Evaluation of conditional cash transfers and mHealth audio messaging in reduction of risk factors for childhood malnutrition in internally displaced persons camps in Somalia: A 2 × 2 factorial cluster-randomised controlled trial.

BACKGROUND: Cash transfer programmes are increasingly used in humanitarian contexts to help address people's needs across multiple sectors. However, their impact on the key objectives of reducing malnutrition and excess mortality remains unclear. mHealth interventions show great promise in many areas of public health, but evidence for their impact on reducing the risk factors for malnutrition is uncertain. We therefore implemented a trial to determine the impacts of 2 interventions in a protracted humanitarian context, a cash transfer conditionality and mHealth audio messages. METHODS AND FINDINGS: A 2 × 2 factorial cluster-randomised trial was implemented in camps for internally displaced people (IDP) near Mogadishu, Somalia, starting in January 2019. The main study outcomes were assessed at midline and endline and included coverage of measles vaccination and the pentavalent immunisation series, timely vaccination, caregiver's health knowledge, and child diet diversity. Twenty-three clusters (camps) were randomised to receive or not receive conditional cash transfers (CCTs) and an mHealth intervention, and 1,430 households were followed up over 9 months. All camps received cash transfers made at emergency humanitarian level (US$70/household/month) for 3 months followed by a further 6 months at a safety net level (US$35). To be eligible to receive cash, households in camps receiving CCT were required to take their children <5 years age to attend a single health screening at a local clinic and were issued with a home-based child health record card. Participants in camps receiving the mHealth intervention were asked (but not required) to listen to a series of audio messages about health and nutrition that were broadcast to their mobile phone twice a week for 9 months. Participants and investigators were not blinded. Adherence to both interventions was monitored monthly and found to be high (>85%). We conducted intention-to-treat analysis. During the humanitarian intervention phase, the CCT improved coverage of measles vaccination (MCV1) from 39.2% to 77.5% (aOR 11.7, 95% CI [5.2, 26.1]; p < 0.001) and completion of the pentavalent series from 44.2% to 77.5% (aOR 8.9, 95% CI [2.6, 29.8]; p = < 0.001). By the end of the safety net phase, coverage remained elevated from baseline at 82.2% and 86.8%, respectively (aOR 28.2, 95% CI [13.9, 57.0]; p < 0.001 and aOR 33.8, 95% CI [11.0, 103.4]; p < 0.001). However, adherence to timely vaccination did not improve. There was no change in the incidence of mortality, acute malnutrition, diarrhoea, or measles infection over the 9 months of follow-up. Although there was no evidence that mHealth increased Mother's knowledge score (aOR 1.32, 95% CI [0.25, 7.11]; p = 0.746) household dietary diversity increased from a mean of 7.0 to 9.4 (aOR 3.75, 95% CI [2.04, 6.88]; p < 0.001). However, this was not reflected by a significant increase in child diet diversity score, which changed from 3.19 to 3.63 (aOR 2.1, 95% CI [1.0, 4.6]; p = 0.05). The intervention did not improve measles vaccination, pentavalent series completion, or timely vaccination, and there was no change in the incidence of acute malnutrition, diarrhoea, measles infection, exclusive breastfeeding, or child mortality. No significant interactions between the interventions were found. Study limitations included the limited time available to develop and test the mHealth audio messages and the necessity to conduct multiple statistical tests due to the complexity of the study design. CONCLUSIONS: A carefully designed conditionality can help achieve important public health benefits in humanitarian cash transfer programmes by substantially increasing the uptake of child vaccination services and, potentially, other life-saving interventions. While mHealth audio messages increased household diet diversity, they failed to achieve any reductions in child morbidity, malnutrition, or mortality. TRIAL REGISTRATION: ISRCTN ISRCTN24757827. Registered November 5, 2018.

Understanding multilevel barriers to childhood vaccination uptake among Internally Displaced Populations (IDPs) in Mogadishu, Somalia: a qualitative study.

