H
S and H
O
are two redox regulating molecules that play important roles in many physiological and pathological processes. While each of them has distinct biosynthetic pathways and signaling ...mechanisms, the crosstalk between these two species is also known to cause critical biological responses such as protein S-persulfidation. So far, many chemical tools for the studies of H
S and H
O
have been developed, such as the donors and sensors for H
S and H
O
. However, these tools are normally targeting single species (e.g., only H
S or only H
O
). As such, the crosstalk and synergetic effects between H
S and H
O
have hardly been studied with those tools. In this work, we report a unique H
S/H
O
dual donor system by employing 1-thio-β-d-glucose and glucose oxidase (GOx) as the substrates. This enzymatic system can simultaneously produce H
S and H
O
in a slow and controllable fashion, without generating any bio-unfriendly byproducts. This system was demonstrated to cause efficient S-persulfidation on proteins. In addition, we expanded the system to thiolactose and thioglucose-disulfide; therefore, additional factors (β-galactosidase and cellular reductants) could be introduced to further control the release of H
S/H
O
. This dual release system should be useful for future research on H
S and H
O
.
The goal of this study was to develop intraoperative biomaterials for use in endoscopic submucosal dissection (ESD) procedures that are stable during storage, easy to use, and effective in clinical ...practice. Therefore, injectable thermosensitive hydrogels were developed based on lactobionic acid-modified chitosan/chitosan/β-glycerophosphate (CSLA/CS/GP) hydrogel lyophilizate powders, and their properties were compared with original hydrogels that had not been freeze-dried. The results indicated that the lyophilizate powders retained their thermosensitive properties, and gels could be formed within 5 min at 37 °C. Compared to the original hydrogels, the injectability of the hydrogels derived from lyophilizate powders increased significantly. These novel materials maintained their original porous network lamellar structure but exhibited improved mechanical strength and tissue adhesion. Their application with L929 and GES-1 cells revealed that the lyophilizate powder hydrogels demonstrated good cytocompatibility and clearly protected the cells in an acidic environment. The results of submucosal injection experiments involving porcine stomach tissue indicated that the heights of the cushions created by CSLA/CS/GP lyophilizate powder hydrogels lasted longer than those generated with normal saline. The thermosensitive hydrogels based on lyophilizate powders may contribute to practical clinical applications involving ESD, and may also have potential value for other applications in the digestive tract.
•Lyophilizate powder hydrogels are promising intraoperative biomaterials for ESD.•Lyophilized powders are stable during storage, easy to use.•The hydrogels derived from lyophilizate powder display excellent injectability.
Tracheoesophageal fistula (TEF) is an abnormal connection between the trachea and esophagus that severely impairs quality of life. Current treatment options have limitations, including conservative ...treatment, surgical repair, and esophageal stent implantation. Here, we introduced laponite (LP) nano-clay to improve chitosan-based hydrogels' rheological properties and mechanical properties and developed an endoscopically injectable nanocomposite shear-thinning hydrogel to seal and repair fistulas as an innovative material for the treatment of TEF. Excellent injectability, rheological properties, mechanical strength, self-healing, biodegradability, biocompatibility, and tissue repair characterize the new hydrogel. The introduction of LP nano-clay improves the gel kinetics problem of hydrogels to realize the sol–gel transition immediately after injection, avoiding gel flow to non-target sites. The addition of LA nano-clay can significantly improve the rheological properties and mechanical strength of hydrogels, and hydrogel with LP content of 3 % shows better comprehensive performance. The nanocomposite hydrogel also shows good cytocompatibility and can promote wound repair by promoting the migration of HEEC cells and the secretion of VEGF and FGF. These findings suggest that this nanocomposite hydrogel is a promising biomaterial for TEF treatment.
IntroductionCurrent evidence on epidemiology and outcomes of invasively mechanically ventilated intensive care unit (ICU) patients is predominantly gathered in resource-rich settings. Patient casemix ...and patterns of critical illnesses, and probably also ventilation practices are likely to be different in resource-limited settings. We aim to investigate the epidemiological characteristics, ventilation practices and clinical outcomes of patients receiving mechanical ventilation in ICUs in Asia.Methods and analysisPRoVENT-iMIC (study of PRactice of VENTilation in Middle-Income Countries) is an international multicentre observational study to be undertaken in approximately 60 ICUs in 11 Asian countries. Consecutive patients aged 18 years or older who are receiving invasive ventilation in participating ICUs during a predefined 28-day period are to be enrolled, with a daily follow-up of 7 days. The primary outcome is ventilatory management (including tidal volume expressed as mL/kg predicted body weight and positive end-expiratory pressure expressed as cm H2O) during the first 3 days of mechanical ventilation—compared between patients at no risk for acute respiratory distress syndrome (ARDS), patients at risk for ARDS and in patients with ARDS (in case the diagnosis of ARDS can be made on admission). Secondary outcomes include occurrence of pulmonary complications and all-cause ICU mortality.Ethics and disseminationPRoVENT-iMIC will be the first international study that prospectively assesses ventilation practices, outcomes and epidemiology of invasively ventilated patients in ICUs in Asia. The results of this large study, to be disseminated through conference presentations and publications in international peer-reviewed journals, are of ultimate importance when designing trials of invasive ventilation in resource-limited ICUs. Access to source data will be made available through national or international anonymised datasets on request and after agreement of the PRoVENT-iMIC steering committee.Trial registration number NCT03188770; Pre-results.
