Selenium Differentially Regulates Flavonoid Accumulation and Antioxidant Capacities in Sprouts of Twenty Diverse Mungbean(Vigna radiata(L.)Wilczek)Genotypes

Seed germination with selenium(Se)is promising for producing Se-biofortified foods.Mungbean(Vigna radiata(L.)Wilczek)sprout is freshly eaten as a salad dressed with sauce,making it superior for Se biofortification.Since the Se safety range for the human body is extremely narrow,it is imperative to evaluate the genotypic responses of mungbean sprouts to Se.This study evaluated the Se enrichment capacity and interaction withflavonoids and antioxidant systems in sprouts of 20 mungbean germplasms.Selenium treatment was done by immersing mung-bean seeds in 20μM sodium selenite solution for 8 h.Afterward,the biomass,Se amounts,flavonoid(particularly vitexin and isovitexin)contents,antioxidant capacity,and key biosynthetic gene expressions were measured.Sprout Se content was 2.0-7.0μg g^(-1) DW among the 20 mungbean germplasms.Selenium treatment differentially affected the biomass,totalflavonoid,vitexin,isovitexin,antioxidant enzyme activities,and antioxidant capacities of the mungbean germplasms.Eight germplasms showed increased biomass(p<0.05),the highest increasing by 127%,but 13 did not phenotypically respond to Se treatment.Seven and six germplasms showed varied levels of vitexin and isovitexin increment after Se treatment,the highest measuring 2.67-and 2.87-folds for vitexin and isovitexin,respectively.Two mungbeanflavonoid biosynthesis genes,chalcone synthase(VrCHS)and chalcone isomerase(VrCHI)were significantly up-regulated in the germplasms with increased vitexin and isovitexin levels(p<0.05).Moreover,Se enrichment capacity was significantly correlated with the vitexin,isovitexin,and antiox-idant capacities.In conclusion,mungbean sprouts could be a useful Se-biofortified food,but the Se enrichment capacity and nutritional response must be determined for each germplasm before commercialization.

Analysis of Phenotypes Associated with Deficiency of PAX6 Haplotypes in Chinese Aniridia Families

Objective To examine the clinical phenotype and genetic deficiencies present in Chinese aniridia families with PAX6 haplotype deficiency.Methods A comprehensive questionnaire and ophthalmological assessments were administered to both affected patients and unaffected relatives.The clinical feature analysis included the evaluation of visual acuity,intraocular pressure,slit-lamp anterior segment examination,fundus photography,and spectral domain optical coherence tomography.To identify the mutation responsible for aniridia,targeted next-generation sequencing was used as a beneficial technique.Results A total of 4 mutations were identified,consisting of two novel frameshift mutations(c.314delA,p.K105Sfs*33 and c.838_845dup AACACACC,p.S283Tfs*85),along with two recurring nonsense mutations(c.307C>T,p.R103X and c.619A>T,p.K207*).Complete iris absence,macular foveal hypoplasia,and nystagmus were consistent in these PAX6 haplotype-deficient Chinese aniridia families,while corneal lesions,cataracts,and glaucoma exhibited heterogeneity both among the families and within the same family.Conclusion In our study,two novel PAX6 mutations associated with aniridia were identified in Chinese families,which expanded the phenotypic and genotypic spectrum of PAX6 mutations.We also analyzed the clinical characteristics of PAX6 haplotype deficiency in Chinese aniridia families.

Comprehensive understanding of glioblastoma molecular phenotypes:classification,characteristics,and transition

Among central nervous system-associated malignancies,glioblastoma(GBM)is the most common and has the highest mortality rate.The high heterogeneity of GBM cell types and the complex tumor microenvironment frequently lead to tumor recurrence and sudden relapse in patients treated with temozolomide.In precision medicine,research on GBM treatment is increasingly focusing on molecular subtyping to precisely characterize the cellular and molecular heterogeneity,as well as the refractory nature of GBM toward therapy.Deep understanding of the different molecular expression patterns of GBM subtypes is critical.Researchers have recently proposed tetra fractional or tripartite methods for detecting GBM molecular subtypes.The various molecular subtypes of GBM show significant differences in gene expression patterns and biological behaviors.These subtypes also exhibit high plasticity in their regulatory pathways,oncogene expression,tumor microenvironment alterations,and differential responses to standard therapy.Herein,we summarize the current molecular typing scheme of GBM and the major molecular/genetic characteristics of each subtype.Furthermore,we review the mesenchymal transition mechanisms of GBM under various regulators.

