An Overview of Crosslinked Enzyme Aggregates: Concept of Development and Trends of Applications.

Enzymes are commonly used as biocatalysts for various biological and chemical processes in industrial applications. However, their limited operational stability, catalytic efficiency, poor reusability, and high-cost hamper further industrial usage. Thus, crosslinked enzyme aggregates (CLEAs) are developed as a better enzyme immobilization tool to extend the enzymes' operational stability. This immobilization method is appealing because it is simpler due to the absence of ballast and permits the collective use of crude enzyme cocktails. CLEAs, so far, have been successfully developed using a variety of enzymes, viz., hydrolases, proteases, amidases, lipases, esterases, and oxidoreductase. Recent years have seen the emergence of novel strategies for preparing better CLEAs, which include the combi- and multi-CLEAs, magnetics CLEAs, and porous CLEAs for various industrial applications, viz., laundry detergents, organic synthesis, food industries, pharmaceutical applications, oils, and biodiesel production. To better understand the different strategies for CLEAs' development, this review explores these strategies and highlights the relevant concerns in designing innovative CLEAs. This article also details the challenges faced during CLEAs preparation and solutions for overcoming them. Finally, the trending strategies to improve the preparation of CLEAs alongside their industrial application trends are also discussed.

Stroke Riskometer Application (SRA™) influence on lifestyle changes of home bound familial Malaysian stroke caregivers: a randomised controlled trial in a primary care based longer term stroke care facility.

BACKGROUND: In countries where access to Specialist stroke care services are limited, primary care physicians often manage stroke patients and the caregiving family members. This study aimed to evaluate the impact of Stroke Riskometer Application (SRA™) on promoting healthier lifestyles among familial stroke caregivers for primary prevention. METHODS: A parallel, open-label, 2-arm prospective, pilot randomised controlled trial was conducted at a long-term stroke service at a university based primary care clinic. All stroke caregivers aged ≥ 18 years, proficient in English or Malay and smartphone operation were invited. From 147 eligible caregivers, 76 participants were randomised to either SRA™ intervention or conventional care group (CCG) after receiving standard health counselling. The intervention group had additional SRA™ installed on their smartphones, which enabled self-monitoring of modifiable and non-modifiable stroke risk factors. The Stroke Riskometer app (SRATM) and Life's Simple 7 (LS7) questionnaires assessed stroke risk and lifestyle practices. Changes in clinical profile, lifestyle practices and calculated stroke risk were analysed at baseline and 3 months. The trial was registered in the Australia-New Zealand Clinical Trial Registry, ACTRN12618002050235. RESULTS: The demographic and clinical characteristics of the intervention and control group study participants were comparable. Better improvement in LS7 scores were noted in the SRA™ arm compared to CCG at 3 months: Median difference (95% CI) = 0.88 (1.68-0.08), p = 0.03. However, both groups did not show significant changes in median stroke risk and relative risk scores at 5-, 10-years (Stroke risk 5-years: Median difference (95% CI) = 0.53 (0.15-1.21), p = 0.13, 10-years: Median difference (95% CI) = 0.81 (0.53-2.15), p = 0.23; Relative risk 5-years: Median difference (95% CI) = 0.84 (0.29-1.97), p = 0.14, Relative risk 10-years: Median difference (95% CI) = 0.58 (0.36-1.52), p = 0.23). CONCLUSION: SRA™ is a useful tool for familial stroke caregivers to make lifestyle changes, although it did not reduce personal or relative stroke risk after 3 months usage. TRIAL REGISTRATION: No: ACTRN12618002050235 (Registration Date: 21st December 2018).

Anxiety among hospitalized COVID-19 patients: a case-control study from a tertiary teaching hospital in Malaysia.

Introduction: Anxiety has been increasingly recognized as part of the psychosocial health issues in COVID-19 patients. However, the impact of this topic may be underestimated in low- and middle-income countries. This study aimed to estimate the prevalence of and risk factors of anxiety in COVID-19 patients compared to controls in a local tertiary teaching hospital in Malaysia. Methods: In this case-control study, we analyzed data on adult patients aged 18 years and above hospitalized for COVID-19 infection with matched hospitalized controls. The demographic, clinical data and anxiety measures using the Generalized Anxiety Disorder-7 questionnaire were analyzed using univariate and multivariate analysis. Results: 86.6% in the COVID-19 group had anxiety, significantly higher than 13.4% in the control group (p = 0.001). The COVID-19 group was significantly associated with the GAD-7 severity (p = 0.001). The number of COVID-19 patients in the mild, moderate, and severe anxiety groups was 48 (84.2%), 37 (86%), and 18 (94.7%), respectively. Multiple logistic regression showed significant predictors for anxiety, including COVID-19 diagnosis and neurological symptoms. Anxiety was found 36.92 times higher in the patients with COVID-19 compared to those without COVID-19 (OR 36.92;95% CI 17.09, 79.78, p = 0.001). Patients with neurological symptoms were at risk of having anxiety (OR 2.94; 95% CI 1.03, 8.41, p = 0.044). Discussion: COVID-19 patients experience a significant disruption in psychosocial functioning due to hospitalization. The burden of anxiety is notably high, compounded by a diagnosis of COVID-19 itself and neurological symptomatology. Early psychiatric referrals are warranted for patients at risk of developing anxiety symptoms.

