OBJECTIVE: To determine, in a population-based survey, the prevalence of lower urinary tract symptoms (LUTS), erectile dysfunction (ED) and incontinence in community-dwelling men in multiethnic Malaysia, as currently available Western demographic data might not be applicable in the Asian population.
SUBJECTS AND METHODS: A cross-sectional population-based survey was carried out in the State of Penang, Malaysia, with a target population of men aged > or = 40 years. Using a multistage study design, random systematic sampling was used to represent the target population, who were weighted based on ethnicity and rural-urban ratios so as to represent the general population distribution. Trained field-workers conducted direct interviews and administered the American Urological Association Symptom Index (AUA-SI), the International Index of Erectile Function (IIEF-5) questionnaire and questions on incontinence based on the International Continence Society 2002 definition.
RESULTS: In all, 418 men aged > or = 40 years were interviewed, of whom 353 completed the AUA-SI questionnaire (84.5% response rate). The prevalence of mild, moderate and severe LUTS was 80.6%, 6% and 0.3%, respectively. The prevalent symptoms were frequency and nocturia. There was moderate and severe ED in 45.9% of men, whereas incontinence was reported by 8.2%. The AUA-SI correlated strongly with age (R = 0.291, P < 0.001), IIEF-5 (R = - 0.265, P < 0.001) and diabetes mellitus.
CONCLUSION: The prevalence and severity of LUTS, ED and incontinence increased with age in this multiethnic Asian population, in which ED correlated strongly with LUTS. Compared to the Western population, the prevalence of LUTS was significantly lower, while the prevalence of ED and incontinence were comparable.
Comparative DDT-susceptibility status and glutathion s-transferase (GST) activity of Malaysian Anopheles maculatus, Culex quinquefasciatus and Aedes aegypti was investigated to ascertain the role of this enzyme in DDT resistance. The standardised WHO dose-mortality bioassay tests were used to determine DDT susceptibility in these mosquitos, whilst GST microassay (Brogdon and Barber, 1990) was conducted to measure the activity of this enzyme in mosquito homogenate. It appeared that DDT susceptibility status of Malaysian mosquitos was not correlated with GST activity.
Pros and cons of Percutaneous Nephrolithotripsy (PCNL) versus Extracorporeal Shockwave Lithotripsy (ESWL) have often been highlighted when one discusses on the management of renal stones. An oft quoted point is that PCNL entails a prolonged hospital stay whereas ESWL sessions are day surgical in nature. However, PCNL has superior stone clearance rate as compared to ESWL especially for lower pole stones. In addition, PCNL is more suitable for large bulk stones and when ancillary procedures are required e.g. endopyelotomy. The first 50 cases of successful tubeless PCNL were reported by Bellman et al in 1997. The remarkable recovery of patients in their series encouraged them to employ this technique as their technique of choice for the majority of their cases. A similar technique was employed on endopyelotomy by Liang et al and they concluded that this was a safe, less morbid and effective technique. We report our first case of tubeless PCNL.
To determine if a volume-adjusted increase in the number of biopsy cores could detect more prostate cancers than the standard sextant biopsy alone, without increasing morbidity, and to determine its applicability in Malaysian patients, as a standard sextant biopsy misses 20-25% of prostate malignancies.
SARS-CoV-2 virus continues to evolve and mutate causing most of the mutated variants resist to many of the therapeutic monoclonal antibodies (mAbs). Despite several mAbs retained neutralizing capability for Omicron BA.1 and BA.2, reduction in neutralization potency was reported. Hence, effort of searching for mAb that is broader in neutralization breadth without losing the neutralizing ability is continued. MW06 was reported with capability in neutralizing most of the variants of concern (VOC) and it binds to the conserved region (left flank) near epitope mAb sotrovimab (S309). In this study, binding affinity of mAb MW06 and its cocktail formulation with MW05 for receptor binding domain (RBD) SARS-CoV-2 virus was investigated under molecular dynamics simulations (MDs). Binding free energies computed by Molecular Mechanics Generalised Born Surface Area (MM-GBSA) algorithm predicted the binding affinity of MW06 for RBD BA.1 (-53 kcal/mol) as strong as RBD wildtype (-58 kcal/mol) while deterioration was observed for RBD BA.2 (-43 kcal/mol). Alike S309 and MW06, simulated cocktail mAb (MW05 and MW06)-RBD interactions suggested the neutralizing capability of the cocktail formulation for RBD BA.1 and BA.2 reduced. Meanwhile, residue pairs that favour the communication between the mAb and RBD have been identified by decomposing the free energy per pairwise residue basis. Apart from understanding the effects of mutation occurred in the RBD region on human angiotensin-converting enzyme 2 (hACE2) binding, impact of heavily mutated RBD on mAb-RBD interactions was investigated in this study as well. In addition to energetic profile obtained from MDs, plotting the dynamics cross-correlation map of the mAb-RBD complex under elastic network model (ENM) was aimed to understand the cross-correlations between residue fluctuations. It allows simple and rapid analysis on the motions or dynamics of the protein residues of mAbs and RBD in complex. Protein residues having correlated motions are normally part of the structural domains of the protein and their respective motions and protein function are related. Motion of mutated RBD residues and mAb residues was less correlated while their respective interactions energy computed to be higher. The combined techniques of MDs and ENM offered simplicity in understanding dynamics and energy contribution that explain binding affinity of mAb-RBD complexes.
