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Fulltext Down-regulation of steroidogenesis-related genes and its accompanying fertility decline in streptozotocin-induced diabetic male rats: ameliorative effect of metformin

Nna VU, Bakar ABA, Ahmad A, Mohamed M

Andrology, 2019 01;7(1):110-123.
PMID: 30515996 DOI: 10.1111/andr.12567

BACKGROUND: Metformin has long been used for glycemic control in diabetic state. Recently, other benefits of metformin beyond blood glucose regulation have emerged.
OBJECTIVES: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats.
MATERIALS AND METHODS: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks.
RESULTS: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD, as well as the level of StAR protein and activities of CYP11A1, 3β-HSD, and 17β-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre- and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome.
DISCUSSION AND CONCLUSION: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state.

Matched MeSH terms: DNA Fragmentation
Effect of dietary fiber on the methanogen community in the hindgut of Lantang gilts

Cao Z, Liang JB, Liao XD, Wright AD, Wu YB, Yu B

Animal, 2016 Oct;10(10):1666-76.
PMID: 27052363 DOI: 10.1017/S1751731116000525

The primary objective of this study was to investigate the effect of dietary fiber on methanogenic diversity and community composition in the hindgut of indigenous Chinese Lantang gilts to explain the unexpected findings reported earlier that Lantang gilts fed low-fiber diet (LFD) produced more methane than those fed high-fiber diet (HFD). In total, 12 Lantang gilts (58.7±0.37 kg) were randomly divided into two dietary groups (six replicates (pigs) per group) and fed either LFD (NDF=201.46 g/kg) or HFD (NDF=329.70 g/kg). Wheat bran was the main source of fiber for the LFD, whereas ground rice hull (mixture of rice hull and rice bran) was used for the HFD. Results showed that the methanogens in the hindgut of Lantang gilts belonged to four known species (Methanobrevibacter ruminantium, Methanobrevibacter wolinii, Methanosphaera stadtmanae and Methanobrevibacter smithii), with about 89% of the methanogens belonging to the genus Methanobrevibacter. The 16S ribosomal RNA (rRNA) gene copies of Methanobrevibacter were more than three times higher (P0.05) was observed in 16S rRNA gene copies of Fibrobacter succinogenes between the two dietary groups, and 18S rRNA gene copies of anaerobic fungi in gilts fed LFD were lower than (P<0.05) those fed HFD. To better explain the effect of different fiber source on the methanogen community, a follow-up in vitro fermentation using a factorial design comprised of two inocula (prepared from hindgut content of gilts fed two diets differing in their dietary fiber)×four substrates (LFD, HFD, wheat bran, ground rice hull) was conducted. Results of the in vitro fermentation confirmed that the predominant methanogens belonged to the genus of Methanobrevibacter, and about 23% methanogens was found to be distantly related (90%) to Thermogymnomonas acidicola. In vitro fermentation also seems to suggest that fiber source did change the methanogens community. Although the density of Methanobrevibacter species was positively correlated with CH4 production in both in vivo (P<0.01, r=0.737) and in vitro trials (P<0.05, r=0.854), which could partly explain the higher methane production from gilts fed LFD compared with those in the HFD group. Further investigation is needed to explain how the rice hull affected the methanogens and inhibited CH4 emission from gilts fed HFD.

Matched MeSH terms: DNA, Bacterial/genetics; DNA, Bacterial/chemistry; DNA, Ribosomal/genetics; DNA, Ribosomal/chemistry; Sequence Analysis, DNA/veterinary
Phylogenetic analysis of different breeds of domestic chickens in selected area of Peninsular Malaysia inferred from partial cytochrome b gene information and RAPD markers

Yap FC, Yan YJ, Loon KT, Zhen JL, Kamau NW, Kumaran JV

Anim Biotechnol, 2010 Oct;21(4):226-40.
PMID: 20967642 DOI: 10.1080/10495398.2010.506334

