Inhibition of Monkeypox virus replication by RNA interference

The Orthopoxvirus genus of Poxviridae family is comprised of several human pathogens, including cowpox (CPXV), Vaccinia (VACV), monkeypox (MPV) and Variola (VARV) viruses. Species of this virus genus cause human diseases with various severities and outcome ranging from mild conditions to death in fulminating cases. Currently, vaccination is the only protective measure against infection with these viruses and no licensed antiviral drug therapy is available. In this study, we investigated the potential of RNA interference pathway (RNAi) as a therapeutic approach for orthopox virus infections using MPV as a model. Based on genome-wide expression studies and bioinformatic analysis, we selected 12 viral genes and targeted them by small interference RNA (siRNA). Forty-eight siRNA constructs were developed and evaluated in vitro for their ability to inhibit viral replication. Two genes, each targeted with four different siRNA constructs in one pool, were limiting to viral replication. Seven siRNA constructs from these two pools, targeting either an essential gene for viral replication (A6R) or an important gene in viral entry (E8L), inhibited viral replication in cell culture by 65-95% with no apparent cytotoxicity. Further analysis with wild-type and recombinant MPV expressing green fluorescence protein demonstrated that one of these constructs, siA6-a, was the most potent and inhibited viral replication for up to 7 days at a concentration of 10 nM. These results emphasis the essential role of A6R gene in viral replication, and demonstrate the potential of RNAi as a therapeutic approach for developing oligonucleotide-based drug therapy for MPV and other orthopox viruses

Partner relationship satisfaction and maternal emotional distress in early pregnancy

<p>Abstract</p> <p>Background</p> <p>Recognition of maternal emotional distress during pregnancy and the identification of risk factors for this distress are of considerable clinical- and public health importance. The mental health of the mother is important both for herself, and for the physical and psychological health of her children and the welfare of the family. The first aim of the present study was to identify risk factors for maternal emotional distress during pregnancy with special focus on partner relationship satisfaction. The second aim was to assess interaction effects between relationship satisfaction and the main predictors.</p> <p>Methods</p> <p>Pregnant women enrolled in the Norwegian Mother and Child Cohort Study (n = 51,558) completed a questionnaire with questions about maternal emotional distress, relationship satisfaction, and other risk factors. Associations between 37 predictor variables and emotional distress were estimated by multiple linear regression analysis.</p> <p>Results</p> <p>Relationship dissatisfaction was the strongest predictor of maternal emotional distress (β = 0.25). Other predictors were dissatisfaction at work (β = 0.11), somatic disease (β = 0.11), work related stress (β = 0.10) and maternal alcohol problems in the preceding year (β = 0.09). Relationship satisfaction appeared to buffer the effects of frequent moving, somatic disease, maternal smoking, family income, irregular working hours, dissatisfaction at work, work stress, and mother's sick leave (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>Dissatisfaction with the partner relationship is a significant predictor of maternal emotional distress in pregnancy. A good partner relationship can have a protective effect against some stressors.</p

