The objective of this study was to determine the relationship between nutritional status, physical activity and quality of life among gastrointestinal cancer survivors.
Effects of high-protein diets that are rich in saturated fats on cell adhesion molecules, thrombogenicity and other nonlipid markers of atherosclerosis in humans have not been firmly established. We aim to investigate the effects of high-protein Malaysian diets prepared separately with virgin olive oil (OO), palm olein (PO) and coconut oil (CO) on cell adhesion molecules, lipid inflammatory mediators and thromobogenicity indices in healthy adults.
We have performed computational molecular modelling to study the polarization switching and hysteresis loop behaviours of DNA and RNA nucleobases using the PM3 semi-empirical quantum mechanical approaches. All the nucleobases: adenine (A), thymine (T), guanine (G), cytosine (C), and uracil (U) were modelled. Our study indicates that all the nucleobases exhibit a zero-field polarization due to the presence of polar atoms or molecules such as amidogen and carbonyl. The shape of polarization P versus an applied electric field E hysteresis loop is square, implying typical ferroelectrics behaviour. The total energy U as a function of an applied electric field E exhibits a butterfly-like loop. The presence of zero-field polarization and ferroelectrics hysteresis loop behaviours in nucleobases may support the hypothesis of the existence of bioferroelectricity in DNA and RNA. We also found an interesting relationship between the minimum electric field required for switching [Formula: see text] and the ratio of the topological polar surface area (TPSA) to the total surface area (TSA) of a nucleobase. In particular, the [Formula: see text] of a nucleobase is inversely proportional to the TPSA/TSA ratio. This work may provide useful information for understanding the possible existence of ferroelectricity in biomaterials.
Global public health has been a critical problem by the sudden increase of the COVID-19 outbreak. The papain-like protease (PLpro) of SARS-CoV-2 is a key promising target for antiviral drug development since it plays a pivotal role in viral replication and innate immunity. Here, we employed the all-atom molecular dynamics (MD) simulations and binding free energy calculations based on MM-PB(GB)SA and SIE methods to elucidate and compare the binding behaviors of five inhibitors derived from peptidomimetic inhibitors (VIR250 and VIR251) and naphthalene-based inhibitors (GRL-0617, compound 3, and compound Y96) against SARS-CoV-2 PLpro. The obtained results revealed that all inhibitors interacting within the PLpro active site are mostly driven by vdW interactions, and the hydrogen bond formation in residues G163 and G271 with peptidomimetics and the Q269 residue with naphthalene-based inhibitors was essential for stabilizing the protein-ligand complexes. Among the five studied inhibitors, VIR250 exhibited the most binding efficiency with SARS-CoV-2 PLpro, and thus, it was chosen for the rational drug design. Based on the computationally designed ligand-protein complexes, the replacement of aromatic rings including heteroatoms (e.g., thiazolopyridine) at the P2 and P4 sites could help to improve the inhibitor-binding efficiency. Furthermore, the hydrophobic interactions with residues at P1-P3 sites can be increased by enlarging the nonpolar moieties (e.g., ethene) at the N-terminal of VIR250. We expect that the structural data obtained will contribute to the development of new PLpro inhibitors with more inhibitory potency for COVID-19.
Several modifiable risk factors for sudden infant death syndrome (SIDS) have been identified such as sleeping prone or on the side, sleeping on a soft surface, bed-sharing, no prenatal care and maternal ante-natal smoking. A cross-sectional survey of infant sleep and care practices was conducted among parents of babies aged below 8 months to determine the prevalence and predictors of non-supine sleep position and the prevalence of other high-risk infant care practices for SIDS. Of 263 infants, 24.7% were placed to sleep in the non-supine position and age of infants was a factor positively associated with this (adjusted odds ratio 1.275, 95% CI=1.085, 1.499). The most common modifiable risk factor was the presence of soft toys or bedding in the infants' bed or cot (89.4%). Results from this study indicate that although the predominant sleep position of Malaysian infants in this population is supine, the majority of infants were exposed to other care practices which have been shown to be associated with SIDS.