The present investigation was carried out in an attempt to study the phylogenetic analysis of different breeds of domestic chickens in Peninsular Malaysia inferred from partial cytochrome b gene information and random amplified polymorphic DNA (RAPD) markers. Phylogenetic analysis using both neighbor-joining (NJ) and maximum parsimony (MP) methods produced three clusters that encompassed Type-I village chickens, the red jungle fowl subspecies and the Japanese Chunky broilers. The phylogenetic analysis also revealed that majority of the Malaysian commercial chickens were randomly assembled with the Type-II village chickens. In RAPD assay, phylogenetic analysis using neighbor-joining produced six clusters that were completely distinguished based on the locality of chickens. High levels of genetic variations were observed among the village chickens, the commercial broilers, and between the commercial broilers and layer chickens. In this study, it was found that Type-I village chickens could be distinguished from the commercial chickens and Type-II village chickens at the position of the 27th nucleotide of the 351 bp cytochrome b gene. This study also revealed that RAPD markers were unable to differentiate the type of chickens, but it showed the effectiveness of RAPD in evaluating the genetic variation and the genetic relationships between chicken lines and populations.

Matched MeSH terms: DNA/genetics; DNA, Mitochondrial/genetics; Sequence Analysis, DNA; Random Amplified Polymorphic DNA Technique
Genetic diversity of Asian water buffalo (Bubalus bubalis): mitochondrial DNA D-loop and cytochrome b sequence variation

Lau CH, Drinkwater RD, Yusoff K, Tan SG, Hetzel DJ, Barker JS

Anim. Genet., 1998 Aug;29(4):253-64.
PMID: 9745663

Swamp and river buffalo mitochondrial DNA (mtDNA) was sequenced for 303 bp of the cytochrome b gene for 54 animals from 14 populations, and for 158 bp of the D-loop region for 80 animals from 11 populations. Only one cytochrome b haplotype was found in river buffalo. Of the four haplotypes identified in swamp buffalo, one found in all populations is apparently ancestral both to the other swamp haplotypes and to the river haplotype. The phylogenetic relationships among the 33 D-loop haplotypes, with a cluster of 11 found in swamp buffalo only, also support the evolution of domesticated swamp and river buffalo from an ancestral swamp-like animal, most likely represented today by the wild Asian buffalo (Bubalus arnee). The time of divergence of the swamp and river types, estimated from the D-loop data, is 28,000 to 87,000 years ago. We hypothesise that the species originated in mainland south-east Asia, and that it spread north to China and west to the Indian subcontinent, where the rive type evolved and was domesticated. Following domestication in China, the domesticated swamp buffalo spread through two separate routes, through Taiwan and the Philippines to the eastern islands of Borneo and Sulawesi, and south through mainland south-east Asia and then to the western islands of Indonesia.

Matched MeSH terms: DNA, Mitochondrial/chemistry*; Sequence Analysis, DNA/veterinary
Fulltext Diet Composition of the Wild Stump-Tailed Macaque (Macaca arctoides) in Perlis State Park, Peninsular Malaysia, Using a Chloroplast tRNL DNA Metabarcoding Approach: A Preliminary Study

Osman NA, Abdul-Latiff MAB, Mohd-Ridwan AR, Yaakop S, Nor SM, Md-Zain BM

Animals (Basel), 2020 Nov 26;10(12).
PMID: 33255964 DOI: 10.3390/ani10122215

Understanding dietary diversity is a fundamental task in the study of stump-tailed macaque, Macaca arctoides in its natural habitat. However, direct feeding observation and morphological identification using fecal samples are not effective and nearly impossible to obtain in natural habitats because this species is sensitive to human presence. As ecological methods are challenging and time-consuming, DNA metabarcoding offers a more powerful assessment of the diet. We used a chloroplast tRNL DNA metabarcoding approach to identify the diversity of plants consumed by free-ranging M. arctoides in the Malaysia-Thailand border region located in Perlis State Park, Peninsular Malaysia. DNA was extracted from three fecal samples, and chloroplast tRNL DNA was amplified and sequenced using the Illumina MiniSeq platform. Sequences were analyzed using the CLC Genomic Workbench software. A total of 145 plant species from 46 families were successfully identified as being consumed by M. arctoides. The most abundant species were yellow saraca, Saraca thaipingensis (11.70%), common fig, Ficus carica (9.33%), aramata, Clathrotropis brachypetala (5.90%), sea fig, Ficus superba (5.44%), and envireira, Malmea dielsiana (1.70%). However, Clathrotropis and Malmea are not considered Malaysian trees because of limited data available from Malaysian plant DNA. Our study is the first to identify plant taxa up to the species level consumed by stump-tailed macaques based on a DNA metabarcoding approach. This result provides an important understanding on diet of wild M. arctoides that only reside in Perlis State Park, Malaysia.

