Intravenous tissue plasminogen activator (tPA) remains the cornerstone of recanalization therapy for acute ischemic stroke (AIS), albeit with varying degrees of response. The triglyceride-glucose ...(TyG) index is a novel marker of insulin resistance, but association with outcomes among AIS patients who have received tPA has not been well elucidated. We studied 698 patients with AIS who received tPA from 2006 to 2018 in a comprehensive stroke centre. TyG index was calculated using the formula: lnfasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2. TyG index was significantly lower in patients that survived at 90-days than those who died (8.61 Interquartile Range: 8.27-8.99 vs 8.76 interquartile range: 8.39-9.40, p = 0.007). In multivariate analysis, TyG index was significantly associated with 90-day mortality (OR: 2.12, 95% CI: 1.39-3.23, p = 0.001), poor functional outcome (OR: 1.41 95% CI: 1.05-1.90, p = 0.022), and negatively associated with early neurological improvement (ENI) (OR: 0.68, 95% CI: 0.52-0.89, p = 0.004). There was no association between TyG index and symptomatic intracranial hemorrhage. 'High TyG' (defined by TyG index ≥ 9.15) was associated with mortality, poor functional outcomes and no ENI. In conclusion, the TyG index, a measure of insulin resistance, was significantly associated with poorer clinical outcomes in AIS patients who received tPA.
A simple method based on potentiostatic polymerization was developed for the preparation of ternary manganese oxide-based nanocomposite films. The ternary nanocomposites, which were characterized ...using x-ray diffraction spectroscopy and x-ray photoelectron spectroscopy, showed that the manganese oxide within the film consisted of MnO2 and Mn2O3. Electrochemical measurements showed that the ternary nanocomposite electrode exhibited high specific capacitance (up to 320.6F/g), which was attributed to the morphology of a polypyrrole/graphene/manganese-oxide (PPy/GR/MnOx) ternary nanocomposite. The experimental approach maximized the pseudocapacitive contribution from redox-active manganese oxide (MnOx) and polypyrrole (PPy), as well as the electrochemical double layer capacitive (EDLC) characteristic from graphene (GR) sheets. Long cyclic measurements indicated that the specific capacitance of the ternary nanocomposite film could retain 93% of its initial value over 1000 charge/discharge cycles, in the potential range of −0.2 to 0.7V versus silver/silver chloride electrode (Ag/AgCl).
We conducted a comprehensive humidifier disinfectant exposure characterization for 374 subjects with lung disease who presumed their disease was related to humidifier disinfectant use (patient group) ...and for 303 of their family members (family group) for an ongoing epidemiological study. We visited the homes of the registered patients to investigate disinfectant use characteristics. Probability of exposure to disinfectants was determined from the questionnaire and supporting evidence from photographs demonstrating the use of humidifier disinfectant, disinfectant purchase receipts, any residual disinfectant, and the consistency of their statements. Exposure duration was estimated as cumulative disinfectant use hours from the questionnaire. Airborne disinfectant exposure intensity (μg/m3) was estimated based on the disinfectant volume (ml) and frequency added to the humidifier per day, disinfectant bulk level (μg/ml), the volume of the room (m3) with humidifier disinfectant, and the degree of ventilation. Overall, the distribution patterns of the intensity, duration, and cumulative exposure to humidifier disinfectants for the patient group were higher than those of the family group, especially for pregnant women and patients ≤6 years old. Further study is underway to evaluate the association between the disinfectant exposures estimated here with clinically diagnosed lung disease.
Gestational Diabetes Mellitus (GDM) affects one in six births worldwide. Mothers with GDM have an increased risk of developing post-partum Type-2 Diabetes Mellitus (T2DM). However, their uptake of ...post-partum diabetes screening is suboptimal, including those in Singapore. Literature reports that the patient-doctor relationship, mothers' concerns about diabetes, and family-related practicalities are key factors influencing the uptake of such screening. However, we postulate additional factors related to local society, healthcare system, and policies in influencing post-partum diabetes screening among mothers with GDM.