BACKGROUND: Disparities in vaccination coverage exist in Somalia with Internally Displaced Persons (IDPs) being among the groups with the lowest coverage. We implemented an adapted Participatory Learning and Action (PLA) intervention, which focused on routine vaccinations among displaced populations living in Mogadishu IDP camps. The intervention was successful in improving maternal knowledge and vaccination coverage but unsuccessful in improving timely vaccination. We conducted a qualitative study to understand this result and analyze the multi-level barriers to routine childhood immunization uptake. METHOD: In this qualitative study we used observation data from 40 PLA group discussions with female caregivers and purposively sampled nine vaccination service providers and six policy makers for interview. We also reviewed national-level vaccine policy documents and assessed the quality of health facilities in the study area. We used the socioecological framework to structure our analysis and analyzed the data in NVivo. RESULTS: The barriers to childhood vaccination among IDPs at the individual level were fear due to lack of knowledge, mistrust of vaccines, concerns about side effects and misinformation; opportunity costs; and costs of transportation. At the interpersonal level, family members played an important role as did the extent of decision-making autonomy. Community factors such as cultural practices, gender roles, and household evictions influenced vaccination. Organizational issues at health facilities such as waiting times, vaccine stock-outs, distance to the facility, language differences, and hesitancy of health workers to open multi-dose vials affected vaccination. At the policy level, confusion about the eligible age for routine vaccination and age restrictions for catch-up vaccination and certain antigens such as BCG were important barriers. CONCLUSION: Complex and interrelated factors affect childhood vaccination uptake among IDPs in Somalia. Interventions that address multiple barriers simultaneously will have the greatest impact given the complex nature of vulnerabilities in this population. There is a need to strengthen the health system and connect it with existing community structures to increase demand for services. Our research highlights the importance of formative research before implementing interventions. Further research on the integration of health service strengthening with PLA to improve childhood vaccination among IDPs is recommended. TRIAL REGISTRATION NUMBER: ISRCTN-83,172,390. Date of registration: 03/08/2021.

Differences in the Genomic Profiles of Immunoparalyzed and Nonimmunoparalyzed Children With Sepsis: A Pilot Study.

OBJECTIVES: Sepsis-induced immunoparalysis represents a pathologic downregulation of leukocyte function shown to be associated with adverse outcomes, although its mechanisms remain poorly understood. Our goal was to compare genome-wide gene expression profiles of immunoparalyzed and nonimmunoparalyzed children with sepsis to identify genes and pathways associated with immunoparalysis. DESIGN: Prospective observational study. PATIENTS: Twenty-six children with lower respiratory tract infection meeting criteria for sepsis, severe sepsis, or septic shock admitted to the PICU. SETTING: Two tertiary care PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Innate immune function was assayed ex vivo by measuring release of tumor necrosis factor-α from whole blood after incubation with lipopolysaccharide for 4 hours. Immunoparalysis was defined as a tumor necrosis factor-α production capacity less than 200 pg/mL. Ten of the 26 children were immunoparalyzed. There were 17 significant differentially expressed genes when comparing genome-wide gene expression profiles of immunoparalyzed and nonimmunoparalyzed children (false discovery rate < 0.05). Nine genes showed increased expression in immunoparalyzed children (+1.5- to +8.8-fold change). Several of these dampen the immune system. Eight showed decreased expression in immunoparalyzed children (-1.7- to -3.9-fold change), several of which are involved in early regulation and activation of immune function. Functional annotation clustering using differentially expressed genes with p value of less than 0.05 showed three clusters related to immunity with significant enrichment scores (2.2-4.5); the most significant gene ontology terms in these clusters were antigen processing and presentation and negative regulation of interleukin-6 production. Network analysis identified potential protein interactions that may be involved in the development of immunoparalysis in children. CONCLUSIONS: In this exploratory analysis, immunoparalyzed children with sepsis showed increased expression of genes that dampen the immune system and decreased expression of genes involved in regulation and activation of the immune system. Analysis also implicated other proteins as potentially having as yet unidentified roles in the development of immunoparalysis.

Feasibility and efficacy of sepsis management guidelines in a pediatric intensive care unit in Saudi Arabia: a quality improvement initiative.

