Catechol‐O‐methyltransferase gene val158met polymorphism and depressive symptoms during early childhood

Catechol‐O‐Methyltransferase (COMT) is a critical regulator of catecholamine levels in the brain. A functional polymorphism of the COMT gene, val158met, has been linked to internalizing symptoms (i.e., depression and anxiety) in adolescents and adults. We extended this research by investigating whether the val158met polymorphism was associated with childhood symptoms of depression and anxiety in two independent samples of young children (Ns = 476 and 409). In both samples, preschool‐aged children were genotyped for the COMT val158met polymorphism. Symptoms of psychopathology were assessed via parent interviews and primary caregiver reports. In both samples, children homozygous for the val allele had higher levels of depressive symptoms compared to children with at least one copy of the met allele. Our findings extend previous research in older participants by showing links between the COMT val158met polymorphism and internalizing symptoms in early childhood. © 2013 Wiley Periodicals, Inc.     

The hypertension team: the role of the pharmacist, nurse, and teamwork in hypertension therapy

Team-based care is one of the key components of the patient-centered medical home. Studies have consistently demonstrated that teams involving pharmacists or nurses in patient management can significantly improve blood pressure control. These findings have been demonstrated in several meta-analyses and systematic reviews. These reviews have generally found that team-based care can reduce systolic blood pressure by 4-10 mm Hg over usual care. However, these reviews have also concluded that many of the studies had various limitations and that additional research should be conducted. The present state of the art review paper will highlight newer studies, many of which were funded by the National Institutes of Health. Newer strategies involve telephone and/or web-based management which is an evolving area to improve blood pressure control in large populations. Social media and other technology is currently being investigated to assist pharmacists or nurses in communicating with patients to improve hypertension management. Few cost-effectiveness analyses have been performed but generally have found favorable costs for team-based care when considering the potential to reduce morbidity and mortality. The authors will suggest additional research that needs to be conducted to help evaluate strategies to best implement team-based care to improve blood pressure management.     

The ins and outs of Mycobacterium tuberculosis protein export

Mycobacterium tuberculosis is an important pathogen that infects approximately one-third of the world's population and kills almost two million people annually. An important aspect of M.?tuberculosis physiology and pathogenesis is its ability to export proteins into and across the thick mycobacterial cell envelope, where they are ideally positioned to interact with the host. In addition to the specific proteins that are exported by M.?tuberculosis, the systems through which these proteins are exported represent potential targets for future drug development. M.?tuberculosis possesses two well-known and conserved export systems: the housekeeping Sec pathway and the Tat pathway. In addition, M.?tuberculosis possesses specialized export systems including the accessory SecA2 pathway and five ESX pathways. Here we review the current understanding of each of these export systems, with a focus on M.?tuberculosis, and discuss the contribution of each system to disease and physiology.     

A systematic review and meta‐analysis of clinical variables used in Huntington disease research

Treatment effect in Huntington disease (HD) clinical trials has relied on primary outcome measures such as total motor score or functional rating scales. However, these measures have limited sensitivity, particularly in pre‐ to early stages of the disease. We performed a systematic review of HD clinical studies to identify endpoints that correlate with disease severity. Using standard HD keywords and terms, we identified 749 published studies from 1993 to 2011 based on the availability of demographic, biochemical, and clinical measures. The average and variability of each measure was abstracted and stratified according to pre‐far, pre‐close, early, mild, moderate, and severe HD stages. A fixed‐effect meta‐analysis on selected variables was conducted at various disease stages. A total of 1,801 different clinical variables and treatment outcomes were identified. Unified Huntington Disease Rating Scale (UHDRS) Motor, UHDRS Independence, and Trail B showed a trend toward separation between HD stages. Other measures, such as UHDRS Apathy, Verbal Fluency, and Symbol Digit, could only distinguish between pre‐ and early stages of disease and later stages, whereas other measures showed little correlation with increasing HD stages. Using cross‐sectional data from published HD clinical trials, we have identified potential endpoints that could be used to track HD disease progression and treatment effect. Longitudinal studies, such as TRACK‐HD, are critical for assessing the value of potential markers of disease progression for use in future HD therapeutic trials. A list of variables, references used in this meta‐analysis, and database is available at http://www.cmmt.ubc.ca/research/investigators/leavitt/publications . © 2013 International Parkinson and Movement Disorder Society     

Measurement of upper limb function in ALS: a structured review of current methods and future directions

Journal of Neurology - Measurement of upper limb function is critical for tracking clinical severity in amyotrophic lateral sclerosis (ALS). The Amyotrophic Lateral Sclerosis Rating Scale-revised...     

Electrocardiographic manifestations: diagnosis of atrioventricular block in the Emergency Department

Patients with bradycardia are commonly encountered by the Emergency Physician. Of the possible bradydysrhythmias, atrioventricular blocks (AVB) represent a significant portion of these presentations. In this article, we provide four illustrative cases of patients presenting to the Emergency Department (ED) with AVB. We review the various types of AV block dysrhythmias (1st, 2nd, and 3rd degrees) and their underlying etiologies. This discussion also focuses on the presentation, clinical considerations, management and acute treatment of AVB dysrhythmias in the emergent setting.     

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Annals of Surgical Oncology - Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly...     

Analysis of naturally processed peptides eluted from HLA DRB1 *0402 and *0404

Understanding the structural features of naturally processed peptides found within the major histocompatibility complex (MHC) class II peptide binding groove from disease-associated MHC molecules may provide insights into the nature of potential disease-related antigens. Class II MHC/peptide complexes were purified by immunoaffinity from transformed B cell lines homozygous for DRB1*0404 (an allele associated with rheumatoid arthritis) and *0402 (a closely related allele not associated with this disease). Peptides were eluted at acidic pH, fractionated by reversed phase HPLC, and analyzed by capillary electrophoresis. Those fractions containing a single dominant peptide were sequenced by automated Edman degradation and tandem mass spectrometry. The predominant peptide species identified came from non-polymorphic regions of the HLA class I molecules expressed by each cell line. Peptides from DRB1*0404 were found to be nested clusters derived from positions 26–43 of the HLA-B and -C α-chain. DRB1*0402 contained as the predominant peptide species a nested cluster from positions 129–145 of the HLA-B α-chain. The primary structure of the class I derived peptides was consistent with that seen by peptides exhibiting promiscuous DR binding behavior. Processing of MHC-derived peptides by MHC class II molecules is a common occurrence in the transformed B cell lines analyzed. © 1996 Wiley-Liss, Inc.