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Aging processes affect the brain in many ways, ranging from cellular to functional levels which lead to cognitive decline and increased oxidative stress. The aim of this study was to investigate the potentials of Lactobacillus plantarum DR7 on brain health including cognitive and memory functions during aging and the impacts of high fat diet during a 12-week period. Male Sprague-Dawley rats were separated into six groups: (1) young animals on normal diet (ND, (2) young animals on a high fat diet (HFD), (3) aged animals on ND, (4) aged animals on HFD, (5) aged animals on HFD and L. plantarum DR7 (10 9 cfu/day) and (6) aged animals receiving HFD and lovastatin. To induce ageing, all rats in group 3 to 6 were injected sub-cutaneously at 600 mg/kg/day of D-galactose daily. The administration of DR7 has reduced anxiety accompanied by enhanced memory during behavioural assessments in aged-HFD rats ( P <0.05). Hippocampal concentration of all three pro-inflammatory cytokines were increased during aging but reduced upon administration of both statin and DR7. Expressions of hippocampal neurotransmitters and apoptosis genes showed reduced expressions of indoleamine dioxygenase and P53 accompanied by increased expression of TPH1 in aged- HFD rats administered with DR7, indicating potential effects of DR7 along the pathways of serotonin and oxidative senescence. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging. This study provided an insight into potentials of L. plantarum DR7 as a prospective dietary strategy to improve cognitive functions during aging.

Acute hepatopancreatic necrosis disease (AHPND) is an important shrimp disease of economic importance which causes mass mortality of cultivated penaeid shrimps in Southeast Asian countries, Mexico and South America. This disease was originally caused by Vibrio parahaemolyticus (VP AHPND ) which is reported to harbour a transferable plasmid carrying the virulent PirAB-like toxin genes (pirAB vp ). However, little is known about the pathogenicity of VP AHPND . To extend our understanding, comparative genomic analyses was performed in this study to identify the genetic differences and to understand the phylogenetic relationship of VP AHPND strains. Seven Vibrio parahaemolyticus strains (five VP AHPND strains and two non-VP AHPND strains) were sequenced and 31 draft genomes of V. parahaemolyticus were retrieved from NCBI database and incorporated into the genomic comparison to elucidate their genomic diversity. The study showed that the genome sizes of the VP AHPND strains were approximately 5 Mbp. Ten sequence types (STs) were identified among the VP AHPND strains using in silico-Multilocus Sequence Typing analysis (MLST) and ST 970 was the predominant ST. Phylogenetic analysis based on MLST and single nucleotide polymorphisms (SNP) showed that the VP AHPND strains were genetically diverse. Based on the comparative genomic analysis, several functional proteins were identified from diiferent categories associated with virulence-related proteins, secretory proteins, conserved domain proteins, transporter proteins, and phage proteins. The CRISPR analysis showed that VP AHPND strains contained less number of CRISPRs elements than non-VP AHPND strains while six prophages regions were identified in the genomes, suggested the lack of CRISPR might promote prophage insertion. The genomic information in this study provide improved understanding of the virulence of these VP AHPND strains., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, we hypothesized that different strains of Lactobacillus can alleviate hyperlipidemia and liver steatosis via activation of 5' adenosine monophosphate-activated protein kinase ( AMPK ), an enzyme that is involved in cellular energy homeostasis, in aged rats. Male rats were fed with a high-fat diet (HFD) and injected with D-galactose daily over 12 weeks to induce aging. Treatments included ( n = 6) (i) normal diet (ND), (ii) HFD, (iii) HFD-statin (lovastatin 2 mg/kg/day), (iv) HFD- Lactobacillus fermentum DR9 (10 log CFU/day), (v) HFD- Lactobacillus plantarum DR7 (10 log CFU/day), and (vi) HFD- Lactobacillus reuteri 8513d (10 log CFU/day). Rats administered with statin, DR9, and 8513d reduced serum total cholesterol levels after eight weeks ( p < 0.05), while the administration of DR7 reduced serum triglycerides level after 12 weeks ( p < 0.05) as compared to the HFD control. A more prominent effect was observed from the administration of DR7, where positive effects were observed, ranging from hepatic gene expressions to liver histology as compared to the control ( p < 0.05); downregulation of hepatic lipid synthesis and β-oxidation gene stearoyl-CoA desaturase 1 ( SCD1 ), upregulation of hepatic sterol excretion genes of ATP-binding cassette subfamily G member 5 and 8 ( ABCG5 and ABCG8 ), lesser degree of liver steatosis, and upregulation of hepatic energy metabolisms genes AMPKα1 and AMPKα2 . Taken altogether, this study illustrated that the administration of selected Lactobacillus strains led to improved lipid profiles via activation of energy and lipid metabolisms, suggesting the potentials of Lactobacillus as a promising natural intervention for alleviation of cardiovascular and liver diseases.