The qualitative research study aimed to explore the facilitators and barriers to post-partum diabetes screening among mothers with GDM in an Asian community.
In-depth interviews were carried out on mothers with GDM at a public primary care clinic in Singapore. Mothers were recruited from those who brought their child for vaccination appointments and their informed consent was obtained. Both mothers who completed post-partum diabetes screening within 12 weeks after childbirth and those who did not were purposively recruited. The social ecological model (SEM) provides the theoretical framework to identify facilitators and barriers at the individual, interpersonal, organizational, and policy levels.
Twenty multi-ethnic Asian mothers with GDM were interviewed. At the individual and interpersonal level, self-perceived risk of developing T2DM, understanding the need for screening and the benefits of early diagnosis, availability of confinement nanny in Chinese family, alternate caregivers, emotional, and peer support facilitated post-partum diabetes screening. Barriers included fear of the diagnosis and its consequences, preference for personal attention and care to child, failure to find trusted caregiver, competing priorities, and unpleasant experiences with the oral glucose tolerance test. At the organizational and public policy level, bundling of scheduled appointments, and standardization of procedure eased screening but uptake was hindered by inconvenient testing locations, variable post-partum care practices and advice in the recommendations for diabetes screening.
Based on the SEM, facilitators and barriers towards post-partum diabetes screening exist at multiple levels, with some contextualized to local factors. Interventions to improve its uptake should be multi-pronged, targeting not only at personal but also familial, health system, and policy factors to ensure higher level of success.
Summary
Chronic, untreated hepatitis C virus (HCV) infection is associated with a poor clinical prognosis and a detrimental impact on patients' lives, including on work productivity. To estimate the ...value of productivity losses due to genotype 1 (GT1) HCV infection in Hong Kong, Singapore, South Korea and Taiwan and to estimate the potential productivity gains associated with treating patients with ledipasvir/sofosbuvir (LDV/SOF) therapy, an economic model was developed with a time horizon of 1 year. Hepatitis C virus patients entered the model at 12 weeks post‐treatment, having achieved or not achieved sustained virological response (SVR). Absenteeism and presenteeism rates were taken from a pooled analysis of data from the ION 1‐3 studies. These rates were converted into hours of lost productivity, multiplied by the average wage and applied to the total employed, adult GT1 population in each country. Results were compared assuming no treatment, and assuming all patients were treated with LDV/SOF. Total productivity losses due to untreated HCV were: $11.3 million, $17.1 m, $146.0 m and $349.1 m in Hong Kong, Singapore, South Korea and Taiwan. LDV/SOF treatment resulted in economic gains of $4.5 m, $6.8 m, $58.7 m and $138 m, respectively. These gains were due to reduced presenteeism. The results were sensitive to changes in the prevalence of HCV and the average wage. In conclusion, productivity losses due to untreated HCV infection represent a substantial economic burden. By instituting universal HCV treatment with LDV/SOF (or other therapies with high SVR rates), productivity gains can be achieved.
Circular RNA (circRNA) is a newly validated class of single-stranded RNA, ubiquitously expressed in mammalian tissues and possessing key functions including acting as microRNA sponges and as ...transcriptional regulators by binding to RNA-binding proteins. While independent studies confirm the expression of circRNA in various tissue types, genome-wide circRNA expression in the heart has yet to be described in detail.
We performed deep RNA-sequencing on ribosomal-depleted RNA isolated from 12 human hearts, 25 mouse hearts and across a 28-day differentiation time-course of human embryonic stem cell-derived cardiomyocytes. Using purpose-designed bioinformatics tools, we uncovered a total of 15 318 and 3017 cardiac circRNA within human and mouse, respectively. Their abundance generally correlates with the abundance of their cognate linear RNA, but selected circRNAs exist at disproportionately higher abundance. Top highly expressed circRNA corresponded to key cardiac genes including Titin (TTN), RYR2, and DMD. The most abundant cardiac-expressed circRNA is a cytoplasmic localized single-exon circSLC8A1-1. The longest human transcript TTN alone generates up to 415 different exonic circRNA isoforms, the majority (83%) of which originates from the I-band domain. Finally, we confirmed the expression of selected cardiac circRNA by RT-PCR, Sanger sequencing and single molecule RNA-fluorescence in situ hybridization.
