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Background: The association between isolated diastolic hypertension (IDH) and cardiovascular events has been inconsistently reported. This meta-analysis of cohort studies was designed to investigate the effect of the 2018 European Society of Cardiology (ESC) definition of IDH on the risk of composite cardiovascular events, cardiovascular mortality, all-cause mortality, and all strokes including ischemic stroke (IS) and hemorrhagic stroke (HS).Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to July 6, 2021. Cohort studies that investigated the association between IDH and cardiovascular events risk, compared to normotension, were included. Pooled hazard ratios (HRs) and 95% CIs were calculated using a random-effects models and heterogeneity was evaluated using Q-test and I2 statistic. The robustness of the associations was identified using sensitivity analysis. The methodological quality of the studies was assessed using the Newcastle–Ottawa scale. Publication bias was assessed using funnel plot, trim-and-fill method, Begg's test, and Egger's test.Results: A total of 15 cohort studies (13 articles) including 489,814 participants were included in this meta-analysis. The follow-up period ranged from 4.3 to 29 years. IDH was significantly associated with an increased risk of composite cardiovascular events (HR 1.28, 95% CI: 1.07–1.52, p = 0.006), cardiovascular mortality (HR 1.45, 95% CI: 1.07–1.95, p = 0.015), all strokes (HR 1.44, 95% CI: 1.04–2.01, p = 0.03), and HS (HR 1.64, 95% CI: 1.18–2.29, p = 0.164), but not associated with all-cause mortality (HR 1.20, 95% CI: 0.97–1.47, p = 0.087) and IS (HR 1.56, 95% CI: 0.87–2.81, p = 0.137). Subgroup analysis further indicated that IDH in the younger patients (mean age ≤ 55 years) and from Asia were significantly associated with an increased risk of composite cardiovascular events, while the elderly patients (mean age ≥ 55 years), Americans, and Europeans were not significantly associated with an increased risk of composite cardiovascular events.Conclusion: This meta-analysis provides evidence that IDH defined using the 2018 ESC criterion is significantly associated with an increased risk of composite cardiovascular events, cardiovascular mortality, all strokes and HS, but not significantly associated with all-cause death and IS. These findings also emphasize the importance for patients with IDH to have their blood pressure within normal, especially in the young adults and Asians.Trial Registration: PROSPERO, Identifier: CRD42021254108.

Routine mammography screening is currently the standard tool for finding cancers at an early stage, when treatment is most successful. Current breast screening programmes are one-size-fits-all which all women above a certain age threshold are encouraged to participate. However, breast cancer risk varies by individual. The BREAst screening Tailored for HEr (BREATHE) study aims to assess acceptability of a comprehensive risk-based personalised breast screening in Singapore. Advancing beyond the current age-based screening paradigm, BREATHE integrates both genetic and non-genetic breast cancer risk prediction tools to personalise screening recommendations. BREATHE is a cohort study targeting to recruit ~3,500 women. The first recruitment visit will include questionnaires and a buccal cheek swab. After receiving a tailored breast cancer risk report, participants will attend an in-person risk review, followed by a final session assessing the acceptability of our risk stratification programme. Risk prediction is based on: a) Gail model (non-genetic), b) mammographic density and recall, c) BOADICEA predictions (breast cancer predisposition genes), and d) breast cancer polygenic risk score. For national implementation of personalised risk-based breast screening, exploration of the acceptability within the target populace is critical, in addition to validated predication tools. To our knowledge, this is the first study to implement a comprehensive risk-based mammography screening programme in Asia. The BREATHE study will provide essential data for policy implementation which will transform the health system to deliver a better health and healthcare outcomes.