A unique strain of Vibrio parahaemolyticus (designated as VP AHPND ) causes acute hepatopancreatic necrosis disease (AHPND), a deadly bacterial disease associated with mass mortality in cultured shrimps since 2009. AHPND is responsible for severe economic losses worldwide, causing multimillion-dollar loss annually. Because of the rapid and high mortality rates in shrimps, substantial research has been carried out to develop rapid detection techniques. Also, recent technological advances such as the next-generation sequencing (NGS) have made it possible to elucidate relevant information about a pathogen in a single assay. This review summarizes the current research pertaining to VP AHPND , focusing on diagnosis and contribution of NGS technologies in the genomic studies of AHPND., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Springer Nature Switzerland AG 2020.)

This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5'adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 ( P <0.05). Plasma lipid peroxidation was lower ( P <0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control ( P <0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.

Salmonella enterica serovar Typhimurium (S. Typhimurium) and the monophasic variant Salmonella I 4,[5],12:i:- are two clinically-important non-typhoidal Salmonella serovars worldwide. However, the genomic information of these two organisms, especially the monophasic variant, is still lacking in Malaysia. The objective of the study was to compare the genomic features of a monophasic variant and two endemic S. Typhimurium strains isolated from humans. All three strains were subjected to whole genome sequencing followed by comparative genomic and phylogenetic analyses. Extensive genomic deletion in the fljAB operon (from STM2757 to iroB) is responsible for the monophasic phenotype of STM032/04. The two S. Typhimurium genomes (STM001/70 and STM057/05) were essentially identical, despite being isolated 35 years apart. All three strains were of sequence type ST19. Both S. Typhimurium genomes shared unique prophage regions not identified in the monophasic STM032/04 genome. Core genome phylogenetic analyses showed that the monophasic STM032/04 was closely-related to the S. Typhimurium LT2, forming a distinctive clade separated from the two endemic S. Typhimurium strains in Malaysia. The presence of serovar Typhimurium-specific mdh gene, conserved Gifsy and Fels-1 prophages, and the close genomic resemblance with S. Typhimurium LT2 suggested that the monophasic STM032/04 was originated from an LT2-like S. Typhimurium ancestor in Malaysia, following an evolutionary path different from the S. Typhimurium strains. In conclusion, the monophasic Salmonella I 4,[5],12:i:- and the S. Typhimurium strains isolated in Malaysia descended from different phylogenetic lineages. The high genomic resemblance between the two S. Typhimurium strains isolated for at least 35 years apart indicated their successful evolutionary lineage. The identification of multiple virulence and antimicrobial resistance determinants in the Salmonella I 4,[5],12:i:- and S. Typhimurium genomes explained the pathogenic nature of the organisms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Three strains of Gram-staining-positive, coccus-shaped, lactic acid bacteria, designated as HibF3 T , HibF2 and HibF5 were isolated from fresh flowers of hibiscus, and a fourth, DF1 T , was isolated from fresh flowers of durian tree, in Penang, Malaysia. Taxonomic characterisation was performed by polyphasic analysis. Sequence similarities of the 16S rRNA gene and the housekeeping rpoA and pheS genes of these strains with their closely-related lactococcal and streptococcal relatives were 92-94, 78 and 81 %, respectively. The results of phylogenetic analysis indicated that strains DF1 T , HibF2, HibF5 and HibF3 T were clustered together but were clearly separated from species of the genera Streptococcus and Lactococcus, indicating that they represent members of a novel genus of the family Streptococcaceae. Calculation of average nucleotide identity (ANI) values between the genomes of DF1 T and HibF3 T yielded values of 92.50-92.93 %. ANI values below the cut-off value and distinctive chemotaxonomic characteristics supported the hypothesis that these strains represented two novel species. Major cellular fatty acids in DF1 T , HibF2 and HibF5 were C18 : 1ω7c and C16 : 0, while C12 : 0 and C14 : 0 were also dominant, in addition to C18 : 1ω7c and C16 : 0, in HibF3 T . A novel genus is proposed with the name Floricoccus gen. nov. which consists of two species, Floricoccus tropicus sp. nov as the type species, and Floricoccus penangensis sp. nov. The respective type strains are DF1 T (=LMG 29833 T =JCM 31733 T ) and HibF3 T (=LMG 29831 T =DSM 31735 T ).

