Ventricular assist device implantation in a patient with systemic right ventricle and pectus excavatum

Systemic right ventricular failure is a common finding in patients with transposition of the great arteries. Some of these patients require ventricular assist device implantation. We describe the feasibility of HeartMate 3 [Abbott, Illinois, United States] implantation in a patient with transposition of the great arteries, high human leukocyte antigen sensitization, and severe pectus excavatum using a two-stage approach. Learning objectives: 1. To notice the challenges faced while implanting HeartMate 3 [Abbott, Illinois, United States] in patients with congenital heart disease and anatomical limitations. 2. To understand that despite the difficulties, HeartMate 3 implantation is possible, worthwhile, and sometimes the only choice in a patient with end-stage heart failure and congenital heart disease

‘That is because we are alone’:A relational qualitative study of socio-spatial inequities in maternal and newborn health programme coverage in rural Uttar Pradesh, India

This qualitative study was conducted in Uttar Pradesh state, India to explore how interrelated socio-economic position and spatial characteristics of four diverse villages may have influenced equity in coverage of community-based maternal and newborn health (MNH) services. We conducted social mapping and three focus group discussions in each village, among women of lower and higher socio-economic position who recently gave birth, and with community health workers (n = 134). Data were analysed in NVivo 11.0 using thematic framework analysis. The extent of socio-economic hierarchies and spatial disparateness within the village, combined with distance to larger centers, together shaped villages’ level of socio-spatial remoteness. Disadvantaged socio-economic groups expressed being more often spatially isolated, with less access to infrastructure, resources or services, which was heightened if the village was physically distant from larger centers. In more socio-spatially remote villages, inequities in coverage of MNH services that disadvantaged lower socio-economic position groups were compounded as these groups more often experienced ASHA vacancies, as well as greater distance to and poorer perceived quality of health services nearest the village. The results inform a conceptual framework of ‘socio-spatial remoteness’ that can guide public health research and programmes to more comprehensively address health inequities within India and beyond.</p

Separating mouse malignant cell line (EL4) from neonate spermatogonial stem cells utilizing microfluidic device in vitro

Background: Some children who have survived cancer will be azoospermic in the future. Performing isolation and purification procedures for spermatogonial stem cells (SSC) is very critical. In this regard, performing the process of decontamination of cancerous cells is the initial step. The major objective of the present study is to separate the malignant EL4 cell line in mice and spermatogonial stem cells in vitro. Methods: The spermatogonial stem cells of sixty neonatal mice were isolated, and the procedure of co-culturing was carried out by EL4 which were classified into 2 major groups: (1) the control group (co-culture in a growth medium) and (2) the group of co-cultured cells which were separated using the microfluidic device. The percentage of cells was assessed using flow cytometry technique and common laboratory technique of immunocytochemistry and finally was confirmed through the laboratory technique of reverse transcription-polymerase chain reaction (RT-PCR). Results: The actual percentage of EL4 and SSC after isolation was collected at two outlets: the outputs for the smaller outlet were 0.12 for SSC and 42.14 for EL4, while in the larger outlet, the outputs were 80.38 for SSC and 0.32 for EL4; in the control group, the percentages of cells were 21.44 for SSC and 23.28 for EL4 (based on t test (p � 0.05)). Conclusions: The present study demonstrates that the use of the microfluidic device is effective in separating cancer cells from spermatogonial stem cells. © 2020 The Author(s)

Correction to: Separating mouse malignant cell line (EL4) from neonate spermatogonial stem cells utilizing microfluidic device in vitro (Stem Cell Research & Therapy, (2020), 11, 1, (191), 10.1186/s13287-020-01671-1)

The original article 1 displays incorrect affiliation information; the correct affiliations for each author can be viewed in this Correction article. © 2020, The Author(s)

Assessment of an antibody-in-lymphocyte supernatant assay for the etiological diagnosis of pneumococcal pneumonia in children

New diagnostic tests for the etiology of childhood pneumonia are needed. We evaluated the antibody-in-lymphocyte supernatant (ALS) assay to detect immunoglobulin (Ig) G secretion from ex vivo peripheral blood mononuclear cell (PBMC) culture, as a potential diagnostic test for pneumococcal pneumonia. We enrolled 348 children with pneumonia admitted to Patan Hospital, Kathmandu, Nepal between December 2015 and September 2016. PBMCs sampled from participants were incubated for 48 h before harvesting of cell culture supernatant (ALS). We used a fluorescence-based multiplexed immunoassay to measure the concentration of IgG in ALS against five conserved pneumococcal protein antigens. Of children with pneumonia, 68 had a confirmed etiological diagnosis: 12 children had pneumococcal pneumonia (defined as blood or pleural fluid culture-confirmed; or plasma CRP concentration ≥60 mg/l and nasopharyngeal carriage of serotype 1 pneumococci), and 56 children had non-pneumococcal pneumonia. Children with non-pneumococcal pneumonia had either a bacterial pathogen isolated from blood (six children); or C-reactive protein <60 mg/l, absence of radiographic consolidation and detection of a pathogenic virus by multiplex PCR (respiratory syncytial virus, influenza viruses, or parainfluenza viruses; 23 children). Concentrations of ALS IgG to all five pneumococcal proteins were significantly higher in children with pneumococcal pneumonia than in children with non-pneumococcal pneumonia. The concentration of IgG in ALS to the best-performing antigen discriminated between children with pneumococcal and non-pneumococcal pneumonia with a sensitivity of 1.0 (95% CI 0.73–1.0), specificity of 0.66 (95% CI 0.52–0.78) and area under the receiver-operating characteristic curve (AUROCC) 0.85 (95% CI 0.75–0.94). Children with pneumococcal pneumonia were older than children with non-pneumococcal pneumonia (median 5.6 and 2.0 years, respectively, p < 0.001). When the analysis was limited to children ≥2 years of age, assay of IgG ALS to pneumococcal proteins was unable to discriminate between children with pneumococcal pneumonia and non-pneumococcal pneumonia (AUROCC 0.67, 95% CI 0.47–0.88). This method detected spontaneous secretion of IgG to pneumococcal protein antigens from cultured PBMCs. However, when stratified by age group, assay of IgG in ALS to pneumococcal proteins showed limited utility as a test to discriminate between pneumococcal and non-pneumococcal pneumonia in children

