The pathophysiology of restricted repetitive behavior

Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson’s disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism

The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: an overview of Network organization, procedures and interventions

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here we describe the Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the U.S. The PrecISE Network was designed to conduct phase II/proof of concept clinical trials of precision interventions in the severe asthma population, and is supported by the National Heart Lung and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the Network will evaluate up to six interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for of severe asthma

Characterization of Ocular Tissues Using Microindentation and Hertzian Viscoelastic Models

Microindentation permits biomechanical characterization of small specimens of ocular tissues and demonstrates that although properties of periocular fatty tissues vary markedly by location, comparable bovine and human tissues behave similarly

Carotid revascularization and medical management for asymptomatic carotid stenosis: Protocol of the CREST-2 clinical trials

Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus intensive medical therapy versus intensive medical therapy alone. The risk factor targets of centrally directed intensive medical therapy are LDL cholesterol <70 mg/dl and systolic blood pressure <140 mmHg. Study outcomes The primary outcome is the composite of stroke and death within 44 days following randomization and stroke ipsilateral to the target vessel thereafter, up to four years. Change in cognition and differences in major and minor stroke are secondary outcomes. Sample size Enrollment of 1240 patients in each trial provides 85% power to detect a treatment difference if the event rate in the intensive medical therapy alone arm is 4.8% higher or 2.8% lower than an anticipated 3.6% rate in the revascularization arm. Discussion Management of asymptomatic carotid stenosis requires contemporary randomized trials to address whether carotid endarterectomy or carotid stenting plus intensive medical therapy is superior in preventing stroke beyond intensive medical therapy alone. Whether carotid endarterectomy or carotid stenting has favorable effects on cognition will also be tested. Trial registration United States National Institutes of Health Clinicaltrials.gov NCT02089217

Current status of surgery in dermatology.

An article titled Current issues in dermatologic office-based surgery was published in the JAAD in October 1999 (volume 41, issue 4, pp. 624-634). The article was developed by the Joint American Academy of Dermatology/American Society for Dermatologic Surgery Liaison Committee. A number of subjects were addressed in the article including surgical training program requirements for dermatology residents and selected advances in dermatologic surgery that had been pioneered by dermatologists. The article concluded with sections on credentialing, privileging, and accreditation of office-based surgical facilities. Much has changed since 1999, including more stringent requirements for surgical training during dermatology residency, and the establishment of 57 accredited Procedural Dermatology Fellowship Training Programs. All of these changes have been overseen and approved by the Residency Review Committee for Dermatology and the Accreditation Committee for Graduate Medical Education. The fertile academic environment of academic training programs with interaction between established dermatologic surgeons and fellows, as well as the inquisitive nature of many of our colleagues, has led to the numerous major advances in dermatologic surgery, which are described herein