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Simple Summary: Patients with previous cancer are more likely to suffer from a heart attack than those without cancer. Although risk stratification scores are commonly used both to guide management and estimate mortality after a heart attack, it is unclear if such scores can be applied to patients with previous cancer. As such, this study aimed to determine the performance of the well-established GRACE (Global Registry of Acute Coronary Events) score by combining large national cancer and heart attack databases. This study showed that although the GRACE score was more accurate in patients without cancer, it greatly underestimated the risk of death in patients with previous cancer. Specific risk stratification scores are required for patients with previous cancer who have a heart attack. Background Patients with prior cancer are at increased risk of acute coronary syndrome (ACS) with poorer post-ACS outcomes. We aimed to ascertain if the Global Registry of Acute Coronary Events (GRACE) score accurately predicts mortality risk among patients with ACS and prior cancer. Methods We linked nationwide ACS and cancer registries from 2007 to 2018 in Singapore. A total of 24,529 eligible patients had in-hospital and 1-year all-cause mortality risk calculated using the GRACE score (2471 prior cancer; 22,058 no cancer). Results Patients with prior cancer had two-fold higher all-cause mortality compared to patients without cancer (in-hospital: 22.8% versus 10.3%, p < 0.001; 1-year: 49.0% vs. 18.7%, p < 0.001). Cardiovascular mortality did not differ between groups (in-hospital: 5.2% vs. 4.8%, p = 0.346; 1-year: 6.9% vs. 6.1%, p = 0.12). The area under the receiver operating characteristic curve of the GRACE score for prediction of all-cause mortality was less for prior cancer (in-hospital: 0.64 vs. 0.80, p < 0.001; 1-year: 0.66 vs. 0.83, p < 0.001). Among patients with prior cancer and a high-risk GRACE score > 140, in-hospital revascularization was not associated with lower cardiovascular mortality than without in-hospital revascularization (6.7% vs. 7.6%, p = 0.50). Conclusions The GRACE score performs poorly in risk stratification of patients with prior cancer and ACS. [ABSTRACT FROM AUTHOR]

This study aimed to explore barriers to hearing aid adoption amongst older adults in mainland China. Semi-structured interviews were audio-recorded and analysed using qualitative thematic analysis. The study included 12 older adults who had seen ENTs and had not adopted hearing aids. Three overarching themes and ten subthemes were generated to explain why older adults in mainland China do not adopt hearing aids: (1) Desire a cure for hearing loss, (2) Lack of a perceived need for hearing aids, and (3) Negative impressions of, and misconceptions about, hearing aids. Although barriers are similar to those reported in Western societies, the under-developed hearing healthcare infrastructure, Chinese health beliefs, Chinese culture, and low health literacy play important roles in preventing older adults to adopt hearing aids in mainland China. To identify barriers to hearing aid adoption and address them, hearing health practitioners should learn what older adults know about their hearing loss, how they perceive the effects of hearing loss, and how they feel about hearing aids. [ABSTRACT FROM AUTHOR]

Objective: Cut-offs for high-sensitivity troponin (hs-Tn) elevations to define prognostically significant peri-operative myocardial injury (PMI) in cardiac surgery is not well-established. We evaluated the associations between peri-operative high-sensitivity troponin T (hs-TnT) elevations and 1-year all-cause mortality in patients undergoing cardiac surgery. Methods: The prognostic significance of baseline hs-TnT and various thresholds for post-operative hs-TnT elevation at different time-points on 1-year all-cause mortality following cardiac surgery were assessed after adjusting for baseline hs-TnT and EuroSCORE in a post-hoc analysis of the ERICCA trial. Results: 1206 patients met the inclusion criteria. Baseline elevation in hs-TnT >x1 99th percentile upper reference limit (URL) was significantly associated with 1-year all-cause mortality (adjusted hazard ratio 1.90, 95% confidence interval 1.15–3.13). In the subgroup with normal baseline hs-TnT (n = 517), elevation in hs-TnT at all post-operative time points was associated with higher 1-year mortality, reaching statistical significance for elevations above: ≥100 × URL at 6 h; ≥50 × URL at 12 and 24 h; ≥35 × URL at 48 h; and ≥30 × URL at 72 h post-surgery. Elevation in hs-TnT at 24 h ≥ 50 × URL had the optimal sensitivity and specificity (73% and 75% respectively). When the whole cohort of patients was analysed, including those with abnormal baseline hs-TnT (up to 10 × URL), the same threshold had optimal sensitivity and specificity (66% and 70%). Conclusions: Both baseline and post-operative hs-TnT elevations are independently associated with 1-year all-cause mortality in patients undergoing cardiac surgery. The optimal threshold to define a prognostically significant PMI in our study was ≥50 × URL elevation in hs-TnT at 24 h. [ABSTRACT FROM AUTHOR]

Risk stratification plays a key role in identifying acute myocardial infarction (AMI) patients at higher risk of mortality. However, current AMI risk scores such as the Global Registry of Acute Coronary Events (GRACE) score were derived from predominantly Caucasian populations and may not be applicable to Asian populations. We previously developed an AMI risk score from the national-level Singapore Myocardial Infarction Registry (SMIR) confined to ST-segment elevation myocardial infarction (STEMI) patients and did not include non-STEMI (NSTEMI) patients. Here, we derived a modified SMIR risk score for both STEMI and NSTEMI patients and compared its performance to the GRACE 2.0 score for predicting 1-year all-cause mortality in our multi-ethnic population. The most significant predictor of 1-year all-cause mortality in our population using the GRACE 2.0 score was cardiopulmonary resuscitation on admission (adjusted hazards ratio [HR] 6.50), while the most significant predictor using the SMIR score was age 80–89 years (adjusted HR 7.78). Although the variables used in the GRACE 2.0 score and SMIR score were not exactly the same, the c-statistics for 1-year all-cause mortality were similar between the two scores (GRACE 2.0 0.841 and SMIR 0.865). In conclusion, we have shown that in a multi-ethnic Asian AMI population undergoing PCI, the SMIR score performed as well as the GRACE 2.0 score. [ABSTRACT FROM AUTHOR]

Patients with cancer are at increased risk of myocardial infarction (MI) and stroke. Guidelines do not address lipid profile targets for these patients. Within the lipid profiles, we hypothesized that patients with cancer develop MI or stroke at lower low density lipoprotein cholesterol (LDL-C) concentrations than patients without cancer and suffer worse outcomes. We linked nationwide longitudinal MI, stroke and cancer registries from years 2007–2017. We identified 42,148 eligible patients with MI (2421 prior cancer; 39,727 no cancer) and 43,888 eligible patients with stroke (3152 prior cancer; 40,738 no cancer). Median LDL-C concentration was lower in the prior cancer group than the no cancer group at incident MI [2.43 versus 3.10 mmol/L, adjusted ratio 0.87 (95% CI 0.85–0.89)] and stroke [2.81 versus 3.22 mmol/L, adjusted ratio 0.93, 95% CI 0.91–0.95)]. Similarly, median triglyceride and total cholesterol concentrations were lower in the prior cancer group, with no difference in high density lipoprotein cholesterol. Prior cancer was associated with higher post-MI mortality [adjusted hazard ratio (HR) 1.48, 95% CI 1.37–1.59] and post-stroke mortality (adjusted HR 1.95, 95% CI 1.52–2.52). Despite lower LDL-C concentrations, patients with prior cancer had worse post-MI and stroke mortality than patients without cancer. [ABSTRACT FROM AUTHOR]

