The N-degron pathway mediates the autophagic degradation of cytosolic mitochondrial DNA during sterile innate immune responses.

The human body reacts to tissue damage by generating damage-associated molecular patterns (DAMPs) that activate sterile immune responses. To date, little is known about how DAMPs are removed to avoid excessive immune responses. Here, we show that proteasomal dysfunction induces the release of mitochondrial DNA (mtDNA) as a DAMP that activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway and is subsequently degraded through the N-degron pathway.

BCKDK loss impairs mitochondrial Complex I activity and drives alpha-synuclein aggregation in models of Parkinson's disease.

Mitochondrial dysfunction and α-synuclein (αSyn) aggregation are key contributors to Parkinson's Disease (PD). While genetic and environmental risk factors, including mutations in mitochondrial-associated genes, are implicated in PD, the precise mechanisms linking mitochondrial defects to αSyn pathology remain incompletely understood, hindering the development of effective therapeutic interventions. Here, we identify the loss of branched chain ketoacid dehydrogenase kinase (BCKDK) as a mitochondrial risk factor that exacerbates αSyn pathology by disrupting Complex I function.

Asthma Exacerbation Risk in Pregnancy and Postpartum: Assessing the Impact of Gestational Diabetes Mellitus and Other Key Factors.

Background: Asthma, affecting approximately 13% of pregnancies worldwide, and gestational diabetes mellitus (GDM), present in about 14%, are both associated with adverse maternal and perinatal outcomes. This study aims to address a lack of current knowledge about how GDM affects asthma during pregnancy.

Objective: To determine whether GDM is associated with an increased risk of asthma exacerbations during pregnancy and the first year postpartum.

Management of pleural effusion in mechanically ventilated critically ill patients: A systematic review and guideline.

Background: Mechanically ventilated critically ill patients often develop pleural effusions, which may impact lung compliance and expansion. This systematic review explores the management of pleural effusion in the critically ill population.

Methods: A comprehensive literature search was performed.

Perioperative complications and cervical malalignment requiring revision following cervical C3 laminectomy and C4-6 laminoplasty.

Background: Degenerative cervical myelopathy is one of the most common causes of spinal cord dysfunction. Cervical laminoplasty is an excellent surgical procedure that address the underlying pathology along with motion preservation with various advantages over other surgical options. While the advantages are intuitive and are being proven in multiple recent studies, concerns regarding failure still remains precluding wider utilization despite evidence to the contrary.

Stress by Design: A Scoping Review of Structural Stress of Emergency Telecommunicators.

Background: Most agree that occupational stress is caused by workplace strains, tensions, and demands that originate from characteristics of the work. The accumulation of multiple types of stress has been found to have calamitous effects on health and well-being. One such occupation, emergency telecommunicators, experiences a multitude of stressors within their day-to-day work environment.

A New Perspective on Drugs for Duchenne Muscular Dystrophy: Proposals for Better Respiratory Outcomes and Improved Regulatory Pathways.

New drugs for Duchenne muscular dystrophy (DMD) are emerging rapidly. However, we and others believe these drugs are achieving regulatory approval prematurely. It is the cardiorespiratory complications of DMD that cause the disease's major morbidities and that determine survival.

Global disparities in drug-related adverse events of patients with multiple myeloma: a pharmacovigilance study.

Multiple myeloma (MM) is a complex hematological malignancy of clonal plasma cells driven by alterations to the chromosomal material leading to uncontrolled proliferation in the bone marrow. Ethnic and racial disparities persist in the prevalence, diagnosis, management, and outcomes of MM. These disparities are multifaceted and intersect with various factors, including demographics, geography, socioeconomic status, genetics, and access to healthcare.

Intraoperative Molecular Imaging With Pafolacianine: Histologic Characteristics of Identified Nodules.

Background: With increased early detection efforts, surgery for early-stage lung cancer is expected to rise. Pafolacianine is the first FDA approved targeted optical imaging agent indicated as an adjunct for intraoperative identification of malignant and nonmalignant pulmonary lesions in adult patients with known or suspected cancer in the lung.

Methods: This is a retrospective review of the malignant and nonmalignant lesions identified by pafolacianine with intraoperative molecular imaging (IMI) in the multi-center Phase 2 and Phase 3 ELUCIDATE clinical trials.

The physicochemical properties of lipopolysaccharide chemotypes regulate activation of the contact pathway of blood coagulation.

Lipopolysaccharide (LPS) is the primary pathogenic factor in Gram-negative sepsis. While the presence of LPS in the bloodstream during infection is associated with disseminated intravascular coagulation, the mechanistic link between LPS and blood coagulation activation remains ill-defined. The contact pathway of coagulation-a series of biochemical reactions that initiates blood clotting when plasma factors XII (FXII) and XI (FXI), prekallikrein (PK) and high molecular weight kininogen (HK) interact with anionic surfaces-has been shown to be activated in Gram-negative septic patients.

A team-based approach to type 2 diabetes and cardiovascular care.

The Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) program is an innovative, patient-centered system of care developed by the University Hospitals Harrington Heart and Vascular Institute in Cleveland, Ohio in the US for the management of high-risk patients with type 2 diabetes (T2D) and prediabetes at high risk for cardiovascular-kidney-metabolic (CKM) syndrome and its consequences. At its core, CINEMA is a multidisciplinary team of care experts, working together outside of traditional silos. The patient meets with the entire team up to 4 times each year to address all aspects of cardiovascular (CV) and T2D care.

