Mpox (Formally Known as Monkeypox)

Mpox originates from the Mpox virus, which belongs to the Orthopoxvirus genus of the Poxviridae family.1, 2, 3 Other Orthopoxvirus species include the variola virus (the now eradicated smallpox virus), vaccinia virus (a virus used in the creation of the smallpox vaccine), and cowpox virus.1, 2, 3 The identified clades consist of the West African clade and the Congo Basin clade, each with varying fatality rates of 1% and 10%, respectively.1, 2, 3, 4 Since the eradication of smallpox in 1980, the Mpox virus has emerged as the most relevant Orthopoxvirus infection in humans

Lipid-DNAs as Solubilizers of mTHPC

Hydrophobic drug candidates require innovative formulation agents. We designed and synthesized lipidDNA polymers containing varying numbers of hydrophobic alkyl chains. The hydrophobicity of these amphiphiles is easily tunable by introducing a defined number of alkyl chain-modified nucleotides during standard solid-phase synthesis of DNA using an automated DNA synthesizer. We observed that the resulting self-assembled micelles solubilize the poorly water-soluble drug, meta-tetra-hydroxyphenyl-chlorin (mTHPC) used in photodynamic therapy (PDT) with high loading concentrations and loading capacities. A cell viability study showed that mTHPCloaded micelles exhibit good biocompatibility without irradiation, and high PDT efficacy upon irradiation. LipidDNAs provide a novel class of drug-delivery vehicle, and hybridization of DNA offers a potentially facile route for further functionalization of the drug-delivery system with, for instance, targeting or imaging moieties

Benzodiazepine Use and Misuse Among Patients in a Methadone Program

<p>Abstract</p> <p>Background</p> <p>Benzodiazepines (BZD) misuse is a serious public health problem, especially among opiate-dependent patients with anxiety enrolled in methadone program because it puts patients at higher risk of life-threatening multiple drug overdoses. Both elevated anxiety and BZD misuse increase the risk for ex-addicts to relapse. However, there is no recent study to assess how serious the problem is and what factors are associated with BZD misuse. This study estimates the prevalence of BZD misuse in a methadone program, and provides information on the characteristics of BZD users compared to non-users.</p> <p>Methods</p> <p>An anonymous survey was carried out at a methadone program in Baltimore, MD, and all patients were invited to participate through group meetings and fliers around the clinic on a voluntary basis. Of the 205 returned questionnaires, 194 were complete and entered into final data analysis. Those who completed the questionnaire were offered a $5 gift card as an appreciation.</p> <p>Results</p> <p>47% of the respondents had a history of BZD use, and 39.8% used BZD without a prescription. Half of the BZD users (54%) started using BZD after entering the methadone program, and 61% of previous BZD users reported increased or resumed use after entering methadone program. Compared to the non-users, BZD users were more likely to be White, have prescribed medication for mental problems, have preexistent anxiety problems before opiate use, and had anxiety problems before entering methadone program. They reported more mental health problems in the past month, and had higher scores in anxiety state, depression and perceived stress (p < .05).</p> <p>Conclusions</p> <p>Important information on epidemiology of BZD misuse among methadone-maintenance patients suggests that most methadone programs do not address co-occurring anxiety problems, and methadone treatment may trigger onset or worsening of BZD misuse. Further study is needed to explore how to curb misuse and abuse of BZD in the addiction population, and provide effective treatments targeting simultaneously addiction symptoms, anxiety disorders and BZD misuse.</p

Working in the Public Interest Law Conference

Entirely student organized, WIPI seeks to bring together eminent practitioners in their respective fields, students, and faculty to discuss practical approaches to lawyering which can best serve the poor. Practical methods of challenging poverty are often not covered in traditional law school courses. This conference seeks to remedy that and provide dynamic, creative ways to combat poverty through the vehicle of the law

Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study

Background: The Global Enteric Multicenter Study (GEMS) was a 3-year case-control study that measured the burden, aetiology, and consequences of moderate-to-severe diarrhoea (MSD) in children aged 0–59 months. GEMS-1A, a 12-month follow-on study, comprised two parallel case-control studies, one assessing MSD and the other less-severe diarrhoea (LSD). In this report, we analyse the risk of death with each diarrhoea type and the specific pathogens associated with fatal outcomes. Methods: GEMS was a prospective, age-stratified, matched case-control study done at seven sites in Africa and Asia. Children aged 0–59 months with MSD seeking care at sentinel health centres were recruited along with one to three randomly selected matched community control children without diarrhoea. In the 12-month GEMS-1A follow-on study, children with LSD and matched controls, in addition to children with MSD and matched controls, were recruited at six of the seven sites; only cases of MSD and controls were enrolled at the seventh site. We compared risk of death during the period between enrolment and one follow-up household visit done about 60 days later (range 50–90 days) in children with MSD and LSD and in their respective controls. Approximately 50 pathogens were detected using, as appropriate, classic bacteriology, immunoassays, gel-based PCR and reverse transcriptase PCR, and quantitative real-time PCR (qPCR). Specimens from a subset of GEMS cases and controls were also tested by a TaqMan Array Card that compartmentalised probe-based qPCR for 32 enteropathogens. Findings: 223 (2·0%) of 11 108 children with MSD and 43 (0·3%) of 16369 matched controls died between study enrolment and the follow-up visit at about 60 days (hazard ratio [HR] 8·16, 95% CI 5·69–11·68, p<0·0001). 12 (0·4%) of 2962 children with LSD and seven (0·2%) of 4074 matched controls died during the follow-up period (HR 2·78, 95% CI 0·95–8·11, p=0·061). Risk of death was lower in children with dysenteric MSD than in children with nondysenteric MSD (HR 0·20, 95% CI 0·05–0·87, p=0·032), and lower in children with LSD than in those with nondysenteric MSD (HR 0·29, 0·14–0·59, p=0·0006). In children younger than 24 months with MSD, infection with typical enteropathogenic Escherichia coli, enterotoxigenic E coli encoding heat-stable toxin, enteroaggregative E coli, Shigella spp (non-dysentery cases), Aeromonas spp, Cryptosporidium spp, and Entamoeba histolytica increased risk of death. Of 61 deaths in children aged 12–59 months with non-dysenteric MSD, 31 occurred among 942 children qPCRpositive for Shigella spp and 30 deaths occurred in 1384 qPCR-negative children (HR 2·2, 95% CI 1·2–3·9, p=0·0090), showing that Shigella was strongly associated with increased risk of death. Interpretation: Risk of death is increased following MSD and, to a lesser extent, LSD. Considering there are approximately three times more cases of LSD than MSD in the population, more deaths are expected among children with LSD than in those with MSD. Because the major attributable LSD-associated and MSD-associated pathogens are the same, implementing vaccines and rapid diagnosis and treatment interventions against these major pathogens are rational investments

The Deep X-ray Radio Blazar Survey (DXRBS). I. Methods and First Results

We have undertaken a survey of archived, pointed ROSAT PSPC data for blazars by correlating the ROSAT WGACAT database with several publicly available radio catalogs, restricting our candidate list to serendipitous flat radio spectrum sources (alpha_r <= 0.70). Here we discuss our survey methods, identification procedure and first results. Our survey is found to be ~ 95% efficient at finding flat-spectrum radio-loud quasars (FSRQs, 59 of our first 85 IDs) and BL Lacertae objects (22 of our first 85 IDs), a figure which is comparable to or greater than that achieved by other radio and X-ray survey techniques. The identifications presented here show that all previous samples of blazars (even when taken together) did not representatively survey the blazar population, missing critical regions of (L_X,L_R) parameter space within which large fractions of the blazar population lie. Particularly important is the identification of a large population of FSRQs (>~ 25% of DXRBS FSRQs) with ratios of X-ray to radio luminosity >~ 10^-6 (alpha_rx <~ 0.78). In addition, due to our greater sensitivity, DXRBS has already more than doubled the number of FSRQs in complete samples with 5 GHz (radio) luminosities between 10^31.5 and 10^33.5 erg/s/Hz and fills in the region of parameter space between X-ray selected and radio-selected samples of BL Lacs. DXRBS is the very first sample to contain statistically significant numbers of blazars at low luminosities, approaching what should be the lower end of the FSRQ luminosity function.Comment: 34 pages, 7 figures, 6 tables, LaTeX file, uses aaspp4.sty. To appear in the Astronomical Journa

The Burden of Cryptosporidium Diarrheal Disease among Children < 24 Months of Age in Moderate/High Mortality Regions of Sub-Saharan Africa and South Asia, Utilizing Data from the Global Enteric Multicenter Study (GEMS).

