record and calculated every 15 minutes to predict a composite adverse event (AE): all-cause mortality, transfer to intensive care, cardiac arrest, or rapid response team evaluation.

INCREASED CITRULLINATED HISTONE H3 LEVELS AND ACCELERATED THROMBIN KINETICS IN TRAUMA PATIENTS WHO DEVELOP VENOUS THROMBOEMBOLISM.

Background: Neutrophil extracellular traps (NETs), and its formation and release, known as NETosis, may play a role in the initiation of thrombin generation (TG) in trauma. The objective of this study was to assess whether trauma patients, who develop symptomatic venous thromboembolism (VTE), have increased levels of plasma citrullinated histone H3 (CitH3) and accelerated TG kinetics.

Methods: Patients presenting to a Level I Trauma Center as trauma activations had samples collected within 12 hours of time of injury (TOI), alongside healthy volunteers (HV).

SPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.

Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life.

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.

An examination of sexual function & distress among sexual minority & heterosexual women seeking care at menopause and sexual health specialty clinics.

Background: Sexual minority women (SMW) have worse mental and physical health outcomes compared to heterosexual women, but literature on sexual function in SMW compared to heterosexual women is lacking.

Aim: To evaluate sexual function and sexual distress in women across sexual orientations.

Method: Questionnaire data were analyzed for women aged 18 and older who presented to women's health clinics at Mayo Clinic in Minnesota, Arizona, and Florida from 2016 to 2023.

Pathophysiology and Management of Refractory Trigeminal Neuralgia.

Purpose Of Review: Discuss the current understanding of the pathophysiology and management of refractory trigeminal neuralgia (TN). This includes a discussion on why TN can recur after microvascular decompression and a discussion on "outside of the box" options when both first- and second-line management strategies have been exhausted.

Recent Findings: This review discusses second- and third-line oral medication options, botulinum toxin A, repeat microvascular decompression, repeat ablative procedures, internal neurolysis, trigeminal branch blockade, and neuromodulation using TMS or peripheral stimulation.

Performance of dehydroepiandrosterone sulfate and baseline cortisol in assessing adrenal insufficiency.

Context: Diagnosing adrenal insufficiency (AI) often requires complex testing which can be time consuming and expensive. Dehydroepiandrosterone sulfate (DHEAS) is a promising marker of hypothalamic-pituitary-adrenal (HPA) axis function, however its diagnostic performance has not yet been evaluated in a large-scale study.

Objective: Evaluate the performance of DHEAS and baseline cortisol in assessing AI.

Proceedings of the Conference "CMV Vaccine Development-How Close Are We?" (27-28 September 2023).

Congenital cytomegalovirus (cCMV) is the most common infectious cause of disability in children, including sensorineural hearing loss. There is interest in developing a pre-conception vaccine that could confer protective immunity on a woman of child-bearing age, hence resulting in a reduced cCMV disease burden. Other populations, including solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients, could also benefit from CMV vaccination.

Using high-frequency oscillations from brief intraoperative neural recordings to predict the seizure onset zone.

Background: While high-frequency oscillations (HFOs) and their stereotyped clusters (sHFOs) have emerged as potential neuro-biomarkers for the rapid localization of the seizure onset zone (SOZ) in epilepsy, their clinical application is hindered by the challenge of automated elimination of pseudo-HFOs originating from artifacts in heavily corrupted intraoperative neural recordings. This limitation has led to a reliance on semi-automated detectors, coupled with manual visual artifact rejection, impeding the translation of findings into clinical practice.

Methods: In response, we have developed a computational framework that integrates sparse signal processing and ensemble learning to automatically detect genuine HFOs of intracranial EEG data.

Interhypothalamic adhesions: prevalence, structure, and location-based classification map in pediatric patients undergoing MRI.

Purpose: Interhypothalamic adhesions (IHAs) have been reported only in the pediatric population, with unknown prevalence and histological composition. We aim to demonstrate their prevalence, assess their persistence through longitudinal imaging, classify IHAs by anatomical distribution, explore their structure, and report associated pathologies.

Methods: A retrospective review was conducted on consecutive pediatric brain MRI studies obtained between January 2012, and December 2013.

Structure-derived insights from blood factors binding to the surfaces of different adenoviruses.

The tropism of adenoviruses (Ads) is significantly influenced by the binding of various blood factors. To investigate differences in their binding, we conducted cryo-EM analysis on complexes of several human adenoviruses with human platelet factor-4 (PF4), coagulation factors FII (Prothrombin), and FX. While we observed EM densities for FII and FX bound to all the species-C adenoviruses examined, no densities were seen for PF4, even though PF4 can co-pellet with various Ads.

Community-Engaged Approaches for Improving the Inclusion of Diverse Communities in a Nutrition Clinical Trial.

Background: Cardiometabolic disease (CMD) disproportionately affects African American/Black (AA) and Latino communities. CMD disparities are exacerbated by their underrepresentation in clinical trials for CMD treatments including nutritional interventions. The study aimed to (1) form a precision nutrition community consultant panel (PNCCP) representative of Latino and AA communities in Los Angeles to identify barriers and facilitators to recruitment and retention of diverse communities into nutrition clinical trials and (2) develop culturally informed strategies to improve trial diversity.

Exogenous insulin does not reduce protein catabolism in pre-diabetic cystic fibrosis patients: A randomized clinical trial.

Background: Cystic Fibrosis (CF) patients historically suffered from undernutrition, infection and inflammation. Insulin insufficiency-related protein catabolism further compromised health. We aimed to determine whether insulin improves protein catabolism in CF youth with abnormal glucose tolerance (AGT).

Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer.

Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR).

Lipoprotein (a) testing patterns among subjects with a measured lipid panel: The Mayo Clinic experience.

Objective: Lipoprotein(a) [Lp(a)] has been associated with Atherosclerotic Cardiovascular Disease (ASCVD). Approximately 20 % of the population has elevated Lp(a). Despite its well-recognized role in ASCVD, universal screening remains controversial.