Effects of phosphorus content (510 to 987 ppm) on the gelatinization and retrogradation of 6 potato cultivars (Benimaru, Hokkaikogane, Irish Cobbler, Konafubuki, Sakurafubuki, and Touya) were studied. Pasting properties were analyzed by RVA, thermal properties by DSC, and mechanical properties of the starch gels by TA. Phosphorus was positively correlated with swelling power (r= 0.84) and negatively correlated with solubility (r= 0.83). Phosphorus content showed significant effect on certain pasting properties of potato starch such as peak viscosity, breakdown, and setback. Phosphorus content showed a significant positive correlation with peak viscosity (r= 0.95) and breakdown (r= 0.90). Increasing concentration of phosphorus tends to decrease the setback. Phosphorus content had no influence on thermal properties and mechanical properties of potato starch gel.
This study aimed to investigate the potential association of TYK2 and STAT3 genes with the susceptibility to Crohn's disease (CD) among Malaysians. DNA samples were obtained from 80 CD patients and 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism methods were employed for genotyping, followed by statistical analysis. In our current study, none of the single nucleotide polymorphisms of either TYK2 or STAT3 was statistically associated with the susceptibility to CD in our local population (P > 0.05). In contrast, there was a statistically significant association between the G/G homozygotes of the STAT3 rs2293152 and the healthy control group (χ(2) = 6.229, P < 0.05). In conclusion, our study does not support the role of the TYK2 and STAT3 genes influencing CD susceptibility.
Nasopharyngeal carcinoma (NPC) is endemic in Southern China, Taiwan, Malaysia, Singapore, North Africa and Alaska. About 30% of NPC patients develop recurrence or metastasis despite initial radical treatment. Palliative chemotherapy is the first-line treatment for inoperable recurrence or distant metastatic disease. However the standard first-line chemotherapeutic regimen is yet to be established until recently gemcitabine and cisplatin has been proven superior to traditional regimen with 5-FU and cisplatin shown in a phase III randomized-controlled trial. Further palliative systemic treatment options including other chemotherapeutic regimens, targeted therapy and more recently immunotherapy have gradually evolved. We provided a comprehensive review on different traditional chemotherapeutic regimens and highlighted the latest chemotherapeutic treatments as well as the latest development of targeted therapies, immune checkpoint inhibitors and other immunotherapeutic options in this setting.
INTRODUCTION: Non-communicable diseases (NCD) is a global health threat. the Chronic Care Model (CCM) was proven effective in improving NCD management and outcomes in developed countries. Evidence from developing countries including Malaysia is limited and feasibility of CCM implementation has not been assessed. this study intends to assess the feasibility of public primary health care clinics (PHC) in providing care according to the CCM.
METHODOLOGY: A cross-sectional survey was conducted to assess the public PHC ability to implement the components of CCM. All public PHC with Family Medicine Specialist in Selangor and Kuala Lumpur were invited to participate. A site feasibility questionnaire was distributed to collect site investigator and clinic information as well as delivery of care for diabetes and hypertension.
RESULTS: there were a total of 34 public PHC invited to participate with a response rate of 100%. there were 20 urban and 14 suburban clinics. the average number of patients seen per day ranged between 250-1000 patients. the clinic has a good mix of multidisciplinary team members. All clinics had a diabetic registry and 73.5% had a hypertensive registry. 23.5% had a dedicated diabetes and 26.5% had a dedicated hypertension clinic with most clinic implementing integrated care of acute and NCD cases.
DISCUSSION: the implementation of the essential components of CCM is feasible in public PHCs, despite various constraints. Although variations in delivery of care exists, majority of the clinics have adequate staff that were willing to be trained and are committed to improving patient care.
Metabolic epilepsy is a metabolic abnormality which is associated with an increased risk of epilepsy development in affected individuals. Commonly used antiepileptic drugs are typically ineffective against metabolic epilepsy as they do not address its root cause. Presently, there is no review available which summarizes all the treatment options for metabolic epilepsy. Thus, we systematically reviewed literature which reported on the treatment, therapy and management of metabolic epilepsy from four databases, namely PubMed, Springer, Scopus and ScienceDirect. After applying our inclusion and exclusion criteria as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we reviewed a total of 43 articles. Based on the reviewed articles, we summarized the methods used for the treatment, therapy and management of metabolic epilepsy. These methods were tailored to address the root causes of the metabolic disturbances rather than targeting the epilepsy phenotype alone. Diet modification and dietary supplementation, alone or in combination with antiepileptic drugs, are used in tackling the different types of metabolic epilepsy. Identification, treatment, therapy and management of the underlying metabolic derangements can improve behavior, cognitive function and reduce seizure frequency and/or severity in patients.
