The High Burden of Cholera in Children: Comparison of Incidence from Endemic Areas in Asia and Africa

Cholera is an often forgotten disease affecting the world's forgotten people. When a large cholera outbreak occurs, the disease appears briefly on the radar of public attention. Some unfortunate populations around the world suffer recurrent episodes of cholera but their plight goes unnoticed. We established cholera surveillance in impoverished areas in Jakarta (Indonesia), Kolkata (India), and Beira (Mozambique) where the disease is known to occur regularly. The cholera burden was calculated using the site population as the denominator and the number of cholera cases as the numerator. The lowest overall rate was in Jakarta with 0.5 cases per 1000 population per year. The incidence was three times higher in Kolkata (1.6/1000/year) and eight times higher in Beira (4.0/1000/year), adding to the growing impression of the large cholera problem in Africa. In all sites, children are the most affected. Estimates such as these are useful when considering where and among whom interventions against the disease are most needed. Improvement of water supply and sanitation is the best strategy against cholera and other diarrheal diseases but may not be achievable in these impoverished areas in the near future. Other immediate, short- to medium-term strategies such as vaccination against cholera may be useful

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Inducible Ablation of Melanopsin-Expressing Retinal Ganglion Cells Reveals Their Central Role in Non-Image Forming Visual Responses

Rod/cone photoreceptors of the outer retina and the melanopsin-expressing retinal ganglion cells (mRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light, the pupillary light reflex (PLR), and light modulation of activity. Targeted deletion of the melanopsin gene attenuates these adaptive responses with no apparent change in the development and morphology of the mRGCs. Comprehensive identification of mRGCs and knowledge of their specific roles in image-forming and non-image forming photoresponses are currently lacking. We used a Cre-dependent GFP expression strategy in mice to genetically label the mRGCs. This revealed that only a subset of mRGCs express enough immunocytochemically detectable levels of melanopsin. We also used a Cre-inducible diphtheria toxin receptor (iDTR) expression approach to express the DTR in mRGCs. mRGCs develop normally, but can be acutely ablated upon diphtheria toxin administration. The mRGC-ablated mice exhibited normal outer retinal function. However, they completely lacked non-image forming visual responses such as circadian photoentrainment, light modulation of activity, and PLR. These results point to the mRGCs as the site of functional integration of the rod/cone and melanopsin phototransduction pathways and as the primary anatomical site for the divergence of image-forming and non-image forming photoresponses in mammals

Twenty Years of SUGRA

A brief review is given of the developments of mSUGRA and its extensions since the formulation of these models in 1982. Future directions and prospects are also discussed.Comment: Invited talk at the International Conference BEYOND-2003, Schloss Ringberg, Germany, June 10-14, 2003; 21 pages, Late

Pulmonary tuberculosis among people living with HIV/AIDS attending care and treatment in rural northern Tanzania

Tuberculosis is the commonest opportunistic infection and the number one cause of death in HIV/AIDS patients in developing countries. To address the extent of the tuberculosis HIV coinfection in rural Tanzania we conducted a cross sectional study including HIV/AIDS patients attending care and treatment clinic from September 2006 to March 2007. Sputum samples were collected for microscopy, culture and drug susceptibility testing. Chest X-ray was done for those patients who consented. Blood samples were collected for CD4+ T cells count. The prevalence of tuberculosis was 20/233 (8.5%). Twenty (8.5%) sputum samples were culture positive. Eight of the culture positive samples (40%) were smear positive. Fifteen (75%) of these patients neither had clinical symptoms nor chest X-ray findings suggestive of tuberculosis. Nineteen isolates (95%) were susceptible to rifampicin, isoniazid, streptomycin and ethambutol (the first line tuberculosis drugs). One isolate (5%) from HIV/tuberculosis coinfected patients was resistant to isoniazid. No cases of multi- drug resistant tuberculosis were identified. We found high prevalence of tuberculosis disease in this setting. Chest radiograph suggestive of tuberculosis and clinical symptoms of fever and cough were uncommon findings in HIV/tuberculosis coinfected patients. Tuberculosis can occur at any stage of CD4+T cells depletion