Objective: To study the prevalence of symptomatic BPE among Malaysian men age 50 and above attending prostate health awareness campaign and to identify differences in prevalence between different ethnic groups residing within metropolitan Kuala Lumpur.
Materials and Methods: Demographic data and the completed International Prostate Symptom Score (IPSS), maximal uroflow rate (Qmax) and prostate size of volunteers, aged 50 and above, who attended the prostate health awareness campaign were analyzed. Subjects with known prostate diseases or prostate surgery, bladder disorders and neurological disorders were excluded.
Results: 2086 volunteers attended the campaign. 575 men fulfilled the inclusion criteria and their demographic data, IPSS; peak flow rate and prostate volume were analysed. Overall, 18.9% and 39.6% of the men were severely and moderately symptomatic, respectively. The prevalence of moderate to severe lower urinary tract symptoms (LUTS) in Malays, Chinese and Indians were 70%, 59% and 50% respectively (p=0.004). The commonest bothersome symptoms were nocturia (56%), frequency (50.4%) and sense of incomplete voiding (43.5%). The mean peak flow rate of the subjects was 15.4ml/s. 20.9% and 55.2% of the subjects had peak flow less than 10ml/sec and 15ml/sec respectively. The mean prostate size was 25.1cc. There is no significant difference in term of maximal flow rate and prostate size among Malays, Chinese and Indians in Malaysia. A good correlation was found between the total symptom score and the single disease-specific quality of life question (r=0.69, p<0.001). The correlation between IPSS and peak flow rate (r=-0.22, p<0.001) and prostate volume (r=0.11, p=0.009) was weak. There was no correlation between IPSS and age (r=0.06, p=0.17). The prevalence of symptomatic benign prostate enlargement (BPE) was 39.3%. The prevalence increased 8% per decade from 41.7% for men aged 50 to 59 to 65.4% for men aged 70 or more. There is no significant difference in prevalence of symptomatic BPE among the three ethnic groups. The prevalence of BPO was 15.8%.
Conclusion: The correlation between symptom score, maximal flow rate and prostate size was poor and one cannot predict the value of one parameter by knowing one or more of the other parameters. There is a high prevalence of LUTS suggestive of benign prostatic obstruction in the apparently healthy Malaysian aged 50 and above attending the prostate health awareness campaign.
DRE has been used as a diagnostic and screening tool for prostate cancer for decades. However these are based on Western data and its local applicability has yet to be verified. We held a Prostate Health Awareness Week in August 1998 and a total of 2086 men were screened. All men aged 50 years old and above were included for the study. The subjects were evaluated on DRE findings, PSA levels and if indicated a TRUS-guided biopsy results. We concluded that DRE per se might have limited role in the screening of prostate cancer in Malaysia. Screening using DRE and PSA combined are still recognized as the most cost-effective means. Neither DRE nor PSA alone has high enough specificity for diagnosis of prostate cancer cases. Combining DRE and PSA will definitely increase the specificity significantly.
Study site: e Urology
Clinic of Kuala Lumpur Hospital
In this study, we investigate the binding interactions of two synthetic antiviral peptides (DET2 and DET4) on type II dengue virus (DENV2) envelope protein domain III. These two antiviral peptides are designed based on the domain III of the DENV2 envelope protein, which has shown significant inhibition activity in previous studies and can be potentially modified further to be active against all dengue strains. Molecular docking was performed using AutoDock Vina and the best-ranked peptide-domain III complex was further explored using molecular dynamics simulations. Molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) was used to calculate the relative binding free energies and to locate the key residues of peptide-protein interactions. The predicted binding affinity correlated well with the previous experimental studies. DET4 outperformed DET2 and is oriented within the binding site through favorable vdW and electrostatic interactions. Pairwise residue decomposition analysis has revealed several key residues that contribute to the binding of these peptides. Residues in DET2 interact relatively lesser with the domain III compared to DET4. Dynamic cross-correlation analysis showed that both the DET2 and DET4 trigger different dynamic patterns on the domain III. Correlated motions were seen between the residue pairs of DET4 and the binding site while binding of DET2 results in anti-correlated motion on the binding site. This work showcases the use of computational study in elucidating and explaining the experiment observation on an atomic level.