IntroductionIn very low birth weight (VLBW) infants, hypothermia immediately following birth is common even in countries rich in medical resources. The purpose of this study is to design a standard prevention bundle that decreases the rate of hypothermia among infants after birth and to investigate efficacy of the bundle and short-term outcomes for VLBW infants.MethodsThis quality improvement project was conducted from February 2017 to July 2018 on all VLBW preterm infants admitted at a single referral level III neonatal intensive care unit. The infants were classified into the pre-intervention (February to September 2017) and post-intervention (October 2017 to July 2018) groups according to the time periods when they were recruited. During the pre-intervention period, we analyzed the primary causes of hypothermia, developed solutions corresponding to each cause, integrated all solutions into a prevention bundle, and applied the bundle during the post-intervention period. Afterwards, the incidence of neonatal hypothermia and short-term outcomes, such as intraventricular hemorrhage (IVH), acidosis, and shock requiring inotropic agents, in each group were compared.ResultsA total of 95 VLBW infants were enrolled in the study, including 37 pre-intervention, and 58 post-intervention cases. The incidence of hypothermia in preterm infants decreased significantly upon the implementation of our prevention bundle, both in the delivery room (from 45.9% to 8.6%) and on admission (59.5% to 15.5%). In addition, the short-term outcomes of VLBW infants improved significantly, especially with the decreased incidence of IVH (from 21.6% to 5.2%, P = 0.015).ConclusionsOur standardized prevention bundle for preventing hypothermia in VLBW infants is effective and decreased the IVH rate in VLBW infants. We strongly believe that this prevention bundle is a simple, low-cost, replicable, and effective tool that hospitals can adopt to improve VLBW infant outcomes.

Background: The ongoing COVID-19 pandemic is a global health crisis caused by the spread of SARS-CoV-2. Establishing links between known cases is crucial for the containment of COVID-19. In the healthcare setting, the ability to rapidly identify potential healthcare-associated COVID-19 clusters is critical for healthcare worker and patient safety. Increasing sequencing technology accessibility has allowed routine clinical diagnostic laboratories to sequence SARS-CoV-2 in clinical samples. However, these laboratories often lack specialized informatics skills required for sequence analysis. Therefore, an on-site, intuitive sequence analysis tool that enables clinical laboratory users to analyze multiple genomes and derive clinically relevant information within an actionable timeframe is needed.Results: We propose CalmBelt, an integrated framework for on-site whole genome characterization and outbreak tracking. Nanopore sequencing technology enables on-site sequencing and construction of draft genomes for multiple SARS-CoV-2 samples within 12 h. CalmBelt's interactive interface allows users to analyse multiple SARS-CoV-2 genomes by utilizing whole genome information, collection date, and additional information such as predefined potential clusters from epidemiological investigations. CalmBelt also integrates established SARS-CoV-2 nomenclature assignments, GISAID clades and PANGO lineages, allowing users to visualize relatedness between samples together with the nomenclatures. We demonstrated multiple use cases including investigation of potential hospital transmission, mining transmission patterns in a large outbreak, and monitoring possible diagnostic-escape.Conclusions: This paper presents an on-site rapid framework for SARS-CoV-2 whole genome characterization. CalmBelt interactive web application allows non-technical users, such as routine clinical laboratory users in hospitals to determine SARS-CoV-2 variants of concern, as well as investigate the presence of potential transmission clusters. The framework is designed to be compatible with routine usage in clinical laboratories as it only requires readily available sample data, and generates information that impacts immediate infection control mitigations.

Background Anticoagulants are the cornerstone therapy for the management of venous thromboembolism (VTE) and atrial fibrillation (AF). Pharmacists should be confident and equipped with the skill and updated knowledge in managing anticoagulation therapy. Objective To explore self-reported confidence level of pharmacists, perceived reasons influencing their confidence and socio-demographic associated with high confidence level in the area of anticoagulation. Methods A cross-sectional, self-administered questionnaire survey was carried out among fully registered pharmacists who work in selected government hospitals and clinics in Borneo, Malaysia, from January 2019 to February 2020. Results Overall, responses from 542 fully registered pharmacists were obtained. Proportion of respondents who claimed confident in providing necessary information to patient receiving warfarin (n = 479, 88.3%) was significantly higher (p