Matched MeSH terms: DNA, Chloroplast; DNA, Plant; DNA Barcoding, Taxonomic
Fulltext Seroprevalence and Risk Factors of Toxoplasma gondii in Ruminant Meats from Wet Markets in Klang Valley and Abattoirs in Selangor, Malaysia

Abdul Hamid N, Sadiq MB, Ramanoon SZ, Mansor R, Watanabe M, Md Isa NM, et al.

Animals (Basel), 2020 Jul 06;10(7).
PMID: 32640507 DOI: 10.3390/ani10071139

(1) Background: The objective of this study was to determine the prevalence of T. gondii in meats of cattle, goat and sheep from wet markets in Klang Valley, and abattoirs in Selangor, Malaysia; (2) Methods: A total of 192 meat samples were purchased from 51 wet markets in six districts in Klang Valley (Gombak, Klang, Kuala Lumpur, Hulu Langat, Petaling and Putrajaya). Meanwhile, a total of 200 diaphragm samples were collected from two government abattoirs located in Shah Alam and Banting, Selangor. All meat juices from samples were subjected to an indirect-ELISA kit for the presence of T. gondii IgG antibodies. Furthermore, all 184 meat samples of goat and sheep were subjected to conventional nested PCR (B1 genes) for the detection of T. gondii DNA; (3) Results: T. gondii antibodies were detected in 25% (n = 98/392) of the samples with seroprevalence of 9.1% (19/208, CI: 5.9%-13.8%) in cattle meat; 54.7% (41/75, 95% CI: 43.5%-65.4%) in goat meat and 34.9% (38/109, CI: 26.6%-44.2%) in sheep meat. No T. gondii DNA was detected in any of the meat samples of goat and sheep. T. gondii seropositivity in wet market samples was higher in goat (OR = 37.1 CI 12.4-110.3) and sheep meat (OR 9.03 CI: 3.28-24.8) compared to cattle meat (OR = 1.0) At univariate level, meat from non-licensed abattoirs (OR = 6.0 CI: 2.9-12.3) and female animals (OR = 6.7; CI 1.9-22.6) had higher risks of being seropositive for T. gondii antibodies than licensed abattoirs and male animals, respectively. (4) Conclusions: This is the first report of seroprevalence of T. gondii in ruminant meats for human consumption in Malaysia. The findings signified high exposure of meat samples from wet markets to T. gondii and the need for control measures to reduce the likelihood of infection when such raw or undercooked meats are consumed.

Matched MeSH terms: DNA
Revisiting the question of limited genetic variation within Schistosoma japonicum

Le TH, Blair D, McManus DP

Ann Trop Med Parasitol, 2002 Mar;96(2):155-64.
PMID: 12080976

Recent electrophoretic data have indicated that Schistosoma japonicum in mainland China may be a species complex, with the existence of a cryptic species being predicted from the analysis of schistosome populations from Sichuan province. To investigate the Sichuan form of S. japonicum, 4.9 kbp of mitochondrial DNA from each of three samples of the parasite from China (two from Sichuan and one from Hunan) and one from Sorsogon in the Philippines were amplified, sequenced and characterized. The sequence data were compared with those from the related South-east Asian species of S. mekongi (Khong Island, Laos) and S. mlayensis (Baling, Malaysia) and that from S. japonicm from Anhui (China). At both the nucleotide and amino-acid levels, the variation among the five S. japonicum samples was limited (< 1%). This was consistent with the conclusions drawn from previous molecular studies, in which minimal variation among S. japonicum populations was also detected. In contrast, S. mekongi and S. malayensis, species recognized as separate but closely related, differ from each other by about 10%, and each differs by 25%-26% from S. japonicum. Phylogenetic trees provided a graphic representation of these differences, showing all S. japonicum sequences to be very tightly clustered and distant from S. mekongi and S. malayensis, the last two being clearly distinct from each other. The results thus indicate no significant intra-specific genetic variation among S. japonicum samples collected from different geographical areas and do not support the idea of a distinct form in Sichuan.

