Research priorities for progressive pulmonary fibrosis in the UK.

Introduction: Health research bodies recommend patient involvement and engagement in research and healthcare planning, although their implementation is not yet widespread. This deficiency extends to progressive pulmonary fibrosis (PPF), where crucial aspects remain unknown, including causal mechanisms, curative treatments and optimal symptom management. This study addresses these gaps by seeking stakeholders' perspectives to guide research and treatment directions.

Sexuality Minority Status, Victimization, Mental Health, and Substance Use.

Prior research suggests that sexual minority status is related to victimization, mental health issues, and substance use. However, few studies have sought to connect these relationships in a way supported by theory, and fewer have utilized probability and/or nationally representative samples. The current study seeks to test the relationships among these variables, guided by general strain theory (GST).

Low-Magnitude Mechanical Signals Combined with Zoledronic Acid Reduce Musculoskeletal Weakness and Adiposity in Estrogen-Deprived Mice.

Unlabelled: Combination treatment of Low-Intensity Vibration (LIV) with zoledronic acid (ZA) was hypothesized to preserve bone mass and muscle strength while reducing adipose tissue accrual associated with complete estrogen (E )-deprivation in young and skeletally mature mice. Complete E -deprivation (surgical-ovariectomy (OVX) and daily injection of aromatase inhibitor (AI) letrozole) were performed on 8-week-old C57BL/6 female mice for 4 weeks following commencement of LIV administration or control (no LIV), for 28 weeks. Additionally, 16-week-old C57BL/6 female E -deprived mice were administered ±LIV twice daily and supplemented with ±ZA (2.

Does Forgiveness Enhance Or Detract From Relationship Quality Among Sexual Abuse Survivors?

Many women experience childhood sexual abuse (CSA) during their childhood and CSA often negatively impacts adult's romantic relationships. Consequently, it is important to understand the protective factors that buffer against the detrimental impact of CSA on the quality of women's romantic relationships. Forgiveness may be one such factor.

Case Study of a Comprehensive Team-Based Approach to Increase Colorectal Cancer Screening.

Introduction: Colorectal cancer is the second leading cause of cancer deaths among men and women in West Virginia. In addition, 51% of all colorectal cancers diagnosed in West Virginia from 2012 to 2016 were detected at either regional (31%) or distant (20%) stages indicating a need for improved early detection.

Methods: West Virginia University Cheat Lake Physicians participated in the West Virginia Program to Increase Colorectal Cancer Screening, a program of Cancer Prevention and Control at the WVU Cancer Institute.

Liver-specific overexpression of SIRT3 enhances oxidative metabolism, but does not impact metabolic defects induced by high fat feeding in mice.

The mitochondrial enzyme SIRT3 is an NAD-dependent deacetylase important in cell metabolism, and a decline in its protein expression or activity has been linked with insulin resistance in obesity, ageing and type 2 diabetes. While studies in SIRT3 knockout mice have dramatically improved our understanding of the function of SIRT3, the impact of increasing SIRT3 levels remains under-examined. In this study we investigated the effects of liver-specific SIRT3 overexpression in mice on mitochondrial function and metabolic profile in both isolated hepatocytes and in vivo.

Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity.

Exercise benefits the musculoskeletal system and reduces the effects of cancer. The effects of exercise are multifactorial, where metabolic changes and tissue adaptation influence outcomes. Mechanical signals, a principal component of exercise, are anabolic to the musculoskeletal system and restrict cancer progression.

Leveraging Electronic Health Records Data for Enhanced Colorectal Cancer Screening Efforts.

Introduction: Colorectal cancer is the third most common type of cancer in the United States for men and women combined. While the current threat of disease nationally is significant, the majority of colorectal cancer cases and deaths could be prevented through established screening tests and guidelines. Within the Appalachian region and West Virginia in particular, colorectal cancer is a significant public health problem.

Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity.

Osteoporosis, a condition of skeletal decline that undermines quality of life, is treated with pharmacological interventions that are associated with poor adherence and adverse effects. Complicating efforts to improve clinical outcomes, the incidence of obesity is increasing, predisposing the population to a range of musculoskeletal complications and metabolic disorders. Pharmacological management of obesity has yet to deliver notable reductions in weight and debilitating complications are rarely avoided.

Transcriptional programming of lipid and amino acid metabolism by the skeletal muscle circadian clock.