Prioritizing Health Care Strategies to Reduce Childhood Mortality

IMPORTANCE: Although child mortality trends have decreased worldwide, deaths among children younger than 5 years of age remain high and disproportionately circumscribed to sub-Saharan Africa and Southern Asia. Tailored and innovative approaches are needed to increase access, coverage, and quality of child health care services to reduce mortality, but an understanding of health system deficiencies that may have the greatest impact on mortality among children younger than 5 years is lacking. OBJECTIVE: To investigate which health care and public health improvements could have prevented the most stillbirths and deaths in children younger than 5 years using data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used longitudinal, population-based, and mortality surveillance data collected by CHAMPS to understand preventable causes of death. Overall, 3390 eligible deaths across all 7 CHAMPS sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) between December 9, 2016, and December 31, 2021 (1190 stillbirths, 1340 neonatal deaths, 860 infant and child deaths), were included. Deaths were investigated using minimally invasive tissue sampling (MITS), a postmortem approach using biopsy needles for sampling key organs and fluids. MAIN OUTCOMES AND MEASURES: For each death, an expert multidisciplinary panel reviewed case data to determine the plausible pathway and causes of death. If the death was deemed preventable, the panel identified which of 10 predetermined health system gaps could have prevented the death. The health system improvements that could have prevented the most deaths were evaluated for each age group: stillbirths, neonatal deaths (aged <28 days), and infant and child deaths (aged 1 month to <5 years). RESULTS: Of 3390 deaths, 1505 (44.4%) were female and 1880 (55.5%) were male; sex was not recorded for 5 deaths. Of all deaths, 3045 (89.8%) occurred in a healthcare facility and 344 (11.9%) in the community. Overall, 2607 (76.9%) were deemed potentially preventable: 883 of 1190 stillbirths (74.2%), 1010 of 1340 neonatal deaths (75.4%), and 714 of 860 infant and child deaths (83.0%). Recommended measures to prevent deaths were improvements in antenatal and obstetric care (recommended for 588 of 1190 stillbirths [49.4%], 496 of 1340 neonatal deaths [37.0%]), clinical management and quality of care (stillbirths, 280 [23.5%]; neonates, 498 [37.2%]; infants and children, 393 of 860 [45.7%]), health-seeking behavior (infants and children, 237 [27.6%]), and health education (infants and children, 262 [30.5%]). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, interventions prioritizing antenatal, intrapartum, and postnatal care could have prevented the most deaths among children younger than 5 years because 75% of deaths among children younger than 5 were stillbirths and neonatal deaths. Measures to reduce mortality in this population should prioritize improving existing systems, such as better access to antenatal care, implementation of standardized clinical protocols, and public education campaigns

Sterilization of hydrogen peroxide resistant bacterial spores with stabilized chlorine dioxide

Bacillus pumilus SAFR-032 spores isolated from a clean room environment are known to exhibit enhanced resistance to peroxide, desiccation, UV radiation and chemical disinfection than other spore-forming bacteria. The survival of B. pumilus SAFR-032 spores to standard clean room sterilization practices requires development of more stringent disinfection agents. Here, we report the effects of a stabilized chlorine dioxide-based biocidal agent against spores of B. pumilus SAFR-032 and Bacillus subtilis ATCC 6051. Viability was determined via CFU measurement after exposure. Chlorine dioxide demonstrated efficacy towards sterilization of spores of B. pumilus SAFR-032 equivalent or better than exposure to hydrogen peroxide. These results indicate efficacy of chlorine dioxide delivered through a stabilized chlorine dioxide product as a means of sterilization of peroxide- and UV-resistant spores.This work is supported by the National Institutes of Health (1R01GM090064-01), a NASA EPSCoR Research Infrastructure Development (RID) grant NN07AL49A, and the University of Oklahoma.Ye

Personality and marital satisfaction: A behavioural genetic analysis

Previous research has found that genetic and nonshared environmental factors influence Marital quality (Spotts et al., 2004). The current study explored personality as a source for these genetic and environmental individual differences. A sample of 752 Swedish twin women and their spouses were used. Genetic and environmental influences were found for self-report measures of Marital quality, but only environmental factors contributed to the variance of observational measures of Marital quality. Wives' personality characteristics accounted for genetic and nonshared environmental variance in the wives' own Marital satisfaction, their husbands' Marital satisfaction, and the agreement between the spouses oil the quality of their marriage. Genetic influences on the correlation between wives' genetically influenced personality characteristics and their husbands' marital satisfaction indicate a gene-environment correlation. Contrary to expectations, husbands' personality did not explain large portions of wives' Marital satisfaction beyond that explained by wives' personality. This study emphasizes the importance of spousal personality to the well-being of marriages, and results are discussed within the context of three different theories regarding associations between personality and Marital quality. Copyright © 2005 John Wiley & Sons, Ltd