Lowering low-density lipoprotein (LDL-C) and triglyceride (TG) levels form the cornerstone approach of cardiovascular risk reduction, and a higher high-density lipoprotein (HDL-C) is thought to be protective. However, in acute myocardial infarction (AMI) patients, higher admission LDL-C and TG levels have been shown to be associated with better clinical outcomes - termed the 'lipid paradox'. We studied the relationship between lipid profile obtained within 72 hours of presentation, and all-cause mortality (during hospitalization, at 30-days and 12-months), and rehospitalization for heart failure and non-fatal AMI at 12-months in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients treated by percutaneous coronary intervention (PCI). We included 11543 STEMI and 8470 NSTEMI patients who underwent PCI in the Singapore Myocardial Infarction Registry between 2008–2015. NSTEMI patients were older (60.3 years vs 57.7 years, p < 0.001) and more likely to be female (22.4% vs 15.0%, p < 0.001). In NSTEMI, a lower LDL-C was paradoxically associated with worse outcomes for death during hospitalization, within 30-days and within 12-months (all p < 0.001), but adjustment eliminated this paradox. In contrast, the paradox for LDL-C persisted for all primary outcomes after adjustment in STEMI. For NSTEMI patients, a lower HDL-C was associated with a higher risk of death during hospitalization but in STEMI patients a lower HDL-C was paradoxically associated with a lower risk of death during hospitalization. For this endpoint, the interaction term for HDL-C and type of MI was significant even after adjustment. An elevated TG level was not protective after adjustment. These observations may be due to differing characteristics and underlying pathophysiological mechanisms in NSTEMI and STEMI. [ABSTRACT FROM AUTHOR]

Background: Experiential learning is increasingly important in public health education. Purpose: Based on 33 studies, this is the first scoping review that provides clarity on the types of experiential learning activities (ELAs) used in public health education and the evaluation results from the perspectives of three stakeholders involved: students, faculty, and communities/external agencies. Methodology/Approach: A total of 1,912 citations were sourced from six electronic databases (Education Resources Information Centre, ProQuest Central, PubMed, Scopus, STM Source, and Web of Science) and manual searches (reference lists of included studies) independently by two researchers. A random-effects meta-analysis using forest plots and a meta-synthesis using a thematic synthesis approach were conducted. Findings/Conclusions: There was a diverse range of community-, classroom-, and work-focused ELAs used. Meta-analysis revealed positive outcomes in student satisfaction, problem-solving, and communication skills. This was triangulated with the meta-synthesis results, which also indicated an overwhelmingly positive attitude toward experiential learning by all three stakeholders. Implications: Future educational programs should consider the factors that contributed to the positive experiences from all three stakeholders' perspectives, address the various challenges highlighted in this review to refine the experience, and assess the negative experiences of faculty, and community/external agencies in greater detail. [ABSTRACT FROM AUTHOR]

To evaluate the response and quality of life of palliative gastric radiotherapy in patients with symptomatic locally advanced gastric cancer. Patients with bleeding, pain or obstruction and were treated with palliative gastric radiotherapy to a dose of 36 Gy in 12 daily fractions. The primary outcomes were symptom response rates. Secondary outcomes included overall survival, adverse events and proportion of patients with ≥10‐point absolute improvement in the fatigue, nausea/vomiting and pain subscales in the EORTC Qualify of Life Questionnaire C30 (EORTC QLQ‐C30) and dysphagia/pain subscales in the gastric specific module (STO22) at the end of RT and 1 month after the completion of radiotherapy. Fifty patients were accrued. Median survival duration was 85 days. 40/50 patients (80%) with bleeding, 2/2 (100%) patients with obstruction and 1/1 (100%) patient with pain responded to radiotherapy. Improvements fatigue, nausea/vomiting and pain subscales of the EORTC QLQ‐C30 was seen in 50%, 28% and 44% of patients at the end of RT and in 63%, 31% and 50% of patients 1 month after RT. Improvements in dysphagia/pain subscales of the STO22 was seen in 42% and 28% of patients at then end of RT and 44% and 19% of patients 1 month after RT. Two patients (5%) had grade 3 anorexia and gastritis. Palliative gastric radiotherapy was effective, well tolerated and resulted in improvement in fatigue, dysphagia and pain at the end of radiotherapy and 1 month after the completion of radiotherapy in a significant proportion of patients. [ABSTRACT FROM AUTHOR]

Background: The survival benefit of PCI in ES-SCLC reported by a European randomized trial (RCT) in 2007 was not replicated by a Japanese RCT published in 2017. This study aimed to evaluate the uptake of PCI before and after publication of the European RCT and its association with survival in ES-SCLC.Methods: We identified eligible patients in the only two Singapore national cancer centres from 2003 to 2010. We linked their electronic medical records to the national death registry. We described the utilization of PCI in patients diagnosed from 2003 to 2006 (pre-adoption cohort) with patients diagnosed from 2007 to 2010 (post-adoption cohort). We performed univariable and multivariable Cox regression analysis to assess the association between PCI and survival.Results: We identified 224 patients with ES-SCLC with no brain metastases. Among the 71 patients who had at least stable disease after first line chemotherapy, there was an increase in the use of PCI from the period 2007 to 2010 compared with 2003 to 2006 (32% versus 10%, P = 0.044). PCI was associated with improved OS (hazard ratio 0.22, 95% CI 0.10 to 0.47, P < 0.001) compared to no PCI in the multivariable analysis.Conclusion: There was an increase in the adoption of PCI for ES-SCLC since 2007. PCI was associated with improved survival in patients who did not have mandatory MRI brain imaging prior to PCI and had stable disease or better after first line chemotherapy, suggesting that the results of the European RCT are reproducible in the real-world practice. [ABSTRACT FROM AUTHOR]

Objectives The aim of this retrospective observational study is to assess the association between various radiation heart dosimetric parameters (RHDPs) and acute myocardial infarct (AMI) and overall survival (OS) outcomes in stage III non-small cell lung cancer (NSCLC) treated with definitive radiotherapy with or without chemotherapy. Materials and methods We identified eligible patients treated at two institutions from 2007 to 2014. We linked their electronic medical records to the national AMI and death registries. We performed univariable and multivariable Cox regressions analysis to assess the association between various RHDPs, AMI and OS. Results 120 eligible patients were included with a median follow-up of 17.6 months. Median age was 65.5 years. Median prescription dose was 60 Gy. Median mean heart dose (MHD) was 12.6 Gy. Univariable analysis showed that higher MHD (hazard ratio (HR), 1.03; 95% confidence interval (CI), 1.01–1.06; P = .008) and volume of heart receiving at least 5 Gy (V5) (HR, 1.01; 95% CI, 1.00–1.03; P = .042) were associated with increased hazards for AMI. Univariable analysis showed that higher MHD, V5, V25, V30, V40, V50 and dose to 30% of heart volume were associated with increased hazards for death. Multivariable analysis showed that there was no statistically significant association between various RHDPs and OS. Conclusion The incidence of AMI is low among stage III NSCLC treated with definitive radiotherapy with or without chemotherapy. There is insufficient evidence to conclude that RHDPs are associated with AMI or OS in our study. [ABSTRACT FROM AUTHOR]