OBJECTIVES: Evaluation of feasibility and effectiveness of Surviving Sepsis Campaign (SSC) Guidelines implementation at a Pediatric Intensive Care Unit (PICU) in Saudi Arabia to reduce severe sepsis associated mortality. DESIGN: Retrospective data analysis for a prospective quality improvement (QI) initiative. SETTINGS: PICU at King Saud University Medical City, Saudi Arabia. PARTICIPANTS: Children ≤14 years of age admitted to the PICU from July 2010 to March 2011 with suspected or proven sepsis. Comparisons were made to a previously admitted group of patients with sepsis from October 2009 to June 2010. INTERVENTIONS: Adaptation and implementation of the Surviving Sepsis Campaign-Clinical Practice Guidelines (SSC-CPGs) through AGREE instrument and ADAPTE process. MAIN OUTCOME MEASURES: We reported pre- and post-implementation outcome of interest for this QI initiative, annual sepsis-related mortality rate. Furthermore, we reported follow-up of annual mortality rate until December 2016. RESULTS: Sixty-five patients was included in the study (42 in post-guidelines implementation group and 23 in pre-guidelines implementation group). Mortality was insignificantly lower in the post-implementation group (26.2% vs. 47.8%; P = 0.079). However, when adjusted for severity, identified by number of failing organs in the multivariate regression analysis, the mortality difference was favorable for the post-implementation group (P = 0.006). The lower sepsis-related mortality rate was also sustained, with an average mortality rate of 15.11% for the subsequent years (2012-16). CONCLUSIONS: Adaptation and implementation of SSC Guidelines in our setting support its feasibility and potential benefits. However, a larger study is recommended to explore detailed compliance rates.

Rs37972 and rs37973 single-nucleotide polymorphisms in the glucocorticoid-inducible 1 gene are not associated with asthma risk in a Saudi Arabian population.

OBJECTIVE: Rs37972 and rs37973 variants in the glucocorticoid-induced transcript 1 gene have been associated with inhaled glucocorticosteroid responsiveness in asthmatics; however, some discrepancies have been also reported. This study aims to determine whether rs37972 and rs37973 SNPs are associated with asthma risk in Saudi Arabian asthmatics. METHODS: Two-hundred seventy-one diagnosed asthmatics (3-65 years old) and 387 healthy control subjects of equivalent age were recruited. DNA from peripheral blood was purified, and genotyping of rs37972 and rs37973 SNPs was performed by PCR amplification of segments of interest, followed by Sanger sequencing. RESULTS: The global frequencies of the minor (risk) alleles were 28% ("T" allele, rs37972) and 30% ("G" allele, rs37973). Yates-corrected Chi-square (χ(2)) tests revealed significant differences between asthmatic and healthy groups, in allele frequencies for rs37973 SNP only (χ(2) = 3.98, Yates' p value = 0.046). Regarding genotype frequencies, a significant difference between asthmatic and healthy groups was observed for variant rs37972 only (χ(2) = 8.19, Yates' p value = 0.016). To determine a possible association of the minor "T" and "G" alleles with asthma, both the recessive and dominant genetic models were tested. For rs37973, none of the genotypes were significantly associated with asthma. Concerning rs37972, the dominant model (C/T + T/T versus C/C) indicated a significant "protective" association with asthma, in which C/T + T/T individuals had lower odds of being asthmatics than C/C individuals (OR = 0.67; 95% CI = 0.48-0.94; p = 0.019*). CONCLUSIONS: The minor alleles "T" and "G" of rs37972 and rs37973 SNPs, respectively, were not significantly associated with increased asthma risk in asthma patients from Saudi Arabia.

Recall of exposure in UK farmers and pesticide applicators: trends with follow-up time.

