Factors Related to, and Effective Interventions for, Vaccination Uptake Among Older Adults in Two Asia-Pacific Countries: A Rapid Review.

This rapid review aimed to present a comprehensive overview of barriers, facilitators, and effective interventions that promote vaccination uptake by older adults in the Asia-Pacific region. Rapid review methodology was applied, using two databases (PubMed, Embase). Articles were included if studies were conducted in Australia, Singapore, Indonesia, and the Philippines; included human population ≥50 years of age, and was published from 2016 to August 2022.

Altered Risk-Taking Behavior in Early-Stage Bipolar Disorder With a History of Psychosis.

Altered risk-taking propensity is an important determinant of functional impairment in bipolar disorder. However, prior studies primarily assessed patients with chronic illness, and risk-taking has not been evaluated in the early illness course. This study investigated risk-taking behavior in 39 euthymic early-stage bipolar disorder patients aged 16-40 years who were treated within 3 years from their first-episode mania with psychotic features and 36 demographically-matched healthy controls using the Balloon Analog Risk Task (BART), a well-validated risk-taking performance-based paradigm requiring participants to make responses for cumulative gain at increasing risk of loss.

Evaluation of the Implementation and Effectiveness of Community-Based Brain-Computer Interface Cognitive Group Training in Healthy Community-Dwelling Older Adults: Randomized Controlled Implementation Trial.

Background: Cognitive training can improve cognition in healthy older adults.

Objective: The objectives are to evaluate the implementation of community-based computerized cognitive training (CCT) and its effectiveness on cognition, gait, and balance in healthy older adults.

Methods: A single-blind randomized controlled trial with baseline and follow-up assessments was conducted at two community centers in Singapore.

Early and Sustained Increases in Leukotriene B Levels Are Associated with Poor Clinical Outcome in Ischemic Stroke Patients.

Leukotriene B (LTB) has been implicated in ischemic stroke pathology. We examined the prognostic significance of LTB levels in patients with acute middle cerebral artery (MCA) infarction and their mechanisms in rat stroke models. In ischemic stroke patients with middle cerebral artery infarction, plasma LTB levels were found to increase rapidly, roughly doubling within 24 h when compared to initial post-stroke levels.

Chemotherapy induces expression and release of heparanase leading to changes associated with an aggressive tumor phenotype.

High heparanase expression is associated with enhanced tumor growth, angiogenesis, and metastasis in many types of cancer. However, the mechanisms driving high heparanase expression are not fully understood. In the present study, we discovered that drugs used in the treatment of myeloma upregulate heparanase expression.

Establishment of a Novel Primary Human Skeletal Myoblast Cellular Model for Chikungunya Virus Infection and Pathogenesis.

Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia and is now considered endemic in countries across Asia and Africa. The tissue tropism of CHIKV infection in humans remains, however, ill-defined. Due to the fact that myositis is commonly observed in most patients infected with CHIKV, we sought to develop a clinically relevant cellular model to better understand the pathogenesis of CHIKV infection.

Heparanase-neutralizing antibodies attenuate lymphoma tumor growth and metastasis.

Heparanase is an endoglycosidase that cleaves heparan sulfate side chains of proteoglycans, resulting in disassembly of the extracellular matrix underlying endothelial and epithelial cells and associating with enhanced cell invasion and metastasis. Heparanase expression is induced in carcinomas and sarcomas, often associating with enhanced tumor metastasis and poor prognosis. In contrast, the function of heparanase in hematological malignancies (except myeloma) was not investigated in depth.

Multiple Genetic Mutations Associated with Polymyxin Resistance in Acinetobacter baumannii.

We studied polymyxin B resistance in 10 pairs of clinical Acinetobacter baumannii isolates, two of which had developed polymyxin B resistance in vivo. All polymyxin B-resistant isolates had lower growth rates than and substitution mutations in the lpx or pmrB gene compared to their parent isolates. There were significant differences in terms of antibiotic susceptibility and genetic determinants of resistance in A.

Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection.

Dengue virus (DV) infection is the most prevalent mosquito-borne viral disease and its manifestation has been shown to be contributed in part by the host immune responses. In this study, pathogen recognition receptors, Toll-like receptor (TLR) 2 and TLR6 were found to be up-regulated in DV-infected human PBMC using immunofluorescence staining, flow cytometry and Western blot analyses. Using ELISA, IL-6 and TNF-α, cytokines downstream of TLR2 and TLR6 signaling pathways were also found to be up-regulated in DV-infected PBMC.

Does influenza A infection increase oxidative damage?

Considerable data implicate oxidative damage in influenza pathogenesis. We examined temporal changes in oxidative damage using accurate biomarkers in an adult cohort with acute influenza infection and their relationships with clinical parameters. Clinical information and blood samples were collected during their acute illness and 3 months later.

Does high-dose coenzyme Q10 improve oxidative damage and clinical outcomes in Parkinson's disease?

Evidence on the efficacy of high-dose coenzyme Q10 (CoQ10) in Parkinson's disease (PD) is conflicting. An open-label dose-escalation study was performed to examine the effects of CoQ10 on biomarkers of oxidative damage and clinical outcomes in 16 subjects with early idiopathic PD. Each dose (400, 800, 1200, and 2400 mg/day) was consumed daily for 2 weeks.

Comprehensive gene expression profiling reveals synergistic functional networks in cerebral vessels after hypertension or hypercholesterolemia.

Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk factors i.e.

Comparative analysis of the genome sequences and replication profiles of chikungunya virus isolates within the East, Central and South African (ECSA) lineage.

Background: A comparative analysis of the genomic and replication profiles of different geographical chikungunya virus (CHIKV) isolates of the East, Central and South African (ECSA) lineage was performed.

Findings: Analysis of the data revealed the different growth kinetics for the different isolates. Deep genome sequencing analysis further revealed specific amino acid mutations in the viral nsP1, nsP3, nsP4, E1 and E2 proteins in the different isolates.

Polycomb recruitment attenuates retinoic acid-induced transcription of the bivalent NR2F1 gene.

Polycomb proteins play key roles in mediating epigenetic modifications that occur during cell differentiation. The Polycomb repressive complex 2 (PRC2) mediates the tri-methylation of histone H3 lysine 27 (H3K27me3). In this study, we identify a distinguishing feature of two classes of PRC2 target genes, represented by the Nr2F1 (Coup-TF1) and the Hoxa5 gene, respectively.

Mosquito cellular factors and functions in mediating the infectious entry of chikungunya virus.

Chikungunya virus (CHIKV) is an arthropod-borne virus responsible for recent epidemics in the Asia Pacific regions. A customized gene expression microarray of 18,760 transcripts known to target Aedes mosquito genome was used to identify host genes that are differentially regulated during the infectious entry process of CHIKV infection on C6/36 mosquito cells. Several genes such as epsin I (EPN1), epidermal growth factor receptor pathway substrate 15 (EPS15) and Huntingtin interacting protein I (HIP1) were identified to be differentially expressed during CHIKV infection and known to be involved in clathrin-mediated endocytosis (CME).

Mechanical compaction directly modulates the dynamics of bile canaliculi formation.

Homeostatic pressure-driven compaction is a ubiquitous mechanical force in multicellular organisms and is proposed to be important in the maintenance of multicellular tissue integrity and function. Previous cell-free biochemical models have demonstrated that there are cross-talks between compaction forces and tissue structural functions, such as cell-cell adhesion. However, its involvement in physiological tissue function has yet to be directly demonstrated.

Expression of plasmid-based shRNA against the E1 and nsP1 genes effectively silenced Chikungunya virus replication.

Background: Chikungunya virus (CHIKV) is a re-emerging alphavirus that causes chikungunya fever and persistent arthralgia in humans. Currently, there is no effective vaccine or antiviral against CHIKV infection. Therefore, this study evaluates whether RNA interference which targets at viral genomic level may be a novel antiviral strategy to inhibit the medically important CHIKV infection.

