Modulation of Immunity by Lymphatic Dysfunction in Lymphedema

The debilitating condition known as secondary lymphedema frequently occurs after lymphadenectomy and/or radiotherapy for the treatment of cancer. These therapies can damage lymphatic vessels leading to edema, fibrosis, inflammation and dysregulated adipogenesis, which result in profound swelling of an affected limb. Importantly, lymphedema patients often exhibit impaired immune function which predisposes them to a variety of infections. It is known that lymphadenectomy can compromise the acquisition of adaptive immune responses and antibody production; however the cellular mechanisms involved are poorly understood. Here we discuss recent progress in revealing the cellular and molecular mechanisms underlying poor immune function in secondary lymphedema, which has indicated a key role for regulatory T cells in immunosuppression in this disease. Furthermore, the interaction of CD4+ T cells and macrophages has been shown to play a role in driving proliferation of lymphatic endothelial cells and aberrant lymphangiogenesis, which contribute to interstitial fluid accumulation in lymphedema. These new insights into the interplay between lymphatic vessels and the immune system in lymphedema will likely provide opportunities for novel therapeutic approaches designed to improve clinical outcomes in this problematic disease

Ancestry of the Brazilian TP53 c.1010G>A (p.Arg337His, R337H) founder mutation : clues from haplotyping of short tandem repeats on Chromosome 17p

Rare germline mutations in TP53 (17p13.1) cause a highly penetrant predisposition to a specific spectrum of early cancers, defining the Li-Fraumeni Syndrome (LFS). A germline mutation at codon 337 (p.Arg337His, c1010G>A) is found in about 0.3% of the population of Southern Brazil. This mutation is associated with partially penetrant LFS traits and is found in the germline of patients with early cancers of the LFS spectrum unselected for familial his- tory. To characterize the extended haplotypes carrying the mutation, we have genotyped 9 short tandem repeats on chromosome 17p in 12 trios of Brazilian p.Arg337His carriers. Results confirm that all share a common ancestor haplotype of Caucasian/Portuguese-Ibe- ric origin, distant in about 72–84 generations (2000 years assuming a 25 years intergenera- tional distance) and thus pre-dating European migration to Brazil. So far, the founder p. Arg337His haplotype has not been detected outside Brazil, with the exception of two resi- dents of Portugal, one of them of Brazilian origin. On the other hand, increased meiotic recombination in p.Arg337His carriers may account for higher than expected haplotype diversity. Further studies comparing haplotypes in populations of Brazil and of other areas of Portuguese migration are needed to understand the historical context of this mutation in Brazil.This study was funded by grant # 478430/2012-4 from CNPq (RFA MCT/CNPq - No 14/2012; Universal), Brazil.We would like to thank UFRGS, UFPA, AC Camargo, HC Barretos and University of Minho for their support during this work

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

The Expert Panel was charged with using data from randomized controlled trials (RCTs) and systematic reviews and meta-analyses of RCTs to update the clinical practice recommendations for the treatment of blood cholesterol levels to reduce ASCVD risk. For this guideline, ASCVD includes coronary heart disease (CHD), stroke, and peripheral arterial disease, all of presumed atherosclerotic origin. These recommendations are intended to provide a strong, evidence-based foundation for the treatment of cholesterol for the primary and secondary prevention of ASCVD in women and men

2013 ACC/AHA guideline on the assessment of cardiovascular risk: A report of the American College of Cardiology/American heart Association Task Force on Practice Guidelines

1.1. Organization of the Work Group: The Risk Assessment Work Group (Work Group) was composed of 11 members and 5 ex-officio members, including internists, cardiologists, endocrinologists, and experts in cardiovascular epidemiology, biostatistics, healthcare management and economics, and guideline development. 1.2. Document Review and Approval: A formal peer review process, which included 12 expert reviewers and representatives of federal agencies, was initially completed under the auspices of the NHLBI. This document was also reviewed by 3 expert reviewers nominated by the ACC and the AHA when the management of the guideline transitioned to the ACC/AHA. The ACC and AHA Reviewers’ RWI information is published in this document (Appendix 2). This document was approved for publication by the governing bodies of the ACC and AHA and endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, American Society for Preventive Cardiology, American Society of Hypertension, Association of Black Cardiologists, National Lipid Association, Preventive Cardiovascular Nurses Association, and WomenHeart: The National Coalition for Women With Heart Disease. 1.3. Charge to the Work Group: The Work Group was 1 of 3 work groups appointed by the NHLBI to develop its own recommendations and provide cross-cutting input to 3 Panels for updating guidelines on blood cholesterol, blood pressure (BP), and overweight/obesity. The Work Group was asked to examine the scientific evidence on risk assessment for initial ASCVD events and to develop an approach for quantitative risk assessment that could be used in practice and used or adapted by the risk factor panels (blood cholesterol, hypertension, and obesity) in their guidelines and algorithms. Specifically, the Work Group was charged with 2 tasks: 1) To develop or recommend an approach to quantitative risk assessment that could be used to guide care; and 2) To use systematic review methodology to pose and address a small number of questions judged to be critical to refining and adopting risk assessment in clinical practice

ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable Angina)

The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease. Ischemic heart disease is the single leading cause of death in the U.S. The most common manifestation of this disease is chronic stable angina. Recognizing the importance of the management of this common entity and the absence of national clinical practice guidelines in this area, the task force formed the current committee to develop guidelines for the management of patients with stable angina. Because this problem is frequently encountered in the practice of internal medicine, the task force invited the American College of Physicians-American Society of Internal Medicine (ACP-ASIM) to serve as a partner in this effort by naming four general internists to serve on the committee

Exome chip analysis identifies low-frequency and rare variants in MRPL38 for white matter hyperintensities on brain MRI

International audienc

Suicide risk in schizophrenia: learning from the past to change the future

Suicide is a major cause of death among patients with schizophrenia. Research indicates that at least 5–13% of schizophrenic patients die by suicide, and it is likely that the higher end of range is the most accurate estimate. There is almost total agreement that the schizophrenic patient who is more likely to commit suicide is young, male, white and never married, with good premorbid function, post-psychotic depression and a history of substance abuse and suicide attempts. Hopelessness, social isolation, hospitalization, deteriorating health after a high level of premorbid functioning, recent loss or rejection, limited external support, and family stress or instability are risk factors for suicide in patients with schizophrenia. Suicidal schizophrenics usually fear further mental deterioration, and they experience either excessive treatment dependence or loss of faith in treatment. Awareness of illness has been reported as a major issue among suicidal schizophrenic patients, yet some researchers argue that insight into the illness does not increase suicide risk. Protective factors play also an important role in assessing suicide risk and should also be carefully evaluated. The neurobiological perspective offers a new approach for understanding self-destructive behavior among patients with schizophrenia and may improve the accuracy of screening schizophrenics for suicide. Although, there is general consensus on the risk factors, accurate knowledge as well as early recognition of patients at risk is still lacking in everyday clinical practice. Better knowledge may help clinicians and caretakers to implement preventive measures. This review paper is the results of a joint effort between researchers in the field of suicide in schizophrenia. Each expert provided a brief essay on one specific aspect of the problem. This is the first attempt to present a consensus report as well as the development of a set of guidelines for reducing suicide risk among schizophenia patients