Flexibility and resilience in equity-centered research: lessons learned conducting a randomized controlled trial of a family-based substance use prevention program for American Indian families.

Meaningful and effective community engagement lies at the core of equity-centered research, which is a powerful tool for addressing health disparities in American Indian (AI) communities. It is essential for centering Indigenous wisdom as a source of solutions and disrupting Western-centric perspectives and inequitable and exclusionary research practices. This paper reports on lessons learned implementing an effectiveness trial of the Thiwáhe Glúwaš'akapi program (TG) program (translated as "sacred home in which families are made strong")-a family-based substance use prevention program-in a post-pandemic era with an American Indian reservation community that has confronted extreme challenges.

The conserved HIV-1 spacer peptide 2 triggers matrix lattice maturation.

HIV-1 particles are released in an immature, non-infectious form. Proteolytic cleavage of the main structural polyprotein Gag into functional domains induces rearrangement into mature, infectious virions. In immature virus particles, the Gag membrane binding domain, MA, forms a hexameric protein lattice that undergoes structural transition upon cleavage into a distinct, mature MA lattice.

First-in-Human Evaluation of Safety, Pharmacokinetics and Muscle Glycogen Lowering of a Novel Glycogen Synthase 1 Inhibitor for the Treatment of Pompe Disease.

Pompe disease is a rare glycogen storage disease caused by mutations in the enzyme acid α-glucosidase (GAA) resulting in pathological accumulation of glycogen in muscle tissues leading to progressive weakness and respiratory dysfunction. Enzyme replacement therapy (ERT) with GAA is currently the sole treatment option for patients with Pompe disease. ERT burdens patients with frequent intravenous infusions while insufficiently halting disease progression due to incomplete ERT skeletal muscle distribution.

Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice.

Human T cell leukemia virus type 1 (HTLV-1) immature particles differ in morphology from other retroviruses, suggesting a distinct way of assembly. Here we report the results of cryo-electron tomography studies of HTLV-1 virus-like particles assembled in vitro, as well as derived from cells. This work shows that HTLV-1 uses a distinct mechanism of Gag-Gag interactions to form the immature viral lattice.

Routine Protamine Administration for Bleeding in Transcatheter Aortic Valve Implantation: The ACE-PROTAVI Randomized Clinical Trial.

Importance: Vascular complications after transfemoral transcatheter aortic valve implantation (TAVI) remain an important cause of procedure-related morbidity. Routine reversal of anticoagulation with protamine at the conclusion of transfemoral TAVI could reduce complications, but data remain scarce.

Objective: To evaluate the efficacy and safety of routine protamine administration after transfemoral TAVI.

Interventions to alleviate anxiety and pain during venipuncture in children with chronic gastrointestinal and/or liver disease: A single-center prospective observational study.

Objectives: The goal of this longitudinal study was to reduce anxiety and pain in children with chronic conditions from the gastrointestinal tract during venipuncture. These children undergo regular venipuncture as part of their medical management and the procedure is often accompanied with anxiety and pain. In addition, children as well as their parents and health care professionals (HCPs) often suffer "compassionate pain" because of emotional interference.

Discovery of Hepatitis B Virus Surface Antigen Suppressor GS-8873.

Chronic hepatitis B (CHB) virus infection afflicts hundreds of millions of people and causes nearly one million deaths annually. The high levels of circulating viral surface antigen (HBsAg) that characterize CHB may lead to T-cell exhaustion, resulting in an impaired antiviral immune response in the host. Agents that suppress HBsAg could help invigorate immunity toward infected hepatocytes and facilitate a functional cure.

Introducing and validating a single-item measure of identity leadership: The visual identity leadership scale (VILS).

In the present research, we introduce and validate a single-item measure of identity leadership-the visual identity leadership scale (VILS). The VILS uses Venn diagrams of sets of overlapping circles to denote different degrees of alignment between a leader's characteristics and behaviours and a group's values and goals. Key advantages of the VILS over other existing multi-item scales are that it provides a holistic assessment of identity leadership, is short, and can be adapted to address novel research questions that are impractical to address with existing scales (e.

The Role of Comorbidities in Predicting Functional Improvement After Transcatheter Aortic Valve Implantation.

Background: Patients undergoing transcatheter aortic valve implantation (TAVI) have a high comorbidity burden. We sought to stratify patients into functional outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), a patient-reported outcome with benefits over both the New York Heart Association (NYHA) classification and the original 23-item KCCQ, and to evaluate the importance of comorbidities in predicting failure of functional improvement post-TAVI in a contemporary cohort.

Methods: In total, 366 patients with severe aortic stenosis undergoing TAVI with baseline KCCQ-12 were retrospectively analysed and divided into two groups.

Time-restricted ketogenic diet in amyotrophic lateral sclerosis: a case study.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder. The most devastating variant is bulbar-onset ALS, which portends a median survival of 24 months from the onset of symptoms. Abundant evidence indicates that neuron metabolism and mitochondrial function are impaired in ALS.

Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.

Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule inhibitors of this enzyme. Here, we report the preclinical characterization of MZ-101, a small molecule that potently inhibits GYS1 in vitro and in vivo without inhibiting GYS2, a related isoform essential for synthesizing liver glycogen.

