Defining hypoxaemia from pulse oximeter measurements of oxygen saturation in well children at low altitude in Bangladesh: an observational study

BACKGROUND: WHO defines hypoxaemia, a low peripheral arterial oxyhaemoglobin saturation (SpO2), as <90%. Although hypoxaemia is an important risk factor for mortality of children with respiratory infections, the optimal SpO2 threshold for defining hypoxaemia is uncertain in low-income and middle-income countries (LMICs). We derived a SpO2 threshold for hypoxaemia from well children in Bangladesh residing at low altitude. METHODS: We prospectively enrolled well, children aged 3-35 months participating in a pneumococcal vaccine evaluation in Sylhet district, Bangladesh between June and August 2017. Trained health workers conducting community surveillance measured the SpO2 of children using a Masimo Rad-5 pulse oximeter with a wrap sensor. We used standard summary statistics to evaluate the SpO2 distribution, including whether the distribution differed by age or sex. We considered the 2.5th, 5th and 10th percentiles of SpO2 as possible lower thresholds for hypoxaemia. RESULTS: Our primary analytical sample included 1470 children (mean age 18.6±9.5 months). Median SpO2 was 98% (IQR 96%-99%), and the 2.5th, 5th and 10th percentile SpO2 was 91%, 92% and 94%. No child had a SpO2 <90%. Children 3-11 months had a lower median SpO2 (97%) than 12-23 months (98%) and 24-35 months (98%) (p=0.039). The SpO2 distribution did not differ by sex (p=0.959). CONCLUSION: A SpO2 threshold for hypoxaemia derived from the 2.5th, 5th or 10th percentile of well children is higher than <90%. If a higher threshold than <90% is adopted into LMIC care algorithms then decision-making using SpO2 must also consider the child's clinical status to minimise misclassification of well children as hypoxaemic. Younger children in lower altitude LMICs may require a different threshold for hypoxaemia than older children. Evaluating the mortality risk of sick children using higher SpO2 thresholds for hypoxaemia is a key next step

How are health professionals earning their living in Malawi?

BACKGROUND: The migration of health professionals from southern Africa to developed nations is negatively affecting the delivery of health care services in the source countries. Oftentimes however, it is the reasons for the out-migration that have been described in the literature. The work and domestic situations of those health professionals continuing to serve in their posts have not been adequately studied. METHODS: The present study utilized a qualitative data collection and analysis method. This was achieved through focus group discussions and in-depth interviews with health professionals and administrators to determine the challenges they face and the coping systems they resort to and the perceptions towards those coping methods. RESULTS: Health professionals identified the following as some of the challenges there faced: inequitable and poor remuneration, overwhelming responsibilities with limited resources, lack of a stimulating work environment, inadequate supervision, poor access to continued professionals training, limited career progression, lack of transparent recruitment and discriminatory remuneration. When asked what kept them still working in Malawi when the pressures to emigrate were there, the following were some of the ways the health professionals mentioned as useful for earning extra income to support their families: working in rural areas where life was perceived to be cheaper, working closer to home village so as to run farms, stealing drugs from health facilities, having more than one job, running small to medium scale businesses. Health professionals would also minimize expenditure by missing meals and walking to work. CONCLUSION: Many health professionals in Malawi experience overly challenging environments. In order to survive some are involved in ethically and legally questionable activities such as receiving "gifts" from patients and pilfering drugs. The efforts by the Malawi government and the international community to retain health workers in Malawi are recognized. There is however need to evaluate of these human resources-retaining measures are having the desired effects

Medicago orbicularis Has Antioxidant, Antihemolytic, and Anti-cancerous Activities and Augments Cisplatin-Induced Cytotoxicity in A549 Lung Cancer Cells