BACKGROUND: Occupational epidemiological studies on pesticide use commonly rely on self-reported questionnaire or interview data to assess exposure. Insight into recall accuracy is important, as misclassification of exposures due to imperfect recall can bias risk estimates. METHODS: We assessed the ability of workers in three UK cohorts (Prospective Investigation of Pesticide Applicators' Health [PIPAH], Pesticide Users' Health Study [PUHS], and Study of Health in Agricultural Work [SHAW]) to remember their working history related to pesticide exposure over time periods ranging from 3 to 14 years prior. During 2019-2020, cohort participants were re-surveyed using a similar questionnaire to that used previously. We compared recall of responses at follow-up to those reported at baseline related to crops/areas of work, use of personal protective equipment (PPE) items, hygiene habits, frequency of pesticide use, and application method. To assess the extent of recall, we used sensitivity, specificity, the percentage of overall agreement, and area under the curve (AUC) values. We also examined the presence of over or underestimation of recalled years, and days and hours per year, of working with pesticides using geometric mean ratios (GMR) and regression analysis to investigate any trends based on demographic characteristics. RESULTS: There were 643 individuals who completed both the baseline and follow-up surveys in the three cohorts with response rates ranging from 17 to 46%. There was a strong correlation (rho = 0.77) between the baseline and recalled years working with pesticides, though higher values were reported at follow-up (GMR = 1.18 [95% confidence interval: 1.07-1.30]) with no consistent differences by demographic characteristics. There was stronger agreement in the recalled days compared to hours per year in two of the cohorts. Recall for a number of exposure determinants across short and longer periods entailed overall agreement of >70%, though with some differences: for example, sensitivity for long-term recall of crops was poor (<43% in PUHS), whereas short-term recall of hygiene practices was good (AUC range = 0.65-1.00 in PIPAH). CONCLUSION: Results indicate that recall ability may deteriorate over a longer period. Although low-response rates may require these findings to be interpreted with caution, recall for a number of exposure determinants appeared reliable, such as crops and hygiene practices within 3 years, as well as days per year working with pesticides.

Leveraging Polio Geographic Information System Platforms in the African Region for Mitigating COVID-19 Contact Tracing and Surveillance Challenges: Viewpoint.

BACKGROUND: The ongoing COVID-19 pandemic in Africa is an urgent public health crisis. Estimated models projected over 150,000 deaths and 4,600,000 hospitalizations in the first year of the disease in the absence of adequate interventions. Therefore, electronic contact tracing and surveillance have critical roles in decreasing COVID-19 transmission; yet, if not conducted properly, these methods can rapidly become a bottleneck for synchronized data collection, case detection, and case management. While the continent is currently reporting relatively low COVID-19 cases, digitized contact tracing mechanisms and surveillance reporting are necessary for standardizing real-time reporting of new chains of infection in order to quickly reverse growing trends and halt the pandemic. OBJECTIVE: This paper aims to describe a COVID-19 contact tracing smartphone app that includes health facility surveillance with a real-time visualization platform. The app was developed by the AFRO (African Regional Office) GIS (geographic information system) Center, in collaboration with the World Health Organization (WHO) emergency preparedness and response team. The app was developed through the expertise and experience gained from numerous digital apps that had been developed for polio surveillance and immunization via the WHO's polio program in the African region. METHODS: We repurposed the GIS infrastructures of the polio program and the database structure that relies on mobile data collection that is built on the Open Data Kit. We harnessed the technology for visualization of real-time COVID-19 data using dynamic dashboards built on Power BI, ArcGIS Online, and Tableau. The contact tracing app was developed with the pragmatic considerations of COVID-19 peculiarities. The app underwent testing by field surveillance colleagues to meet the requirements of linking contacts to cases and monitoring chains of transmission. The health facility surveillance app was developed from the knowledge and assessment of models of surveillance at the health facility level for other diseases of public health importance. The Integrated Supportive Supervision app was added as an appendage to the pre-existing paper-based surveillance form. These two mobile apps collected information on cases and contact tracing, alongside alert information on COVID-19 reports at the health facility level; the information was linked to visualization platforms in order to enable actionable insights. RESULTS: The contact tracing app and platform were piloted between April and June 2020; they were then put to use in Zimbabwe, Benin, Cameroon, Uganda, Nigeria, and South Sudan, and their use has generated some palpable successes with respect to COVID-19 surveillance. However, the COVID-19 health facility-based surveillance app has been used more extensively, as it has been used in 27 countries in the region. CONCLUSIONS: In light of the above information, this paper was written to give an overview of the app and visualization platform development, app and platform deployment, ease of replicability, and preliminary outcome evaluation of their use in the field. From a regional perspective, integration of contact tracing and surveillance data into one platform provides the AFRO with a more accurate method of monitoring countries' efforts in their response to COVID-19, while guiding public health decisions and the assessment of risk of COVID-19.

