Performance and costs of a rapid syphilis test in an urban population at high risk for sexually transmitted infections

Introduction. Rapid syphilis screening could facilitate caseidentification in populations at high risk for sexually transmitted infections (STI). The aim of this study was to compare the performance and the cost-effectiveness of a rapid immunochromatography syphilis test with a traditional ELISA screening test in patients with suspected infectious syphilis or patients at high risk for STI/syphilis. Methods. Consecutive patients attending a STI clinic cosensually underwent serological testing with two different tests. Sensitivity, specificity, Positive Predictive Values, Negative Predictive Values and effectiveness of the two tests were evaluated with respect to definitive diagnosis. Results. In our population, the immunochromatography essay (Abbott Determine Syphilis TP) had a sensitivity of 95.0% (95% CI 88.7-97.8) and a specificity of 97.7% (95% CI 94.7-99.0). The ELISA test had a sensitivity of 95.0% (95% CI 88.8-97.9) and a specificity of 97.2% (95% CI 94.1-98.7). The Positive Predictive Value for ELISA was 94.1% (95% CI 87.6-97.3) and 95.0% (95% CI 88.7-97.8) for the rapid test. The Negative Predictive Value was 97.7% (95% CI 94.7-99) for both ELISA and the rapid tests. The cost-effectiveness analysis showed that the rapid test was less expensive than ELISA (? 26.46 vs ? 40.57) and yielded a similar number of right diagnoses. Conclusions. The Abbott Determine Syphilis TP test is an accurate, easy and inexpensive test that could facilitate the rapid detection of syphilis in high-risk urban patients

Low back pain around retirement age and physical occupational exposure during working life

<p>Abstract</p> <p>Background</p> <p>Physical occupational exposure is a risk factor for low back pain in workers but the long term effects of exposure remain unclear. As several countries consider increasing the retirement age, further information on this topic is relevant. This study aimed to describe the prevalence of low back pain among middle aged and aging individuals in the general French population according to physical occupational exposure and retirement status.</p> <p>Methods</p> <p>The study population originated from the French national survey 'Enquête décennale santé 2002'. Low back pain for more than 30 days within the previous twelve months (LBP) was assessed using a French version of the Nordic questionnaire. Occupational exposure was self assessed. Subjects were classified as "exposed" if they were currently or had previously been exposed to handling of heavy loads and/or to tiring postures. The weighted prevalence of LBP was computed separately for men and women, for active (aged 45-59) and retiree (aged 55-74), according to 5-year age group and past/present occupational exposure.</p> <p>Results</p> <p>For active men, the prevalence of LBP was significantly higher in those currently or previously exposed (n = 1051) compared with those never exposed (n = 1183), respectively over 20% versus less than 11%. Among retired men, the prevalence of LBP tended towards equivalence with increasing age among those previously exposed (n = 748) and those unexposed (n = 599).</p> <p>Patterns were quite similar for women with a higher prevalence in exposed active women (n = 741) compared to unexposed (n = 1260): around 25% versus 15%. Similarly, differences between previously exposed (n = 430) and unexposed (n = 489) retired women tended to reduce with age.</p> <p>Conclusion</p> <p>The prevalence of LBP in active workers was associated with occupational exposure. The link with past exposure among retirees decreased with age. These results should be considered for policies dealing with prevention at the workplace and retirement.</p

Perinatal Tobacco Smoke Exposure Increases Vascular Oxidative Stress and Mitochondrial Damage in Non-Human Primates

Epidemiological studies suggest that events occurring during fetal and early childhood development influence disease susceptibility. Similarly, molecular studies in mice have shown that in utero exposure to cardiovascular disease (CVD) risk factors such as environmental tobacco smoke (ETS) increased adult atherogenic susceptibility and mitochondrial damage; however, the molecular effects of similar exposures in primates are not yet known. To determine whether perinatal ETS exposure increased mitochondrial damage, dysfunction and oxidant stress in primates, archived tissues from the non-human primate model Macaca mulatta (M. mulatta) were utilized. M. mulatta were exposed to low levels of ETS (1 mg/m3 total suspended particulates) from gestation (day 40) to early childhood (1 year), and aortic tissues were assessed for oxidized proteins (protein carbonyls), antioxidant activity (SOD), mitochondrial function (cytochrome oxidase), and mitochondrial damage (mitochondrial DNA damage). Results revealed that perinatal ETS exposure resulted in significantly increased oxidative stress, mitochondrial dysfunction and damage which were accompanied by significantly decreased mitochondrial antioxidant capacity and mitochondrial copy number in vascular tissue. Increased mitochondrial damage was also detected in buffy coat tissues in exposed M. mulatta. These studies suggest that perinatal tobacco smoke exposure increases vascular oxidative stress and mitochondrial damage in primates, potentially increasing adult disease susceptibility