Several anti-HIV scaffolds have been proposed as complementary treatments to highly active antiretroviral therapy. AnkGAG1D4, a designed ankyrin repeat protein, formerly demonstrated anti-HIV-1 replication by interfering with HIV-1 Gag polymerization. However, the improvement of the effectiveness was considered. Recently, the dimeric molecules of AnkGAG1D4 were accomplished in enhancing the binding activity against HIV-1 capsid (CAp24). In this study, the interaction of CAp24 against the dimer conformations was elucidated to elaborate the bifunctional property. The accessibility of the ankyrin binding domains was inspected by bio-layer interferometry. By inverting the second module of dimeric ankyrin (AnkGAG1D4NC-CN), the CAp24 interaction KD was significantly reduced. This reflects the capability of AnkGAG1D4NC-CN in simultaneously capturing CAp24. On the contrary, the binding activity of dimeric AnkGAG1D4NC-NC was indistinguishable from the monomeric AnkGAG1D4. The bifunctional property of AnkGAG1D4NC-CN was subsequently confirmed in the secondary reaction with additional p17p24. This data correlates with the MD simulation, which suggested the flexibility of the AnkGAG1D4NC-CN structure. The CAp24 capturing capacity was influenced by the distance of the AnkGAG1D4 binding domains to introduce the avidity mode of AnkGAG1D4NC-CN. Consequently, AnkGAG1D4NC-CN showed superior potency in interfering with HIV-1 NL4-3 WT and HIV-1 NL4-3 MIRCAI201V replication than AnkGAG1D4NC-NC and an affinity improved AnkGAG1D4-S45Y.
Plasmodium knowlesi is a simian malaria parasite currently recognized as the fifth causative agent of human malaria. Recently, naturally acquired P. cynomolgi infection in humans was also detected in Southeast Asia. The main reservoir of both parasites is the long-tailed and pig-tailed macaques, which are indigenous in this region. Due to increased urbanization and changes in land use, there has been greater proximity and interaction between the long-tailed macaques and the general population in Singapore. As such, this study aims to determine the prevalence of simian malaria parasites in local macaques to assess the risk of zoonosis to the general human population. Screening for the presence of malaria parasites was conducted on blood samples from 660 peridomestic macaques collected between Jan 2008 and Mar 2017, and 379 wild macaques collected between Mar 2009 and Mar 2017, using a Pan-Plasmodium-genus specific PCR. Positive samples were then screened using a simian Plasmodium species-specific nested PCR assay to identify the species of parasites (P. knowlesi, P. coatneyi, P. fieldi, P. cynomolgi, and P. inui) present. All the peridomestic macaques sampled were tested negative for malaria, while 80.5% of the 379 wild macaques were infected. All five simian Plasmodium species were detected; P. cynomolgi being the most prevalent (71.5%), followed by P. knowlesi (47.5%), P. inui (42.0%), P. fieldi (32.5%), and P. coatneyi (28.5%). Co-infection with multiple species of Plasmodium parasites was also observed. The study revealed that Singapore's wild long-tailed macaques are natural hosts of the five simian malaria parasite species, while no malaria was detected in all peridomestic macaques tested. Therefore, the risk of simian malaria transmission to the general human population is concluded to be low. However, this can be better demonstrated with the incrimination of the vectors of simian malaria parasites in Singapore.
BACKGROUND: Topical immunotherapy has recently been found useful in the treatment of chronic and extensive Alopecia Areata (AA).
OBJECTIVE: To evaluate the efficacy and safety of diphenylcyclopropenone (DPCP) use among Chinese patients with steroid resistant and extensive AA in our institute.
METHODS: The medical records of 31 Chinese patients treated with DPCP were analysed retrospectively. The efficacy, adverse effects, and relapse rate of DPCP treatment were reviewed.
