An advanced in silico model of the oral mucosa reveals the impact of extracellular spaces on chemical permeation.

Accurately predicting the permeation of chemicals through human epithelial tissues is crucial for pharmaceutical therapeutic design and toxicology. Current mathematical models of multi-layered stratified squamous epithelium such as those in the oral cavity use simplistic 'bricks and mortar' geometries that do not fully account for the complex cellular architecture that may affect chemical permeation in these tissues. Here we aimed to develop a new, advanced mechanistic mathematical model of the human epithelium that more accurately represents chemical tissue permeation.

Feeder-free culture of human pluripotent stem cells drives MDM4-mediated gain of chromosome 1q.

Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection.

Bone-specific physical activity questionnaire-derived skeletal loading score predicts bone geometry, density, and strength indices: a cross-sectional study.

Introduction: The bone-specific physical activity questionnaire (BPAQ) provides a bone-relevant index of physical activity participation according to the mechanical loads experienced across the life span.

Materials And Methods: We aimed to examine relationships between historical bone-relevant physical activity and pQCT-derived parameters of bone strength. We recruited 532 healthy volunteers (277 males, 255 females) across a broad age range (4-97 years).

Geometry and bone mineral density determinants of femoral neck strength changes following exercise.

Physical exercise induces spatially heterogeneous adaptation in bone. However, it remains unclear where the changes in BMD and geometry have the greatest impact on femoral neck strength. The aim of this study was to determine the principal BMD-and-geometry changes induced by exercise that have the greatest effect on femoral neck strength.

The SUMO protease SENP3 regulates mitochondrial autophagy mediated by Fis1.

Mitochondria are unavoidably subject to organellar stress resulting from exposure to a range of reactive molecular species. Consequently, cells operate a poorly understood quality control programme of mitophagy to facilitate elimination of dysfunctional mitochondria. Here, we used a model stressor, deferiprone (DFP), to investigate the molecular basis for stress-induced mitophagy.

The effect of low-intensity whole-body vibration with or without high-intensity resistance and impact training on risk factors for proximal femur fragility fracture in postmenopausal women with low bone mass: study protocol for the VIBMOR randomized controlled trial.

Background: The prevailing medical opinion is that medication is the primary (some might argue, only) effective intervention for osteoporosis. It is nevertheless recognized that osteoporosis medications are not universally effective, tolerated, or acceptable to patients. Mechanical loading, such as vibration and exercise, can also be osteogenic but the degree, relative efficacy, and combined effect is unknown.

Determination of Chemical Irritation Potential Using a Defined Gene Signature Set on Tissue-Engineered Human Skin Equivalents.

There are no physical or visual manifestations that define skin sensitivity or irritation; a subjective diagnosis is made on the basis of the evaluation of clinical presentations, including burning, prickling, erythema, and itching. Adverse skin reaction in response to topically applied products is common and can limit the use of dermatological or cosmetic products. The purpose of this study was to evaluate the use of human skin equivalents based on immortalized skin keratinocytes and evaluate the potential of a 22-gene panel in combination with multivariate analysis to discriminate between chemicals known to act as irritants and those that do not.

Assessment of femoral neck strength and bone mineral density changes following exercise using 3D-DXA images.

Physical exercise induces spatially heterogeneous bone changes in the proximal femur. Recent advances have enabled 3D dual-energy X-ray Absorptiometry (DXA)-based finite element (FE) models to estimate bone strength. However, its ability to detect exercise-induced BMD and strength changes is unclear.

A Nurse Educator's Perspective About Institutional Racism and White Supremacy in Nursing Education.

In the United States, nursing education programs at mostly white institutions are led by faculty that are 80% white. This absence of diversity is a symptom of systemic racism and white supremacy, reinforced through built systems of inequity and economic constraints that influence accessibility of nursing education programs. White cultural norms drive standards of professionalism and assimilation within nursing education programs.

Effects of supervised high-intensity resistance and impact training or machine-based isometric training on regional bone geometry and strength in middle-aged and older men with low bone mass: The LIFTMOR-M semi-randomised controlled trial.

Introduction: Few data exist on the effects of bone-targeted exercise on geometric and biomechanical indices of bone strength in men. The Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR-M) trial was designed to compare the efficacy and safety of two novel, supervised, twice-weekly, high-intensity exercise programs in middle-aged and older men with osteopenia and osteoporosis on musculoskeletal health and risk factors related to falls and fractures. The current report includes secondary outcomes of the LIFTMOR-M exercise intervention trial.

Multiscale modelling of drug transport and metabolism in liver spheroids.

In early preclinical drug development, potential candidates are tested in the laboratory using isolated cells. These experiments traditionally involve cells cultured in a two-dimensional monolayer environment. However, cells cultured in three-dimensional spheroid systems have been shown to more closely resemble the functionality and morphology of cells .

A Comparison of Bone-Targeted Exercise Strategies to Reduce Fracture Risk in Middle-Aged and Older Men with Osteopenia and Osteoporosis: LIFTMOR-M Semi-Randomized Controlled Trial.

The Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR-M) trial examined efficacy and safety of two novel exercise programs in older men with low BMD. Men with low hip and/or LS BMD were randomized to high-intensity progressive resistance and impact training (HiRIT) or machine-based isometric axial compression (IAC) and compared to a nonrandomized matched control (CON). Outcomes included: hip and LS BMD; calcaneal ultrasound parameters; anthropometry; body composition; function (timed up-and-go [TUG], five-times sit-to-stand [FTSTS]); back extensor strength (BES); leg extensor strength (LES); compliance and adverse events.

Factors that predict glycaemic response to sodium-glucose linked transporter (SGLT) inhibitors.

Aim: To determine the clinical and biochemical variables associated with change in HbA1c in patients with type 2 diabetes who start sodium-glucose linked transporter (SGLT) inhibitor therapy.

Methods: We performed a prospective cohort study (ACTRN12616000833460) of 48 adults (30 male, 18 female) with type 2 diabetes who attended a tertiary hospital diabetes clinic. Fasting serum and urine samples, collected during clinic visits prior to and at 1, 12 and 24 weeks after commencing SGLT inhibitor treatment, were analysed for HbA1c, electrolytes, urea, creatinine and glucose.

Enjoyment and acceptability of different exercise modalities to improve bone health in young adult women.

Issue Addressed: Osteoporosis presents a serious public health issue and physical activity is recognised as the most effective modifiable risk factor for the condition. The reasons behind physical activity participation, however, are complex. We therefore aimed to explore the experiences related to a bone-targeted exercise intervention, determine enjoyment and acceptability of each exercise mode, and identify barriers and facilitators to osteogenic exercise for young adult women.

Regional changes in indices of bone strength of upper and lower limbs in response to high-intensity impact loading or high-intensity resistance training.

It is well known that the bone response to physical activity is highly dependent on the nature of the loads imposed. Despite this, few direct comparisons of the effect of impact-style loading and resistance training on bone have been made. We therefore aimed to compare the effects of 10-month, twice-weekly, high-impact loading and 10-month, twice-weekly, high-intensity resistance training on indices of bone strength of both the upper and lower limbs of young adult women.

Haptoglobin expression in human colorectal cancer.

Aims and experimental design. The acute-phase protein haptoglobin (Hp) has been recently detected in colorectal cancer (CRC) tissue, where its expression correlates with metastasis. Recently, we identified Hp as a CDw75 antigen-expressing protein in colorectal tissue.

Characterisation of a functional rat hepatocyte spheroid model.

Many in vitro liver cell models, such as 2D systems, that are used to assess the hepatotoxic potential of xenobiotics suffer major limitations arising from a lack of preservation of physiological phenotype and metabolic competence. To circumvent some of these limitations there has been increased focus on producing more representative 3D models. Here we have used a novel approach to construct a size-controllable 3D hepatic spheroid model using freshly isolated primary rat hepatocytes (PRH) utilising the liquid-overlay technique whereby PRH spontaneously self-assemble in to 3D microtissues.

Exercise, Osteoporosis, and Bone Geometry.

Exercise is commonly recommended in the prevention and management of osteoporosis. The most common method to monitor bone mass and its response to interventions is bone densitometry. While closely associated with risk of fracture, densitometry-derived areal bone mineral density (aBMD) does not provide a reliable indication of bone geometry or morphological adaptation to stimuli.

High-Intensity Resistance and Impact Training Improves Bone Mineral Density and Physical Function in Postmenopausal Women With Osteopenia and Osteoporosis: The LIFTMOR Randomized Controlled Trial.

Optimal osteogenic mechanical loading requires the application of high-magnitude strains at high rates. High-intensity resistance and impact training (HiRIT) applies such loads but is not traditionally recommended for individuals with osteoporosis because of a perceived high risk of fracture. The purpose of the LIFTMOR trial was to determine the efficacy and to monitor adverse events of HiRIT to reduce parameters of risk for fracture in postmenopausal women with low bone mass.

A protocol for a randomised controlled trial of the bone response to impact loading or resistance training in young women with lower than average bone mass: the OPTIMA-Ex trial.

Introduction: The aim of the Osteoporosis Prevention Through Impact and Muscle-loading Approaches to Exercise trial is to compare the bone response to two known osteogenic stimuli - impact loading exercise and resistance training. Specifically, we will examine the effect of a 10-month, twice-weekly, high-intensity impact loading exercise intervention and a 10-month, twice-weekly, high-intensity resistance training intervention on bone mass and strength at clinically important skeletal sites. The intervention groups will be compared against a home-based 'positive' control group.

The LIFTMOR-M (Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men) trial: protocol for a semirandomised controlled trial of supervised targeted exercise to reduce risk of osteoporotic fracture in older men with low bone mass.

Introduction: The primary aim of the proposed study is to examine the efficacy of an 8-month supervised, high-intensity progressive resistance training and impact loading programme in comparison with a supervised machine-based isometric exercise training programme using the bioDensity system in older men with low bone mass. We will also determine the safety and acceptability of each exercise training mode. Intervention group responses will be compared with those of a self-selected, non-randomised control sample of sex-matched and age-matched men who will follow their usual lifestyle activities for 8 months.