Matched MeSH terms: DNA, Mitochondrial/genetics; DNA, Helminth/genetics
Fulltext P53/MDM2 co-expression correlates with the tumour differentiation in oral squamous cell carcinoma - a retrospective study and a systematic review

Choon, Y.F., Ramanathan, A., Ali, H., Ghani, W.M.N., Cheong, S.C., Zain, R.B.

Ann Dent, 2011;18(1):8-17.
MyJurnal

Background: MDM2 and p53 are involved in a negative feedback loop where p53 regulates MDM2 at the transcriptional level. MDM2, in turn, downregulates p53. This co-ordinated interaction between these proteins is set to play an important role in the regulation of cell cycle progression following DNA damage to cells. The over-expression of both p53 and MDM2 has been reported in various cancers. However there are only few studies discussing the co-expression of MDM2 with p53 in oral squamous cell carcinoma Aim: The purpose of this study was to determine the correlation of co-expression of p53, MDM2, and Ki-67 proteins with clinico-pathological factors in oral squamous cell carcinoma (OSCC) and to conduct a systematic review of the co-expression of p53/MDM2.

Method: This is a retrospective descriptive study and a systematic review. Formalin-fixed paraffinembedded tissues from 45 OSCC cases were stained by immunohistochemistry (IHC) for p53, MDM2, and Ki-67 proteins.

Results: Immuno-reactivity for p53, MDM2, and Ki-67 was seen in 75.6%, 97.8%, and 62.2% cases of OSCC respectively. The co-expression of p53 and MDM2 (p53/MDM2) was detected in 97.1%, however there was no significant correlation between p53 and MDM2 expression. Notably, p53/MDM2 coexpression was significantly associated with tumour differentiation (p-value = 0.045). The Ki-67LI was not significantly associated with neither MDM2 nor p53/MDM2 co-expression (p-value = 0.268, 0.916 respectively).

Conclusion: The expression of MDM2 was not signif icantly associated with p53 expression suggesting that MDM2 expression is mediated by p53-independent pathways or mutated p53 could not induce the expression of MDM2 in this set of OSCCs. The only clinico-pathological parameter that correlates significantly with co-expression of p53/MDM2 is tumour differentiation where it is suggestive that the co-expression of these 2 proteins is indicative of aggressive tumour behavior.

Matched MeSH terms: DNA Damage
Fulltext A Demonstration Of The Polymerase Chain Reaction Technique In Class Teaching

Yusof, R., Abdul Rahman, P.S., Rahim, Z.H.A.

Ann Dent, 1999;6(1):-.
MyJurnal

The application of PCR technique in genetic screening was demonstrated using the genetic materials from buccal cells of the students in the class. Two factors were taken into consideration when designing the experiments. The DNA region to be amplified should not be associated with any disease state. This is to eliminate any emotional and ethical problems associated with the experiments. In this practical, the presence and absence of a 38 bp sequence in the intron of COLIA2 gene were studied. The students were also shown on how to analyse the presence of homozygous and heterozygous alleles and the genetic variations that might be observed in the different ethnic groups of students. Another factor was the time taken to complete the experiment. Our experience showed that this experiment would take at least six hours to obtain and analyse the results. It is therefore suitable to be used in class teaching.

Matched MeSH terms: DNA
Fulltext Determinants of dna yield and quality from different non-invasive sampling methods

Karen-Ng, L.P., Hassan, S., Marhazlinda, J., Zain, R.B., Choon, Y.F.

Ann Dent, 2012;19(2):62-65.
MyJurnal

The purpose of this study was to determine the
DNA yield and quality from different non-invasive
sampling methods and to identify the method which
gave the highest DNA yield. Method: Thirty-eight
volunteers had been recruited in this study where
blood, buccal cells and saliva were collected using
various collection techniques. Buccal cells were
collected by 1) cytobrush and 2) saline mouth rinsing
or “swish”. Meanwhile saliva was collected by passive
drooling method. Upon processing the white blood
cell (WBC), buccal cells and saliva samples, DNA
extraction was performed according to the
manufacturer’s protocol. Quantification and quality
(DNA ratio at A260/A280) of the extracted DNA were
determined using NanoDropND-1000®. T-test was
performed to compare means between DNA obtained
from various collection methods. Results: DNA yields
from buccal cells collected with cytobrush, “swish”,
saliva and WBC (mean ± SD) were (8.2 ± 5.9)ng/μl,
(28.2 ± 14.9)ng/μl, (5.9 ± 9.5)ng/μl and (105.3 ±
75.0)ng/μl respectively. Meanwhile the mean DNA
ratio at A260/A280 for cytobrush, “swish”, saliva and
WBC were 2.3, 2.0, 1.7 and 1.8 respectively. Post hoc
test with Bonferroni correction suggested that DNA
yield from “swish” technique exhibited the least mean
different as compared to the DNA extracted from WBC
(p

