The Lsm Proteins: Ring Architectures for RNA Capture

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CpG island methylation of TMS1/ASC and CASP8 genes in cervical cancer

<p>Abstract</p> <p>Background</p> <p>Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration that serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers.</p> <p>Aims</p> <p>This study describes the methylation status of <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes in cervical cancer. We also examined the prevalence of <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes methylation in cervical cancer tissue and none - neo plastic samples in an effort to correlate with smoking habit and clinicopathological features.</p> <p>Method</p> <p>Target DNA was modified by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequently amplified by Methylation Specific (MS) PCR with primers specific for methylated versus unmethylated DNA. The PCR product was detected by gel electrophoresis and combined with the clinical records of patients.</p> <p>Results</p> <p>The methylation pattern of the <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes in specimens of cervical cancer and adjacent normal tissues were detected [5/80 (6.2%), 3/80 (3.75%)-2/80 (2.5%), 1/80 (1.2%) respectively]. No statistical differences were seen in the extent of differentiation, invasion, pathological type and smoking habit between the methylated and unmethylated tissues (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>The present study conclude that the frequency of <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes methylation in cervical cancer are rare (< 6%), and have no any critical role in development of cervical cancer.</p

Use of garenoxacin: a new generation antibiotic for surgical infections

Background: The management of skin and skin structure infections (SSSI) still continues to be global challenge. USFDA has given strong recommendation for adequate empirical antibiotic coverage to avoid further complication of the wounds. Wound complications, especially in the diabetic population, patients with low immunity remains a big challenge though other factors like site of the wound, age of the patients also play an important role.Methods: A retrospective observational study was conducted to analyze clinical utility of garenoxacin for surgical prophylaxis. A total of 100 patients, 30 patients with diabetic foot and 70 patients with post-surgical intraabdominal wounds who were prescribed garenoxacin 2×200 mg as stat dose prophylactically. Swab culture from the wound slough and drain tube samples were sent for culture/sensitivity on day 0, day 5, and day 7. Wound healing was evaluated by estimating slough discharge, size of the wound, vascularity, and overall healing. They were categorized as treatment failure group, when sough/drain-discharge reduction was ≤50%, improved if sough/drain-discharge reduction was 50-75% and cure when sough/drain-discharge reduction was 75-100%.Results: The healthy granulation tissue was observed post 7 days therapy of garenoxacin 2×200 mg in diabetic foot ulcer (DFU) patients when administered empirically before surgical debridement. In patients with post-operative infectious intraabdominal wounds, the most common isolated organisms were Enterococcus, Acinetobacter and Klebsiella. Post garenoxacin therapy used as switch therapy empirically for 5 days resulted in 100% sterile culture. While evaluating slough/drain-discharge in DFU patients, 84% patients showed cure and 16% showed improvement at the end of day 7 and in patients with post-operative infectious intra-abdominal wounds cure was observed in 86% patients showed cure and 14% patient showed improvement. No side effects were reported during the study.Conclusions: Administration of garenoxacin used as empirical therapy for surgical prophylaxis and as switch therapy in patients with DFU s and post-surgical infectious wounds for the period of 5-7 days has been found effective indicating its wide spectrum of action

Stratified glucocorticoid monotherapy is safe and effective for most cases of giant cell arteritis

Funding: We are grateful to Versus Arthritis (grant 12159) for supporting our work.Peer reviewedPublisher PD

Decoding the 5' nucleotide bias of PIWI-interacting RNAs

PIWI-interacting RNAs (piRNAs) are at the center of a small RNA-based immune system that defends genomes against the deleterious action of mobile genetic elements (transposons). PiRNAs are highly variable in sequence with extensive targeting potential. Their diversity is restricted by their preference to start with a Uridine (U) at the 5' most position (1U-bias), a bias that remains poorly understood. Here we uncover that the 1U-bias of Piwi-piRNAs is established by consecutive discrimination against all nucleotides but U, first during piRNA biogenesis and then upon interaction with Piwi's specificity loop. Sequence preferences during piRNA processing also restrict U across the piRNA body with the potential to directly impact target recognition. Overall, the uncovered signatures could modulate specificity and efficacy of piRNA-mediated transposon restriction, and provide a substrate for purifying selection in the ongoing arms race between genomes and their mobile parasites