Background: Magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) has been overwhelmingly applied to motor regions to date and our understanding of frontotemporal metabolic signatures is relatively limited. The association between metabolic alterations and cognitive performance in also poorly characterised. Material and Methods: In a multimodal, prospective pilot study, the structural, metabolic, and diffusivity profile of the hippocampus was systematically evaluated in patients with ALS. Patients underwent careful clinical and neurocognitive assessments. All patients were non-demented and exhibited normal memory performance. 1H-MRS spectra of the right and left hippocampi were acquired at 3.0T to determine the concentration of a panel of metabolites. The imaging protocol also included high-resolution T1-weighted structural imaging for subsequent hippocampal grey matter (GM) analyses and diffusion tensor imaging (DTI) for the tractographic evaluation of the integrity of the hippocampal perforant pathway zone (PPZ). Results: ALS patients exhibited higher hippocampal tNAA, tNAA/tCr and tCho bilaterally, despite the absence of volumetric and PPZ diffusivity differences between the two groups. Furthermore, superior memory performance was associated with higher hippocampal tNAA/tCr bilaterally. Both longer symptom duration and greater functional disability correlated with higher tCho levels. Conclusion: Hippocampal 1H-MRS may not only contribute to a better academic understanding of extra-motor disease burden in ALS, but given its sensitive correlations with validated clinical metrics, it may serve as practical biomarker for future clinical and clinical trial applications. Neuroimaging protocols in ALS should incorporate MRS in addition to standard structural, functional, and diffusion sequences.

Dengue cases have been rising in recent years. In 2019 alone, over 658,301 of the 5.6 million reported cases originated from Southeast Asia (SEA). Research has also shown detrimental outcomes for pregnant infected women. Despite this, existing literature describing dengue’s effects on pregnancy in SEA is insufficient. Through this narrative review, we sought to describe dengue’s effects on pregnancy systemically and emphasize the existing gaps in the literature. We extensively searched various journals cited in PubMed and Ovid Medline, national clinical practice guidelines, and governmental reports. Dengue in pregnancy increases the risk of pre-eclampsia, Dengue Hemorrhagic Fever (DHF), fetal distress, preterm delivery, Caesarean delivery, and maternal mortality. Vertical transmission, intrauterine growth restriction, and stillbirth are possible sequelae of dengue in fetuses. We found that trimester-specific physiological impacts of dengue in pregnancy (to both mother and child) and investigations and management methods demanded further research, especially in the SEA region.

Background and Aim: The risk factors for bile leakage after hepatectomy without biliary reconstruction are controversial. This study investigated the risk factors for bile leakage after hepatectomy without biliary reconstruction.Methods: We searched databases (Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science) for articles published between January 1, 2000, and May 1, 2021, to evaluate the risk factors for bile leakage after hepatectomy without biliary reconstruction.Results: A total of 16 articles were included in this study, and the overall results showed that sex (OR: 1.21, 95% CI: 1.04–1.42), diabetes (OR: 1.21, 95% CI: 1.05–1.38), left trisectionectomy (OR: 3.53, 95% CI: 2.32–5.36), central hepatectomy (OR: 3.28, 95% CI: 2.63–4.08), extended hemihepatectomy (OR: 2.56, 95% CI: 1.55–4.22), segment I hepatectomy (OR: 2.56, 95% CI: 1.50–4.40), intraoperative blood transfusion (OR:2.40 95%CI:1.79–3.22), anatomical hepatectomy (OR: 1.70, 95% CI: 1.19–2.44) and intraoperative bleeding ≥1,000 ml (OR: 2.46, 95% CI: 2.12–2.85) were risk factors for biliary leakage. Age >75 years, cirrhosis, underlying liver disease, left hepatectomy, right hepatectomy, benign disease, Child–Pugh class A/B, and pre-operative albumin

Abstract Using an established CRISPR-Cas mediated genome editing technique for streptomycetes, we explored the combinatorial biosynthesis potential of the auroramycin biosynthetic gene cluster in Streptomyces roseosporous. Auroramycin is a potent anti-MRSA polyene macrolactam. In addition, auroramycin has antifungal activities, which is unique among structurally similar polyene macrolactams, such as incednine and silvalactam. In this work, we employed different engineering strategies to target glycosylation and acylation biosynthetic machineries within its recently elucidated biosynthetic pathway. Auroramycin analogs with variations in C-, N- methylation, hydroxylation and extender units incorporation were produced and characterized. By comparing the bioactivity profiles of five of these analogs, we determined that unique disaccharide motif of auroramycin is essential for its antimicrobial bioactivity. We further demonstrated that C-methylation of the 3, 5-epi-lemonose unit, which is unique among structurally similar polyene macrolactams, is key to its antifungal activity.

