Pharmacologic Inhibition of Myostatin With a Myostatin Antibody Improves the Skeletal Muscle and Bone Phenotype of Male Insulin-Deficient Diabetic Mice.

Type 1 diabetes (T1D) is associated with low bone and muscle mass, increased fracture risk, and impaired skeletal muscle function. Myostatin, a myokine that is systemically elevated in humans with T1D, negatively regulates muscle mass and bone formation. We investigated whether pharmacologic myostatin inhibition in a mouse model of insulin-deficient, streptozotocin (STZ)-induced diabetes is protective for bone and skeletal muscle.

Old-growth trees host a unique suite of arbuscular mycorrhizal fungi and other root-associated fungal taxa in their canopy soil environment.

Canopy soils occur on tree branches throughout the temperate rainforests of the Pacific Northwest Coast and are recognized as a defining characteristic of these ecosystems. Certain tree species extend adventitious roots into these canopy soil environments. Yet, research on adventitious root-associated fungi remains limited.

Arbuscular mycorrhizae influence raspberry growth and soil fertility under conventional and organic fertilization.

Introduction: Introducing beneficial soil biota such as arbuscular mycorrhizal fungi (AMF) to agricultural systems may improve plant performance and soil fertility. However, whether bioinocula species composition affects plant growth and soil fertility, and whether fertilizer source influences AMF colonization have not been well characterized. The objectives of this research were to: (1) assess if AMF bioinocula of different species compositions improve raspberry ( L.

Boredom in a Time of Uncertainty: State and Trait Boredom's Associations with Psychological Health during COVID-19.

Throughout the COVID-19 pandemic, studies have demonstrated increases in boredom and its negative impact on mental health. This cross-sectional study examines state and trait boredom at four different points of the pandemic using an online sample of participants from the United States ( = 783). The results showed significant increases in boredom proneness, state boredom, substance use, loneliness, and distress.

Heterogeneity and altered β-cell identity in the TallyHo model of early-onset type 2 diabetes.

A primary underlying defect makes β-cells "susceptible" to no longer compensate for the peripheral insulin resistance and to trigger the onset of type 2 diabetes (T2D). New evidence suggests that in T2D, β-cells are not destroyed but experience a loss of identity, reverting to a progenitor-like state and largely losing the ability to sense glucose and produce insulin. We assessed (using fluorescence microscopy and histomorphometry correlated with the glycaemic status) the main β-cell identity modifications as diabetes progresses in the TallyHo/JngJ (TH) male mice, a polygenic model of spontaneous T2D, akin to the human phenotype.

Systematic review of physical activity interventions assessing physical and mental health outcomes on patients with severe mental illness (SMI) within secure forensic settings.

Unlabelled: WHAT IS KNOWN ON THE SUBJECT?: Individuals with a severe mental illness (SMI) are less physically active and have a lower life expectancy than the general population due to increased risks of cardiometabolic diseases (obesity, diabetes and respiratory diseases) and other health risks. Physical activity has been used as an adjunct therapy for individuals with SMI yielding improvements in cognitive functioning, quality of life and a reduction in psychiatric symptoms. Individuals with SMI residing within a secure forensic setting have reduced physical activity opportunities, possibly due to a number of factors including low motivation and restricted access to exercise facilities combined with a lack of knowledge and/or confidence in staff members to assist in physical activity programmes.

A highly efficient method for the production and purification of recombinant human CXCL8.

Chemokines play diverse and fundamental roles in the immune system and human disease, which has prompted their structural and functional characterisation. Production of recombinant chemokines that are folded and bioactive is vital to their study but is limited by the stringent requirements of a native N-terminus for receptor activation and correct disulphide bonding required to stabilise the chemokine fold. Even when expressed as fusion proteins, overexpression of chemokines in E.

Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer.

Although precision medicine has had a mixed impact on the clinical management of patients with advanced-stage cancer overall, for NSCLC, and more specifically for lung adenocarcinoma, the advances have been dramatic, largely owing to the genomic complexity and growing number of druggable oncogene drivers. Furthermore, although tumor tissue is historically the "accepted standard" biospecimen for these molecular analyses, there are considerable innate limitations. Thus, liquid biopsy represents a practical alternative source for investigating tumor-derived somatic alterations.

RASopathies: The musculoskeletal consequences and their etiology and pathogenesis.

The RASopathies comprise an ever-growing number of clinical syndromes resulting from germline mutations in components of the RAS/MAPK signaling pathway. While multiple organs and tissues may be affected by these mutations, this review will focus on how these mutations specifically impact the musculoskeletal system. Herein, we review the genetics and musculoskeletal phenotypes of these syndromes in humans.

Strengthening the Connection Between Acquired Brain Injury (ABI) and Family Violence: The Importance of Ongoing Monitoring, Research and Inclusive Terminology.

Family violence (FV) harms communities worldwide so FV prevention strategies and effective responses are urgently needed. This article reports on FV apparent in a study which explored the experiences of people with both ABI and justice system encounters in Victoria, Australia. One hundred interviews and one focus group consulted people with ABI, their families and carers, and various stakeholder groups in the Victorian justice system in Australia.