Aims The aim of the current study was to create a typology of patients with first-episode psychosis based on sociodemographic and clinical characteristics, service use and outcomes using cluster analysis. Methods Data from all respondents who were accepted into the Early Psychosis Intervention Programme ( EPIP), Singapore from 2007 to 2011 were analysed. A two-step clustering method was carried out to classify the patients into distinct clusters. Results Two clusters were identified. Cluster 1 comprised largely of younger people with mean age of 25.5 (6.0) years at treatment contact, who were predominantly male (55.3%), single (98.3%) and living with parents (86.3%). Cluster 1 had a higher proportion of people diagnosed with the schizophrenia spectrum disorder (71.4%) and with a positive family history of psychiatric illness. Patients in cluster 2 were generally older with a mean age of 33.6 (4.7) years and the majority were women (74.2%). Cluster 1 had people with higher Positive and Negative Syndrome Scale ( PANSS) scores at baseline as compared with cluster 2. After a 1-year follow up, their scores were still poorer than their counterparts in cluster 2, especially for PANSS negative score. The functioning level of people in cluster 1 showed less improvement than the people in cluster 2 after a year of treatment. Conclusions There is a compelling need to develop new therapies and intensively treat young people presenting with psychosis as this group tends to have poorer outcomes even after 1 year of treatment. [ABSTRACT FROM AUTHOR]

A compact dual-coupled shorting probe (DCSP)-loaded patch antenna for dual-band global positioning system (GPS) application is presented. Due to the use of shorting loaded technique, the overall size of the antenna is only $\frac{{\lambda_0}} {8}\cdot 8 \times \frac{{\lambda_0}} {8}\cdot 8 \times \frac{{\lambda_0}} {19}$, and high-permittivity substrate is replaced by low-cost F4b substrate. The DCSP technique that this communication proposed enables this antenna to resonate at L1/L2 GPS bands. Simulated and measured voltage standing-wave ratio (VSWR) is below 1.5 over both the bands, and boresight RHCP gain is 4.49 and 4.12 dBic over a large ground plane with 41 and 57 MHz 3-dB gain bandwidth at the L2 and L1 band, respectively. Therefore, the proposed antenna is a good candidate for low-cost, dual-band, and compact patch antenna. [ABSTRACT FROM AUTHOR]

In this paper, a novel design of wideband compact patch antenna is proposed for the handheld application of global navigation satellite system (GNSS). In order to meet the size requirement of the handheld application, the shorting load is employed as the miniaturization technique and the overall size of the proposed antenna is only 70 mm (length) × 70 mm (width) × 25 mm (height). Due to the narrow bandwidth of the shorting loaded patch antenna, shorting probe with enlarged width, as well as the air substrate, is adopted to enhance the bandwidth of the proposed antenna and make it fulfil the GNSS bandwidth requirement. Simulation and measured results show that the proposed antenna has a bandwidth of 41.5% for VSWR < 1.5 from 1.05 to 1.6 GHz and 35.7% 3-dB axial ratio bandwidth from 1.15 to 1.65 GHz. [ABSTRACT FROM PUBLISHER]

Abstract: In our effort to identify testis-specific genes we found Fank1, which encodes a protein containing a fibronectin type III domain in the amino terminus and five ankyrin repeats in its carboxyl terminus. FANK1 displays a high degree of sequence conservation in 11 vertebrate species during evolution. Bioinformatic and experimental analyses revealed that Fank1 was exclusively expressed in the testis in both mice and humans. Fank1 mRNA was expressed in mid to late pachytene spermatocytes as well as spermatids in steps 1–14. FANK1 protein was localized in the nuclei of the same cells within the seminiferous epithelium. Consistent with its nuclear localization, a gene ontology analysis suggests that FANK1 has a DNA binding activity and thus may function as a transcription factor. Given the highly restricted expression of FANK1, it may have a role in regulating gene expression in the transition from the meiotic phase to the haploid phase during spermatogenesis. [Copyright &y& Elsevier]

To investigate the differential short-term effects of selective estrogen receptor (ER) modulators (SERMs) on uterus, we treated adult ovariectomized rats with a novel SERM, ospemifene (Osp), two previously established SERMs (tamoxifen and raloxifene (Ral)) and estradiol. The expression of two estrogen-regulated early response genes c-fos and vascular endothelial growth factor (VEGF), and DNA synthesis were analysed at 1–24 h after treatment of ovariectomized rats. Induction of c-fos mRNA by each of the SERMs showed a biphasic pattern with peaks at 3 and 20 h, respectively. The maximum level of VEGF mRNA was observed at 1 h after raloxifene and 6 h after tamoxifen or ospemifene treatment. Maximum levels of the c-fos and VEGF mRNA after raloxifene treatment were higher than those seen after treatments with E2 or a corresponding dose of tamoxifen or ospemifene. DNA synthesis was significantly increased by ospemifene, tamoxifen and raloxifene both in luminal and glandular epithelium. The stimulation was transient, peaking at 16 h. In comparison, the maximum level observed at 16 h after E2 treatment sustained at least until 24 h. DNA synthesis in stromal cells was increased by the SERMs but not by E2 at 24 h. When treated together with E2, the SERMs were able to antagonise E2-stimulated DNA synthesis at 16 h. Our results demonstrate that the initial response of uterus to ospemifene, raloxifene and tamoxifen includes activation of early response genes and even transient stimulation of DNA synthesis in spite of their different long-term effects. However, the early stimulatory events may be mediated by different mechanisms leading to diverging pathways in various tissue compartments and development of differential SERM-specific long-term responses of uterus. [Copyright &y& Elsevier]

Background: Air quality is an important determinant of cardiovascular health such as ischemic heart disease and acute ischemic stroke (AIS) with substantial mortality and morbidity reported across the globe. However, associations between air quality and AIS in the current literature remain inconsistent, with few studies undertaken in cosmopolitan cities located in the tropics. Objectives: We evaluated the associations between individual ambient air pollutants and AIS. Methods: We performed a nationwide, population-based, time-stratified case-crossover analysis on all AIS cases reported to the Singapore Stroke Registry from 2009 to 2018. We estimated the incidence rate ratio (IRR) of AIS across different concentrations of each pollutant by quartiles (referencing the 25th percentile), in single-pollutant conditional Poisson models adjusted for time-varying meteorological effects. We stratified our analysis by predetermined subgroups deemed at higher risk. Results: A total of 51,675 episodes of AIS were included. Ozone (O3) (IRR4th quartile: 1.05, 95% confidence interval (CI): 1.01–1.08) and carbon monoxide (CO) (IRR2nd quartile: 1.05, 95% CI: 1.02–1.08, IRR3rd quartile: 1.07, 95% CI: 1.04–1.10, IRR4th quartile: 1.07, 95% CI: 1.04–1.11) were positively associated with AIS incidence. The increased incidence of AIS due to O3 and CO persisted for 5 days after exposure. Those under 65 years of age were more likely to experience AIS when exposed to CO. Individuals with atrial fibrillation (AF) were more susceptible to exposure from O3, CO, and PM10. Current/ex-smokers were more vulnerable to the effect of O3. Conclusion: Air pollution increases the incidence of AIS, especially in those with AF and in those who are current or ex-smokers. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease is an established risk factor for heart failure. However, the impact of incident heart failure on the subsequent risk of renal failure has not been systematically assessed in diabetic population. We sought to study the risk of progression to end stage kidney disease (ESKD) after incident heart failure in Asian patients with type 2 diabetes. Methods: In this prospective cohort study, 1985 outpatients with type 2 diabetes from a regional hospital and a primary care facility in Singapore were followed for a median of 8.6 (interquartile range 6.2–9.6) years. ESKD was defined as a composite of progression to sustained eGFR below 15 ml/min/1.73m2, maintenance dialysis or renal death, whichever occurred first. Results: 180 incident heart failure events and 181 incident ESKD events were identified during follow-up. Of 181 ESKD events, 38 (21%) occurred after incident heart failure. Compared to those did not progress to ESKD after incident heart failure (n = 142), participants who progressed to ESKD after heart failure occurrence were younger, had higher HbA1c and higher urine albumin-to-creatinine ratio at baseline. The excess risk of ESKD manifested immediately after heart failure occurrence, persisted for two years and was moderated thereafter. Cox regression suggested that, compared to counterparts with no heart failure event, participants with heart failure occurrence had 9.6 (95% CI 5.0- 18.3) fold increased risk for incident ESKD after adjustment for baseline cardio-renal risk factors including eGFR and albuminuria. It appeared that heart failure with preserved ejection fraction had a higher risk for ESKD as compared to those with reduced ejection fraction (adjusted HR 13.7 [6.3–29.5] versus 6.5 [2.3–18.6]). Conclusion: Incident heart failure impinges a high risk for progression to ESKD in individuals with type 2 diabetes. Our data highlight the need for intensive surveillance of kidney function after incident heart failure, especially within the first two years after heart failure diagnosis. [ABSTRACT FROM AUTHOR]

