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Breast cancer has a diverse aetiology characterized by the heterogeneous expression of hormone receptors and signalling molecules, resulting in varied sensitivity to chemotherapy. The adverse side effects of chemotherapy coupled with the development of drug resistance have prompted the exploration of natural products to combat cancer. Lactoferricin B (LfcinB) is a natural peptide derived from bovine lactoferrin that exhibits anticancer properties. LfcinB was evaluated in vitro for its inhibitory effects on cell lines representing different categories of breast cancer and in vivo for its suppressive effects on tumour xenografts in NOD-SCID mice. The different breast cancer cell lines exhibited varied levels of sensitivity to apoptosis induced by LfcinB in the order of SKBR3>MDA-MB-231>MDA-MB-468>MCF7, while the normal breast epithelial cells MCF-10A were not sensitive to LfcinB. The peptide also inhibited the invasion of the MDA-MB-231 and MDA-MB-468 cell lines. In the mouse xenograft model, intratumoural injections of LfcinB significantly reduced tumour growth rate and tumour size, as depicted by live imaging of the mice using in vivo imaging systems (IVIS). Harvested tumour volume and weight were significantly reduced by LfcinB treatment. LfcinB, therefore, is a promising and safe candidate that can be considered for the treatment of breast cancer., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Malaysia has the highest rate of diabetes mellitus (DM) in the Southeast Asian region, and has ongoing air pollution and periodic haze exposure., Methods: Diabetes data were derived from the Malaysian National Health and Morbidity Surveys conducted in 2006, 2011 and 2015. The air pollution data (NO x , NO 2 , SO 2 , O 3 and PM 10 ) were obtained from the Department of Environment Malaysia. Using multiple logistic and linear regression models, the association between long-term exposure to these pollutants and prevalence of diabetes among Malaysian adults was evaluated., Results: The PM 10 concentration decreased from 2006 to 2014, followed by an increase in 2015. Levels of NO x decreased while O 3 increased annually. The air pollutant levels based on individual modelled air pollution exposure as measured by the nearest monitoring station were higher than the annual averages of the five pollutants present in the ambient air. The prevalence of overall diabetes increased from 11.4% in 2006 to 21.2% in 2015. The prevalence of known diabetes, underdiagnosed diabetes, overweight and obesity also increased over these years. There were significant positive effect estimates of known diabetes at 1.125 (95% CI, 1.042, 1.213) for PM 10 , 1.553 (95% CI, 1.328, 1.816) for O 3 , 1.271 (95% CI, 1.088, 1.486) for SO 2 , 1.124 (95% CI, 1.048, 1.207) for NO 2 , and 1.087 (95% CI, 1.024, 1.153) for NO x for NHMS 2006. The adjusted annual average levels of PM 10 [1.187 (95% CI, 1.088, 1.294)], O 3 [1.701 (95% CI, 1.387, 2.086)], NO 2 [1.120 (95% CI, 1.026, 1.222)] and NO x [1.110 (95% CI, 1.028, 1.199)] increased significantly from NHMS 2006 to NHMS 2011 for overall diabetes. This was followed by a significant decreasing trend from NHMS 2011 to 2015 [0.911 for NO 2 , and 0.910 for NO x ]., Conclusion: The findings of this study suggest that long-term exposure to O 3 is an important associated factor of underdiagnosed DM risk in Malaysia. PM 10 , NO 2 and NO x may have mixed effect estimates towards the risk of DM, and their roles should be further investigated with other interaction models. Policy and intervention measures should be taken to reduce air pollution in Malaysia.