Next-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding have transformed the field of molecular microbiology, epidemiology, infection treatments and vaccine developments. We review the key findings of the publicly accessible genomes of Salmonella enterica serovar Typhi since the first complete genome to the most recent release of thousands of Salmonella Typhi genomes, which remarkably shape the genomic research of S. Typhi and other pathogens. Important new insights acquired from the genome sequencing of S. Typhi, pertaining to genomic variations, evolution, population structure, antibiotic resistance, virulence, pathogenesis, disease surveillance/investigation and disease control are discussed. As the numbers of sequenced genomes are increasing at an unprecedented rate, fine variations in the gene pool of S. Typhi are captured in high resolution, allowing deeper understanding of the pathogen's evolutionary trends and its pathogenesis, paving the way to bringing us closer to eradication of typhoid through effective vaccine/treatment development., (© 2017 John Wiley & Sons Ltd.)

Enterococcus faecium is both a commensal of the human intestinal tract and an opportunistic pathogen. The increasing incidence of enterococcal infections is mainly due to the ability of this organism to develop resistance to multiple antibiotics, including vancomycin. The aim of this study was to perform comparative genome analyses on four vancomycin-resistant Enterococcus faecium (VRE fm ) strains isolated from two fatal cases in a tertiary hospital in Malaysia. Two sequence types, ST80 and ST203, were identified which belong to the clinically important clonal complex (CC) 17. This is the first report on the emergence of ST80 strains in Malaysia. Three of the studied strains (VREr5, VREr6, VREr7) were each isolated from different body sites of a single patient (patient Y) and had different PFGE patterns. While VREr6 and VREr7 were phenotypically and genotypically similar, the initial isolate, VREr5, was found to be more similar to VRE2 isolated from another patient (patient X), in terms of the genome contents, sequence types and phylogenomic relationship. Both the clinical records and genome sequence data suggested that patient Y was infected by multiple strains from different clones and the strain that infected patient Y could have derived from the same clone from patient X. These multidrug resistant strains harbored a number of virulence genes such as the epa locus and pilus-associated genes which could enhance their persistence. Apart from that, a homolog of E. faecalis bee locus was identified in VREr5 which might be involved in biofilm formation. Overall, our comparative genomic analyses had provided insight into the genetic relatedness, as well as the virulence potential, of the four clinical strains., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Here, we report the draft whole-genome sequence of "Anthococcus," a novel genus of the family Streptococcaceae isolated from fresh flowers of a durian (Durio zibethinus) tree. The draft genome of Anthococcus sp. strain DF1 contains 2,157,756 bp, with a G+C content of 33.0%., (Copyright © 2016 Chuah et al.)

Background: Listeria monocytogenes is an important foodborne pathogen that causes considerable morbidity in humans with high mortality rates. In this study, we have sequenced the genomes and performed comparative genomics analyses on two strains, LM115 and LM41, isolated from ready-to-eat food in Malaysia., Results: The genome size of LM115 and LM41 was 2,959,041 and 2,963,111 bp, respectively. These two strains shared approximately 90% homologous genes. Comparative genomics and phylogenomic analyses revealed that LM115 and LM41 were more closely related to the reference strains F2365 and EGD-e, respectively. Our virulence profiling indicated a total of 31 virulence genes shared by both analysed strains. These shared genes included those that encode for internalins and L. monocytogenes pathogenicity island 1 (LIPI-1). Both the Malaysian L. monocytogenes strains also harboured several genes associated with stress tolerance to counter the adverse conditions. Seven antibiotic and efflux pump related genes which may confer resistance against lincomycin, erythromycin, fosfomycin, quinolone, tetracycline, and penicillin, and macrolides were identified in the genomes of both strains., Conclusions: Whole genome sequencing and comparative genomics analyses revealed two virulent L. monocytogenes strains isolated from ready-to-eat foods in Malaysia. The identification of strains with pathogenic, persistent, and antibiotic resistant potentials from minimally processed food warrant close attention from both healthcare and food industry.

