Immunization with recombinant enterovirus 71 viral capsid protein 1 fragment stimulated antibody responses in hamsters

Enterovirus 71 (EV71) causes severe neurological diseases resulting in high mortality in young children worldwide. Development of an effective vaccine against EV71 infection is hampered by the lack of appropriate animal models for efficacy testing of candidate vaccines. Previously, we have successfully tested the immunogenicity and protectiveness of a candidate EV71 vaccine, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt-VP1(1-100)) protein, in a mouse model of EV71 infection. A drawback of this system is its limited window of EV71 susceptibility period, 2 weeks after birth, leading to restricted options in the evaluation of optimal dosing regimens. To address this issue, we have assessed the NPt-VP1(1-100) candidate vaccine in a hamster system, which offers a 4-week susceptibility period to EV71 infection. Results obtained showed that the NPt-VP1(1-100) candidate vaccine stimulated excellent humoral immune response in the hamsters. Despite the high level of antibody production, they failed to neutralize EV71 viruses or protect vaccinated hamsters in viral challenge studies. Nevertheless, these findings have contributed towards a better understanding of the NPt-VP1(1-100) recombinant protein as a candidate vaccine in an alternative animal model system

Reduced Newcastle disease virus-induced oncolysis in a subpopulation of cisplatin-resistant MCF7 cells is associated with survivin stabilization

Abstract Background Cisplatin resistance is a serious problem in cancer treatment. To overcome it, alternative approaches including virotherapy are being pursued. One of the candidates for anticancer virotherapy is the Newcastle disease virus (NDV). Even though NDV's oncolytic properties in various cancer cells have been widely reported, information regarding its effects on cisplatin resistant cancer cells is still limited. Therefore, we tested the oncolytic efficacy of a strain of NDV, designated as AF2240, in a cisplatin-resistant breast cancer cell line. Methods Cisplatin-resistant cell line (MCF7-CR) was developed from the MCF7 human breast adenocarcinoma cell line by performing a seven-cyclic exposure to cisplatin. Following NDV infection, fluorescence-activated cell sorting (FACS) analysis and immunoblotting were used to measure cell viability and viral protein expression, respectively. Production of virus progeny was then assessed by using the plaque assay technique. Results Infection of a mass population of the MCF7-CR with NDV resulted in 50% killing in the first 12 hours post-infection (hpi), comparable to the parental MCF7. From 12 hpi onwards, the remaining MCF7-CR became less susceptible to NDV killing. This reduced susceptibility led to increased viral protein synthesis and virus progeny production. The reduction was also associated with a prolonged cell survival via stabilization of the survivin protein. Conclusions Our findings showed for the first time, the involvement of survivin in the reduction of NDV-induced oncolysis in a subpopulation of cisplatin-resistant cells. This information will be important towards improving the efficacy of NDV as an anticancer agent in drug resistant cancers.</p

Public Hospital Pharmacists’ Perceptions and Knowledge of Antibiotic Use and Resistance: A Multicenter Survey

Antimicrobial Stewardship Program (ASP) has been implemented in major public hospitals in Malaysia, with pharmacists playing a key role in ensuring the appropriate use of antibiotics. This survey aimed to assess the practices, perceptions, and knowledge of public hospital pharmacists on antibiotic use and resistance. A cross-sectional survey involving pharmacists from six public hospitals in Penang was conducted using a self-administered validated questionnaire. The majority of pharmacists perceived that polypharmacy (92%, n = 270) and overuse of broad-spectrum antibiotics (85%, n = 252) can potentially induce resistance of microorganisms and that ensuring the rational use of antibiotics is a shared responsibility between clinicians and pharmacists (94%, n = 278). A large majority of the pharmacists think that formal training in infectious disease should be a pre-requisite for pharmacists in ASP (93%, n = 273). In terms of antibiotic selection, the availability of antibiotics in hospital (81%, n = 234) and patient&rsquo;s clinical condition (68%, n = 196) are more of a concern to the pharmacists. A total of 65% of the respondents (n = 192) demonstrated good levels of knowledge with a mean knowledge score of 10.1 out of 13 (95% CI: 9.95; 10.31). Pharmacists from the managerial level, ward pharmacy, in-patient, and medication therapy adherence clinic (MTAC) unit had better knowledge of antibiotics compared to pharmacists from other units (p &lt; 0.001). Antibiotic knowledge gap had been identified among pharmacists in different work settings, and longer years of service does not warrant good antibiotic knowledge

Validation of the Visual Cognitive Assessment Test (VCAT) for the Early Diagnosis of Cognitive Impairment in Multilingual Population in Malaysia

As Malaysia undergoes a demographic transformation of population aging, the prevalence of dementia is expected to rise, posing a major public health threat issue. Early screening to detect cognitive impairment is important to implement appropriate clinical interventions. The Visual Cognitive Assessment Test (VCAT) is a language-neutral cognitive assessment screening tool suitable for multilingual populations. This study was aimed to validate the VCAT screening tool for the detection of cognitive impairment amongst the population of Malaysia. A total of 184 participants were recruited, comprising 79 cognitively healthy participants (CHP), 46 mild cognitive impairment (MCI) patients, and 59 mild dementia (Alzheimer&rsquo;s disease and Vascular Dementia) patients from five hospitals between May 2018 and December 2019 to determine the usefulness of VCAT. Diagnostic performance was assessed using area under the curve (AUC), and receiver operating characteristic (ROC) analysies was performed to determine the recommended cutoff scores. ROC analyses for the VCAT was comparable with that of MoCA (Montreal Cognitive Assessment) in differentiating between CHP, MCI, and mild dementia (AD and VaD) participants. The findings of this study suggest the following optimal cutoff score for VCAT: Dementia 0&ndash;19, MCI 20&ndash;23, Normal 24&ndash;30. The mean &plusmn; SD time to complete the VCAT was 10.0 &plusmn; 2.75 min in the CHP group and 15.4 &plusmn; 4.52 min in the CI group. Results showed that 76.0% of subjects thought that the instructions in VCAT were similar or easier to understand compared with MoCA. This study showed that the VCAT is a valid and useful screening tool for patients with cognitive impairment in Malaysia and is feasible to be used in the clinical settings