Age and oxidative stress regulate Nrf2 homeostasis in human articular chondrocytes.

Objective: The purpose of this study was to investigate the effect of age and oxidative stress on regulation of nuclear factor erythroid-2-related factor 2 (Nrf2) in young, old, and osteoarthritic (OA) human articular chondrocytes.

Design: Levels of Nrf2 in primary human chondrocytes isolated from young, old, and OA donors were measured by immunoblotting, qPCR, and immunohistochemistry. Effects on levels of Nrf2, antioxidant proteins regulated by Nrf2, as well as p65, and the anabolic response to insulin-like growth factor-1 (IGF-1) were evaluated after induction of oxidative stress with menadione, Nrf2 knockdown with siRNA, and/or Nrf2 activation with RTA-408.

Preparation and anticancer actions of CuET-nanoparticles dispersed by bovine serum albumin.

Diethyldithiocarbamate-copper complex (CuET) shows promising anticancer effect; nonetheless, preclinical evaluations of CuET are hindered due to poor solubility. We prepared bovine serum albumin (BSA)-dispersed CuET nanoparticles (CuET-NPs) to overcome the shortcoming. Results from a cell-free redox system demonstrated that CuET-NPs reacted with glutathione, leading to form hydroxyl radical.

Mitochondrial citrate metabolism and efflux regulate BeWo differentiation.

Cytotrophoblasts fuse to form and renew syncytiotrophoblasts necessary to maintain placental health throughout gestation. During cytotrophoblast to syncytiotrophoblast differentiation, cells undergo regulated metabolic and transcriptional reprogramming. Mitochondria play a critical role in differentiation events in cellular systems, thus we hypothesized that mitochondrial metabolism played a central role in trophoblast differentiation.

Polyvictimization, polystrengths, and their contribution to subjective well-being and posttraumatic growth.

Objective: The negative biopsychosocial outcomes associated with exposure to victimization are well-known, however, limited research has examined the protective factors that can enhance well-being and growth following polyvictimization from in-person and digital sources. This study examines the contribution of adversities and a range of psychological and social strengths on perceptions of subjective well-being and posttraumatic growth (PTG).

Method: A sample of 478 individuals aged 12-75 (57.

Charting infants' motor development at home using a wearable system: validation and comparison to physical growth charts.

Background: Early neurodevelopmental care and research are in urgent need of practical methods for quantitative assessment of early motor development. Here, performance of a wearable system in early motor assessment was validated and compared to developmental tracking of physical growth charts.

Methods: Altogether 1358 h of spontaneous movement during 226 recording sessions in 116 infants (age 4-19 months) were analysed using a multisensor wearable system.

The increase in medical admissions with anorexia nervosa during the COVID-19 pandemic in Western Australia.

Objective: A comparative study to describe the increase in medical admissions of children and adolescents with anorexia nervosa (AN) in Western Australia in 2019 (pre-pandemic) and 2020 (peri-pandemic).

Method: Patient demographics, physiological parameters, length of stay, time to assessment by the Eating Disorder Service (EDS), and commencement of specialist eating disorder (ED) outpatient treatment was collected for adolescents admitted with AN between 1st January 2019 and 31st December 2020.

Results: The number of admissions doubled from 126 in 2019 to 268 in 2020.

Awareness and use of short-fill e-liquids by youth in England in 2021: findings from the ITC Youth Tobacco and Vaping Survey.

Background: Refillable e-cigarettes were popular among youth in England in 2021. The UK Tobacco and Related Products Regulations (TRPR) limits e-liquids to 20 mg/mL of nicotine in a 10 mL bottle. Short-fill e-liquids, which are not covered by TRPR regulations, are typically nicotine-free and come in larger, underfilled bottles allowing customisation with the addition of 'nicotine shots'.

Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism.

Organelle interactions play a significant role in compartmentalizing metabolism and signaling. Lipid droplets (LDs) interact with numerous organelles, including mitochondria, which is largely assumed to facilitate lipid transfer and catabolism. However, quantitative proteomics of hepatic peridroplet mitochondria (PDM) and cytosolic mitochondria (CM) reveals that CM are enriched in proteins comprising various oxidative metabolism pathways, whereas PDM are enriched in proteins involved in lipid anabolism.

D2 receptor blockade eliminates exercise-induced changes in cortical inhibition and excitation.

