scholarly journals CEACAMs serve as toxin-stimulated receptors for enterotoxigenicEscherichia coli

2020 ◽  
Vol 117 (46) ◽  
pp. 29055-29062
Author(s):  
Alaullah Sheikh ◽  
Brunda Tumala ◽  
Tim J. Vickers ◽  
David Alvarado ◽  
Matthew A. Ciorba ◽  
...  
Keyword(s):  
Diarrheal Disease ◽  
Molecular Pathogenesis ◽  
Intestinal Lumen ◽  
Watery Diarrhea ◽  
Middle Income ◽  
Cellular Targets ◽  
Host Interactions ◽  
Intestinal Epithelia ◽  
Risk Of Death ◽  
Low Middle Income Countries

The enterotoxigenicEscherichia coli(ETEC) are among the most common causes of diarrheal illness and death due to diarrhea among young children in low-/middle-income countries (LMICs). ETEC have also been associated with important sequelae including malnutrition and stunting, placing children at further risk of death from diarrhea and other infections. Our understanding of the molecular pathogenesis of acute diarrheal disease as well as the sequelae linked to ETEC are still evolving. It has long been known that ETEC heat-labile toxin (LT) activates production of cAMP in the cell, signaling the modulation of cellular ion channels that results in a net efflux of salt and water into the intestinal lumen, culminating in watery diarrhea. However, as LT also promotes ETEC adhesion to intestinal epithelial cells, we postulated that increases in cAMP, a critical cellular “second messenger,” may be linked to changes in cellular architecture that favor pathogen–host interactions. Indeed, here we show that ETEC use LT to up-regulate carcinoembryonic antigenrelated cell adhesion molecules (CEACAMs) on the surface of small intestinal epithelia, where they serve as critical bacterial receptors. Moreover, we show that bacteria are specifically recruited to areas of CEACAM expression, in particular CEACAM6, and that deletion of this CEACAM abrogates both bacterial adhesion and toxin delivery. Collectively, these results provide a paradigm for the molecular pathogenesis of ETEC in which the bacteria use toxin to drive up-regulation of cellular targets that enhances subsequent pathogen–host interactions.

scholarly journals Erythropoietin monotherapy for neuroprotection after neonatal encephalopathy in low-to-middle income countries: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Phoebe Ivain ◽  
Paolo Montaldo ◽  
Aamir Khan ◽  
Ramyia Elagovan ◽  
Constance Burgod ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Neonatal Encephalopathy ◽  
Neurodevelopmental Outcomes ◽  
Term Infants ◽  
Middle Income ◽  
Middle Income Countries ◽  
Pooled Data ◽  
Risk Of Death ◽  
Low Middle Income Countries ◽  
Near Term

Abstract Objective We examined whether erythropoietin monotherapy improves neurodevelopmental outcomes in near-term and term infants with neonatal encephalopathy (NE) in low-middle income countries (LMICs). Methods We searched Pubmed, Embase, and Web of Science databases to identify studies that used erythropoietin (1500–12,500 units/kg/dose) or a derivative to treat NE. Results Five studies, with a total of 348 infants in LMICs, were retrieved. However, only three of the five studies met the primary outcome of death or neuro-disability at 18 months of age or later. Erythropoietin reduced the risk of death (during the neonatal period and at follow-up) or neuro-disability at 18 months or later (p < 0.05). Death or neuro-disability occurred in 27.6% of the erythropoietin group and 49.7% of the comparison group (risk ratio 0.56 (95% CI: 0.42–0.75)). Conclusion The pooled data suggest that erythropoietin monotherapy may improve outcomes after NE in LMICs where therapeutic hypothermia is not available.

scholarly journals The influence of human genetic variation on early transcriptional responses and protective immunity following immunization with Rotarix vaccine in infants in Ho Chi Minh City in Vietnam: A study protocol for an open single-arm interventional trial

2020 ◽  
Vol 5 ◽  
pp. 246
Author(s):  
Ruklanthi de Alwis ◽  
Tran My Phuc ◽  
Benjamin Yu Hang Bai ◽  
Nhi Le Thi Quynh ◽  
Pham Thi Thanh Tam ◽  
...  
Keyword(s):  
Human Genetics ◽  
Diarrheal Disease ◽  
Open Label ◽  
Transcriptional Responses ◽  
Middle Income ◽  
Interventional Trial ◽  
Genetic Heritability ◽  
Low Middle Income Countries ◽  
Diarrheal Episode ◽  
Expanded Program On Immunization