Poststroke shoulder pain (PSSP), also known as hemiplegic shoulder pain, is a common condition that occurs after a stroke. It can cause physical distress and interfere with daily activities. PSSP can be caused by factors such as impaired motor control and altered nervous activity. Treatment options include analgesia, positioning, range of motion exercises, and physical modalities. Medications such as baclofen, antidepressants, and antiepileptics can be used as first-line treatments. Referral to a specialist may be necessary for severe pain or limited range of motion. A multidisciplinary approach is recommended for optimal treatment outcomes. [Extracted from the article]

Abstract Background Mutant peptides presented by cancer cells are superior vaccine candidates than self peptides. The efficacy of mutant K-Ras, P53 and EGFR (Epidermal Growth Factor Receptor) peptides have been tested as cancer vaccines in pancreatic, colorectal, and lung cancers. The immunogenicity of EGFR Del19 mutations, frequent in Chinese lung adenocarcinoma patients, remains unclear. Results We predicted the HLA binding epitopes of Del19 mutations of EGFR in Chinese lung adenocarcinoma patients with NetMHC software. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the EGFR-reactive IgG in lung cancer patients. Del19 mutations may be presented by multiple HLA Class I molecules, with delE746_A750 presented by 37.5% of Chinese population. For HLA Class II molecules, Del19 mutations of EGFR may be presented by multiple HLA-DRB1 molecules, with delE746_A750 presented by 58.1% of Chinese population. Serum reactivity to wild type EGFR protein was significantly higher in patients with Del19 EGFR mutations than those with EGFR L858R point mutation or with EGFR wild type genotype. Conclusions These findings suggest that Del19 mutations of EGFR, with an estimated frequency of 40% in Chinese lung adenocarcinoma patients, may serve as unique targets for immunotherapy in Chinese lung cancer patients.

We aimed to explore the association between skin-to-skin contact (SSC) duration after caesarean sections (CSs) and breastfeeding outcomes. A prospective study was conducted in four hospitals in China during January and August 2021. A total of 679 participants with singleton pregnancy who delivered by elective CS after 37 gestational weeks using epidural or spinal anesthesia were included. Logistic regression was applied to assess the association between SSC duration and early initiation of breastfeeding (EIBF), as well as the promoting factors for exclusive breastfeeding (EBF) at hospital discharge. Immediate SSC after CSs was strongly associated with higher rates of EIBF (p < 0.001) and EBF at hospital discharge (p = 0.002). The EIBF rates increased with longer duration of SSC, with the at least 90 min SSC group having the highest EIBF rate (74.5%). Skin-to-skin contact durations of at least 90 min, 60–89 min and 30–59 min were significantly associated with 8.53 times (OR = 8.53, 95%CI: 4.94–14.72, Padj < 0.001), 8.04 times (95%CI: 4.68–13.80, Padj < 0.001) and 6.28 times (95%CI: 3.75–10.51, Padj < 0.001), respectively, higher EIBF rates compared to those without immediate SSC. After multiple-testing correction, the rates of EBF at hospital discharge were found to be independent of the duration of SSC (Padj = 0.12). Early initiation of breastfeeding was not a significant predictor of EBF. Our results suggested that SSC is important for EIBF in Chinese baby-friendly hospitals. Skin-to-skin contact should be practiced after CS to promote breastfeeding and providing SSC with longer duration is encouraged to obtain the full benefit; if it is not feasible, a minimum of 30 min SSC could achieve improved EIBF and EBF at discharge.