Matched MeSH terms: DNA
The association of mitochondrial DNA 5178 C > a polymorphism with plasma lipid levels among three ethnic groups

Lal S, Madhavan M, Heng CK

Ann. Hum. Genet., 2005 Nov;69(Pt 6):639-44.
PMID: 16266403

Mitochondria are eukaryotic cytoplasmic organelles responsible for oxidative phosphorylation. The C to A nucleotide transversion in the NADH dehydrogenase subunit 2 (MT-ND2) coding region of mitochondrial DNA has been reported to be associated with plasma lipid levels, adult onset diseases and longevity. We have examined the role of this polymorphism in relation to plasma lipid levels and age in a total of 713 healthy individuals belonging to 3 ethnic groups in Singapore. The frequency of the A allele was significantly higher (p < 0.05) among the Chinese (0.15) in comparison to the Malays (0.05) and Indians (0.02). No significant difference in the frequency of the allele was observed between healthy and coronary artery disease subjects, and between age-stratified subjects. We found that the polymorphism is significantly associated in an ethnic- and gender-specific manner with plasma apoB levels in the Chinese males (p < 0.05). This is the first epidemiological report of the mt5178 C > A polymorphism and its association with plasma lipid levels in Asian populations outside Japan.

Matched MeSH terms: DNA, Mitochondrial/genetics*
Molecular Characterisation of α- and β-Thalassaemia among Indigenous Senoi Orang Asli Communities in Peninsular Malaysia

Koh DXR, Raja Sabudin RZA, Mohd Yusoff M, Hussin NH, Ahmad R, Othman A, et al.

Ann. Hum. Genet., 2017 Sep;81(5):205-212.
PMID: 28620953 DOI: 10.1111/ahg.12201

Thalassaemia is a public health problem in Malaysia, with each ethnic group having their own common mutations. However, there is a lack on data on the prevalence and common mutations among the indigenous people. This cross-sectional study was performed to determine the common mutations of α- and β-thalassaemia among the subethnic groups of Senoi, the largest Orang Asli group in Peninsular Malaysia. Blood samples collected from six Senoi subethnic groups were analysed for full blood count and haemoglobin analysis (HbAn). Samples with abnormal findings were then screened for α- and β-globin gene mutations. Out of the 752 samples collected, 255 showed abnormal HbAn results, and 122 cases showing abnormal red cell indices with normal HbAn findings were subjected to molecular screening. DNA analysis revealed a mixture of α- and β-globin gene mutations with 25 concomitant cases. The types of gene abnormalities detected for α-thalassaemia were termination codon (T>C) Hb CS (αCS α), Cd59 (G>A) haemoglobin Adana (Hb Adana) (αCd59 α), initiation codon (ATG>A-G) (αIniCd α), two-gene deletion (-SEA ), and single-gene 3.7-kb deletion (-α3.7 ). For β-thalassaemia, there were Cd26 (G>A) Hb E (βE ), Cd19 (A>G) Haemoglobin Malay (Hb Malay) (βCd19 ), and IVS 1-5 (G>C) (βIVS 1-5 ).

Matched MeSH terms: DNA Mutational Analysis
Fulltext Isolated hepatitis B core antibody positive among vaccinated cohort in Malaysia