Cancer is the second leading cause of death, worldwide. Lung cancer is the leading cause of cancer-related mortality. Plant-based therapeutics and herbal medicine have played a vital role in the development of several anti-cancerous agents, and has been used to reduce the severe side effects of chemotherapy as well. Since the anti-lung cancer properties of the plant Medicago. orbicularis are not explored yet, we identified its phytochemical composition and investigated the anti-oxidant, anti-hemolytic, and anti-cancerous properties of extracts of this plant in A549 human lung adenocarcinoma cells. Results show that all parts of M. orbicularis (stems, leaves, and fruits) exhibit remarkable anti-oxidant and hemolytic activities. In addition, all extracts showed a dose-dependent anti-cancerous cytotoxic activity against A549 cells; with fruit extracts being the most potent. This cytotoxic effect could be related, at least partly, to the induction of apoptosis, where M. orbicularis fruit extracts activated Caspase-3 and PARPP-1, and reduced the ratio of anti-apoptotic BCL-2/ pro-apoptotic BAX, thereby promoting cellular death. Furthermore, the use of M. orbicularis, in combination with a conventional chemotherapeutic agent, cisplatin, was assessed. Indeed, combination of cisplatin and M. orbicularis fruit extracts was more cytotoxic and induced more aggregation of A549 cells than either treatment alone. GC-MS analysis and total polyphenol and flavonoid content determination indicated that M. orbicularis is rich in compounds that have anti-cancerous effects. M. orbicularis may be a potential source of anti-cancerous agents to manage progression of lung cancer and its resistance to therapy.This work was supported by the a grant from the Lebanese University to SN and student grants number QUST-1-BRC-2022-315; QUST-1-BRC-2022-316, QUST-1-BRC-2023-836; and QUST-1-BRC-2023-846 to AS. Publication fees APC were covered by Qatar National Library (QNL)

Permeable biosorbent barrier for wastewater remediation

Chromium is one of the heavy metals that significantly affect water quality in Mongolia. The present study is focused on the remediation of surface water contaminated with chromium (III) by a permeable barrier in order to prevent sediment pollution. The adsorption capacity of the selected materials (13X zeolite and vermiculite) was investigated at different sorbent dosages, pH and initial Cr(III) concentration. The equilibrium adsorption studies showed that vermiculite has a higher Cr(III) removal efficiency in comparison with 13X zeolite. A fungal isolate obtained from the sediment samples collected near Tuul River (Mongolia) was selected from enriched Luria-Bertani medium, showing a good performance for Cr(III) removal (78.2\% for an initial concentration of 50 mg/L). The fungal isolate was genetically typed by DNA sequencing and was identified as belonging to the Alternaria alternata species. 13X zeolite showed the best performance for Cr removal in the permeable barrier assays compared to vermiculite, achieving a total removal of 96\\% and a global uptake of 2.49 mg/g. After 13 days of operation none of the barriers reached saturation with chromium.A previous version of the paper has been presented in the 2nd EWaS International Conference: BEfficient & Sustainable Water Systems Management toward Worth Living Development^, Chania, Crete, Greece, 1-4 June 2016. This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. Bruna Silva is thankful to the FCT for the concession of a Post-Doc grant (SFRH/BPD/112354/2015). Sampling process was supported by the collaborative research grant of National Academy of Sciences of Taiwan and Science and Technology Foundation of Mongolia, project code NCS-NECS2013003 and co-funded by the Young Scientist Grant (SEAS-2015075) of National University of Mongolia. E. Tuuguu would like to acknowledge the Erasmus-Mundus AREAS+ program for the opportunity to conduct research at CEB-University of Minho.info:eu-repo/semantics/publishedVersio

Exploiting visual cues for safe and flexible cyber-physical production systems

Human workers are envisioned to work alongside robots and other intelligent factory modules, and fulfill supervision tasks in future smart factories. Technological developments, during the last few years, in the field of smart factory automation have introduced the concept of cyber-physical systems, which further expanded to cyber-physical production systems. In this context, the role of collaborative robots is significant and depends largely on the advanced capabilities of collision detection, impedance control, and learning new tasks based on artificial intelligence. The system components, collaborative robots, and humans need to communicate for collective decision-making. This requires processing of shared information keeping in consideration the available knowledge, reasoning, and flexible systems that are resilient to the real-time dynamic changes on the industry floor as well as within the communication and computer network infrastructure. This article presents an ontology-based approach to solve industrial scenarios for safety applications in cyber-physical production systems. A case study of an industrial scenario is presented to validate the approach in which visual cues are used to detect and react to dynamic changes in real time. Multiple scenarios are tested for simultaneous detection and prioritization to enhance the learning surface of the intelligent production system with the goal to automate safety-based decisions

