Predictors of Recurrent Ischemic Stroke in Obese Patients With Type 2 Diabetes Mellitus: A Population-based Study.

BACKGROUND: Diabetes and obesity are established risk factors for stroke. The current study aimed to assess risk factors of ischemic stroke recurrence in diabetic patients based on their body mass index (BMI). METHODS: A total of 4005 diabetic patients who had a history of ischemic stroke were identified in a retrospective cross-sectional dataset from the Malaysian National Neurology Registry. Patients were classified based on BMI, and multivariable regression analysis was used to evaluate the association between risk factors and recurrent ischemic stroke. RESULTS: Among obese patients, those with ischemic heart disease (aOR, 1.873; 95% CI, 1.131-3.103), received formal education (aOR, 2.236; 95% CI, 1.306-3.830), and received anti-diabetic medication (aOR, 1.788; 95% CI, 1.180-2.708) had a higher stroke recurrence risk, while receiving angiotensin receptors blockers (aOR, 0.261; 95% CI, 0.126-0.543) lowered the odds of recurrence. Overweight patients with hypertension (aOR, 1.011; 95% CI, 1.002-1.019) for over 10 years (aOR, 3.385; 95% CI, 1.088-10.532) and diabetes prior to the first stroke (aOR, 1.823; 95% CI, 1.020-3.259) as well as those received formal education (aOR, 2.403; 95% CI, 1.126-5.129) had higher odds of stroke recurrence, while receiving angiotensin-converting enzyme inhibitors (aOR, 0.244; 95% CI, 0.111-0.538) lowered the recurrence risk. Normal weight East Malaysians (aOR, 0.351; 95% CI, 0.164-0.750) receiving beta-blockers (aOR, 0.410; 95% CI, 0.174-0.966) had lower odds of stroke recurrence. CONCLUSIONS: Ischemic heart disease, hypertension, receiving anti-hypertensive agents, and educational level were independent predictors of recurrent stroke in obese patients. Managing the modifiable risk factors can decrease the odds of stroke recurrence.

A novel multiplex PCR-RFLP method for simultaneous detection of the MTHFR 677 C > T, eNOS +894 G > T and - eNOS -786 T > C variants among Malaysian Malays.

BACKGROUND: Hyperhomocysteinemia as a consequence of the MTHFR 677 C > T variant is associated with cardiovascular disease and stroke. Another factor that can potentially contribute to these disorders is a depleted nitric oxide level, which can be due to the presence of eNOS +894 G > T and eNOS -786 T > C variants that make an individual more susceptible to endothelial dysfunction. A number of genotyping methods have been developed to investigate these variants. However, simultaneous detection methods using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis are still lacking. In this study, a novel multiplex PCR-RFLP method for the simultaneous detection of MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C variants was developed. A total of 114 healthy Malay subjects were recruited. The MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C variants were genotyped using the novel multiplex PCR-RFLP and confirmed by DNA sequencing as well as snpBLAST. Allele frequencies of MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C were calculated using the Hardy Weinberg equation. METHODS: The 114 healthy volunteers were recruited for this study, and their DNA was extracted. Primer pair was designed using Primer 3 Software version 0.4.0 and validated against the BLAST database. The primer specificity, functionality and annealing temperature were tested using uniplex PCR methods that were later combined into a single multiplex PCR. Restriction Fragment Length Polymorphism (RFLP) was performed in three separate tubes followed by agarose gel electrophoresis. PCR product residual was purified and sent for DNA sequencing. RESULTS: The allele frequencies for MTHFR 677 C > T were 0.89 (C allele) and 0.11 (T allele); for eNOS +894 G > T, the allele frequencies were 0.58 (G allele) and 0.43 (T allele); and for eNOS -786 T > C, the allele frequencies were 0.87 (T allele) and 0.13 (C allele). CONCLUSIONS: Our PCR-RFLP method is a simple, cost-effective and time-saving method. It can be used to successfully genotype subjects for the MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C variants simultaneously with 100% concordance from DNA sequencing data. This method can be routinely used for rapid investigation of the MTHFR 677 C > T and eNOS +894 G > T and eNOS -786 T > C variants.

Population-based Study Comparing Predictors of Ischemic Stroke Recurrence After Index Ischemic Stroke in Non-elderly Adults with or without Diabetes.