Use of verbal autopsy for establishing causes of child mortality in camps for internally displaced people in Mogadishu, Somalia: a population-based, prospective, cohort study.

BACKGROUND: People in humanitarian emergencies are likely to experience excess mortality but information on the causes of death is often unreliable or non-existent. This study aimed to provide evidence on the causes of death among children younger than 5 years in camps for internally displaced people in southern Somalia, during periods of protracted displacement and emergency influx amid the 2017 drought and health emergency. METHODS: We did a prospective, cohort study in 25 camps in the Afgooye corridor, on the outskirts of Mogadishu, Somalia. All internally displaced children aged 6-59 months were included and followed up with monthly household visits by community health workers. Nutrition, health, and vaccination status were ascertained and verbal autopsy interviews were done with the caregivers of deceased children. We calculated death rates in these children and used verbal autopsy to establish the cause-specific mortality fraction (CSMF). Bayesian InterVA software was used to assign likely causes to each death. FINDINGS: Between March, 2016, and March, 2018, 3898 children were followed up. 153 deaths were recorded during 34 746 person-months of observation. The death rate among children younger than 5 years exceeded emergency thresholds (>2 deaths per 10 000 children per day), reaching a peak of seven deaths per 10 000 children per day during the emergency influx. Verbal autopsy data were gathered for 80% of deaths, and the CSMF for the three leading causes of death were diarrhoeal diseases (25·9%), measles (17·8%), and severe malnutrition (8·8%). Coverage of measles vaccination during the first 3 months of the emergency was 42% and the CSMF for measles doubled during the influx. During protracted displacement, symptoms that could be attributable to HIV/AIDS related deaths accounted for 1·6% of the CSMF. INTERPRETATION: It is feasible to establish a health and nutrition surveillance system that ascertains causes of death, using verbal autopsy, in this humanitarian context. These data can inform policy, response planning, and priority setting. The high mortality rate from infectious diseases and malnutrition among children younger than 5 years suggests the need for strengthening a range of public health interventions, including vaccination and provision of water, sanitation, and hygiene. FUNDING: UK Department of International Development.

Forced evictions and their social and health impacts in Southern Somalia: a qualitative study in Mogadishu Internally Displaced Persons (IDP) camps.

BACKGROUND: Forced evictions are common in conflict-affected settings. More than 500 internally displaced persons (IDPs) are evicted daily in Mogadishu. Context specific research is necessary to inform responsive humanitarian interventions and to monitor the effectiveness of these interventions on IDPs health. OBJECTIVE: This study explored the causes of forced evictions and their health impacts among IDPs in southern Somalia. METHODS: We used a qualitative approach, conducting 20 semi-structured interviews, six key informant interviews and four focus group discussions. We used maximum variation sampling to include a wide range of participants and used the framework approach and Nvivo software to analyse the data. RESULTS: In this context, landlords often rented land without proper tenure agreements, resulting in risk of forced evictions. Informal tenure agreements led to fluctuations in rent, and IDPs were evicted because tenancy laws were inadequate and failed to protect IDP rights. IDP settlements often increased the value of land by clearing scrub, and landlords often sought to profit from this by evicting IDPs at short notice if a buyer was found for the land. The effect of eviction on an already marginalised population was wide ranging, increasing their exposure to violence, loss of assets, sexual assault, disruption of livelihoods, loss of social networks and family separation. Evicted IDPs reported health issues such as diarrhoea, malaria, pneumonia, measles and skin infections, as well as stress, anxiety, psychological distress and trauma. CONCLUSION: Forced evictions remain one of the biggest challenges for IDPs as they exacerbate existing vulnerabilities. Prioritizing implementation of legal protection for IDP tenure rights is necessary to prevent unlawful evictions of IDPs. Humanitarian agencies should aim to respond more effectively to protect evictees and provide support to prevent poor health outcomes. Further quantitative research is needed to further examine the relationship between forced evictions and health outcomes.

