Changes to the Natural Killer Cell Repertoire after Therapeutic Hepatitis B DNA Vaccination

BACKGROUND: Improvements to the outcome of adaptive immune responses could be achieved by inducing specific natural killer (NK) cell subsets which can cooperate with dendritic cells to select efficient T cell responses. We previously reported the induction or reactivation of T cell responses in chronic hepatitis B patients vaccinated with a DNA encoding hepatitis B envelope proteins during a phase I clinical trial. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined changes in the peripheral NK cell populations occurring during this vaccine trial using flow cytometry analysis. Despite a constant number of NK cells in the periphery, a significant increase in the CD56(bright) population was observed after each vaccination and during the follow up. Among the 13 different NK cell markers studied by flow cytometry analysis, the expression of CD244 and NKG2D increased significantly in the CD56(bright) NK population. The ex vivo CD107a expression by CD56(bright) NK cells progressively increased in the vaccinated patients to reach levels that were significantly higher compared to chronically HBV-infected controls. Furthermore, modifications to the percentage of the CD56(bright) NK cell population were correlated with HBV-specific T cell responses detected by the ELISPOT assay. CONCLUSIONS/SIGNIFICANCE: These changes in the CD56(bright) population may suggest a NK helper effect on T cell adaptive responses. Activation of the innate and adaptive arms of the immune system by DNA immunization may be of particular importance to the efficacy of therapeutic interventions in a context of chronic infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT00988767

First-year compliance with the Nevada Clean Indoor Air Act

Objectives: We quantitatively evaluated compliance with the Nevada Clean Indoor Air Act (NCIAA) by different types of businesses in Nevada and determined whether compliance affected indoor concentrations of benzene and 3-ethenyl pyridine (3-EP), markers of tobacco smoke. Methods: Managers of 181 businesses in Washoe County, Nevada, were interviewed about business characteristics and practices and policies related to smoking. During unannounced visits, compliance data and air samples (n=66) were collected from interviewed businesses and from an additional sample (n = 56) of businesses without knowledge of the study. Results: Overall compliance, as defined by the NCIAA, was low (28.2%). Benzene concentrations were higher in casino restaurants than in other businesses, although most complied with the requirements of the ban. Neither benzene nor 3-EP concentrations differed significantly between compliant and non-compliant businesses. Conclusions: The finding that casino restaurants had poorer air quality despite their compliance with the NCIAA suggests that compliance alone may not be sufficient to reduce exposure to secondhand smoke, particularly in buildings with both nonsmoking and smoking areas

Need for timely paediatric HIV treatment within primary health care in rural South Africa

<p>Background: In areas where adult HIV prevalence has reached hyperendemic levels, many infants remain at risk of acquiring HIV infection. Timely access to care and treatment for HIV-infected infants and young children remains an important challenge. We explore the extent to which public sector roll-out has met the estimated need for paediatric treatment in a rural South African setting.</p> <p>Methods: Local facility and population-based data were used to compare the number of HIV infected children accessing HAART before 2008, with estimates of those in need of treatment from a deterministic modeling approach. The impact of programmatic improvements on estimated numbers of children in need of treatment was assessed in sensitivity analyses.</p> <p>Findings: In the primary health care programme of HIV treatment 346 children <16 years of age initiated HAART by 2008; 245(70.8%) were aged 10 years or younger, and only 2(<1%) under one year of age. Deterministic modeling predicted 2,561 HIV infected children aged 10 or younger to be alive within the area, of whom at least 521(20.3%) would have required immediate treatment. Were extended PMTCT uptake to reach 100% coverage, the annual number of infected infants could be reduced by 49.2%.</p> <p>Conclusion: Despite progress in delivering decentralized HIV services to a rural sub-district in South Africa, substantial unmet need for treatment remains. In a local setting, very few children were initiated on treatment under 1 year of age and steps have now been taken to successfully improve early diagnosis and referral of infected infants.</p&gt

Are CT-derived muscle measurements prognostic, independent of systemic inflammation in good performance status patients with advanced cancer?

The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1–68.1). On univariate analysis, cancer type (p < 0.05) and mGPS (p < 0.001) were significantly associated with OS. On multivariate analysis, only mGPS (p < 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS (p < 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer

Acceptance matters:Disengagement and attrition among LGBT personnel in the U.S. Military

Introduction: The U.S. military has undergone profound changes in its policies toward lesbian, gay, bisexual, and transgender (LGBT) service members (SMs) over the past decade. Although emerging evidence indicates that some LGBT SMs perceive their co-workers as supportive, a sizable group report continued victimization, harassment, and fear of disclosing their LGBT identity. Because employee perception of cohesion and belonging affects retention in the workplace, such discrimination is likely to affect retention of LGBT military personnel. Methods: Survey data come from a study funded by the U.S. Department of Defense (2017-2018) and completed by 544 active-duty SMs (non-LGBT n = 296; LGBT n = 248). Multinomial logistic regressions were used to examine military career intentions among SMs according to socio-demographics, perceived acceptance, and unit climate. Results: One in 3 transgender SMs plan to leave the military upon completion of their service commitment, compared with 1 in 5 cisgender LGB SMs and 1 in 8 non-LGBT SMs. LGBT SMs were twice as likely as non-LGBT SMs to be undecided about their military career path after controlling for confounding variables. Lower perceived LGBT acceptance was associated with a higher risk of attrition among LGBT SMs. Lower perceived unit cohesion was associated with attrition risk for all SMs. Discussion: These findings suggest that, although some LGBT SMs may feel accepted, the U.S. military could do more to improve its climate of acceptance to prevent attrition, especially for transgender SMs. Taking measures to prioritize unit cohesion would improve retention of qualified LGBT and non-LGBT SMs.</p

