Blue carbon sink capacity of mangroves determined by leaves and their associated microbiome.

Mangroves play a globally significant role in carbon capture and storage, known as blue carbon ecosystems. Yet, there are fundamental biogeochemical processes of mangrove blue carbon formation that are inadequately understood, such as the mechanisms by which mangrove afforestation regulates the microbial-driven transfer of carbon from leaf to below-ground blue carbon pool. In this study, we addressed this knowledge gap by investigating: (1) the mangrove leaf characteristics using state-of-the-art FT-ICR-MS; (2) the microbial biomass and their transformation patterns of assimilated plant-carbon; and (3) the degradation potentials of plant-derived carbon in soils of an introduced (Sonneratia apetala) and a native mangrove (Kandelia obovata). We found that biogeochemical cycling took entirely different pathways for S. apetala and K. obovata. Blue carbon accumulation and the proportion of plant-carbon for native mangroves were high, with microbes (dominated by K-strategists) allocating the assimilated-carbon to starch and sucrose metabolism. Conversely, microbes with S. apetala adopted an r-strategy and increased protein- and nucleotide-biosynthetic potentials. These divergent biogeochemical pathways were related to leaf characteristics, with S. apetala leaves characterized by lower molecular-weight, C:N ratio, and lignin content than K. obovata. Moreover, anaerobic-degradation potentials for lignin were high in old-aged soils, but the overall degradation potentials of plant carbon were age-independent, explaining that S. apetala age had no significant influences on the contribution of plant-carbon to blue carbon. We propose that for introduced mangroves, newly fallen leaves release nutrient-rich organic matter that favors growth of r-strategists, which rapidly consume carbon to fuel growth, increasing the proportion of microbial-carbon to blue carbon. In contrast, lignin-rich native mangrove leaves shape K-strategist-dominated microbial communities, which grow slowly and store assimilated-carbon in cells, ultimately promoting the contribution of plant-carbon to the remarkable accumulation of blue carbon. Our study provides new insights into the molecular mechanisms of microbial community responses during reforestation in mangrove ecosystems.

Association study of MCCC1/LAMP3 and DGKQ variants with Parkinson's disease in patients of Malay ancestry.

BACKGROUND: Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (MCCC1)/lysosome-associated membrane protein 3 (LAMP3) loci (rs10513789, rs12637471, rs12493050) reduce the risk of Parkinson's disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (DGKQ) gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry. METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays. RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis. CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.

SLC17A3 rs9379800 and Ischemic Stroke Susceptibility at the Northern Region of Malaysia.

OBJECTIVES: The relationships of Paired Like Homeodomain 2 (PITX2), Ninjurin 2 (NINJ2), TWIST-Related Protein 1 (TWIST1), Ras Interacting Protein 1 (Rasip1), Solute Carrier Family 17 Member 3 (SLC17A3), Methylmalonyl Co-A Mutase (MUT) and Fer3 Like BHLH Transcription Factor (FERD3L) polymorphisms and gene expression with ischemic stroke have yet to be determined in Malaysia. Hence, this study aimed to explore the associations of single nucleotide polymorphisms (SNPs) and gene expression with ischemic stroke risk among population who resided at the Northern region of Malaysia. MATERIALS AND METHODS: Study subjects including 216 ischemic stroke patients and 203 healthy controls were recruited upon obtaining ethical clearance. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism assays. Gene expression levels were quantified by real-time polymerase chain reaction assays. Statistical and genetic analyses were conducted with SPSS version 22.2, PLINK version 1.07 and multifactor dimensionality reduction software. RESULTS: Study subjects with G allele, CG or GG genotypes of SLC17A3 rs9379800 demonstrated increased risk of ischemic stroke with the odds ratios ranging from 1.76-fold to 3.14-fold (p<0.05). When stratified study subjects according to the ethnicity, SLC17A3 rs9379800 G allele and CG genotype contributed to 2.14- and 2.96-fold of ischemic stroke risk among Malay population significantly, in the multivariate analysis (p<0.05). However, no significant associations were observed for PITX2, NINJ2, TWIST1, Rasip1, and MUT polymorphisms with ischemic stroke risk in the multivariate analysis for the pooled cases and controls as well as when stratified them according to the ethnicity. Lower mRNA expression levels of Rasip1, SLC17A3, MUT and FERD3L were observed among cases (p<0.05). After FDR adjustment, the mRNA level of SLC17A3 remained significantly associated with ischemic stroke among Malay population (q=0.034). CONCLUSION: In conclusion, this study suggests that SLC17A3 rs9379800 polymorphism and its gene expression contribute to significant ischemic stroke risk among Malaysian population, particularly the Malay who resided at the Northern Region of the country. Our findings can provide useful information for the future diagnosis, management and treatment of ischemic stroke patients.