Hudu SA, Malik YA, Niazlin MT, Harmal NS, Alshrari AS, Sekawi Z

Ann Saudi Med, 2013;33(6):591-4.
PMID: 24413864 DOI: 10.5144/0256-4947.2013.591

BACKGROUND AND OBJECTIVES: Hepatitis B core antibodies (anti-HBc) are detected in almost every patient with previous exposure to hepatitis B virus (HBV). However, with this marker alone, one cannot understand the activity of the disease; therefore, this study aimed to identify the implication of isolated hepatitis B core antibody and evaluate the effect of hepatitis B vaccine booster in isolated anti-HBc among adults who received the HBV vaccine as infants.
DESIGN AND SETTINGS: A prospective cohort study of vaccinated undergraduate students of University Putra Malaysia.
PATIENTS AND METHODS: A total of 408 undergraduate students who received infant hepatitis B vaccination volunteered for this study; 5 mL of venous blood was taken from the volunteers. Hepatitis B surface antigen (HBsAg) and core antibodies were tested using a commercially available enzyme-linked immunosorbent assay kit according to the manufacturer's instructions (DRG international Inc., USA). Molecular detection of hepatitis B viral DNA was performed using nested polymerase chain reaction.
RESULTS: The prevalence of isolated anti-HBc among the vaccinated cohort was found to be 5.0%, out of which 80% had a hepatitis B surface antibodies (anti-HBs) titer higher than 10 IU/L, while 20% had less than 10 IU/L anti-HBs titer. All the anti-HBc positivesubjects had detectable hepatitis B viral DNA in their serum. Anamnestic response was found to be 100% among isolated anti-HBc with negative antibody.
CONCLUSION: Isolated anti-HBc developed protective levels of anti-HBs after a single dose of recombinant hepatitis B vaccination. HBV DNA was detected in all isolated anti-HBc indicating occult chronic HBV infection with undetectable HBsAg.

Matched MeSH terms: DNA, Viral/blood*
Fulltext Francisella philomiragia bacteremia in an immunocompromised patient: a rare case report

Chua HS, Soh YH, Loong SK, AbuBakar S

Ann Clin Microbiol Antimicrob, 2021 Oct 03;20(1):72.
PMID: 34602092 DOI: 10.1186/s12941-021-00475-2

BACKGROUND: Francisella philomiragia is a very rare opportunistic pathogen of humans which causes protean diseases such as pneumonia and other systemic infections. Subsequent failure of prompt treatment may result in poor prognosis with mortality among infected patients.
CASE PRESENTATION: The present report describes a case of F. philomiragia bacteraemia first reported in Malaysia and Asian in a 60-year-old patient with underlying end-stage renal disease (ESRF) and diabetes mellitus. He presented with Acute Pulmonary Oedema with Non-ST-Elevation Myocardial Infarction (NSTEMI) in our hospital. He was intubated in view of persistent type I respiratory failure and persistent desaturation despite post haemodialysis. Blood investigation indicated the presence of ongoing infection and inflammation. The aerobic blood culture growth of F. philomiragia was identified using the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (Score value: 2.16) and confirmed by 16S Ribosomal DNA (16S rDNA) sequencing. He was discharged well on day 26 of admission, after completing one week of piperacillin/tazobactam and two weeks of doxycycline.
CONCLUSION: Clinical suspicion should be raised if patients with known risk factors are presenting with pneumonia or pulmonary nodules especially as these are the most common manifestations of F. philomiragia infection. Early diagnosis via accurate laboratory identification of the organism through MALDI-TOF mass spectrometry and molecular technique such as 16S rDNA sequencing are vital for prompt treatment that results in better outcomes for the afflicted patients.

Matched MeSH terms: DNA, Ribosomal/genetics; Sequence Analysis, DNA
Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy

Ricos MG, Hodgson BL, Pippucci T, Saidin A, Ong YS, Heron SE, et al.

Ann Neurol, 2016 Jan;79(1):120-31.
PMID: 26505888 DOI: 10.1002/ana.24547

Focal epilepsies are the most common form observed and have not generally been considered to be genetic in origin. Recently, we identified mutations in DEPDC5 as a cause of familial focal epilepsy. In this study, we investigated whether mutations in the mammalian target of rapamycin (mTOR) regulators, NPRL2 and NPRL3, also contribute to cases of focal epilepsy.

Matched MeSH terms: Sequence Analysis, DNA
Fulltext Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial

Chi KN, Sandhu S, Smith MR, Attard G, Saad M, Olmos D, et al.

