The HIF-1α and mTOR Pathways Amplify Heterotopic Ossification.

Fibrodysplasia ossificans progressiva (FOP; MIM# 135100) is an ultra-rare congenital disorder caused by gain-of-function point mutations in the Activin receptor A type I (, also known as ) gene. FOP is characterized by episodic heterotopic ossification (HO) in skeletal muscles, tendons, ligaments, or other soft tissues that progressively causes irreversible loss of mobility. FOP mutations cause mild ligand-independent constitutive activation as well as ligand-dependent bone morphogenetic protein (BMP) pathway hypersensitivity of mutant ACVR1.

Female Adult Acne and Androgen Excess: A Report From the Multidisciplinary Androgen Excess and PCOS Committee.

In endocrine and reproductive endocrine literature, adult female acne is considered as a possible clinical expression of hyperandrogenism, with most polycystic ovary syndrome (PCOS) guidelines considering acne as a condition of androgen excess. Adult female acne, however, in the dermatological literature is considered as an inflammatory skin disease and new guidelines on adult female acne have been produced by dermatological societies, with little perspective from any endocrine or reproductive endocrine points of view. An expert task force was appointed by the AE-PCOS society to determine the current state of knowledge and provide evidence-based recommendations that could be valid for all specialists taking care of female adult acne.

Clearance of Senescent Cells From Injured Muscle Abrogates Heterotopic Ossification in Mouse Models of Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease caused by mutations in activin A receptor type I/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor, resulting in the formation of extraskeletal or heterotopic ossification (HO) and other features consistent with premature aging. During the first decade of life, episodic bouts of inflammatory swellings (flare-ups) occur, which are typically triggered by soft tissue trauma. Through an endochondral process, these exacerbations ultimately result in skeletal muscles, tendons, ligaments, fascia, and aponeuroses transforming into ectopic bone, rendering movement impossible.

Status of Palliative Oncology Care for Children and Young People in Sub-Saharan Africa: A Perspective Paper on Priorities for New Frontiers.

Purpose: The burden of cancer disproportionately affects low- and middle-income countries. Low 5-year survival figures for children with cancer in low-income countries are due to late presentation at diagnosis, treatment abandonment, absence of sophisticated multidisciplinary care, and lack of adequate resources. The reasons for late presentation are partly due to limited awareness of cancer symptoms, high treatment costs, and facility-level barriers to timely access to treatment.

Off-on-off-on use of imatinib in three children with fibrodysplasia ossificans progressiva.

The compassionate use of available medications with unproven efficacy is often in conflict with their clinical evaluation in placebo-controlled clinical trials. For ultra-rare diseases where no approved treatments exist, such as fibrodysplasia ossificans progressiva (FOP), routine clinical trial enrollment for available medications may be difficult to achieve. Therefore adaptive methods of evaluation are often desirable.

Compartment Syndrome of the Thigh in a Patient with Fibrodysplasia Ossificans Progressiva.

Introduction: The severe pain that commonly accompanies appendicular flare-ups of fibrodysplasia ossificans progressiva (FOP) is often ascribed to compartment syndrome, but no documentation exists.

Case Report: We revisited the case of an adult with classic FOP who underwent measurement of compartment pressure of the thigh during an acute, severely painful flare-up of the thigh. The intracompartmental pressure of the thigh was measured at 95--110 mm of mercury (normal compartment pressure is 0--8 mmHg).

Spatial patterns of heterotopic ossification in fibrodysplasia ossificans progressiva correlate with anatomic temperature gradients.

Progressive heterotopic ossification (HO) is a hallmark of fibrodysplasia ossificans progressiva (FOP); however, this tissue transformation is not random. Rather, we noticed that HO in FOP progresses in well-defined but inexplicable spatial and temporal patterns that correlate precisely with infrared thermographs of the human body. FOP is caused by gain-of-function mutations in Activin A receptor type I (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor kinase.

Firearm Violence, Access to Care, and Gentrification: A Moving Target for American Trauma Systems.

Objective: We aimed to determine whether gentrification predicts the movement of shooting victims over time and if this process has decreased access to care.

Background: Trauma centers remain fixed in space, but the populations they serve do not. Nationally, gentrification has displaced disadvantaged communities most at risk for violent injury, potentially decreasing access to care.

Retirement: An idiosyncratic vade mecum.

Many physicians tend to regard their upcoming retirement with great trepidation. They are worried that after years of productive activity they will become useless and lose all their connections with medicine. This essay will try to impress on readers that this way of thinking is absolutely incorrect, and it will provide some personal insights regarding the retirement process.

Fibrodysplasia ossificans progressiva (FOP): A disorder of osteochondrogenesis.

