DUX4-induced HSATII RNA accumulation drives protein aggregation impacting RNA processing pathways.

Unlabelled: RNA-driven protein aggregation leads to cellular dysregulation by sequestering regulatory proteins, disrupting normal cellular processes, and contributing to the development of diseases and tumorigenesis. Here, we show that double homeobox 4 (DUX4), an early embryonic transcription factor and causative gene of facioscapulohumeral muscular dystrophy (FSHD), induces the accumulation of stable intranuclear RNAs, including nucleolar-associated RNA and human satellite II (HSATII) repeat RNA. Stable intranuclear RNAs drive protein aggregation in DUX4-expressing muscle cells.

Focused ultrasound and concurrent chemotherapy for the treatment of advanced pancreatic cancer: A systematic review.

Background And Objectives: The combination of focused ultrasound (FUS) and chemotherapy is a novel treatment for pancreatic cancer. This paper reviews the literature on this combined therapy.

Methods: The medical literature was searched according to PRISMA guidelines.

Regional and bilateral MRI and gene signatures in facioscapulohumeral dystrophy: implications for clinical trial design and mechanisms of disease progression.

Identifying the aberrant expression of DUX4 in skeletal muscle as the cause of facioscapulohumeral dystrophy (FSHD) has led to rational therapeutic development and clinical trials. Several studies support the use of MRI characteristics and the expression of DUX4-regulated genes in muscle biopsies as biomarkers of FSHD disease activity and progression. We performed lower-extremity MRI and muscle biopsies in the mid-portion of the tibialis anterior (TA) muscles bilaterally in FSHD subjects and validated our prior reports of the strong association between MRI characteristics and expression of genes regulated by DUX4 and other gene categories associated with FSHD disease activity.

The Effect of a Tobacco Use Reduction Program on the Prevalence of Smoking and Tobacco Use and Quitting Behavior Among People Living With HIV/AIDS in Michigan.

HIV has evolved from a serious infectious disease to a manageable chronic disease. Tobacco use has a devastating effect on the health of people living with HIV/AIDS (PLWH). The Michigan Tobacco Use Reduction Program for PLWH was established in 2015 to learn about tobacco use among PLWH, gather information on entities that provide health care services to PLWH, and improve tobacco treatment services for this population.

Evaluating the safety, tolerability, and immunogenicity of a 24-valent pneumococcal conjugate vaccine (VAX-24) in healthy adults aged 18 to 64 years: a phase 1/2, double-masked, dose-finding, active-controlled, randomised clinical trial.

Background: Despite substantial reductions in pneumococcal disease with the availability of pneumococcal conjugate vaccines, a significant burden of pneumococcal disease remains due to the diversity of serotypes combined with serotype replacement. We developed a new vaccine candidate, VAX-24 (24-valent pneumococcal conjugate vaccine), using cell-free protein synthesis to produce a variant of cross-reactive material 197 (eCRM) as the carrier protein, increasing serotype coverage while minimising carrier suppression. The aim of this clinical trial was to assess the safety, tolerability, and immunogenicity of three different doses of VAX-24 compared to pneumococcal 20-valent conjugate vaccine (PCV20).

Risk Factors for Postoperative Infections in Cardiac Surgery Patients: A Retrospective Study.

Background and objective Cardiac surgery is one of the most common surgical procedures globally; its incidence has been on the rise due to the faster pace of population aging thanks to technological and epidemiological advances. Patients who undergo cardiac surgeries may face various postoperative complications that might affect their survival, and one of these major complications is infection. Nosocomial pneumonia, surgical site infection (SSI), mediastinitis, bacteremia, and sepsis are common infections encountered after surgeries.

DUX4 expression in cancer induces a metastable early embryonic totipotent program.

The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether this generates cells similar to early embryonic stem cells. Here we identified cancer cell lines that express DUX4 and showed that DUX4 is transiently expressed in a small subset of the cells.

A Phase 1 Two-Arm, Randomized, Double-Blind, Active-Controlled Study of Live, Oral Plasmid-Derived Adenovirus Type 4 and Type 7 Vaccines in Seronegative Adults.

PXVX0047 is an investigational vaccine developed for active immunization to prevent febrile acute respiratory disease (ARD) caused by adenovirus serotypes 4 (Ad4) and 7 (Ad7). PXVX0047 consists of a modernized, plasmid-derived vaccine that was generated using a virus isolated from Wyeth Ad4 and Ad7 vaccine tablets. A phase 1 two-arm, randomized, double-blind, active-controlled study was conducted to evaluate the safety profile and immunogenicity of the investigational adenovirus vaccines.

Changes in Healthcare During the Past 30 Years: Can the National Health Service in the United Kingdom Survive?

At the turn of the century, the National Health Service (NHS) in the United Kingdom (UK) was considered one of the top public healthcare systems in the world. Not only was it comprehensive and inclusive, but it was also free at the point of delivery for the entire UK population. It was also largely available to visitors and the families of residents that lived outside the UK.

Human DUX4 and mouse Dux interact with STAT1 and broadly inhibit interferon-stimulated gene induction.

DUX4 activates the first wave of zygotic gene expression in the early embryo. Mis-expression of DUX4 in skeletal muscle causes facioscapulohumeral dystrophy (FSHD), whereas expression in cancers suppresses IFNγ induction of major histocompatibility complex class I (MHC class I) and contributes to immune evasion. We show that the DUX4 protein interacts with STAT1 and broadly suppresses expression of IFNγ-stimulated genes by decreasing bound STAT1 and Pol-II recruitment.