Impact of an SGLT2-loss of function mutation on renal architecture, histology, and glucose homeostasis.

Inhibitors of sodium/glucose co-transporter 2 (SGLT2) are currently in clinical use for type 2 diabetes (T2D) treatment due to their anti-hyperglycemic effect exerted by the inhibition of glucose reabsorption in the kidney. Inhibition of SGLT2 is associated with improvement of renal outcomes in chronic kidney disease associated with T2D. Our study aimed to describe the renal-specific phenotypic consequences of the SGLT2-loss of function "Jimbee" mutation within the Slc5a2 mouse gene in a non-diabetic/non-obese background.

Canagliflozin, an SGLT2 inhibitor, corrects glycemic dysregulation in TallyHO model of T2D but only partially prevents bone deficits.

Higher fracture risk in type 2 diabetes (T2D) is attributed to disease-specific deficits in micro-structural and material properties of bone, although the primary cause is not yet established. The TallyHO (TH) mouse is a polygenic model of early-onset T2D and obesity analogous to adolescent-onset T2D in humans. Due to incomplete penetrance of the phenotype, ~25% of male TH mice never develop hyperglycemia, providing a strain-matched, non-diabetic control.

Genetic ablation of SGLT2 function in mice impairs tissue mineral density but does not affect fracture resistance of bone.

Selective sodium-dependent glucose co-transporter 2 inhibitors (SGLT2Is) are oral hypoglycemic medications utilized increasingly in the medical management of hyperglycemia among persons with type 2 diabetes (T2D). Despite favorable effects on cardiovascular events, specific SGLT2Is have been associated with an increased risk for atypical fracture and amputation in subgroups of the T2D population, a population that already has a higher risk for typical fragility fractures than the general population. To better understand the effect of SGLT2 blockade on skeletal integrity, independent of diabetes and its co-morbidities, we utilized the "Jimbee" mouse model of slc5a2 gene mutation to investigate the impact of lifelong SGLT2 loss-of-function on metabolic and skeletal phenotype.

Constitutive activation of MEK1 in osteoprogenitors increases strength of bone despite impairing mineralization.

Recent clinical studies have revealed that a somatic mutation in MAP2K1, causing constitutive activation of MEK1 in osteogenic cells, occurs in melorheostotic bone disease in humans. We have generated a mouse model which expresses an activated form of MEK1 (MEK1DD) specifically in osteoprogenitors postnatally. The skeletal phenotype of these mice recapitulates many features of melorheostosis observed in humans, including extra-cortical bone formation, abundant osteoid formation, decreased mineral density, and increased porosity.

Relative importance of competition and plant-soil feedback, their synergy, context dependency and implications for coexistence.

Plants interact simultaneously with each other and with soil biota, yet the relative importance of competition vs. plant-soil feedback (PSF) on plant performance is poorly understood. Using a meta-analysis of 38 published studies and 150 plant species, we show that effects of interspecific competition (either growing plants with a competitor or singly, or comparing inter- vs.

'I am not drunk, I have an ABI': findings from a qualitative study into systematic challenges in responding to people with acquired brain injuries in the justice system.

The over-representation of acquired brain injury (ABI) amongst prisoner and juvenile justice populations is a significant issue across jurisdictions. This article reports on the findings of over 100 interviews conducted in Victoria, Australia with people who have an ABI, as well as key stakeholder groups who work in, or with, the justice system. The study identified systemic problems faced by people with ABI along multiple points of the justice system continuum.

The impact of SGLT2 inhibitors, compared with insulin, on diabetic bone disease in a mouse model of type 1 diabetes.

Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover.

Effects of Type 1 Diabetes on Osteoblasts, Osteocytes, and Osteoclasts.

Purpose Of Review: To describe the effects of type 1 diabetes on bone cells.

Recent Findings: Type 1 diabetes (T1D) is associated with low bone mineral density, increased risk of fractures, and poor fracture healing. Its effects on the skeleton were primarily attributed to impaired bone formation, but recent data suggests that bone remodeling and resorption are also compromised.

Nutlin-3 treatment spares cisplatin-induced inhibition of bone healing while maintaining osteosarcoma toxicity.

The majority of Osteosarcoma (OS) patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. These protocols include distraction osteogenesis (DO), which is characterized by direct new bone formation. Cisplatin (CDP) is extensively used for OS chemotherapy and recent studies, using a mouse DO model, have demonstrated that CDP has profound negative effects on bone repair.

Risk factors for heat illness among British soldiers in the hot Collective Training Environment.

Background: Heat illness is a preventable disorder in military populations. Measures that protect vulnerable individuals and contribute to effective Immediate Treatment may reduce the impact of heat illness, but depend upon adequate understanding and awareness among Commanders and their troops.

Objective: To assess risk factors for heat illness in British soldiers deployed to the hot Collective Training Environment (CTE) and to explore awareness of Immediate Treatment responses.