Background: Although cardiorespiratory exercise is known to affect cortical excitatory and inhibitory activity, the neurochemical mechanisms driving this effect are poorly understood. Animal models of Parkinson's disease identify dopamine D2 receptor expression as a candidate mechanism, but the link between the D2 receptor and exercise-induced changes in cortical activity in humans is unknown.

Objective: Here, we examined the effect of a selective dopamine D2 receptor antagonist, sulpiride, on exercise-induced changes in cortical activity.

Pharmacy students' perceived barriers to spiritual care: A qualitative study.

Background: Spiritual care (SC) is an important component of whole person care, a goal that many pharmacists embrace. Knowledge about barriers to incorporating SC in pharmacy practice may allow understanding of how to increase its provision.

Objectives: The objective of the study was to investigate pharmacy students' perceived personal and professional barriers to incorporating SC in pharmacy practice.

Quantifying the interconnectedness between poverty, health access, and rabies mortality.

The global 2030 goal set by the World Organization for Animal Health (WOAH), the World Health Organization (WHO), and the Food and Agriculture Organization (FAO), to eliminate dog-mediated human rabies deaths, has undeniably been a catalyst for many countries to re-assess existing dog rabies control programmes. Additionally, the 2030 agenda for Sustainable Development includes a blueprint for global targets which will benefit both people and secure the health of the planet. Rabies is acknowledged as a disease of poverty, but the connections between economic development and rabies control and elimination are poorly quantified yet, critical evidence for planning and prioritisation.

Changes to Birth Plans Due to COVID-19: A Survey of Utah Midwives and Doulas.

Introduction: This study seeks to understand the experiences of Utah midwives and doulas caring for patients during the recent coronavirus disease 2019 (COVID-19) pandemic. Specifically, the goal of the study was to describe the perceived impact on the community birth system and explore differences in the access and use of personal protective equipment (PPE) between in- and out-of-hospital births.

Methods: This study used a cross-sectional, descriptive study design.

How do patients and other members of the public engage with the orphan drug development? A narrative qualitative synthesis.

Background: The diversity of patient experiences of orphan drug development has until recently been overlooked, with the existing literature reporting the experience of some patients and not others. The current evidence base (the best available current research) is dominated by quantitative surveys and patient reported outcome measures defined by researchers. Where research that uses qualitative methods of data collection and analysis has been conducted, patient experiences have been studied using content analysis and automatic textual analysis, rather than in-depth qualitative analytical methods.

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia.

Venetoclax+azacitidine is the standard of care for newly-diagnosed patients with acute myeloid leukemia (AML) for whom intensive chemotherapy is inappropriate. Efforts to optimize this regimen are necessary. We designed a clinical trial to investigate two hypotheses: i) higher doses of venetoclax are tolerable and more effective, and ii) azacitidine can be discontinued after deep remissions.

How Single Amino Acid Substitutions Can Disrupt a Protein Hetero-Dimer Interface: Computational and Experimental Studies of the LigAB Dioxygenase from sp. Strain SYK-6.

Protocatechuate 4,5-dioxygenase (LigAB) is a heterodimeric enzyme that catalyzes the dioxygenation of multiple lignin derived aromatic compounds. The active site of LigAB is at the heterodimeric interface, with specificity conferred by the alpha subunit and catalytic residues contributed by the beta subunit. Previous research has indicated that the phenylalanine at the 103 position of the alpha subunit (F103α) controls selectivity for the C5 position of the aromatic substrates, and mutations of this residue can enhance the rate of catalysis for substrates with larger functional groups at this position.

The APE2 nuclease is essential for DNA double-strand break repair by microhomology-mediated end joining.

Microhomology-mediated end joining (MMEJ) is an intrinsically mutagenic pathway of DNA double-strand break (DSB) repair essential for proliferation of homologous recombination (HR)-deficient tumors. Although targeting MMEJ has emerged as a powerful strategy to eliminate HR-deficient (HRD) cancers, this is limited by an incomplete understanding of the mechanism and factors required for MMEJ repair. Here, we identify the APE2 nuclease as an MMEJ effector.

Adrenergic control of functional characteristics of the cardiovascular system in the South American rattlesnake, Crotalus durissus.

In squamate reptiles, extensive innervation of the heart and vascular beds allows for continuous modulation of the cardiovascular system by the autonomic nervous system. The systemic vasculature is the main target of excitatory sympathetic adrenergic fibers, while the pulmonary circulation has been described as less responsive to both nervous and humoral modulators. However, histochemical evidence has demonstrated the presence of adrenergic fibers in pulmonary circulation.