Lactate dehydrogenase: Relationship with the diagnostic GLIM criterion for cachexia in patients with advanced cancer

Background: Although suggestive of dysregulated metabolism, the relationship between serum LDH level, phenotypic/aetiologic diagnostic Global Leadership Initiative on Malnutrition (GLIM) criteria and survival in patients with advanced cancer has yet to examined. Methods: Prospectively collected data from patients with advanced cancer, undergoing anti-cancer therapy with palliative intent, across nine sites in the UK and Ireland between 2011–2016, was retrospectively analysed. LDH values were grouped as &lt;250/250–500/&gt;500 Units/L. Relationships were examined using χ2 test for linear-by-linear association and binary logistics regression analysis. Results: A total of 436 patients met the inclusion criteria. 46% (n = 200) were male and 59% (n = 259) were ≥65 years of age. The median serum LDH was 394 Units/L and 33.5% (n = 146) had an LDH &gt; 500 Units/L. LDH was significantly associated with ECOG-PS (p &lt; 0.001), NLR (p &lt; 0.05), mGPS (p &lt; 0.05) and 3-month survival (p &lt; 0.001). LDH was significantly associated with 3-month survival independent of weight loss (p &lt; 0.01), BMI (p &lt; 0.05), skeletal muscle mass (p &lt; 0.01), metastatic disease (p &lt; 0.05), NLR (p &lt; 0.05) and mGPS (p &lt; 0.01). Discussion: LDH was associated with performance status, systemic inflammation and survival in patients with advanced cancer. LDH measurement may be considered as an aetiologic criteria and become a potential therapeutic target in the treatment of cancer cachexia

Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (≥0.034 nmol/l) into either a normoandrogenic (n = 23) or hyperandrogenic (n = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS

Region-specific drivers cause low organic carbon stocks and sequestration rates in the saltmarsh soils of southern Scandinavia

Saltmarshes are known for their ability to act as effective sinks of organic carbon (OC) and their protection and restoration could potentially slow down the pace of global warming. However, regional estimates of saltmarsh OC storage are often missing, including for the Nordic region. To address this knowledge gap, we assessed OC storage and accumulation rates in 17 saltmarshes distributed along the Danish coasts and investigated the main drivers of soil OC storage. Danish saltmarshes store a median of 10 kg OC m−2 (interquartile range, IQR: 13.5–7.6) in the top meter and sequester 31.5 g OC m−2 yr−1 (IQR: 41.6–15.7). In a global context, these values are comparatively low. Soils with abundant clay (&gt; 20%), older and stable saltmarshes in mesohaline settings, and with low proportion of algal organic material showed higher OC densities, stocks, and accumulation rates. Grazing led to significantly higher OC stocks than neighboring ungrazed locations, likely due to trampling modifying soil abiotic conditions (higher erosion-resistance and higher clay content) that slow carbon decay. Scaling up, Danish saltmarsh soils, comprising about 1% of the country's area, have the potential to yearly capture up to 0.1% of Denmark's annual consumption-based CO2 emissions. Our research expands the baseline data needed to advance blue carbon research and management in the Nordic region while highlighting the need for a more comprehensive approach to saltmarsh management that considers the full range of services of these ecosystems and does not only focus on climate benefits.</p

Validating child vaccination status in a demographic surveillance system using data from a clinical cohort study: evidence from rural South Africa

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Childhood vaccination coverage can be estimated from a range of sources. This study aims to validate vaccination data from a longitudinal population-based demographic surveillance system (DSS) against data from a clinical cohort study.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The sample includes 821 children in the Vertical Transmission cohort Study (VTS), who were born between December 2001 and April 2005, and were matched to the Africa Centre DSS, in northern KwaZulu-Natal. Vaccination information in the surveillance was collected retrospectively, using standardized questionnaires during bi-annual household visits, when the child was 12 to 23 months of age. DSS vaccination information was based on extraction from a vaccination card or, if the card was not available, on maternal recall. In the VTS, vaccination data was collected at scheduled maternal and child clinic visits when a study nurse administered child vaccinations. We estimated the sensitivity of the surveillance in detecting vaccinations conducted as part of the VTS during these clinic visits.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Vaccination data in matched children in the DSS was based on the vaccination card in about two-thirds of the cases and on maternal recall in about one-third. The sensitivity of the vaccination variables in the surveillance was high for all vaccines based on either information from a South African Road-to-Health (RTH) card (0.94-0.97) or maternal recall (0.94-0.98). Addition of maternal recall to the RTH card information had little effect on the sensitivity of the surveillance variable (0.95-0.97). The estimates of sensitivity did not vary significantly, when we stratified the analyses by maternal antenatal HIV status. Addition of maternal recall of vaccination status of the child to the RTH card information significantly increased the proportion of children known to be vaccinated across all vaccines in the DSS.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; Maternal recall performs well in identifying vaccinated children aged 12-23 months (both in HIV-infected and HIV-uninfected mothers), with sensitivity similar to information extracted from vaccination cards. Information based on both maternal recall and vaccination cards should be used if the aim is to use surveillance data to identify children who received a vaccination.&lt;/p&gt