Evaluation of the tolerability and effectiveness of Tenecteplase in patients with ST-Segment-Elevation Myocardial Infarction in a Secondary Hospital in Malaysia: A Retrospective Case Series.

BACKGROUND: In Malaysia, knowledge regarding the clinical efficacy of tenecteplase (TNK), a fibrin-specific tissue-plasminogen activator, is limited. OBJECTIVES: To evaluate the effectiveness and tolerability of TNK in patients with ST-segment-elevation myocardial infarction in a secondary referral Malaysian hospital. METHODS: This was a single-center retrospective case series based on the medical records of patients with ST-segment-elevation myocardial infarction admitted to the cardiac care unit between January 2016 and May 2019. Data regarding the mortality status and date of death were collected from the database of the National Registration Department of Malaysia. RESULTS: Data for 30 patients with ST-segment-elevation myocardial infarction, who received weight-adjusted doses of TNK, were analyzed. The patients' mean (SD) age was 62 (14) years, and 77% were men. The median time to treatment was 265 minutes (interquartile range = 228-660 minutes), and the clinical success rate of thrombolysis was 79%. The overall all-cause in-hospital mortality rate was 33%. The 1-year survival rates were higher in patients achieving a time to treatment ≤360 minutes (P = 0.03), with a trend toward greater survival in this group at 30 days. Similarly, a trend toward lower in-hospital all-cause mortality was observed in this group (21% vs 50%; P = 0.12). Only 1 patient (3%), who had a HAS-BLED score based on hypertension, abnormal liver/renal function, stroke history, bleeding history or predisposition, labile international normalized ratio, old age, drug/alcohol use of 5, developed major bleeding that required blood transfusion. No cases of ischemic stroke, nonmajor bleeding, in-hospital reinfarction, or TNK-induced allergic reaction were identified. CONCLUSIONS: We hypothesized that the mortality-related outcomes of TNK in patients with ST-segment-elevation myocardial infarction were influenced by TTT, with TTT ≤360 minutes indicating a better prognosis than TTT >360 minutes. TNK-induced bleeding-related complications were minimal in low-risk patients. Further local studies are needed to compare TNK's profile with that of streptokinase, which is a common agent currently used in clinical practice in Malaysian public hospitals. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

Association of NOTCH3 Gene Polymorphisms with Ischemic Stroke and its Subtypes: A Meta-Analysis.

Background and objectives: NOTCH3 gene variations play a significant role in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, the role of NOTCH3 gene polymorphisms in the risk of ischemic stroke, and its subtypes such as atherothrombotic or lacunar strokes, remains unclear. Aims: Hence, we carried out a meta-analysis to examine whether the NOTCH3 rs1043994, rs1044009 and rs3815188 polymorphisms are associated with ischemic stroke and its major subtypes. Materials and Methods: All relevant studies were systematically screened and meta-analyzed using Review Manager (Revman) version 5.3. The strength of the association between NOTCH3 polymorphisms and ischemic stroke risk and its subtypes were measured as odds ratios and 95% confidence intervals, under different genetic models. Results: A total of ten studies were identified, five of which considered NOTCH3 rs1043994 (2077 cases/2147 controls), five of which considered NOTCH3 rs1044009 (2315 cases/3053 controls), and nine of which considered NOTCH3 rs3815188 (2819 cases/2769 controls). These studies were meta-analyzed for their association with ischemic stroke risk. Four studies (874 cases/2002 controls) of the NOTCH3 rs3815188 polymorphism and three studies of the NOTCH3 rs1043994 (643 cases/1552 controls) polymorphism were meta-analyzed for lacunar stroke risk. Three studies (1013 cases/1972 controls) of the NOTCH3 rs3815188 polymorphism were meta-analyzed for atherothrombotic stroke risk. The meta-analysis results showed a lack of association between all of the studied polymorphisms and the risk of ischemic stroke and its major subtypes (i.e., atherothrombotic and lacunar). Conclusions: NOTCH3 polymorphisms are not significantly associated with the risk of ischemic stroke and its subtypes (p < 0.05).

Meta-Analysis of Factor V, Factor VII, Factor XII, and Factor XIII-A Gene Polymorphisms and Ischemic Stroke.

Numerous studies examined the association between factors FV, FVII, FXII, and FXIII-A gene polymorphisms and ischemic stroke, but conclusive evidence is yet to be obtained. Thus, this meta-analysis aimed to investigate the novel association of FV rs1800595, FVII rs5742910, FXII rs1801020, and FXIII-A rs5982 and rs3024477 polymorphisms with ischemic stroke risk. A systematic review was performed on articles retrieved before June 2018. Relevant data were extracted from eligible studies and meta-analyzed using RevMan version 5.3. The strength of association between studied polymorphisms and ischemic stroke risk was calculated as odds ratios and 95% confidence intervals, by applying both fixed- and random-effect models. A total of 25 studies involving 6100 ischemic stroke patients and 9249 healthy controls were incorporated in the final meta-analysis model. Specifically, rs1800595, rs5742910, rs1801020, rs5982, and rs3024477 consisted of 673, 3668, 922, 433, and 404 cases, as well as 995, 4331, 1285, 1321, and 1317 controls, respectively. The pooled analysis indicated that there was no significant association of FV rs1800595, FVII rs5742910, FXII rs1801020, FXIII-A rs5982, and FXIII-A rs3024477 polymorphisms with ischemic stroke risk, under any genetic models (dominant, recessive, over-dominant, and allelic). The present meta-analysis concluded that FV rs1800595, FVII rs5742910, FXII rs1801020, and FXIII-A rs5982 and rs3024477 polymorphisms are not associated with ischemic stroke risk.

Polymorphisms of MTHFR, eNOS, ACE, AGT, ApoE, PON1, PDE4D, and Ischemic Stroke: Meta-Analysis.

INTRODUCTION: The association between ischemic stroke and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR; 677C>T and 1298A>C), endothelial nitric oxide synthase (eNOS; -786T>C, +894G>T, and variable number tandem repeat [VNTR]), phosphodiesterase 4D (PDE4D; SNPs 83 and 87), angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) 235M>T, paraoxonase 1 (PON1) 192Q>R, and apolipoprotein E (ApoE) ε2ε3ε4 remains inconclusive. Therefore, this updated meta-analysis aimed to clarify the presumed influence of genetic polymorphisms on ischemic stroke by meta-analyzing the comprehensive coverage of all individual association studies. METHODS: All case-control studies published in different languages such as English, Japanese, Korean, Spanish, Chinese, Hungarian, Ukrainian, or Russian were identified from databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated via fixed- and random-effect models. Sensitivity analysis, heterogeneity test, Hardy Weinberg Equilibrium, and Egger's regression analyses were performed in this study. RESULTS: A total of 490 case-control studies with 138,592 cases and 159,314 controls were included in this meta-analysis. Pooled ORs from all the genetic models indicated that MTHFR 677TT and 1298CC, eNOS +894TT and VNTR, PDE4D SNP 83, ACE DD, AGT 235TT, PON1 192RR, and ApoE ε4 polymorphisms were increasing the risks of ischemic stroke. Nevertheless, PDE4D SNP 87 and eNOS -786T>C polymorphisms are not associated with ischemic stroke risks. CONCLUSIONS: Hence, the evidence from this meta-analysis concluded that MTHFR (677C>T and 1298A>C), eNOS (+894G>T and VNTR), PDE4D SNP 83, ACE I/D, AGT 235M>T, PON1 192Q>R, and ApoE ε2ε3ε4 polymorphisms predispose individuals to ischemic stroke.

Conversion and characterization of activated carbon fiber derived from palm empty fruit bunch waste and its kinetic study on urea adsorption.