Circadian clocks are fundamental physiological regulators of energy homeostasis, but direct transcriptional targets of the muscle clock machinery are unknown. To understand how the muscle clock directs rhythmic metabolism, we determined genome-wide binding of the master clock regulators brain and muscle ARNT-like protein 1 (BMAL1) and REV-ERBα in murine muscles. Integrating occupancy with 24-hr gene expression and metabolomics after muscle-specific loss of BMAL1 and REV-ERBα, here we unravel novel molecular mechanisms connecting muscle clock function to daily cycles of lipid and protein metabolism.

An Emic, Mixed Methods Approach to Defining and Measuring Positive Parenting Among Low-Income, Black Families.

Research Findings: This within-group exploratory sequential mixed methods investigation sought to identify how ethnically diverse, urban-residing, low-income Black families conceptualize positive parenting. During the item development phase 119 primary caregivers from Head Start programs participated in focus groups and interviews. These qualitative data were content analyzed using a three-stage iterative process that resulted in the development of a final set of 72 items for a paper-and-pencil measure.

Increased mitochondrial calcium uniporter in adipocytes underlies mitochondrial alterations associated with insulin resistance.

Intracellular calcium influences an array of pathways and affects cellular processes. With the rapidly progressing research investigating the molecular identity and the physiological roles of the mitochondrial calcium uniporter (MCU) complex, we now have the tools to understand the functions of mitochondrial Ca in the regulation of pathophysiological processes. Herein, we describe the role of key MCU complex components in insulin resistance in mouse and human adipose tissue.

Aromatase inhibitor-induced bone loss increases the progression of estrogen receptor-negative breast cancer in bone and exacerbates muscle weakness in vivo.

Aromatase inhibitors (AIs) cause muscle weakness, bone loss, and joint pain in up to half of cancer patients. Preclinical studies have demonstrated that increased osteoclastic bone resorption can impair muscle contractility and prime the bone microenvironment to accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases.

Murine models of breast cancer bone metastasis.

Bone metastases cause significant morbidity and mortality in late-stage breast cancer patients and are currently considered incurable. Investigators rely on translational models to better understand the pathogenesis of skeletal complications of malignancy in order to identify therapeutic targets that may ultimately prevent and treat solid tumor metastasis to bone. Many experimental models of breast cancer bone metastases are in use today, each with its own caveats.

Excess TGF-β mediates muscle weakness associated with bone metastases in mice.

Cancer-associated muscle weakness is a poorly understood phenomenon, and there is no effective treatment. Here we find that seven different mouse models of human osteolytic bone metastases-representing breast, lung and prostate cancers, as well as multiple myeloma-exhibited impaired muscle function, implicating a role for the tumor-bone microenvironment in cancer-associated muscle weakness. We found that transforming growth factor (TGF)-β, released from the bone surface as a result of metastasis-induced bone destruction, upregulated NADPH oxidase 4 (Nox4), resulting in elevated oxidization of skeletal muscle proteins, including the ryanodine receptor and calcium (Ca(2+)) release channel (RyR1).

Overexpression of SIRT1 in rat skeletal muscle does not alter glucose induced insulin resistance.

SIRT1 is a NAD+-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 expression affect markers of muscle mitochondrial content and also determined whether SIRT1 influenced muscle insulin resistance induced by acute glucose oversupply. In male Wistar rats either SIRT1 or a deacetylase inactive mutant form (H363Y) was electroprated into the tibialis cranialis (TC) muscle.

Single-Limb Irradiation Induces Local and Systemic Bone Loss in a Murine Model.

Increased fracture risk is commonly reported in cancer patients receiving radiotherapy, particularly at sites within the field of treatment. The direct and systemic effects of ionizing radiation on bone at a therapeutic dose are not well-characterized in clinically relevant animal models. Using 20-week-old male C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and microarchitecture were evaluated prospectively by microcomputed tomography and histomorphometry and compared to contralateral-shielded bone (left hindlimb) and non-irradiated control bone.

Erratum to "Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock" [Mol Metab 3 (2014) 29-41].

[This corrects the article DOI: 10.1016/j.molmet.

The microenvironment matters: estrogen deficiency fuels cancer bone metastases.

Factors released during osteoclastic bone resorption enhance disseminated breast cancer cell progression by stimulating invasiveness, growth, and a bone-resorptive phenotype in cancer cells. Postmenopausal bone loss may accelerate progression of breast cancer growth in bone, explaining the anticancer benefit of the bone-specific antiresorptive agent zoledronic acid in the postmenopausal setting. Clin Cancer Res; 20(11); 2817-9.

Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock.

Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation.