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  1. Chaiyasothi T, Nathisuwan S, Dilokthornsakul P, Vathesatogkit P, Thakkinstian A, Reid C, et al.
    Front Pharmacol, 2019;10:547.
    PMID: 31191304 DOI: 10.3389/fphar.2019.00547
    Background: Currently, there is a lack of information on the comparative efficacy and safety of non-statin lipid-lowering agents (NST) in cardiovascular (CV) disease risk reduction when added to background statin therapy (ST). This study determine the relative treatment effects of NST on fatal and non-fatal CV events among statin-treated patients. Methods: A network meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing non-statin lipid-modifying agents among statin-treated patients was performed. PubMed, EMBASE, CENTRAL, and Clinicaltrial.gov were searched up to April 10, 2018. The primary outcomes were CV and all-cause mortalities. Secondary CV outcomes were coronary heart disease (CHD) death, non-fatal myocardial infarction (MI), any stroke, and coronary revascularization. Risks of discontinuations were secondary safety outcomes. Results: Sixty-seven RCTs including 259,429 participants with eight interventions were analyzed. No intervention had significant effects on the primary outcomes (CV mortality and all-cause mortality). For secondary endpoints, proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK) plus statin (PCSK/ST) significantly reduced the risk of non-fatal MI (RR 0.82, 95% CI 0.72-0.93, p = 0.003), stroke (RR 0.74, 95% CI 0.65-0.85, p < 0.001), coronary revascularization (RR 0.84, 95% CI 0.75-0.94, p = 0.003) compared to ST. Combinations of ST and all NST except PCSK and ezetimibe showed higher rate of discontinuation due to adverse events compared to ST. Conclusions: None of NST significantly reduced CV or all-cause death when added to ST. PCSKs and to a lesser extent, ezetimibe may help reduce cardiovascular events with acceptable tolerability profile among broad range of patients.
    Matched MeSH terms: Coronary Disease
  2. Ashari KS, Roslan NS, Omar AR, Bejo MH, Ideris A, Mat Isa N
    PeerJ, 2019;7:e6948.
    PMID: 31293824 DOI: 10.7717/peerj.6948
    Salmonella enterica subsp. enterica serovar Stanley (S. Stanley) is a pathogen that contaminates food, and is related to Salmonella outbreaks in a variety of hosts such as humans and farm animals through products like dairy items and vegetables. Despite the fact that several vaccines of Salmonella strains had been constructed, none of them were developed according to serovar Stanley up to this day. This study presents results of genome sequencing and analysis on our S. Stanley UPM 517 strain taken from fecal swabs of 21-day-old healthy commercial chickens in Perak, Malaysia and used Salmonella enterica subsp. enterica serovar Typhimurium LT2 (S. Typhimurium LT2) as a reference to be compared with. First, sequencing and assembling of the Salmonella Stanley UPM 517 genome into a contiguous form were done. The work was then continued with scaffolding and gap filling. Annotation and alignment of the draft genome was performed with S. Typhimurium LT2. The other elements of virulence estimated in this study included Salmonella pathogenicity islands, resistance genes, prophages, virulence factors, plasmid regions, restriction-modification sites and the CRISPR-Cas system. The S. Stanley UPM 517 draft genome had a length of 4,736,817 bp with 4,730 coding sequence and 58 RNAs. It was discovered via genomic analysis on this strain that there were antimicrobial resistance properties toward a wide variety of antibiotics. Tcf and ste, the two fimbrial virulence clusters related with human and broiler intestinal colonizations which were not found in S. Typhimurium LT2, were atypically discovered in the S. Stanley UPM 517 genome. These clusters are involved in the intestinal colonization of human and broilers, respectively. There were seven Salmonella pathogenicity islands (SPIs) within the draft genome, which contained the virulence factors associated with Salmonella infection (except SPI-14). Five intact prophage regions, mostly comprising of the protein encoding Gifsy-1, Fels-1, RE-2010 and SEN34 prophages, were also encoded in the draft genome. Also identified were Type I-III restriction-modification sites and the CRISPR-Cas system of the Type I-E subtype. As this strain exhibited resistance toward numerous antibiotics, we distinguished several genes that had the potential for removal in the construction of a possible vaccine candidate to restrain and lessen the pervasiveness of salmonellosis and to function as an alternative to antibiotics.
    Matched MeSH terms: Disease Outbreaks
  3. Abdul Kadir A, Abdul Kadir A, Abd Hamid R, Mat Jais AM, Omar J, Sadagatullah AN, et al.
    Biomed Res Int, 2019;2019:6979585.
    PMID: 31355276 DOI: 10.1155/2019/6979585
    Objectives: The objective of the study is to evaluate the chondroprotective activity of Channa striatus (Channa) and glucosamine sulphate (glucosamine) on histomorphometric examinations, serum biomarker, and inflammatory mediators in experimental osteoarthritis (OA) rabbit model.

    Design: Anterior cruciate ligament transection (ACLT) was performed to induce OA in thirty-three male New Zealand white rabbits and were randomly divided into three groups: Channa, glucosamine, and control group. The control group received drinking water and the Channa and glucosamine groups were orally administered with 51.4 mg/kg of Channa extract and 77.5 mg/kg of glucosamine sulphate in drinking water, respectively, for eight weeks and then sacrificed. The articular cartilage was evaluated macroscopically and histologically using semiquantitative and quantitative methods. Serum cartilage oligomeric matric protein (COMP), cyclooxygenase 2 (COX-2) enzyme, and prostaglandin E2 (PGE2) were also determined.

    Results: Macroscopic analysis revealed that Channa group have a significantly lower severity grade of total macroscopic score compared to the control (p < 0.001) and glucosamine (p < 0.05) groups. Semiquantitative histology scoring showed that both Channa and glucosamine groups had lower severity grading of total histology score compared to the control group (p < 0.001). In comparison with the control, Channa group had lower histopathological changes in three compartments of the joint compared to glucosamine group which had lower histological scoring in two compartments only. The cartilage thickness, area, and roughness of both Channa (p < 0.05) and glucosamine (p < 0.05) groups were superior compared to the control group. However, the Channa group demonstrated significantly less cartilage roughness compared to the glucosamine group (p < 0.05). Serum COMP levels were lower in both Channa (p < 0.05) and glucosamine (p < 0.05) groups compared to the control group.

    Conclusion: Both oral administration of Channa extract and glucosamine exhibited chondroprotective action on an ACLT OA-induced rabbit model. However, Channa was superior to glucosamine in maintaining the structure of the cartilage.

    Matched MeSH terms: Disease Models, Animal
  4. Paul M, Asmi NH, Omar EK, Abdullah S, Mohamad I
    Oman Med J, 2019 Jan;34(1):74-77.
    PMID: 30671189 DOI: 10.5001/omj.2019.13
    Mantle cell lymphoma (MCL) is a rare, aggressive subtype of non-Hodgkin lymphoma with a poor prognosis and high recurrence rate. It seldom affects the Waldeyer's ring let alone the nasopharynx. Patients usually present at late stages of the disease leading to poor failure-free and overall survival rates. Intensive chemotherapy regimes and autologous stem cell transplantation have reported increased survival rates. We report a relapsed case of nasopharyngeal MCL, which previously occurred in the gastrointestinal tract. The patient had undergone a hemicolectomy for colon intussusception secondary to the intraluminal lymphoma mass. He was unable to complete the treatment regime for MCL due to the adverse side effects. Oropharyngeal mass was discovered during routine outpatient follow-up, which was confirmed as nasopharyngeal MCL. We discuss the prognosis, disease progression, and possible treatments.
    Matched MeSH terms: Disease Progression
  5. Omar A, Ganapathy SS, Anuar MFM, Khoo YY, Jeevananthan C, Maria Awaluddin S, et al.
    BMC Public Health, 2019 Jan 24;19(1):110.
    PMID: 30678685 DOI: 10.1186/s12889-018-6384-7
    BACKGROUND: Mortality indicators are essential for monitoring population health. Although Malaysia has a functional death registration system, the quality of information on causes of death still needs improvement, since approximately 30% of deaths are classified to poorly defined causes. This study was conducted to verify registered causes in a sample of deaths in 2013 and utilise the findings to estimate cause-specific mortality indicators for Malaysia in 2013.

    METHODS: This is a cross-sectional study involving a nationally representative sample of 14,497 deaths distributed across 19 districts. Registered causes of deaths were verified using standard medical record review protocols for hospital deaths, and locally adapted international standard verbal autopsy procedures for deaths outside hospitals. The findings were used to measure the validity and reliability of the registration data, as well as to establish plausible cause-specific mortality fractions for hospital and non-hospital deaths, which were subsequently used as the basis for estimating national cause-specific mortality indicators.

    RESULTS: The overall response rate for the study was 67%. Verified causes of 5041 hospital deaths and 3724 deaths outside hospitals were used to derive national mortality estimates for 2013 by age, sex and cause. The study was able to reclassify most of the ill-defined deaths to a specific cause. The leading causes of deaths for males were Ischaemic Heart Disease (15.4%), Cerebrovascular diseases (13.7%), Chronic Obstructive Pulmonary Disease (8.5%) and Road Traffic Accident (8.0%). Among females, the leading causes were Cerebrovascular diseases (18.3%), Ischaemic Heart Disease (12.7%), Lower Respiratory Infections (11.5%) and Diabetes Mellitus (7.2%).

    CONCLUSIONS: Investigation of registered causes of death using verbal autopsy and medical record review yielded adequate information to enable estimation of cause-specific mortality indicators in Malaysia. Strengthening the national mortality statistics system must be made a priority as it is a core data source for policy and evaluation of the public health and healthcare sectors in Malaysia.
    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive
  6. Nusrat T, Akter N, Haque M, Rahman NAA, Dewanjee AK, Ahmed S, et al.
    Pathogens, 2019 Sep 12;8(3).
    PMID: 31547453 DOI: 10.3390/pathogens8030151
    BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care units (ICU), which accounts for 25% of all ICU infection. Documenting carbapenem-resistant gram-negative bacilli is very important as these strains may often cause outbreaks in the ICU setting and are responsible for the increased mortality and morbidity or limiting therapeutic options. The classical phenotypic method cannot provide an efficient means of diagnosis of the metallo-β-lactamases (MBLs) producer. Polymerase chain reaction (PCR) assays have lessened the importance of the phenotypic approach by detecting metallo-β-lactamase resistance genes such as New Delhi metallo-β-lactamase (NDM), Imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), Sao Paulo metallo-β-lactamase (SPM), Germany Imipenemase (GIM).

    OBJECTIVE: To compare the results of the Combined Disc Synergy Test (CDST) with that of the multiplex PCR to detect MBL-producing gram-negative bacilli.

    MATERIALS AND METHOD: A total of 105 endotracheal aspirates (ETA) samples were collected from the ICU of a public school in Bangladesh. This cross-sectional study was carried out in the Department of Microbiology, Chittagong for quantitative culture, CDST test, and multiplex PCR for blaIMP, blaVIM, blaNDM genes of MBL producers.

    RESULTS: Among the 105 clinically suspected VAP cases, the quantitative culture was positive in 95 (90%) and among 95 g-negative bacilli isolated from VAP patients, 46 (48.42%) were imipenem resistant, 30 (65.22%) were MBL producers by CDST, 21 (45.65%) were identified as MBL producers by multiplex PCR.

    CONCLUSION: PCR was highly sensitive and specific for the detection of MBL producers.

    Matched MeSH terms: Disease Outbreaks
  7. Khammas ASA, Hassan HA, Salih SQM, Kadir H, Ibrahim RM, Nasir NNM, et al.
    Porto Biomed J, 2018 09 19;4(2):e31.
    PMID: 31595260 DOI: 10.1016/j.pbj.0000000000000031
    Objectives: Nonalcoholic fatty liver disease (NAFLD) is a very common liver disorder in Western countries. As of late, it has been found to be prevalent in Asia as well. It is a benign disease unless it develops into necroinflammation and fibrosis. This study was proposed to determine the prevalence and risk factors of sonography-detected NAFLD among Malaysian adults in Klang Valley, West Malaysia.

    Study design: An observational cross-sectional study.

    Methods: The participants were aged between 45 and 75 years who participated in a screening program at the Golden Horses Health Sanctuary in Klang Valley. Lipid profile and anthropometric measurements were collected from the subjects' medical records. Ultrasound machine and a structured self-administered questionnaire were used as instruments for recruiting data from the subjects. The subjects who consumed alcohol (>140 g/wk for men and >70 g/wk for females), had hepatitis B or C viruses, liver insults, and surgery, and taken lipid-lowering medications were excluded from the study.

    Results: A total of 628 subjects were analyzed, and 235 (37.4%) subjects were diagnosed with definite NAFLD. They comprised 518 (82.5%) Chinese, 92 (14.6%) Malays, and 18 (2.9%) Indians. Peak prevalence of NAFLD was found in 53 to 60 years age group. The higher prevalence of NAFLD was among men (48.3%) than women (27.3%) and among Indians (61.1%) and Malays (51.1%) than among Chinese (34.2%). NAFLD has been found to be strongly correlated with male sex, high body mass index (≥23.0 kg/m2), hypertriglyceridemia, low high-density lipoprotein cholesterol, diabetes mellitus, and hypertension.

    Conclusion: NAFLD is quite common among adults in Malaysian urban population. The prevalence of NAFLD was inordinately high among the 53 to 60 years age group, male sex, Indians, and Malays (as compared with Chinese). Age >60 years, male sex, high body mass index (≥23.0 kg/m2), hypertriglyceridemia, and diabetes mellitus were proven to be risk predictors for NAFLD.

    Matched MeSH terms: Non-alcoholic Fatty Liver Disease
  8. Tey HJ, Ng CH
    PeerJ, 2019;7:e7667.
    PMID: 31592138 DOI: 10.7717/peerj.7667
    Background: From genome wide association studies on Alzheimer's disease (AD), it has been shown that many single nucleotide polymorphisms (SNPs) of genes of different pathways affect the disease risk. One of the pathways is endocytosis, and variants in these genes may affect their functions in amyloid precursor protein (APP) trafficking, amyloid-beta (Aβ) production as well as its clearance in the brain. This study uses computational methods to predict the effect of novel SNPs, including untranslated region (UTR) variants, splice site variants, synonymous SNPs (sSNPs) and non-synonymous SNPs (nsSNPs) in three endocytosis genes associated with AD, namely PICALM, SYNJ1 and SH3KBP1.

    Materials and Methods: All the variants' information was retrieved from the Ensembl genome database, and then different variation prediction analyses were performed. UTRScan was used to predict UTR variants while MaxEntScan was used to predict splice site variants. Meta-analysis by PredictSNP2 was used to predict sSNPs. Parallel prediction analyses by five different software packages including SIFT, PolyPhen-2, Mutation Assessor, I-Mutant2.0 and SNPs&GO were used to predict the effects of nsSNPs. The level of evolutionary conservation of deleterious nsSNPs was further analyzed using ConSurf server. Mutant protein structures of deleterious nsSNPs were modelled and refined using SPARKS-X and ModRefiner for structural comparison.

    Results: A total of 56 deleterious variants were identified in this study, including 12 UTR variants, 18 splice site variants, eight sSNPs and 18 nsSNPs. Among these 56 deleterious variants, seven variants were also identified in the Alzheimer's Disease Sequencing Project (ADSP), Alzheimer's Disease Neuroimaging Initiative (ADNI) and Mount Sinai Brain Bank (MSBB) studies.

    Discussion: The 56 deleterious variants were predicted to affect the regulation of gene expression, or have functional impacts on these three endocytosis genes and their gene products. The deleterious variants in these genes are expected to affect their cellular function in endocytosis and may be implicated in the pathogenesis of AD as well. The biological consequences of these deleterious variants and their potential impacts on the disease risks could be further validated experimentally and may be useful for gene-disease association study.

    Matched MeSH terms: Alzheimer Disease
  9. Osman O, Fong MY, Devi S
    Virus Res, 2008 Jul;135(1):48-52.
    PMID: 18406488 DOI: 10.1016/j.virusres.2008.02.006
    In a previous study, we have reported the detection and isolation of dengue virus in Brunei (Osman, O., Fong, M.Y., Devi, S., 2007. A preliminary study of dengue infection in Brunei. JJID 60 (4), 205-208). DEN-2 was the predominant serotype followed by DEN-1. The full genomic sequences of 3 DEN-2 viruses isolated during the 2005-2006 dengue incident in Brunei were determined. Twenty-five primer sets were designed to amplify contiguous overlapping fragments of approximately 500-600 base pairs spanning the entire sequence of the viral genome. The amplified PCR products were sent for sequencing and their nucleotides and the deduced amino acids were determined. All three DEN-2 virus isolated were clustered in the Cosmopolitan genotype of the DEN-2 classification by Twiddy et al. This work constitutes the first complete genetic characterization of three Brunei DEN-2 virus strains.
    Matched MeSH terms: Disease Outbreaks
  10. Wan Mohd Yunus WMA, Badri SKZ, Panatik SA, Mukhtar F
    Front Psychiatry, 2020;11:566221.
    PMID: 33664679 DOI: 10.3389/fpsyt.2020.566221
    Background and Aims: Malaysia's first Movement Control Order (MCO) or "lockdown" was in place for 6 weeks to curb the spread of coronavirus disease (COVID-19). Consequently, all universities were forced to close temporarily with abrupt changes to teaching and learning activities. However, there has been a lack of consensus regarding students' actual psychological status and mental health during the MCO implementation. This study investigates the link, state, and differences of negative emotional symptoms, happiness, and work-life balance among university students during the COVID-19 pandemic. Methodology: This study recruited 1,005 university students across Malaysia. Data was collected online using Qualtrics to measure negative emotional symptoms (The Depression, Anxiety, and Stress Scale), happiness (The Oxford Happiness Inventory), and work-life balance (Work-Family Conflict Scale). All data was analyzed using SPSS version 25 and AMOS version 26 using T-test, ANOVA, logistic regression analyses, and path analysis method. Findings: Findings indicated that 22, 34.3, and 37.3% of the university students scored moderate to extremely severe levels of stress, anxiety, and depression symptoms, respectively. Half scored rather happy or very happy (50%) for happiness levels. Meanwhile, 50.4 and 39.4% scored high to very high levels of work-to-family and family-to-work conflict. Significant differences in stress, anxiety, depression, happiness, work-family conflict, and family-work conflict were recorded across different demographic factors. Happiness was found to be a protective factor with a lesser likelihood of experiencing severe stress (OR = 0.240, 95% CI: 0.180, 0.321), anxiety (OR = 0.336, 95% CI: 0.273, 0.414), and depression (OR = 0.121, 95% CI: 0.088, 0.165) with higher happiness levels. Higher score of work-to-family conflict contributes to greater odds of having severe levels of anxiety (OR = 1.453, 95% CI: 1.161, 1.818). While greater likelihood of developing severe stress (OR = 1.468, 95% CI: 1.109, 1.943) and severe anxiety (OR = 1.317, 95% CI: 1.059, 1.638) under increasing score of family-to-work conflict. Besides, happiness is found to negatively linked with lower negative emotional symptoms, while work-family conflict and family-work conflict are positively linked with higher negative emotional symptoms. Conclusion: Lockdown implementation during the COVID-19 pandemic appears to have a significant impact on university students' negative emotional symptoms, happiness, and work-life balance. Happiness was found to be a protective factor while the state of work-life balance is a risk factor that can predict students' negative emotional symptoms.
    Matched MeSH terms: Communicable Disease Control
  11. Alrasheedy AA, Abdulsalim S, Farooqui M, Alsahali S, Godman B
    Risk Manag Healthc Policy, 2021;14:729-741.
    PMID: 33654441 DOI: 10.2147/RMHP.S292354
    Background: Individuals' knowledge, attitude and practice towards preventive and precautionary measures of COVID-19 are essential to control the spread of the disease. Consequently, the aims of the study were to evaluate knowledge, attitude and practice of pharmacy students towards the pandemic and to assess its psychological impact on them to provide future guidance.

    Methods: A cross-sectional, questionnaire-based study was conducted via a web-based survey in May 2020. All pharmacy students enrolled at Unaizah College of Pharmacy, Qassim University, were invited to take part in the study.

    Results: A total of 232 out of 460 students took part in the study, giving a response rate of 50.43%. The mean total knowledge score was 9.87 ± 2.04 (maximum attainable score, 12). The majority of the participants (n=163; 70.3%) believed COVID-19 is a health threat to their community in the early months of the pandemic. Moreover, the majority (93%) also believed that the lockdown at the beginning of the pandemic was necessary to contain the pandemic. Encouragingly, 86.6% reported that they did not go to any crowded places during the pandemic with more female students avoiding crowded places compared to male students (91.6% versus 78.7%, respectively, P = 0.005). The majority (91%) also reported that they were following the strategies recommended by the authorities to prevent the spread of the virus. Encouragingly, 54.3% reported that the pandemic either had no effect or just a limited effect on their studies. However, 38.5% reported that they always felt or frequently felt nervous or anxious during the pandemic.

    Conclusion: The study showed that pharmacy students had good knowledge as well as positive attitudes and good practices towards COVID-19 and the preventive measures. However, during the early months, the pandemic did have a negative psychological impact on a number of students. Consequently, proactive psychological and social support services to the students should be considered during the current and future pandemics. In addition, it is important to consider and proactively address key issues that could cause stress and anxiety among students when shifting to distance learning and assessments.

    Matched MeSH terms: Communicable Disease Control
  12. Chai CS, Mos SB, Ng DL, Goh GM, Su AT, Ibrahim MAB, et al.
    BMC Pulm Med, 2020 Sep 29;20(1):254.
    PMID: 32993591 DOI: 10.1186/s12890-020-01295-4
    BACKGROUND: The Spanish chronic obstructive pulmonary disease (COPD) guideline phenotypes patients according to the exacerbation frequency and COPD subtypes. In this study, we compared the patients' health-related quality of life (HRQoL) according to their COPD phenotypes.

    METHODS: This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23th January 2018 to 22th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c).

    RESULTS: Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the 185 COPD patients, 65.9% had exposure to biomass fuel and 69.1% were ex- or current smokers. The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p 

    Matched MeSH terms: Pulmonary Disease, Chronic Obstructive
  13. Cardosa M, Osman ZJ, Nicholas M, Tonkin L, Williams A, Abd Aziz K, et al.
    Transl Behav Med, 2012 Mar;2(1):30-37.
    PMID: 22448204
    Self-management of chronic illnesses has been widely recognised as an important goal on quality of life, health service utilisation and cost grounds. This study describes the first published account on the application of this approach to people suffering from chronic pain conditions in a Southeast Asian country, Malaysia. A heterogeneous sample of chronic pain patients in Malaysia attended a 2-week cognitive-behavioural pain management programme (PMP) aimed at improving daily functional activities and general psychological well-being. Complete datasets from 70 patients out of 102 patients who attended 11 programmes conducted from 2002 to 2007, as well as the 1-month and 1-year follow-up sessions at the hospital clinic, are reported. The pre- to post-treatment results on self-report measures indicate that significant gains were achieved on the dimensions of pain, disability and psychological well-being. These gains were maintained at both 1-month and 1-year follow-ups. The results mirror those reported from similar interventions in Europe and North America and indicate the concept of self-management of a chronic illness is acceptable and meaningful to Asian patients. Importantly, the achieved outcomes were independent of gender and ethnic group status.
    Matched MeSH terms: Chronic Disease
  14. Samsudin A, Eames I, Brocchini S, Khaw PT
    J Glaucoma, 2016 Jan;25(1):e39-45.
    PMID: 25719236 DOI: 10.1097/IJG.0000000000000243
    PURPOSE: ExPress devices are available as P50 and P200 models, the numbers related to their luminal diameters in μm. We compared their Poiseuille's Law-based theoretical resistance values with experimental values and correlated these with their luminal dimensions derived from electron microscopy.

    METHODS: Scanning electron microscopy was performed on P50 and P200 devices. Bench-top flow studies were performed to find the resistances of the devices. Devices were also incorporated into a perfused, ex vivo porcine sclera model to test and compare their control of pressure, with and without overlying scleral flaps, and with trabeculectomies.

    RESULTS: The luminal dimensions of the P200 device were 206.4±3.3 and 204.5±0.9 μm at the subconjunctival space and anterior chamber ends, respectively. Those of the P50 device were 205.0±5.8 and 206.9±3.7 μm, respectively. There were no significant differences between the P200 and P50 devices (all P>0.05). The resistances of the P200 and P50 devices were 0.010±0.001 and 0.054±0.002 mm Hg/μL/min, respectively (P<0.05). Equilibrium pressures with overlying scleral flaps were 17.81±3.30 mm Hg for the P50, 17.31±4.24 mm Hg for the P200, and 16.28±6.67 mm Hg for trabeculectomies (P=0.850).

    CONCLUSIONS: The luminal diameters of both devices are externally similar. The effective luminal diameter of the P50 is much larger than 50 μm. Both devices have low resistance values, making them unlikely to prevent hypotony on their own. They lead to similar equilibrium pressures as the trabeculectomy procedure when inserted under the scleral flap.

    Matched MeSH terms: Disease Models, Animal
  15. Yang X, Leslie G, Doroszuk A, Schneider S, Allen J, Decker B, et al.
    J Clin Oncol, 2020 03 01;38(7):674-685.
    PMID: 31841383 DOI: 10.1200/JCO.19.01907
    PURPOSE: To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized.

    METHODS: We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes.

    RESULTS: We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10-2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer.

    CONCLUSION: These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

    Matched MeSH terms: Genetic Predisposition to Disease
  16. Law ZK, Ali A, Krishnan K, Bischoff A, Appleton JP, Scutt P, et al.
    Stroke, 2020 01;51(1):121-128.
    PMID: 31735141 DOI: 10.1161/STROKEAHA.119.026128
    Background and Purpose- Blend, black hole, island signs, and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage. We explored the value of these noncontrast computed tomography signs in predicting hematoma expansion and functional outcome in our cohort of intracerebral hemorrhage. Methods- The TICH-2 (Tranexamic acid for IntraCerebral Hemorrhage-2) was a prospective randomized controlled trial exploring the efficacy and safety of tranexamic acid in acute intracerebral hemorrhage. Baseline and 24-hour computed tomography scans of trial participants were analyzed. Hematoma expansion was defined as an increase in hematoma volume of >33% or >6 mL on 24-hour computed tomography. Poor functional outcome was defined as modified Rankin Scale of 4 to 6 at day 90. Multivariable logistic regression was performed to identify predictors of hematoma expansion and poor functional outcome. Results- Of 2325 patients recruited, 2077 (89.3%) had valid baseline and 24-hour scans. Five hundred seventy patients (27.4%) had hematoma expansion while 1259 patients (54.6%) had poor functional outcome. The prevalence of noncontrast computed tomography signs was blend sign, 366 (16.1%); black hole sign, 414 (18.2%); island sign, 200 (8.8%); and hypodensities, 701 (30.2%). Blend sign (adjusted odds ratio [aOR] 1.53 [95% CI, 1.16-2.03]; P=0.003), black hole (aOR, 2.03 [1.34-3.08]; P=0.001), and hypodensities (aOR, 2.06 [1.48-2.89]; P<0.001) were independent predictors of hematoma expansion on multivariable analysis with adjustment for covariates. Black hole sign (aOR, 1.52 [1.10-2.11]; P=0.012), hypodensities (aOR, 1.37 [1.05-1.78]; P=0.019), and island sign (aOR, 2.59 [1.21-5.55]; P=0.014) were significant predictors of poor functional outcome. Tranexamic acid reduced the risk of hematoma expansion (aOR, 0.77 [0.63-0.94]; P=0.010), but there was no significant interaction between the presence of noncontrast computed tomography signs and benefit of tranexamic acid on hematoma expansion and functional outcome (P interaction all >0.05). Conclusions- Blend sign, black hole sign, and hypodensities predict hematoma expansion while black hole sign, hypodensities, and island signs predict poor functional outcome. Noncontrast computed tomography signs did not predict a better response to tranexamic acid. Clinical Trial Registration- URL: https://www.isrctn.com. Unique identifier: ISRCTN93732214.
    Matched MeSH terms: Disease Progression
  17. Kotepui M, Masangkay FR, Kotepui KU, Milanez GJ
    BMC Infect Dis, 2021 Mar 12;21(1):259.
    PMID: 33711940 DOI: 10.1186/s12879-021-05941-y
    BACKGROUND: Plasmodium cynomolgi is a simian malaria parasite that has been reported as a naturally acquired human infection. The present study aims to systematically review reports on naturally acquired P. cynomolgi in humans, mosquitoes, and macaques to provide relevant data for pre-emptive surveillance and preparation in the event of an outbreak of zoonotic malaria in Southeast Asia.

    METHODS: The protocol of the systematic review was registered at PROSPERO with approval ID CRD42020203046. Three databases (Web of Science, Scopus, and MEDLINE) were searched for studies reporting the prevalence of P. cynomolgi infections in Southeast Asian countries between 1946 and 2020. The pooled prevalence or pooled proportion of P. cynomolgi parasitemia in humans, mosquitoes, and macaques was estimated using a random-effects model. Differences in the clinical characteristics of P. cynomolgi infections were also estimated using a random-effects model and presented as pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs).

    RESULTS: Thirteen studies reporting on the prevalence of naturally acquired P. cynomolgi in humans (3 studies, 21 cases), mosquitoes (3 studies, 28 cases), and macaques (7 studies, 334 cases) were included. The results demonstrated that the pooled proportion of naturally acquired P. cynomolgi in humans was 1% (95% CI, 0.1%, I2, 0%), while the pooled proportion of P. cynomolgi infecting mosquitoes was 18% (95% CI, 10-26%, I2, 32.7%). The pooled prevalence of naturally acquired P. cynomolgi in macaques was 47% (95% CI, 27-67%, I2, 98.3%). Most of the cases of naturally acquired P. cynomolgi in humans were reported in Cambodia (62%) and Malaysia (38%), while cases of P. cynomolgi in macaques were reported in Malaysia (35.4%), Singapore (23.2%), Indonesia (17.3%), Philippines (8.5%), Laos (7.93%), and Cambodia (7.65%). Cases of P. cynomolgi in mosquitoes were reported in Vietnam (76.9%) and Malaysia (23.1%).

    CONCLUSIONS: This study demonstrated the occurrence of naturally acquired P. cynomolgi infection in humans, mosquitoes, and macaques. Further studies of P. cynomolgi in asymptomatic human cases in areas where vectors and natural hosts are endemic are extensively needed if human infections with P. cynomolgi do become public health problems.

    Matched MeSH terms: Disease Outbreaks
  18. Salvaraji L, Jeffree MS, Avoi R, Akhir HM, Rahim SSSA, Lukman KA
    Medeni Med J, 2020;35(4):304-309.
    PMID: 33717622 DOI: 10.5222/MMJ.2020.82246
    Objective: Increasing amount of waste concurrently increases the risk of exposure to hazardous materials among waste collectors. Vigorous exertion in the field intensifies the abundance of contaminated inspirable droplets. If left undetected and untreated, it may provoke significant pernicious health effects and redundant burdens to employees and employers. The purpose of this study is to determine the prevalence of respiratory symptoms and their associated factors among domestic waste collectors.

    Method: A cross-sectional study was conducted in Kota Kinabalu, Sabah between January and April 2020. Data were collected using a validated questionnaire which encompasses details about sociodemographic, health status, environment, and employment characteristics.

