Priority actions for the non-communicable disease crisis

The UN High-Level Meeting on Non-Communicable Diseases (NCDs) in September, 2011, is an unprecedented opportunity to create a sustained global movement against premature death and preventable morbidity and disability from NCDs, mainly heart disease, stroke, cancer, diabetes, and chronic respiratory disease. The increasing global crisis in NCDs is a barrier to development goals including poverty reduction, health equity, economic stability, and human security. The Lancet NCD Action Group and the NCD Alliance propose five overarching priority actions for the response to the crisis--leadership, prevention, treatment, international cooperation, and monitoring and accountability--and the delivery of five priority interventions--tobacco control, salt reduction, improved diets and physical activity, reduction in hazardous alcohol intake, and essential drugs and technologies. The priority interventions were chosen for their health effects, cost-effectiveness, low costs of implementation, and political and financial feasibility. The most urgent and immediate priority is tobacco control. We propose as a goal for 2040, a world essentially free from tobacco where less than 5% of people use tobacco. Implementation of the priority interventions, at an estimated global commitment of about US$9 billion per year, will bring enormous benefits to social and economic development and to the health sector. If widely adopted, these interventions will achieve the global goal of reducing NCD death rates by 2% per year, averting tens of millions of premature deaths in this decade.     

Stilbenoids from Gnetum macrostachyum Attenuate Human Platelet Aggregation and Adhesion

Platelets play a critical role in pathogenesis of cardiovascular disorders and strokes. The inhibition of platelet function is beneficial for the treatment and prevention of these diseases. The phytochemical investigation of stilbenoids from Gnetum macrostachyum Hook. f. led to the isolation of trans‐resveratrol (1), isorhapotigenin (2), gnetol (3), bisisorhapontigenin B (4), gnetin C (5), parvifolol A (6), latifolol (7) and gnetuhainin C (8). The isolated stilbenoids were evaluated for in vitro antiplatelet activities via agonist‐induced platelet aggregation and static platelet‐collagen adhesion assays using washed human platelets. Compounds 1, 2 and 3 were active in the inhibition of arachidonic acid (AA)‐induced platelet aggregation. Compound 2 and its dimer, compound 4, were the most active stilbenoids in thrombin‐induced platelet aggregation. Moreover, compounds 4, 5 and 6, tended to be more potent than monomeric and trimeric stilbenoids in a human platelet‐collagen adhesion assay under static conditions. This is the first report of the antiplatelet activity of stilbenoids isolated from G. macrostachyum. Copyright © 2012 John Wiley & Sons, Ltd.     

Follicular carcinoma of thyroid following successful liver transplantation – A report

Dantuluri S, Urs A, Karthik SV. Follicular carcinoma of thyroid following successful liver transplantation – A report. Abstract: Follicular carcinoma of the thyroid is a relatively rare malignancy in childhood even in paediatric solid organ transplant recipients. The risk of developing de novo malignancies after liver transplantation is higher compared to the general population. We report an 18‐yr‐old girl who had successfully undergone liver transplantation five yr earlier for neonatal sclerosing cholangitis complicated by the development of dysplastic nodules. Baseline immunosuppression was with tacrolimus and prednisolone. Mycophenolate mofetil was later added in view of steroid‐resistant episodes of graft rejection. She subsequently suffered from marked obesity and essential hypertension needing antihypertensive medication. Five yr after liver transplantation, she presented with a right‐sided thyroid swelling that was rapidly progressive with no associated lymphadenopathy and normal systemic examination. Ultrasound of her neck revealed a solid lesion in the right lobe of the thyroid gland with ill‐defined margins, and a diagnostic right thyroid lobectomy confirmed the diagnosis of follicular carcinoma with focal capsular and vascular invasion. She underwent total thyroidectomy and currently remains well on thyroxine supplements. Our report highlights the need for high level of suspicion and prompt investigation into any abnormal lesion in the long‐term follow‐up of solid organ transplant recipients.     

In vivo depletion of CD11c+ dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens

Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections. Here, we report a novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo. We show that in vivo DC are required to cross-prime CTL precursors. Our results thus define a unique in vivo role of DC, i.e., the sensitization of the immune system for cell-associated antigens. DC-depleted mice fail to mount CTL responses to infection with the intracellular bacterium Listeria monocytogenes and the rodent malaria parasite Plasmodium yoelii.     

Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample

Several prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European-American families (n = 62, 37%), but a substantial proportion were African-American kindreds (n = 60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the 13q32 region were genotyped and the data analyzed using semi-parametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z-score of 2.57; P = 0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cM of the peak reported by Brzustowicz et al. [1999: Am J Hum Genet 65:1096-1103].     

Group A rotavirus-associated diarrhea in children seeking treatment in Indonesia

BACKGROUND: Globally, group A rotavirus causes significant morbidity and mortality among children. Limited data exist on the epidemiology of rotavirus disease among Indonesian children. OBJECTIVES: We describe the epidemiology of rotavirus-associated diarrhea among Indonesian children <6 years of age, including clinical symptoms and genotypes. STUDY DESIGN: We conducted a hospital-based, case series study at four referral hospitals between February 2004 and February 2005 among children with diarrhea. Rotavirus positivity was defined by a positive result from either EIA or RT-PCR. A semi-nested RT-PCR was used to determine specific rotavirus genotypes. RESULTS: 1660 stools were tested for pathogens. The overall rotavirus prevalence was 45.5%. Children with rotavirus-associated diarrhea were significantly younger (p<0.0001) and more likely to be hospitalized (81.3% versus 72.2%; p<0.0001). Symptoms associated with rotavirus included, vomiting, fever, nausea, fatigue and dehydration, while bloody stool was significantly less common with rotavirus-associated diarrhea. CONCLUSION: Rotavirus was an important contributor of morbidity to our study sample. Rotavirus genotyping demonstrated a temporal shift from G1-G4 to G9, but this was highly associated with the P[8] gene, suggesting that a multivalent rotavirus vaccine, incorporating G9 P[8] antigen, may reduce the burden of diarrheal illnesses among Indonesian children.