Identification of S-RNase genotype and analysis of its origin and evolutionary patterns in Malus plants

Identification of the S genotype of Malus plants will greatly promote the discovery of new genes,the cultivation and production of apple,the breeding of new varieties,and the origin and evolution of self-incompatibility in Malus plants.In this experiment,88 Malus germplasm resources,such as Aihuahong,Xishuhaitang,and Reguanzi,were used as materials.Seven gene-specific primer combinations were used in the genotype identification.PCR amplification using leaf DNA produced a single S-RNase gene fragment in all materials.The results revealed that 70 of the identified materials obtained a complete S-RNase genotype,while only one S-RNase gene was found in 18 of them.Through homology comparison and analysis,13 S-RNase genotypes were obtained:S_(1)S_(2)(Aihuahong,etc.),S_(1)S_(28)(Xixian Haitang,etc.),S_(1)S_(51)(Hebei Pingdinghaitang),S_(1)S_(3)(Xiangyangcun Daguo,etc.),S_(2)S_(3)(Zhaiyehaitang,etc.),S_(3)S_(51)(Xishan 1),S_(3)S_(28)(Huangselihaerde,etc.),S_(2)S_(28)(Honghaitang,etc.),S_(4)S_(28)(Bo 11),S_(7)S_(28)(Jiuquan Shaguo),S_(10)S_e(Dongchengguan 13),S_(10)S_(21)(Dongxiangjiao)and S_(3)S_(51)(Xiongyue Haitang).Simultaneously,the frequency of the S gene in the tested materials was analyzed.The findings revealed that different S genes had varying frequencies in Malus resources,as well as varying frequencies between intraspecific and interspecific.S_(3) had the highest frequency of 68.18%,followed by S_(1)(42.04%).In addition,the phylogenetic tree and origin evolution analysis revealed that the S gene differentiation was completed prior to the formation of various apple species,that cultivated species also evolved new S genes,and that the S_(50) gene is the oldest S allele in Malus plants.The S_(1),S_(29),and S_(33) genes in apple-cultivated species,on the other hand,may have originated in M.sieversii,M.hupehensis,and M.kansuensis,respectively.In addition to M.sieversii,M.kansuensis and M.sikkimensis may have also played a role in the origin and evolution of some Chinese apples.

Correlation between genotypes of Orientia tsutsugamushi and clinical characteristics of patients with scrub typhus in Guangzhou,China

Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus patients.Methods:Clinical data of patients with scrub typhus admitted to different types of medical institutions in Guangzhou from September 2012 to December 2016 were collected using medical records.Demographic data,clinical manifestations,as well as hematological and biochemical indicators of patients infected with different genotypes were analyzed and compared.Results:A total of 192 patients were included in this study,including 121 patients with Karp genotype of O.tsutsugamushi infection(63.0%),36 patients with Gilliam genotype(19.0%),23 patients with Kato genotype(12.0%),and 12 patients with TA763 genotype(6.0%)infection.The median value of albumin in patients with Karp genotype infection was significantly lower than that of Gilliam-infected patients(P=0.032).Patients with Karp genotype infection had a significantly longer hospital stay(9 days)than those with Gilliam genotype(7 days)(P=0.009)and Kato genotype infection(6 days)(P=0.005).Karp-infected patients also represented for the largest number of patients with complicated organ involvement(88/133,66.2%).Furthermore,Karp-infected patients had higher risk of developing multiple organ dysfunction syndrome(18.2%)and requiring intensive care unit treatment(15.9%).Besides,patients with Gilliam genotype(8 days)and TA763 genotype infection(7.5 days)had shorter fever duration than those with Karp genotype(9 days)and Kato genotype(9 days)infection,respectively.Conclusions:Genotypes of Orientia tsutsugamushi were associated with varying clinical manifestations,organ involvement,and treatment outcomes,suggesting that genotypes ranged in virulence.

