MATERIALS AND METHODS: This was a pilot study of N=50 women, who were planning for IVF treatment in University Malaya Medical Centre, Kuala Lumpur, Malaysia from July to December 2023. Women without prior nutritional treatment were consented and assigned to either the multinutrient supplementation (Omega 3, coenzyme Q10, folic acid, selenium, vitamin E, catechins) as the study group or 5mg folic acid daily as control group for at least a month prior to their IVF treatment. All women were treated using an antagonist protocol and ovarian stimulation was started with 200 -300IU of urinary HMG and or recombinant FSH. Antagonists (Ganirelix) commenced when the leading follicle reached a diameter of 11 mm. Triggering with hCG or GnRH agonist when at least 3 follicles of 17 mm in diameter were achieved. Oocyte retrieval was performed 36th hour after trigger. Conventional IVF/ICSI was used for fertilisation. All parameters recorded and analysed using SPSS.
RESULTS: The mean age (36.44 ± 3.33 vs 35.32 ± 3.47 years) and body mass index (25.28 ± 4.12 vs 24.80 ± 4.36 kg/m2) of women in multinutrient supplementation group was similar to control group. The Follicular Output Rate (FORT) in women on multinutrient supplementation showed a trend towards benefit compared to control group, although it is not statistically significant (68.12 ± 19.47 vs 64.91 ± 20.06, p=0.493). The mean number of MII oocytes retrieved from mature follicles and number of good quality embryo on day 3 after fertilisation were not statistically significant between the two groups (6.65 ±3.84 vs 6.09 ± 3.01, p=0.626 and 4.00 ± 3.10 vs 3.45 ± 2.30, p=0.549, respectively). In addition, there were no differences in endometrial thickness before embryo transfer in both groups (10.35 ± 1.32mm vs 10.36 ± 2.04mm, p=0.320). However, the total dose of follicle stimulating hormone and duration of controlled ovarian stimulation were lower in the study group compared to control group (2410 ± 656.82 IU vs 2706.82 ± 536.15 IU, p= 0.119 and 8.90 ± 2.13 days vs 9.68 ± 1.29 days, p=0.164, respectively).
CONCLUSION: A multinutrient supplementation given for a minimum of 28 days, may have a positive effect on FORT and lower use of gonadotropin. More and larger sample research is warranted to prove this effect.
METHODS: The P. knowlesi dihdyrofolate-reductase (pkdhfr) gene was sequenced from 449 P. knowlesi malaria cases from Sabah (Malaysian Borneo) and genotypes evaluated for association with clinical and epidemiological factors. Homology modelling using the pvdhfr template was used to assess the effect of pkdhfr mutations on the pyrimethamine binding pocket.
RESULTS: Fourteen non-synonymous mutations were detected, with the most common being at codon T91P (10.2%) and R34L (10.0%), resulting in 21 different genotypes, including the wild-type, 14 single mutants, and six double mutants. One third of the P. knowlesi infections were with pkdhfr mutants; 145 (32%) patients had single mutants and 14 (3%) had double-mutants. In contrast, among the 47 P. falciparum isolates sequenced, three pfdhfr genotypes were found, with the double mutant 108N+59R being fixed and the triple mutants 108N+59R+51I and 108N+59R+164L occurring with frequencies of 4% and 8%, respectively. Two non-random spatio-temporal clusters were identified with pkdhfr genotypes. There was no association between pkdhfr mutations and hyperparasitaemia or malaria severity, both hypothesized to be indicators of H-H transmission. The orthologous loci associated with resistance in P. falciparum were not mutated in pkdhfr. Subsequent homology modelling of pkdhfr revealed gene loci 13, 53, 120, and 173 as being critical for pyrimethamine binding, however, there were no mutations at these sites among the 449 P. knowlesi isolates.
CONCLUSION: Although moderate diversity was observed in pkdhfr in Sabah, there was no evidence this reflected selective antifolate drug pressure in humans.
METHODS: In the present study, graphene oxide-polyethylene glycol (GOPEG) nanocarrier is designed and loaded with two anticancer drugs; Protocatechuic acid (PCA) and Chlorogenic acid (CA). The designed anticancer nanocomposite was further coated with folic acid to target the cancer cells, as their surface membranes are overexpressed with folate receptors.
RESULTS: The particle size distribution of the designed nanocomposite was found to be narrow, 9-40 nm. The release profiles of the loaded drugs; PCA and CA was conducted in human body simulated PBS solutions of pH 7.4 (blood pH) and pH 4.8 (intracellular lysosomal pH). Anticancer properties were evaluated against cancerous cells i.e. liver cancer, HEPG2 and human colon cancer, HT-29 cells. The cytocompatbility was assessed on normal 3T3 fibroblasts cells.
CONCLUSION: The size of the final designed anticancer nanocomposite formulation, GOPEG-PCACA-FA was found to be distributed at 9-40 nm with a median of 8 nm. The in vitro release of the drugs PCA and CA was found to be of sustained manner which took more than 100 h for the release. Furthermore, the designed formulation was biocompatible with normal 3T3 cells and showed strong anticancer activity against liver and colon cancer cells.
