Sfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function.

We have previously reported that the cortical bone thinning seen in mice lacking the Wnt signaling antagonist is due in part to impaired periosteal apposition. The periosteum contains cells which function as a reservoir of stem cells and contribute to cortical bone expansion, homeostasis, and repair. However, the local or paracrine factors that govern stem cells within the periosteal niche remain elusive.

Cardiovascular Risk Assessment and Management for Pediatricians.

Childhood and adolescence provide a unique window of opportunity to prevent atherosclerotic cardiovascular disease later in life, especially for pediatric groups at risk. The growing list of pediatric groups at risk includes individuals with chronic inflammatory disorders, organ transplants, familial hypercholesterolemia, endocrine disorders, childhood cancer, chronic kidney diseases, congenital heart diseases, and premature birth, as well as increasing numbers of children and adolescents with traditional risk factors such as obesity, hypertension, hyperlipidemia, and hyperglycemia. Here, we focus on recent advances in cardiovascular risk assessment and management and their implications for pediatric practice.

Cumulative In-Hospital Costs Associated With Single-Ventricle Palliation.

Background: In the SVR (Single Ventricle Reconstruction) Trial, 1-year survival in recipients of right ventricle to pulmonary artery shunts (RVPAS) was superior to that in those receiving modified Blalock-Taussig-Thomas shunts (MBTTS), but not in subsequent follow-up. Cost analysis is an expedient means of evaluating value and morbidity.

Objectives: The purpose of this study was to evaluate differences in cumulative hospital costs between RVPAS and MBTTS.

A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 () Gene Confers Enhanced Calcineurin Activity and May Cause FSGS.

Background: Podocyte dysfunction is the main pathologic mechanism driving the development of FSGS and other morphologic types of steroid-resistant nephrotic syndrome (SRNS). Despite significant progress, the genetic causes of most cases of SRNS have yet to be identified.

Methods: Whole-genome sequencing was performed on 320 individuals from 201 families with familial and sporadic NS/FSGS with no pathogenic mutations in any known NS/FSGS genes.

Sexual orientation and social network size moderate associations between stigma and problematic alcohol use among male sex workers in the US Northeast: an observational study.

Unlabelled: Background Stigma is associated with poor health among sexual minority individuals. However, no studies have examined the relationship between stigma and problematic drinking among male sex workers (MSWs). This study examined the relationship between sex work stigma and problematic alcohol use among MSWs.

New insights and perspectives on the genetics of obsessive-compulsive disorder.

Psychiatric genetic research has exploded in search of polygenic risk factors over the past decade, but because of the complexity and heterogeneity of mental illnesses, using the current understanding of the genome has not reached the conclusion of finding a cause for psychiatric disorders. Obsessive-compulsive disorder is a relatively common and often debilitating neuropsychiatric disorder that has not been the primary focus in psychiatric research. Clinicians and researchers who have dedicated to investigate the genetics of obsessive-compulsive disorder have detected a strong genetic involvement.

Predictors and Moderators of Cognitive and Behavioral Therapy Outcomes for OCD: A Patient-Level Mega-Analysis of Eight Sites.

Cognitive (CT) and behavioral treatments (BT) for OCD are efficacious separately and in combination. Tailoring treatment to patient-level predictors and moderators of outcome has the potential to improve outcomes. The present study combined data from eight treatment clinics to examine the benefits of BT (n = 125), CT (n = 108), and CBT (n = 126), and study predictors across all treatments and moderators of outcome by treatment type.

Assessment of Hospitalist-Subspecialist Agreement About Who Should Be in Charge and Comparison With Actual Assignment Practices.

Background: A key juncture in patient hospitalization is determining which type of physician should be primarily responsible for directing treatment. We (1) examine the frequency hospitalists and subspecialists agree on preferred assignments and (2) compare preferred assignment with actual assignment.

Methods: Using a mixed methods approach, we first surveyed 66 physicians in 8 specialties about hospitalist assignments versus subspecialist assignments for 176 diagnoses at an academic children's hospital.

Targeting skeletal endothelium to ameliorate bone loss.

Recent studies have identified a specialized subset of CD31endomucin (CD31EMCN) vascular endothelium that positively regulates bone formation. However, it remains unclear how CD31EMCN endothelium levels are coupled to anabolic bone formation. Mice with an osteoblast-specific deletion of Shn3, which have markedly elevated bone formation, demonstrated an increase in CD31EMCN endothelium.

Melanocytic naevi with perineurial differentiation: a distinctive variant of neurotised naevi and a diagnostic pitfall with desmoplastic melanoma.

Aims: Spindle cell differentiation is not an uncommon finding in common acquired naevi, and may represent a form of neurotisation with Schwannian differentiation of melanocytes. Perineurial differentiation in this context appears to be very rare, and is only poorly documented in the literature. We therefore aimed to study this rare form of neurotisation in melanocytic naevi more comprehensively.

