Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth

Specificity of a whole blood IGRA in German nursing students

<p>Abstract</p> <p>Background</p> <p>Interferon-gamma release assays (IGRA) are used for tuberculosis (TB) screening in healthcare workers (HCWs). However, data on specificity of IGRA in serial testing of HCWs is sparse. Therefore the specificity and the negative predictive value of the IGRA - QuantiFERON-TB Gold In-Tube (QFT) - in German nursing students was investigated.</p> <p>Methods</p> <p>194 nursing students at the start of their professional career were tested with the QFT. 14 nursing students were excluded from the specificity analysis, due to exposure to mycobacterium tuberculosis. Two of these subjects were QFT- positive. None of them developed disease during the year of follow-up. A study group of 180 students, all with very low risk of prior TB infection, remained in the specificity analysis. Subjects were monitored for at least two years with respect to the development of active TB disease. IGRA was performed at the start of the training and after one year.</p> <p>Results</p> <p>The mean age of the study group (n = 180) was 23 years (range 18-53) with 70.9% female and 99.4% German born. The specificity of QFT was 98.9% (178/180; 95% CI 0.96-0.99); lowering the cut-off from 0.35 IU/ml to 0.1 IU/ml would have decreased specificity only slightly to 97.8% (176/180; 95% CI 0.94-0.99). Of the 154 nursing students available for re-testing, one student who initially scored positive reverted to negative, and one student initially negative converted to positive. None of the monitored group with initially negative QFT results developed TB disease, indicating a high negative predictive value of the IGRA in this population.</p> <p>Conclusions</p> <p>Following our data, QFT can serve as an effective tool in pre-employment TB screenings for HCWs. As its negative results were stable over time, specificity of the QFT in serial testing of HCWs is high. As the risk of acquiring TB infection in the German healthcare system appears to be low, our data supports the recommendation of performing TB screening only in those HCWs with known contact to TB patients or infectious materials.</p

The Merging of Two Dynasties—Identification of an African Cotton Leaf Curl Disease-Associated Begomovirus with Cotton in Pakistan

Cotton leaf curl disease (CLCuD) is a severe disease of cotton that occurs in Africa and Pakistan/northwestern India. The disease is caused by begomoviruses in association with specific betasatellites that differ between Africa and Asia. During survey of symptomatic cotton in Sindh (southern Pakistan) Cotton leaf curl Gezira virus (CLCuGV), the begomovirus associated with CLCuD in Africa, was identified. However, the cognate African betasatellite (Cotton leaf curl Gezira betasatellite) was not found. Instead, two Asian betasatellites, the CLCuD-associated Cotton leaf curl Multan betasatellite (CLCuMB) and Chilli leaf curl betasatellite (ChLCB) were identified. Inoculation of the experimental plant species Nicotiana benthamiana showed that CLCuGV was competent to maintain both CLCuMB and ChLCB. Interestingly, the enations typical of CLCuD were only induced by CLCuGV in the presence of CLCuMB. Also in infections involving both CLCuMB and ChLCB the enations typical of CLCuMB were less evident. This is the first time an African begomovirus has been identified on the Indian sub-continent, highlight the growing threat of begomoviruses and particularly the threat of CLCuD causing viruses to cotton cultivation in the rest of the world

Early Secreted Antigen ESAT-6 of Mycobacterium tuberculosis Promotes Protective T Helper 17 Cell Responses in a Toll-Like Receptor-2-dependent Manner

Despite its relatively poor efficacy, Bacillus Calmette-Guérin (BCG) has been used as a tuberculosis (TB) vaccine since its development in 1921. BCG induces robust T helper 1 (Th1) immune responses but, for many individuals, this is not sufficient for host resistance against Mycobacterium tuberculosis (M. tb) infection. Here we provide evidence that early secreted antigenic target protein 6 (ESAT-6), expressed by the virulent M. tb strain H37Rv but not by BCG, promotes vaccine-enhancing Th17 cell responses. These activities of ESAT-6 were dependent on TLR-2/MyD88 signalling and involved IL-6 and TGF-β production by dendritic cells. Thus, animals that were previously infected with H37Rv or recombinant BCG containing the RD1 region (BCG::RD1) exhibited improved protection upon re-challenge with virulent H37Rv compared with mice previously infected with BCG or RD1-deficient H37Rv (H37RvΔRD1). However, TLR-2 knockout (TLR-2-/-) animals neither showed Th17 responses nor exhibited improved protection in response to immunization with H37Rv. Furthermore, H37Rv and BCG::RD1 infection had little effect on the expression of the anti-inflammatory microRNA-146a (miR146a) in dendritic cells (DCs), whereas BCG and H37RvΔRD1 profoundly induced its expression in DCs. Consistent with these findings, ESAT-6 had no effect on miR146a expression in uninfected DCs, but dramatically inhibited its upregulation in BCG-infected or LPS-treated DCs. Collectively, our findings indicate that, in addition to Th1 immunity induced by BCG, RD1/ESAT-6-induced Th17 immune responses are essential for optimal vaccine efficacy