Ann Oncol, 2023 Sep;34(9):772-782.
PMID: 37399894 DOI: 10.1016/j.annonc.2023.06.009

BACKGROUND: Patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA alterations have poor outcomes. MAGNITUDE found patients with homologous recombination repair gene alterations (HRR+), particularly BRCA1/2, benefit from first-line therapy with niraparib plus abiraterone acetate and prednisone (AAP). Here we report longer follow-up from the second prespecified interim analysis (IA2).
PATIENTS AND METHODS: Patients with mCRPC were prospectively identified as HRR+ with/without BRCA1/2 alterations and randomized 1 : 1 to niraparib (200 mg orally) plus AAP (1000 mg/10 mg orally) or placebo plus AAP. At IA2, secondary endpoints [time to symptomatic progression, time to initiation of cytotoxic chemotherapy, overall survival (OS)] were assessed.
RESULTS: Overall, 212 HRR+ patients received niraparib plus AAP (BRCA1/2 subgroup, n = 113). At IA2 with 24.8 months of median follow-up in the BRCA1/2 subgroup, niraparib plus AAP significantly prolonged radiographic progression-free survival {rPFS; blinded independent central review; median rPFS 19.5 versus 10.9 months; hazard ratio (HR) = 0.55 [95% confidence interval (CI) 0.39-0.78]; nominal P = 0.0007} consistent with the first prespecified interim analysis. rPFS was also prolonged in the total HRR+ population [HR = 0.76 (95% CI 0.60-0.97); nominal P = 0.0280; median follow-up 26.8 months]. Improvements in time to symptomatic progression and time to initiation of cytotoxic chemotherapy were observed with niraparib plus AAP. In the BRCA1/2 subgroup, the analysis of OS with niraparib plus AAP demonstrated an HR of 0.88 (95% CI 0.58-1.34; nominal P = 0.5505); the prespecified inverse probability censoring weighting analysis of OS, accounting for imbalances in subsequent use of poly adenosine diphosphate-ribose polymerase inhibitors and other life-prolonging therapies, demonstrated an HR of 0.54 (95% CI 0.33-0.90; nominal P = 0.0181). No new safety signals were observed.
CONCLUSIONS: MAGNITUDE, enrolling the largest BRCA1/2 cohort in first-line mCRPC to date, demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered mCRPC, emphasizing the importance of identifying this molecular subset of patients.

Matched MeSH terms: Recombinational DNA Repair
Fulltext Prevalence and molecular characterisation of Schistosoma haematobium among primary school children in Kebbi State, Nigeria

Umar S, Shinkafi SH, Hudu SA, Neela V, Suresh K, Nordin SA, et al.

Ann Parasitol, 2017;63(2):133-139.
PMID: 28822206 DOI: 10.17420/ap6302.97

Schistosomiasis is the major source of morbidity in Sub-Saharan Africa and Asia. It is estimated that 207 million people are infected, of which 97% are in Africa. The aim of this study was the determining of prevalence as well as the phylogeny of S. haematobium among school children in Argungu Emirate, Kebbi State Nigeria. A total of 325 urine samples was collected from school children between 7 to 14 years. S. heamatobium eggs was examined under dissecting microscope and DNA was extracted from urine sample and COX1 gene was amplified by nested PCR. The PCR products were purified, sequenced and analysed. This study showed a prevalence of 32.09%, with male pupils having the highest prevalence. S. haematobium infections in children who fetch water in the river have 24 times higher risk of being infected while those who bath in the river have 158 times higher risk of being infected. Our sequences were phylogenetically related to S. haematobium isolate U82266 from Kenya and consistence with the predominant species in Africa. This was the first S. haematobium and S. mansoni co-infection reported in Nigeria. S. haematobium infection is prevalent among school age and significantly associated with water contact.

Matched MeSH terms: DNA
KCNQ1 variants associate with type 2 diabetes in Malaysian Malay subjects

Saif-Ali R, Muniandy S, Al-Hamodi Z, Lee CS, Ahmed KA, Al-Mekhlafi AM, et al.