Background: Patients with cancer are at increased risk of acute myocardial infarction (AMI). It is unclear if the Atherosclerotic Cardiovascular Disease (ASCVD) risk score at incident AMI is reflective of this higher risk in patients with prior cancer than those without. Methods: We linked nationwide AMI and cancer registries from 2008 to 2019. A total of 18,200 eligible patients with ASCVD risk score calculated at incident AMI were identified (1086 prior cancer; 17,114 no cancer). Results: At incident AMI, age-standardized mean ASCVD risk was lower in the prior cancer group (18.6%) than no cancer group (20.9%) (p < 0.001). Prior to incident AMI, smoking, hypertension, hyperlipidemia and diabetes mellitus were better controlled in the prior cancer group. However post-AMI, prior cancer was associated with lower guideline-directed medical therapy usage and higher all-cause mortality (adjusted hazard ratio 1.85, 95% confidence interval 1.66–2.07). Conclusions: AMI occurred despite better control of cardiovascular risk factors and lower age-standardized estimated mean 10-year ASCVD risk among patients with prior cancer than no cancer. Prior cancer was associated with lower guideline-directed medical therapy post-AMI and higher mortality.

Blockchain technology and its applications have recently become a research hotspot. Its three core technologies, distributed ledger, smart contract, and consensus mechanism, provide trust-enhancing features such as tamper-proof records, full traceability, and data decentralization for a wide range of applications. This paper investigates the use of blockchain technology in environmental health. It investigates indicators such as the number of articles published, author collaboration network, research institution network, and keyword co-occurrence in this field between 2014 and 2021. It describes and analyzes the development and connotations of these indicators. Many scholars have conducted in-depth studies on blockchain in various areas. Still, there are few cross-over studies on environmental health and a lack of cross-over studies on technology application in multiple fields. The current study investigates the evolution of research on the application of blockchain technology in environmental health, as well as potential development patterns and research trends, to provide a theoretical foundation for the application and sustainability of blockchain technology in this field.

The recent COVID-19 pandemic has highlighted the urgency to develop effective antiviral therapies against the disease. Murine hepatitis virus (MHV) is a coronavirus that infects mice and shares some sequence identity to SARS-CoV-2. Both viruses belong to the Betacoronavirus genus, and MHV thus serves as a useful and safe surrogate model for SARS-CoV-2 infections. Clinical trials have indicated that remdesivir is a potentially promising antiviral drug against COVID-19. Using an in vitro model of MHV infection of RAW264.7 macrophages, the safety and efficacy of monotherapy of remdesivir, chloroquine, ivermectin, and doxycycline were investigated. Of the four drugs tested, remdesivir monotherapy exerted the strongest inhibition of live virus and viral RNA replication of about 2-log10 and 1-log10, respectively (at 6 µM). Ivermectin treatment showed the highest selectivity index. Combination drug therapy was also evaluated using remdesivir (6 µM) together with chloroquine (15 µM), ivermectin (2 µM) or doxycycline (15 µM) – above their IC50 values and at high macrophage cell viability of over 95%. The combination of remdesivir and ivermectin exhibited highly potent synergism by achieving significant reductions of about 7-log10 of live virus and 2.5-log10 of viral RNA in infected macrophages. This combination also resulted in the lowest cytokine levels of IL-6, TNF-α, and leukemia inhibitory factor. The next best synergistic combination was remdesivir with doxycycline, which decreased levels of live virus by ~3-log10 and viral RNA by ~1.5-log10. These results warrant further studies to explore the mechanisms of action of the combination therapy, as well as future in vivo experiments and clinical trials for the treatment of SARS-CoV-2 infection.