BACKGROUND AND PURPOSE: Factors associated with ischemic stroke (IS) recurrence and the contribution of pharmacological treatment as secondary preventions among nondiabetics especially in the non-elderly population are unclear and not widely investigated. This was a population-based study that aimed to identify recurrent IS predictors and to determine the possible impact of secondary preventive medications on the IS recurrence in non-elderly adults with or without diabetes. METHODS: Data of 3386 patients <60 years old who had a history of index IS were extracted from the Malaysian National Neurology Registry (NNEUR) from 2009 to 2016. Recurrent IS was defined as any IS event recorded after the index IS in the NNEUR database. Multivariate logistic regression analysis was performed by using SPSS version 22. RESULTS: Ischemic heart disease (IHD) was the significant predictor of IS recurrence in non-elderly adults both with or without diabetes (adjusted odds ratio (AOR) of 3.210; 95%CI: 1.909-5.398 and 2.989; 95%CI: 1.515-5.894) respectively). Receiving antiplatelet as secondary stroke prevention (AOR: 0.194; 95%CI: 0.046-0.817) and continuation of antidiabetic medication after the index IS event (AOR: 0.510; 95%CI: 0.298-0.872) reduced the odds of IS recurrence only in non-elderly diabetic adults. Among non-elderly adults without diabetes, hyperlipidemia and every increased in 1 mmHg of systolic blood pressure significantly increased the odds of IS recurrence following the indexing event (AOR: 1.796; 95%CI: 1.058-3.051 and 1.009; 95%CI: 1.002-1.016 respectively). CONCLUSION: IHD was found as the main predictor of IS recurrence regardless of diabetes status in non-elderly adults after the index IS event. Receiving antidiabetic and antiplatelet medications upon discharge after index IS were significant predictors of recurrent IS in non-elderly diabetic adults. A proper randomized clinical trial may be required to determine the impact of secondary preventive medication on IS recurrence, especially in non-elderly adults.

Synergistic Antimicrobial Effect of a Seaweed-Probiotic Blend Against Acute Hepatopancreatic Necrosis Disease (AHPND)-Causing Vibrio parahaemolyticus.

The outbreak of acute hepatopancreatic necrosis disease (AHPND) has caused great economic losses to the shrimp culture sector. However, the use of antibiotics to fight this disease has resulted in negative impacts on human health and the environment. Thus, the use of natural alternatives to antibiotics may be a better solution. In this study, four Bacillus species obtained from the guts of shrimps (Fenneropenaeus penicillatus and Penaeus monodon) showed antimicrobial activity against the AHPND-causing Vibrio parahaemolyticus strain 3HP using the cross-streaking and agar spot methods. Two of the Bacillus isolates, B2 and BT, also showed good probiotic properties, exhibiting tolerance to bile, good adhesion to shrimp mucus, non-hemolytic, susceptibility to antibiotics and being safe towards hosts. Moreover, a seaweed-probiotic blend (a combination of Bacillus B2 and 20 mg/ml of the red seaweed Gracilaria sp.) exhibited synergistic in vitro inhibition against V. parahaemolyticus strain 3HP, with an observed inhibition zone of 5.0 mm. The broth co-culture experiment results further indicated that the seaweed-probiotic blend inhibited V. parahaemolyticus through competitive exclusion. The in vivo challenge trials also confirmed that this seaweed-probiotic blend significantly reduced the mortality of shrimps post-challenge with the AHPND-causing V. parahaemolyticus strain 3HP (p < 0.05) compared to the negative control (mortality rate = 13.88% vs 72.19%). Thus, this seaweed-probiotic blend may serve as an alternative to antibiotics in controlling the outbreak of AHPND.

Genetic, historical and linguistic perspectives on the origin of the Kelantanese Malays.

The Kelantanese Malays who resided in the remote northeastern regions of the Malay Peninsula in the Kelantan state are believed to have a unique genetic signature. The objective of this review is to analyze the populational sub-structure of the Kelantanese Malays from historical, genetic and linguistic perspectives. Historical data suggest that the Semang were composed of the Jahai, Bateq and Kensiu sub-tribes, whereas the Senoi were composed of only the Temiar sub-tribe. The Mendriq sub-tribe is believed to be the first group of aborigines to land in Kelantan. Subsequently, genetic analysis showed that the Kelantanese Malays are an independent clade at the base of the phylogenetic tree and contain genetic material similar to that of the Semang, specifically the Jahai and the Kensiu sub-tribes. The genetic data are supported by the fact that the Aslian language, a branch of the Austroasiatic languages that is widely spoken by the Semang, was potentially transmitted through agricultural activities. However, the potential limitation of this mini-review is the lack of primary reliable sources covering the historical, linguistic and genetic features of the Kelantanese Malays.

Burden of stroke in Cambodia.