Background: Rotavirus (RoV) remains the leading cause of acute gastroenteritis in infants and children aged under five years in both high- and low-middle-income countries (LMICs). In LMICs, RoV infections are associated with substantial mortality. Two RoV vaccines (Rotarix and Rotateq) are widely available for use in infants, both of which have been shown to be highly efficacious in Europe and North America. However, for unknown reasons, these RoV vaccines have markedly lower efficacy in LMICs. We hypothesize that poor RoV vaccine efficacy across in certain regions may be associated with genetic heritability or gene expression in the human host. Methods/design: We designed an open-label single-arm interventional trial with the Rotarix RoV vaccine to identify genetic and transcriptomic markers associated with generating a protective immune response against RoV. Overall, 1,000 infants will be recruited prior to Expanded Program on Immunization (EPI) vaccinations at two months of age and vaccinated with oral Rotarix vaccine at two and three months, after which the infants will be followed-up for diarrheal disease until 18 months of age. Blood sampling for genetics, transcriptomics, and immunological analysis will be conducted before each Rotarix vaccination, 2-3 days post-vaccination, and at each follow-up visit (i.e. 6, 12 and 18 months of age). Stool samples will be collected during each diarrheal episode to identify RoV infection. The primary outcome will be Rotarix vaccine failure events (i.e. symptomatic RoV infection despite vaccination), secondary outcomes will be antibody responses and genotypic characterization of the infection virus in Rotarix failure events. Discussion: This study will be the largest and best powered study of its kind to be conducted to date in infants, and will be critical for our understanding of RoV immunity, human genetics in the Vietnam population, and mechanisms determining RoV vaccine-mediated protection. Registration: ClinicalTrials.gov, ID: NCT03587389. Registered on 16 July 2018.

scholarly journals Hierarchy of Loss in Functional Capability: Findings From a 15-Year Follow-Up in a Brazilian Aging Cohort

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 664-664
Author(s):  
Cesar de Oliveira ◽  
Dorina Cadar ◽  
Jane Biddulph ◽  
Juliana Vaz de Melo Mambrini ◽  
Fabiola Bof de Andrad ◽  
...  
Keyword(s):  
Activities Of Daily Living ◽  
Daily Living ◽  
Middle Income ◽  
Functional Loss ◽  
Middle Income Countries ◽  
Risk Of Death ◽  
Disability Rate ◽  
Low Middle Income Countries ◽  
Hierarchical Pattern

Abstract Functional loss among older adults is known to follow a hierarchical sequence, but little is known about this in low-middle income countries. We examined longitudinally the hierarchy of loss in physical functioning in 1,602 older Brazilian adults (aged 60+) from the Bambui Cohort Study of Aging. Functional loss was ascertained using self-reported difficulties in six basic activities of daily living (BADL). The incidence for each BADL limitation was assessed using survival analysis while controlling for the competing risk of death. Over the 15-year follow-up, the incidence in BADL disability rate was highest for dressing, followed by getting out of bed, bathing/showering, walking across a room, using the toilet or eating. The findings from this 15-year follow-up Brazilian aging cohort support a hierarchical pattern of disability in activities of daily living based on both prevalence and incidence of disabilities over time, and they suggest gender differences in the incidence of disability.

The Impact of Covid 19 on Pregnant Women and Child Health

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1367-1373
Author(s):  
Nikhil Sanjay Mujbaile ◽  
Smita Damke
Keyword(s):  
Social Issues ◽  
Middle Income ◽  
Web Based ◽  
Middle Income Countries ◽  
Low Middle Income Countries ◽  
The Social ◽  
Social Separation ◽  
The Impact ◽  
And Child Health ◽  
General Wellbeing