    Results: A total of 290 waste collectors with a mean age of 40 (±9) years old were participated in the study. Most of them were from Kadazan-Dusun-Murut ethnic origin with educational background till secondary school. The average monthly income of the workers was USD 298.45 (±171.9) per month, and they had been in service for 11 (±9.04) years. Respiratory symptoms were seen in 21% of the workers. The identified significant risk factors were determined as underlying chronic diseases (OR=2.34; 95% CI=1.054, 5.219) and contact with pets (OR=1.87; 95% CI=1.004, 3.288).

    Conclusion: Respiratory symptoms are prevalent amidst domestic waste collectors and related to their health and field activities.

    Matched MeSH terms: Chronic Disease
  19. Sang C, Yan H, Chan WK, Zhu X, Sun T, Chang X, et al.
    Front Med (Lausanne), 2021;8:637652.
    PMID: 33708783 DOI: 10.3389/fmed.2021.637652
    Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of fibrosis. Liver biopsy remains the gold standard for the confirmation of fibrosis in NAFLD patients. Effective and non-invasive diagnosis of advanced fibrosis is essential to disease surveillance and treatment decisions. Herein we used routine medical test markers and logistic regression to differentiate early and advanced fibrosis in NAFLD patients from China, Malaysia, and India (n1 = 540, n2 = 147, and n3 = 97) who were confirmed by liver biopsy. Nine parameters, including age, body mass index, fasting blood glucose, presence of diabetes or impaired fasting glycemia, alanine aminotransferase, γ-glutamyl transferase, triglyceride, and aspartate transaminase/platelet count ratio, were selected by stepwise logistic regression, receiver operating characteristic curve (ROC), and hypothesis testing and were used for model construction. The area under the ROC curve (auROC) of the model was 0.82 for differentiating early and advanced fibrosis (sensitivity = 0.69, when specificity = 0.80) in the discovery set. Its diagnostic ability remained good in the two independent validation sets (auROC = 0.89 and 0.71) and was consistently superior to existing panels such as the FIB-4 and NAFLD fibrosis score. A web-based tool, LiveFbr, was developed for fast access to our model. The new model may serve as an attractive tool for fibrosis classification in NAFLD patients.
    Matched MeSH terms: Non-alcoholic Fatty Liver Disease
  20. Gopalsamy B, Chia JSM, Farouk AAO, Sulaiman MR, Perimal EK
    Molecules, 2020 Aug 26;25(17).
    PMID: 32858809 DOI: 10.3390/molecules25173880
    Zerumbone, a monocyclic sesquiterpene from the wild ginger plant Zingiber zerumbet (L.) Smith, attenuates allodynia and hyperalgesia. Currently, its mechanisms of action in neuropathic pain conditions remain unclear. This study examines the involvement of potassium channels and opioid receptors in zerumbone-induced analgesia in a chronic constriction injury (CCI) neuropathic pain mice model. Male Institute of Cancer Research (ICR) mice were subjected to CCI and behavioral responses were tested on day 14. Responses toward mechanical allodynia and thermal hyperalgesia were tested with von Frey's filament and Hargreaves' tests, respectively. Symptoms of neuropathic pain were significantly alleviated following treatment with zerumbone (10 mg/kg; intraperitoneal, i.p.). However, when the voltage-dependent K+ channel blocker tetraethylammonium (TEA, 4 mg/kg; i.p.), ATP-sensitive K+ channel blocker, glibenclamide (GLIB, 10 mg/kg; i.p.); small-conductance Ca2+-activated K+ channel inhibitor apamin (APA, 0.04 mg/kg; i.p.), or large-conductance Ca2+-activated K+ channel inhibitor charybdotoxin (CHAR, 0.02 mg/kg; i.p.) was administered prior to zerumbone (10 mg/kg; i.p.), the antiallodynic and antihyperalgesic effects of zerumbone were significantly reversed. Additionally, non-specific opioid receptors antagonist, naloxone (NAL, 10 mg/kg; i.p.), selective µ-, δ- and κ-opioid receptor antagonists; β-funaltrexamine (β-FN, 40 mg/kg; i.p.), naltrindole (20 mg/kg; s.c.), nor-binaltorphamine (10 mg/kg; s.c.) respectively attenuated the antiallodynic and antihyperalgesic effects of zerumbone. This outcome clearly demonstrates the participation of potassium channels and opioid receptors in the antineuropathic properties of zerumbone. As various clinically used neuropathic pain drugs also share this similar mechanism, this compound is, therefore, a highly potential substitute to these therapeutic options.
    Matched MeSH terms: Disease Models, Animal
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