Urea removal is an important process in household wastewater purification and hemodialysis treatment. The efficiency of the urea removal can be improved by utilizing activated carbon fiber (ACF) for effective urea adsorption. In this study, ACF was prepared from oil palm empty fruit bunch (EFB) fiber via physicochemical activation using sulfuric acid as an activating reagent. Based on the FESEM result, ACF obtained after the carbonization and activation processes demonstrated uniform macropores with thick channel wall. ACF was found better prepared in 1.5:1 acid-to-EFB fiber ratio; where the pore size of ACF was analyzed as 1.2 nm in diameter with a predominant micropore volume of 0.39 cm3 g-1 and a BET surface area of 869 m2 g-1. The reaction kinetics of urea adsorption by the ACF was found to follow a pseudo-second order kinetic model. The equilibrium amount of urea adsorbed on ACF decreased from 877.907 to 134.098 mg g-1 as the acid-to-fiber ratio increased from 0.75 to 4. During the adsorption process, the hydroxyl (OH) groups on ACF surface were ionized and became electronegatively charged due to the weak alkalinity of urea solution, causing ionic repulsion towards partially anionic urea. The ionic repulsion force between the electronegatively charged ACF surface and urea molecules became stronger when more OH functional groups appeared on ACF prepared at higher acid impregnation ratio. The results implied that EFB fiber based ACF can be used as an efficient adsorbent for the urea removal process.

LEPTOSPIROSIS INCIDENCE AND MORTALITY IN MALAYSIA.

Leptospirosis is endemic in Southeast Asia, Central and South America, the Caribbean, and Oceania. Malaysia was categorized as a probable endemic country without any available data. Thus, this study was conducted to determine incidence, case fatality rate and mortality rate of leptospirosis. Leptospirosis is a notifiable disease in Malaysia since 2010 whereby probable or confirmed cases must be notified to relevant health district office. There were 3,665 and 4,457 probable and laboratory confirmed leptospirosis cases notified in 2012 and 2013, respectively. In the 2-year period, the most common age group of patients was 19 years old or less (23.3%) with male:female ratio of 2.61:1. Students consisted about 16.9% of patients, followed by agriculture-based or plantation workers (14.7%). Overall age-standardized incidence rate of leptospirosis in Malaysia for 2012 and 2013 was 29.02 per 100,000. Overall case fatality rate was 1.47% for 2-year period and overall age-standardized mortality rate was 0.45 per 100,000. Leptospirosis is an emerging public health concern in Malaysia and may pose a significant health impact and burden to the nation in the coming years if not well controlled.

Highly hydrophilic and nonionic poly(2-vinyloxazoline)-grafted silica: a novel organic phase for high-selectivity hydrophilic interaction chromatography.

A new hydrophilic and nonionic poly(2-vinyloxazoline)-grafted silica (Sil-VOX(n)) phase was synthesized and applied for the separation of nucleosides and nucleobases in hydrophilic interaction chromatography (HILIC). Polymerization and immobilization onto silica were confirmed by using characterization techniques including (1)H NMR spectroscopy, elemental analysis, and diffuse reflectance infrared Fourier transform spectroscopy. The hydrophilicity or wettability of Sil-VOX(n) was observed by measuring the contact angle (59.9°). The chromatographic results were compared with those obtained with a conventional HILIC silica column. The Sil-VOX(n) phase showed much better separation of polar test analytes than the silica column, and the elution order was different. Differences in selectivity between these two columns indicate that the stationary phase cannot function merely as an inert support for a water layer into which the solutes are partitioned from the bulk mobile phase. To elucidate the interaction mechanism, the separation of dihydroxybenzene isomers was performed on both columns in normal-phase liquid chromatography. Sil-VOX(n) was very sensitive to the dipole moments of the positional isomers of polycyclic aromatic compounds in normal-phase liquid chromatography. The interaction mechanism for Sil-VOX(n) in HILIC separation is also described.

Worry about performance: a unique dimension of caregiver burden.

BACKGROUND: Recent studies that describe the multidimensionality of the Zarit Burden Interview (ZBI) challenge the traditional dual-factor paradigm of personal and role strains (Whitlatch et al., 1991). These studies consistently reported a distinct dimension of worry about caregiver performance (WaP) comprising items 20 and 21.The present study aims to compare WaP against conventional ZBI domains in a predominantly Chinese multi-ethnic Asian population. METHODS: We studied 130 consecutive dyads of family caregivers and patients. Factor analysis of the 22-item ZBI revealed four factors of burden. We compared WaP (factor 4) with the other three factors, personal strain, and role strain via: internal consistency; inter-factor correlation; item-to-total ratio across Clinical Dementia Rating (CDR) stages; predictors of burden; and interaction effect on total ZBI score using two-way analysis of variance. RESULTS: WaP correlated poorly with the other factors (r = 0.05-0.21). It had the highest internal consistency (Cronbach's α = 0.92) among the factors. Unlike other factors, WaP was highly endorsed in mild cognitive impairment and did not increase linearly with disease severity, peaking at CDR 1. Multiple regression revealed younger caregiver age as the major predictor of WaP, compared with behavioral and functional problems for other factors. There was a significant interaction between WaP and psychological strain (p = 0.025). CONCLUSION: Our results corroborate earlier studies that WaP is a distinct burden dimension not correspondent with traditional ZBI domains. WaP is germane to many Asian societies where obligation values to care for family members are strongly influential. Further studies are needed to better delineate the construct of WaP.