A comprehensive situation assessment of injection practices in primary health care hospitals in Bangladesh

<p>Abstract</p> <p>Background</p> <p>Understanding injection practices is crucial for evidence-based development of intervention initiatives. This study explored the extent of injection use and injection safety practices in primary care hospitals in Bangladesh.</p> <p>Methods</p> <p>The study employed both quantitative and qualitative research methods. The methods used were - a retrospective audit of prescriptions (n = 4320), focus group discussions (six with 43 participants), in-depth interviews (n = 38) with a range service providers, and systematic observation of the activities of injection providers (n = 120), waste handlers (n = 48) and hospital facilities (n = 24). Quantitative and qualitative data were assessed with statistical and thematic analysis, respectively, and then combined.</p> <p>Results</p> <p>As many as 78% of our study sample (n = 4230) received an injection. The most commonly prescribed injections (n = 3354) including antibiotics (78.3%), IV fluids (38.6%), analgesics/pain killers (29.4%), vitamins (26.7%), and anti-histamines (18.5%). Further, 43.7% (n = 1145) of the prescribed antibiotics (n = 2626) were given to treat diarrhea and 42.3% (n = 600) of IV fluids (n = 1295) were used to manage general weakness conditions. Nearly one-third (29.8%; n = 36/120) of injection providers reported needle-stick injuries in the last 6 months with highest incidences in Rajshahi division followed by Dhaka division. Disposal of injection needles, syringes and other materials was not done properly in 83.5% (n = 20/24) of the facilities. Health providers' safety concerns were not addressed properly; only 23% (n = 28/120) of the health providers and 4.2% (n = 2/48) of the waste handlers were fully immunized against Hepatitis B virus. Moreover, 73% (n = 87/120) of the injection providers and 90% (n = 43/48) of the waste handlers were not trained in injection safety practices and infection prevention. Qualitative data further confirmed that both providers and patients preferred injections, believing that they provide quick relief. The doctors' perceived injection use as their prescribing norm that enabled them to prove their professional credibility and to remain popular in a competitive health care market. Additionally, persistent pressure from hospital administration to use up injections before their expiry dates also influenced doctors to prescribe injections regardless of actual indications.</p> <p>Conclusions</p> <p>As far as the patients and providers' safety is concerned, this study demonstrated a need for further research exploring the dynamics of injection use and safety in Bangladesh. In a context where a high level of injection use and unsafe practices were reported, immediate prevention initiatives need to be operated through continued intervention efforts and health providers' training in primary care hospitals in Bangladesh.</p

Translation and psychometric testing of the Farsi version of the Seattle angina questionnaire

Abstract Background Angina pectoris causes substantial psychological and functional disabilities and adversely effects quality of life in patients. The aim of this study was to investigate the psychometric properties including validity and reliability of the Farsi version of the Seattle angina questionnaire. Methods The ‘forward-backward’ procedure was applied to translate this questionnaire from English to Farsi. The translated version of the Seattle angina questionnaire was assessed in terms of validity and reliability with a convenience sample of 200 patients suffering from angina pectoris who were recruited from the inpatient ward (post CCU) and outpatient department at two teaching hospitals in an urban area of Iran. Validity was assessed using content, face and construct validity. The calculation of the Cronbach’s alpha coefficient and the test-retest method helped with the assessment of reliability of the questionnaire’s five subscales. Construct validity of the questionnaire was evaluated using exploratory factor analysis. Results The results of exploratory factor analysis indicated a five-factor solution for the questionnaire including ‘physical limitation in middle to strenuous activities’, ‘physical limitation in slight activities’, ‘angina pattern and discomfort of treatment’, ‘treatment satisfaction’ and ‘disease perception’ that jointly accounted for 64.42% of variance observed. Convergent validity was mostly supported by the pattern of association between the Seattle angina questionnaire-Farsi version and the SF-36. Cronbach’s alpha of the subscales ranged from 0.60 to 0.86 and test-retest scores ranged from 0.79 to 0.97 indicating a good range of reliability. Conclusions The Seattle angina questionnaire-Farsi version had acceptable psychometric properties. Therefore, it can be used to assess health-related quality of life and assess the effects of different medical and nursing interventions on patients’ quality of life