Carotid Artery, Internal ; diagnostic imaging ; Cerebrovascular Disorders ; diagnostic imaging ; physiopathology ; Extremities ; physiopathology ; Humans ; Ischemic Attack, Transient ; complications ; diagnostic imaging ; drug therapy ; Male ; Middle Aged ; Middle Cerebral Artery ; diagnostic imaging ; Thromboembolism ; diagnostic imaging ; physiopathology ; Ultrasonography, Doppler, Transcranial

INTRODUCTIONIntravenous thrombolysis has been shown to improve outcome after acute cerebral infarction if given within 3 hours of symptom onset. There are no data in Singapore on the timing of hospital presentation after acute cerebral infarction as well as factors and reasons for delayed presentation.

MATERIALS AND METHODSAs intravenous thrombolysis has recently been licensed for use in acute cerebral infarction in Singapore, we studied 100 consecutive acute cerebral infarction admitted to the Singapore General Hospital for timing of hospital presentation, reasons associated with delay in presentation and hypothetical acceptance of intravenous thrombolysis.

RESULTSOnly 9% of patients presented to hospital within 2 hours of symptom onset. Factors associated with hospital presentation within 2 hours were a large stroke and lack of pre-hospital consultation. Failure to recognise the severity of symptoms and inability to seek medical attention unaided were the 2 most common reasons for delayed presentation. One-third of patients or their relatives hypothetically would accept intravenous thrombolysis, suggesting that a thrombolysis service is feasible at the Singapore General Hospital. However, it would be hindered by the low proportion of patients who present early to hospital after symptom onset.

CONCLUSIONOur results support the need for a public education programme to highlight the identification of stroke symptoms and the need to present to hospital as soon as possible after the onset of stroke symptoms.

Acute Disease ; Aged ; Cerebral Infarction ; drug therapy ; physiopathology ; Emergency Service, Hospital ; Female ; Fibrinolytic Agents ; therapeutic use ; Hospitals, General ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Patient Acceptance of Health Care ; statistics & numerical data ; Prospective Studies ; Singapore ; Time Factors ; Treatment Outcome

Background/Aims: Data on treatment efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) for chronic hepatitis C virus (HCV) infection in Asian patients with severe renal impairment are limited. This study aimed to study the treatment and side effects of GLE/PIB in these patients infected with non-1 genotype (GT) HCV. Methods: We prospectively recruited patients with Child’s A cirrhosis and eGFR <30 mL/min/1.73 m2 in Hong Kong and Taiwan during 2017–2018 to receive GLE/PIB treatment. Results: Twenty-one patients (GT2, n=7; GT3, n=6; and GT6, n=8) received GLE/PIB for 11.2±1.8 weeks. All except one were treatment-naïve. GLE/PIB was initiated in 16 patients while on dialysis (seven on peritoneal dialysis [PD] and nine on hemodialysis) and in five patients before dialysis. One patient died of PD-related peritonitis during treatment and two were lost to follow up. The SVR12 rate in the remaining 18 patients was 100%. All patients achieved undetectable levels at 4-, 12-, 24- and 48-week after treatment. Patients with deranged alanine aminotransferase showed normalization after 4 weeks and the response was sustained for 48 weeks. No significant adverse event was observed. Conclusions GLE/PIB treatment was associated with high efficacy and tolerability in HCV-infected patients with severe renal impairment.

Adult ; Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; therapy ; Critical Care ; Female ; Humans ; Length of Stay ; Male ; Middle Aged ; Pandemics ; Patient Positioning ; Pneumonia, Viral ; complications ; therapy ; Prone Position ; Respiratory Distress Syndrome, Adult ; therapy ; virology ; Respiratory Function Tests ; Retrospective Studies ; Treatment Outcome

INTRODUCTIONCoronary artery disease (CAD) is the leading cause of death following ischaemic stroke. We aimed to study the prevalence and associations of concomitant CAD among ischaemic stroke patients in Singapore.

MATERIALS AND METHODSWe prospectively studied 2686 consecutive Asian ischaemic stroke patients.

RESULTSCAD was prevalent among 24% of the study patients. Older age, hypertension, diabetes, hyperlipidaemia, atrial fibrillation, large stroke and South Asian ethnicity were independently associated with CAD.