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder of extraskeletal bone formation, but could appropriately be viewed as a seminal disorder of osteochondrogenesis. Many, if not most, of the musculoskeletal features of FOP are related to dysregulated chondrogenesis including abnormal articular cartilage formation, abnormal diarthrodial joint specification, growth plate dysplasia, osteochondroma formation, heterotopic endochondral ossification (HEO), and precocious arthropathy. In FOP, causative activating mutations of Activin receptor A type I (ACVR1), a bone morphogenetic protein (BMP) type I receptor, are responsible for the osteochondrodysplasia that impacts developmental phenotypes as well as postnatal features of this illustrative disorder.

Factors Associated With Discharge Home Among Medical ICU Patients in an Early Mobilization Program.

Objectives: One goal of early mobilization programs is to facilitate discharge home after an ICU hospitalization, but little is known about which factors are associated with this outcome. Our objective was to evaluate factors associated with discharge home among medical ICU patients in an early mobilization program who were admitted to the hospital from home.

Design: Retrospective cohort study of medical ICU patients in an early mobilization program.

Dispersal patterns of Trypanosoma cruzi in Arequipa, Peru.

Anthropogenic environmental alterations such as urbanization can threaten native populations as well as create novel environments that allow human pests and pathogens to thrive. As the number and size of urban environments increase globally, it is more important than ever to understand the dispersal dynamics of hosts, vectors and pathogens of zoonotic disease systems. For example, a protozoan parasite and the causative agent of Chagas disease in humans, Trypanosoma cruzi, recently colonized and spread through the city of Arequipa, Peru.

Sexual reproduction in a natural Trypanosoma cruzi population.

Background: Sexual reproduction provides an evolutionary advantageous mechanism that combines favorable mutations that have arisen in separate lineages into the same individual. This advantage is especially pronounced in microparasites as allelic reassortment among individuals caused by sexual reproduction promotes allelic diversity at immune evasion genes within individuals which is often essential to evade host immune systems. Despite these advantages, many eukaryotic microparasites exhibit highly-clonal population structures suggesting that genetic exchange through sexual reproduction is rare.

Association of Prepubertal and Adolescent Androgen Concentrations With Timing of Breast Development and Family History of Breast Cancer.

Importance: Early breast development is a risk factor for breast cancer, and girls with a breast cancer family history (BCFH) experience breast development earlier than girls without a BCFH.

Objectives: To assess whether prepubertal androgen concentrations are associated with timing of breast development (analysis 1) and to compare serum androgen concentrations in girls with and without a BCFH (analysis 2).

Design, Setting, And Participants: Prospective cohort study of 104 girls aged 6 to 13 years at baseline using data collected between August 16, 2011, and March 24, 2016, from the Lessons in Epidemiology and Genetics of Adult Cancer From Youth (LEGACY) Girls Study, New York site.

Preliminary support for the role of reward relevant effort and chronotype in the depression/insomnia comorbidity.

Background: The presence of insomnia in the context of depression is linked to a number of poor outcomes including reduced treatment response, increased likelihood of relapse, and greater functional impairment. Given the frequent co-occurrence of depression and insomnia, research into systems and processes relevant to both disorders, specifically reward processing and circadian rhythm disruption, may help parse this complex comorbidity.

Methods: A pilot study was conducted on a sample of 10 veterans with clinically significant depression and insomnia symptoms.

ECSIT links TLR and BMP signaling in FOP connective tissue progenitor cells.

Clinical and laboratory observations strongly suggest that the innate immune system induces flare-ups in the setting of dysregulated bone morphogenetic protein (BMP) signaling in fibrodysplasia ossificans progressiva (FOP). In order to investigate the signaling substrates of this hypothesis, we examined toll-like receptor (TLR) activation and bone morphogenetic protein (BMP) signaling in connective tissue progenitor cells (CTPCs) from FOP patients and unaffected individuals. We found that inflammatory stimuli broadly activate TLR expression in FOP CTPCs and that TLR3/TLR4 signaling amplifies BMP pathway signaling through both ligand dependent and independent mechanisms.

Acute and chronic rapamycin use in patients with Fibrodysplasia Ossificans Progressiva: A report of two cases.

Fibrodysplasia Ossificans Progressiva (FOP) is an ultrarare genetic disorder of progressive, disabling heterotopic ossification for which there is presently no definitive treatment. Several recent studies in genetic mouse models of FOP support involvement of the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the pathophysiology of FOP and propose the repurposed use of rapamycin, an inhibitor of mTORC1 signaling in clinical trials for the management of FOP. Here we report two patients with the classic FOP mutation who received rapamycin-one for four months on a compassionate basis for treatment of acute flare-ups of the neck and back that were refractory to corticosteroid therapy-and the other for 18years for chronic immunosuppression following liver transplantation for intercurrent cytomegalovirus infection.

Driving-Related Coping Thoughts in Post-9/11 Combat Veterans With and Without Comorbid PTSD and TBI.

Veterans with a history of PTSD, TBI, and combat driving may experience driving anxiety on their return home and may benefit from using targeted coping strategies.