Ann Acad Med Singap, 2011 Nov;40(11):488-92.
PMID: 22206064

INTRODUCTION: Type 2 diabetes (T2D) candidate gene: potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) was suggested by conducting a genome wide association study (GWAS) in Japanese population. Association studies have been replicated among East Asian populations; however, the association between this gene and T2D in Southeast Asian populations still needs to be studied. This study aimed to investigate the association of KCNQ1 common variants with type 2 diabetes in Malaysian Malay subjects.
MATERIALS AND METHODS: The KCNQ1 single nucleotide polymorphisms (SNPs): rs2237892, rs2283228, and rs2237895 were genotyped in 234 T2D and 177 normal Malay subjects.
RESULTS: The risk allele of the rs2283228 (A) was strongly associated with T2D (OR = 1.7, P = 0.0006) while the rs2237892 (C) was moderately associated with T2D (OR = 1.45, P = 0.017). The recessive genetic models showed that rs2283228 was strongly associated with T2D (OR = 2.35, P = 0.00005) whereas rs2237892 showed a moderate association with T2D (OR = 1.69, P = 0.01). The haplotype block (TCA), which contained the protective allele, correlated with a protection from T2D (OR = 0.5, P = 0.003). Furthermore, the diplotype (CAA-TCA) that contained the protective haplotype was protected against T2D (OR = 0.46, P = 0.006).
CONCLUSION: The KCNQ1 SNPs, haplotypes and diplotypes are associated with T2D in the Malaysian Malay subjects.

Matched MeSH terms: Sequence Analysis, DNA
Molecular heterogeneity of beta-thalassaemia in Malaysia: a practical approach to diagnosis

Thong MK, Law HY, Ng IS

Ann Acad Med Singap, 1996 Jan;25(1):79-83.
PMID: 8779552

The beta-thalassaemia mutations in 20 Malaysian children with beta-thalassaemia major were characterised by using a multi-modal approach, consisting of a slot-blot hybridisation with selected allele-specific oligonucleotides (ASO), followed by reverse dot-blot assay (RDB), amplification refractory mutation system (ARMS) and genomic sequencing. This strategy yielded a 94.4% mutation detection rate. The 6 most common mutations were codons 41/42 (-TTCT), IVS II nt 654(C --> T), IVS I nt 5(G --> C), IVS I nt 1(G -->T), codon 35 (-C) and codon 19 (A --> G), which accounted for 83.3% of all mutations detected. A strategy of initial screening with the above 6 selected ASOs for slot-blot hybridisation followed by RDB assay for the less common Asian mutations would give a mutation identification of 91.7%. Another feasible approach would be to analyse alleles from a particular racial group, by a judicious selection of 4 ASOs common to that particular subpopulation and then supplement this with RDB assay. This could yield a 100% coverage for the Chinese subpopulation in Malaysia. With these strategies, a practical approach has been identified to overcome the pitfalls posed by the molecular heterogeneity of beta-thalassaemia to enable prenatal diagnosis and carrier screening to be carried out. Regional collaborative studies are to be encouraged as an indispensable tool in providing better health care services to our patients.

Matched MeSH terms: DNA/analysis*
Tocotrienol-rich fraction from palm oil and gene expression in human breast cancer cells

Nesaretnam K, Ambra R, Selvaduray KR, Radhakrishnan A, Canali R, Virgili F

Ann N Y Acad Sci, 2004 Dec;1031:143-57.
PMID: 15753141

Vitamin E is important not only for its cellular antioxidant and lipid-lowering properties, but also as an antiproliferating agent. It has also been shown to contribute to immunoregulation, antibody production, and resistance to implanted tumors. It has recently been shown that tocotrienols are the components of vitamin E responsible for growth inhibition in human breast cancer cells in vitro as well as in vivo through estrogen-independent mechanisms. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. In order to investigate the molecular basis of the effect of a tocotrienol-rich fraction (TRF) from palm oil, we performed a cDNA array analysis of cancer-related gene expression in estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells. The human breast cancer cells were incubated with or without 8 mug/mL of tocotrienols for 72 h. RNA was subsequently extracted and subjected to reverse transcription before being hybridized onto cancer arrays. Tocotrienol supplementation modulated significantly 46 out of 1200 genes in MDA-MB-231 cells. In MCF-7 cells, tocotrienol administration was associated with a lower number of affected genes. Interestingly, only three were affected in a similar fashion in both cell lines: c-myc binding protein MM-1, 23-kDa highly basic protein, and interferon-inducible protein 9-27 (IFITM-1). These proteins are most likely involved in the cell cycle and can exert inhibitory effects on cell growth and differentiation of the tumor cell lines. These data suggest that tocotrienols are able to affect cell homeostasis, possibly independent of their antioxidant activity.

Matched MeSH terms: DNA, Complementary/analysis

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