• MoS 2 @GA-Fe enhanced the Fe(III)-based Fenton reaction in the tumor microenvironment. • The degradation of MoS 2 had a "snowball effect" for the Fenton reaction. • Hydrogen sulfide was also produced for cancer treatment. • The MoS 2 @GA-Fe nanoreactor showed excellent antitumor efficiency and biosafety. We report the preparation of gallic acid (GA)-modified MoS 2 nanosheets (MoS 2 @GA) with high Fe(III) loading. The MoS 2 @GA-Fe can function as a "Fenton Nanoreactor" in the tumor microenvironment (TME), in which GA-Fe(III) can be reduced to GA-Fe(II) by glutathione (GSH) and amounts of reactive hydroxyl radicals (•OH) are generated during the Fenton reaction. Notably, the MoS 2 degrades into small fragments during the process, and more Mo(IV) reaction sites are exposed on the surface, resulting in a "snowball effect" and enhanced •OH production. Furthermore, unsaturated S atoms can capture protons in the TME and form hydrogen sulfide (H 2 S). We combined the photoacoustic imaging and magnetic resonance imaging contrast properties of MoS 2 @GA-Fe and constructed an imaging-guided chemodynamic treatment, featuring excellent antitumor efficiency and biosafety. The TME-responsive "Fenton Nanoreactor" provides a promising strategy with enhanced translational potency for tumor therapy. [ABSTRACT FROM AUTHOR]

Aims: This review assessed the efficacy of self-care interventions to improve biophysical, psychosocial or behavioural outcomes among older adults with diabetes.Methods: Computerised and manual searches were performed. A total of 18 randomised control trials were included in the review, of which eight were subsequently included in the meta-analysis.Results: Most studies were from the United States of America and adopted a collaborative approach with participants. The specific needs of older adults were often not considered, and there was a predominance of biophysical measures. Meta-analysis revealed that among intervention condition participants, there were improvements in HbA1c (pooled weighted mean difference (WMD) -0.33, 95%CI -0.48 to -0.17), systolic blood pressure (WMD -1.55, 95%CI -2.93 to -0.18), diastolic blood pressure (WMD -1.41 95%CI -2.08 to -0.20), triglyceride (WMD -13.25, 95%CI -23.31 to -3.20), high-density lipoprotein (WMD 2.05, 95%CI 1.04 to 3.06) and Diabetes Self-Care Activities score (mean 4.10, 95%CI 3.11 to 5.10) compared to the control group. There was no significant change for low-density lipoprotein (WMD -5.93, 95%CI -12.08 to 0.22).Conclusions: While continuing to adopt a collaborative approach, future self-care interventions should incorporate psychosocial and behavioural outcomes, consider the specific needs of older adults, and focus on more ethnically diverse populations. [ABSTRACT FROM AUTHOR]

Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70–0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55–0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66–0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68–0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57–0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40–0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48–0.86). This were consistent for left ventricular ejection fraction < 50% or ≥ 50%. In conclusion, in AMI managed with revascularization, both BB and ACEI/ARB were associated with a lower incidence of 12-month all-cause mortality. Combined BB and ACEI/ARB was associated with the lowest incidence of all-cause mortality and HF hospitalization. [ABSTRACT FROM AUTHOR]

Ambient air pollution is a risk factor for both acute and chronic diseases and poses serious health threats to the world population. We aim to study the relationship between air pollution and all-cause mortality in the context of a city-state exposed to the Southeast Asian haze problem. The primary exposure was ambient air pollution, as measured by the Pollutants Standards Index (PSI). The outcome of interest was all-cause mortality from 2010–2015. A time-stratified case-crossover design was performed. A conditional Poisson regression model, including environmental variables such as PSI, temperature, wind speed, and rainfall, was fitted to the daily count of deaths to estimate the incidence rate ratio (IRR) of mortality per unit increase in PSI, accounting for overdispersion and autocorrelation. To account for intermediate exposure effects (maximum lag of 10 days), a distributed lag non-linear model was used. There were 105,504 deaths during the study period. Increment in PSI was significantly associated with an increased risk of mortality. The adjusted IRR of mortality per the 10-unit increase in PSI was 1.01 (95%CI = 1.00–1.01). The lag effect was stronger when PSI was in the unhealthy range compared to the good and moderate ranges. At lag = 7 days, PSI appeared to have an adverse effect on mortality, although the effect was not significant. These findings provide evidence on the general health hazard of exposure to air pollution and can potentially guide public health policies in the region. [ABSTRACT FROM AUTHOR]

Background: Autophagy is a conserved catabolic process, which plays an important role in regulating tumor cell motility and degrading protein aggregates. Chemotherapy-induced autophagy may lead to tumor distant metastasis and even chemo-insensitivity in the therapy of hepatocellular carcinoma (HCC). Therefore, a vast majority of HCC cases do not produce a significant response to monotherapy with autophagy inhibitors. Results: In this work, we developed a biomimetic nanoformulation (TH-NP) co-encapsulating Oxaliplatin (OXA)/hydroxychloroquine (HCQ, an autophagy inhibitor) to execute targeted autophagy inhibition, reduce tumor cell migration and invasion in vitro and attenuate metastasis in vivo. The tumor cell-specific ligand TRAIL was bioengineered to be stably expressed on HUVECs and the resultant membrane vesicles were wrapped on OXA/HCQ-loaded PLGA nanocores. Especially, TH-NPs could significantly improve OXA and HCQ effective concentration by approximately 21 and 13 times in tumor tissues compared to the free mixture of HCQ/OXA. Moreover, the tumor-targeting TH-NPs released HCQ alkalized the acidic lysosomes and inhibited the fusion of autophagosomes and lysosomes, leading to effective blockade of autophagic flux. In short, the system largely improved chemotherapeutic performance of OXA on subcutaneous and orthotopic HCC mice models. Importantly, TH-NPs also exhibited the most effective inhibition of tumor metastasis in orthotopic HCCLM3 models, and in the HepG2, Huh-7 or HCCLM3 metastatic mice models. Finally, we illustrated the enhanced metastasis inhibition was attributed to the blockade or reverse of the autophagy-mediated degradation of focal adhesions (FAs) including E-cadherin and paxillin. Conclusions: TH-NPs can perform an enhanced chemotherapy and antimetastatic effect, and may represent a promising strategy for HCC therapy in clinics. [ABSTRACT FROM AUTHOR]