Higher education policy and talent training are failing to meet the ever-changing expectations of employers and society in Taiwan, resulting in a gap between university education and employment. This study used social cognitive career theory (SCCT) to explore the relationships among self-efficacy, transformational leadership (TL), student employability (SE), and problem-based learning (PBL) in higher education institutions (HEIs). The analysis of 637 undergraduates from 16 Taiwanese HEIs using structural equation modeling (SEM) shows significant positive correlations among self-efficacy, PBL, TL, and SE, with PBL and self-efficacy as key mediators. Based on these findings, the researchers propose feasible suggestions for related issues and future research.
Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log10 PFU viral reduction with IC50value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.
Aedes aegypti, Aedes albopictus and Culex quinquefasciatus are vectors of dengue fever and West Nile virus diseases. This study was conducted to determine the toxicity, mechanism of action and the binding interaction of three active phenylpropanoids from Piper sarmentosum (Piperaceae) toward late 3rd or early 4th larvae of above vectors. A bioassay guided-fractionation on the hexane extract from the roots of Piper sarmentosum led to the isolation and identification of three active phenylpropanoids; asaricin 1, isoasarone 2 and trans-asarone 3. The current study involved evaluation of the toxicity and acetylcholinesterase (AChE) inhibition of these compounds against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae. Asaricin 1 and isoasarone 2 were highly potent against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae causing up to 100% mortality at ≤ 15 μg/mL concentration. The ovicidal activity of asaricin 1, isoasarone 2 and trans-asarone 3 were evaluated through egg hatching. Asaricin 1 and isoasarone 2 showed potent ovicidal activity. Ovicidal activity for both compounds was up to 95% at 25μg/mL. Asaricin 1 and isoasarone 2 showed strong inhibition on acetylcholinesterase with relative IC50 values of 0.73 to 1.87 μg/mL respectively. These findings coupled with the high AChE inhibition may suggest that asaricin 1 and isoasarone 2 are neuron toxic compounds toward Aedes aegypti, Aedes albopictus and Culex quinquefasciatus. Further computational docking with Autodock Vina elaborates the possible interaction of asaricin 1 and isoasarone 2 with three possible binding sites of AChE which includes catalytic triads (CAS: S238, E367, H480), the peripheral sites (PAS: E72, W271) and anionic binding site (W83). The binding affinity of asaricin 1 and isoasarone 2 were relatively strong with asaricin 1 showed a higher binding affinity in the anionic pocket.
There are a multitude of factors influencing student employability, with all previous studies basing their conclusions upon predetermined variables according to different theories and exploring the relevance between them. In this study, teachers' knowledge transfer and market orientation-are put forward on the basis of the marketing concepts in order to explore the conspicuousness between various factors within the structural model. This study uses students from colleges in Taiwan and mainland China, and purposive sampling is adopted to acquire samples required for statistics. A total of 1,222 valid questionnaires were collected from Taiwanese and Mainland China students. The results indicate that knowledge transfer, market orientation and absorptive capacity have significant impacts on student employability, that the absorptive capacity has a positive moderating effect on the influence of knowledge transfer and market orientation on student employability. Based on results and findings, this study will provide suggestions for theoretical and practical implications.
PURPOSE: We determined the clinical efficacy and safety of terazosin in the treatment of patients with female lower urinary tract symptoms.
MATERIALS AND METHODS: A total of 100 females 20 to 70 years old who met the inclusion criteria of total International Prostate Symptom Score 8 or greater, symptom duration 1 or more months, and did not meet any exclusion criteria were entered into the study. Subjects were randomized to receive terazosin or placebo in titrated dose from 1 mg od, 1 mg twice daily to 2 mg twice daily during 14 weeks. Successful treatment outcomes use primary end point of International Prostate Symptom Score quality of life 2 or less and secondary end point of total International Prostate Symptom Score 7 or less. Other outcome measures included International Prostate Symptom Score individual item scores, King's Health Questionnaire quality of life domains, objective assessment parameters of 24-hour frequency volume chart, maximum flow rate and post-void residual urine.