SARS-CoV-2 Main Protease Targets Host Selenoproteins and Glutathione Biosynthesis for Knockdown via Proteolysis, Potentially Disrupting the Thioredoxin and Glutaredoxin Redox Cycles.

Associations between dietary selenium status and the clinical outcome of many viral infections, including SARS-CoV-2, are well established. Multiple independent studies have documented a significant inverse correlation between selenium status and the incidence and mortality of COVID-19. At the molecular level, SARS-CoV-2 infection has been shown to decrease the expression of certain selenoproteins, both in vitro and in COVID-19 patients.

The feasibility and acceptability of Project POWER: a mindfulness-infused, cognitive-behavioral group intervention to address mental and sexual health needs of young pregnant women in Liberia.

Background: Following 14 years of civil war in Liberia, war exposure, gender-based violence, and extreme poverty have been identified as key challenges affecting the mental and sexual health of young pregnant women and the health of their unborn children. Despite ongoing efforts to rebuild the country's healthcare infrastructure, empirical and culturally tailored interventions to address the consequences of war are severely limited. To address these concerns, we developed Project POWER (Progressing Our Well-being, Emotions, and Relationships), a mindfulness-infused, cognitive-behavioral intervention for young adult pregnant women.

Health-Related Quality of Life among American Indian and Alaska Native People: Exploring Associations with Adversities and Psychosocial Strengths.

Identifying psychosocial strengths that support physical health can lead to better pathways to prevention and intervention. Relying on the resilience portfolio model as a conceptual framework, this study explores strengths in three domains (regulation, meaning making, and interpersonal) to identify promising protective factors to support physical health-related quality of life (P-HRQOL), controlling for prior exposure to adversity, age, and gender. This study uses data from four resilience portfolio model studies collected in the southern United States, combined to increase the number of people who identified as American Indian/Alaska Native.

The mitochondrial pyruvate carrier complex potentiates the efficacy of proteasome inhibitors in multiple myeloma.

Multiple myeloma (MM) is a hematological malignancy that emerges from antibody-producing plasma B cells. Proteasome inhibitors, including the US Food and Drug Administration-approved bortezomib (BTZ) and carfilzomib (CFZ), are frequently used for the treatment of patients with MM. Nevertheless, a significant proportion of patients with MM are refractory or develop resistance to this class of inhibitors, which represents a significant challenge in the clinic.

Association of Fully Branded and Standardized e-Cigarette Packaging With Interest in Trying Products Among Youths and Adults in Great Britain.

Importance: e-Cigarette vaping among youths and adults has increased in Great Britain. The design of e-cigarette packaging may appeal to youths. Regulations that reduce the appeal of e-cigarettes to youths may deter adult smokers from trying e-cigarettes to help them quit smoking.

The Importance of Diversity, Equity, and Inclusion for Effective, Ethical Leadership.

Diversity, equity, and inclusion (DEI) increases performance through input of differing ideas and perspectives, leading to outcomes such as increased diagnostic accuracy, patient satisfaction, quality of care, and retention of talent. DEI can be difficult to establish due to the presence of unaddressed biases and ineffective policies against discrimination and noninclusive behaviors. Nevertheless, these complexities can be overcome through the integration of principles of DEI into the standard operations of health care, incentivizing DEI efforts through leadership curriculums, and highlighting the value proposition of diversifying our workforce as a critical asset to success.

Ethnic Minorities' Experiences of Cardiac Rehabilitation: A Scoping Review.

Cardiac rehabilitation (CR) can improve cardiovascular risk factors, decrease cardiac mortality, and promote healthy lifestyle behaviours. However, services remain underutilized by groups of ethnic minorities. The purpose of the study was to identify patients' personal CR experiences to identify the differences CR makes towards minorities' lifestyle.

CRISPR/dCas9-KRAB-Mediated Suppression of Restores p53-Mediated Apoptosis in Melanoma Cells.

Overexpression of S100B is routinely used for disease-staging and for determining prognostic outcomes in patients with malignant melanoma. Intracellular interactions between S100B and wild-type (WT)-p53 have been demonstrated to limit the availability of free WT-p53 in tumor cells, inhibiting the apoptotic signaling cascade. Herein, we demonstrate that, while oncogenic overexpression of is poorly correlated (R < 0.