Typhoid fever, caused by Salmonella enterica serovar Typhi, remains an important public health burden in Southeast Asia and other endemic countries. Various genotyping methods have been applied to study the genetic variations of this human-restricted pathogen. Multilocus sequence typing (MLST) is one of the widely accepted methods, and recently, there is a growing interest in the re-application of MLST in the post-genomic era. In this study, we provide the global MLST distribution of S. Typhi utilizing both publicly available 1,826 S. Typhi genome sequences in addition to performing conventional MLST on S. Typhi strains isolated from various endemic regions spanning over a century. Our global MLST analysis confirms the predominance of two sequence types (ST1 and ST2) co-existing in the endemic regions. Interestingly, S. Typhi strains with ST8 are currently confined within the African continent. Comparative genomic analyses of ST8 and other rare STs with genomes of ST1/ST2 revealed unique mutations in important virulence genes such as flhB, sipC, and tviD that may explain the variations that differentiate between seemingly successful (widespread) and unsuccessful (poor dissemination) S. Typhi populations. Large scale whole-genome phylogeny demonstrated evidence of phylogeographical structuring and showed that ST8 may have diverged from the earlier ancestral population of ST1 and ST2, which later lost some of its fitness advantages, leading to poor worldwide dissemination. In response to the unprecedented increase in genomic data, this study demonstrates and highlights the utility of large-scale genome-based MLST as a quick and effective approach to narrow the scope of in-depth comparative genomic analysis and consequently provide new insights into the fine scale of pathogen evolution and population structure.

Extraintestinal pathogenic Escherichia coli (ExPEC) that causes extraintestinal infections often harbor plasmids encoding fitness traits such as resistance and virulence determinants that are of clinical importance. We determined the complete nucleotide sequence of plasmid pEC302/04 from a multidrug-resistant E. coli EC302/04 which was isolated from the tracheal aspirate of a patient in Malaysia. In addition, we also performed comparative sequence analyses of 18 related IncFIIA plasmids to determine the phylogenetic relationship and diversity of these plasmids. The 140,232 bp pEC302/04 is a multireplicon plasmid that bears three replication systems (FII, FIA, and FIB) with subtype of F2:A1:B1. The plasmid is self-transmissible with a complete transfer region. pEC302/04 also carries antibiotic resistance genes such as bla TEM-1 and a class I integron containing sul1, cml and aadA resistance genes, conferring multidrug resistance (MDR) to its host, E. coli EC302/04. Besides, two iron acquisition systems (SitABCD and IutA-IucABCD) which are the conserved virulence determinants of ExPEC-colicin V or B and M (ColV/ColBM)-producing plasmids were identified in pEC302/04. Multiple toxin-antitoxin (TA)-based addiction systems (i.e., PemI/PemK, VagC/VagD, CcdA/CcdB, and Hok/Sok) and a plasmid partitioning system, ParAB, and PsiAB, which are important for plasmid maintenance were also found. Comparative plasmid analysis revealed only one conserved gene, the repA1 as the core genome, showing that there is an extensive diversity among the IncFIIA plasmids. The phylogenetic relationship of 18 IncF plasmids based on the core regions revealed that ColV/ColBM-plasmids and non-ColV/ColBM plasmids were separated into two distinct groups. These plasmids, which carry highly diverse genetic contents, are also mosaic in nature. The atypical combination of genetic materials, i.e., the MDR- and ColV/ColBM-plasmid-virulence encoding regions in a single ExPEC plasmid is rare but of clinical importance. Such phenomenon is bothersome when the plasmids are transmissible, facilitating the spread of virulence and resistance plasmids among pathogenic bacteria. Notably, certain TA systems are more commonly found in particular ExPEC plasmid types, indicating the possible relationships between certain TA systems and ExPEC pathogenesis.

