Genetic signatures of Mycobacterium tuberculosis Nonthaburi genotype revealed by whole genome analysis of isolates from tuberculous meningitis patients in Thailand.

Genome sequencing plays a key role in understanding the genetic diversity of Mycobacterium tuberculosis (M.tb). The genotype-specific character of M. tb contributes to tuberculosis severity and emergence of drug resistance. Strains of M. tb complex can be classified into seven lineages. The Nonthaburi (NB) genotype, belonging to the Indo-Oceanic lineage (lineage 1), has a unique spoligotype and IS6110-RFLP pattern but has not previously undergone a detailed whole genome analysis. In addition, there is not much information available on the whole genome analysis of M. tb isolates from tuberculous meningitis (TBM) patients in public databases. Isolates CSF3053, 46-5069 and 43-13838 of NB genotype were obtained from the cerebrospinal fluids of TBM Thai patients in Siriraj Hospital, Bangkok. The whole genomes were subjected to high throughput sequencing. The sequence data of each isolate were assembled into draft genome. The sequences were also aligned to reference genome, to determine genomic variations. Single nucleotide polymorphisms (SNPs) were obtained and grouped according to the functions of the genes containing them. They were compared with SNPs from 1,601 genomes, representing the seven lineages of M. tb complex, to determine the uniqueness of NB genotype. Susceptibility to first-line, second-line and other antituberculosis drugs were determined and related to the SNPs previously reported in drug-resistant related genes. The assembled genomes have an average size of 4,364,461 bp, 4,154 genes, 48 RNAs and 64 pseudogenes. A 500 base pairs deletion, which includes ppe50, was found in all isolates. RD239, specific for members of Indo Oceanic lineage, and RD147c were identified. A total of 2,202 SNPs were common to the isolates and used to classify the NB strains as members of sublineage 1.2.1. Compared with 1,601 genomes from the seven lineages of M. tb complex, mutation G2342203C was found novel to the isolates in this study. Three mutations (T28910C, C1180580T and C152178T) were found only in Thai NB isolates, including isolates from previous study. Although drug susceptibility tests indicated pan-susceptibility, non-synonymous SNPs previously reported to be associated with resistance to anti-tuberculous drugs; isoniazid, ethambutol, and ethionamide were identified in all the isolates. Non-synonymous SNPs were found in virulence genes such as the genes playing roles in apoptosis inhibition and phagosome arrest. We also report polymorphisms in essential genes, efflux pumps associated genes and genes with known epitopes. The analysis of the TBM isolates and the availability of the variations obtained will provide additional resources for global comparison of isolates from pulmonary tuberculosis and TBM. It will also contribute to the richness of genomic databases towards the prediction of antibiotic resistance, level of virulence and of origin of infection

Why do women not use antenatal services in low and middle income countries? A metasynthesis of qualitative studies

Background: Almost 50% of women in low & middle income countries (LMIC’s) don’t receive adequate antenatal care. Women’s views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies. Methods and Findings: Using a pre-determined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMIC’s who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line of argument synthesis. We derived policy relevant hypotheses from the findings. We included 21 papers representing the views of more than 1230 women from 15 countries. Three key themes were identified: ‘Pregnancy as socially risky and physiologically healthy’; ‘Resource use and survival in conditions of extreme poverty’and ‘Not getting it right first time’. The line of argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralized, risk-focused antenatal care programmes may be at odds with the resources, beliefs and experiences of pregnant women who underuse antenatal services. Conclusions: Our findings suggest that there may be a mis-alignment between current antenatal provision and the social and cultural context of some women in LMIC’s. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences are likely to be underused, especially when attendance generates increased personal risks of lost family resource or physical danger during travel; when the promised care is not delivered due to resource constraints; and when women experience covert or overt abuse in care settings