Clinical Outcomes Associated With Balloon Aortic Valvuloplasty in the Contemporary Era.

Background: Severe aortic stenosis is the most common acquired valvular disorder. Balloon aortic valvuloplasty (BAV) is considered for patients who are not suitable for surgical aortic valve replacement (SAVR) and transcatheter aortic valve insertion (TAVI). The American Heart Association and European Society of Cardiology recommend BAV as a bridging procedure for SAVR and TAVI due to the significant morbidity and mortality associated with it.

Psychological Resilience Factors and Their Association With Weekly Stressor Reactivity During the COVID-19 Outbreak in Europe: Prospective Longitudinal Study.

Background: Cross-sectional relationships between psychosocial resilience factors (RFs) and resilience, operationalized as the outcome of low mental health reactivity to stressor exposure (low "stressor reactivity" [SR]), were reported during the first wave of the COVID-19 pandemic in 2020.

Objective: Extending these findings, we here examined prospective relationships and weekly dynamics between the same RFs and SR in a longitudinal sample during the aftermath of the first wave in several European countries.

Methods: Over 5 weeks of app-based assessments, participants reported weekly stressor exposure, mental health problems, RFs, and demographic data in 1 of 6 different languages.

Unconventional stabilization of the human T-cell leukemia virus type 1 immature Gag lattice.

Human T-cell leukemia virus type 1 (HTLV-1) has an atypical immature particle morphology compared to other retroviruses. This indicates that these particles are formed in a way that is unique. Here we report the results of cryo-electron tomography (cryo-ET) studies of HTLV-1 virus-like particles (VLPs) assembled , as well as derived from cells.

Reduced loneliness mediates the effects of multiple group identifications on well-being.

Membership of multiple groups and identification with those groups have been found to be positively related to individuals' health and well-being. The present research sought to replicate this finding in two large, representative samples. Moreover, we sought to extend previous work by shedding light on the mechanisms mediating the effects of multiple group membership on positive health outcomes.

Combined spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS): a case series.

Background: Spontaneous Coronary Artery Dissection (SCAD) and Takotsubo Syndrome (TTS) are two different entities with several shared risk factors, but their management is different. They can co-exist in patients with chest pain which affects their management. We present two cases of combined SCAD and TTS in patients presented with chest pain.

Structural insights into HIV-1 polyanion-dependent capsid lattice formation revealed by single particle cryo-EM.

The HIV-1 capsid houses the viral genome and interacts extensively with host cell proteins throughout the viral life cycle. It is composed of capsid protein (CA), which assembles into a conical fullerene lattice composed of roughly 200 CA hexamers and 12 CA pentamers. Previous structural analyses of individual CA hexamers and pentamers have provided valuable insight into capsid structure and function, but detailed structural information about these assemblies in the broader context of the capsid lattice is lacking.

Two structural switches in HIV-1 capsid regulate capsid curvature and host factor binding.

The mature HIV-1 capsid protects the viral genome and interacts with host proteins to travel from the cell periphery into the nucleus. To achieve this, the capsid protein, CA, constructs conical capsids from a lattice of hexamers and pentamers, and engages in and then relinquishes multiple interactions with cellular proteins in an orchestrated fashion. Cellular host factors including Nup153, CPSF6, and Sec24C engage the same pocket within CA hexamers.

An examination and extension of the Peltzman effect during the Covid-19 pandemic.

Since the first COVID-19 case was confirmed in Germany, the German government has introduced various measures to counteract the pandemic. The implementation of safety measures can have counterproductive effects: people engage in risk compensatory behavior (fewer safety behaviors) after regulations are introduced and obligated by the government, which is known as the Peltzman effect (Peltzman, 1975). Based on the Peltzman effect, the researchers of this study hypothesized that people complied less with safety behaviors and took more health risks (e.

Assessing Performing Artists in Medical and Health Practice - The Dancers, Instrumentalists, Vocalists, and Actors Screening Protocol.

Training in the performing arts exposes individuals to often extreme physical and psychological demands, which are linked to high occupational injury rates. The intense demands of performing artists have been likened to those of sport athletes. However, distinct differences in these demands necessitate specialized approaches to the health care of performing artists.

Effects of general and corona-specific stressors on mental burden during the SARS-CoV-2 pandemic in Germany.

The SARS-CoV-2 pandemic turned out to be a serious threat to mental and physical health. However, the relative contribution of corona-specific (DH) and general stressors (DH) on mental burden, and specific protective and risk factors for mental health are still not well understood. In a representative sample ( = 3,055) of the German adult population, mental health, potential risk, and protective factors as well as DH and DH exposure were assessed online during the SARS-CoV-2 pandemic (June and July 2020).

Characterization of a KDM5 small molecule inhibitor with antiviral activity against hepatitis B virus.

Chronic hepatitis B (CHB) is a global health care challenge and a major cause of liver disease. To find new therapeutic avenues with a potential to functionally cure chronic Hepatitis B virus (HBV) infection, we performed a focused screen of epigenetic modifiers to identify potential inhibitors of replication or gene expression. From this work we identified isonicotinic acid inhibitors of the histone lysine demethylase 5 (KDM5) with potent anti-HBV activity.