Salmonella enterica serovar Typhi (S. Typhi) is a foodborne pathogen that causes typhoid fever and infects only humans. The ability of S. Typhi to survive outside the human host remains unclear, particularly in human carrier strains. In this study, we have investigated the catabolic activity of a human carrier S. Typhi strain in both planktonic and biofilm cells using the high-throughput Biolog Phenotype MicroArray, Minimum Biofilm Eradication Concentration (MBEC) biofilm inoculator (96-well peg lid) and whole genome sequence data. Additional strains of S. Typhi were tested to further validate the variation of catabolism in selected carbon substrates in the different bacterial growth phases. The analyzes of the carbon utilization data indicated that planktonic cells of the carrier strain, S. Typhi CR0044 could utilize a broader range of carbon substrates compared to biofilm cells. Pyruvic acid and succinic acid which are related to energy metabolism were actively catabolised in the planktonic stage compared to biofilm stage. On the other hand, glycerol, L-fucose, L-rhamnose (carbohydrates) and D-threonine (amino acid) were more actively catabolised by biofilm cells compared to planktonic cells. Notably, dextrin and pectin could induce strong biofilm formation in the human carrier strain of S. Typhi. However, pectin could not induce formation of biofilm in the other S. Typhi strains. Phenome data showed the utilization of certain carbon substrates which was supported by the presence of the catabolism-associated genes in S. Typhi CR0044. In conclusion, the findings showed the differential carbon utilization between planktonic and biofilm cells of a S. Typhi human carrier strain. The differences found in the carbon utilization profiles suggested that S. Typhi uses substrates mainly found in the human biliary mucus glycoprotein, gallbladder, liver and cortex of the kidney of the human host. The observed diversity in the carbon catabolism profiles among different S. Typhi strains has suggested the possible involvement of various metabolic pathways that might be related to the virulence and pathogenesis of this host-restricted human pathogen. The data serve as a caveat for future in-vivo studies to investigate the carbon metabolic activity to the pathogenesis of S. Typhi.

Background: Typhoid fever is an infectious disease of global importance that is caused by Salmonella enterica subsp. enterica serovar Typhi (S. Typhi). This disease causes an estimated 200,000 deaths per year and remains a serious global health threat. S. Typhi is strictly a human pathogen, and some recovered individuals become long-term carriers who continue to shed the bacteria in their faeces, thus becoming main reservoirs of infection., Results: A comparative genomics analysis combined with a phylogenomic analysis revealed that the strains from the outbreak and carrier were closely related with microvariations and possibly derived from a common ancestor. Additionally, the comparative genomics analysis with all of the other completely sequenced S. Typhi genomes revealed that strains BL196 and CR0044 exhibit unusual genomic variations despite S. Typhi being generally regarded as highly clonal. The two genomes shared distinct chromosomal architectures and uncommon genome features; notably, the presence of a ~10 kb novel genomic island containing uncharacterised virulence-related genes, and zot in particular. Variations were also detected in the T6SS system and genes that were related to SPI-10, insertion sequences, CRISPRs and nsSNPs among the studied genomes. Interestingly, the carrier strain CR0044 harboured far more genetic polymorphisms (83% mutant nsSNPs) compared with the closely related BL196 outbreak strain. Notably, the two highly related virulence-determinant genes, rpoS and tviE, were mutated in strains BL196 and CR0044, respectively, which revealed that the mutation in rpoS is stabilising, while that in tviE is destabilising. These microvariations provide novel insight into the optimisation of genes by the pathogens. However, the sporadic strain was found to be far more conserved compared with the others., Conclusions: The uncommon genomic variations in the two closely related BL196 and CR0044 strains suggests that S. Typhi is more diverse than previously thought. Our study has demonstrated that the pathogen is continually acquiring new genes through horizontal gene transfer in the process of host adaptation, providing novel insight into its unusual genomic dynamics. The understanding of these strains and virulence factors, and particularly the strain that is associated with the large outbreak and the less studied asymptomatic Typhi carrier in the population, will have important impact on disease control.

Kosakonia radicincitans (formerly known as Enterobacter radicincitans), an endophytic bacterium was isolated from the symptomatic tissues of bacterial wilt diseased banana (Musa spp.) plant in Malaysia. The total genome size of K. radicincitans UMEnt01/12 is 5 783 769 bp with 5463 coding sequences (CDS), 75 tRNAs, and 9 rRNAs. The annotated draft genome of the K. radicincitans UMEnt01/12 strain might shed light on its role as a bacterial wilt-associated bacterium.

Escherichia coli is an important etiologic agent of lower respiratory tract infections (LRTI). Multidrug-resistant E. coli EC302/04 was isolated from a tracheal aspirate, and its genome sequence is expected to provide insights into antimicrobial resistance as well as adaptive and virulence mechanisms of E. coli involved in LRTI.