Inequality of access in irrigation systems of the mid-hills of Nepal

Access to, and control over, water for irrigation is one of the most important factors for increasing agricultural productivity, thereby affecting household food security and levels of poverty in developing countries. However, investments in the irrigation sector have often failed to consider equity aspects of irrigation interventions. Using data from 199 households from three irrigation systems in the mid-hills of Nepal, we analyse access and control of water in different levels of socio-economic heterogeneities. The results demonstrate that efforts to improve livelihoods of the rural poor should give due consideration to the distributional aspects of irrigation interventions, with authority for allocating the level of access to irrigation water given to the farmers throughout the system

The RACK1 signal anchor protein from Trypanosoma brucei associates with eukaryotic elongation factor 1A: a role for translational control in cytokinesis

RACK1 is a WD-repeat protein that forms signal complexes at appropriate locations in the cell. RACK1 homologues are core components of ribosomes from yeast, plants and mammals. In contrast, a cryo-EM analysis of trypanosome ribosomes failed to detect RACK1, thus eliminating an important translational regulatory mechanism. Here we report that TbRACK1 from Trypanosoma brucei associates with eukaryotic translation elongation factor-1a (eEF1A) as determined by tandem MS of TAP-TbRACK1 affinity eluates, co-sedimentation in a sucrose gradient, and co-precipitation assays. Consistent with these observations, sucrose gradient purified 80S monosomes and translating polysomes each contained TbRACK1. When RNAi was used to deplete cells of TbRACK1, a shift in the polysome profile was observed, while the phosphorylation of a ribosomal protein increased. Under these conditions, cell growth became hypersensitive to the translational inhibitor anisomycin. The kinetoplasts and nuclei were misaligned in the postmitotic cells, resulting in partial cleavage furrow ingression during cytokinesis. Overall, these findings identify eEF1A as a novel TbRACK1 binding partner and establish TbRACK1 as a component of the trypanosome translational apparatus. The synergy between anisomycin and TbRACK1 RNAi suggests that continued translation is required for complete ingression of the cleavage furrow

Perspectives of chalcopyrite-based CIGSe thin-film solar cell: a review

Solar photovoltaic (PV) is empowering, reliable, and ecofriendly technology for harvesting energy which can be assessed from the fact that PV panels with total electricity generation capacity of 505 GW have been installed by the end of 2018. Thin-film solar cells based on copper indium gallium selenide (CIGSe) are promising photovoltaic absorber material owing to an alternative to crystalline silicon (c-Si)-based solar cells because of the huge potential for low-cost solar electricity production with minimal usage of raw materials. The efficiency record of 23.4% was achieved recently in CIGSe solar cells, which was comparable to c-Si solar cells (27.6%). The manufacturing cost of $0.34/W is expected for 15% efficient CIGSe module. The present review article discusses the perspectives of CISe/CIGSe-based thin-film solar cells with the focus on absorber material. Different vacuum and non-vacuum techniques for fabricating these materials are discussed along with the operation of solar cells and their manufacturability. The working mechanism of CIGSe solar cells with the characteristic features of the open-circuit voltage and current density as well as the factors influencing the efficiency in different fabrication techniques are reviewed. Moreover, some strategies toward the improvement of solar cells performance contemplating modified deposition are reviewed. Furthermore, how these strategies can be executed in order to make it cost effective methods is also discussed in detail. Prevailing constrictions for the commercial maturity are deliberated, and future perspectives for improvement at lab as well as industrial scalabilities are outlined

Diaphragm dysfunction as a potential determinant of dyspnea on exertion in patients 1 year after COVID-19-related ARDS

Some COVID-19 patients experience dyspnea without objective impairment of pulmonary or cardiac function. This study determined diaphragm function and its central voluntary activation as a potential correlate with exertional dyspnea after COVID-19 acute respiratory distress syndrome (ARDS) in ten patients and matched controls. One year post discharge, both pulmonary function tests and echocardiography were normal. However, six patients with persisting dyspnea on exertion showed impaired volitional diaphragm function and control based on ultrasound, magnetic stimulation and balloon catheter-based recordings. Diaphragm dysfunction with impaired voluntary activation can be present 1 year after severe COVID-19 ARDS and may relate to exertional dyspnea. This prospective case–control study was registered under the trial registration number NCT04854863 April, 22 2021

Caesarean Section rates in South Asian cities: Can midwifery help stem the rise?

