The catch 22 of condoms in US correctional facilities

<p>Abstract</p> <p>Background</p> <p>Despite the high prevalence of sexually transmitted infections (STIs) and HIV infection in US correctional settings, most jails and prisons in the United States prevent inmates from using condoms to prevent STIs/HIV.</p> <p>Discussion</p> <p>This article makes the following arguments to justify a scalable and feasible next step in the prevention of HIV/STIs among inmates: condoms are a basic and essential part of HIV/STI prevention, HIV/STI transmission occurs in the context of corrections, and several model programs show the feasibility of condom distribution in prisons. A lower end estimate for HIV incidence among incarcerated applied to 2,000,000 new inmates annually results in thousands of new HIV infections acquired each year in corrections that could be prevented with condoms in corrections facilities. Programs from parts of the United States, Canada, and much of Europe show how programs distributing condoms in correctional facilities can be safe and effective.</p> <p>Summary</p> <p>Public health and corrections officials must work together to ensure that condoms and broader sexual disease prevention programs are integrated into US jail and prison health systems.</p

Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

Impact of RNA degradation on gene expression profiling

<p>Abstract</p> <p>Background</p> <p>Gene expression profiling is a highly sensitive technique which is used for profiling tumor samples for medical prognosis. RNA quality and degradation influence the analysis results of gene expression profiles. The impact of this influence on the profiles and its medical impact is not fully understood. As patient samples are very valuable for clinical studies, it is necessary to establish criteria for the RNA quality to be able to use these samples in later analysis.</p> <p>Methods</p> <p>To investigate the effects of RNA integrity on gene expression profiling, whole genome expression arrays were used. We used tumor biopsies from patients diagnosed with locally advanced rectal cancer. To simulate degradation, the isolated total RNA of all patients was subjected to heat-induced degradation in a time-dependent manner. Expression profiling was then performed and data were analyzed bioinformatically to assess the differences.</p> <p>Results</p> <p>The differences introduced by RNA degradation were largely outweighed by the biological differences between the patients. Only a relatively small number of probes (275 out of 41,000) show a significant effect due to degradation. The genes that show the strongest effect due to RNA degradation were, especially, those with short mRNAs and probe positions near the 5' end.</p> <p>Conclusions</p> <p>Degraded RNA from tumor samples (RIN > 5) can still be used to perform gene expression analysis. A much higher biological variance between patients is observed compared to the effect that is imposed by degradation of RNA. Nevertheless there are genes, very short ones and those with the probe binding side close to the 5' end that should be excluded from gene expression analysis when working with degraded RNA. These results are limited to the Agilent 44 k microarray platform and should be carefully interpreted when transferring to other settings.</p

Structural Dynamic of a Self-Assembling Peptide d-EAK16 Made of Only D-Amino Acids

We here report systematic study of structural dynamics of a 16-residue self-assembling peptide d-EAK16 made of only D-amino acids. We compare these results with its chiral counterpart L-form, l-EAK16. Circular dichroism was used to follow the structural dynamics under various temperature and pH conditions. At 25°C the d-EAK16 peptide displayed a typical beta-sheet spectrum. Upon increasing the temperature above 70°C, there was a spectrum shift as the 218 nm valley widens toward 210 nm. Above 80°C, the d-EAK16 peptide transformed into a typical alpha-helix CD spectrum without going through a detectable random-coil intermediate. When increasing the temperature from 4°C to 110°C then cooling back from 110°C to 4°C, there was a hysteresis: the secondary structure from beta-sheet to alpha-helix and then from alpha-helix to beta-sheet occurred. d-EAK16 formed an alpha-helical conformation at pH0.76 and pH12 but formed a beta-sheet at neutral pH. The effects of various pH conditions, ionic strength and denaturing agents were also noted. Since D-form peptides are resistant to natural enzyme degradation, such drastic structural changes may be exploited for fabricating molecular sensors to detect minute environmental changes. This provides insight into the behaviors of self-assembling peptides made of D-amino acids and points the way to designing new peptide materials for biomedical engineering and nanobiotechnology