Identification of clinical subphenotypes of sepsis after laparoscopic surgery

Objective:Some patients exhibit septic symptoms following laparoscopic surgery,leading to a poor prognosis.Effective clinical subphenotyping is critical for guiding tailored therapeutic strategies in these cases.By identifying predisposing factors for postoperative sepsis,clinicians can implement targeted interventions,potentially improving outcomes.This study outlines a workflow for the subphenotype methodology in the context of laparoscopic surgery,along with its practical application.Methods:This study utilized data routinely available in clinical case systems,enhancing the applicability of our findings.The data included vital signs,such as respiratory rate,and laboratory measures,such as blood sodium levels.The process of categorizing clinical routine data involved technical complexities.A correlation heatmap was used to visually depict the relationships between variables.Ordering points were used to identify the clustering structure and combined with Consensus K clustering methods to determine the optimal categorization.Results:Our study highlighted the intricacies of identifying clinical subphenotypes following laparoscopic surgery,and could thus serve as a valuable resource for clinicians and researchers seeking to explore disease heterogeneity in clinical settings.By simplifying complex methodologies,we aimed to bridge the gap between technical expertise and clinical application,fostering an environment where professional medical knowledge is effectively utilized in subphenotyping research.Conclusion:This tutorial could primarily serve as a guide for beginners.A variety of clustering approaches were explored,and each step in the process contributed to a comprehensive understanding of clinical subphenotypes.

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes

●AIM:To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes.●METHODS:Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited.Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients’medical records.A hierarchical cluster analysis was performed.The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts.●RESULTS:A total of 164 children(299 eyes)were divided into two clusters based on their ocular features.Cluster 1(96 eyes)had a shorter axial length(mean±SD,19.44±1.68 mm),a low prevalence of macular abnormalities(1.04%),and no retinal abnormalities or posterior cataracts.Cluster 2(203 eyes)had a greater axial length(mean±SD,20.42±2.10 mm)and a higher prevalence of macular abnormalities(8.37%),retinal abnormalities(98.52%),and posterior cataracts(4.93%).Compared with the eyes in Cluster 2(57.14%),those in Cluster 1(71.88%)had a 2.2 times higher chance of good best-corrected visual acuity[<0.7 logMAR;OR(95%CI),2.20(1.25–3.81);P=0.006].●CONCLUSION:This retrospective study categorizes congenital cataracts into two distinct clusters,each associated with a different likelihood of visual outcomes.This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit,thereby making strides toward precision medicine in the field of congenital cataracts.

Association between the Different Phenotypes of Polycystic Ovary Syndrome and the Outcome in in Vitro Fertilization at Human Reproductive Center Paul et Chantal Biya-Yaoundé

Background: In Vitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) represents the final step in the management of Polycystic Ovarian Syndrome (PCOS). Our objective was to study the association between PCOS phenotypes and IVF/ICSI results in women admitted to Gynaecological Endoscopic Surgery and Human Reproductive Teaching Hospital (CHRACERH). Material and Method: We carried out a cohort study with historical-prospective data collection over a period of seven years (January 2016 to March 2023) at Chracerh. PCOS patients were subdivided into 4 subgroups A, B, C and D. Results: We recruited 128 patients including 64 PCOS patients divided into four phenotypes and 64 non-PCOS patients constituting the control group. Phenotype D without hyperandrogenism had used the lowest dose of gonadotropins, i.e. 1939.7 ± 454.3 IU, and had produced a greater quantity of estradiol on the day ovulation was triggered (6529.8 ± 4324.8 ng/ml). The average number of punctured follicles and mature oocytes were higher in the phenotype D group. Ovarian hyperstimulation syndrome (OHSS) occurred mainly in phenotype D (3/35), with an estimated prevalence of 2.3%. The fertilization rate seemed lower in the hyperandrogenic phenotypes A, B, C compared to the group without hyperandrogenism without significant difference (p = 0.461). The biological pregnancy rate and live birth rate were comparable between the different groups. Conclusion: Phenotype D used less dose of gonadotropins. Biological pregnancy and live birth rates were comparable between the different phenotypes.

Characterization of early maturing elite genotypes based on MTSI and MGIDI indexes:an illustration in upland cotton(Gossypium hirsutum L.)