METHODS: Plasmodium falciparum DNA was collected from the Thailand-Myanmar, Thailand-Malaysia and Thailand-Cambodia borders during 2008-2016 (N = 233). Semi-nested PCR and nucleotide sequencing were used to assess mutations in Plasmodium falciparum dihydrofolate reductase (pfdhfr), P. falciparum dihydropteroate synthase (pfdhps). Gene amplification of Plasmodium falcipaurm GTP cyclohydrolase-1 (pfgch1) was assessed by quantitative real-time PCR. The association between pfdhfr/pfdhps mutations and pfgch1 copy numbers were evaluated.
RESULTS: Mutations in pfdhfr/pfdhsp and pfgch1 copy number fluctuated overtime through the study period. Altogether, 14 unique pfdhfr-pdfhps haplotypes collectively containing quadruple to octuple mutations were identified. High variation in pfdhfr-pfdhps haplotypes and a high proportion of pfgch1 multiple copy number (51% (73/146)) were observed on the Thailand-Myanmar border compared to other parts of Thailand. Overall, the prevalence of septuple mutations was observed for pfdhfr-pfdhps haplotypes. In particular, the prevalence of pfdhfr-pfdhps, septuple mutation was observed in the Thailand-Myanmar (50%, 73/146) and Thailand-Cambodia (65%, 26/40) border. In Thailand-Malaysia border, majority of the pfdhfr-pfdhps haplotypes transaction from quadruple (90%, 9/10) to quintuple (65%, 24/37) during 2008-2016. Within the pfdhfr-pfdhps haplotypes, during 2008-2013 the pfdhps A/S436F mutation was observed only in Thailand-Myanmar border (9%, 10/107), while it was not identified later. In general, significant correlation was observed between the prevalence of pfdhfr I164L (ϕ = 0.213, p-value = 0.001) or pfdhps K540E/N (ϕ = 0.399, p-value ≤ 0.001) mutations and pfgch1 gene amplification.
CONCLUSIONS: Despite withdrawal of SP as anti-malarial treatment for 17 years, the border regions of Thailand continue to display high prevalence of antifolate and anti-sulfonamide resistance markers in falciparum malaria. Significant association between pfgch1 amplification and pfdhfr (I164L) or pfdhps (K540E) resistance markers were observed, suggesting a compensatory mutation.
METHODS: This study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders.
RESULTS: Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant.
CONCLUSIONS: We identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.
MATERIALS AND METHODS: A total of 292 subjects were recruited, comprising 150 ischaemic stroke patients and 142 control subjects who were age and sex matched. Plasma homocysteine, serum folate and vitamin B12 were measured in all subjects. Genotyping was carried out using PCR-RFLP.
RESULTS: The homocysteine levels were significantly higher (P = 0.001) in the stroke group (11.35 ± 2.75 μmol/L) compared to the control group (10.38 ± 2.79 μmol/L). The MTHFR C677T genotype distribution for the stroke group was 46%, 40% and 14%, respectively for CC, CT and TT genotypes and 59.9%, 33.8% and 6.3%, respectively for the control group. The genotype and allelic frequencies were significantly different between the 2 groups, with P = 0.02 and P = 0.004 respectively. No significant difference was seen in the genotype distribution inter-ethnically. An increasing tHcy was seen with every additional T allele, and the differences in the tHcy for the different genotypes were significant in both the control (P <0.001) and stroke groups (P <0.001).
CONCLUSION: This study shows that TT genotype of the methylenetetrahydrofolate reductase C677T polymorphic gene is an important determinant for homocysteine levels in Malaysian ischaemic stroke patients.
Methods: In this clinical trial study, 98 participants were randomly allocated to an HBM group (n = 48) and a control group (n = 50). The HBM group received an audiovisual compact disc (CD) that contained information about nutritional behaviour of colorectal cancer (CRC) prevention based on HBM that lasted 45 min. Both groups completed questionnaires regarding demographic factors, knowledge and HBM constructs, and a three-day dietary recall at the beginning of the study, 1 week after, and 3 months after the education. The outcome of this study was measured by the amount of food servings consumed and dietary micronutrient intake.
Results: At the baseline, there were no significant differences between groups regarding demographic factors. Findings showed that self-efficacy (P < 0.001), severity (P < 0.001), and benefits (P < 0.001) were perceived to be higher, and knowledge (P < 0.001) was increased in the HBM group compared to control group 3 months after education. There was a significant increase in fruit and vegetable (P < 0.001) and dairy (P = 0.001) intake and a significant decrease in red meat servings (P = 0.016) in the HBM group compared to the control group. Also, intake of vitamin D (P < 0.001), folate (P < 0.001), calcium (P = 0.008), and dietary fibre (P < 0.001) was increased in the HBM group compared to the control group 3 months after education.
Conclusion: Education plans based on HBM and implemented through multimedia can change nutritional beliefs and behaviours for the prevention of colorectal cancer.