Sixteen-Syndrome in a Young Patient with Systemic Lupus Erythematosus.

Sixteen syndrome is rare variant of one and a half syndrome resulting from lesion affecting bilateral dorsal pontine structures. This report describes a case of 16 syndrome in systemic lupus erythematosus (SLE). A 28 year old woman with underlying lupus was presented with sudden left side body weakness and diplopia. Examination showed features of 16 syndrome with one and a half syndrome, facial diplegia and left hemiparesis. Neuroimaging revealed an acute infarct of bilateral dorsal pons. The patient was placed on antiplatelet therapy. However, she developed left leg deep vein thrombosis and pulmonary embolism after one week. She was then given subcutaneous low molecular weight heparin, followed by warfarin and cycles of cyclophosphamide. Her hemiparesis, ocular symptoms, and facial diplegia improved after one year. SLE increases the risk of stroke and thrombotic events in a young patient. Achieving disease remission is important to prevent stroke in SLE patients.

Fabrication, characterization and application of electrospun polysulfone membrane for phosphate ion removal in real samples.

Due to simplicity and flexibility, electrospinning technique can produce many types of fibers at nanoscale via different operational parameters for various applications including industrial wastewater treatment, air filtration and so on. Nonetheless, the study on the electrospinning operational parameter is very limited and many researchers are still using trial-and-error method to design their targeted fiber. In this study, a series of electrospun polysulfone (PSF; 20% w/v) nanofibrous membranes that made up from different ratios of dimethylformamide (DMF) and tetrahydrofuran (THF) mixtures in order to achieve different dielectric constant (ϵ) of solvent system. The fabricated PSF nanofibers were characterized by field emission scanning electron microscopy (FESEM), tensile strength tester and contact angle measurement. The THF-DMF binary solvent system with ϵ = 16.33 to 27.97 produced a smooth surface electrospun PSF nanofibers, while THF mono solvent system (ϵ = 7.60) and DMF mono solvent system (ϵ = 36.70) produced a rough and porous surface electrospun PSF nanofibers. This finding is contradicted with the common finding in which only a binary solvent is able to fabricate a rough or grooved surface electrospun nanofibers. In addition, the dielectric constant can be another key factor, besides boiling point and solubility of binary solvent system, that induces phase separation in the polymeric solution jet and eventually fabricate non-smooth surface electrospun nanofibers. The fabricated electrospun PSF nanofibrous membranes showed high efficiency in phosphate removal.

Movement Disorders Resulting From Bilateral Basal Ganglia Lesions in End-Stage Kidney Disease: A Systematic Review.

OBJECTIVE: The basal ganglia (BG) are susceptible to fluctuations in blood urea levels, sometimes resulting in movement disorders. We described patients with end-stage kidney disease (ESKD) presenting with movement disorders associated with bilateral BG lesions on imaging. METHODS: We report four patients and systematically reviewed all published cases of ESKD presenting with movement disorders and bilateral BG lesions (EBSCOhost and Ovid). RESULTS: Of the 72 patients identified, 55 (76.4%) were on regular dialysis. Parkinsonism was the most common movement disorder (n = 39; 54.2%), followed by chorea (n = 24; 33.3%). Diabetes mellitus (n = 51; 70.8%) and hypertension (n = 16; 22.2%) were the most common risk factors. Forty-three (59.7%) were of Asian ethnicity. Complete clinical resolution was reported in 17 (30.9%) patients, while 38 (69.1%) had incomplete clinical resolution with relapse. Complete radiological resolution occurred in 14 (34.1%) patients. CONCLUSION: Movement disorders associated with BG lesions should be recognized as a rare and potentially reversible metabolic movement disorder in patients with ESKD.

Adverse environmental effects of disposable face masks due to the excess usage.