The Covid illness (COVID-19) pandemic has spread rapidly all through the world and has had a drawn-out impact. The Pandemic has done incredible damage to society and made genuine mental injury to numerous individuals. Mental emergencies frequently cause youngsters to deliver sentiments of relinquishment, despondency, insufficiency, and fatigue and even raise the danger of self-destruction. Youngsters with psychological instabilities are particularly powerless during the isolate and colonial removing period. Convenient and proper assurances are expected to forestall the event of mental and social issues. The rising advanced applications and wellbeing administrations, for example, telehealth, web-based media, versatile wellbeing, and far off intuitive online instruction can connect the social separation and backing mental and conduct wellbeing for youngsters. Because of the mental advancement qualities of youngsters, this investigation additionally outlines intercessions on the mental effect of the COVID-19 Pandemic. Further difficulties in Low Middle-Income Countries incorporate the failure to actualize successful general wellbeing estimates, for example, social separating, hand cleanliness, definitive distinguishing proof of contaminated individuals with self-disconnection and widespread utilization of covers The aberrant impacts of the Pandemic on youngster wellbeing are of extensive concern, including expanding neediness levels, upset tutoring, absence of admittance to the class taking care of plans, decreased admittance to wellbeing offices and breaks in inoculation and other kid wellbeing programs. Kept tutoring is critical for kids in Low Middle-Income Countries. Arrangement of safe situations is mainly testing in packed asset obliged schools. 

Risk Factors of Mortality Among Patients with Stroke in Low Middle-Income Countries:  A Series of 180 Patients

2020 ◽  
Author(s):  
Larrey Kamabu ◽  
Hervé Monka Lekuya ◽  
Bienvenu Muhindo Kasusula ◽  
Nicole Kavugho Mutimani ◽  
Louange Maha Kathaka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Middle Income ◽  
Middle Income Countries ◽  
Low Middle Income Countries

scholarly journals Maternal mortality in six low and lower-middle income countries from 2010 to 2018: risk factors and trends

2020 ◽  
Vol 17 (S3) ◽  
Author(s):  
Melissa Bauserman ◽  
Vanessa R. Thorsten ◽  
Tracy L. Nolen ◽  
Jackie Patterson ◽  
Adrien Lokangaka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Maternal Mortality ◽  
Maternal Deaths ◽  
Middle Income ◽  
Maternal Risk ◽  
Live Births ◽  
Middle Income Countries ◽  
Risk Of Death ◽  
Increased Risk ◽  
Over Time

Abstract Background Maternal mortality is a public health problem that disproportionately affects low and lower-middle income countries (LMICs). Appropriate data sources are lacking to effectively track maternal mortality and monitor changes in this health indicator over time. Methods We analyzed data from women enrolled in the NICHD Global Network for Women’s and Children’s Health Research Maternal Newborn Health Registry (MNHR) from 2010 through 2018. Women delivering within research sites in the Democratic Republic of Congo, Guatemala, India (Nagpur and Belagavi), Kenya, Pakistan, and Zambia are included. We evaluated maternal and delivery characteristics using log-binomial models and multivariable models to obtain relative risk estimates for mortality. We used running averages to track maternal mortality ratio (MMR, maternal deaths per 100,000 live births) over time. Results We evaluated 571,321 pregnancies and 842 maternal deaths. We observed an MMR of 157 / 100,000 live births (95% CI 147, 167) across all sites, with a range of MMRs from 97 (76, 118) in the Guatemala site to 327 (293, 361) in the Pakistan site. When adjusted for maternal risk factors, risks of maternal mortality were higher with maternal age > 35 (RR 1.43 (1.06, 1.92)), no maternal education (RR 3.40 (2.08, 5.55)), lower education (RR 2.46 (1.54, 3.94)), nulliparity (RR 1.24 (1.01, 1.52)) and parity > 2 (RR 1.48 (1.15, 1.89)). Increased risk of maternal mortality was also associated with occurrence of obstructed labor (RR 1.58 (1.14, 2.19)), severe antepartum hemorrhage (RR 2.59 (1.83, 3.66)) and hypertensive disorders (RR 6.87 (5.05, 9.34)). Before and after adjusting for other characteristics, physician attendance at delivery, delivery in hospital and Caesarean delivery were associated with increased risk. We observed variable changes over time in the MMR within sites. Conclusions The MNHR is a useful tool for tracking MMRs in these LMICs. We identified maternal and delivery characteristics associated with increased risk of death, some might be confounded by indication. Despite declines in MMR in some sites, all sites had an MMR higher than the Sustainable Development Goals target of below 70 per 100,000 live births by 2030. Trial registration The MNHR is registered at NCT01073475.

scholarly journals Triaging and adaptations of surveillance of cancer services in the COVID pandemic