Theory of Change (ToC) and Social Return of Investment (SROI) are planning tools that help projects craft strategic approaches in order to create the most impact. In 2018, the Management & Ecology of Malaysian Elephants (MEME) carried out planning exercises using these tools to develop an Asian elephant conservation project with agriculture communities. First, a problem tree was constructed together with stakeholders, with issues arranged along a cause-and-effect continuum. There were 17 main issues identified, ranging from habitat connectivity and fragmentation, to the lack of tolerance toward wild elephants. All issues ultimately stemmed from a human mindset that favors human-centric development. The stakeholders recognize the need to extend conservation efforts beyond protected areas and move toward coexistence with agriculture communities for the survival of the wild elephants. We mapped previous Human-Elephant Conflict (HEC) management methods and other governmental policies in Malaysia against the problem tree, and provided an overview of the different groups of stakeholders. The ToC was developed and adapted for each entity, while including Asian elephants as a stakeholder in the project. From the SROI estimation, we extrapolated the intrinsic value of the wild Asian elephant population in Johor, Malaysia, to be conservatively worth at least MYR 7.3 million (USD 1.8 million) per year. From the overall calculations, the potential SROI value of the project is 18.96 within 5 years, meaning for every ringgit invested in the project, it generates MYR 18.96 (USD 4.74) worth of social return value. There are caveats with using these value estimations outside of the SROI context, which was thoroughly discussed. The SROI provides projects with the ability to justify to funders the social return values of its activities, which we have adapted to include the intrinsic value of an endangered megafauna. Moreover, SROI encourages projects to consider unintended impacts (i.e., replacement, displacement, and deadweight), and acknowledge contributions from stakeholders. The development of the problem tree and ToC via SROI approach, can help in clarifying priorities and encourage thinking out of the box. For this case study, we presented the thinking process, full framework and provided evidences to support the Theory of Change.

Abstract Objectives Currently, there are no guidelines to help triage nurses identify high‐risk emergency department chest pain patients. Patient self‐reporting of Emergency Department Assessment of Chest Pain Score (EDACS) could facilitate more reliable triage compared to nursing gestalt, but this novel concept is untested. This study hypothesizes that because EDACS requires minimal clinical gestalt to derive, self‐reported EDACS (S‐EDACS) at triage is likely to correlate well with traditional physician‐reported EDACS (P‐EDACS) and have potential application as a triage tool. Methods This single‐center pilot prospective cohort study analyzed 60 patients who completed a self‐reported questionnaire upon triage to determine their S‐EDACS. This was matched against P‐EDACS, derived from an identical questionnaire completed by the blinded treating physician. Secondary endpoint of major adverse cardiovascular events (MACE) within 30 days (all‐cause mortality, myocardial infarction, coronary revascularization) was assessed by 2 blinded emergency physicians who independently reviewed the electronic medical records. S/P‐EDACS also were benchmarked against nursing gestalt (based on triage to low/high‐acuity areas) and emergency physician gestalt (disposition and admitting/discharge diagnoses). Results There was perfect agreement between S/P‐EDACS in this study (K = 1.00). Fifteen patients (25.0%) had minor discordances in their absolute S/P‐EDACS that did not affect risk stratification. Of these, 11/15 (73.3%) had higher S‐EDACS, suggesting S‐EDACS is more likely to safely overcall MACE risk. S‐EDACS outperformed nursing gestalt, triaging a greater proportion of patients (71.7% vs 35.0%) as low risk without compromising patient safety, and demonstrated similar accuracy as emergency physician gestalt. Conclusion S‐EDACS strongly correlates with P‐EDACS with perfect agreement and has potential to be used as a triage tool.

Carbon-Dots (C-Dots) have drawn much attention in recent years owing to their remarkable properties such as high biocompatibility, low toxicity, nano-scale size, and ease of modification with good tuneable photoluminescence performance. These unique properties have led C-Dots to become a promising platform for bioimaging, metal ion sensing and an antibacterial agent. C-Dots can be prepared using the top-down and bottom-up approaches, in which the latter method is commonly used for large scale and low-cost synthesis. C-Dots can be synthesized using sustainable raw materials or green biomass since it is environmentally friendly, in-expensive and most importantly, promotes the minimization of waste production. However, using biomass waste to produce high-quality C-Dots is still a matter of concern waiting for resolution, and this will be the main focus of this review. Fundamental understanding of C-Dots such as structure analysis, physical and chemical properties of C-Dots, various synthesis methodology and type of raw materials used are also discussed and correlated comprehensively. Additionally, factors affecting the bandgap of the C-Dots and the strategies to overcome these shortcomings are also covered. Moreover, formation mechanism of C-Dots focusing on the hydrothermal method, option and challenges to scale up the C-Dots production are explored. It is expected that the great potential of producing C-Dots from agricultural waste a key benefit in view of their versatility in a wide range of applications.

