NFAT restricts osteochondroma formation from entheseal progenitors.

Osteochondromas are common benign osteocartilaginous tumors in children and adolescents characterized by cartilage-capped bony projections on the surface of bones. These tumors often cause pain, deformity, fracture, and musculoskeletal dysfunction, and they occasionally undergo malignant transformation. The pathogenesis of osteochondromas remains poorly understood.

Impact of high-fat diet on the proteome of mouse liver.

Chronic overnutrition, for instance, high-fat diet (HFD) feeding, is a major cause of rapidly growing incidence of metabolic syndromes. However, the mechanisms underlying HFD-induced adverse effects on human health are not clearly understood. HFD-fed C57BL6/J mouse has been a popular model employed to investigate the mechanisms.

Mass spectrometry insights into a tandem ubiquitin-binding domain hybrid engineered for the selective recognition of unanchored polyubiquitin.

Unanchored polyubiquitin chains are emerging as important regulators of cellular physiology with diverse roles paralleling those of substrate-conjugated polyubiquitin. However tools able to discriminate unanchored polyubiquitin chains of different isopeptide linkages have not been reported. We describe the design of a linker-optimized ubiquitin-binding domain hybrid (t-UBD) containing two UBDs, a ZnF-UBP domain in tandem with a linkage-selective UBA domain, which exploits avidity effects to afford selective recognition of unanchored Lys48-linked polyubiquitin chains.

Elucidating the Functional Roles of Spatial Organization in Cross-Membrane Signal Transduction by a Hybrid Simulation Method.

The ligand-binding of membrane receptors on cell surfaces initiates the dynamic process of cross-membrane signal transduction. It is an indispensable part of the signaling network for cells to communicate with external environments. Recent experiments revealed that molecular components in signal transduction are not randomly mixed, but spatially organized into distinctive patterns.

Substance use stigma: Reliability and validity of a theory-based scale for substance-using populations.

Background: Substance use disorders consistently rank among the most stigmatized conditions worldwide. Thus, substance use stigma fosters health inequities among persons with substance use disorders and remains a key barrier to successful screening and treatment efforts. Current efforts to measure substance use stigma are limited.

Recent advances in the management of pulmonary sarcomatoid carcinoma.

Pulmonary sarcomatoid carcinoma (PSC) is a unique and biologically fascinating group of poorly differentiated non-small cell lung cancer (NSCLC), however it is highly aggressive with poor overall survival compared to other types of NSCLC. Radical surgery remains the standard of care for early localized disease but this has shown to result in high recurrence rates. Traditional palliative chemotherapy is associated with poor response in advanced/metastatic PSC.

Evaluation of care access and hypertension control in a community health worker driven non-communicable disease programme in rural Uganda: the chronic disease in the community project.

The burden of non-communicable diseases continues to grow throughout the developing world. Health systems in low- and middle-income regions face significant human resource shortages, which limit the ability to meet the growing need for non-communicable disease care. Specially trained community health workers may be useful in filling that provider gap.

Enhanced virulence of Histoplasma capsulatum through transfer and surface incorporation of glycans from Cryptococcus neoformans during co-infection.

Cryptococcus neoformans (Cn) and Histoplasma capsulatum (Hc) co-exist in the environment and occasionally co-infect individuals, which can lead to severe disease/lethal outcomes. We investigated specific interactions between Cn-Hc to determine the impact of synchronous infection in virulence and disease. Co-infected mice had significantly higher mortality than infection with either species or acapsular Cn-Hc.

GATA4 regulates Fgf16 to promote heart repair after injury.

Although the mammalian heart can regenerate during the neonatal stage, this endogenous regenerative capacity is lost with age. Importantly, replication of cardiomyocytes has been found to be the key mechanism responsible for neonatal cardiac regeneration. Unraveling the transcriptional regulatory network for inducing cardiomyocyte replication will, therefore, be crucial for the development of novel therapies to drive cardiac repair after injury.

Ruptured anterior spinal artery aneurysm from a herniated cervical disc. A case report and review of the literature.

Background: Subarachnoid hemorrhage (SAH) caused by a ruptured cervical anterior spinal artery aneurysm is extremely rare and in the setting of cervical spondylosis. This case presentation reviews the diagnosis, management, and treatment of such aneurysms.

Case Presentation: An 88-year-old female presented with the worst headache of her life without focal deficits.

Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors.

Circulating cancer cells can putatively colonize distant organs to form metastases or to reinfiltrate primary tumors themselves through a process termed "tumor self-seeding." Here we exploit this biological attribute to deliver tumor necrosis factor alpha (TNF), a potent antitumor cytokine, directly to primary and metastatic tumors in a mechanism that we have defined as "tumor self-targeting." For this purpose, we genetically engineered mouse mammary adenocarcinoma (TSA), melanoma (B16-F10), and Lewis lung carcinoma cells to produce and release murine TNF.