Background: Angiogenin, an enzyme belonging to the ribonucleases A superfamily, plays an important role in vascular biology. Here, we sought to study the association of plasma angiogenin and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes (T2D). Methods: This prospective study included 1083 T2D individuals recruited from a secondary hospital and a primary care facility. The primary outcome was a composite of four-point MACE (nonfatal myocardial infarction, stroke, unstable angina pectoris leading to hospitalization and cardiovascular death). Circulating angiogenin was measured by a proximity extension assay. Cox regression models were used to evaluate the association of baseline plasma angiogenin with the risk of MACE. Results: During a median follow-up of 9.3 years, 109 (10%) MACE were identified. Plasma angiogenin was significantly higher in participants with MACE than in those without MACE (P < 0.001). Doubling of plasma angiogenin concentration was associated with a 3.10-fold (95% CI 1.84–5.22) increased risk for MACE. The association was only moderately attenuated after adjustment for demographic and cardiometabolic risk factors (adjusted HR 2.38, 95% CI 1.34–4.23) and remained statistically significant after additional adjustment for estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (uACR) (adjusted HR 1.90, 95% CI 1.02–3.53). A consistent outcome was obtained when plasma angiogenin was analysed as a categorical variable in tertiles. Conclusions: Plasma angiogenin was associated with the risk of future cardiovascular events in patients with T2D and may be a promising novel biomarker for identifying high-risk T2D patients for early management. [ABSTRACT FROM AUTHOR]

Background: Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). In addition to glucose, other glucose-related indices, such as HbA1c, glucose-HbA1c ratio (GHR), and stress-hyperglycaemia ratio (SHR) are potential predictors of clinical outcomes following AMI. However, the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting 1-year all cause mortality in diabetic and non-diabetic ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients. Methods: We undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values using the Youden's formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-off values in the diabetic and non-diabetic subgroups, stratified by the type of AMI. Results: There were 5841 STEMI and 4105 NSTEMI in the study. In STEMI patients, glucose, GHR, and SHR were independent predictors of 1-year all-cause mortality [glucose: OR 2.19 (95% CI 1.74–2.76); GHR: OR 2.28 (95% CI 1.80–2.89); SHR: OR 2.20 (95% CI 1.73–2.79)]. However, in NSTEMI patients, glucose and HbA1c were independently associated with 1-year all-cause mortality [glucose: OR 1.38 (95% CI 1.01–1.90); HbA1c: OR 2.11 (95% CI 1.15–3.88)]. In diabetic STEMI patients, SHR performed the best in terms of area-under-the-curve (AUC) analysis (glucose: AUC 63.3%, 95% CI 59.5–67.2; GHR 68.8% 95% CI 64.8–72.8; SHR: AUC 69.3%, 95% CI 65.4–73.2). However, in non-diabetic STEMI patients, glucose, GHR, and SHR performed equally well (glucose: AUC 72.0%, 95% CI 67.7–76.3; GHR 71.9% 95% CI 67.7–76.2; SHR: AUC 71.7%, 95% CI 67.4–76.0). In NSTEMI patients, glucose performed better than HbA1c for both diabetic and non-diabetic patients in AUC analysis (For diabetic, glucose: AUC 52.8%, 95% CI 48.1–57.6; HbA1c: AUC 42.5%, 95% CI 37.6–47. For non-diabetic, glucose: AUC 62.0%, 95% CI 54.1–70.0; HbA1c: AUC 51.1%, 95% CI 43.3–58.9). The optimal cut-off values for glucose, GHR, and SHR in STEMI patients were 15.0 mmol/L, 2.11, and 1.68 for diabetic and 10.6 mmol/L, 1.72, and 1.51 for non-diabetic patients respectively. For NSTEMI patients, the optimal glucose values were 10.7 mmol/L for diabetic and 8.1 mmol/L for non-diabetic patients. Conclusions: SHR was the most consistent independent predictor of 1-year all-cause mortality in both diabetic and non-diabetic STEMI, whereas glucose was the best predictor in NSTEMI patients. [ABSTRACT FROM AUTHOR]

The antibacterial and antioxidant packaging films were fabricated by incorporating licorice residue extracts (LREs) into oxidized starch (OS) films. The bioactive fraction (BF) was firstly obtained from LREs by using bioassay-guided isolation method. The BF showed potent anti-Gram(+) bacteria effects, especially against methicillin-resistant S. aureus (MRSA) with MIC of 32.5 μg/mL. The present results also indicated that the addition of BF could significantly decrease the moisture content, water vapor permeability, light transmittance of OS films. Notably, the antibacterial and antioxidant activities of OS films significantly enhanced with the concentration of BF increasing. Moreover, the films with the highest concentration of BF showed the lowest tensile strength (4.23 MPa) and the highest elongation at break (63.89%). Meanwhile, the bioactive films could release bioactive compounds such as licochalcone A and licochalcone B into the alcoholic and fatty food simulants. Taken together, the active OS films containing LREs have the potential for application in food packaging films, due to its potential against MRSA and antioxidant activity as well as good physicochemical properties. • The oxidized starch films containing licorice residue extracts (LERs) were for the first time synthesized and characterized. • The films' properties were improved by the addition of bioactive fraction from LERs. • The synthesized films have potent antioxidant activity and potential against methicillin-resistant S. aureus. [ABSTRACT FROM AUTHOR]

We aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention. [ABSTRACT FROM AUTHOR]

Introduction: There are few data investigating the impact of angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) and beta-blocker use on long-term heart failure (HF) outcomes in AMI. Methods: State legislature mandates that all patients hospitalized for AMI enter the Singapore MI Registry. Heart failure rehospitalization is ascertained through linkage with the national Death and Mediclaims Registries. In multivariable analysis accounting for age, sex, race, prior diabetes, prior hypertension, prior hyperlipidemia, prior MI/PCI/CABG, smoking status, troponin level, renal function, Killip class and left ventricular ejection fraction (LVEF), we investigated the association between discharge use of ACEI/ARB and beta-blockers with one-year HF rehospitalization episodes. Mortality was modelled as a competing risk. Results: From 2007-2013, there were 22,641 non-STEMI and 12,551 STEMI cases in Singapore (population ~5.5 million). High rates of pre-discharge revascularization were observed in both non-STEMI and STEMI patients, exceeding 50% and 70% respectively (Table). Discharge ACEI/ARB exceeded 65% and 70% respectively for non-STEMI and STEMI while discharge beta-blocker use exceeded 80% for both groups. The adjusted hazard ratio for one-year HF rehospitalization was 0.90 (95% confidence interval 0.82-0.99, P=0.030) for ACEI/ARB and 1.01 (95% confidence interval 0.90-1.14, P=0.840) for beta-blockers. Conclusion: In a contemporary AMI population managed aggressively with inhospital revascularization, discharge use of ACEI/ARB was associated with a reduction in one-year HF rehospitalization while discharge beta-blocker use was not. [ABSTRACT FROM AUTHOR]

Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed the "smoker's paradox." Given the known detrimental effects of smoking on the cardiovascular system, it has been proposed that the beneficial effect of smoking on outcomes is due to age differences between smokers and non-smokers and is therefore a smoker's pseudoparadox. The aim of this study was to evaluate the association between smoking status and clinical outcomes in ST-segment elevation (STEMI) and non-STEMI (NSTEMI) patients treated by percutaneous coronary intervention (PCI), using a national multi-ethnic Asian registry. In unadjusted analyses, current smokers had better clinical outcomes following STEMI and NSTEMI. However, after adjusting for age, the protective effect of smoking was lost, confirming a smoker's pseudoparadox. Interestingly, although current smokers had increased risk for recurrent MI within 1 year after PCI in both STEMI and NSTEMI patients, there was no increase in mortality. In summary, we confirm the existence of a smoker's pseudoparadox in a multi-ethnic Asian cohort of STEMI and NSTEMI patients and report increased risk of recurrent MI, but not mortality, in smokers. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to study the associations between plasma metabolites in the tryptophan-kynurenine pathway and the risk of progression to end-stage kidney disease (ESKD) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Plasma tryptophan, kynurenine, 3-hydroxykynurenine, kynurenic acid, and xanthurenic acid concentrations were measured in discovery (n = 1,915) and replication (n = 346) cohorts. External validation was performed in Chronic Renal Insufficiency Cohort (CRIC) participants with diabetes (n = 1,312). The primary outcome was a composite of incident ESKD (progression to estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2, sustained dialysis, or renal death). The secondary outcome was annual eGFR decline. RESULTS: In the discovery cohort, tryptophan was inversely associated with risk for ESKD, and kynurenine-to-tryptophan ratio (KTR) was positively associated with risk for ESKD after adjustment for clinical risk factors, including baseline eGFR and albuminuria (adjusted hazard ratios [HRs] 0.62 [95% CI 0.51, 0.75] and 1.48 [1.20, 1.84] per 1 SD). High levels of kynurenic acid and xanthurenic acid were associated with low risks of ESKD (0.74 [0.60, 0.91] and 0.74 [0.60, 0.91]). Consistently, high levels of tryptophan, kynurenic acid, and xanthurenic acid were independently associated with a slower eGFR decline, while a high KTR was predictive of a faster eGFR decline. Similar outcomes were obtained in the replication cohort. Furthermore, the inverse association between kynurenic acid and risk of ESKD was externally validated in CRIC participants with diabetes (adjusted HR 0.78 [0.65, 0.93]). CONCLUSIONS: Accelerated catabolism of tryptophan in the kynurenine pathway may be involved in progressive loss of kidney function. However, shunting the kynurenine pathway toward the kynurenic acid branch may potentially slow renal progression. [ABSTRACT FROM AUTHOR]

As is well known, the global navigation satellite system (GNSS) antenna always suffers from the size problem. The authors' propose that two shorting probes in parallel are loaded on a patch antenna and a dual‐band compact GNSS antenna, which has a smaller electrical size of only 60 mm (0.23λ) × 60 mm ×18 mm (0.07λ) × (λ being the wavelength in free space). A dual‐layer feed network is also designed to achieve circular polarised radiation. Simulated and measured results show that the proposed antenna has good and stable performance over both dual operating bands. [ABSTRACT FROM AUTHOR]

This systematic review aims to evaluate the effectiveness of systems-based practice (SBP) curricula from the perspective of health professions students and workers. A total of 8468 citations were sourced from six electronic databases and manual searches conducted independently by two researchers, of which 44 studies were eventually included. A meta-analysis using a random effects model and a meta-synthesis using the thematic synthesis approach were conducted. Most studies targeted medical students, residents, and resident physicians from various clinical specialties. Almost half of all studies focused on didactic or knowledge-based interventions to teach SBP. About a third of all studies measured non-self-evaluated knowledge change, clinical abilities, and clinical outcomes. Both meta-analysis and meta-synthesis results revealed positive outcomes of increased knowledge of SBP, increased recognition of SBP as a core competency in one's profession, and increased application of SBP knowledge in one's profession. Meta-synthesis results also revealed negative outcomes at the institutional and teacher/health professions level. This review highlights the importance of SBP education and supports the effectiveness of SBP curricula. There is a need to address the negative outcomes at the institutional and teacher/health professions level. Moreover, future studies could investigate the integration of self-assessment outcomes with comparison to some external standard. [ABSTRACT FROM AUTHOR]

A small portion of cytoplasm is generally retained as the cytoplasmic droplet (CD) on the flagellum of spermatozoa after spermiation in mice. CDs are believed to play a role in osmoadaptation by allowing water entrance or exit. However, many lines of evidence suggest that CDs may have roles beyond osmoregulation. To gain more insights, we purified CDs from murine epididymal spermatozoa and conducted proteomic analyses on proteins highly enriched in CDs. Among 105 proteins identified, 71 (68%) were enzymes involved in energy metabolism. We also found that sperm mitochondria underwent a reactivation process and glycolytic enzymes were further distributed and incorporated into different regions of the flagellum during epididymal sperm maturation. Both processes appeared to require CDs. Our data suggest that the CD represents a transient organelle that serves as an energy source essential for epididymal sperm maturation. [ABSTRACT FROM AUTHOR]

99 patients with symptomatic locally advanced rectal cancer who were treated with palliative radiation alone were reviewed. Dose-fractionation ranged from 18 to 54 Gy. Response rate ranged from 62.5 to 86.7%, with a median response duration ranging 4.2–5.4 months. Median survival was 6.9 months. Using a BED cut-off of 39Gy 10, no dose–response relationship was found. [ABSTRACT FROM AUTHOR]

Aim: To provide a comprehensive evaluation of the quality of the data at the Singapore Cancer Registry (SCR).Methods: Quantitative and semi-quantitative methods were used to assess the comparability, completeness, accuracy and timeliness of data for the period of 1968-2013, with focus on the period 2008-2012.Results: The SCR coding and classification systems follow international standards. The overall completeness was estimated at 98.1% using the flow method and 97.5% using the capture-recapture method, for the period of 2008-2012. For the same period, 91.9% of the cases were morphologically verified (site-specific range: 40.4-100%) with 1.1% DCO cases. The under-reporting in 2011 and 2012 due to timely publication was estimated at 0.03% and 0.51% respectively.Conclusion: This review shows that the processes in place at the SCR yields data which are internationally comparable, relatively complete, valid, and timely, allowing for greater confidence in the use of quality data in the areas of cancer prevention, treatment and control. [ABSTRACT FROM AUTHOR]

Acute ischemic strokes (AIS) are closely linked with air pollution, and there is some evidence that traditional cardiovascular risk factors may alter the relationship between air pollution and strokes. We investigated the effect of atrial fibrillation (AF) on the association of AIS with air pollutants. This was a nationwide, population-based, case-only study that included all AIS treated in public healthcare institutions in Singapore from 2009 to 2018. Using multivariable logistic regression, adjusted for time-varying meteorological effects, we examined how AF modified the association between AIS and air pollutant exposure. A total of 51,673 episodes of AIS were included, with 10,722 (20.7%) having AF. The odds of AIS in patients with AF is higher than those without AF for every 1 µg/m3 increase in O3 concentration (adjusted OR [aOR]: 1.005, 95% CI 1.003–1.007) and every 1 mg/m3 increase in CO concentration (aOR: 1.193, 95% CI 1.050–1.356). However, the odds of AIS in patients with AF is lower than those without AF for every 1 µg/m3 increase in SO2 concentration (aOR: 0.993, 95% CI 0.990–0.997). Higher odds of AIS among AF patients as O3− and CO concentrations increase are also observed in patients aged ≥65 years and non-smokers. The results suggest that AF plays an important role in exacerbating the risk of AIS as the levels of O3 and CO increase. [ABSTRACT FROM AUTHOR]

• Chemically-engineered Spirulina as a multifunctional swimming microrobot. • Biogenic intracellular deposition of gold nanoparticles. • Gold-enhanced imaging and photothermal efficacy. • Digital subtraction angiography enabled real-time yet deep tracking. Helical micro-/nanoswimmers have been extensively explored as a miniaturized robotic tool for advanced biomedicine in the past two decades. However, the integration of biomedical functions on the existing swimmers remains insufficient to allow further in vivo developments. We propose a chemically engineered Spirulina microalgae with biogenic gold nanoparticles deposited in its cells and magnetite nanoparticles assembled on its surface. This biohybrid helical microswimmer is naturally of many desired functions and can be easily functionalized through surface modification and/or intracellular loading. The gold-enabled digital subtraction angiography of multimodal imaging function is highlighted herein. Such imaging modality makes real-time tracking possible in deep anatomical regions, guaranteeing precise in vivo navigation of our swimmers to specific lesions. Meanwhile, the gold-enhanced photothermal efficacy is also noteworthy. It regulates swimmer degradation via controlling photothermal heat and can be harnessed to implement targeted therapy, for which the targeting process and therapeutic effect are successfully demonstrated in a fluidic chip. Furthermore, the fabrication method is straightforward and cost-effective, suitable for mass production. All these results clarify the functionalization strategy enabled by biogenic intracellular deposition and provide a multifunctional biohybrid microswimmer. [ABSTRACT FROM AUTHOR]