Our data provide a detailed circRNA expression landscape in hearts. There is a high-abundance of specific cardiac-expressed circRNA. These findings open up a new avenue for future investigation into this emerging class of RNA.
Global warming is a critical issue and has great impact on all living organisms, including algae. Generally, algae play significant roles in aquatic ecosystems and employ diverse strategies to ...survive under abiotic stress. For example, heat stress affects membrane fluidity, and algae, in response, can modify their membrane fatty acid composition to maintain homoeostasis. Moreover, they protect their proteins and enzymes using molecular chaperones or degrade denatured proteins in processes involving ubiquitin. In addition, algae regulate their carbohydrate concentrations and structures to utilise the energy of endogenous carbon sources efficiently and protect other molecules via accumulation of compatible solutes. Algae regulate the photosynthetic machinery to acclimatise to stress conditions. In fact, algae have a range of acclimation and repair strategies; and in the case where these strategies fail, programmed cell death (PCD) will be activated. Among algae, green algae have been massively studied due to their broad-range applications such as pharmaceutical, biofuel production and wastewater management, and being a suitable model to study plant and photosynthesis. Enhanced knowledge about the genes and proteins involved in the acclimation of green algae would enlighten our understanding of their acclimation pathways, and enable the genetic improvement of stress-tolerant strains. Thus, the mechanisms and pathways associated with green algal acclimation and repair strategies with an emphasis on temperature-related stress are highlighted in this review.
Hutchinson-Gilford progeria (HGPS) is a premature ageing syndrome caused by a mutation in LMNA, resulting in a truncated form of lamin A called progerin. Progerin triggers loss of the heterochromatic ...marker H3K27me3, and premature senescence, which is prevented by telomerase. However, the mechanism how progerin causes disease remains unclear. Here, we describe an inducible cellular system to model HGPS and find that LAP2α (lamina-associated polypeptide-α) interacts with lamin A, while its interaction with progerin is significantly reduced. Super-resolution microscopy revealed that over 50% of telomeres localize to the lamina and that LAP2α association with telomeres is impaired in HGPS. This impaired interaction is central to HGPS since increasing LAP2α levels rescues progerin-induced proliferation defects and loss of H3K27me3, whereas lowering LAP2 levels exacerbates progerin-induced defects. These findings provide novel insights into the pathophysiology underlying HGPS, and how the nuclear lamina regulates proliferation and chromatin organization.
Post-acute coronary syndrome (ACS) depression is a common but not well understood complication experienced by ACS patients. Research on the effectiveness of various therapies remains limited. Hence, ...we sought to conduct a network meta-analysis to assess the efficacy of different interventions for post-ACS depression in improving patient outcomes.
Three electronic databases were searched for randomised controlled trials describing different depression treatment modalities in post-ACS patients. Each article was screened based on inclusion criteria and relevant data were extracted. A bivariate analysis and a network meta-analysis was performed using risk ratios (RR) and standardized mean differences (SMD) for binary and continuous outcomes, respectively. A total of 30 articles were included in our analysis. Compared to standard care, psychosocial therapy was associated with the greatest reduction in depression scores (SMD:-1.21, 95% CI: -1.81 to -0.61, p<0.001), followed by cognitive behavioural therapy (CBT) (SMD: -0.75, 95% CI: -0.99 to -0.52, p<0.001), antidepressants (SMD: -0.73, 95% CI: -1.14 to -0.31, p<0.001), and lastly, combination therapy (SMD: -0.15, 95% CI: -0.28 to -0.03, p = 0.016). No treatment modalities was found to be more effective in reducing depression scores when compared to one another. Additional analysis showed that these treatment modalities did not have significant impact on the overall mortality, cardiac mortality and recurrent myocardial infarction.
This network meta-analysis found that the treatment effect of the various psychological modalities on depression severity were similar. Future trials on psychological interventions assessing clinical outcomes and improvement in adherence to ACS-specific interventions are needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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