Impact of Collaborative Care for Underserved Patients with PTSD in Primary Care: a Randomized Controlled Trial.

Background: The effectiveness of collaborative care of mental health problems is clear for depression and growing but mixed for anxiety disorders, including posttraumatic stress disorder (PTSD). We know little about whether collaborative care can be effective in settings that serve low-income patients such as Federally Qualified Health Centers (FQHCs).

Objective: We compared the effectiveness of minimally enhanced usual care (MEU) versus collaborative care for PTSD with a care manager (PCM).

Patients Receiving Integrative Medicine Effectiveness Registry (PRIMIER) of the BraveNet practice-based research network: study protocol.

Background: Integrative medicine (IM) provides patient-centered care and addresses the full range of physical, emotional, mental, social, spiritual, and environmental influences that affect a person's health. IM is a "whole systems" approach that employs multiple modalities as opposed to an isolated complementary therapy. Thus, studying outcomes of IM is more challenging than evaluating an isolated intervention.

The role of speckle tracking echocardiography in assessment of lipopolysaccharide-induced myocardial dysfunction in mice.

Background: Sepsis-induced myocardial dysfunction is a common and severe complication of septic shock. Conventional echocardiography often fails to reveal myocardial depression in severe sepsis due to hemodynamic changes; in contrast, decline of strain measurements by speckle tracking echocardiography (STE) may indicate impaired cardiac function. This study investigates the role of STE in detecting lipopolysaccharide (LPS)-induced cardiac dysfunction with mouse models.

Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36.

Nuclear receptor SET domain containing protein 2 (NSD2) catalyzes the methylation of histone H3 lysine 36 (H3K36). It is a determinant in Wolf-Hirschhorn syndrome and is overexpressed in human multiple myeloma. Despite the relevance of NSD2 to cancer, there are no potent, selective inhibitors of this enzyme reported.

Structured scaffolding for reflection and problem solving in diabetes self-management: qualitative study of mobile diabetes detective.

Objective: To investigate subjective experiences and patterns of engagement with a novel electronic tool for facilitating reflection and problem solving for individuals with type 2 diabetes, Mobile Diabetes Detective (MoDD).

Methods: In this qualitative study, researchers conducted semi-structured interviews with individuals from economically disadvantaged communities and ethnic minorities who are participating in a randomized controlled trial of MoDD. The transcripts of the interviews were analyzed using inductive thematic analysis; usage logs were analyzed to determine how actively the study participants used MoDD.

Chronic dietary chlorpyrifos causes long-term spatial memory impairment and thigmotaxic behavior.

Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity.

Diabetes and cervical myelopathy.

Diabetes may affect the typical physical findings associated with cervical spondylotic myelopathy, as coexisting diabetic neuropathy may dampen expected hyperreflexia and also produce non-dermatomal extremity numbness. Most large studies of surgically treated diabetic patients with cervical spondylotic myelopathy have focused upon infection rates rather than exploring any differences in the presenting physical signs. We conducted a retrospective study of the pattern of presenting neurological signs and symptoms and of the clinical outcomes in 438 patients surgically treated for cervical spondylotic myelopathy, 79 of whom had diabetes.

Using Healthy Defaults in Walt Disney World Restaurants to Improve Nutritional Choices.

A retrospective study of kids' meals purchased at Walt Disney World was conducted to determine acceptance rates for healthy sides and beverages. Purchase data from all 145 Walt Disney World restaurants were analyzed using a log-linear model and a Poisson regression. Across all restaurants, 47.

Functional genomics screen identifies YAP1 as a key determinant to enhance treatment sensitivity in lung cancer cells.

Survival for lung cancer patients remains dismal and is largely attributed to treatment resistance. To identify novel target genes the modulation of which could modify platinum resistance, we performed a high-throughput RNAi screen and identified Yes-associated protein (YAP1), a transcription coactivator and a known oncogene, as a potential actionable candidate. YAP1 ablation significantly improved sensitivities not only to cisplatin but also to ionizing radiation, both of which are DNA-damaging interventions, in non-small cell lung cancer (NSCLC) cells.

Blood Pressure Visit Intensification Study in Treatment: Trial design.

Background: There is a presumption that, for patients with uncontrolled blood pressure (BP), early follow-up, that is, within 4 weeks of an elevated reading, improves BP control. However, data are lacking regarding effective interventions for increasing clinician frequency of follow-up visits and whether such interventions improve BP control.

Methods/design: Blood Pressure Visit Intensification Study in Treatment involves a multimodal approach to improving intensity of follow-up in 12 community health centers using a stepped wedge study design.