Electrochemical impedance spectroscopy characterization of nanoporous alumina dengue virus biosensor.

The Faradaic electrochemical impedance technique is employed to characterize the impedance change of a nanoporous alumina biosensor in response towards the specific binding of dengue serotype 2 (Denv2) viral particles to its serotype 2-specific immunoglobulin G antibody within the thin alumina layer. The optimal equivalent circuit model that matches the impedimetric responses of the sensor describes three distinct regions: the electrolyte solution (R(s)), the porous alumina channels (including biomaterials) (Q(1), R(1)) and the conductive electrode substrate layer (Q(2), R(2)). Both channel resistance R(1) and capacitance Q(1) change in response to the increase of the Denv2 virus concentration.

Replication of alphaviruses: a review on the entry process of alphaviruses into cells.

Alphaviruses are small, enveloped viruses, ~70 nm in diameter, containing a single-stranded, positive-sense, RNA genome. Viruses belonging to this genus are predominantly arthropod-borne viruses, known to cause disease in humans. Their potential threat to human health was most recently exemplified by the 2005 Chikungunya virus outbreak in La Reunion, highlighting the necessity to understand events in the life-cycle of these medically important human pathogens.

Narasin, a novel antiviral compound that blocks dengue virus protein expression.

Background: Dengue virus (DENV) is a mosquito-borne virus that causes a spectrum of human diseases ranging from mild dengue fever to dengue haemorrhagic fever and dengue shock syndrome in severe cases. Currently, there is no effective antiviral therapy or vaccine against DENV infection.

Methods: In order to identify potential antiviral agents against DENV, we performed high-throughput cell-based screening on a highly purified natural products library.

Developments towards antiviral therapies against enterovirus 71.

Enterovirus 71 (EV71) has emerged as a clinically important neurotropic virus that can cause acute flaccid paralysis and encephalitis, leading to cardiopulmonary failure and death. Recurring outbreaks of EV71 have been reported in several countries. The current lack of approved anti-EV71 therapy has prompted intense research into antiviral development.

The essential role of clathrin-mediated endocytosis in the infectious entry of human enterovirus 71.

Little is currently known about the infectious entry process of human enterovirus 71 (HEV71) into host cells, which may represent potential anti-viral targeting sites. In this study a targeted small-interfering RNA (siRNA) screening platform assay was established and validated to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics, and endosomal trafficking essential for HEV71 infection. Screen evaluation was conducted via the expression of well characterized dominant-negative mutants, bioimaging studies (double-labeled immunofluorescence assays, transmission electron microscopy analysis), secondary siRNA-based dosage dependence studies, and drug inhibition assays.

Six cases of daptomycin-non-susceptible Staphylococcus aureus bacteraemia in Singapore.

We report what we believe to be the first six cases of daptomycin-non-susceptible Staphylococcus aureus infections from Singapore. These strains were rapidly isolated after bacteraemic patients were switched to daptomycin following initial prolonged unsuccessful therapy with vancomycin, despite confirmation of daptomycin susceptibility just prior to initiating daptomycin therapy. The majority of post-vancomycin therapy strains exhibited marked thickening of their cell walls on electron microscopic examination.

Do viruses subvert cholesterol homeostasis to induce host cubic membranes?

Biological membranes with cubic morphology are a hallmark of stressed or diseased cellular conditions; both protein-protein interactions and lipid alterations appear to contribute to their biogenesis, yet their specific cellular functions are unknown. The occurrence of cubic membranes strikingly correlates with viral infections; notably, virus entry, proliferation, and release are processes closely linked to cellular cholesterol metabolism, and dys-regulation of cholesterol synthesis at the level of HMG-CoA reductase also induces cubic membrane formation, in the absence of viral infection. We propose that virus-induced cubic membranes could result from viral interference of cellular cholesterol homeostasis, generating a protective membrane environment to facilitate virus assembly and proliferation.