Background: The importance of Cryptosporidium as a pediatric enteropathogen in developing countries is recognized. Methods: Data from the Global Enteric Multicenter Study (GEMS), a 3-year, 7-site, case-control study of moderate-to-severe diarrhea (MSD) and GEMS-1A (1-year study of MSD and less-severe diarrhea [LSD]) were analyzed. Stools from 12,110 MSD and 3,174 LSD cases among children aged <60 months and from 21,527 randomly-selected controls matched by age, sex and community were immunoassay-tested for Cryptosporidium. Species of a subset of Cryptosporidium-positive specimens were identified by PCR; GP60 sequencing identified anthroponotic C. parvum. Combined annual Cryptosporidium-attributable diarrhea incidences among children aged <24 months for African and Asian GEMS sites were extrapolated to sub-Saharan Africa and South Asian regions to estimate region-wide MSD and LSD burdens. Attributable and excess mortality due to Cryptosporidium diarrhea were estimated. Findings: Cryptosporidium was significantly associated with MSD and LSD below age 24 months. Among Cryptosporidium-positive MSD cases, C. hominis was detected in 77.8% (95% CI, 73.0%-81.9%) and C. parvum in 9.9% (95% CI, 7.1%-13.6%); 92% of C. parvum tested were anthroponotic genotypes. Annual Cryptosporidium-attributable MSD incidence was 3.48 (95% CI, 2.27–4.67) and 3.18 (95% CI, 1.85–4.52) per 100 child-years in African and Asian infants, respectively, and 1.41 (95% CI, 0.73–2.08) and 1.36 (95% CI, 0.66–2.05) per 100 child-years in toddlers. Corresponding Cryptosporidium-attributable LSD incidences per 100 child-years were 2.52 (95% CI, 0.33–5.01) and 4.88 (95% CI, 0.82–8.92) in infants and 4.04 (95% CI, 0.56–7.51) and 4.71 (95% CI, 0.24–9.18) in toddlers. We estimate 2.9 and 4.7 million Cryptosporidium-attributable cases annually in children aged <24 months in the sub-Saharan Africa and India/Pakistan/Bangladesh/Nepal/Afghanistan regions, respectively, and ~202,000 Cryptosporidium-attributable deaths (regions combined). ~59,000 excess deaths occurred among Cryptosporidium-attributable diarrhea cases over expected if cases had been Cryptosporidium-negative. Conclusions: The enormous African/Asian Cryptosporidium disease burden warrants investments to develop vaccines, diagnostics and therapies

Interactions between the adducin 2 gene and antihypertensive drug therapies in determining blood pressure in people with hypertension

<p>Abstract</p> <p>Background</p> <p>As part of the NHLBI Family Blood Pressure Program, the Genetic Epidemiology Network of Arteriopathy (GENOA) recruited 575 sibships (n = 1583 individuals) from Rochester, MN who had at least two hypertensive siblings diagnosed before age 60. Linkage analysis identified a region on chromosome 2 that was investigated using 70 single nucleotide polymorphisms (SNPs) typed in 7 positional candidate genes, including adducin 2 (<it>ADD2</it>).</p> <p>Method</p> <p>To investigate whether blood pressure (BP) levels in these hypertensives (n = 1133) were influenced by gene-by-drug interactions, we used cross-validation statistical methods (i.e., estimating a model for predicting BP levels in one subgroup and testing it in a different subgroup). These methods greatly reduced the chance of false positive findings.</p> <p>Results</p> <p>Eight SNPs in <it>ADD2 </it>were significantly associated with systolic BP in untreated hypertensives (p-value < 0.05). Moreover, we also identified SNPs associated with gene-by-drug interactions on systolic BP in drug-treated hypertensives. The TT genotype at SNP rs1541582 was associated with an average systolic BP of 133 mmHg in the beta-blocker subgroup and 148 mmHg in the diuretic subgroup after adjusting for overall mean differences among drug classes.</p> <p>Conclusion</p> <p>Our findings suggest that hypertension candidate gene variation may influence BP responses to specific antihypertensive drug therapies and measurement of genetic variation may assist in identifying subgroups of hypertensive patients who will benefit most from particular antihypertensive drug therapies.</p

The InterLACE study: design, data harmonization and characteristics across 20 studies on women's health

The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women's reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE

A quality metric for homology modeling: the H-factor

<p>Abstract</p> <p>Background</p> <p>The analysis of protein structures provides fundamental insight into most biochemical functions and consequently into the cause and possible treatment of diseases. As the structures of most known proteins cannot be solved experimentally for technical or sometimes simply for time constraints, <it>in silico </it>protein structure prediction is expected to step in and generate a more complete picture of the protein structure universe. Molecular modeling of protein structures is a fast growing field and tremendous works have been done since the publication of the very first model. The growth of modeling techniques and more specifically of those that rely on the existing experimental knowledge of protein structures is intimately linked to the developments of high resolution, experimental techniques such as NMR, X-ray crystallography and electron microscopy. This strong connection between experimental and <it>in silico </it>methods is however not devoid of criticisms and concerns among modelers as well as among experimentalists.</p> <p>Results</p> <p>In this paper, we focus on homology-modeling and more specifically, we review how it is perceived by the structural biology community and what can be done to impress on the experimentalists that it can be a valuable resource to them. We review the common practices and provide a set of guidelines for building better models. For that purpose, we introduce the H-factor, a new indicator for assessing the quality of homology models, mimicking the R-factor in X-ray crystallography. The methods for computing the H-factor is fully described and validated on a series of test cases.</p> <p>Conclusions</p> <p>We have developed a web service for computing the H-factor for models of a protein structure. This service is freely accessible at <url>http://koehllab.genomecenter.ucdavis.edu/toolkit/h-factor</url>.</p