Introduction: Caesarean section (CS) is a life-saving surgical intervention for delivering a baby when complications arisein childbirth. World Health Organization recommends a rate of CS from 10% to 15%. However, CS rates increased steadily in recent decades and have almost doubled from 12.1% in 2000 to 21.1% in 2015. Therefore, this has become a global public health problem. The main purpose of the scoping review article is to give an overview and analysis of the rising CS use in four South Asian countries: Bangladesh, India, Nepal and Pakistan. Methods: A scoping review was carried-out using several bibliographic electronic databases (MEDLINE, EMBASE, SCOPUS, CINAHL and Web of Science), organizational websites and open access journal databases. Literature was searched from December 2011 to December 2018 for articles reporting hospital-based CS rates.Inclusion criteria were primary studies conducted ininstitutional setting in Bangladesh, India, Nepal and Pakistan and published in the English language. Results: We have included 43 studies. Together these studies show that the rate of CS is increasing in all four countries: Nepal, Bangladesh, Pakistan and India. However, this isuneven with very low rates in rural and very high rates in urban settings, theco-existence of ‘Too Little Too Late & Too Much Too Soon’. Hospital based studies have shown that the CS rate is higher in urban and private hospitals. Age, education andsocio-economic status of women, urban residence and distance from health facility are associated with CSs. CS is higher among highlyeducated affluent urban women in private hospitals in South Asian Countries. Conclusion: Rising CS rates in South Asian cities, particularly in specific groups of women, present a challenge to hospital staff and managers and policy-makers. The challenge is to avoid ‘Too Much Too Soon’ in otherwise healthy urban women and avoid ‘Too Little Too Late’ in women living in remote and rural area and in poor urban women

Assessment of health-related quality of life of stroke survivors in southeast communities in Nigeria

The prevalence of stroke in Nigeria has continued to be a major public health challenge. Recovery from a stroke episode can be a long-impacting process with reduced quality of life outcomes. Past studies have explored the quality of life (QoL) of stroke survivors. However, none have explored the QoL of stroke survivors in Southeastern Nigeria. This study therefore describes the QoL of Nigerian stroke survivors in Southeastern Nigeria. One hundred and one participants (44 male and 58 female) were recruited into the study. QoL domains were assessed using the stroke-specific Health-Related Quality of Life in Stroke Patients (HRQOLISP). The physical domain was significantly lower than other domains measured (mean = 2.52, SD = 0.76), contributing to poor quality of life. On the other hand, the spiritual domain had the greatest positive influence on QoL (mean = 3.70, SD = 0.50). We found the physical domain was the poorest part of stroke survivors’ stroke experience. The spiritual domain had a positive impact on improving QoL. There is a need for research on interventions relating to the physical rehabilitation of stroke survivors and a review of how the spiritual domain can be enhanced to improve QoL

Small Molecule Inhibitors of 15-PGDH Exploit a Physiologic Induced-Fit Closing System

15-prostaglandin dehydrogenase (15-PGDH) is a negative regulator of tissue stem cells that acts via enzymatic activity of oxidizing and degrading PGE2, and related eicosanoids, that support stem cells during tissue repair. Indeed, inhibiting 15-PGDH markedly accelerates tissue repair in multiple organs. Here we have used cryo-electron microscopy to solve the solution structure of native 15-PGDH and of 15-PGDH individually complexed with two distinct chemical inhibitors. These structures identify key 15-PGDH residues that mediate binding to both classes of inhibitors. Moreover, we identify a dynamic 15-PGDH lid domain that closes around the inhibitors, and that is likely fundamental to the physiologic 15-PGDH enzymatic mechanism. We furthermore identify two key residues, F185 and Y217, that act as hinges to regulate lid closing, and which both inhibitors exploit to capture the lid in the closed conformation, thus explaining their sub-nanomolar binding affinities. These findings provide the basis for further development of 15-PGDH targeted drugs as therapeutics for regenerative medicine