Recent sexual violence exposure is associated with immune biomarkers of HIV susceptibility in women.

PROBLEM: HIV/AIDS and sexual violence act synergistically and compromise women's health. Yet, immuno-biological mechanisms linking sexual violence and increased HIV susceptibility are poorly understood. METHODS: We conducted a cross-sectional pilot study of HIV-uninfected women, comparing 13 women exposed to forced vaginal penetration within the past 12 weeks (Exposed) with 25 Non-Exposed women. ELISA assays were conducted for 49 biomarkers associated with HIV pathogenesis in plasma and cervicovaginal lavage (CVL). Differences between Exposed and Non-Exposed were analyzed by linear and logistic regression, using propensity score weighting to control for age, race, socioeconomic status, menstrual cycle, and contraceptive use. RESULTS: In CVL, Exposed women had significantly reduced chemokines MIP-3α (p < .01), MCP-1 (p < .01), and anti-HIV/wound-healing thrombospondin-1 (p = .03). They also had significantly increased inflammatory cytokine IL-1α (p < 0.01) and were more likely to have detectable wound-healing PDGF (p = .02). In plasma, Exposed women had reduced chemokines MIP-3α (p < .01) and IL-8 (p < .01), anti-inflammatory cytokine TGF-ß (p = .02), anti-HIV/antimicrobial HBD-2 (p = .02), and wound-healing MMP-1 (p = 0.02). They also had increased thrombospondin-1 (p < .01) and Cathepsin B (p = .01). After applying the stringent method of false discovery rate adjustment, differences for IL-1α (p = .05) and MCP-1 (p = .03) in CVL and MIP-3α (p = .03) in plasma remained significant. CONCLUSIONS: We report systemic and mucosal immune dysregulation in women exposed to sexual violence. As these biomarkers have been associated with HIV pathogenesis, dysregulation may increase HIV susceptibility.

Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic.

Importance: Multiple inflammatory syndrome in children (MIS-C) occurs in association with the COVID-19 pandemic. Objective: To describe the clinical characteristics and geographic and temporal distribution of the largest cohort of patients with MIS-C in the United States to date. Design, Setting, and Participants: Cross-sectional analysis was conducted on clinical and laboratory data collected from patients with MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 and met MIS-C case definition. Main Outcomes and Measures: Geographic and temporal distribution of MIS-C was compared with that of COVID-19 nationally, by region, and level of urbanicity by county. Clinical and laboratory findings and changes over time were described by age group and by presence or absence of preceding COVID-19. Results: A total of 1733 patients with MIS-C were identified; 994 (57.6%) were male and 1117 (71.3%) were Hispanic or non-Hispanic Black. Gastrointestinal symptoms, rash, and conjunctival hyperemia were reported by 53% (n = 931) to 67% (n = 1153) of patients. A total of 937 patients (54%) had hypotension or shock, and 1009 (58.2%) were admitted for intensive care. Cardiac dysfunction was reported in 484 patients (31.0%), pericardial effusion in 365 (23.4%), myocarditis in 300 (17.3%), and coronary artery dilatation or aneurysms in 258 (16.5%). Patients aged 0 to 4 years had the lowest proportion of severe manifestations, although 171 patients (38.4%) had hypotension or shock and 197 (44.3%) were admitted for intensive care. Patients aged 18 to 20 years had the highest proportions with myocarditis (17 [30.9%]), pneumonia (20 [36.4%]), acute respiratory distress syndrome (10 [18.2%]), and polymerase chain reaction positivity (39 [70.9%]). These older adolescents also had the highest proportion reporting preceding COVID-19-like illness (63%). Nationally, the first 2 MIS-C peaks followed the COVID-19 peaks by 2 to 5 weeks. The cumulative MIS-C incidence per 100 000 persons younger than 21 years was 2.1 and varied from 0.2 to 6.3 by state. Twenty-four patients (1.4%) died. Conclusions and Relevance: In this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19.

