High-fat and high-carbohydrate diets increase bone fragility through TGF-β-dependent control of osteocyte function.

Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood.

Aging impairs the osteocytic regulation of collagen integrity and bone quality.

Poor bone quality is a major factor in skeletal fragility in elderly individuals. The molecular mechanisms that establish and maintain bone quality, independent of bone mass, are unknown but are thought to be primarily determined by osteocytes. We hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling (PLR), which maintains bone material properties.

miR181a/b-1 controls osteocyte metabolism and mechanical properties independently of bone morphology.

Bone derives its ability to resist fracture from bone mass and quality concurrently; however, many questions about the molecular mechanisms controlling bone quality remain unanswered, limiting the development of diagnostics and therapeutics. Despite the increasing evidence on the importance of miR181a/b-1 in bone homeostasis and disease, whether and how osteocyte-intrinsic miR181a/b-1 controls bone quality remains elusive. Osteocyte-intrinsic deletion of miR181a/b-1 in osteocytes in vivo resulted in compromised overall bone mechanical behavior in both sexes, although the parameters affected by miR181a/b-1 varied distinctly based on sex.

The Multifaceted Effects of Osteocytic TGFβ Signaling on the Skeletal and Extraskeletal Functions of Bone.

Purpose Of Review: To summarize the fundamental role of transforming growth factor beta (TGFβ) signaling in osteocytes and highlight the physiological and pathophysiological conditions stemming from the deregulation of this pathway in osteocytes.

Recent Findings: Osteocytes perform a myriad of skeletal and extraskeletal functions, including mechanosensing, coordinating bone remodeling, local bone matrix turnover, and maintaining systemic mineral homeostasis and global energy balance. Transforming growth factor-beta (TGFβ) signaling, which is crucial for embryonic and postnatal bone development and maintenance, has been found to be essential for several osteocyte functions.

Zoledronic acid improves bone quality and muscle function in a high bone turnover state.

Summary: Zoledronic acid (ZA) prevents muscle weakness in mice with bone metastases; however, its role in muscle weakness in non-tumor-associated metabolic bone diseases and as an effective treatment modality for the prevention of muscle weakness associated with bone disorders, is unknown. We demonstrate the role of ZA-treatment on bone and muscle using a mouse model of accelerated bone remodeling, which represents the clinical manifestation of non-tumor associated metabolic bone disease. ZA increased bone mass and strength and rescued osteocyte lacunocanalicular organization.

Race, the Vaginal Microbiome, and Spontaneous Preterm Birth.

Previous studies have investigated the associations between the vaginal microbiome and preterm birth, with the aim of determining whether differences in community patterns meaningfully alter risk and could therefore be the target of intervention. We report on vaginal microbial analysis of a nested case-control subset of the Pregnancy, Infection, and Nutrition (PIN) Study, including 464 White women (375 term birth and 89 spontaneous preterm birth, sPTB) and 360 Black women (276 term birth and 84 sPTB). We found that the microbiome of Black women has higher alpha-diversity, higher abundance of Lactobacillus iners, and lower abundance of Lactobacillus crispatus.

Prioritization of Genes Relevant to Bone Fragility Through the Unbiased Integration of Aging Mouse Bone Transcriptomics and Human GWAS Analyses.

Identifying new genetic determinants of bone mineral density (BMD) and fracture promises to yield improved diagnostics and therapies for bone fragility. However, prioritizing candidate genes from genome-wide screens can be challenging. To overcome this challenge, we prioritized mouse genes that are differentially expressed in aging mouse bone based on whether their human homolog is associated with human BMD and/or fracture.

Is prenatal diet associated with the composition of the vaginal microbiome?

Background: The vaginal microbiome has been associated with adverse pregnancy outcomes, but information on the impact of diet on microbiome composition is largely unexamined.

Objective: To estimate the association between prenatal diet and vaginal microbiota composition overall and by race.

Methods: We leveraged a racially diverse prenatal cohort of North Carolina women enrolled between 1995 and 2001 to conduct this analysis using cross-sectional data.

