ALBERT

Description: Background: The gut microbiota plays an important role in human health and disease by acting as a metabolic organ. Metagenomic sequencing has shown how dysbiosis in the gut microbiota is associated with human metabolic diseases such as obesity and diabetes. Modeling may assist to gain insight into the metabolic implication of an altered microbiota. Fast and accurate reconstruction of metabolic models for members of the gut microbiota, as well as methods to simulate a community of microorganisms, are therefore needed. The Integrated Microbial Genomes (IMG) database contains functional annotation for nearly 4,650 bacterial genomes. This tremendous new genomic information adds new opportunities for systems biology to reconstruct accurate genome scale metabolic models (GEMs). Results: Here we assembled a reaction data set containing 2,340 reactions obtained from existing genome-scale metabolic models, where each reaction is assigned with KEGG Orthology. The reaction data set was then used to reconstruct two genome scale metabolic models for gut microorganisms available in the IMG database Bifidobacterium adolescentis L2-32, which produces acetate during fermentation, and Faecalibacterium prausnitzii A2-165, which consumes acetate and produces butyrate. F. prausnitzii is less abundant in patients with Crohn's disease and has been suggested to play an anti-inflammatory role in the gut ecosystem. The B. adolescentis model, iBif452, comprises 699 reactions and 611 unique metabolites. The F. prausnitzii model, iFap484, comprises 713 reactions and 621 unique metabolites. Each model was validated with in vivo data. We used OptCom and Flux Balance Analysis to simulate how both organisms interact. Conclusions: The consortium of iBif452 and iFap484 was applied to predict F. prausnitzii's demand for acetate and production of butyrate which plays an essential role in colonic homeostasis and cancer prevention. The assembled reaction set is a useful tool to generate bacterial draft models from KEGG Orthology.

Description: Background: Carnitine is a key molecule in energy metabolism that helps transport activated fatty acids into the mitochondria. Its homeostasis is achieved through oral intake, renal reabsorption and de novo biosynthesis. Unlike dietary intake and renal reabsorption, the importance of de novo biosynthesis pathway in carnitine homeostasis remains unclear, due to lack of animal models and description of a single patient defective in this pathway.Case presentationWe identified by array comparative genomic hybridization a 42 months-old girl homozygote for a 221 Kb interstitial deletions at 11p14.2, that overlaps the genes encoding Fibin and butyrobetaine-gamma 2-oxoglutarate dioxygenase 1 (BBOX1), an enzyme essential for the biosynthesis of carnitine de novo. She presented microcephaly, speech delay, growth retardation and minor facial anomalies. The levels of almost all evaluated metabolites were normal. Her serum level of free carnitine was at the lower limit of the reference range, while her acylcarnitine to free carnitine ratio was normal. Conclusions: We present an individual with a completely defective carnitine de novo biosynthesis. This condition results in mildly decreased free carnitine level, but not in clinical manifestations characteristic of carnitine deficiency disorders, suggesting that dietary carnitine intake and renal reabsorption are sufficient to carnitine homeostasis. Our results also demonstrate that haploinsufficiency of BBOX1 and/or Fibin is not associated with Primrose syndrome as previously suggested.

Description: Background: The unattractive appearance of the surface of pear fruit caused by the postharvest disorder friction discolouration (FD) is responsible for significant consumer dissatisfaction in markets, leading to lower returns to growers. Developing an understanding of the genetic control of FD is essential to enable the full application of genomics-informed breeding for the development of new pear cultivars. Biochemical constituents [phenolic compounds and ascorbic acid (AsA)], polyphenol oxidase (PPO) activity, as well as skin anatomy, have been proposed to play important roles in FD susceptibility in studies on a limited number of cultivars. However, to date there has been no investigation on the biochemical and genetic control of FD, employing segregating populations. In this study, we used 250 seedlings from two segregating populations (POP369 and POP356) derived from interspecific crosses between Asian (Pyrus pyrifolia Nakai and P. bretschneideri Rehd.) and European (P. communis) pears to identify genetic factors associated with susceptibility to FD. Results: Single nucleotide polymorphism (SNP)-based linkage maps suitable for QTL analysis were developed for the parents of both populations. The maps for population POP369 comprised 174 and 265 SNP markers for the male and female parent, respectively, while POP356 maps comprised 353 and 398 SNP markers for the male and female parent, respectively. Phenotypic data for 22 variables were measured over two successive years (2011 and 2012) for POP369 and one year (2011) only for POP356. A total of 221 QTLs were identified that were linked to 22 phenotyped variables, including QTLs associated with FD for both populations that were stable over the successive years. In addition, clear evidence of the influence of developmental factors (fruit maturity) on FD and other variables was also recorded. Conclusions: The QTLs associated with fruit firmness, PPO activity, AsA concentration and concentration of polyphenol compounds as well as FD are the first reported for pear. We conclude that the postharvest disorder FD is controlled by multiple small effect QTLs and that it will be very challenging to apply marker-assisted selection based on these QTLs. However, genomic selection could be employed to select elite genotypes with lower or no susceptibility to FD early in the breeding cycle.