IntroductionHIV viral load (VL) testing in resource-limited settings is often centralised, limiting access. In Myanmar, we assessed outcomes according to VL access and the VL cascade (case management ...after a first high VL result) before and after near point-of-care (POC) VL was introduced.MethodsRoutine programme data from people living with HIV (PLHIV) on antiretroviral therapy (ART) were used. We assessed the odds of getting a VL test done by year. Attrition and mortality two years after ART initiation were compared between three groups of PLHIV with different access to VL testing using Kaplan-Meier analysis. We compared VL cascades in those with a first VL result before and after near POC VL testing became available. With logistic regression, predictors of confirmed virological failure after a first high VL in the POC era were explored.ResultsAmong 4291 PLHIV who started ART between July 2009 and June 2018, 794 (18.5%) became eligible for VL testing when it was not available, 2388 (55.7%) when centralised laboratory-based VL testing was available, and 1109 (25.8%) when near POC VL testing was available. Between 2010 and 2019, the odds of getting a VL test among those eligible increased with each year (OR: 5.21 95% CI: 4.95-5.48). Attrition and mortality were not different in the three groups. When comparing PLHIV with a first VL result before and after implementation of the near POC VL testing, in the latter, more had a first VL test (92% versus 15%, p<0.001), less had a first high VL result (5% versus 14%, p<0.001), and more had confirmed virological failure (67% versus 47%, p = 0.013). Having a first VL ≥5000 copies/mL after near POC implementation was associated with confirmed virological failure (adjusted OR: 2.61 95% CI: 1.02-6.65).ConclusionNear POC VL testing enabled rapid increase of VL coverage and a well-managed VL cascade in Myanmar.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•64% of residents in a SARS-CoV-2-affected dormitory were infected by July 2020•< 0.2% of the Singapore general population were infected with SARS-CoV-2 in 2020•SARS-CoV-2 spread can be suppressed ...with prompt, wide-ranging interventions•High-risk, crowded settings require special consideration in preparedness planning•Lowering densities in these settings is key to reducing vulnerability to outbreaks
Since January 2020, Singapore has implemented comprehensive measures to suppress SARS-CoV-2. Despite this, the country has experienced contrasting epidemics, with limited transmission in the community and explosive outbreaks in migrant worker dormitories.
To estimate SARS-CoV-2 infection incidence among migrant workers and the general population in Singapore.
Prospective serological cohort studies.
Two cohort studies — in a migrant worker dormitory and in the general population in Singapore.
478 residents of a SARS-CoV-2-affected migrant worker dormitory were followed up between May and July 2020, with blood samples collected on recruitment and after 2 and 6 weeks. In addition, 937 community-dwelling adult Singapore residents, for whom pre-pandemic sera were available, were recruited. These individuals also provided a serum sample on recruitment in November/December 2020.
Exposure to SARS-CoV-2 in a densely populated migrant worker dormitory and in the general population.
The main outcome measures were the incidences of SARS-CoV-2 infection in migrant workers and in the general population, as determined by the detection of neutralizing antibodies against SARS-CoV-2, and adjusting for assay sensitivity and specificity using a Bayesian modeling framework.
No evidence of community SARS-CoV-2 exposure was found in Singapore prior to September 2019. It was estimated that < 2 per 1000 adult residents in the community were infected with SARS-CoV-2 in 2020 (cumulative seroprevalence: 0.16%; 95% CrI: 0.008–0.72%). Comparison with comprehensive national case notification data suggested that around 1 in 4 infections in the general population were associated with symptoms. In contrast, in the migrant worker cohort, almost two-thirds had been infected by July 2020 (cumulative seroprevalence: 63.8%; 95% CrI: 57.9–70.3%); no symptoms were reported in almost all of these infections.
Our findings demonstrate that SARS-CoV-2 suppression is possible with strict and rapid implementation of border restrictions, case isolation, contact tracing, quarantining, and social-distancing measures. However, the risk of large-scale epidemics in densely populated environments requires specific consideration in preparedness planning. Prioritization of these settings in vaccination strategies should minimize the risk of future resurgences and potential spillover of transmission to the wider community.
•DYNC1H1 is a key factor for developmental and epileptic encephalopathies.•Besides developmental and neuromuscular problems, epilepsy may develop in the DYNC1H1 variant.•Brain malformation is common ...in DYNC1H1 variant-associated epilepsy.•DYNC1H1 variant-associated epilepsy develop in the motor domain by de novo mutations.•Early-onset epilepsy may be an extended phenotype of DYNC1H1-related disorders.
DYNC1H1 variants are associated with peripheral neuronal dysfunction and brain morphology abnormalities resulting in neurodevelopmental delay. However, few studies have focused on the association between DYNC1H1 variants and epilepsy. Herein, we report a case of drug-resistant focal epilepsy associated with a pathogenic variant of DYNC1H1. We further summarized the clinical, genetic, and neuroimaging characteristics of patients with DYNC1H1 variant–associated epilepsy from the relevant literature. This report expands the phenotypic spectrum of DYNC1H1-related disorder to include early-onset epilepsy, which is frequently associated with neurodevelopmental delay and intellectual disability, malformations of cortical development, and neuromuscular, ophthalmic, and orthopedic involvement.
Melioidosis in Myanmar Win, Mo Mo; Ashley, Elizabeth A; Zin, Khwar Nyo ...
Tropical medicine and infectious disease,
2018-Mar-01, 2018-03-01, 20180301, Letnik:
3, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Sporadic cases of melioidosis have been diagnosed in Myanmar since the disease was first described in Yangon in 1911. Published and unpublished cases are summarized here, along with results from ...environmental and serosurveys. A total of 298 cases have been reported from seven states or regions between 1911 and 2018, with the majority of these occurring before 1949. Findings from soil surveys confirm the presence of
in the environment in all three regions examined. The true epidemiology of the disease in Myanmar is unknown. Important factors contributing to the current gaps in knowledge are lack of awareness among clinicians and insufficient laboratory diagnostic capacity in many parts of the country. This is likely to have led to substantial under-reporting.
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