RESULTS: Using a primary end point, 32 of 40 (80%) evaluable terazosin subjects responded in contrast to 22 of 40 (55%) evaluable placebo subjects (p <0.02). The secondary end point revealed a successful outcome in 85% of terazosin subjects vs 55% in placebo (p <0.01). Of the 7 International Prostate Symptom Score individual item scores, only item scores of frequency and straining showed statistically significant reductions with terazosin (p <0.01). All King's Health Questionnaire quality of life domains except domain of severity measures showed statistically significant improvement with terazosin (p <0.05). There were no differences between treatment groups in all objective assessment parameters. Of all evaluable subjects 23 of 40 (58%) on placebo experienced adverse events vs 16 of 40 (40%) on terazosin (p >0.05).
CONCLUSIONS: Terazosin proved to be more effective and safe than placebo in patients with female lower urinary tract symptoms.
Protein-protein interaction plays an essential role in almost all cellular processes and biological functions. Coupling molecular dynamics (MD) simulations and nanoparticle tracking analysis (NTA) assay offered a simple, rapid, and direct approach in monitoring the protein-protein binding process and predicting the binding affinity. Our case study of designed ankyrin repeats proteins (DARPins)-AnkGAG1D4 and the single point mutated AnkGAG1D4-Y56A for HIV-1 capsid protein (CA) were investigated. As reported, AnkGAG1D4 bound with CA for inhibitory activity; however, it lost its inhibitory strength when tyrosine at residue 56 AnkGAG1D4, the most key residue was replaced by alanine (AnkGAG1D4-Y56A). Through NTA, the binding of DARPins and CA was measured by monitoring the increment of the hydrodynamic radius of the AnkGAG1D4-gold conjugated nanoparticles (AnkGAG1D4-GNP) and AnkGAG1D4-Y56A-GNP upon interaction with CA in buffer solution. The size of the AnkGAG1D4-GNP increased when it interacted with CA but not AnkGAG1D4-Y56A-GNP. In addition, a much higher binding free energy (∆GB) of AnkGAG1D4-Y56A (-31 kcal/mol) obtained from MD further suggested affinity for CA completely reduced compared to AnkGAG1D4 (-60 kcal/mol). The possible mechanism of the protein-protein binding was explored in detail by decomposing the binding free energy for crucial residues identification and hydrogen bond analysis.
Hand, foot and mouth disease (HFMD) is a childhood disease caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Capsid loops are important epitopes for EV-A71 and CV-A16. Seven chimeric EV-A71 (ChiE71) involving VP1 BC (45.5% similarity), DE, EF, GH and HI loops, VP2 EF loop and VP3 GH loop (91.3% similarity) were substituted with corresponding CV-A16 loops. Only ChiE71-1-BC, ChiE71-1-EF, ChiE71-1-GH and ChiE71-3-GH were viable. EV-A71 and CV-A16 antiserum neutralized ChiE71-1-BC and ChiE71-1-EF. Mice immunized with inactivated ChiE71 elicited high IgG, IFN-γ, IL-2, IL-4 and IL-10. Neonatal mice receiving passive transfer of WT EV-A71, ChiE71-1-EF and ChiE71-1-BC immune sera had 100%, 80.0% and no survival, respectively, against lethal challenges with EV-A71, suggesting that the substituted CV-A16 loops disrupted EV-A71 immunogenicity. Passive transfer of CV-A16, ChiE71-1-EF and ChiE71-1-BC immune sera provided 40.0%, 20.0% and 42.9% survival, respectively, against CV-A16. One-day-old neonatal mice immunized with WT EV-A71, ChiE71-1-BC, ChiE71-1-EF and CV-A16 achieved 62.5%, 60.0%, 57.1%, and no survival, respectively, after the EV-A71 challenge. Active immunization using CV-A16 provided full protection while WT EV-A71, ChiE71-1-BC and ChiE71-1-EF immunization showed partial cross-protection in CV-A16 lethal challenge with survival rates of 50.0%, 20.0% and 40%, respectively. Disruption of a capsid loop could affect virus immunogenicity, and future vaccine design should include conservation of the enterovirus capsid loops.
To determine the prevalence, severity, and quality-of-life (QOL) impact of female lower urinary tract symptoms (FLUTS); to determine the patterns, reasons, and factors contributing to the women's treatment-seeking behavior; and to describe the relationship between the social demographic characteristics and FLUTS.