The genome sequence analysis of a clinical Vibrio cholerae VC35 strain from an outbreak case in Malaysia indicates multiple genes involved in host adaptation and a novel Na(+)-driven multidrug efflux pump-coding gene in the genome of Vibrio cholerae with the highest similarity to VMA&#95;001754 of Vibrio mimicus VMA223.

Salmonella enterica serovar Typhi is a human pathogen that causes typhoid fever predominantly in developing countries. In this article, we describe the whole genome sequence of the S. Typhi strain CR0044 isolated from a typhoid fever carrier in Kelantan, Malaysia. These data will further enhance the understanding of its host persistence and adaptive mechanism.

Many of the developing countries of the Southeast Asian region are significantly affected by endemic typhoid fever, possibly as a result of marginal living standards. It is an important public health problem in countries such as Papua New Guinea, which is geographically close to some of the foci of endemicity in Asia. The severity of the disease varies in different regions, and this may be attributable to genetic diversity among the native strains. Genome sequence data on strains from different countries are needed to clearly understand their genetic makeup and virulence potential. We describe the genomes of two Salmonella Typhi isolates from patients with fatal and nonfatal cases of typhoid fever in Papua New Guinea. We discuss in brief the underlying sequencing methodology, assembly, genome statistics, and important features of the two draft genomes, which form an essential step in our functional molecular infection epidemiology program centering on typhoid fever. The comparative genomics of these and other isolates would enable us to identify genetic rearrangements and mechanisms responsible for endemicity and the differential severity of pathogenic salmonellae in Papua New Guinea and elsewhere.

Salmonella enterica serovar Typhi is the causative agent of typhoid fever, which causes nearly 21.7 million illnesses and 217,000 deaths globally. Herein, we describe the whole-genome sequence of the Salmonella Typhi strain ST0208, isolated from a sporadic case of typhoid fever in Kuala Lumpur, Malaysia. The whole-genome sequence and comparative genomics allow an in-depth understanding of the genetic diversity, and its link to pathogenicity and evolutionary dynamics, of this highly clonal pathogen that is endemic to Malaysia.

Among enteric pathogens, Salmonella enterica serovar Typhi is responsible for the largest number of food-borne outbreaks and fatalities. The ability of the pathogen to cause systemic infection for extended durations leads to a high cost of disease control. Chronic carriers play important roles in the evolution of Salmonella Typhi; therefore, identification and in-depth characterization of isolates from clinical cases and carriers, especially those from zones of endemicity where the pathogen has not been extensively studied, are necessary. Here, we describe the genome sequence of the highly virulent Salmonella Typhi strain BL196/05 isolated during the outbreak of typhoid in Kelantan, Malaysia, in 2005. The whole-genome sequence and comparative genomics of this strain should enable us to understand the virulence mechanisms and evolutionary dynamics of this pathogen in Malaysia and elsewhere.

