Risk Factors for Hepatitis C Virus Transmission to Health Care Workers after Occupational Exposure: A European Case-Control Study

Background. Additional studies are required to identify risk factors for hepatitis C virus (HCV) transmission to health care workers after occupational exposure to HCV. Methods. We conducted a matched case-control study in 5 European countries from 1 January 1991 through 31 December 2002. Case patients were health care workers who experienced seroconversion after percutaneous or mucocutaneous exposure to HCV. Control subjects were HCV-exposed health care workers who did not experience seroconversion and were matched with case patients for center and period of exposure. Results. Sixty case patients and 204 control subjects were included in the study. All case patients were exposed to HCV-infected fluids through percutaneous injuries. The 37 case patients for whom information was available were exposed to viremic source patients. As risk factors for HCV infection, multivariate analysis identified needle placement in a source patient's vein or artery (odds ratio [OR], 100.1; 95% confidence interval [CI], 7.3-1365.7), deep injury (OR, 155.2; 95% CI, 7.1-3417.2), and sex of the health care worker (OR for male vs. female, 3.1; 95% CI, 1.0-10.0). Source patient HCV load was not introduced in the multivariate model. In unmatched univariate analysis, the risk of HCV transmission increased 11-fold for health care workers exposed to source patients with a viral load >6 log10 copies/mL (95% CI, 1.1-114.1), compared with exposures to source patients with a viral load ⩽4 log10 copies/mL. Conclusion. In this study, HCV occupational transmission was found to occur after percutaneous exposures. The risk of HCV transmission after percutaneous exposure increased with deep injuries and procedures involving hollow-bore needle placement in the source patient's vein or artery. These results highlight the need for widespread adoption of needlestick-prevention devices in health care settings, together with other preventive measure

Longitudinal study of computerised cardiotocography in early fetal growth restriction.

OBJECTIVES: To explore if in early fetal growth restriction (FGR) the longitudinal pattern of short-term fetal heart rate (FHR) variation (STV) can be used for identifying imminent fetal distress and if abnormalities of FHR registration associate with two-year infant outcome. METHODS: The original TRUFFLE study assessed if in early FGR the use of ductus venosus Doppler pulsatility index (DVPI), in combination with a safety-net of very low STV and / or recurrent decelerations, could improve two-year infant survival without neurological impairment in comparison to computerised cardiotocography (cCTG) with STV calculation only. For this secondary analysis we selected women, who delivered before 32 weeks, and who had consecutive STV data for more than 3 days before delivery, and known infant two-year outcome data. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values except the last one were calculated. Life table analysis and Cox regression analysis were used to calculate the day by day risk for a low STV or very low STV and / or FHR decelerations (DVPI group safety-net) and to assess which parameters were associated to this risk. Furthermore, it was assessed if STV pattern, lowest STV value or recurrent FHR decelerations were associated with two-year infant outcome. RESULTS: One hundred and fourty-nine women matched the inclusion criteria. Using the individual STV regression lines prediction of a last STV below the cCTG-group cut-off had a sensitivity of 0.42 and specificity of 0.91. For each day after inclusion the median risk for a low STV(cCTG criteria) was 4% (Interquartile range (IQR) 2% to 7%) and for a very low STV and / or recurrent decelerations (DVPI safety-net criteria) 5% (IQR 4 to 7%). Measures of STV pattern, fetal Doppler (arterial or venous), birthweight MoM or gestational age did not improve daily risk prediction usefully. There was no association of STV regression coefficients, a last low STV or /and recurrent decelerations with short or long term infant outcomes. CONCLUSION: The TRUFFLE study showed that a strategy of DVPI monitoring with a safety-net delivery indication of very low STV and / or recurrent decelerations could increase infant survival without neurological impairment at two years. This post-hoc analysis demonstrates that in early FGR the day by day risk of an abnormal cCTG as defined by the DVPI protocol safety-net criteria is 5%, and that prediction of this is not possible. This supports the rationale for cCTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DVPI is in the normal range

The synthetic bacterial lipopeptide Pam3CSK4 modulates respiratory syncytial virus infection independent of TLR activation

Respiratory syncytial virus (RSV) is an important cause of acute respiratory disease in infants, immunocompromised subjects and the elderly. However, it is unclear why most primary RSV infections are associated with relatively mild symptoms, whereas some result in severe lower respiratory tract infections and bronchiolitis. Since RSV hospitalization has been associated with respiratory bacterial co-infections, we have tested if bacterial Toll-like receptor (TLR) agonists influence RSVA2- GFP infection in human primary cells or cell lines. The synthetic bacterial lipopeptide Pam3-Cys-Ser-Lys4 (Pam3CSK4), the prototype ligand for the heterodimeric TLR1/TLR2 complex, enhanced RSV infection in primary epithelial, myeloid and lymphoid cells. Surprisingly, enhancement was optimal when lipopeptides and virus were added simultaneously, whereas addition of Pam3CSK4 immediately after infection had no effect. We have identified two structurally related lipopeptides without TLR-signaling capacity that also modulate RSV infection, whereas Pam3CSK4-reminiscent TLR1/2 agonists did not, and conclude that modulation of infection is independent of TLR activation. A similar TLR-independent enhancement of infection could also be demonstrated for wild-type RSV strains, and for HIV-1, measles virus and human metapneumovirus. We show that the effect of Pam3CSK4 is primarily mediated by enhanced binding of RSV to its target cells. The Npalmitoylated cystein

Genomic and biological characterization of chiltepin yellow mosaic virus, a new tymovirus infecting Capsicum annuum var. aviculare in Mexico.