Polycomb-mediated silencing in neuroendocrine prostate cancer

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PCa) for which the median survival remains less than a year. Current treatments are only palliative in nature, and the lack of suitable pre-clinical models has hampered previous efforts to develop novel therapeutic strategies. Addressing this need, we have recently established the first in vivo model of complete neuroendocrine transdifferentiation using patient-derived xenografts. Few genetic differences were observed between parental PCa and relapsed NEPC, suggesting that NEPC likely results from alterations that are epigenetic in nature. Thus, we sought to identify targetable epigenetic regulators whose expression was elevated in NEPC using genome-wide profiling of patient-derived xenografts and clinical samples. RESULTS: Our data indicate that multiple members of the polycomb group (PcG) family of transcriptional repressors were selectively upregulated in NEPC. Notably, CBX2 and EZH2 were consistently the most highly overexpressed epigenetic regulators across multiple datasets from clinical and xenograft tumor tissues. Given the striking upregulation of PcG genes and other transcriptional repressors, we derived a 185-gene list termed 'neuroendocrine-associated repression signature' (NEARS) by overlapping transcripts downregulated across multiple in vivo NEPC models. In line with the striking upregulation of PcG family members, NEARS was preferentially enriched with PcG target genes, suggesting a driving role for PcG silencing in NEPC. Importantly, NEARS was significantly associated with high-grade tumors, metastatic progression, and poor outcome in multiple clinical datasets, consistent with extensive literature linking PcG genes and aggressive disease progression. CONCLUSIONS: We have explored the epigenetic landscape of NEPC and provided evidence of increased PcG-mediated silencing associated with aberrant transcriptional regulation of key differentiation genes. Our results position CBX2 and EZH2 as potential therapeutic targets in NEPC, providing opportunities to explore novel strategies aimed at reversing epigenetic alterations driving this lethal disease

Absence of N-terminal acetyltransferase diversification during evolution of eukaryotic organisms

Protein N-terminal acetylation is an ancient and ubiquitous co-translational modification catalyzed by a highly conserved family of N-terminal acetyltransferases (NATs). Prokaryotes have at least 3 NATs, whereas humans have six distinct but highly conserved NATs, suggesting an increase in regulatory complexity of this modification during eukaryotic evolution. Despite this, and against our initial expectations, we determined that NAT diversification did not occur in the eukaryotes, as all six major human NATs were most likely present in the Last Eukaryotic Common Ancestor (LECA). Furthermore, we also observed that some NATs were actually secondarily lost during evolution of major eukaryotic lineages; therefore, the increased complexity of the higher eukaryotic proteome occurred without a concomitant diversification of NAT complexes

Ubidecarenone in the treatment of mitochondrial myopathies: A multi-center double-blind trial

Forty-four patients with mitochondrial myopathies were treated with Ubidecarenone (CoQ10) for 6 months in an open multi-center trial. No side effects of the drug were observed. Sixteen patients showing at least 25% decrease of post-exercise lactate levels were selected as responders. Responsiveness was apparently not related to CoQ10 level in serum and platelets or to the presence or absence of mtDNA deletions. The responders were treated for a further 3 months with CoQ10 or placebo in the second blind part of the trial; no significant differences were observed between the 2 groups. It is not clear why CoQ10 had therapeutic effects in some patients and not in others with the same clinical presentation and biochemical defect, and we failed to identify candidate responders before treatment. At the dose of CoQ10 used in this study (2 mg/kg/day) the therapy requires a long administration time before a response is seen. \ua9 1990