2020 ◽  
pp. 1-3
Author(s):  
Shirley Lewis ◽  
Lavanya Gurram ◽  
Umesh Velu ◽  
Krishna Sharan
Keyword(s):  
Cancer Patients ◽  
Clinical Examination ◽  
Cancer Care ◽  
Middle Income ◽  
Face To Face ◽  
Middle Income Countries ◽  
Cancer Services ◽  
Low Middle Income Countries

Abstract Introduction: Coronavirus disease (COVID-19) has significantly challenged the access to cancer care and follow-up for a patient with cancer. Methods: Based on published literature and our experiences, it is reasonable to presume that clinical examination and follow-up visits have been significantly curtailed worldwide in order to adhere to the new norms during the pandemic. Although telephonic and telemedicine consultations may help bridge a few gaps, completely dispensing with in-person consultation has its challenges, especially in low middle-income countries. Telephonic consultations could facilitate triaging of ambulatory cancer patients and allocation of face-to-face consultations for high priority patients. Conclusions: We propose a telephonic consultation-based triaging approach for ambulatory cancer patients in order to identify those needing in-hospital consultations.

scholarly journals Exploration of recovery of people living with severe mental illness (SMI) in low/middle-income countries (LMICs): a scoping review

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e045005
Author(s):  
Fadia Gamieldien ◽  
Roshan Galvaan ◽  
Bronwyn Myers ◽  
Zarina Syed ◽  
Katherine Sorsdahl
Keyword(s):  
Mental Illness ◽  
Severe Mental Illness ◽  
Scoping Review ◽  
Data Extraction ◽  
Flow Diagram ◽  
Personal Recovery ◽  
Middle Income ◽  
Middle Income Countries ◽  
Provider Perspectives ◽  
Low Middle Income Countries

ObjectiveTo examine the literature on how recovery of people with severe mental illness (SMI) is conceptualised in low/middle-income countries (LMICs), and in particular what factors are thought to facilitate recovery.DesignScoping review.Data sources and eligibilityWe searched 14 electronic databases, hand searched citations and consulted with experts during the period May–December 2019. Eligible studies were independently screened for inclusion and exclusion by two reviewers. Unresolved discrepancies were referred to a third reviewer.Data extraction and synthesisAll bibliographical data and study characteristics were extracted using a data charting form. Selected studies were analysed through a thematic analysis emerging from extracted data.ResultsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram offers a summary of the results: 4201 titles, 1530 abstracts and 109 full-text articles were screened. Ten articles were selected for inclusion: two from Turkey, two from India, and one each from China, Swaziland, Indonesia, Egypt, South Africa and Vietnam. Although most studies used qualitative methods, data collection and sampling methods were heterogeneous. One study reported on service provider perspectives while the rest provided perspectives from a combination of service users and caregivers. Three themes emerged from the data analysis. First, studies frame recovery as a personal journey occurring along a continuum. Second, there was an emphasis on social relationships as a facilitator of recovery. Third, spirituality emerged as both a facilitator and an indicator of recovery. These themes were not mutually exclusive and some overlap exists.ConclusionAlthough there were commonalities with how high-income countries describe recovery, we also found differences in conceptualisation. These differences in how recovery was understood reflect the importance of framing the personal recovery concept in relation to local needs and contextual issues found in LMICs. This review highlighted the current sparse evidence base and the need to better understand recovery from SMI in LMICs.

scholarly journals Universal newborn hearing screening in South Africa: a single-centre study

2021 ◽  
Vol 5 (1) ◽  
pp. e000976
Author(s):  
Ayanda Gina ◽  
Nadja F Bednarczuk ◽  
Asitha Jayawardena ◽  
Peter Rea ◽  
Qadeer Arshad ◽  
...  
Keyword(s):  
Auditory Brainstem ◽  
Hearing Screening ◽  
Newborn Hearing Screening ◽  
Middle Income ◽  
Middle Income Countries ◽  
Low Middle Income Countries ◽  
Universal Newborn Hearing Screening ◽  
Newborn Hearing ◽  
Single Centre Study ◽  
Societal Level

Hearing screening for newborn babies is an established protocol in many high-income countries. Implementing such screening has yielded significant socioeconomic advantages at both an individual and societal level. This has yet to permeate low/middle-income countries (LMIC). Here, we illustrate how newborn hearing screening needs to be contextually adapted for effective utilisation and implementation in an LMIC. Specifically, this advocates the use of auditory brainstem testing as the first-line approach. We propose that such adaptation serves to maximise clinical efficacy and community participation at a reduced cost.

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