Airways Expression of SARS-CoV-2 Receptor, ACE2, and TMPRSS2 Is Lower in Children Than Adults and Increases with Smoking and COPD.

It has been reported that angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the main cell entry proteins for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and play a critical role in causing coronavirus disease 2019 (COVID-19). To investigate the expression level of these SARS-CoV-2 host cell entry genes in the lung airway, we used public gene expression datasets. We have found a differential expression of ACE2 and TMPRSS2 in nasal and bronchial airways relative to age and diseases status. Children were found to have significantly lower expression of COVID-19 receptors in the upper and lower airways (nasal and bronchial). Moreover, the lung airway expression of both ACE2 and TMPRSS2 was found to be significantly upregulated in smokers compared with non-smokers, and in patients with chronic obstructive pulmonary disease (COPD) compared with healthy subjects. No difference was observed in the blood expression levels of ACE2 and TMPRSS2 between children and adults, or in COPD or diabetic patients. However, a significant increase in blood expression levels of these genes was observed in patients with essential hypertension, whereas only ACE2 was upregulated in the blood of asthmatics. These results suggest that the observed difference in COVID-19 severity between children and adults could, in part, be attributed to the difference in ACE2 and TMPRSS2 airways tissue expression levels.

Virulence genes and previously unexplored gene clusters in four commensal Neisseria spp. isolated from the human throat expand the neisserial gene repertoire.

Commensal non-pathogenic Neisseria spp. live within the human host alongside the pathogenic Neisseria meningitidis and Neisseria gonorrhoeae and due to natural competence, horizontal gene transfer within the genus is possible and has been observed. Four distinct Neisseria spp. isolates taken from the throats of two human volunteers have been assessed here using a combination of microbiological and bioinformatics techniques. Three of the isolates have been identified as Neisseria subflava biovar perflava and one as Neisseria cinerea. Specific gene clusters have been identified within these commensal isolate genome sequences that are believed to encode a Type VI Secretion System, a newly identified CRISPR system, a Type IV Secretion System unlike that in other Neisseria spp., a hemin transporter, and a haem acquisition and utilization system. This investigation is the first to investigate these systems in either the non-pathogenic or pathogenic Neisseria spp. In addition, the N. subflava biovar perflava possess previously unreported capsule loci and sequences have been identified in all four isolates that are similar to genes seen within the pathogens that are associated with virulence. These data from the four commensal isolates provide further evidence for a Neisseria spp. gene pool and highlight the presence of systems within the commensals with functions still to be explored.

Dysregulation in Genital Tract Soluble Immune Mediators in Postmenopausal Women Is Distinct by HIV Status.

A rise in new HIV diagnoses among older adults is characterized by poor prognosis and reduced survival times. Although heterosexual transmission remains the main route of infection in women, little is known regarding immune functions in the genital tract of postmenopausal women, especially those who are HIV positive. Furthermore, effects of hormone replacement therapy (HRT) on the genital tract immune system are unclear. Using the Women's Interagency HIV Study repository, we obtained cervical-vaginal lavage (CVL) samples from premenopausal and postmenopausal HIV-positive and HIV-negative women, some of whom were on HRT. Samples were assayed for interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, secretory leukocyte protease inhibitor (SLPI), Elafin, human beta defensin-2 (HBD2), and macrophage inflammatory protein (MIP)-3α using ELISA. Anti-HIV activity in CVL was measured using TZM-bl indicator cells. Among HIV-positive women, the plasma viral load was significantly higher and CD4 count was significantly lower in postmenopausal compared with premenopausal women. Postmenopausal women, irrespective of HIV status, had significantly lower levels of HBD2 compared with premenopausal women. Among the HIV-negative individuals, postmenopausal women had significantly lower levels of MIP-3α, IL-6, and SLPI compared with premenopausal women. In contrast, HIV-positive postmenopausal women had significantly higher levels of TNF-α compared with HIV-positive premenopausal women. In most cases, HRT groups resembled the postmenopausal groups. No significant differences in anti-HIV activity by menopausal or by HIV status were noted. Our findings indicate that the female genital tract immune microenvironment is distinct by menopausal status and HIV status. Further studies are needed to assess the risk of HIV acquisition/transmission in this population.