Stroke incidence in the South West District of the Penang Island, Malaysia: PEARLs: Penang Acute Stroke Research Longitudinal Study.

OBJECTIVES: This community based incidence study aims to report the stroke incidence in the south-west region of the Penang Island. METHODS: All strokes occurring in the population of residents in the southwest region of the Penang Island, Malaysia during a period of 12 months, from April 2010 to March 2011 were screened and assessed. Standard definitions for stroke were used. All stroke cases were ascertained using multiple overlapping sources. Incidence rate was based on first ever in a lifetime stroke cases. All recurrent strokes were excluded from the incidence count. RESULTS: The overall stroke incidence rate in the study region during the study period was 67 per 100,000 after age adjustment to 2010 Malaysian population. CONCLUSION: This study provides the first stroke incidence data in Malaysia and is vital for effective health system planning.

Impact of deprescribing intervention on potentially inappropriate medications and clinical outcomes among hospitalized older adults in Malaysia: a randomized controlled trial (REVMED RCT) protocol.

BACKGROUND: Polypharmacy and the use of potentially inappropriate medications (PIMs) are prevalent among older patients admitted to hospitals, posing a heightened risk of adverse drug events. This trial aims to evaluate the effectiveness of a pharmacist-led deprescribing intervention in reducing medications, PIM and improving clinical outcomes, using the locally developed Malaysian Potentially Inappropriate Prescribing Screening tool in Older Adults (MALPIP). METHODS: This is an 18-month cluster-randomized, open-label, parallel-arm controlled trial conducted at 14 public hospitals in the Perak state of Malaysia. Patients aged 60 and above, who have at least one medication and one comorbidity are eligible. A stratified-cluster randomization design is employed, with 7 hospitals assigned to the control arm and 7 hospitals assigned to the intervention arm. The MALPIP screening tool will be used in the intervention group to review the medications. If PIM is detected, the pharmacists will discuss with doctors and decide whether to stop or reduce the dose. The primary outcomes of this trial are the total number of medications and number of PIM. The secondary outcomes include fall, emergency department visits, readmissions, quality of life and mortality. Outcomes will be measured during enrolment, discharge, 6, 12, and 18 months. DISCUSSION: This REVMED trial aims to test the hypothesis that a pharmacist-led deprescribing intervention initiated in the hospital will reduce the total number of medications and PIM 18 months after hospital discharge, reducing fall, emergency department visits, readmissions, mortality and lead to improvement in quality of life. Trial findings will quantify the clinical outcomes associated with reducing medications and PIM for hospitalized older adults with polypharmacy. TRIAL REGISTRATION NUMBER: This trial was prospectively registered at clinicaltrials.gov (NCT05875623) on the 25th of May 2023. NCT05875623 Clinicaltrials.gov URL: NCT05875623 registered on 25th July 2023.

Genetic study of early-onset Parkinson's disease in the Malaysian population.

BACKGROUND: About 5-10% of Parkinson's disease (PD) cases are early onset (EOPD), with several genes implicated, including GBA1, PRKN, PINK1, and SNCA. The spectrum and frequency of mutations vary across populations and globally diverse studies are crucial to comprehensively understand the genetic architecture of PD. The ancestral diversity of Southeast Asians offers opportunities to uncover a rich PD genetics landscape, and identify common regional mutations and new pathogenic variants. OBJECTIVES: This study aimed to investigate the genetic architecture of EOPD in a multi-ethnic Malaysian cohort. METHODS: 161 index patients with PD onset ≤50 years were recruited from multiple centers across Malaysia. A two-step approach to genetic testing was used, combining a next-generation sequencing-based PD gene panel and multiplex ligation-dependent probe amplification (MLPA). RESULTS: Thirty-five patients (21.7%) carried pathogenic or likely pathogenic variants involving (in decreasing order of frequency): GBA1, PRKN, PINK1, DJ-1, LRRK2, and ATP13A2. Pathogenic/likely pathogenic variants in GBA1 were identified in thirteen patients (8.1%), and were also commonly found in PRKN and PINK1 (11/161 = 6.8% and 6/161 = 3.7%, respectively). The overall detection rate was even higher in those with familial history (48.5%) or age of diagnosis ≤40 years (34.8%). PRKN exon 7 deletion and the PINK1 p.Leu347Pro variant appear to be common among Malay patients. Many novel variants were found across the PD-related genes. CONCLUSIONS: This study provides novel insights into the genetic architecture of EOPD in Southeast Asians, expands the genetic spectrum in PD-related genes, and highlights the importance of diversifying PD genetic research to include under-represented populations.