The widespread use of disposable face masks as a preventative strategy to address transmission of the SARS-CoV-2 virus has been a key environmental concern since the pandemic began. This has led to an unprecedented new form of contamination from improperly disposed masks, which liberates significant amounts of heavy metals and toxic chemicals in addition to volatile organic compounds (VOCs). Therefore, this study monitored the liberation of heavy metals, VOCs, and microfibers from submerged disposable face masks at different pH (4, 7 and 12), to simulate distinct environmental conditions. Lead (3.238% ppb), cadmium (0.672 ppb) and chromium (0.786 ppb) were found in the analyzed leachates. By pyrolysis, 2,4-dimethylhept-1-ene and 4-methylheptane were identified as the VOCs produced by the samples. The chemically degraded morphology in the FESEM images provided further evidence that toxic heavy metals and volatile organic compounds had been leached from the submerged face masks, with greater degradation observed in samples submerged at pH 7 and higher. The results are seen to communicate the comparable danger of passively degrading disposable face masks and the release of micro- or nanofibers into the marine environment. The toxicity of certain heavy metals and chemicals released from discarded face masks warrants better, more robust manufacturing protocols and increased public awareness for responsible disposal to reduce the adverse impact on ecology and human health.

Regional and national differences in stroke thrombolysis use and disparities in pricing, treatment availability, and coverage.

BACKGROUND: Major disparities have been reported in recombinant tissue plasminogen activator (rtPA) availability among countries of different socioeconomic status. AIMS: To characterize variability of rtPA price, its availability, and its association with and impact on each country's health expenditure (HE) resources. METHODS: We conducted a global survey to obtain information on rtPA price (50 mg vial, 2020 US Dollars) and availability. Country-specific data, including low, lower middle (LMIC), upper middle (UMIC), and high-income country (HIC) classifications, and gross domestic product (GDP) and HE, both nominally and adjusted for purchasing power parity (PPP), were obtained from World Bank Open Data. To assess the impact of rtPA cost, we computed the rtPA price as percentage of per capita GDP and HE and examined its association with the country income classification. RESULTS: rtPA is approved and available in 109 countries. We received surveys from 59 countries: 27 (46%) HIC, 20 (34%) UMIC, and 12 (20%) LMIC. Although HIC have significantly higher per capita GDP and HE compared to UMIC and LMIC (p < 0.0001), the median price of rtPA is non-significantly higher in LMICs (USD 755, interquartile range, IQR (575-1300)) compared to UMICs (USD 544, IQR (400-815)) and HICs (USD 600, IQR (526-1000)). In LMIC, rtPA cost accounts for 217.4% (IQR, 27.1-340.6%) of PPP-adjusted per capita HE, compared to 17.6% (IQR (11.2-28.7%), p < 0.0001) for HICs. CONCLUSION: We documented significant variability in rtPA availability and price among countries. Relative costs are higher in lower income countries, exceeding the available HE. Concerted efforts to improve rtPA affordability in low-income settings are necessary.

Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial: Rationale, design and progress.

BACKGROUND: Patients who suffer intracerebral hemorrhage (ICH) are at very high risk of recurrent ICH and other serious cardiovascular events. A single-pill combination (SPC) of blood pressure (BP) lowering drugs offers a potentially powerful but simple strategy to optimize secondary prevention. OBJECTIVES: The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC "Triple Pill," three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH. DESIGN: An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130-160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety. RESULTS: Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024. CONCLUSION: Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality / 대한뇌졸중학회지

Background@#and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. @*Methods@#We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). @*Results@#There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. @*Conclusions@#During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Malaysia Stroke Council guide on acute stroke care service during COVID-19 Pandemic

@#On the 18th of March 2020, the Malaysia government declared a movement control order (MCO) due to the unprecedented COVID-19 pandemic. Although the majority of patients presented with respiratory-related symptoms, COVID-19 patients may present atypically with neurological manifestations and may even have an increased risk of stroke. The Malaysia Stroke Council is concerned regarding the level of care given to stroke patients during this pandemic. During the recent National Stroke Workflow Steering Committee meeting, a guide was made based on the currently available evidences to assist Malaysian physicians providing acute stroke care in the hospital setting in order to provide the best stroke care while maintaining their own safety. The guide comprises of prehospital stroke awareness, hyperacute stroke care, stroke care unit and intensive care unit admission, post-stroke rehabilitation and secondary prevention practice. We urge continuous initiative to provide the best stroke care possible and ensure adequate safety for both patients and the stroke care team.

Concurrent stroke and ST-elevation myocardial infarction: Is it a contraindication for intravenous tenecteplase?

@#Acute ischemic stroke (AIS) and acute ST-elevation myocardial infarction (STEMI) are leading causes of mortality worldwide. Concurrent AIS presentation with STEMI is rare and potentially fatal. Most importantly to date many centres in Malaysia are still not aware on how to treat this condition. We report a case of AIS, which was treated with intravenous tenecteplase (TNK) according to ischemic stroke dosage and lead to improvement of neurological deficit.