In Cambodia, stroke is not ranked among the top 10 leading causes of death, but infectious disease are among the top three leading causes of death. This finding could be attributed to a lack of awareness among Cambodians of the signs and symptoms of stroke or to poor reporting, incomplete data, lack of neurologists and neurosurgeons, or low accessibility to the hospitals. The only study of stroke in Cambodia is the Prevalence of Non-Communicable Disease Risk Factors in Cambodia survey, which identified several stroke-related risk factors in the population. Tobacco chewing or smoking is the main risk factor for stroke in Cambodia. Traditional therapies, such as oyt pleung (moxibustion) and jup (cupping), are widely practiced for stroke rehabilitation. In Cambodia, there are few neurologists and few important equipment, such as magnetic resonance imaging machines and computed tomography scanners. The Cambodian government should cooperate with the World Health Organization and the United Nations Children's Fund to attract foreign expertise and technologies to treat stroke patients.

The burden of stroke in the Lao People's Democratic Republic.

In the Lao People's Democratic Republic (Laos), stroke is ranked as the third leading cause of death, with a 9·01% mortality rate. To date, neither the prevalence nor the incidence of stroke has been recorded in Laos. This omission may be attributed to a lack of awareness among Laotians of the signs and symptoms of stroke, incomplete data, or insufficient database recording. The only risk factor for stroke that has been studied extensively is cigarette smoking; studies have found that smokers have twice the risk of stroke. Unfortunately, smoking is increasing among youths, adults, and even healthcare professionals. The Southeast Asia Tobacco Control Alliance stated that 42% of hospitalized stroke patients are smokers. Laos is one of the least developed countries in the world, and the country has only one fully trained neurologist for the growing number of stroke cases. The Laos government should seek help from international bodies, such as the World Health Organization, to monitor and rehabilitate stroke patients and prevent stroke occurrence and recurrence.

Burden of stroke in the Philippines.

Based on disability-adjusted life-years, stroke is the second leading cause of death and among the top five diseases with the greatest burden. Although two community-based studies have been conducted to determine the prevalence of stroke in the Philippines, the incidence has not been nationally recorded to date. The prevalence ranged from 1·9% to 6·59%, and 'Wiihabilitation', a rehabilitation stroke therapy, is widely practiced. A clinical trial for stroke rehabilitation using the Chinese Medicine NeuroAid®, which consists of several herbs, is ongoing in many hospitals across the Philippines. Due to their ready availability, phytomedicines are widely used, especially in the rural areas, for the treatment of hypertension, diabetes mellitus, and hypercholesterolemia, which are predisposing factors for stroke in the Philippines. Due to the increasing number of stroke cases annually, the government of the Philippines should emphasize primary and secondary prevention strategies.

Burden of stroke in Bangladesh.

Stroke is the third leading cause of death in Bangladesh. The World Health Organization ranks Bangladesh's mortality rate due to stroke as number 84 in the world. The reported prevalence of stroke in Bangladesh is 0.3%, although no data on stroke incidence have been recorded. Hospital-based studies conducted in past decades have indicated that hypertension is the main cause of ischaemic and haemorrhagic stroke in Bangladesh. The high number of disability-adjusted life-years lost due to stroke (485 per 10,000 people) show that stroke severely impacts Bangladesh's economy. Although two non-governmental organizations, BRAC and the Centre for the Rehabilitation of the Paralysed, are actively involved in primary stroke prevention strategies, the Bangladeshi government needs to emphasize healthcare development to cope with the increasing population density and to reduce stroke occurrence.

Burden of stroke in Malaysia.

Stroke is one of the top five leading causes of death and one of the top 10 causes for hospitalization in Malaysia. Stroke is also in the top five diseases with the greatest burden of disease, based on disability-adjusted life years. However, prospective studies on stroke in Malaysia are limited. To date, neither the prevalence of stroke nor its incidence nationally has been recorded. Hypertension is the major risk factor for stroke. The mean age of stroke patients in Malaysia is between 54.5 and 62.6 years. Traditional medicine is commonly practiced. With the increasing number of stroke cases annually, more government and nongovernment organizations should be involved in primary and secondary prevention strategies.

Burden of stroke in Nepal.

Based on disability-adjusted life years, stroke is one of the major causes of death and is among the top five diseases in Nepal. Despite this fact, information on the prevalence, morbidity, and mortality of stroke in Nepal is limited to urban areas, with no official reports published on the epidemiology of stroke throughout the country. The mean age of stroke patients in Nepal is between 59 and 62 years, with males affected more frequently. Hypertension, cigarette smoking, alcohol consumption, and diabetes are the main predisposing factors for stroke, and ischemic stroke is more common (63%) than hemorrhagic stroke (37%). Because of a lack of facilities and specialists, most stroke patients, especially in the rural areas, seek traditional healers to treat their conditions. More governmental and non-governmental organizations should be involved in improving facilities and implementing prevention strategies.