Development of a Malaysian potentially inappropriate prescribing screening tool in older adults (MALPIP): a Delphi study.

INTRODUCTION: Polypharmacy and potentially inappropriate medications (PIM) are common among older adults. To guide appropriate prescribing, healthcare professionals often rely on explicit criteria to identify and deprescribe inappropriate medications, or to start medications due to prescribing omission. However, most explicit PIM criteria were developed with inadequate guidance from quality metrics or integrating real-world data, which are rich and valuable data source. AIM: To develop a list of medications to facilitate appropriate prescribing among older adults. METHODS: A preliminary list of PIM and potential prescribing omission (PPO) were generated from systematic review, supplemented with local pharmacovigilance data of adverse reaction incidents among older people. Twenty-one experts from nine specialties participated in two Delphi to determine the list of PIM and PPO in February and March 2023. Items that did not reach consensus after the second Delphi round were adjudicated by six geriatricians. RESULTS: The preliminary list included 406 potential candidates, categorised into three sections: PIM independent of diseases, disease dependent PIM and omitted drugs that could be restarted. At the end of Delphi, 92 items were decided as PIM, including medication classes, such as antacids, laxatives, antithrombotics, antihypertensives, hormones, analgesics, antipsychotics, antidepressants, and antihistamines. Forty-two disease-specific PIM criteria were included, covering circulatory system, nervous system, gastrointestinal system, genitourinary system, and respiratory system. Consensus to start potentially omitted treatment was achieved in 35 statements across nine domains. CONCLUSIONS: The newly developed PIM criteria can serve as a useful tool to guide clinicians and pharmacists in identifying PIMs and PPOs during medication review and facilitating informed decision-making for appropriate prescribing.

Multidimensionality of the Zarit Burden Interview across the severity spectrum of cognitive impairment: an Asian perspective.

BACKGROUND: We aimed to examine the multidimensionality of the Zarit Burden Interview (ZBI) beyond the conventional dual-factor structure among caregivers of persons with cognitive impairment in a predominantly Chinese multiethnic Asian population, and ascertain how these dimensions vary across the spectrum of disease severity. METHODS: We studied 130 consecutive dyads of primary caregivers and patients attending a memory clinic over a six-month period. Caregiver burden was measured by the 22-item ZBI, and disease severity was staged via the Clinical Dementia Rating (CDR) scale. We performed principal component analysis (PCA) with varimax rotation to determine the factor structure of the ZBI. The magnitude of burden in each factor was expressed as the item to total ratio (ITR) and plotted against the stages of cognitive impairment. Descriptive and inferential statistics were applied to study the relationships between dimensions with disease and caregiver characteristics. RESULTS: We identified four factors: demands of care and social impact, control over the situation, psychological impact, and worry about caregiving performance. ITRs of the first three factors increased with severity of disease and were related to recipients' functional status and disease characteristics. ITR in the dimension of worry about performance was endorsed highest across the spectrum of disease severity, starting as early as the stage of mild cognitive impairment and peaking at CDR 1. CONCLUSION: Multidimensionality of ZBI was confirmed in our local setting. Each dimension of burden was unique and expressed differentially across disease severity. The dimension of worry about performance merits further study.

Recent advances on microalgae cultivation for simultaneous biomass production and removal of wastewater pollutants to achieve circular economy.

Microalgae are known for containing high value compounds and its significant role in sequestering carbon dioxide. This review mainly focuses on the emerging microalgae cultivation technologies such as nanomaterials technology that can improve light distribution during microalgae cultivation, attached cultivation and co-cultivation approaches that can improve growth and proliferation of algal cells, biomass yield and lipid accumulation in microalgal. This review includes a comprehensive discussion on the use of microbubbles technology to enhance aerated bubble capacity in photobioreactor to improve microalgal growth. This is followed by discussion on the role of microalgae as phycoremediation agent in removal of contaminants from wastewater, leading to better water quality and high productivity of shellfish. The review also includes techno-economic assessment of microalgae biorefinery technology, which is useful for scaling up the microalgal biofuel production system or integrated microalgae-shellfish cultivation system to support circular economy.