Background Globally,the cultivation of cotton is constrained by its tendency for extended periods of growth.Early maturity plays a potential role in rainfed-based multiple cropping system especially in the current era of climate change.In the current study,a set of 20 diverse Gossypium hirsutum genotypes were evaluated in two crop seasons with three planting densities and assessed for 11 morphological traits related to early maturity.The study aimed to identify genotype(s)that mature rapidly and accomplish well under diverse environmental conditions based on the two robust multivariate techniques called multi-trait stability index(MTSI)and multi-trait genotype-ideotype distance index(MGIDI).Results MTSI analysis revealed that out of the 20 genotypes,three genotypes,viz.,NNDC-30,A-2,and S-32 accomplished well in terms of early maturity traits in two seasons.Furthermore,three genotypes were selected using MGIDI method for each planting densities with a selection intensity of 15%.The strengths and weaknesses of the genotypes selected based on MGIDI method highlighted that the breeders could focus on developing early-maturing genotypes with specific traits such as days to first flower and boll opening.The selected genotypes exhibited positive genetic gains for traits related to earliness and a successful harvest during the first and second pickings.However,there were negative gains for traits related to flowering and boll opening.Conclusion The study identified three genotypes exhibiting early maturity and accomplished well under different planting densities.The multivariate methods(MTSI and MGIDI)serve as novel approaches for selecting desired genotypes in plant breeding programs,especially across various growing environments.These methods offer exclusive benefits and can easily construe and minimize multicollinearity issues.

Hepatitis B virus genotypes in precision medicine of hepatitis Brelated hepatocellular carcinoma:Where we are now

Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.

Chromosome-level genome assembly of the glass catfish(Kryptopterus vitreolus)reveals molecular clues to its transparent phenotype

Glass catfish(Kryptopterus vitreolus)are notable in the aquarium trade for their highly transparent body pattern.This transparency is due to the loss of most reflective iridophores and light-absorbing melanophores in the main body,although certain black and silver pigments remain in the face and head.To date,however,the molecular mechanisms underlying this transparent phenotype remain largely unknown.To explore the genetic basis of this transparency,we constructed a chromosome-level haplotypic genome assembly for the glass catfish,encompassing 32 chromosomes and 23344 protein-coding genes,using PacBio and Hi-C sequencing technologies and standard assembly and annotation pipelines.Analysis revealed a premature stop codon in the putative albinism-related tyrp1b gene,encoding tyrosinase-related protein 1,rendering it a nonfunctional pseudogene.Notably,a synteny comparison with over 30 other fish species identified the loss of the endothelin-3(edn3b)gene in the glass catfish genome.To investigate the role of edn3b,we generated edn3b^(−/−)mutant zebrafish,which exhibited a remarkable reduction in black pigments in body surface stripes compared to wild-type zebrafish.These findings indicate that edn3b loss contributes to the transparent phenotype of the glass catfish.Our high-quality chromosome-scale genome assembly and identification of key genes provide important molecular insights into the transparent phenotype of glass catfish.These findings not only enhance our understanding of the molecular mechanisms underlying transparency in glass catfish,but also offer a valuable genetic resource for further research on pigmentation in various animal species.

Serological Investigation into the Infected Genotypes of Patients with Japanese Encephalitis in the Coastal Provinces of China

Objective Genotypes(G)1,3,and 5 of the Japanese encephalitis virus(JEV)have been isolated in China,but the dominant genotype circulating in Chinese coastal areas remains unknown.We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis(JE)in the coastal provinces of China.Methods In this study,we collected serum specimens from patients with JE in three coastal provinces of China(Guangdong,Zhejiang,and Shandong)from 2018 to 2020 and conducted JEV cross-neutralization tests against G1,G3,and G5.Results Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong(92 patients),Zhejiang(192 patients),and Guangdong(77 patients),China,from 2018 to 2020.Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV.Two cases were confirmed to be infected with G1 JEV,32 with G3 JEV,and two with G5 JEV.Conclusion G3 was the primary infection genotype among JE cases with a definite infection genotype,and the infection caused by G5 JEV was confirmed serologically in China.

