METHODS: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.
RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.
CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.
METHODS: Clinical data, including age at symptom onset, was collected from 289 patients who presented to our multidisciplinary clinic from 2016 until 2024. A least squares linear regression model was constructed from the logarithm of approximated incidence and the logarithm of age. Population incidence was approximated by adjusting the absolute numbers of patients in 5 year groups by the size of the general population in the respective age group.
RESULTS: A linear relationship between log of incidence versus log of age was observed, with a slope of 4.57 (95% CI, 3.3-5.8) and an r2 value of 0.93, suggesting a 6-step process.
CONCLUSION: Progression toward symptom onset in Malaysian ALS patients appears consistent with a multistep model of disease as observed in other cohorts.
METHODS: A total of 25 survivors of NiV infection from the 1998 outbreak were recruited for sample collection. The serum IgG antibody response to NiV antigens, specifically nucleocapsid (N), fusion glycoprotein (F) and attachment glycoprotein (G) was evaluated using ELISA. Additionally, the samples were tested for neutralizing antibodies and memory B cell responses.
RESULTS: Detection rates of anti-NiV-F and anti-NiV-G were 56% and 60%, respectively, among the survivors at a 1:100 dilution, whereas only 20% were specifically reactive to rNiV-N. Notably, all samples that tested positive for NiV-F and NiV-G at this dilution also exhibited neutralizing antibodies, highlighting the specificity of these assays. Live virus neutralization assay showed that 72% of survivors had detectable neutralizing antibodies, with varying titers, indicating long-lasting immune memory. Furthermore, memory B cell responses specific to NiV-F and NiV-G were observed in six randomly selected survivors, suggesting the presence of enduring immunological memory.
CONCLUSIONS: These findings highlight the potential of NiV-F and NiV-G as reliable markers for NiV exposure and underscore the need for continuous surveillance and research. Such efforts are crucial for advancing vaccine development and improving preparedness for future NiV outbreaks.
METHODS: In this study, the morphophical changes and apoptosis induction of WEHI 3B leukemia cell line treated with NDV strain AF2240 were studied by scanning electron microscopes and transmission electron microscopes techniques.
RESULT: Electron microscopy indicated that NDV strain AF 2240 significantly altered cell morphology and reduced cell viability. Furthermore, early apoptosis was observed 6 h post-inoculation by fluorescence microscope.
CONCLUSION: Our results suggest that NDV has ability to induce significant apoptoic structural changes in WEHI 3B leukemia cell line. These findings provide new insights into the mechanism of action of NDV virotherapy and could lead to the development of more effective treatments for leukemia.
METHODS: We estimated incidence, prevalence, death, and disability-adjusted life-year (DALY) counts and age-standardised rates per 100 000 people per year for overall stroke, ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage, for 204 countries and territories from 1990 to 2021. We also calculated burden of stroke attributable to 23 risk factors and six risk clusters (air pollution, tobacco smoking, behavioural, dietary, environmental, and metabolic risks) at the global and regional levels (21 GBD regions and Socio-demographic Index [SDI] quintiles), using the standard GBD methodology. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline.
FINDINGS: In 2021, stroke was the third most common GBD level 3 cause of death (7·3 million [95% UI 6·6-7·8] deaths; 10·7% [9·8-11·3] of all deaths) after ischaemic heart disease and COVID-19, and the fourth most common cause of DALYs (160·5 million [147·8-171·6] DALYs; 5·6% [5·0-6·1] of all DALYs). In 2021, there were 93·8 million (89·0-99·3) prevalent and 11·9 million (10·7-13·2) incident strokes. We found disparities in stroke burden and risk factors by GBD region, country or territory, and SDI, as well as a stagnation in the reduction of incidence from 2015 onwards, and even some increases in the stroke incidence, death, prevalence, and DALY rates in southeast Asia, east Asia, and Oceania, countries with lower SDI, and people younger than 70 years. Globally, ischaemic stroke constituted 65·3% (62·4-67·7), intracerebral haemorrhage constituted 28·8% (28·3-28·8), and subarachnoid haemorrhage constituted 5·8% (5·7-6·0) of incident strokes. There were substantial increases in DALYs attributable to high BMI (88·2% [53·4-117·7]), high ambient temperature (72·4% [51·1 to 179·5]), high fasting plasma glucose (32·1% [26·7-38·1]), diet high in sugar-sweetened beverages (23·4% [12·7-35·7]), low physical activity (11·3% [1·8-34·9]), high systolic blood pressure (6·7% [2·5-11·6]), lead exposure (6·5% [4·5-11·2]), and diet low in omega-6 polyunsaturated fatty acids (5·3% [0·5-10·5]).
