Effects of temperature on the transmission of Yersinia Pestis by the flea, Xenopsylla Cheopis, in the late phase period

<p>Abstract</p> <p>Background</p> <p>Traditionally, efficient flea-borne transmission of <it>Yersinia pestis</it>, the causative agent of plague, was thought to be dependent on a process referred to as blockage in which biofilm-mediated growth of the bacteria physically blocks the flea gut, leading to the regurgitation of contaminated blood into the host. This process was previously shown to be temperature-regulated, with blockage failing at temperatures approaching 30°C; however, the abilities of fleas to transmit infections at different temperatures had not been adequately assessed. We infected colony-reared fleas of <it>Xenopsylla cheopis </it>with a wild type strain of <it>Y. pestis </it>and maintained them at 10, 23, 27, or 30°C. Naïve mice were exposed to groups of infected fleas beginning on day 7 post-infection (p.i.), and every 3-4 days thereafter until day 14 p.i. for fleas held at 10°C, or 28 days p.i. for fleas held at 23-30°C. Transmission was confirmed using <it>Y. pestis</it>-specific antigen or antibody detection assays on mouse tissues.</p> <p>Results</p> <p>Although no statistically significant differences in per flea transmission efficiencies were detected between 23 and 30°C, efficiencies were highest for fleas maintained at 23°C and they began to decline at 27 and 30°C by day 21 p.i. These declines coincided with declining median bacterial loads in fleas at 27 and 30°C. Survival and feeding rates of fleas also varied by temperature to suggest fleas at 27 and 30°C would be less likely to sustain transmission than fleas maintained at 23°C. Fleas held at 10°C transmitted <it>Y. pestis </it>infections, although flea survival was significantly reduced compared to that of uninfected fleas at this temperature. Median bacterial loads were significantly higher at 10°C than at the other temperatures.</p> <p>Conclusions</p> <p>Our results suggest that temperature does not significantly effect the per flea efficiency of <it>Y. pestis </it>transmission by <it>X. cheopis</it>, but that temperature is likely to influence the dynamics of <it>Y. pestis </it>flea-borne transmission, perhaps by affecting persistence of the bacteria in the flea gut or by influencing flea survival. Whether <it>Y. pestis </it>biofilm production is important for transmission at different temperatures remains unresolved, although our results support the hypothesis that blockage is not necessary for efficient transmission.</p

Genome-Wide Progesterone Receptor Binding: Cell Type-Specific and Shared Mechanisms in T47D Breast Cancer Cells and Primary Leiomyoma Cells

Progesterone, via its nuclear receptor (PR), exerts an overall tumorigenic effect on both uterine fibroid (leiomyoma) and breast cancer tissues, whereas the antiprogestin RU486 inhibits growth of these tissues through an unknown mechanism. Here, we determined the interaction between common or cell-specific genome-wide binding sites of PR and mRNA expression in RU486-treated uterine leiomyoma and breast cancer cells.ChIP-sequencing revealed 31,457 and 7,034 PR-binding sites in breast cancer and uterine leiomyoma cells, respectively; 1,035 sites overlapped in both cell types. Based on the chromatin-PR interaction in both cell types, we statistically refined the consensus progesterone response element to G•ACA• • •TGT•C. We identified two striking differences between uterine leiomyoma and breast cancer cells. First, the cis-regulatory elements for HSF, TEF-1, and C/EBPα and β were statistically enriched at genomic RU486/PR-targets in uterine leiomyoma, whereas E2F, FOXO1, FOXA1, and FOXF sites were preferentially enriched in breast cancer cells. Second, 51.5% of RU486-regulated genes in breast cancer cells but only 6.6% of RU486-regulated genes in uterine leiomyoma cells contained a PR-binding site within 5 kb from their transcription start sites (TSSs), whereas 75.4% of RU486-regulated genes contained a PR-binding site farther than 50 kb from their TSSs in uterine leiomyoma cells. RU486 regulated only seven mRNAs in both cell types. Among these, adipophilin (PLIN2), a pro-differentiation gene, was induced via RU486 and PR via the same regulatory region in both cell types.Our studies have identified molecular components in a RU486/PR-controlled gene network involved in the regulation of cell growth, cell migration, and extracellular matrix function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine fibroids and breast cancer

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC

Regulation of microRNA biogenesis and turnover by animals and their viruses

Item does not contain fulltextMicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes

Effects of psychological and psychosocial interventions on sport performance:a meta-analysis