Multidimensional evaluation of salt tolerance in groundnut genotypes through biochemical responses

The manuscript explores the complex interplay between groundnut genotypes,salt tolerance and hormonal influence,shedding light on the dynamic responses of three specific groundnut genotypes,KDG-128,TG-37 A and GG-20,to salt treatments and gibberellic acid(GA3).The study encompasses germination,plant growth,total protein content and oil content as key parameters.Through comprehensive analysis,it identifies TG-37 A and KDG-128 as salt-tolerant genotypes,and GG-20 as salt-susceptible genotypes,which highlighting the potential for targeted breeding efforts to develop more resilient groundnut varieties.Moreover,the quantification of protein and oil content under different treatments provides vital data for optimizing nutritional profiles in groundnut cultivars.Principal Component Analysis(PCA) underscores the significance of the first principal component(PC1)in explaining the majority of variance,capturing primary trends and differences in plant length.Analysis of Variance(ANOVA) and hierarchical analysis confirm the presence of statistically significant differences in protein and oil content among the genotypes.Pearson's correlation coefficient matrix analysis reveals strong positive correlations between plant length and protein content,plant length and oil content,and a moderately positive correlation between protein content and oil content.These findings provide valuable insights into groundnut physiology,salt tolerance,and nutritional composition,with implications for future research in sustainable agriculture and crop improvement.

Genotype-based precision nutrition strategies for the prediction and clinical management of type 2 diabetes mellitus

Globally,type 2 diabetes mellitus(T2DM)is one of the most common metabolic disorders.T2DM physiopathology is influenced by complex interrelationships between genetic,metabolic and lifestyle factors(including diet),which differ between populations and geographic regions.In fact,excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM,whereas habitual intakes of plant-based healthy diets usually exert a protective effect.Moreover,genomic studies have allowed the characterization of sequence DNA variants across the human genome,some of which may affect gene expression and protein functions relevant for glucose homeostasis.This comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression,some of which have demonstrated a value as biomarkers of personal responses to certain nutritional interventions.Also,novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle recommendations.Furthermore,progresses in other omics areas(epigenomics,metagenomics,proteomics,and metabolomics)are improving current understanding of genetic insights in T2DM clinical outcomes.Although more investigation is still needed,the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening,prevention,diagnosis,management,and prognosis of T2DM through precision nutrition.

Risk factors for hepatocellular carcinoma associated with hepatitis C genotype 3 infection:A systematic review

BACKGROUND Hepatitis C virus(HCV)is a blood-borne virus which globally affects around 79 million people and is associated with high morbidity and mortality.Chronic infection leads to cirrhosis in a large proportion of patients and often causes hepatocellular carcinoma(HCC)in people with cirrhosis.Of the 6 HCV genotypes(G1-G6),genotype-3 accounts for 17.9%of infections.HCV genotype-3 responds least well to directly-acting antivirals and patients with genotype-3 infection are at increased risk of HCC even if they do not have cirrhosis.AIM To systematically review and critically appraise all risk factors for HCC secondary to HCV-G3 in all settings.Consequently,we studied possible risk factors for HCC due to HCV-G3 in the literature from 1946 to 2023.METHODS This systematic review aimed to synthesise existing and published studies of risk factors for HCC secondary to HCV genotype-3 and evaluate their strengths and limitations.We searched Web of Science,Medline,EMBASE,and CENTRAL for publications reporting risk factors for HCC due to HCV genotype-3 in all settings,1946-2023.RESULTS Four thousand one hundred and forty-four records were identified from the four databases with 260 records removed as duplicates.Three thousand eight hundred and eighty-four records were screened with 3514 excluded.Three hundred and seventy-one full-texts were assessed for eligibility with seven studies included for analysis.Of the seven studies,three studies were retrospective case-control trials,two retrospective cohort studies,one a prospective cohort study and one a cross-sectional study design.All were based in hospital settings with four in Pakistan,two in South Korea and one in the United States.The total number of participants were 9621 of which 167 developed HCC(1.7%).All seven studies found cirrhosis to be a risk factor for HCC secondary to HCV genotype-3 followed by higher age(five-studies),with two studies each showing male sex,high alpha feto-protein,directly-acting antivirals treatment and achievement of sustained virologic response as risk factors for developing HCC.CONCLUSION Although,studies have shown that HCV genotype-3 infection is an independent risk factor for end-stage liver disease,HCC,and liver-related death,there is a lack of evidence for specific risk factors for HCC secondary to HCV genotype-3.Only cirrhosis and age have demonstrated an association;however,the number of studies is very small,and more research is required to investigate risk factors for HCC secondary to HCV genotype-3.