Examining the consequences of dehumanization and adultification in justification of police use of force against Black girls and boys.

Objective: Given the greater contact that Black youth have with the legal system compared with White youth, it is important to consider the differential ways that police use of force against these youth is perceived. Black youth may be at greater risk than White youth for animalistic (being seen as animal-like) and mechanistic (being seen as object-like) dehumanization, which, along with a tendency for Black youth to be perceived as older (adultification), may impact observers' perceptions of police use of force toward Black youth. This study examined whether dehumanization and adultification were associated with the perceptions of force used and harm caused by police.

Human DUX4 and porcine DUXC activate similar early embryonic programs in pig muscle cells: implications for preclinical models of FSHD.

Human DUX4 and its mouse ortholog Dux are normally expressed in the early embryo-the 4-cell or 2-cell cleavage stage embryo, respectively-and activate a portion of the first wave of zygotic gene expression. DUX4 is epigenetically suppressed in nearly all somatic tissue, whereas facioscapulohumeral dystrophy (FSHD)-causing mutations result in its aberrant expression in skeletal muscle, transcriptional activation of the early embryonic program and subsequent muscle pathology. Although DUX4 and Dux both activate an early totipotent transcriptional program, divergence of their DNA binding domains limits the use of DUX4 expressed in mice as a preclinical model for FSHD.

Identifying Facilitators, Barriers, and Potential Solutions of Adopting Exoskeletons and Exosuits in Construction Workplaces.

Exoskeletons and exosuits (collectively termed EXOs) have the potential to reduce the risk of work-related musculoskeletal disorders (WMSDs) by protecting workers from exertion and muscle fatigue due to physically demanding, repetitive, and prolonged work in construction workplaces. However, the use of EXOs in construction is in its infancy, and much of the knowledge required to drive the acceptance, adoption, and application of this technology is still lacking. The objective of this research is to identify the facilitators, barriers, and corresponding solutions to foster the adoption of EXOs in construction workplaces through a sequential, multistage Delphi approach.

Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial.

Background: Chikungunya virus (CHIKV) disease is an ongoing public health threat. We aimed to evaluate the safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted formulation of a CHIKV virus-like particle (VLP) vaccine.

Methods: This randomised, double-blind, parallel-group, phase 2 trial was conducted at three clinical trial centres in the USA.

Cerebral oximetry in adult cardiac surgery to reduce the incidence of neurological impairment and hospital length-of-stay: A prospective, randomized, controlled trial.

Background: Cerebral oximetry using near-infrared spectroscopy (NIRS) has been shown to reduce neurological dysfunction and hospital length-of-stay after adult cardiac surgery in some but not all studies. We audited maintaining cerebral saturations at or above baseline and showed improved neurological and length-of-stay outcomes. Our hypothesis for this study was that our NIRS protocol would improve neurological and length-of-stay outcomes.

Vasoplegic Syndrome Post-cardiopulmonary Bypass in a Renal Transplant Patient: The Brain Is Not the Index Organ.

Vasoplegia syndrome (VS) is seen in cardiac surgery post-cardiopulmonary bypass (CPB) and defined by increasing requirements for more than one vasoactive agent to which the patient's response is reduced. It is also associated with normal or high cardiac output (CO). Prolonged CPB time is the second commonest precipitating factor.

The Dilemma: Whether to Proceed or Postpone a Patient With Pyrexia at Induction of Anesthesia for Coronary Artery Bypass Graft Surgery.

Routine surgery may be postponed if a patient has high white blood cells (WBC) and/or pyrexia. However, postponement carries the risk of myocardial ischaemia or infarction in a patient having coronary artery bypass graft (CABG) surgery. Our case raises this dilemma in a high-risk patient that was further compromised by acute right ventricular (RV) dysfunction.

Variations of intestinal malrotation in adults: A case report of midgut volvulus and literature review for the surgeon.

Introduction: Intestinal malrotation is a rare congenital abnormality occurring in 0.2-1% of the population. Adult presentations comprise only 0.

Update on CVD 103-HgR single-dose, live oral cholera vaccine.

Cholera remains endemic in >50 countries, putting millions at risk, especially young children for whom killed vaccines offer limited protection. An oral, live attenuated vaccine - CVD 103-HgR (Vaxchora vaccine) - was licensed by the US FDA in 2016 for adults aged 18-64 years traveling to endemic regions, based on clinical trials in human volunteers showing the vaccine was well tolerated and conferred 90% efficacy within 10 days. The evidence base for Vaxchora vaccine has expanded with additional clinical trial data, in older adults (aged 46-64 years) and children (aged 2-17 years), demonstrating that the vaccine produces a strong vibriocidal antibody response.

Outcomes in Cardiac Surgery Based on Preoperative, Mean Intraoperative and Stratified Cerebral Oximetry Values.

Introduction: Cardiac surgery is associated with significant morbidity and longer length-of-stay (LOS) than most other surgeries. Regional cerebral oximetry (rSO) using near-infrared spectroscopy (NIRS) on the patient's forehead monitors cerebral oxygenation during surgery and cardiopulmonary bypass (CPB). Its purpose is to detect and manage periods of cerebral hypoxia which may otherwise go undetected, thereby reducing morbidity.

Valproic acid autoinduction: a case-based review.

Although valproic acid (VPA) induces the metabolism of multiple other drugs, the clinical reports of VPA autoinduction are rare. A comprehensive literature search yielded only one published case series, which provided the rationale to conduct a review of the published cases along with a new case of VPA autoinduction. Although there may be myriad of reasons for lack of published cases of VPA autoinduction, potential underreporting may be one of the core reasons.