Objective: To investigate the association between dietary patterns (DP) and overweight risk in the Malaysian Adult Nutrition Surveys (MANS) of 2003 and 2014., Design: DP were derived from the MANS FFQ using principal component analysis. The cross-sectional association of the derived DP with prevalence of overweight was analysed., Setting: Malaysia., Participants: Nationally representative sample of Malaysian adults from MANS (2003, n 6928; 2014, n 3000)., Results: Three major DP were identified for both years. These were 'Traditional' (fish, eggs, local cakes), 'Western' (fast foods, meat, carbonated beverages) and 'Mixed' (ready-to-eat cereals, bread, vegetables). A fourth DP was generated in 2003, 'Flatbread & Beverages' (flatbread, creamer, malted beverages), and 2014, 'Noodles & Meat' (noodles, meat, eggs). These DP accounted for 25·6 and 26·6 % of DP variations in 2003 and 2014, respectively. For both years, Traditional DP was significantly associated with rural households, lower income, men and Malay ethnicity, while Western DP was associated with younger age and higher income. Mixed DP was positively associated with women and higher income. None of the DP showed positive association with overweight risk, except for reduced adjusted odds of overweight with adherence to Traditional DP in 2003., Conclusions: Overweight could not be attributed to adherence to a single dietary pattern among Malaysian adults. This may be due to the constantly morphing dietary landscape in Malaysia, especially in urban areas, given the ease of availability and relative affordability of multi-ethnic and international foods. Timely surveys are recommended to monitor implications of these changes.

Leptospirosis is probably the most widespread zoonotic disease in the world especially in tropical countries. There has been an increase in individual studies, which assessed the frequency of leptospirosis in flood conditions. Some studies showed contact with floods was significantly associated with the occurrence of leptospirosis while other studies reported differently. The objective of this meta-analysis was to synthesize the evidence on the risk factors which are associated with human leptospirosis following flooding. We set up the inclusion criteria and searched for the original studies, addressing leptospirosis in human with related to flood in health-related electronic databases including PubMed, Embase, Ovid Medline, google scholar and Scopus sources. We used the terms 'leptospirosis', 'flood', 'risk factor' and terms from the categories were connected with "OR" within each category and by "AND" between categories. The initial search yielded 557 citations. After the title and abstract screening, 49 full-text papers were reviewed and a final of 18 observational studies met the pre-specified inclusion criteria. Overall, the pooled estimates of 14 studies showed that the contact with flooding was a significant factor for the occurrence of leptospirosis (pooled OR: 2.19, 95%CI: 1.48-3.24, I2:86%). On stratification, the strength of association was greater in the case-control studies (pooled OR: 4.01, 95%CI: 1.26-12.72, I2:82%) than other designs (pooled OR:1.77,95%CI:1.18-2.65, I2:87%). Three factors such as 'being male'(pooled OR:2.06, 95%CI:1.29-2.83), the exposure to livestock animals (pooled OR: 1.95, 95%CI:1.26-2.64), the lacerated wound (pooled OR:4.35, 95%CI:3.07-5.64) were the risk factors significantly associated with the incidence of leptospirosis following flooding in the absence of within-study heterogeneity (I2: 0%). We acknowledge study limitations such as publication bias and type 2 statistical errors. We recommended flood control and other environmental modifications that are expected to reduce the risk of leptospiral infection, and a multi-sectoral effort to this aspect would have long-term benefits., Competing Interests: The authors have declared that no competing interests exist.

The detection and identification of two endocytobiotic bacterial strains, one affiliated to the "Candidatus Caedibacter acanthamoebae"/"Ca. Paracaedimonas acanthamoeba", and another to the endosymbiont of Acanthamoeba UWC8 and "Ca. Jidaibacter acanthamoeba" are described. For endocytobiont screening, we developed a PCR method with a set of broad-range bacterial 16S rRNA primers to substitute the commonly used but technically demanding fluorescent in situ hybridization technique. Our PCR test alone without sequencing failed to discriminate the endocytobiont-containing and endocytobiont-free Acanthamoeba sp. due to the presence of mismatched primers to host mitochondrial DNA. We highlighted the need to perform bacterial primer checking against the Acanthamoeba genome to avoid false positive detection in PCR. Although the genetic aspect of "Ca. Caedibacter acanthamoebae"/"Ca. Paracaedimonas acanthamoeba" and the endosymbiont of Acanthamoeba UWC8/"Ca. Jidaibacter acanthamoeba" are well studied, knowledge pertaining to their morphologies are quite vague. Hence, we used transmission electron microscopy to examine our endocytobionts which are affiliated to previously described intracellular bacteria of Acanthamoeba sp. We used good-quality TEM images for the localization and the fate of the current endocytobionts inside different life stages of the hosts. Furthermore, to the best of our knowledge, our TEM findings are the first to provide morphological evidence for the clearance of defective Acanthamoeba endocytobionts via an autophagic-like process., Competing Interests: The authors have declared that no competing interests exist.

The free-living protozoan Acanthamoeba is an opportunistic pathogen that is ubiquitous in our environment. However, its role in affecting indoor air quality and ill-health of indoor occupants is relatively unknown. The present study investigated the presence of Acanthamoeba from the ventilation system and its correlation with other indoor air quality parameters, used in the industry code of practice and its potential as an indicator for indoor air quality. Indoor air quality assessments were carried out in nine commercial buildings with approval from the building management, and the parameters assessed were as recommended by the Department of Occupational Safety and Health. The presence of Acanthamoeba was determined through dust swabs from the ventilation system and indoor furniture. Logistic regression was performed to study the correlation between assessed parameters and occupants' complaints. A total of 107 sampling points were assessed and 40.2% of the supplying air diffuser and blowing fan and 15% of the furniture were positive for cysts. There was a significant correlation between Acanthamoeba detected from the ventilation system with ambient total fungus count (r=0.327; p=0.01) and respirable particulates (r=0.276; p=0.01). Occupants' sick building syndrome experience also correlated with the presence of Acanthamoeba in the ventilation system (r=0.361; p=0.01) and those detected on the furniture (r=0.290; p=0.01). Logistic regression showed that there was a five-fold probability of sick building syndrome among occupants when Acanthamoeba was detected in the ventilation system.

Intestinal parasitic infections (IPIs) have been recognized as one of the most significant causes of illness among disadvantaged communities. Many studies have been conducted on the prevalence of IPIs in Malaysia. However, these studies mostly focused on the indigenous groups in Peninsular Malaysia. The present study was conducted to provide the current baseline data on prevalence of IPIs, anaemia, malnutrition and associated risk factors among the indigenous communities in Sarawak, situation at northwest Borneo island of Malaysia. A cross sectional study was conducted among the longhouses communities. Stool samples were obtained and examined for the presence of IPIs using microscopy technique. Haemoglobin measurement was done using a portable haemoglobin analyzer. Malnutrition (i.e., stunting, underweight and wasting) was assessed using the WHO Anthro software. Statistical analysis was carried out using SPSS software. A total of 341participants took part in this study. The overall prevalence of IPIs was 57.5%. Multivariate analysis indicated that the absence of toilets (OR = 1.6; 95% CI = 1.1-2.7; p = 0.002) and close contact with animals (OR = 1.8; 95% CI = 1.3-2.9; p = 0.027) as significant predictors for IPIs. The incidence of anaemia was 36.4%. The incidence of underweight, wasting and stunting were 22.2%, 5.6% and 35.4%, respectively. Multivariate analysis demonstrated that low level of parental education attainment (OR = 1.9; 95% CI = 1.2-3.0; p = 0.006) was identified as significant predictor for anaemia. The incidence of wasting was significantly associated with mild anaemia (OR = 1.2; 95% CI = 0.9-1.7; p = 0.024). Low household income was identified as significant predictor for stunting (OR = 2.1; 95% CI = 9.8-22.2; p = 0.001) and underweight (OR = 1.9; 95% CI = 5.6-18.7; p = 0.037), respectively. Essentially, the present study highlighted that intestinal parasitic infections, anaemia and malnutrition are still prevalent among rural indigenous community in Sarawak. Improvement of socioeconomic status, periodic mass deworming, iron supplementation and health education program should be included in the control and prevention of public health strategies., Competing Interests: The authors declare that they have no conflict of interest.