Background: This study quantified long-term absolute and relative mortality risks of survivors of breast cancer with subsequent childbirth., Methods: The Singapore Birth Register (n = 319,437), Swedish Multi-Generation Register (n = 11 million) and population-based cancer registries were linked to identify 492 women with childbirth after breast cancer. For these women, cumulative mortality risks and standardized mortality ratios (SMRs) were calculated and compared with those of 8529 women aged less than 40 years with breast cancer without subsequent childbirth, and with those predicted by Adjuvant! Online., Results: Women with subsequent childbirth had a lower 15-year cumulative overall mortality rate than other women with breast cancer (16.8 (95 per cent confidence interval (c.i.) 13.3 to 20.9) versus 40.7 (39.5 to 41.9) per cent), but a higher relative mortality risk than the background population (SMR 13.6, 95 per cent c.i. 10.6 to 17.3). Mortality risks decreased significantly with increasing interval between diagnosis and subsequent childbirth. Mean 10-year cumulative mortality risks of women with subsequent childbirth were within the range of 10-year mortality predicted by Adjuvant! Online for women with T1 N0 tumours in otherwise perfect health., Conclusion: This study reinforced the view that pregnancy after breast cancer is not detrimental to survival. However, women who gave birth after this diagnosis had substantially higher mortality risks than young women in the general population. This information may be a valuable addition to routine mortality estimates., (Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Background: The relationship between multiparity and premenopausal breast cancer risk is different in Caucasian, African-American and Hispanic women. For Asian women, this relationship has never been well studied., Methods: Within the Singapore Birth Registry, we selected all women who had a first child between 1986 and 2002 (169,936 Chinese, 40,521 Malay, 17,966 Indian). We linked them to the Singapore Cancer Registry data to identify those who developed breast cancer after childbirth (n = 527). We used multivariate Cox analysis to examine the relationship between parity, ethnicity and premenopausal breast cancer risk., Results: Compared to Chinese, Malay women had increased and Indian women had decreased risks of premenopausal breast cancer (adjusted Hazard Ratios [HRadj] 1.25 [1.0-1.6] and 0.48 [0.3-0.8] respectively). Multiparity did not modify the risk of premenopausal breast cancer in Chinese and Indians. In Malays there was a significant risk reduction with increasing parity (P (trend )0.037). Malay women with one, two and >or=3 children had premenopausal breast cancer risks (HR(adj)) of 1.86 (1.2-3.0), 1.52 (1.1-2.2) and 0.87 (0.6-1.3) respectively compared to their Chinese counterparts., Conclusions: The impact of multiparity on premenopausal breast cancer risk differs across ethnic groups in Singapore. Increasing parity reduces the risk of premenopausal breast cancer in Malay, but not in Chinese and Indian women. Uniparous Malay women have twice the risk of premenopausal breast cancer compared to uniparous Chinese. This excess risk disappears after giving birth to >or=3 children. Indian women have lower premenopausal breast cancer risks than Chinese, regardless of their parity status.

We present theoretical and experimental results on an interference effect caused by boundary reflections on the optical scattering loss in high-index-contrast planar waveguides. Analytical expressions for the polarization-dependent scattering loss are derived using a surface Green's function. For high-index-contrast waveguides of submicrometer dimensions a significant deviation from accepted theory arises, including scattering loss suppression owing to a thin-film interference effect. Our theoretical predictions are confirmed by loss measurements on silicon-on-insulator channel waveguides.

A monolithically integrated asymmetric graded index (GRIN) or step-index (GRIN) mode converters for microphotonic waveguides are proposed and described. The design parameters and tolerances are calculated for amorphous silicon (a-Si) couplers integrated with silicon-on-insulator waveguides. The GRIN and step-index couplers operate over a wide wavelength range with low polarization dependence, and the lithographic resolution needed is only +/-1 microm. Finally, experimental results are presented for a single layer 3 microm thick step-index a-Si coupler integrated on a 0.8 microm thick SOI waveguide. The measured variation of coupling efficiency with coupler length is in agreement with theory, with an optimal coupling length of 15 microm for this device.

A novel mode transformer was fabricated that transforms a modal area by a factor of 100. Using the mode transformer improves the efficiency of mode transformation by an order of magnitude compared with that when no mode transformer is used. With this mode transformer, input-output coupling of miniaturized, on-chip integrated optical circuits to external optical fibers is achieved with low loss. The mode transformer's design, fabricated in silicon, is scalable to virtually any waveguide size, facilitating continuous miniaturization in silicon optoelectronics.

The goal of this study was to determine the frequency of alternative therapy use in postmenopausal women with early stage breast cancer who were enrolled in a randomized clinical trial designed to determine the value of breast irradiation after treatment with breast-conserving surgery and tamoxifen. A questionnaire was given to 300 patients, ages 52 to 90 years, after completion of radiation therapy (if any). Of the 290 respondents, 78 (27%) had used some form of alternative therapy. Of these, 60.3% started after the diagnosis of breast cancer. Users of alternative therapies were significantly younger than nonusers (67.0 +/- 8.4 years versus 70.0 +/- 8.7 years, p = 0.009) and they used a median of one type of therapy per person (range 1-13). Users of alternative therapies were more likely to have experienced symptoms (stiffness, pain, numbness, or swelling) in the ipsilateral shoulder or arm after treatment of their breast cancers compared to nonusers (odds ratio [OR] = 2.0, p = 0.02). This relationship between alternative therapy use and symptoms was strongest in the group who started alternative therapies after breast cancer diagnosis (OR = 2.1, p = 0.05). On multivariate analysis, younger age and radiotherapy treatment were related to alternative therapy use. In conclusion, 27% of patients with early stage breast cancer used alternative therapy. Users were more likely to be younger and to experience shoulder or arm symptoms after breast-conserving surgery with radiation.