Mechanosensitive miR-100 coordinates TGFβ and Wnt signaling in osteocytes during fluid shear stress.

Organism scale mechanical forces elicit cellular scale changes through coordinated regulation of multiple signaling pathways. The mechanisms by which cells integrate signaling to generate a unified biological response remains a major question in mechanobiology. For example, the mechanosensitive response of bone and other tissues requires coordinated signaling by the transforming growth factor beta (TGFβ) and Wnt pathways through mechanisms that are not well-defined.

The relationship of cumulative psychosocial adversity with antepartum depression and anxiety.

Background: Exposure to multiple psychosocial risk factors may increase vulnerability for mental health conditions during pregnancy. This analysis examined the relationship of a novel psychosocial adversity index with the co-occurrence and persistence of depression and anxiety throughout pregnancy.

Methods: This cross-sectional analysis included 1797 pregnant women screened in the second/third trimesters for depression and anxiety symptoms and for eight contextual and individual psychosocial factors.

Fluid shear stress generates a unique signaling response by activating multiple TGFβ family type I receptors in osteocytes.

Bone is a dynamic tissue that constantly adapts to changing mechanical demands. The transforming growth factor beta (TGFβ) signaling pathway plays several important roles in maintaining skeletal homeostasis by both coupling the bone-forming and bone-resorbing activities of osteoblasts and osteoclasts and by playing a causal role in the anabolic response of bone to applied loads. However, the extent to which the TGFβ signaling pathway in osteocytes is directly regulated by fluid shear stress (FSS) is unknown, despite work suggesting that fluid flow along canaliculi is a dominant physical cue sensed by osteocytes following bone compression.

Reproductive Endocrinology Reference Intervals for Transgender Men on Stable Hormone Therapy.

Background: Gender-affirming therapy with testosterone is commonly prescribed to aid in the masculinization of transgender men. Sex-hormone concentrations are routinely measured, but interpretation of results can be difficult due to the lack of published reference intervals.

Methods: Healthy transgender individuals who had been prescribed testosterone (n = 82) for at least a year were recruited from internal medicine and primary care clinics that specialize in transgender medical care.

Assessment of Osteocytes: Techniques for Studying Morphological and Molecular Changes Associated with Perilacunar/Canalicular Remodeling of the Bone Matrix.

Recent advances have revived interest in the concept of osteocyte perilacunar/canalicular remodeling (PLR) and have motivated efforts to identify the mechanisms regulating this process in bone in the context of normal physiology and pathological conditions. Here, we describe several methods that are evaluating morphological changes associated with PLR function of osteocytes.

Mechanosensitive Control of Articular Cartilage and Subchondral Bone Homeostasis in Mice Requires Osteocytic Transforming Growth Factor β Signaling.

Objective: Transforming growth factor β (TGFβ) signaling plays a complex tissue-specific and nonlinear role in osteoarthritis (OA). This study was conducted to determine the osteocytic contributions of TGFβ signaling to OA.

Methods: To identify the role of osteocytic TGFβ signaling in joint homeostasis, we used 16-week-old male mice (n = 9-11 per group) and female mice (n = 7-11 per group) with an osteocyte-intrinsic ablation of TGFβ receptor type II (TβRII mice) and assessed defects in cartilage degeneration, subchondral bone plate (SBP) thickness, and SBP sclerostin expression.

Reproductive Endocrinology Reference Intervals for Transgender Women on Stable Hormone Therapy.

Background: Transgender women and nonbinary people seeking feminizing therapy are often prescribed estrogen as a gender-affirming hormone, which will alter their reproductive hormone axis. Testosterone, estradiol, and other reproductive hormones are commonly evaluated to assess therapy, but reference intervals specific to transgender women have not been established. The objective of this study was to derive reference intervals for commonly measured analytes related to reproductive endocrinology in a cohort of healthy gender nonconforming individuals on stable feminizing hormone therapy.

TGFβ Regulation of Perilacunar/Canalicular Remodeling Is Sexually Dimorphic.

