ATM-dependent DNA damage surveillance in T-cell development and leukemogenesis: the DSB connection

Summary:  The immune system is capable of recognizing and eliminating an enormous array of pathogens due to the extremely diverse antigen receptor repertoire of T and B lymphocytes. However, the development of lymphocytes bearing receptors with unique specificities requires the generation of programmed double strand breaks (DSBs) coupled with bursts of proliferation, rendering lymphocytes susceptible to mutations contributing to oncogenic transformation. Consequently, mechanisms responsible for monitoring global genomic integrity must be activated during lymphocyte development to limit the oncogenic potential of antigen receptor locus recombination. Mutations in ATM (ataxia-telangiectasia mutated), a kinase that coordinates DSB monitoring and the response to DNA damage, result in impaired T-cell development and predispose to T-cell leukemia. Here, we review recent evidence providing insight into the mechanisms by which ATM promotes normal lymphocyte development and protects from neoplastic transformation.     

The Impact of Community Diversity and Consolidated Inequality on Dropping Out of High School

Abstract: Data from the National Education Longitudinal Study were combined with census data at the zip code level to examine the impact of neighborhood racial and ethnic diversity and consolidated inequality, in addition to individual, family, and school factors, on the likelihood of dropping out of high school. Results indicate that while the effects for diversity and consolidated inequality did not support the stated hypotheses, main effects for family risk and prior academic achievement were significant and in the stated direction. Also, when controlling for individual, family, school, and neighborhood characteristics, African Americans were less likely than White students to drop out of school. Implications for contextual effects research and educational outcomes are discussed.     

Melioidosis: an important cause of pneumonia in residents of and travellers returned from endemic regions.

Melioidosis is endemic in South East Asia, Asia and northern Australia. Infection usually follows percutaneous inoculation or inhalation of the causative bacterium, Burkholderia pseudomallei, which is present in soil and surface water in the endemic region. While 20-36% of melioidosis cases have no evident predisposing risk factor, the vast majority of fatal cases have an identified risk factor, the most important of which are diabetes, alcoholism and chronic renal disease. Half of all cases present with pneumonia, but there is great clinical diversity, from localised skin ulcers or abscesses without systemic illness to fulminant septic shock with multiple abscesses in the lungs, liver, spleen and kidneys. At least 10% of cases present with a chronic respiratory illness (sick > 2 months) mimicking tuberculosis and often with upper lobe infiltrates and/or cavities on chest radiography. As with tuberculosis, latency with reactivation decades after infection can also occur, although this is rare. Confirmation of diagnosis is by culture of B. pseudomallei from blood, sputum, throat swab or other samples. Microbiology laboratories need to be informed of the possibility of melioidosis, as those not familiar with it can misidentify the organism. Antibiotic therapy is initial intensive therapy with i.v. ceftazidime or meropenem or imipenem +/- cotrimoxazole for > or = 10 days, followed by eradication therapy with cotrimoxazole +/- doxycycline +/- chloramphenicol (first 4 weeks only) for > or = 3 months. Melioidosis has been increasingly recognised in returning travellers in Europe and recently melioidosis and colonisation with B. pseudomallei have been documented in cystic fibrosis patients visiting or resident in endemic areas.     

The Evidence Base Supporting the Subtyping of Gamblers in Treatment

Introduction Recent reviews found problem gamblers are heterogeneous and recommended subtyping gamblers in treatment studies. Objective Review factors (stage of change, preferred gambling activity, co-occurring disorder, and temporal instability of symptoms) for subtyping by evaluating the evidence for their effects on gambling treatment. Methods Literature review, evidence grading. Results Evidence is limited that any of the reviewed factors affects gambling treatment. Substantial evidence from prospective studies and other evidence from cross-sectional studies and the strong placebo response among pathological gamblers support the temporal instability of gambling symptoms. Conclusions Multiple studies are needed to develop the evidence base needed to subtype gamblers in treatment. Changes in the diagnostic criteria of pathological gambling may be necessary, especially to specify the persistence of gambling-related symptoms.     

Right aortic arch detected in fetal life.

OBJECTIVE: To evaluate the prenatal distribution, associated conditions and outcome of the different types of right aortic arch (RAA) detected in fetal life. METHODS: This was a retrospective review of all cases of RAA detected prenatally between 1998 and 2005 in two tertiary referral centers. RESULTS: In the study period 71 cases of RAA were detected; 26 (37%) had RAA with aberrant left subclavian artery, 23 (32%) had RAA with mirror-image branching, 20 (28%) had RAA of unknown type and two (3%) had double aortic arch. While 20/26 cases with RAA and aberrant left subclavian artery were isolated findings, all 23 cases with RAA and mirror-image branching were associated with cardiac defects, namely tetralogy of Fallot (43%) or pulmonary atresia with ventricular septal defect (22%). Of the 20 cases with RAA, 19 of unknown type were associated with heterotaxy syndromes and had additional cardiac malformations and ambiguities of the situs. The two cases with DAA were isolated findings. Seven cases in our series (10%) had a microdeletion 22q11 and these were significantly associated with extracardiac malformations. The outcome in our series depended solely on the associated cardiac and extracardiac malformations, with the exception of one infant with isolated DAA, in whom a surgical correction was warranted. CONCLUSIONS: RAA detected in fetal life is associated frequently with other cardiac/non-cardiac malformations, heterotaxy syndromes and microdeletions 22q11. The associated conditions vary depending on the branching type of the brachiocephalic vessels and the presence of extracardiac malformations.     

Making clinical decisions for dental care: concepts to consider

Clinical decisions are often made with incomplete information, yet patient care decisions are made every day. Patients vary clinically, uncertainty exists in diagnostic and prognostic information, and many preventive and treatment alternatives have not been formally assessed for their effectiveness. Because scientific information will never answer all clinical questions, clinical decisions are partially based on probabilistic information.
This paper describes how to apply clinical decision making to diagnosing and managing dental caries and periodontal diseases. By using explicit information to quantify probabilities and outcomes, clinical decision making analyzes decisions made under uncertain conditions and the uncertain impact of clinical information.
Clinical decision making incorporates concepts for preventing, diagnosing and treating dental caries and periodontal diseases: risk assessment, evidence-based dentistry, and multiple oral health outcomes. This information can serve as a tool for clinicians to augment clinical judgment and expertise.