Description: Background: Anaemia during pregnancy can lead to adverse maternal and perinatal outcomes. The WHO recommends that all pregnant women in areas where anaemia is prevalent receive supplements of iron and folic acid. However, due to many factors, the use of iron and folic acid supplementation is still low in many countries. This study was conducted to assess the rates of iron-folic supplementation and the associated factors during pregnancy and the effects of taking iron-folic acid supplementation on rates of maternal anaemia and low birth weight (LBW) infants. Methods: A cross-sectional study was conducted at Khartoum Hospital, Sudan. Enrolled women answered a questionnaire on socio-demographics characteristics, their pregnancy and delivery. Results: Of 856 women, 788 (92.1%) used iron-folic acid supplementation during pregnancy and 65.4% used folic acid. While place of residence, occupation and level of education were not associated with iron-folic acid usage, older age (OR = 3, CI = 1.4-6.3) and use of antenatal care (OR = 14.3, CI = 7.4-27.5) were associated with iron-folic acid use. Primiparity (OR = 3.8, CI = 1.9-7.6), maternal employment (OR = 3.9, CI = 2.25-6.77) and use of antenatal care (OR = 7.9, CI = 4.1-15) were the factors associated with folic acid. Using iron-folic acid was protective against anaemia (OR = 0.39, CI = 0.2-0.7) and LBW infants (OR = 0.3, CI = 0.17-0.68). Conclusion: There was a high rate of iron-folic acid supplementation use among pregnant women in Khartoum, Sudan, which was beneficial in preventing anaemia in expectant mothers and infants of LBW.

Description: Background: Advances in genomic technologies have enabled the accumulation of vast amount of genomic data, including gene expression data for multiple species under various biological and environmental conditions. Integration of these gene expression datasets is a promising strategy to alleviate the challenges of protein functional annotation and biological module discovery based on a single gene expression data, which suffers from spurious coexpression. Results: We propose a joint mining algorithm that constructs a weighted hybrid similarity graph whose nodes are the coexpression links. The weight of an edge between two coexpression links in this hybrid graph is a linear combination of the topological similarities and co-appearance similarities of the corresponding two coexpression links. Clustering the weighted hybrid similarity graph yields recurrent coexpression link clusters (modules). Experimental results on Human gene expression datasets show that the reported modules are functionally homogeneous as evident by their enrichment with biological process GO terms and KEGG pathways.

Description: Background: HCC is the fifth most common cancer globally. Our study was conducted to (1)investigate the trends and clinico-pathological characteristics of Hepatocellular carcinoma among native South Asian patients in Pakistan, (2)to estimate the prevalence as well as the trends of viral marker negative HCC and (3) to compare the clinico-pathological, radiological characteristics, applicability of treatment at diagnosis and prognostic factors among patients with both viral marker negative and viral marker positive-HCC being consulted at Aga Khan University Hospital(AKUH), Karachi, Pakistan.MethodPatients 〉=18 years, already diagnosed to have HCC and visiting AKUH during 1999--2009 were identified using ICD code 1550. The diagnosis of HCC was made in the presence of characteristic features of HCC on triple-phasic CT scan/MRI or with histological findings on biopsy. Results: 645 patients were enrolled. Of these 546(84.7%) were viral-HCC and 99(15.3%) were viral marker negative HCC. Among viral-HCC group underlying etiology of cirrhosis was HCV in 67.9%, HBV in 21.8% and concomitant HBV with HCV or HDV in 10.3% cases. Majority (62.8%) patients had advanced HCC. Larger tumor size (p 〈 0.001), shorter duration between diagnosis of cirrhosis and HCC (p 0.03), concomitant Diabetes Mellitus (p 〈 0.001) were found significant factors associated with viral marker negative HCC. Conclusion: The burden of hepatocellular carcinoma is rising among native South Asian population and the viral marker negative HCC are not uncommon in our population. Viral marker negative HCC tend not to be under surveillance as compared to viral-HCC and are diagnosed mostly at advanced stage & when they became symptomatic.