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Age-related associations of hypertension and diabetes mellitus with chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>Studies suggest end-stage renal disease incidence and all-cause mortality rates among patients with chronic kidney disease (CKD) differ by age. The association of diabetes mellitus and hypertension with CKD across the adult lifespan is not well established.</p> <p>Methods</p> <p>Data from NHANES 1999–2004 were used to determine the association of risk factors for stage 3 or 4 CKD (n = 12,518) and albuminuria (n = 12,778) by age grouping (20 to 49, 50 to 69, and ≥70 years). Stage 3 or 4 CKD was defined as an estimated glomerular filtration rate of 15 to 59 ml/min/1.73 m²and albuminuria as an albumin to creatinine ratio ≥30 mg/g.</p> <p>Results</p> <p>For adults 20 to 49, 50 to 69 and ≥70 years of age, the prevalence ratios (95% confidence interval) of stage 3 or 4 CKD associated with hypertension were 1.94 (0.86 – 4.35), 1.51 (1.09 – 2.07), 1.31 (1.15 – 1.49), respectively (p-trend = 0.038). The analogous prevalence ratios (95% confidence interval) were 3.01 (1.35 – 6.74), 1.61 (1.15 – 2.25), 1.40 (1.15 – 1.69), respectively, for diagnosed diabetes mellitus (p-trend = 0.067); and 2.67 (0.53 – 13.4), 1.35 (0.69 – 2.63), 1.08 (0.78 – 1.51), respectively, for undiagnosed diabetes mellitus (p-trend = 0.369). The prevalence ratios of albuminuria associated with hypertension and diagnosed and undiagnosed diabetes mellitus were lower at older age (each p < 0.05).</p> <p>Conclusion</p> <p>Among US adults, diabetes mellitus and hypertension are associated with CKD and albuminuria regardless of age. However, the associations were stronger at younger ages.</p

Doyne lecture 2016:intraocular health and the many faces of inflammation

Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses

Serological profile of first SARS-CoV-2 reinfection cases detected within the SIREN study.

OBJECTIVES: To describe the serological profile of first two SARS-CoV-2 confirmed reinfections in the national healthcare worker cohort study SARS-CoV-2 Immunity and Reinfection Evaluation (SIREN) and potentially identify correlates of protection against reinfection. METHODS: In addition to routine testing within the SIREN study, viral culture, sequencing and phylogenetic analysis were performed. Total antibody testing (Anti-SARS-CoV-2 nucleocapsid and Anti-SARS-CoV-2 spike) were complemented by receptor binding domain indirect ELISA and neutralising antibody assays. RESULTS: The first two SARS-CoV-2 confirmed reinfections had mild symptomatic illness episodes from which infectious virus was recovered at the time of reinfection. The recovered viruses and their sequences were closely related to viruses circulating locally during the time of reinfection and serology was consistent with reinfection. Prior to reinfection, both cases had ELISA and immunoblot detectable anti-N antibodies, but lacked live virus neutralising antibody. Within days following reinfection, neutralising antibodies became detectable and anti-N and anti-S binding antibodies were boosted. CONCLUSIONS: We hypothesise that titres of neutralising antibody can be used as a correlate of protection against reinfection. Further analysis using a case-control design is essential in order to confirm this hypothesis

Protocol for faecal microbiota transplantation in ulcerative colitis (FMTUC): a randomised feasibility study

Background The interaction of the gut microbiota with the human host is implicated in the pathogenesis of inflammatory and immunological diseases including ulcerative colitis (UC). Faecal microbiota transplantation (FMT) as a method of restoring gut microbial diversity is of increasing interest as a therapeutic approach in the management of UC. The current literature lacks consensus about the dose of FMT, route of administration and duration of response. Methods and analysis This single-blinded randomised trial will explore the feasibility of FMT in 30 treatment-naïve patients with histologically confirmed distal UC limited to the recto-sigmoid region (up to 40 cm from the anal verge). This study aims to estimate the magnitude of treatment response to FMT under controlled conditions. The intervention (FMT) will be administered by rectal retention enema. It will test the feasibility of randomising patients to: (i) single FMT dose, (ii) five daily FMT doses or (iii) control (no FMT dose). All groups will receive standard antibiotic gut decontamination and bowel preparation before FMT. Recruitment will take place over a 24-month period with a 12-week patient follow-up. Trial objectives include evaluation of the magnitude of treatment response to FMT, investigation of the clinical value of metabolic phenotyping for predicting the clinical response to FMT and testing the recruitment rate of donors and patients for a study in FMT. This feasibility trial will enable an estimate of number of patients needed, help determine optimal study conditions and inform the choice of endpoints for a future definitive phase III study. Ethics and dissemination The trial is approved by the regional ethics committee and is sponsored by Abertawe Bro Morgannwg University’s Health Board. Written informed consent from all patients will be obtained. Serious adverse events will be reported to the sponsor. Trial results will be disseminated via peer review publication and shared with trial participants. Trial registration number ISRCTN58082603; Pre-results