Understanding the roles of community health workers in improving perinatal health equity in rural Uttar Pradesh, India: a qualitative study

Background: Despite substantial reductions in perinatal deaths (stillbirths and early neonatal deaths), India’s perinatal mortality rates remain high, both nationally and in individual states. Rates are highest among disadvantaged socio-economic groups. To address this, India’s National Health Mission has trained community health workers called Accredited Social Health Activists (ASHAs) to counsel and support women by visiting them at home before and after childbirth. We conducted a qualitative study to explore the roles of ASHAs’ home visits in improving equity in perinatal health between socio-economic position groups in rural Uttar Pradesh (UP), India. Methods: We conducted social mapping in four villages of two districts in UP, followed by three focus group discussions in each village (12 in total) with ASHAs and women who had recently given birth belonging to ‘higher’ and ‘lower’ socio-economic position groups (n = 134 participants). We analysed the data in NVivo and Dedoose using a thematic framework approach. Results: Home visits enabled ASHAs to build trusting relationships with women, offer information about health services, schemes and preventive care, and provide practical support for accessing maternity care. This helped many women and families prepare for birth and motivated them to deliver in health facilities. In particular, ASHAs encouraged women who were poorer, less educated or from lower caste groups to give birth in public Community Health Centres (CHCs). However, women who gave birth at CHCs often experienced insufficient emergency obstetric care, mistreatment from staff, indirect costs, lack of medicines, and referrals to higher-level facilities when complications occurred. Referrals often led to delays and higher fees that placed the greatest burden on families who were considered of lower socio-economic position or living in remote areas, and increased their risk of experiencing perinatal loss. Conclusions: The study found that ASHAs built relationships, counselled and supported many pregnant women of lower socio-economic positions. Ongoing inequities in health facility births and perinatal mortality were perpetuated by overlapping contextual issues beyond the ASHAs’ purview. Supporting ASHAs’ integration with community organisations and health system strategies more broadly is needed to address these issues and optimise pathways between equity in intervention coverage, processes and perinatal health outcomes

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis

Planck early results. VI. The High Frequency Instrument data processing

We describe the processing of the 336 billion raw data samples from the High Frequency Instrument (HFI) which we performed to produce six temperature maps from the first 295 days of Planck-HFI survey data. These maps provide an accurate rendition of the sky emission at 100, 143, 217, 353, 545 and 857GHz with an angular resolution ranging from 9.9 to 4.4 . The white noise level is around 1.5 μK degree or less in the 3 main CMB channels (100–217 GHz). The photometric accuracy is better than 2% at frequencies between 100 and 353 GHz and around 7% at the two highest frequencies. The maps created by the HFI Data Processing Centre reach our goals in terms of sensitivity, resolution, and photometric accuracy. They are already sufficiently accurate and well-characterised to allow scientific analyses which are presented in an accompanying series of early papers. At this stage, HFI data appears to be of high quality and we expect that with further refinements of the data processing we should be able to achieve, or exceed, the science goals of the Planck project

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health

Anemia prevalence in women of reproductive age in low- and middle-income countries between 2000 and 2018

Anemia is a globally widespread condition in women and is associated with reduced economic productivity and increased mortality worldwide. Here we map annual 2000–2018 geospatial estimates of anemia prevalence in women of reproductive age (15–49 years) across 82 low- and middle-income countries (LMICs), stratify anemia by severity and aggregate results to policy-relevant administrative and national levels. Additionally, we provide subnational disparity analyses to provide a comprehensive overview of anemia prevalence inequalities within these countries and predict progress toward the World Health Organization’s Global Nutrition Target (WHO GNT) to reduce anemia by half by 2030. Our results demonstrate widespread moderate improvements in overall anemia prevalence but identify only three LMICs with a high probability of achieving the WHO GNT by 2030 at a national scale, and no LMIC is expected to achieve the target in all their subnational administrative units. Our maps show where large within-country disparities occur, as well as areas likely to fall short of the WHO GNT, offering precision public health tools so that adequate resource allocation and subsequent interventions can be targeted to the most vulnerable populations.Peer reviewe