Incidence and risk factors of delirium in patients with acute ischaemic stroke

@#Background & Objectives: The reported incidence of post-stroke delirium varies substantially in current medical literature. The impact of delirium on mortality and morbidity is significant and there is need for sustained research on the topic. We aimed to determine the incidence, risk factors and outcome of delirium in acute ischaemic stroke. Methods: We conducted a cross-sectional observational study on consecutive patients with ischaemic stroke. The Confusion Assessment Method was used to diagnose delirium within seven days of stroke onset. Results: Two hundred and eighty patients were recruited (mean age 63.6 years) and 36 (12.9%) developed delirium. After adjustments for covariates, age >65 years (odds ratio, OR 5.2; 95% confidence interval 1.6-17.5); pre-existing dementia (6.5; 1.1-38.2); TACI (7.2; 1.5-35); and a National Institute of Health Stroke Scale of ≥10 (6.8; 1.7-26.4), were independently associated with a risk of developing delirium. Lacunar infarcts were not associated with delirium (0.07; 0.03-0.16). The majority of patients with delirium were cared for in a dedicated stroke unit but this proportion was not significant compared to those without delirium (69.4% vs 58.2%, p=0.20). Delirious patients had significantly higher in-patient mortality (8.3% vs 0%, p=0.002) and longer length of hospital stay (6.94 vs 3.98 days, p< 0.001). Conclusions: One in 8 patients with ischaemic stroke in our centre developed delirium. Older age, pre-existing dementia and severe stroke were independent predictors of delirium. Patients with lacunar infarcts did not develop delirium as often as those with other stroke types. Delirium significantly increased in-patient mortality and length of hospital stay.

A validation study of the Bahasa Malaysia version of the National Institute of Health Stroke Scale

@#Background & Objectives: The National Institute of Health Stroke Scale (NIHSS) provides a valid and quick assessment of stroke severity in hyperacute stroke management. Stroke patients who are eligible for reperfusion therapy require prompt assessment. There is no validated Bahasa Malaysia (BM) version of the NIHSS that allows easier assessment by BM-speaking health professionals. This study aimed to translate and validate a BM version of the NIHSS. Methods: The English NIHSS was translated to BM, then back translated to ensure linguistic accuracy. We also adapted the language assessment of the NIHSS to be more culturally appropriate. Training and certification videos were downloaded from the NIH website and dubbed into BM. We determined intra-class correlation and unweighted kappa as the best measure of reliability. Median scores were used in the analysis for language items. Results: One hundred and one raters participated in the test-retest reliability study. Agreement between the original NIHSS and our translated version of the BM-NIHSS was good (ICC = 0.738, 95% CI: 0.611 to 0.823). Fair to moderate agreement was found on item-by-item analysis (unweighted κ=0.20-0.50) despite high observed agreement. Fifty patients participated in the language assessment arm. Scores were better in BM for reading, naming objects and repetition (Mdn = 100, p < 0.001). There was no difference in the median scores for the description component. Conclusions: The BM-NIHSS is a valid translation of the NIHSS, and may be used in clinical practice by BM-speaking healthcare professionals.

Rituximab-induced lung disease

Pulmonary toxicity is a rare complication of Rituximab therapy. Although Rituximab is relatively safe and can be administered in an outpatient setting, Rituximab-associated lung disease has been reported and may cause mortality despite early detection. Typically the pulmonary toxicity occurs at around the fourth cycle of Rituximab. High index of suspicion is crucial and other concurrent pathology such as infective causes should be excluded. Radiological imaging and histological confirmation should be obtained and early treatment with corticosteroid should be initiated. Patients should receive counselling regarding respiratory symptoms and possible pulmonary toxicity.

Awareness of Glycosylated Haemoglobin (HbA1c) Among Type 2 Diabetes Mellitus Patients in Hospital Putrajaya

The glycosylated haemoglobin (HbA1c) test is the most widely accepted laboratory test for evaluating long term glycaemic control. Patient’s understanding of HbA1c can lead to better glycaemic control. This study is aimed to determine the awareness and level of understanding of HbA1c among type 2 DM patients and its association with glycaemic control. A cross-sectional descriptive study among Type 2 DM patients undergoing routine follow up in an endocrine clinic of a tertiary centre in Malaysia. Patients were invited to answer a validated questionnaire which assessed their awareness and understanding of HbA1c. Their last HbA1c results were retrieved from the laboratory information system. A total of 92 participants were recruited. Fifty-six (60.9%) were aware of the term HbA1c. Fifty percent were categorised as having good HbA1c understanding, with age, monthly income and level of education being the factors associated with understanding. No significant association was noted between HbA1c understanding and glycaemic control, although more patients with good HbA1c understanding had achieved the target glycaemic control compared to those with poor understanding. The level of HbA1c awareness and understanding was acceptable. Factors associated with understanding were age, income and level of education. Continuing efforts however, must be made to improve patients understanding of their disease and clinical disease biomarkers.