RESULTS: Thirty-one (16 male, 15 female) Chinese patients with extensive, steroid resistant Alopecia Areata and a mean age of 28.9 years (SE 10.4) were treated. The mean age of onset was 17.8 years (SE 8.8) with an average disease duration of 11.2 years (SE 7.7). Ten patients had a history of atopy and 4 had a history of thyroid disease. Nail changes were found in 14 patients and a family history of AA was found in 2 patients. Thirteen patients (41.9%) had experienced total hair loss. Two patients abandoned the treatment due to severe side effects. Of the remaining 29 patients, 4 (13.8%), 7 (24.1%), 5 (17.2%), and 13 (44.8%) achieved >90% complete response, >50-90% partial response, >10-50% minimal response, and <10% no response hair regrowth, respectively. Adverse effects included pruritus, erythema, vesiculation, scaling, cervical lymphadenopathy, dyspigmentation and urticarial reactions. Relapse occurred (>25% hair loss) in 69.23% of patients after 18 months of follow up.
CONCLUSIONS: DPCP is an effective and tolerable treatment for Chinese patients with extensive, steroid resistant AA.
Background: Overprescription of antibiotics is a continuing problem in primary care. This study aims to assess the antibiotic prescribing rates and antibiotic choices for upper respiratory tract infections (URTI) and urinary tract infections (UTI) in Malaysian primary care.
Method: Antibiotic prescribing data for URTI and UTI was extracted from a morbidity survey of randomly selected primary care clinics in Malaysia.
Results: Analysis was performed of 1163 URTI and 105 UTI encounters. Antibiotic prescribing rates for URTI and UTI were 33.8% and 57.1% respectively. Antibiotic prescribing rates were higher in private clinics compared to public clinics for URTI, but not for UTI. In URTI encounters, the majority of antibiotics prescribed were penicillins and macrolides, but penicillin V was notably underused. In UTI encounters, the antibiotics prescribed were predominantly penicillins or cotrimoxazole.
Discussion: Greater effort is needed to bring about evidence based antibiotic prescribing in Malaysian primary care, especially for URTIs in private clinics.
Keywords: general practice, prescriptions, drug; upper respiratory tract infection; urinary tract infection; antibiotics, guideline; evidence based medicine
Study site: Klinik Kesihatan, Malaysia
Pregnant adolescents are a high-risk population for suicide. However, a knowledge gap still exists on how sexual and religious knowledge, attitudes and practices (KAP) influence suicidal ideation (SI) in teenage pregnancy. We aim to explore the interplay between psychiatric diagnoses, sociodemographic factors and KAP of sexual and religious issues as risk factors of SI among 114 pregnant Malaysian adolescents from 6 rehabilitation centers and a tertiary hospital. Single sexual partner was an independent predictor of SI, suggesting the role of less sexual experience as a risk factor for SI after controlling for major depression. Participants who were unsure versus those who agreed with the statement that most religions' viewed sex outside marriage as wrong had a lower risk of SI after controlling for major depression. Pregnant adolescents with a single sexual partner were significantly associated with current SI. Ambivalence towards religious prohibitions on premarital sex may protect against suicidal ideation.
Certain proteins have demonstrated proficient human immunodeficiency virus (HIV-1) life cycle disturbance. Recently, the ankyrin repeat protein targeting the HIV-1 capsid, AnkGAG1D4, showed a negative effect on the viral assembly of the HIV-1NL4-3 laboratory strain. To extend its potential for future clinical application, the activity of AnkGAG1D4 in the inhibition of other HIV-1 circulating strains was evaluated. Chimeric NL4-3 viruses carrying patient-derived Gag/PR-coding regions were generated from 131 antiretroviral drug-naïve HIV-1 infected individuals in northern Thailand during 2001⁻2012. SupT1, a stable T-cell line expressing AnkGAG1D4 and ankyrin non-binding control (AnkA32D3), were challenged with these chimeric viruses. The p24CA sequences were analysed and classified using the K-means clustering method. Among all the classes of virus classified using the p24CA sequences, SupT1/AnkGAG1D4 demonstrated significantly lower levels of p24CA than SupT1/AnkA32D3, which was found to correlate with the syncytia formation. This result suggests that AnkGAG1D4 can significantly interfere with the chimeric viruses derived from patients with different sequences of the p24CA domain. It supports the possibility of ankyrin-based therapy as a broad alternative therapeutic molecule for HIV-1 gene therapy in the future.