Description: Background: The main purpose of the study was to assess the prevalence, body distributions and factors associated with musculoskeletal pain (MSP) among medical students in a private Malaysian medical college.MethodThis cross-sectional study was conducted among 232 medical students in a private medical college using an online questionnaire. The questionnaire was a modified Standardized Nordic Questionnaire focused on neck, shoulder and low back pain in the past week and the past year. Results: Two hundred and thirty two medical students responded to the questionnaire out of 642. Mean age was 20.7 +/- 2.1 years. The majority were female (62.9%), Malay (80.6%) and in the preclinical years (72%). One hundred and six (45.7%) of all students had at least one site of MSP in the past week and 151 (65.1%) had at least one site of MSP in the past year. MSP in the past week was associated significantly with the academic year, (OR 2.0, 95% CI 1.15-3.67, P = 0.015), history of trauma (OR 2.6, 95% CI 1.2-5.3, P = 0.011), family history of MSP (OR 2.1, 95% CI 1.1-3.9, P = 0.023) and Body Mass Index (BMI) (P = 0.028). MSP in the past year was significantly associated with computer use (P = 0.027), daily hours of computer use (median +/- IQR (5.0 +/-3.0), history of trauma (OR 7.5, 95% CI 2.24-2.56, P 〈 0.01) and family history of MSP (OR 2.5, 95% CI 1.31-4.90, P = 0.006). On multivariate analysis, factors associated with MSP during the past week were a family history of MSP (p = 0.029) and BMI (p = 0.03). Factors associated with MSP during the past year were being in clinical years (p = 0.002, computer use (p = 0.038), and a history of trauma (p = 0.030). Conclusion: MSP among medical students was relatively high, thus, further clinical assessment is needed in depth study of ergonomics. The study results indicate that medical school authorities should take measures to prevent MSP due to factors related to medical school. Students should make aware of importance of weight reduction to reduce MSP.

Description: Background: Fascioliasis is an often-neglected zoonotic disease and currently is an emerging infection in Iraq. Fascioliasis has two distinct phases, an acute phase, exhibiting the hepatic migratory stage of the fluke's life cycle, and a chronic biliary phase manifested with the presence of the parasite in the bile ducts through hepatic tissue. The incidence of Fascioliasis in Sulaimaniyah governorate was unexpected observation. We believe that shedding light on this disease in our locality will increase our physician awareness and experience in early detection, treatment in order to avoid unnecessary surgeries.FindingsWe retrospectively evaluated this disease in terms of the demographic features, clinical presentations, and managements by reviewing the medical records of 18 patients, who were admitted to the Sulaimani Teaching Hospital and Kurdistan Centre for Gastroenterology and Hepatology. Patients were complained from hepatobiliary and/or upper gastrointestinal symptoms and diagnosed accidentally with Fascioliasis during hepatobiliary surgeries and ERCP by direct visualization of the flukes and stone analysis. Elevated liver enzymes, white blood cells count and eosinophilia were notable laboratory indices. The dilated CBD, gallstones, liver cysts and abscess were found common in radiological images. Fascioliasis diagnosed during conventional surgical CBD exploration and choledochodoudenostomy, open cholecystectomy, surgical drainage of liver abscess, ERCP and during gallstone analysis. Conclusion: Fascioliasis is indeed an emerging disease in our locality, but it is often underestimated and ignored. We recommend the differential diagnosis of patients suffering from Rt. Hypochondrial pain, fever and eosinophilia. The watercress ingestion was a common factor in patient's history.

Description: Currently there are definitions from many agencies and research societies defining "bioinformatics" as deriving knowledge from computational analysis of large volumes of biological and biomedical data. Should this be the bioinformatics research focus? We will discuss this issue in this review article. We would like to promote the idea of supporting human-infrastructure (HI) with no-boundary thinking (NT) in bioinformatics (HINT).

Description: Background: The surface of the human eye is covered by corneal epithelial cells (CECs) which regenerate from a small population of limbal epithelial stem cells (LESCs). Cell therapy with LESCs is a non-penetrating treatment for preventing blindness due to LESC deficiency or dysfunction. Our aim was to identify new putative molecular markers and upstream regulators in the LESCs and associated molecular pathways. Results: Genome-wide microarray transcriptional profiling was used to compare LESCs to differentiated human CECs. Ingenuity-based pathway analysis was applied to identify upstream regulators and pathways specific to LESCs. ELISA and flow cytometry were used to measure secreted and surface expressed proteins, respectively. More than 2 fold increase and decrease in expression could be found in 1830 genes between the two cell types. A number of molecules functioning in cellular movement (381), proliferation (567), development (552), death and survival (520), and cell-to-cell signaling (290) were detected having top biological functions in LESCs and several of these were confirmed by flow cytometric surface protein analysis. Custom-selected gene groups related to stemness, differentiation, cell adhesion, cytokines and growth factors as well as angiogenesis could be analyzed. The results show that LESCs play a key role not only in epithelial differentiation and tissue repair, but also in controlling angiogenesis and extracellular matrix integrity. Some pro-inflammatory cytokines were found to be important in stemness-, differentiation- and angiogenesis-related biological functions: IL-6 and IL-8 participated in most of these biological pathways as validated by their secretion from LESC cultures. Conclusions: The gene and molecular pathways may provide a more specific understanding of the signaling molecules associated with LESCs, therefore, help better identify and use these cells in the treatment of ocular surface diseases.