Causal association between 731 immunocyte phenotypes and liver cirrhosis: A bidirectional two-sample mendelian randomization analysis

BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis.AIM To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization(MR)study.METHODS Data on 731 immunocyte phenotypes were obtained from genome-wide assoc-iation studies.Liver cirrhosis data were derived from the Finn Gen dataset,which included 214403 individuals of European ancestry.We used inverse variable weighting as the primary analysis method to assess the causal relationship.Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.RESULTS The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis[P<0.05,odds ratio(OR)>1]and that 9 immu-nocyte phenotypes were negatively correlated with liver cirrhosis(P<0.05,OR<1).Liver cirrhosis was positively linked to 9 immune cell phenotypes(P<0.05,OR>1)and negatively linked to 10 immune cell phenotypes(P<0.05;OR<1).None of these associations showed heterogeneity or horizontally pleiotropy(P>0.05).CONCLUSION This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis.These findings offer new directions for the treatment of liver cirrhosis.

Subclinical hepatitis E virus genotype 1 infection:The concept of“dynamic human reservoir”

Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world.Asymptomatic HEV viremia in the general population,especially among blood donors,has been reported in the literature worldwide.The clinical implications related to this asymptomatic viremia are unclear and need further exploration.Detection of viremia due to HEV genotype 1 infection,apparently among healthy blood donors is also reported without much knowledge about its infection rate.Similarly,while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations,instances of transmission have also been documented albeit without significant clinical consequences.Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern.Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen.In absence of known animal reservoir,where HEV exists in between outbreak is a mystery that needs further exploration.However,occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir.Since HEV genotype 1 infection cannot cause chronicity,subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period.This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it.In view of existing evidence,we propose the concept of“Dynamic Human Reservoir.”Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community.The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature.This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.

Associations between NOD2/CARD15 genotype andphenotype in Crohn’s disease-Are we there yet?

There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their size and on the presence of specific clinical and genetic information provided in the published material from 2001 to 2005. Twelve studies provided raw data to carry out comparisons of disease location while ten studies included analysis of NOD2/CARD15 genotypes. NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated highly significant differences among studies. Meta-analysis confirmed significant associations between NOD2/CARD15 variants and both ileal and ileocolonic disease locations, and with both stricturing and penetrating forms of disease behavior. This review underlines the significant phenotypic differences that exist among populations, including similar ethnic groups, and has demonstrated the need for further studies of patients with long-term “inflammatory” Crohn’s disease.

Relationship between genotype and phenotype of flagellin C in Salmonella

AIM: To discover the relationship between the genotype and antigen serotype of flagellin C among Salmonella strains. METHODS: Fragment of Salmonella flagellin C in plasmid pLS408 was cloned, sequenced and compared with the corresponding sequence in other strains. Salmonella strains including two typhi strains, one paratyphoid strain, one enteritidis and one typhimurium strain were isolated from outpatients. Genome DNA was purified respectively from these clinical isolates, then the corresponding flagellin C fragment was amplified by polymerase chain reaction,and the amplification products were analyzed by agarose gel electrophoresis. RESULTS: The cloned fragment includes 582 nucleotides encoding the variable region and partial conservative region of Salmonella flagellin C in plasmid pLS408. With comparison to the corresponding sequences reported previously, there is only a little difference from other strains with the same flagellar serotype in both nucleotide and amino acid level. Specific PCR products were amplified in Salmonella strains with flagellar serotype H-1-d including S. muenchen, typhi and typhimurium, but not in S. paratyphoid C or S. enteritidis strains. CONCLUSION: In this experiment, the specificity of nucleotide sequence could be found in flagellin C central variable regions as it exists in flagellar serotypes in Salmonella. It may be helpful to developing a rapid, sensitive, accurate and PCR-based method to detect Salmonella strains with serotype H-1-d.

Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: Phenotype-genotype correlations

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.