Epidemiological study on strongyloidiasis in humans is currently lacking in Malaysia. Thus, a cross-sectional study was carried out to determine the prevalence of Strongyloides stercoralis infection among the inhabitants of longhouse indigenous communities in Sarawak. A single stool and blood sample were collected from each participant and subjected to microscopy, serological and molecular techniques. Five species of intestinal parasites were identified by stool microscopy. None of the stool samples were positive for S. stercoralis . However, 11% of 236 serum samples were seropositive for strongyloidiasis. Further confirmation using molecular technique on stool samples of the seropositive individuals successfully amplified 5 samples, suggesting current active infections. The prevalence was significantly higher in adult males and tended to increase with age. S. stercoralis should no longer be neglected in any intestinal parasitic survey. Combination of more than 1 diagnostic technique is necessary to increase the likelihood of estimating the 'true' prevalence of S. stercoralis .

Airborne bacteria are significant biotic constituents of bioaerosol. Bacteria at high concentrations in the air can compromise indoor air quality (IAQ) and result in many diseases. In tropical environments like Malaysia that extensively utilize air-conditioning systems, this is particularly significant due to continuous recirculation of indoor air and the potential implications for human health. Currently, there is a lack of knowledge regarding the impact of airborne bacteria on IAQ in Malaysia. This study was prompted by a need for reliable baseline data on airborne bacteria in the indoor environment of tropical equatorial Malaysia, that may be used as a reference for further investigations on the potential role played by airborne bacteria as an agent of disease in this region. It was further necessitated due to the threat of bioterrorism with the potentiality of release of exotic pathogenic microorganisms into indoor or outdoor air. Before scientists can detect the latter, a gauge of the common microorganisms in indoor (as well as outdoor) air needs to be ascertained, hence the expediency of this study. Bacterial counts from the broad-based and targeted study were generally in the order of 10(2) colony-forming units (CFU) per m(3) of air. The most prevalent airborne bacteria found in the broad-based study that encompassed all five levels of the building were Gram-positive cocci (67.73%), followed by Gram-positive rods (24.26%) and Gram-negative rods (7.10%). Gram-negative cocci were rarely detected (0.71%). Amongst the genera identified, Kytococcus sp., Micrococcus sp., Staphylococcus sp., Leifsonia sp., Bacillus sp. and Corynebacterium sp. predominated in indoor air. The most dominant bacterial species were Kytococcus sedentarius, Staphylococcus epidermidis and Micrococcus luteus. The opportunistic and nosocomial pathogen, Stenotrophomonas maltophilia was also discovered at a high percentage in the cafeteria. The bacteria isolated in this study have been increasingly documented to cause opportunistic infections in immuno-compromised patients, sometimes with fatal outcomes. Furthermore, some of them are becoming increasingly resistant to antibiotics. Hence, we propose that indoor reservoirs of these bacteria and their associated clinical and more subtle health effects, if any, be investigated further.

Toxoplasma gondii is a parasite that generates latent cysts in the brain; reactivation of these cysts may lead to fatal toxoplasmic encephalitis, for which treatment remains unsuccessful. We assessed spiramycin pharmacokinetics coadministered with metronidazole, the eradication of brain cysts and the in vitro reactivation. Male BALB/c mice were fed 1,000 tachyzoites orally to develop chronic toxoplasmosis. Four weeks later, infected mice underwent different treatments: (i) infected untreated mice (n = 9), which received vehicle only; (ii) a spiramycin-only group (n = 9), 400 mg/kg daily for 7 days; (iii) a metronidazole-only group (n = 9), 500 mg/kg daily for 7 days; and (iv) a combination group (n = 9), which received both spiramycin (400 mg/kg) and metronidazole (500 mg/kg) daily for 7 days. An uninfected control group (n = 10) was administered vehicle only. After treatment, the brain cysts were counted, brain homogenates were cultured in confluent Vero cells, and cysts and tachyzoites were counted after 1 week. Separately, pharmacokinetic profiles (plasma and brain) were assessed after a single dose of spiramycin (400 mg/kg), metronidazole (500 mg/kg), or both. Metronidazole treatment increased the brain spiramycin area under the concentration-time curve from 0 h to ∞ (AUC(0-∞)) by 67% without affecting its plasma disposition. Metronidazole plasma and brain AUC(0-∞) values were reduced 9 and 62%, respectively, after spiramycin coadministration. Enhanced spiramycin brain exposure after coadministration reduced brain cysts 15-fold (79 ± 23 for the combination treatment versus 1,198 ± 153 for the untreated control group [P < 0.05]) and 10-fold versus the spiramycin-only group (768 ± 125). Metronidazole alone showed no effect (1,028 ± 149). Tachyzoites were absent in the brain. Spiramycin reduced in vitro reactivation. Metronidazole increased spiramycin brain penetration, causing a significant reduction of T. gondii brain cysts, with potential clinical translatability for chronic toxoplasmosis treatment.