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

A case report of vibration-induced hand comorbidities in a postwoman

<p>Abstract</p> <p>Background</p> <p>Prolonged exposure to hand-transmitted vibration is associated with an increased occurrence of symptoms and signs of disorders in the vascular, neurological and osteoarticular systems of the upper limbs. However, the available epidemiological evidence is derived from studies on high vibration levels caused by vibratory tools, whereas little is known about possible upper limb disorders caused by chronic exposure to low vibration levels emitted by fixed sources.</p> <p>Case presentation</p> <p>We present the case of a postwoman who delivered mail for 15 years using a low-powered motorcycle. The woman was in good health until 2002, when she was diagnosed with bilateral Raynaud's phenomenon. In March 2003 a bilateral carpal tunnel syndrome was electromyographically diagnosed; surgical treatment was ineffective. Further examinations in 2005 highlighted the presence of chronic tendonitis (right middle finger flexor).</p> <p>Risk assessment</p> <p>From 1987, for 15 years, our patient rode her motorcycle for 4 h/day, carrying a load of 20-30 kg. For about a quarter of the time she drove over country roads. Using the information collected about the tasks carried out every day by the postwoman and some measurements performed on both handles of the motorcycle, as well as on both iron parts of the handlebars, we reconstructed the woman's previous exposure to hand-arm vibration. 8-hour energy-equivalent frequency weighted acceleration was about 2.4 m/s². The lifetime dose was 1.5 × 10⁹(m²/s⁴)hd.</p> <p>Conclusions</p> <p>The particular set of comorbidities presented by our patient suggests a common pathophysiological basis for all the diseases. Considering the level of exposure to vibrations and the lack of specific knowledge on the effects of vibration in women, we hypothesize an association between the work exposure and the onset of the diseases.</p

Polymorphisms associated with the risk of lung cancer in a healthy Mexican Mestizo population: Application of the additive model for cancer

Lung cancer is the leading cause of cancer mortality in Mexico and worldwide. In the past decade, there has been an increase in the number of lung cancer cases in young people, which suggests an important role for genetic background in the etiology of this disease. In this study, we genetically characterized 16 polymorphisms in 12 low penetrance genes (AhR, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, GSTPI, XRCC1, ERCC2, MGMT, CCND1 and TP53) in 382 healthy Mexican Mestizos as the first step in elucidating the genetic structure of this population and identifying high risk individuals. All of the genotypes analyzed were in Hardy-Weinberg equilibrium, but different degrees of linkage were observed for polymorphisms in the CYP1A1 and EPHX1 genes. The genetic variability of this population was distributed in six clusters that were defined based on their genetic characteristics. The use of a polygenic model to assess the additive effect of low penetrance risk alleles identified combinations of risk genotypes that could be useful in predicting a predisposition to lung cancer. Estimation of the level of genetic susceptibility showed that the individual calculated risk value (iCRV) ranged from 1 to 16, with a higher iCRV indicating a greater genetic susceptibility to lung cancer

Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data

<p>Abstract</p> <p>Backgound</p> <p>The genetic mechanisms of prostate tumorigenesis remain poorly understood, but with the advent of gene expression array capabilities, we can now produce a large amount of data that can be used to explore the molecular and genetic mechanisms of prostate tumorigenesis.</p> <p>Methods</p> <p>We conducted a meta-analysis of gene expression data from 18 gene array datasets targeting transition from normal to localized prostate cancer and from localized to metastatic prostate cancer. We functionally annotated the top 500 differentially expressed genes and identified several candidate pathways associated with prostate tumorigeneses.</p> <p>Results</p> <p>We found the top differentially expressed genes to be clustered in pathways involving integrin-based cell adhesion: integrin signaling, the actin cytoskeleton, cell death, and cell motility pathways. We also found integrins themselves to be downregulated in the transition from normal prostate tissue to primary localized prostate cancer. Based on the results of this study, we developed a collagen hypothesis of prostate tumorigenesis. According to this hypothesis, the initiating event in prostate tumorigenesis is the age-related decrease in the expression of collagen genes and other genes encoding integrin ligands. This concomitant depletion of integrin ligands leads to the accumulation of ligandless integrin and activation of integrin-associated cell death. To escape integrin-associated death, cells suppress the expression of integrins, which in turn alters the actin cytoskeleton, elevates cell motility and proliferation, and disorganizes prostate histology, contributing to the histologic progression of prostate cancer and its increased metastasizing potential.</p> <p>Conclusion</p> <p>The results of this study suggest that prostate tumor progression is associated with the suppression of integrin-based cell adhesion. Suppression of integrin expression driven by integrin-mediated cell death leads to increased cell proliferation and motility and increased tumor malignancy.</p