Background: Haemorrhagic stroke (HS) is a major cause of mortality and disability. Previous studies reported inconsistent associations between ambient air pollutants and HS risk.Objective: We evaluated the association between air pollutant exposure and the risk of HS in a cosmopolitan city in the tropics.Methods: We performed a nationwide, population-based, time-stratified case-crossover analysis on all HS cases reported to the Singapore Stroke Registry from 2009 to 2018 (n = 12,636). We estimated the risk of HS across tertiles of air pollutant concentrations in conditional Poisson models, adjusting for meteorological confounders. We stratified our analysis by age, atrial fibrillation and smoking status, and investigated the lagged effects of each pollutant on the risk of HS up to 5 days.Results: All 12,636 episodes of HS were included. The median (1st-to 3rd-quartile) daily pollutant levels from 22 remote stations deployed across the island were as follows: (PM2.5 = 15.9 (12.7-20.5), PM10 = 27.3 (22.7-33.4), O3 = 22.5 (17.3-29.8), NO2 = 23.3 (18.8-28.4), SO2 = 10.2 (5.6-14.4), CO = 0.5 (0.5-0.6). The median (1st-to 3rd-quartile) temperature (°C) was 27.9 (27.1-28.7), that of relative humidity (%) was 79.4 (75.6-83.2), and that of total rainfall (mm) was 0.0 (0.0-4.2). Higher levels of CO were significantly associated with an increased risk of HS (3rd tertile vs 1st tertile: Incidence Rate Ratio (IRR) = 1.06, 95% CI = 1.01-1.12). The increased risk of HS due to CO persisted for at least 5 days after exposure. Individuals under 65 years old and non-smokers had a higher risk of HS when exposed to CO. O3 was associated with increased risk of HS up to 5 days (3rd tertile vs 1st tertile: IRRday 1 = 1.07, 95% CI = 1.02-1.12; IRRday 5 = 1.07, 95% CI = 1.02-1.13).Conclusion: Short-term exposure to ambient CO levels was associated with an increased risk of HS. A reduction in CO emissions may reduce the burden of HS in the population. [ABSTRACT FROM AUTHOR]

Abstract: Spermiogenesis represents the process through which haploid male germ cells differentiate from round spermatids into elongated spermatids and eventually the male gametes called spermatozoa. Haploid cell differentiation is unique to male germ cell development and many unique genes/proteins essential for this process have been discovered. SPEM1 is one of these spermiogenesis-essential proteins encoded by a testis-specific gene exclusively expressed in the developing spermatids. Inactivation of Spem1 in mice results in deformed spermatozoa characterized by “head-bent-back” abnormalities with 100% penetrance. Using yeast two-hybrid screening assays, we identified UBQLN1 as one of the SPEM1-interacting partners. UBQLN1 and SPEM1 were colocalized to the manchette of elongating spermatids. Since UBQLN1 functions through binding and directing poly-ubiquitinated proteins to the proteasome for degradation, interactions between UBQLN1 and SPEM1 suggest a role in the regulation of protein ubiquitination during spermiogenesis. [ABSTRACT FROM AUTHOR]

Study Question: Are there differences in operant learning and memory between mice born through ICSI and naturally conceived control (CTL) mice?Summary Answer: ICSI females exhibited deficits in the acquisition reward learning relative to CTL females, and ICSI males exhibited deficiencies in discrimination learning and memory relative to CTL males.What Is Known Already: Some human outcome studies have suggested that ICSI might be associated with an increased risk of certain cognitive disorders, but only one of two behavioral studies with ICSI mouse models have reported differences between ICSI and CTL females. No studies to date have investigated associative learning in ICSI mice.Study Design, Size, Duration: Groups of 36 ICSI mice (18 male, 18 female) and 37 CTL mice (19 male, 18 female) aged 3-6 months were compared in a series of operant learning procedures that assessed acquisition of a new behavior, discrimination learning and memory. In total, 16 ICSI mice (9 male, 7 female) and 17 CTL mice (10 male, 7 female) received follow-up discrimination learning and memory assessments at 12 months of age (6 months after the end of initial training) to evaluate retention and reacquisition of learned performances.Participants/materials, Setting, Methods: Mice received daily operant learning sessions in experimental chambers in which all stimulus events and the recording of responses were automated. Food rewards were delivered for responding under different conditions of reinforcement, which varied by procedure. Subjects received a successive series of sessions of nose poke acquisition training, discrimination training and the delayed-non-matching-to-position memory procedure. Mixed repeated measures ANOVAs in which the between-subjects factor was group (ICSI vs CTL) and the within-subjects factor was repeated exposures to learning procedures (i.e. sessions) were used to analyze data.Main Results and the Role Of Chance: In comparisons between all mice (i.e. males and females combined), CTL mice exhibited superior performance relative to ICSI in response acquisition (P = 0.03), discrimination (P = 0.001) and memory (P = 0.007). Sex-specific comparisons between the groups yielded evidence of sexual dimorphism. ICSI females exhibited a deficit in acquisition learning relative to CTL females (P < 0.001), but there was not a significant difference between CTL and ICSI males. In the discrimination and memory tasks, ICSI males exhibited deficits relative to CTL males (P = 0.002 and P = 0.02, respectively) but the differences between females in these tasks were not significant. There was no difference in discrimination or memory retention/re-acquisition assessments conducted with mice at 12 months of age. ICSI males and females weighed significantly more than CTL counterparts at all points during the experiment.Large Scale Data: N/A.Limitations, Reasons For Caution: The study was not blinded. All learning assessments utilized food reward; other assessments of operant, Pavlovian and nonassociative learning are needed to fully characterize learning in ICSI mice and speculate regarding the implications for cognitive function in humans conceived via ICSI.Wider Implications Of the Findings: Studying learning and memory processes in mouse models have the potential to shed light on ICSI outcomes at the level of cognitive function. Future research should use multiple learning paradigms, assess both males and females, and investigate the effects of variables related to the ICSI procedure. Studying cognitive function in ICSI is an interdisciplinary endeavor and requires co-ordination between researchers at the genetic and psychological levels of analysis.Study Funding/competing Interest(s): This work was supported, in part, by grants from the NIH (P30GM110767, HD071736 and HD085506 to W.Y.), the Templeton Foundation (61174 to W.Y.) and a New Scholarly Endeavor Grant from the University of Nevada, Reno Office of Research and Innovation (to M.L., Y.W., H.Z., L.H. and W.Y.). The authors declare no competing interests. [ABSTRACT FROM AUTHOR]