Oncology patients are at increased risk of developing deep vein thrombosis (DVT) and its potentially fatal sequel, pulmonary embolism. This is due to multiple factors, including the presence of the malignancy itself, comorbid factors and therapy-related interventions. Issues that are peculiar to venous thrombosis in the oncology setting are discussed, based on a MEDLINE search of the English literature. These include the need to screen for malignancy in idiopathic DVT, a high index of suspicion for venous thrombosis in the cancer patient, the use of vena cava filters, and the anti-neoplastic effects of heparin. Asian patients appear to have a lower incidence of DVT compared to Caucasians. A recommended regimen for prophylaxis of DVT must take into account the varying thrombosis risk associated with different malignancies. Cancer patients not undergoing abdominal, pelvic or orthopaedic surgery (e.g. mastectomy) should use elastic compression stockings and be mobilized early, whereas low-molecular-weight heparin should be given to those undergoing more major surgery. In advanced malignancy, treatment of DVT palliates symptoms. These patients may need long-term anticoagulation with warfarin.

Methylene blue is a vital dye that is used in the treatment of methaemoglobinaemia. It is also used to delineate tissues to facilitate identification during surgery. Discoloration of the urine is known after oral and intravenous administration of the dye. We have used it routinely to detect the presence of defects after colorectal anastomosis. However, there have not been any previous reports of urinary discoloration after brief rectal instillation of the dye. We report a case of self-limiting urinary discoloration after anterior resection with colorectal anastomosis.

Background: The purpose of the current study was to identify the factors that contribute to postoperative arm symptoms following breast conserving surgery in a well-defined cohort of node negative breast carcinoma patients., Methods: A convenience sample of 370 women >/= 50 years of age with node negative breast carcinoma who were participants in a randomized controlled trial designed to assess the need for breast radiation in addition to tamoxifen were surveyed. Axillary dissection was optional for patients 65 years or older and who were clinically node negative., Results: A total of 65.1% (241/370) of women had ipsilateral shoulder or arm symptoms. Multivariate analysis revealed that axillary dissection, breast radiation, and younger age (odds ratio = 11.2, 1.65, and 3.8 respectively) were significantly (P < 0.05) associated with increased ipsilateral shoulder or arm symptoms. Treatment with axillary dissection and breast radiation were significant factors (P < 0.02) associated with the self-reporting of arm swelling (odds ratio = 4.4 and 2.0, respectively). Patients 70 years old or greater reported significantly fewer arm symptoms (odds ratio = 0.26, P < 0.05) after axillary dissection., Conclusions: Arm symptoms were present in about 80% of patients who underwent breast conserving surgery, axillary dissection, and breast radiation in the current study. These symptoms were significantly associated with the use of axillary dissection, breast radiation, and younger age. Older patients experienced fewer arm symptoms after standard treatment for node negative breast carcinoma, and thus older age should not be a contraindication to axillary dissection., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11217)

A retrospective study was done from October 1992 to December 1996 of 48 patients who underwent video-assisted thoracoscopy. A male to female ratio of 3.7:1 was seen, with a mean age of 50 +/- 19 years. The underlying diagnoses included spontaneous pneumothorax (n = 23), malignant pleural effusion (n = 16), lung disease (n = 4), trauma (n = 2), empyema (n = 2) and oesophageal carcinoma (n = 1). The use of this modality is discussed in the treatment of various intrathoracic pathologies.

Infections cause a significant amount of morbidity and mortality in paediatric surgical patients requiring intensive care. The study aims to describe the epidemiology of infection among these patients, to correlate the source of infection with the underlying medical condition, and to determine the antibiotic sensitivity pattern of the organisms. Through a retrospective review over a period of one year, 133 cases were analysed. The overall incidence of infection was 35%. Those who had emergency surgery had the highest infection rate (47%). Respiratory tract infections were the commonest source of infection, and were associated with ventilator therapy rather than the underlying medical condition. The Enterobacteriaceae were the most common isolates seen. From antibiotic sensitivity tests, the empirical antibiotics of choice are gentamicin for suspected gram-negative infection and vancomycin for severe infections where methicillin-resistant Staphylococcus aureus is a likely cause. A high rate of resistance to ampicillin was seen and its use as a first-line monotherapy drug should be discontinued in our patient population.