The characterization of viruses infecting wild plants is a key step towards understanding the ecology of plant viruses. In this work, the complete genomic nucleotide sequence of a new tymovirus species infecting chiltepin, the wild ancestor of Capsicum annuum pepper crops, in Mexico was determined, and its host range has been explored. The genome of 6,517 nucleotides has the three open reading frames described for tymoviruses, putatively encoding an RNA-dependent RNA polymerase, a movement protein and a coat protein. The 5′ and 3′ untranslated regions have structures with typical signatures of the tymoviruses. Phylogenetic analyses revealed that this new virus is closely related to the other tymoviruses isolated from solanaceous plants. Its host range is mainly limited to solanaceous species, which notably include cultivated Capsicum species. In the latter, infection resulted in a severe reduction of growth, indicating the potential of this virus to be a significant crop pathogen. The name of chiltepin yellow mosaic virus (ChiYMV) is proposed for this new tymovirus

Remediating cognitive inflexibility in obsessive compulsive disorder and anorexia nervosa neither moderates nor mediates treatment effects:an exploratory study

Objective: Obsessive compulsive disorder (OCD) and anorexia nervosa (AN) are conditions associated with poor cognitive flexibility, a factor considered to interfere with treatment, but research into the relationship between cognitive flexibility and treatment outcome is limited. This study explores whether baseline measures of cognitive flexibility predict outcomes in OCD and AN, evaluates whether changes in these measures contribute to treatment outcome, and evaluates the effectiveness of adjunctive cognitive remediation therapy (CRT) in improving cognitive flexibility.Methods: This secondary analysis utilized linear mixed model analysis on data from a randomized controlled multicenter clinical trial involving adult participants with OCD (n=71) AND AN (n=61). Participants underwent 10 twice-weekly sessions of either CRT or a non-specific active control intervention (specialized attention therapy; SAT), followed by treatment as usual. Assessments using Yale-Brown Obsessive Compulsive Scale and the Eating Disorder Examination Questionnaire were conducted at baseline, post-CRT/SAT and at 6 and 12 months. Cognitive flexibility was evaluated through the Trail Making Test (TMT), the Color-Word Interference Test (CWIT) and the Detail and Flexibility Questionnaire (DFlex).Results: Levels of cognitive flexibility at baseline did not predict or moderate treatment outcome, nor did change in cognitive flexibility (baseline post-CRT/SAT) mediate treatment outcome, with CRT providing no greater improvement in measures of cognitive flexibility than SAT.Conclusions: This study failed to find any relationship between measures of cognitive flexibility and treatment outcome in OCD and AN, and thus questions hypothetical associations between measures of cognitive flexibility and mechanisms of change in patients with OCD and AN.</p

Maternal Immune Activation During Pregnancy and Obstetric Outcomes:A Population-Based Cohort Study

Objective: Maternal immune activation has been proposed as a mechanism for adverse pregnancy outcomes, yet the mechanisms and effects of timing remain unclear. Immune disruption in early gestation may be particularly detrimental as this is an important period for placental development, which has been associated with the pathology of adverse obstetric outcomes. To increase our understanding of risk factors for adverse obstetric outcomes, we aim to investigate the association between multiple inflammatory and angiogenic markers during early pregnancy and adverse pregnancy outcomes in a large population-based cohort. Design: Prospective population-based pregnancy cohort study (n = 7513). Setting: Rotterdam, the Netherlands. Population: Pregnant women in Rotterdam between April 2002 and January 2006. Methods: Serum inflammatory markers (high-sensitivity (HS)-C-reactive protein (CRP), interleukin (IL)-1β, IL-6, IL-17a, IL-23, interferon (IFN)-γ) and angiogenic factors (sFlt-1 and PlGF) were analysed in repeated measures around 13–20 weeks gestation. A cytokine index was created using principal component analysis. Main Outcome Measures: Hypertensive disorders of pregnancy, spontaneous preterm birth and small for gestational age at birth. Results: HS-CRP, but not the cytokine index, was associated with increased risk of spontaneous preterm birth after multiple testing correction. We found no association of HS-CRP or the cytokine index with hypertensive disorders of pregnancy and small for gestational age at birth after multiple testing correction. Inflammatory and angiogenic factors were associated with each other, yet effect sizes were small. Conclusions: We found no strong evidence of a link between early gestation typical inflammatory marker levels and the risk of adverse pregnancy outcomes.</p

Hepatitis C virus infection among transmission-prone medical personnel

Hepatitis C virus (HCV)-infected physicians have been reported to infect some of their patients during exposure-prone procedures (EPPs). There is no European consensus on the policy for the prevention of this transmission. To help define an appropriate preventive policy, we determined the prevalence of HCV infection among EPP-performing medical personnel in the Academic Medical Center in Amsterdam, the Netherlands. The prevalence of HCV infection was studied among 729 EPP-performing health care workers. Serum samples, stored after post-hepatitis B virus (HBV) vaccination testing in the years 2000–2009, were tested for HCV antibodies. Repeat reactive samples were confirmed by immunoblot assay and the detection of HCV RNA. The average age of the 729 health care workers was 39 years (range 18–66), suggesting a considerable cumulative occupational exposure to the blood. Nevertheless, only one of the 729 workers (0.14%; 95% confidence interval [CI]: <0.01% to 0.85%) was tested and confirmed to be positive for anti-HCV and positive for HCV RNA, which is comparable to the prevalence of HCV among Amsterdam citizens. Against this background, for the protection of personnel and patients, careful follow-up after needlestick injuries may be sufficient. If a zero-risk approach is desirable and costs are less relevant, the recurrent screening of EPP-performing personnel for HCV is superior to the follow-up of reported occupational exposures