Background: Psychologists are increasingly supporting the quest for performance enhancement in sport and there is a need to evaluate the evidence base underpinning their work. Objectives: To synthesize the most rigorous available research that has evaluated psychological, social, and psychosocial interventions with sport performers on variables relating to their athletic performance, and to address some of the perplexing issues in the sport psychology intervention literature (e.g., do interventions have a lasting effect on sport performance?). Methods: Randomized controlled trials were identified through electronic databases, hand-searching volumes of pertinent journals, scrutinizing reference lists of previous reviews, and contacting experts in the evaluation of interventions in this field. Included studies were required to evaluate the effects of psychological, social, or psychosocial interventions on sport performance in athletes when compared to a no-treatment or placebo-controlled treatment comparison group. A random effects meta-analysis calculating the standardized mean difference (Hedges’ g), meta-regressions, and trim and fill analyses were conducted. Data were analyzed at post-test and follow-up (ranging from 1 to 4 weeks after the intervention finished) assessments. Results: Psychological and psychosocial interventions were shown to enhance sport performance at post-test (k = 35, n = 997, Hedges’ g = 0.57, 95 % CI = 0.22–0.92) and follow-up assessments (k = 8, n = 189, Hedges’ g = 1.16, 95 % CI = 0.25–2.08); no social interventions were included or evaluated. Larger effects were found for psychosocial interventions and there was some evidence that effects were greatest in coach-delivered interventions and in samples with a greater proportion of male participants. Conclusions: Psychological and psychosocial interventions have a moderate positive effect on sport performance, and this effect may last at least a month following the end of the intervention. Future research would benefit from following guidelines for intervention reporting

Uridylation and adenylation of RNAs

The posttranscriptional addition of nontemplated nucleotides to the 3′ ends of RNA molecules can have a significant impact on their stability and biological function. It has been recently discovered that nontemplated addition of uridine or adenosine to the 3′ ends of RNAs occurs in different organisms ranging from algae to humans, and on different kinds of RNAs, such as histone mRNAs, mRNA fragments, U6 snRNA, mature small RNAs and their precursors etc. These modifications may lead to different outcomes, such as increasing RNA decay, promoting or inhibiting RNA processing, or changing RNA activity. Growing pieces of evidence have revealed that such modifications can be RNA sequence-specific and subjected to temporal or spatial regulation in development. RNA tailing and its outcomes have been associated with human diseases such as cancer. Here, we review recent developments in RNA uridylation and adenylation and discuss the future prospects in this research area

Long-term ursodeoxycholic acid therapy for primary biliary cirrhosis: a follow-up to 12 years.

BACKGROUND: It is uncertain whether ursodeoxycholic acid therapy slows down the progression of primary biliary cirrhosis, according to two meta-analyses. However, the randomized trials evaluated had only a median of 24 months of follow-up. AIM: To evaluate long-term ursodeoxycholic acid therapy in primary biliary cirrhosis. METHODS: We evaluated 209 consecutive primary biliary cirrhosis patients, 69 compliant with ursodeoxycholic acid and 140 untreated [mean follow-up 5.79 (s.d. = 4.73) and 4.87 (s.d. = 5.21) years, respectively] with onset of all complications documented. Comparison was made following adjustment for baseline differences according to Cox modelling, Mayo and Royal Free prognostic models. RESULTS: Bilirubin and alkaline phosphatase concentrations improved with ursodeoxycholic acid (at 36 months, P = 0.007 and 0.018, respectively). Unadjusted Kaplan-Meier analysis showed benefit (P = 0.028), as 44 (31%) untreated and 15 (22%) ursodeoxycholic acid patients died or had liver transplantation. However, there was no difference when adjusted by Cox modelling (P = 0.267), Mayo (P = 0.698) and Royal Free models (P = 0.559). New pruritus or fatigue or other complications were not different, either before or after adjustment for baseline characteristics. CONCLUSIONS: Long-term ursodeoxycholic acid therapy did not alter disease progression in primary biliary cirrhosis patients despite a significant improvement in serum bilirubin and alkaline phosphatase consistent with, and similar to, those seen in ursodeoxycholic acid cohorts in randomized trials

BRIEF REPORT: Hospitalized Patients' Attitudes About and Participation in Error Prevention

BACKGROUND AND OBJECTIVE: Although many patient safety organizations and hospital leaders wish to involve patients in error prevention, it is unknown whether patients will take the recommended actions or whether error prevention involvement affects hospitalization satisfaction. DESIGN AND PARTICIPANTS: Telephone interviews with 2,078 patients discharged from 11 Midwest hospitals. RESULTS: Ninety-one percent agreed that patients could help prevent errors. Patients were very comfortable asking a medication's purpose (91%), general medical questions (89%), and confirming their identity (84%), but were uncomfortable asking medical providers whether they had washed their hands (46% very comfortable). While hospitalized, many asked questions about their care (85%) and a medication's purpose (75%), but fewer confirmed they were the correct patient (38%), helped mark their incision site (17%), or asked about handwashing (5%). Multivariate logistic regression revealed that patients who felt very comfortable with error prevention were significantly more likely to take 6 of the 7 error-prevention actions compared with uncomfortable patients. CONCLUSIONS: While patients were generally comfortable with error prevention, their participation varied by specific action. Since patients who were very comfortable were most likely to take action, educational interventions to increase comfort with error prevention may be necessary to help patients become more engaged