Based on plasma kinetic theory, the dispersion and Landau damping of Langmuir and ion-acoustic waves carrying finite orbital angular momentum (OAM) were investigated in the κ-deformed Kaniadakis distributed plasma system. The results showed that the peculiarities of the investigated subjects relied on the deformation parameter κ and OAM parameter η. For both Langmuir and ion-acoustic waves, dispersion was enhanced with increased κ, while the Landau damping was suppressed. Conversely, both the dispersion and Landau damping were depressed by OAM. Moreover, the results coincided with the straight propagating plane waves in a Maxwellian plasma system when κ=0 and η→∞. It was expected that the present results would give more insight into the trapping and transportation of plasma particles and energy.

A new electrochemical DNA biosensor based on mercaptopropionic acid (MPA)-capped ZnS quantum dots (MPA-ZnS QDs) immobilization matrix for covalent binding with 20-base aminated oligonucleotide has been successfully developed. Prior to the modification, screen-printed carbon paste electrode (SPE) was self-assembled with multilayer gold nanoparticles (AuNPs) and cysteamine (Cys). The inclusion of MPA-ZnS QDs semiconducting material in modified electrodes has enhanced the electron transfer between the SPE transducer and DNA leading to improved bioanalytical assay of target biomolecules. Electrochemical studies performed by cyclic voltammetry (CV) and differential pulsed voltammetry (DPV) demonstrated that the MPA-ZnS QDs modified AuNPs electrode was able to produce a lower charge transfer resistance response and hence higher electrical current response. Under optimal conditions, the immobilized synthetic DNA probe exhibited high selectivity towards synthetic target DNA. Based on the DPV response of the reduction of anthraquinone monosulphonic acid (AQMS) redox probe, the MPA-ZnS QDs-based electrochemical DNA biosensor responded to target DNA concentration from 1 × 10−9 μM to 1 × 10−3 μM with a sensitivity 1.2884 ± 0.12 µA, linear correlation coefficient (R2) of 0.9848 and limit of detection (LOD) of 1 × 10−11 μM target DNA. The DNA biosensor exhibited satisfactory reproducibility with an average relative standard deviation (RSD) of 7.4%. The proposed electrochemical transducer substrate has been employed to immobilize the aminated Arowana fish (Scleropages formosus) DNA probe. The DNA biosensor showed linearity to target DNA from 1 × 10−11 to 1 × 10−6 µM (R2 = 0.9785) with sensitivity 1.1251 ± 0.243 µA and LOD of 1 × 10−11 µM. The biosensor has been successfully used to determine the gender of Arowana fish without incorporating toxic raw materials previously employed in the hazardous processing conditions of polypyrrole chemical conducting polymer, whereby the cleaning step becomes difficult with thicker films due to high levels of toxic residues from the decrease in polymerization efficacy as films grew.