An Access-Focused Patient-Centric Value Assessment Framework for Medication Formulary Decision-Making in Immune-Mediated Inflammatory Diseases.

The healthcare system in the United States (US) is complex and often fragmented across national and regional health plans which exhibit substantial variability in benefit design and formulary policies for accessing medications. We propose an access-focused value assessment framework for formulary decision-making for medications to manage immune-mediated inflammatory diseases (IMIDs), where patients are at the center of this framework. Formulary decision-making for IMID medications can be a challenging, even daunting, task with continuously evolving and enhanced treat-to-target goals.

Fis1 regulates mitochondrial morphology, bioenergetics, and removal of mtDNA damage in irradiated glioblastoma cells.

In response to external stress, mitochondrial dynamics is often disrupted, but the associated physiologic changes are often uncharacterized. In many cancers, including glioblastoma (GBM), mitochondrial dysfunction has been observed. Understanding how mitochondrial dynamics and physiology contribute to treatment resistance will lead to more targeted and effective therapeutics.

Outcomes after per oral pyloromyotomy based on gastroparesis etiology.

Background: Per oral pyloromyotomy (POP) has been shown to be effective in patients with gastroparesis. The three most common etiologies of gastroparesis are diabetic, postsurgical, and idiopathic. Our aim was to compare outcomes after POP based on the etiology of gastroparesis.

Consensus Radiation Treatment Planning Guidelines Utilizing (68)Ga-DOTATATE PET/CT for Resected Meningiomas.

Background: Meningiomas are the most common primary intracranial tumor. Somatostatin receptor 2 (SSTR 2) is almost universally expressed in meningioma tissue. For patients who require adjuvant radiation, SSTR based (68)Ga-DOTATATE positron emission tomography (PET) imaging can detect additional or residual disease not discernible on magnetic resonance imaging (MRI).

HIGH BODY MASS INDEX IS ASSOCIATED WITH LOWER ADALIMUMAB SERUM LEVELS AND HIGHER DISEASE ACTIVITY IN NON-INFECTIOUS UVEITIS.

Purpose: Adalimumab, a TNF-alpha inhibitor, is the only FDA-approved biologic for non-infectious uveitis (NIU). However, treatment responses vary, potentially due to interindividual pharmacokinetic differences influenced by body mass index (BMI). This study aimed to evaluate the impact of BMI on adalimumab serum trough levels and therapeutic efficacy in patients with NIU.

Evaluation of a far ultraviolet-C device for decontamination of portable equipment in clinical areas.

Contaminated portable equipment may contribute to transmission of healthcare-associated pathogens. We demonstrated that a wall-mounted far ultraviolet-C (UV-C) light technology that delivers far UV-C only when people are not present was effective in reducing contamination on in-use patient transport chairs and physical therapy equipment in equipment rooms. The technology could potentially be used as an adjunctive measure for decontamination of portable equipment in clinical areas.

Diagnostic accuracy of neonatal structural MRI scores to predict 6-year motor outcomes of children born very preterm.

Aims: This study aimed to (1) evaluate associations between Early and Term structural MRI (sMRI) brain abnormality scores and adverse motor outcomes at 6-years corrected age (CA), (2) determine their diagnostic accuracy in predicting adverse motor outcomes and cerebral palsy (CP) at 6-years CA.

Methods: Infants born < 31-weeks gestational age (GA) returning for 6-year follow-up were included. Early and Term sMRI were scored using a validated method, deriving white matter, cortical grey matter, deep grey matter, cerebellar and global brain abnormality scores (GBAS).

Implementation of Universal Germline Genetic Testing Into Standard of Care for Patients With Prostate Cancer: The Time Is Now.

Indications for and implications of germline genetic testing (GGT) in patients with prostate cancer have expanded over the past decade, particularly related to precision therapies and management. GGT has become the standard of care for many cancers such as breast, ovarian, colorectal, pancreatic, and metastatic prostate cancer, and it is imperative that patients be offered timely and equitable access to testing as it can inform patient-physician shared decision making for management of the current cancer as well as anticipatory guidance for disease progression. Additionally, GGT guides screening for and prevention of secondary malignancies for the patient and cascade testing for at-risk family members.

Metastatic Adenoid Cystic Carcinoma to the Pancreas: A Case Report and Review of the Literature.

Although more than 90% of pancreatic tumors represent primary tumors, specifically ductal adenocarcinomas, metastatic tumors are not infrequent at this site. Metastasis of salivary gland tumors to the pancreas is exceedingly rare, with only a few cases reported in the English-language medical literature. Here, we report a patient with metastatic adenoid cystic carcinoma to the pancreas, 24 months following the initial diagnosis, and review the available literature on secondary tumors located in the pancreas with an emphasis on tumors of salivary gland origin.

Psychometric evaluation of the Autism Symptom Dimensions Questionnaire.

Aim: To replicate and extend previous psychometric findings for the Autism Symptom Dimensions Questionnaire (ASDQ).

Method: Using a cross-sectional design in two samples, including a total of 3366 children and adolescents (aged 2-17 years; 1399 with autism spectrum disorder) and a small case series, factor structure, measurement invariance, reliability, construct validity, screening and diagnostic efficiency, and detection of reliable change were examined for the ASDQ.

Results: Strong psychometric properties were observed, including replicable factor structure, strong measurement invariance, adequate-to-excellent scale and conditional reliability, strong convergent and discriminant validity, and good screening efficiency.