Genotype-phenotype associations in individuals with Diamond Blackfan anaemia.

Introduction: Diamond Blackfan anaemia (DBA) is a rare disorder characterized by failure of red blood cell production, congenital abnormalities and cancer predisposition, primarily caused by pathogenic germline variants in genes encoding ribosomal proteins.

Methods: We conducted a genotype-phenotype and outcome study of 121 patients with DBA spanning the 20-year history of the National Cancer Institute's Inherited Bone Marrow Failure Syndromes study. Patient phenotypes were compared by large versus small ribosomal protein genes, across genes with >5 cases (, , and ) and by type of pathogenic variants (hypomorphic versus null, large deletions versus others).

Associations of plasma extracellular microRNAs with new-onset breast cancer in the Framingham heart study.

Breast cancer is the second leading cause of cancer deaths among women. Multiple microRNAs (miRNAs) have been reported to be associated with breast cancer progression or metastasis. The purpose of the current study was to identify plasma extracellular miRNAs associated with incident breast cancer.

Ecological and Reproductive Cycles Drive Henipavirus Seroprevalence in the African Straw-Coloured Fruit Bat ().

Bats are known to host zoonotic viruses, including henipaviruses that cause high fatality rates in humans (Nipah virus and Hendra virus). However, the determinants of zoonotic spillover are generally unknown, as the ecological and demographic drivers of viral circulation in bats are difficult to ascertain without longitudinal data. Here we analyse serological data collected from African straw-coloured fruit bats () in Ghana over the course of 2 years and across four sites, comprising three wild roosts and one captive colony.

Metabolically activated proteostasis regulators that protect against erastin-induced ferroptosis.

We previously showed that the proteostasis regulator compound AA147 (-(2-hydroxy-5-methylphenyl)benzenepropanamide) potently protects against neurotoxic insults, such as glutamate-induced oxytosis. Though AA147 is a selective activator of the ATF6 arm of the unfolded protein response in non-neuronal cells, AA147-dependent protection against glutamate toxicity in cells of neuronal origin is primarily mediated through activation of the NRF2 oxidative stress response. AA147 activates NRF2 through a mechanism involving metabolic activation of AA147 by endoplasmic reticulum (ER) oxidases, affording an AA147-based quinone methide that covalently targets the NRF2 repressor protein KEAP1.

Antibiotic Chemoprophylaxis for Leptospirosis: Previous Shortcomings and Future Needs.

Leptospirosis is a neglected tropical disease that remains potentially life threatening and hard to diagnose. Climate change combined with overlapping reservoir and human habitats will likely lead to increasing incidence, outbreaks, and mortality in the future. Preventative vaccines are either of limited scope and availability, or under development.

The relationship between intraosseous catheter tip placement, flow rates, and infusion pressures in a high bone density cadaveric swine () model.

Background: Intraosseous (IO) infusion is a life-preserving technique when intravenous access is unobtainable. Successful IO infusion requires sufficiently high flow rates to preserve life but at low enough pressures to avoid complications. However, IO catheter tips are often misplaced, and the relative flow rates and pressures between IO catheter tips placed in medullary, trabecular, and cortical bone are not well described, which has important implications for clinical practice.

Plasma Extracellular MicroRNAs Associated With Cardiovascular Disease Risk Factors in Middle-Aged and Older Adults.

Background: Extracellular microRNAs (miRNAs) are a class of noncoding RNAs that remain stable in the extracellular milieu, where they contribute to various physiological and pathological processes by facilitating intercellular signaling. Previous studies have reported associations between miRNAs and cardiovascular diseases (CVDs); however, the plasma miRNA signatures of CVD and its risk factors have not been fully elucidated at the population level.

Methods And Results: Plasma miRNA levels were measured in 4440 FHS (Framingham Heart Study) participants.

Unique clinical and prognostic behavior of patients diagnosed with combined exophytic and inverted papilloma histologic subtype.

Objectives: To evaluate the clinical and prognostic behaviors of sinonasal papillomas.

Methods: Patients diagnosed with sinonasal papilloma were reviewed between 2001 and 2016 at a tertiary rhinology practice. Using pathology-specific electronic medical record software, patients diagnosed with sinonasal papilloma were identified.

Matrisome and Immune Pathways Contribute to Extreme Vascular Outcomes in Williams-Beuren Syndrome.

Background: Supravalvar aortic stenosis (SVAS) is a characteristic feature of Williams-Beuren syndrome (WBS). Its severity varies: ~20% of people with Williams-Beuren syndrome have SVAS requiring surgical intervention, whereas ~35% have no appreciable SVAS. The remaining individuals have SVAS of intermediate severity.

An Emotion-Driven Vocal Biomarker-Based PTSD Screening Tool.

This paper introduces an automated post-traumatic stress disorder (PTSD) screening tool that could potentially be used as a self-assessment or inserted into routine medical visits to aid in PTSD diagnosis and treatment. With an emotion estimation algorithm providing arousal (excited to calm) and valence (pleasure to displeasure) levels through discourse, we select regions of the acoustic signal that are most salient for PTSD detection. Our algorithm was tested on a subset of data from the DVBIC-TBICoE TBI Study, which contains PTSD Check List Civilian (PCL-C) assessment scores.