Background: The aim of this study was to investigate the presence of multidrug resistant yeasts in the faeces of synanthropic wild birds from the Bangsar suburb of Kuala Lumpur., Methods: Species characterisations of yeast isolates and determinations of antimycotic susceptibility profiles were undertaken using the commercial characterization kit, Integral System Yeasts Plus (Liofilchem, Italy)., Results: Fourteen species of yeasts were detected in the bird faecal samples.Candida albicans was present in 28.89% of bird faecal samples, Candida krusei (13.33%), Candida tropicalis (4.44%), Candida glabrata (4.44%), Candida parapsilosis (2.22%), Candida lambica (2.22%), Candida stellatoidea (2.22%), Candida rugosa (2.22%) and Candida lusitaniae (2.22%). Amongst the non-candidal yeast isolates, Cryptococcus laurentii was present in 6.67% of bird faecal samples, Cryptococcus uniguttulatus (4.44%), Saccharomyces cerevisiae (4.44%), Trichosporon pullulans (2.22%), Trichosporon pullulans/Cryptococcus albidus (8.89%) and Rhodotorula rubra/Rhodotorula glutinis (4.44%). Of the isolated yeasts, 18.1% (or 26/144) were found to be resistant to all 11 antimycotic agents they were tested against i.e. Nystatin, Amphotericin B, Flucytosine, Econazole, Ketoconazole, Clotrimazole, Miconazole, Itraconazole, Voriconazole, Fluconazole 16 and Fluconazole 64. 45.8% (or 66/144) of the bird faecal yeast isolates were resistant to four or more of the 11 antimycotic agents they were tested against., Conclusions: This finding is of public health significance as these synanthropic wild birds may be reservoirs for transmission of drug resistant yeast infections to humans.

The aim of the study was to observe the effect of diethylcarbamazine citrate (DEC) on Angiostrongylus malaysiensis infection in albino rats. An attempt was made to vary the dose of DEC and treat infected animals at the larval and adult stages of infection. The doses were varied with an aim at finding an effective dosage. Animals were treated also during the pre-infection period to observe if the drug had any prophylactic properties. The results obtained show that DEC given after infection was effective only when its administration was initiated on day 42 of the infection corresponding to the mature adult stage of the parasite. In addition, it had some prophylactic activity against the infection.

The chemoprophylactic and chemotherapeutic effects of levamisole and mebendazole on Angiostrongylus malaysiensis infection in rats were studied. Both drugs were ineffective in preventing infection while the post-infection treatment showed 100% efficacy. Furthermore, levamisole and mebendazole when given in combination appeared to have an antagonistic effect.

A helminthological examination of 367 wood rats, Rattus tiomanicus, in an oil-palm. estate 24 miles north of Kuala Lumpur conducted during 1973 revealed 8 species of helminths: 5 nematodes. Angiostrongylus malaysiensis (54.2% of the rats infected), Hepatojarakus malayae (48.5%), Nippostrongylus braziliensis (48.0%), Gongylonema neoplasticum (0.3%), Syphacia muris (17.7%); 3 cestodes, Hymenolepis diminuta (6.0%), Hymenolepis nana (7.6%), Hydatigera taeniaeformis (cysticercus) (12.0%) and 1 pentastomid, Armillifer sp. (nymph) (0.8%). Overall helminthic infection rates seemed to be higher than those previously reported in this host species.