INTERPRETATION: Stroke burden has increased from 1990 to 2021, and the contribution of several risk factors has also increased. Effective, accessible, and affordable measures to improve stroke surveillance, prevention (with the emphasis on blood pressure, lifestyle, and environmental factors), acute care, and rehabilitation need to be urgently implemented across all countries to reduce stroke burden.
FUNDING: Bill & Melinda Gates Foundation.
METHODS: The efficacy and cross-reactivity of two vaccine candidates derived from the soluble glycoproteins of both NiV and Hendra virus (HeV) was evaluated in our recently established hamster model.
RESULTS: Both vaccine preparations resulted in strong humoral responses against NiV antigenic targets, demonstrating cross-reactive immunity. Efficacy was determined through challenge of hamsters with NiV Malaysian (NiV-M) strain. 100% of the hamsters survived a lethal challenge dose after prime/boost immunisation with glycoproteins derived from both NiV and HeV in the presence of adjuvant, with clinical signs and pathology being significantly reduced in immunised animals.
DISCUSSION: This is first time the NiV and HeV soluble glycoproteins have been compared in the NiV-M hamster challenge model in the presence of Alhydrogel and AddaVax, providing evidence that glycoproteins from closely related henipavirus species can provide cross-protectivity against infection from alternate henipaviruses, supporting the potential of an effective pan-henipavirus vaccine for use in a frontline outbreak response.
METHODS: Data on notifiable diseases from 2014 to 2022 were sourced from the Klang District Health Office. The 11 diseases with more than 100 notifications each were included in the study. For these 11 diseases, a negative binomial regression model was used to explore the effect of the pandemic on case notifications and registrations by year, and a quasi-Poisson regression model was used to explore the changes by week.
RESULTS: The results showed a reduction in the number of notifications and registrations for all 11 diseases combined during the pandemic compared with previous years. Changes between expected and observed notifications by week were heterogeneous across the diseases.
DISCUSSION: These findings suggest that restrictive public health and social measures in Klang district may have impacted the transmission of other infectious diseases during the COVID-19 pandemic. The differential impact of the pandemic on disease notifications and reporting highlights the large ancillary effects of restrictive public health and social measures and the importance of building resilience into infectious disease surveillance systems.
OBJECTIVES: We aimed to determine the resources and facilities for comprehensive management of PD in Asia focusing on regions (South East Asia, Middle East, Indian Subcontinent, East Asia, and Central Asia) and income levels (high-income countries-HIC, upper middle-income countries-UMIC, lower middle-income countries-LMIC).
METHOD: A survey-based questionnaire was deployed to the MDS affiliate societies or key neurologists in 32 countries in Asia.
RESULTS: Thirty countries/territories participated in the survey. HICs have better availability of and accessibility to most health care professionals. Central Asia has the lowest availability of and accessibility to health care professionals. PD nurses are least available (33.3%) and least easily accessible (6.7%). Levodopa and anticholinergics are the most available (100%), accessible (100%) and affordable (100%) antiparkinsonian medications. Device-aid therapies are more available and accessible in East Asian countries/territories, compared to other regions. Accessibility to allied health professionals is poor (43%). Genetic testing is available in 18 (60%) countries/territories, mostly in HIC (P = 0.031). Community engagement and public health awareness campaigns are available in 21 (70%) countries/territories. Brain bank is available in seven (24.1%) countries/territories, mostly in HIC. Telemedicine is utilized in 21 (70%) countries/territories.
CONCLUSION: This is the first survey-based study to highlight regional and income-based disparities on infrastructures required for comprehensive PD care in Asia. Regional collaborations between HIC and MIC may address some of these disparities.