Holographic Vitrification

We establish the existence of stable and metastable stationary black hole bound states at finite temperature and chemical potentials in global and planar four-dimensional asymptotically anti-de Sitter space. We determine a number of features of their holographic duals and argue they represent structural glasses. We map out their thermodynamic landscape in the probe approximation, and show their relaxation dynamics exhibits logarithmic aging, with aging rates determined by the distribution of barriers.Comment: 100 pages, 25 figure

Potential Molecular Mechanisms of Rare Anti-Tumor Immune Response by SARS-CoV-2 in Isolated Cases of Lymphomas

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex component 3 (GCP3) at its tubulin gamma-1 chain (TUBG1) binding site. (iii) The M protein may also interact with TUBG1, blocking its binding to GCP3. (iv) Both the M and ORF3a proteins may render the GCP2-GCP3 lateral binding where the M protein possibly interacts with GCP2 at its GCP3 binding site and the ORF3a protein to GCP3 at its GCP2 interacting residues. (v) Interactions of the M and ORF3a proteins with these gamma-tubulin ring complex components potentially block the initial process of microtubule nucleation, leading to cell-cycle arrest and apoptosis. (vi) The Spike-RBD may also interact with and block PD-1 signaling similar to pembrolizumab and nivolumab- like monoclonal antibodies and may induce B-cell apoptosis and remission. (vii) Finally, the TRADD interacting “PVQLSY” motif of Epstein-Barr virus LMP-1, that is responsible for NF-kB mediated oncogenesis, potentially interacts with SARS-CoV-2 M(pro), NSP7, NSP10, and spike (S) proteins, and may inhibit the LMP-1 mediated cell proliferation. Taken together, our results suggest a possible therapeutic potential of SARS-CoV-2 in lymphoproliferative disorders

Does vancomycin prescribing intervention affect vancomycin-resistant enterococcus infection and colonization in hospitals? A systematic review

BACKGROUND: Vancomycin resistant enterococcus (VRE) is a major cause of nosocomial infections in the United States and may be associated with greater morbidity, mortality, and healthcare costs than vancomycin-susceptible enterococcus. Current guidelines for the control of VRE include prudent use of vancomycin. While vancomycin exposure appears to be a risk factor for VRE acquisition in individual patients, the effect of vancomycin usage at the population level is not known. We conducted a systematic review to determine the impact of reducing vancomycin use through prescribing interventions on the prevalence and incidence of VRE colonization and infection in hospitals within the United States. METHODS: To identify relevant studies, we searched three electronic databases, and hand searched selected journals. Thirteen studies from 12 articles met our inclusion criteria. Data were extracted and summarized for study setting, design, patient characteristics, types of intervention(s), and outcome measures. The relative risk, 95% confidence interval, and p-value associated with change in VRE acquisition pre- and post-vancomycin prescription interventions were calculated and compared. Heterogeneity in study results was formally explored by stratified analysis. RESULTS: No randomized clinical trials on this topic were found. Each of the 13 included studies used a quasi-experimental design of low hierarchy. Seven of the 13 studies reported statistically significant reductions in VRE acquisition following interventions, three studies reported no significant change, and three studies reported increases in VRE acquisition, one of which reported statistical significance. Results ranged from a reduction of 82.5% to an increase of 475%. Studies of specific wards, which included sicker patients, were more likely to report positive results than studies of an entire hospital including general inpatients (Fisher's exact test 0.029). The type of intervention, endemicity status, type of study design, and the duration of intervention were not found to significantly modify the results. Among the six studies that implemented vancomycin reduction strategies as the sole intervention, two of six (33%) found a significant reduction in VRE colonization and/or infection. In contrast, among studies implementing additional VRE control measures, five of seven (71%) reported a significant reduction. CONCLUSION: It was not possible to conclusively determine a potential role for vancomycin usage reductions in controlling VRE colonization and infection in hospitals in the United States. The effectiveness of such interventions and their sustainability remains poorly defined because of the heterogeneity and quality of studies. Future research using high-quality study designs and implementing vancomycin as the sole intervention are needed to answer this question