Laparoscopic versus conventional appendectomy - a meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Although laparoscopic surgery has been available for a long time and laparoscopic cholecystectomy has been performed universally, it is still not clear whether open appendectomy (OA) or laparoscopic appendectomy (LA) is the most appropriate surgical approach to acute appendicitis. The purpose of this work is to compare the therapeutic effects and safety of laparoscopic and conventional "open" appendectomy by means of a meta-analysis.</p> <p>Methods</p> <p>A meta-analysis was performed of all randomized controlled trials published in English that compared LA and OA in adults and children between 1990 and 2009. Calculations were made of the effect sizes of: operating time, postoperative length of hospital stay, postoperative pain, return to normal activity, resumption of diet, complications rates, and conversion to open surgery. The effect sizes were then pooled by a fixed or random-effects model.</p> <p>Results</p> <p>Forty-four randomized controlled trials with 5292 patients were included in the meta-analysis. Operating time was 12.35 min longer for LA (95% CI: 7.99 to 16.72, p < 0.00001). Hospital stay after LA was 0.60 days shorter (95% CI: -0.85 to -0.36, p < 0.00001). Patients returned to their normal activity 4.52 days earlier after LA (95% CI: -5.95 to -3.10, p < 0.00001), and resumed their diet 0.34 days earlier(95% CI: -0.46 to -0.21, p < 0.00001). Pain after LA on the first postoperative day was significantly less (p = 0.008). The overall conversion rate from LA to OA was 9.51%. With regard to the rate of complications, wound infection after LA was definitely reduced (OR = 0.45, 95% CI: 0.34 to 0.59, p < 0.00001), while postoperative ileus was not significantly reduced(OR = 0.91, 95% CI: 0.57 to 1.47, p = 0.71). However, intra-abdominal abscess (IAA), intraoperative bleeding and urinary tract infection (UIT) after LA, occurred slightly more frequently(OR = 1.56, 95% CI: 1.01 to 2.43, p = 0.05; OR = 1.56, 95% CI: 0.54 to 4.48, p = 0.41; OR = 1.76, 95% CI: 0.58 to 5.29, p = 0.32).</p> <p>Conclusion</p> <p>LA provides considerable benefits over OA, including a shorter length of hospital stay, less postoperative pain, earlier postoperative recovery, and a lower complication rate. Furthermore, over the study period it was obvious that there had been a trend toward fewer differences in operating time for the two procedures. Although LA was associated with a slight increase in the incidence of IAA, intraoperative bleeding and UIT, it is a safe procedure. It may be that the widespread use of LA is due to its better therapeutic effect.</p

Five endometrial cancer risk loci identified through genome-wide association analysis.

We conducted a meta-analysis of three endometrial cancer genome-wide association studies (GWAS) and two follow-up phases totaling 7,737 endometrial cancer cases and 37,144 controls of European ancestry. Genome-wide imputation and meta-analysis identified five new risk loci of genome-wide significance at likely regulatory regions on chromosomes 13q22.1 (rs11841589, near KLF5), 6q22.31 (rs13328298, in LOC643623 and near HEY2 and NCOA7), 8q24.21 (rs4733613, telomeric to MYC), 15q15.1 (rs937213, in EIF2AK4, near BMF) and 14q32.33 (rs2498796, in AKT1, near SIVA1). We also found a second independent 8q24.21 signal (rs17232730). Functional studies of the 13q22.1 locus showed that rs9600103 (pairwise r(2) = 0.98 with rs11841589) is located in a region of active chromatin that interacts with the KLF5 promoter region. The rs9600103[T] allele that is protective in endometrial cancer suppressed gene expression in vitro, suggesting that regulation of the expression of KLF5, a gene linked to uterine development, is implicated in tumorigenesis. These findings provide enhanced insight into the genetic and biological basis of endometrial cancer.I.T. is supported by Cancer Research UK and the Oxford Comprehensive Biomedical Research Centre. T.H.T.C. is supported by the Rhodes Trust and the Nuffield Department of Medicine. Funding for iCOGS infrastructure came from the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692 and C8197/A16565), the US National Institutes of Health (R01 CA128978, U19 CA148537, U19 CA148065 and U19 CA148112), the US Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Susan G. Komen Foundation for the Cure, the Breast Cancer Research Foundation and the Ovarian Cancer Research Fund. SEARCH recruitment was funded by a programme grant from Cancer Research UK (C490/A10124). Stage 1 and stage 2 case genotyping was supported by the NHMRC (552402 and 1031333). Control data were generated by the WTCCC, and a full list of the investigators who contributed to the generation of the data is available from the WTCCC website. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by UK Medical Research Council grant G0000934 and Wellcome Trust grant 068545/Z/02; funding for this project was provided by the Wellcome Trust under award 085475. NSECG was supported by the European Union's Framework Programme 7 CHIBCHA grant and Wellcome Trust Centre for Human Genetics Core Grant 090532/Z/09Z, and CORGI was funded by Cancer Research UK. BCAC is funded by Cancer Research UK (C1287/A10118 and C1287/A12014). OCAC is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07) and the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.356