Introduction: Ambient air pollution is a risk factor for a diverse range of acute and chronic diseases worldwide, including cardiac arrests and respiratory illnesses. This study aims to investigate the relationship between ambient air pollution and all-cause mortality in a city (Singapore) exposed to the Southeast Asian haze problem. Findings will assist in quantifying the healthcare-related economic burden due to airborne pollutants and contribute to our understanding of environmental roles in urban mortality. Hypothesis: It is hypothesized that exposure to increased Pollutant Standards Index (PSI) is associated with increases in all-cause mortality. Methods: A time-stratified case-crossover design was performed with daily all-cause mortality counts in 2010-2015. Examined data were compared against control days of negligible exposure. A conditional Poisson regression model that included potential confounders such as daily ambient temperature, rainfall, and wind speed was fitted to the daily death counts. All models were adjusted for over-dispersion and autocorrelation. PSI was categorized based on National Environment Agency's classification (0-50=Good, 51-100=Moderate, >100=Unhealthy), whereas wind speed, temperature, and rainfall were by tertiles. Results: There were 105504 deaths during the study period. Moderate (Risk ratio/IRR=1.05, 95% CI=1.03-1.07) and unhealthy (Risk Ratio/IRR=1.08, 95% CI=1.03-1.14) PSI levels show significant association with all-cause mortality. Unhealthy temperatures (above 28.5 °C) also show significant association at a Risk Ratio/IRR=1.04, 95% CI=1.02-1.06. Each increment of 30 units in PSI on the same day and previous 1-5 days was significantly associated with 2.51%-3.40% excess risk of mortality (p<0.001). Each increment of 1°C in temperature exhibited health implications in lag day 0-2 with 0.95%-2.00% excess risk of mortality (p<0.05). Conclusions: We found significant short-intermediate term association between ambient air pollution and temperature on all-cause mortality after adjusting for other meteorological indicators. These findings substantiate the health hazards of air pollutant exposure, presenting an argument for concerted efforts to tackle transboundary haze. [ABSTRACT FROM AUTHOR]

Reports that mouse sperm gain small RNAs from the epididymosomes secreted by epididymal epithelial cells and that these "foreign" small RNAs act as an epigenetic information carrier mediating the transmission of acquired paternal traits have drawn great attention because the findings suggest that heritable information can flow from soma to germ line, thus invalidating the long-standing Weismann's barrier theory on heritable information flow. Using small RNA sequencing (sRNA-seq), northern blots, sRNA in situ hybridization, and immunofluorescence, we detected substantial changes in the small RNA profile in murine caput epididymal sperm (sperm in the head of the epididymis), and we further determined that the changes resulted from sperm exchanging small RNAs, mainly tsRNAs and rsRNAs, with cytoplasmic droplets rather than the epididymosomes. Moreover, the murine sperm-borne small RNAs were mainly derived from the nuclear small RNAs in late spermatids. Thus, caution is needed regarding sperm gaining foreign small RNAs as an underlying mechanism of epigenetic inheritance. [Display omitted] • Sperm-borne small RNAs are mainly derived from late spermatids in the testis • The small RNA profile changes when sperm transit through the epididymis • Sperm exchange small RNAs with cytoplasmic droplets (CDs) rather than epididymosomes Wang, Wang, et al. report that small RNA exchanges occur between sperm and their associated cytoplasmic droplets (CDs) during sperm maturation inside the epididymis. Their finding challenges the notion that sperm gain foreign small RNAs from the exosomes released by epididymal epithelial cells. [ABSTRACT FROM AUTHOR]

Objectives Symptom-to-door time ( S2D) is one of the important components of ischaemic time, which might affect the infarct size and outcomes of acute myocardial infarction. The aim of the present study was to identify patients' characteristics associated with delayed symptom-onset-to-arrival at EDs in ST-segment elevation myocardial infarction ( STEMI) patients in Singapore. Methods Retrospective data of STEMI patients presenting to the ED of all public hospitals with onsite primary percutaneous coronary intervention facilities between 2010 and 2012 were obtained from the Singapore Myocardial Infarction Registry. Based on the S2D of 120 min, characteristics of patients were compared between short S2D (≤120 min) and long S2D (>120 min). Multivariate logistic and linear regression analyses were performed. Results Out of 3848 patients, 1682 patients had an S2D of ≤120 min, and 2166 had an S2D >120 min. In the multivariate analyses, older age, Malay ethnicity, diabetes mellitus, presenting symptoms of back and epigastric pain were independently associated with long S2D. Patients who utilised the emergency medical services, presented after office hours and with symptoms of chest pain, breathlessness, diaphoresis and past history of percutaneous transluminal coronary angioplasty/primary percutaneous coronary intervention, were independently associated with short S2D. Patients with long S2D had lower probability of receiving reperfusion treatment with delayed symptom-to-balloon and door-to-balloon time and higher probabilities of complications and mortality. Conclusion The present study shows that longer S2D was associated with older age, ethnicity, diabetes mellitus, delay in receiving early reperfusion treatment and poorer prognosis. [ABSTRACT FROM AUTHOR]

Correct orientation of the mitotic spindle determines the plane of cellular cleavage and is crucial for organ development. In the developing cerebral cortex, spindle orientation defects result in severe neurodevelopmental disorders, but the precise mechanisms that control this important event are not fully understood. Here, we use a combination of high-content screening and mouse genetics to identify the miR-34/449 family as key regulators of mitotic spindle orientation in the developing cerebral cortex. By screening through all cortically expressed mi RNAs in HeLa cells, we show that several members of the miR-34/449 family control mitotic duration and spindle rotation. Analysis of miR-34/449 knockout ( KO) mouse embryos demonstrates significant spindle misorientation phenotypes in cortical progenitors, resulting in an excess of radial glia cells at the expense of intermediate progenitors and a significant delay in neurogenesis. We identify the junction adhesion molecule-A ( JAM-A) as a key target for miR-34/449 in the developing cortex that might be responsible for those defects. Our data indicate that mi RNA-dependent regulation of mitotic spindle orientation is crucial for cell fate specification during mammalian neurogenesis. [ABSTRACT FROM AUTHOR]

As a member of the large Ran-binding protein family, Ran-binding protein 9 (RANBP9) has been suggested to play a critical role in diverse cellular functions in somatic cell lineages in vitro, and this is further supported by the neonatal lethality phenotype in Ranbp9 global knockout mice. However, the exact molecular actions of RANBP9 remain largely unknown. By inactivation of Ranbp9 specifically in testicular somatic and spermatogenic cells, we discovered that Ranbp9 was dispensable for Sertoli cell development and functions, but critical for male germ cell development and male fertility. RIP-Seq and proteomic analyses revealed that RANBP9 was associated with multiple key splicing factors and directly targeted >2,300 mRNAs in spermatocytes and round spermatids. Many of the RANBP9 target and non-target mRNAs either displayed aberrant splicing patterns or were dysregulated in the absence of Ranbp9. Our data uncovered a novel role of Ranbp9 in regulating alternative splicing in spermatogenic cells, which is critical for normal spermatogenesis and male fertility. [ABSTRACT FROM AUTHOR]

Introduction Previous influenza pandemics had second and on occasion third waves in many countries that were at times more severe than the initial pandemic waves. Objective This study aims to determine the seroepidemiology of successive waves of H1N1pdm09 infections in Singapore and the overall risks of infection. Methods We performed a cohort study amongst 838 adults, with blood samples provided upon recruitment and at 5 points from 2009 to 2011 and tested by haemagglutination inhibition ( HI) with A/California/7/2009 (H1N1pdm09). Surveys on key demographic and clinical information were conducted at regular intervals, and associations between seroconversion and these variables were investigated. Results After the initial wave from June to September 2009, second and third waves occurred from November 2009 to February 2010 and April to June 2010, respectively. Seroconversion was 13·5% during the first wave and decreased to 6·2% and 6·8% in subsequent waves. Across the three waves, the elderly and those with higher starting HI titres were at lower risk of seroconversion, while those with larger households were at greater risk. Those with higher starting HI titres were also less likely to have an acute respiratory infection. Conclusions The second and third waves in Singapore had lower serological attack rates than the first wave. The elderly and those with higher HI titres had lower risk, while those in larger households had higher risk of seroconversion. [ABSTRACT FROM AUTHOR]