A microbial optosensor for nitrite was constructed based on biomimetic silica nanoparticles, which were doped with R5, a polypeptide component of silaffin, as a robust biosilica immobilization matrix entrapped with Raoultella planticola and NAD(P)H cofactor during the in vitro biosilicification process of silica nanoparticles. Ruthenium(II)(bipy)2(phenanthroline-benzoylthiourea), the chromophoric pH probe, was physically adsorbed on the resulting biogenic nanosilica. Optical quantitation of the nitrite concentration was performed via reflectance transduction of the bio-doped microbial nanosilica at a maximum reflectance of 608 nm, due to the deprotonation of phen-BT ligands in the ruthenium complex, while the intracellular enzyme expression system catalyzed the enzymatic reduction of nitrite. Reflectance enhancement of the microbial optosensor was linearly proportional to the nitrite concentration from 1–100 mg L−1, with a 0.25 mg L−1 limit of detection and a rapid response time of 4 min. The proposed microbial optosensor showed good stability of >2 weeks, great repeatability for 5 repetitive assays (relative standard deviation, (RSD) = 0.2–1.4%), high reproducibility (RSD = 2.5%), and a negligible response to common interferents found in processed meats, such as NO3−, NH4+, K+, Ca2+, and Mg2+ ions, was observed. The microbial biosensor demonstrated an excellent capacity to provide an accurate estimation of nitrite in several cured meat samples via validation using a standard UV-vis spectrophotometric Griess assay.

The new coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been reported and spread globally. There is an urgent need to take urgent measures to treat and prevent further infection of this virus. Here, we use virtual drug screening to establish pharmacophore groups and analyze the ACE2 binding site of the spike protein with the ZINC drug database and DrugBank database by molecular docking and molecular dynamics simulations. Screening results showed that Venetoclax, a treatment drug for chronic lymphocytic leukemia, has a potential ability to bind to the spike protein of SARS-CoV-2. In addition, our in vitro study found that Venetoclax degraded the expression of the spike protein of SARS-CoV-2 through amino acids Q493 and S494 and blocked the interaction with the ACE2 receptor. Our results suggest that Venetoclax is a candidate for clinical prevention and treatment and deserves further research.

Aristolactam I (ALI) is an active component derived from some Traditional Chinese medicines (TCMs), and also the important metabolite of aristolochic acid. Long-term administration of medicine-containing ALI was reported to be related to aristolochic acid nephropathy (AAN), which was attributed to ALI-induced nephrotoxicity. However, the toxic mechanism of action involved is still unclear. Recently, pathogenic ferroptosis mediated lipid peroxidation was demonstrated to cause kidney injury. Therefore, this study explored the role of ferroptosis induced by mitochondrial iron overload in ALI-induced nephrotoxicity, aiming to identify the possible toxic mechanism of ALI-induced chronic nephropathy. Our results showed that ALI inhibited HK-2 cell activity in a dose-dependent manner and significantly suppressed glutathione (GSH) levels, accompanying by significant increases in intracellular 4-hydroxynonenal (4-HNE) and intracellular iron ions. Moreover, the ALI-mediated cytotoxicity could be reversed by deferoxamine mesylate (DFO). Compared with other inhibitors, Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, obviously alleviated ALI-induced cytotoxicity. Furthermore, we have shown that ALI could remarkably increase the levels of superoxide anion and ferrous ions in mitochondria, and induce mitochondrial damage and condensed mitochondrial membrane density, the morphological characteristics of ferroptosis, all of which could be reversed by DFO. Interestingly, ALI dose-dependently inhibited these protein contents of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4), which could be partly rescued by Tin-protoporphyrin IX (SnPP) and mitoTEMPO co-treatment. In conclusion, our results demonstrated that mitochondrial iron overload-mediated antioxidant system inhibition would assist ALI-induced ferroptosis in renal tubular epithelial cells, and Nrf2-HO-1/GPX4 antioxidative system could be an important intervention target to prevent medicine containing ALI-induced nephropathy.

Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).Results Of 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.

The antecedents of leadership emergence have received increasing attention over the past decades. Extant work has found that traits that involve getting along with other members in social relations can help employees emerge as leaders. However, attachment has been ignored, even though it can provide a distinct relational perspective to getting along. This study investigates the relationship between attachment and leadership emergence as well as the mediating role of negative emotion and the moderating role of initiating structure in the relationship. Specifically, based on multisource data of 100 employees and their supervisors, the results reveal that avoidant attachment and anxious attachment exert a negative impact on leadership emergence via negative emotion. Moreover, the mediating effect on the above relationship is weaker when employees are at a high initiating structure level. The findings imply that insecurely attached employees can also be leaders if they expend more effort and focus more on task completion.