Up-regulation of Intracellular Calcium Handling Underlies the Recovery of Endotoxemic Cardiomyopathy in Mice.

Background: In surviving patients, sepsis-induced cardiomyopathy is spontaneously reversible. In the absence of any experimental data, it is generally thought that cardiac recovery in sepsis simply follows the remission of systemic inflammation. Here the authors aimed to identify the myocardial mechanisms underlying cardiac recovery in endotoxemic mice.

Identifying barriers to and facilitators of tuberculosis contact investigation in Kampala, Uganda: a behavioral approach.

Background: The World Health Organization recommends routine household tuberculosis contact investigation in high-burden countries but adoption has been limited. We sought to identify barriers to and facilitators of TB contact investigation during its introduction in Kampala, Uganda.

Methods: We collected cross-sectional qualitative data through focus group discussions and interviews with stakeholders, addressing three core activities of contact investigation: arranging household screening visits through index TB patients, visiting households to screen contacts and refer them to clinics, and evaluating at-risk contacts coming to clinics.

Brief Report: Anti-RNPC-3 Antibodies As a Marker of Cancer-Associated Scleroderma.

Objective: Prior studies have demonstrated an increased risk of cancer-associated scleroderma in patients with anti-RNA polymerase III (anti-RNAP III) autoantibodies as well as in patients who are triple-negative for anticentromere (anti-CENP), anti-topoisomerase I (anti-topo I), and anti-RNAP III (also known as anti-POL) autoantibodies (referred to as CTP negative). In a recent study of 16 CTP-negative scleroderma patients with coincident cancer, 25% of the patients were found to have autoantibodies to RNPC-3, a member of the minor spliceosome complex. This investigation was undertaken to validate the relationship between anti-RNPC-3 antibodies and cancer and examine the associated clinical phenotype in a large sample of scleroderma patients.

Statement on pregnancy in pulmonary hypertension from the Pulmonary Vascular Research Institute.

Pregnancy outcomes in patients with pulmonary hypertension remain poor despite advanced therapies. Although consensus guidelines recommend against pregnancy in pulmonary hypertension, it may nonetheless occasionally occur. This guideline document sought to discuss the state of knowledge of pregnancy effects on pulmonary vascular disease and to define usual practice in avoidance of pregnancy and pregnancy management.

Adult attention-deficit/hyperactivity disorder treatment and cardiovascular implications.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder afflicting adults worldwide. This article is an update on the evidence supporting medications for adult ADHD, with particular emphasis on cardiovascular implications. Relevant clinical literature was sought using PubMed searches, with an emphasis on new reports from April 2009 to April 2011.

Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden.

Disruption of functional connectivity between brain regions may represent an early functional consequence of β-amyloid pathology prior to clinical Alzheimer's disease. We aimed to investigate if non-demented older individuals with increased amyloid burden demonstrate disruptions of functional whole-brain connectivity in cortical hubs (brain regions typically highly connected to multiple other brain areas) and if these disruptions are associated with neuronal dysfunction as measured with fluorodeoxyglucose-positron emission tomography. In healthy subjects without cognitive symptoms and patients with mild cognitive impairment, we used positron emission tomography to assess amyloid burden and cerebral glucose metabolism, structural magnetic resonance imaging to quantify atrophy and novel resting state functional magnetic resonance imaging processing methods to calculate whole-brain connectivity.

Distinctive prepubertal vulval fibroma: a hitherto unrecognized mesenchymal tumor of prepubertal girls: analysis of 11 cases.

Eleven cases of a distinctive previously unrecognized mesenchymal tumor that arises in the vulvar region in the prepubertal years are described. The tumors presented in the vulva (8 cases arising from labia majora) of prepubertal girls (range, 4-12 years; median, 8 years). The preoperative diagnoses were labial mass or swelling, not otherwise specified in 3 cases, hemangioma in 2 cases, lipoma in 2 cases, and lymphangioma and Bartholin cyst/lymphedema in 1 case each.

A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils.

Lipoxins and their aspirin-triggered 15-epimers are endogenous anti-inflammatory agents that block neutrophil chemotaxis in vitro and inhibit neutrophil influx in several models of acute inflammation. In this study, we examined the effects of 15-epi-16-(p-fluoro)-phenoxy-lipoxin A(4) methyl ester, an aspirin-triggered lipoxin A(4)-stable analog (ATLa), on the protein phosphorylation pattern of human neutrophils. Neutrophils stimulated with the chemoattractant fMLP were found to exhibit intense phosphorylation of a 55-kDa protein that was blocked by ATLa (10-50 nM).

The indications, utilization and safety of gastrointestinal endoscopy in an extremely elderly patient cohort.

Background: In developed nations, increasing proportions of the population now reach advanced age. Physicians may be reluctant to refer such patients for non-critical diagnostic and therapeutic interventions, on the basis of perceived diminution of tolerance, safety and substantive benefits in these patients. We aimed to review the utility and safety of gastrointestinal endoscopy in an extremely elderly cohort.