Validation of Opportunities to Strengthen the National Disaster Medical System: The Military-Civilian NDMS Interoperability Study Quantitative Step.

The National Disaster Medical System (NDMS) Pilot Program was authorized by Congress to improve the interoperability, capabilities, and capacity of the NDMS. To develop a roadmap for planning and research, the mixed methods Military-Civilian NDMS Interoperability Study (MCNIS) was conducted in 2020-2021. The initial qualitative phase of the study identified critical themes for improvement: (1) coordination, collaboration, and communication; (2) funding and incentives to increase private sector preparedness; (3) staffing capacity and competencies; (4) clinical and support surge capacity; (5) training, education, and exercises between federal and private sector partners; and (6) metrics, benchmarks, and modeling to track NDMS performance.

Layperson Perception of Reflux-Related Symptoms.

Objective: To assess for differences of intended meaning in the description of reflux-related symptoms among otolaryngology patients and clinicians.

Study Design: Cross-sectional survey-based study.

Setting: Five tertiary, academic otolaryngology practices.

Eponyms in Otology: A Historical Narrative of Commonly Used Surgical Instruments.

Numerous eponymous instruments are regularly used in the otology surgical suite. This manuscript uses a tympanoplasty to highlight 10 frequently used instruments and the remarkable surgeons behind their creation. Many of these names will be familiar, but we hope our readers will gain an appreciation of these landmark figures that have transformed the practice of otology.

Prostate cancer autoantibodies - applications in diagnosis, prognosis, monitoring disease progression and immunotherapy.

Although PSA testing is widely used in prostate cancer diagnosis, it remains an imperfect assay due to its lack of accuracy. While several urine or tissue-based gene expression assays are available to identify patients with higher risk of adverse disease and to aid in deciding treatment options, there is still a critical need for reliable biomarkers to monitor disease progression and treatment response. Autoantibodies (AAbs) produced by the humoral immune response against tumor associated antigens offer an attractive alternative, as they target a wide variety of prostate cancer specific antigens and can be collected by using clinically non-invasive methods.

Factors associated with emergency physician income.

Objective: Income fairness is important, but there are limited data that describe income equity among emergency physicians. Understanding the magnitude of and factors associated with income differences may be helpful in eliminating disparities. This study analyzed the associations of demographic factors, training, practice setting, and board certification with emergency physician income.

Technology-enhanced simulation in emergency medicine: Updated systematic review and meta-analysis 1991-2021.

Background: Over the past decade, the use of technology-enhanced simulation in emergency medicine (EM) education has grown, yet we still lack a clear understanding of its effectiveness. This systematic review aims to identify and synthesize studies evaluating the comparative effectiveness of technology-enhanced simulation in EM.

Methods: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, ERIC, Web of Science, and Scopus to identify EM simulation research that compares technology-enhanced simulation with other instructional modalities.

Safety and feasibility of selective tongue fat reduction with injected ice-slurry.

Objectives: There is growing evidence that excess adipose tissue within the head and neck contributes to obstructive sleep apnea (OSA), particularly in obese patients. This subset of the population is often difficult to treat with surgical therapies. We theorized that a novel, transcervical method of injectable cryoablation using ice-slurry can achieve low temperatures without causing neurovascular damage or airway distress in a swine model.

Small extracellular vesicle-associated miR-6068 promotes aggressive phenotypes of prostate cancer through miR-6068/HIC2/SIRT1 axis.

Early diagnosis and treatment of patients with aggressive prostate cancer (PCa) remains a clinically unmet need. We aimed to determine the levels of small extracellular vesicle (sEV)-associated microRNAs (miRs); miR-4737, miR-6068, and miR-6076 in a large panel of PCa cells and delineate the biological significance of miR-6068 in promoting PCa cells. sEVs were isolated from the conditioned medium of PCa cells, followed by RNA extraction and quantitative Real-Time PCR analysis.

The Draf III procedure: A review of indications and techniques.

The Draf Ⅲ procedure involves the creation of a common frontal sinus cavity. The most common indication for the Draf Ⅲ procedure is chronic rhinosinusitis of the frontal sinuses despite the failure of more conservative interventions such as bilateral Draf Ⅱa procedures. Primary Draf Ⅲ may be indicated in patients with a high risk of failures such as those with severe polyposis and those with a frontal sinus opening less than 4 mm on computed tomography imaging.

Improvement of depression in a patient with hypothyroidism and deiodinase polymorphism with LT3 Therapy.

We report a 54-year-old man with treatment-resistant depression (TRD) and hypothyroidism who responded to LT3/LT4 combination, rather than LT4 alone. He was able to discontinue all antidepressant medications eventually. Interestingly, the patient has a DIO2 polymorphism.

Analyzing fecal loading and retention patterns by abdominal X-rays of hospitalized older adults: A retrospective study.

Background: Aging may affect ascending colon (AC) differently from descending colon (DC) and increase the risk of fecal loading (FL) in AC.

Methods: Patients aged ≥65 years admitted to a community hospital were analyzed by abdominal x-ray for fecal loads and stool retention patterns. FL was scored between 0 and 5 (severe) on each segment of colon with a possible total score 20.