CONCLUSIONSThe variables found to be associated with CAD are known atherosclerotic risk factors (older age, hypertension, diabetes, hyperlipidaemia) or associations of cardioembolic stroke (atrial fibrillation, large stroke). The over-representation of South Asians with concomitant CAD is consistent with the high burden of CAD in this ethnic group.

Aged ; Brain Ischemia ; complications ; epidemiology ; Coronary Artery Disease ; complications ; epidemiology ; Female ; Humans ; Male ; Prevalence ; Prospective Studies ; Regression Analysis ; Risk Factors ; Singapore ; epidemiology ; Stroke ; complications ; epidemiology ; Survival Rate ; Time Factors

INTRODUCTIONThis study aims to analyse the results of carotid stenting in a tertiary referral centre in Singapore.

MATERIALS AND METHODSRetrospective analysis of all carotid artery stenting (CAS) cases in a single centre from March 1997 to December 2008 was performed. Sixty successful procedures were performed in 61 patients, with bilateral stenting in 1 patient, and 2 failed procedures. The majority were Chinese (78.7%) and males (77.0%), with a high proportion having hypertension (82.0%) and hypercholesterolaemia (78.7%). The majority (91.8%) of patients were high surgical risk candidates, primarily due to cardiac risk factors. Ten patients (16.4%) had prior neck irradiation for nasopharyngeal carcinoma, and 3 patients each (4.9%) had previous endarterectomy and contralateral occlusion. A distal embolic protection device was used in 71.7% of cases.

RESULTSTechnical success was 96.8%. The 30-day stroke and death rate was 13.8%, comparable to reported results for this high surgical risk population.

CONCLUSIONCAS is a technically feasible and a relatively safe alternative to endarterectomy to treat extracranial carotid stenosis, especially in patients who are inoperable or at high surgical risk.

Aged ; Aged, 80 and over ; Angioplasty ; methods ; Angioplasty, Balloon, Coronary ; methods ; Carotid Artery Diseases ; surgery ; Female ; Hospitals, General ; Humans ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Retrospective Studies ; Risk ; Singapore ; Stents

Cytomegalovirus (CMV) is distinct among members of the Herpesviridae family for having the largest dsDNA genome (230 kb). Packaging of large dsDNA genome is known to give rise to a highly pressurized viral capsid, but molecular interactions conducive to the formation of CMV capsid resistant to pressurization have not been described. Here, we report a cryo electron microscopy (cryoEM) structure of the murine cytomegalovirus (MCMV) capsid at a 9.1 Å resolution and describe the molecular interactions among the ∼3000 protein molecules in the MCMV capsid at the secondary structure level. Secondary structural elements are resolved to provide landmarks for correlating with results from sequence-based prediction and for structure-based homology modeling. The major capsid protein (MCP) upper domain (MCPud) contains α-helices and β-sheets conserved with those in MCPud of herpes simplex virus type 1 (HSV-1), with the largest differences identified as a "saddle loop" region, located at the tip of MCPud and involved in interaction with the smallest capsid protein (SCP). Interactions among the bacteriophage HK97-like floor domain of MCP, the middle domain of MCP, the hook and clamp domains of the triplex proteins (hoop and clamp domains of TRI-1 and clamp domain of TRI-2) contribute to the formation of a mature capsid. These results offer a framework for understanding how cytomegalovirus uses various secondary structural elements of its capsid proteins to build a robust capsid for packaging its large dsDNA genome inside and for attaching unique functional tegument proteins outside.
Amino Acid Sequence ; Capsid Proteins ; chemistry ; metabolism ; ultrastructure ; Cryoelectron Microscopy ; Models, Molecular ; Molecular Sequence Data ; Muromegalovirus ; chemistry ; ultrastructure ; Protein Binding ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary

Background: Bamboo shoot has been used as a treatment for epilepsy in traditional Chinese medicine for generations to treat neuronal disorders such as convulsive, dizziness and headaches. 4-hydroxybenzoic acid (4-hba) is a non-flavonoid phenol found abundantly in Dendrocalamus asper shoots (bamboo), fruits (strawberries and apples) and flowers. Kv1.4 is a rapidly inactivating Shaker-related member of the voltage-gated potassium channels with two inactivation mechanisms; the fast N-type and slow C-type. It plays vital roles in repolarisation, hyperpolarisation and signaling the restoration of resting membrane potential through the regulation of the movement of K+ across the cellular membrane. Methods: Chemical compounds from Dendrocalamus asper bamboo shoots were purified and identified as major palmitic acids mixed with other minor fatty acids, palmitic acid, 4-hydroxybenzaldehyde, lauric acid, 4-hydroxybenzoic acid and cholest-4-ene-3-one. The response of synthetic 4-hydroxybenzoic acid was tested on Kv1.4 potassium channel which was injected into viable oocytes that was extracted from Xenopus laevis. The current were detected by the two-microelectrode voltage clamp, holding potential starting from −80 mV with 20 mV stepup until +80 mV. Readings of treatments with 0.1% DMSO, 4-hba concentrations and K channel blockers were taken at +60 mV. The ratio of tail/peak amplitude is the index of the activity of the Kv1.4 channels with n ≥ 6 (number of oocytes tested). The decreases of the ratios of five different concentrations (1 μM, 10 μM, 100 μM, 1 mM and 2.5 mM) were compared with 0.1% DMSO as the control. Results: All concentration showed statistically significant results with P < 0.05 except for 100 μM. The normalised current of the 4-hba concentrations were compared with potassium channel blockers (TEA and 4-AP) and all groups showed statistically significant results. This study also showed that time taken for each concentration to affect Kv1.4 does not play any significant roles. Conclusion: 4-hydroxybenzoic acid was found to be able to enhance the inactivation of Kv1.4 by lowering the membrane potential so that the abnormal neuronal firing can be inhibited. With IC50 slightly higher than 10 μM, increasing concentrations (100 μM, 1 mM and 2.5 mM) had shown to exhibit toxicity effects. The best concentration from this study is 10 μM with Hill slope of 0.1799.

INTRODUCTIONThis study investigated the effect of an access-enhanced intervention on hypertension screening and management, as well as on health behaviours among newly diagnosed hypertensives, in a multi-ethnic low socioeconomic status (SES) community. Factors associated with hypertension screening, treatment, and control in the community were also determined.

MATERIALS AND METHODSThe study involved all residents aged ≥40 years in 2 public rental housing precincts (low SES), between 2009 and 2011, who were followed-up prospectively for 1 year after a 6-month community-based intervention comprising a 3-month access-enhanced screening component and a 3-month follow-up (outreach) component. Blood pressure was measured at baseline and follow-up. Multivariate Cox regression determined predictors of hypertension management at follow-up.

RESULTSThe follow-up rate was 80.9% (467/577). At baseline, 60.4% (282/467) were hypertensive; 53.5% (151/282) were untreated; 54.2% (71/131) uncontrolled. One year later, postintervention, 51.6% (78/151) of untreated hypertensives were treated; combined with treated hypertensives previously uncontrolled, 53.0% (79/149) achieved control. Older age independently predicted treatment (adjusted relative risk, aRR = 1.98, CI, 1.08 to 3.65); majority ethnicity (aRR = 1.76, CI, 1.05 to 2.96), employment (aRR = 1.85, CI, 1.26 to 2.80) and newly treated hypertension (aRR=1.52, CI, 1.01 to 2.32) predicted control. A total of 52.4% (97/185) were irregularly screened at baseline; at follow-up 61.9% (60/97) were regularly screened. Cost and misperceptions were common barriers to screening and treatment. Newly diagnosed hypertensives were also less likely to go for additional cardiovascular screening (aRR = 0.54, CI, 0.29 to 0.99).

CONCLUSIONAn access-enhanced intervention had some success in improving hypertension management within low SES communities; however, it was less successful in improving cardiovascular risk management, especially in encouraging lifestyle changes and additional cardiovascular screening amongst newly diagnosed hypertensives.

Adult ; Age Factors ; Aged ; Antihypertensive Agents ; therapeutic use ; Asian Continental Ancestry Group ; statistics & numerical data ; Diet, Sodium-Restricted ; methods ; Exercise Therapy ; methods ; Female ; Health Services Accessibility ; statistics & numerical data ; Humans ; Hypertension ; diagnosis ; ethnology ; therapy ; Male ; Mass Screening ; Middle Aged ; Multivariate Analysis ; Patient Compliance ; ethnology ; statistics & numerical data ; Patient Dropouts ; statistics & numerical data ; Poverty ; statistics & numerical data ; Proportional Hazards Models ; Prospective Studies ; Risk Reduction Behavior ; Singapore ; Smoking Cessation ; methods ; Social Class ; Treatment Outcome ; Weight Reduction Programs ; methods