Efficacy of heterologous boosting against SARS-CoV-2 using a recombinant interferon-armed fusion protein vaccine (V-01): a randomized, double-blind and placebo-controlled phase III trial.

Waning of neutralizing titres along with decline of protection efficacy after the second dose of COVID-19 vaccines was observed, including China-made inactivated vaccines. Efficacy of a heterologous boosting using one dose of a recombinant SARS-CoV-2 fusion protein vaccine (V-01) in inactivated vaccine-primed population was studied, aimed to restore the immunity. A randomized, double-blind and placebo-controlled phase III trial was conducted in healthy people aged 18 years or older in Pakistan and Malaysia. Each eligible participant received one dose of the V-01 vaccine developed by Livzon Mabpharm Inc. or placebo within the 3-6 months after the two-dose primary regimen, and was monitored for safety and efficacy. The primary endpoint was protection against confirmed symptomatic SARS-CoV-2 infection. A total of 10,218 participants were randomly assigned to receive a vaccine or placebo. Virus-neutralizing antibodies were assessed in 419 participants. A dramatic increase (11.3-fold; 128.3-1452.8) of neutralizing titres was measured in the V-01 group at 14 days after the booster. Over two months of surveillance, vaccine efficacy was 47.8% (95%CI: 22.6-64.7) according to the intention-to-treat principle. The most common adverse events were transient, mild-to-moderate pain at the injection site, fever, headache, and fatigue. Serious adverse events occurred almost equally in V-01 (0.12%) and placebo (0.16%) groups. The heterologous boosting with the V-01 vaccine was safe and efficacious, which could elicit robust humoral immunity under the epidemic of the Omicron variant.Trial registration: ClinicalTrials.gov identifier: NCT05096832.

Dearth of influenza among older adults admitted with respiratory symptoms in Malaysia during the coronavirus disease 2019 pandemic in 2021.

Introduction: Influenza is a common respiratory virus which leads to over 400,000 annual deaths globally. Mortality from influenza is highest among those aged 75 years and over living in Africa and Southeast Asia. Objective: To determine the burden of influenza among older adults presenting to public hospitals with severe acute respiratory infection (SARI) during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This multi-center, prospective, observational study recruited individuals aged 65 years and over who presented to four Malaysian hospitals with SARI from 1 January to 31 December 2021. Those with prior confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were excluded. SARS-CoV-2 was detected through real-time polymerase chain reaction (PCR) with routine diagnostic kits. Influenza A, influenza B and respiratory syncytial virus (RSV) viruses were detected with Xpress Flu/RSV kits using the GeneXpert rapid real-time PCR system (Cepheid, USA). Results: Samples were obtained from 512 participants, comprising 296 (57.8%) men and 216 (42.2%) women, with a mean age (SD) of 74.0 (7.1) years. Inpatient death occurred in 48 (9.6%) individuals. Significant differences existed in age, ethnicity, and comorbidities across study sites. One (0.2%) case of influenza A, two (0.4%) cases of RSV and 63 (12.5%) cases of SARS-CoV-2 infection were detected over the 1-year period. Cases of COVID-19 mirrored national trends derived from open source data, while the dearth of influenza cases mirrored national and global Flunet figures. Conclusion: Our observational study conducted during the COVID-19 pandemic detected only one case of influenza, alongside a high SARS-CoV-2 positivity rate. The poor uptake of influenza vaccination nationally, worsened by the recent pandemic restrictions, could lead to waning immunity from the absence of seasonal exposure. Potentially deadly outbreaks may then occur when lockdown and infection control measures are eventually removed.

Efficacy of Ivermectin Treatment on Disease Progression Among Adults With Mild to Moderate COVID-19 and Comorbidities: The I-TECH Randomized Clinical Trial.

Importance: Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19. Evidence-based data to recommend either for or against the use of ivermectin are needed. Objective: To determine the efficacy of ivermectin in preventing progression to severe disease among high-risk patients with COVID-19. Design, Setting, and Participants: The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients' symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease. Interventions: Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care (n = 241) or standard of care alone (n = 249). The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging. Main Outcomes and Measures: The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events. Results: Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group). Conclusions and Relevance: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04920942.