Infectious and Noninfectious Acute Pericarditis in Children: An 11-Year Experience.

OBJECTIVE: The study was undertaken to determine the etiology, review management, and outcome in children diagnosed with acute pericarditis during 11 years at tertiary pediatric institution. METHODS: Retrospective chart review of children diagnosed between 2004 and 2014. Patients with postsurgical pericardial effusions were excluded. RESULTS: Thirty-two children were identified (median age 10yr/11mo). Pericardiocentesis was performed in 24/32 (75%) patients. The most common cause of pericarditis was infection in 11/32 (34%), followed by inflammatory disorders in 9 (28%). Purulent pericarditis occurred in 5 children including 4 due to Staphylococcus aureus: 2 were methicillin resistant (MRSA). All patients with purulent pericarditis had concomitant infection including soft tissue, bone, or lung infection; all had pericardial drain placement and 2 required pericardiotomy and mediastinal exploration. Other infections were due to Histoplasma capsulatum (2), Mycoplasma pneumoniae (2), Influenza A (1), and Enterovirus (1). Pericarditis/pericardial effusion was the initial presentation in 4 children with systemic lupus erythematosus including one who presented with tamponade and in 2 children who were diagnosed with systemic onset juvenile inflammatory arthritis. Tumors were diagnosed in 2 patients. Five children had recurrent pericarditis. Systemic antibiotics were used in 21/32 (66%) and prednisone was used in 11/32 (34%) patients. CONCLUSION: Infections remain an important cause of pericarditis in children. Purulent pericarditis is most commonly caused by Staphylococcus aureus and is associated with significant morbidity, need of surgical intervention, and prolonged antibiotic therapy. Echocardiography-guided thoracocentesis remains the preferred diagnostic and therapeutic approach. However, pericardiotomy and drainage are needed when appropriate clinical response is not achieved with percutaneous drainage.

Pediatric pain management: More opportunities for better comfort.

Pediatric pain assessment is vital for optimal pediatric practice. After a year of implementation of pediatric pain assessment tools at a tertiary university hospital (King Saud University Medical City, Riyadh, Saudi Arabia), the physicians in the Department of Pediatrics were invited to participate in an interactive lecture about pediatric pain management to assess their awareness about using these tools. Their responses demonstrated that almost half of them were not using any pain scale in their daily practice. These findings highlight the need for a new strategy of implementation. The improvement of pain assessment and management necessitates extensive educational campaign for all health care providers and early audit in order to improve the physicians' awareness and compliance with these changes.

Site selectivity in the binding of inorganic anions to serum transferrin.

Equilibrium constants for the sequential binding of two anions at the specific metal-binding sites of apotransferrin have been measured by difference ultraviolet spectroscopy in 0.1 M N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes) at pH 7.4 and 25 degrees C. Log K1 values for phosphate, phosphite, sulfate, and arsenate fall in the narrow range of 3.5-4.0, while the log K1 for bicarbonate is 2.73. No binding is observed for nitrate, perchlorate, or borate. A dinegative charge appears to be the most important criterion for anion binding. Equilibrium constants have also been measured for binding of anions to both forms of mono(ferric)transferrin. There appears to be a very small site selectivity (0.2 to 0.4 log units) for phosphate, arsenate, and phosphite that favors binding to the N-terminal site, but there is no detectable selectivity for binding of sulfate or bicarbonate. Comparison of the binding affinities and anion selectivity with literature data on anion-binding to protonated macrocyles and cryptates strongly supports the existence of specific anion-binding sites on the protein. Binding constants were also measured in 0.01 M Hepes. The anionic sulfonate group of the buffer appears to have a small effect on anion binding.