Bone fragility is the product of defects in bone mass and bone quality, both of which show sex-specific differences. Despite this, the cellular and molecular mechanisms underpinning the sexually dimorphic control of bone quality remain unclear, limiting our ability to effectively prevent fractures, especially in postmenopausal osteoporosis. Recently, using male mice, we found that systemic or osteocyte-intrinsic inhibition of TGFβ signaling, achieved using the 9.

Endothelial injury, F-actin and vitamin-D binding protein after hematopoietic stem cell transplant and association with clinical outcomes.

Endothelial injury after hematopoietic stem cell transplant is an important initiating factor for early transplant toxicities of thrombotic microangiopathy and acute graft versus host disease. We hypothesized that release of the angiopathic molecule filamentous actin from hematopoietic cells lysed during conditioning prior to stem cell transplant would be associated with clinical outcomes. We detected filamentous actin in the blood of 52% of stem cell transplant recipients in the first 14 days after transplant, and children with detectable filamentous actin had significantly elevated risk of thrombotic microangiopathy (p= 0.

Race/Ethnicity, Gender, and Trajectories of Depressive Symptoms Across Early- and Mid-Life Among the Add Health Cohort.

While disparities in depressive symptoms by race/ethnicity and gender have been documented, left unclear is how such status characteristics intersect to influence mental health, particularly across early life and among a diverse set of population subgroups. This study investigates how intra- and inter-individual trends in depressive symptoms unfold across a 30-year span (ages 12-42) and are structured by the intersection of race/ethnicity and gender among White, Black, Hispanic, and Asian American young adults (N = 18,566). Analyses use data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of adolescents who have been followed through their fourth decade of life.

Association of antepartum depression, generalized anxiety, and posttraumatic stress disorder with infant birth weight and gestational age at delivery.

Background: Low- and middle-income countries bear a disproportionate burden of preterm birth (PTB) and low infant birth weight (LBW) complications where affective and anxiety disorders are more common in the antepartum period than in industrialized countries.

Objective: To evaluate the extent to which early pregnancy antepartum depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD) are associated with infant birth weight and gestational age at delivery among a cohort of pregnant women in Peru.

Methods: Our prospective cohort study consisted of 4408 pregnant women.

TIP60 up-regulates ΔNp63α to promote cellular proliferation.

An estimated 5.4 million cases of nonmelanoma skin cancer are reported in the United States at an associated cost of $4.8 billion.

Tuning Surface Chemoresistivity of Au Ultrathin Films Using Metal Deposition via Surface-Limited Redox Replacement of the Underpotentially Deposited Pb Monolayer.

The presented work investigates the chemoresistivity of Au ultrathin films, whose surface is modified by deposition of few monolayers of Au, Pd, or AuPd alloy. The model adsorbate in this study was the HS ion from 0.1 M NaCl solution having concentrations ranging from 0 to 40 ppm.

The Association Between Acculturation and Prenatal Psychosocial Stress Among Latinas.

Latinas experience high levels of stress in pregnancy, however few studies have investigated how acculturation affects pregnancy mental health among Latinas. The goal of this study was to determine if acculturation was associated with pregnancy stress among pregnant, predominantly Puerto Rican women. Participants (n = 1426) were enrolled in Proyecto Buena Salud, a prospective cohort study of Latinas.

The Depths of Despair Among US Adults Entering Midlife.

Objectives: To test whether indicators of despair are rising among US adults as they age toward midlife and whether this rise is concentrated among low-educated Whites and in rural areas.

Methods: We used data from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of US adolescents in 1994. Our sample was restricted to individuals who participated in 1 or more of 5 waves (1994-2017) and self-identified as non-Hispanic White, non-Hispanic Black, or Hispanic (n = 18 446).

Hematology reference intervals for transgender adults on stable hormone therapy.

Background: The complete blood count (CBC) is a cornerstone of patient care. Several of the normal values for the components of the CBC differ by sex and, therefore, male-specific and female-specific reference intervals are required to interpret these laboratory results. Transgender individuals are often prescribed hormone therapy to affirm their gender, with resulting serum hormone concentrations similar to those of cisgender individuals.