Towards system genetics analysis of head and neck squamous cell carcinoma using the mouse model,cellular platform,and clinical human data

Head and neck squamous cell cancer(HNSCC)is a leading global malignancy.Every year,More than 830000 people are diagnosed with HNSCC globally,with more than 430000 fatalities.HNSCC is a deadly diverse malignancy with many tumor locations and biological characteristics.It originates from the squamous epithelium of the oral cavity,oropharynx,nasopharynx,larynx,and hypopharynx.The most frequently impacted regions are the tongue and larynx.Previous investigations have demonstrated the critical role of host genetic susceptibility in the progression of HNSCC.Despite the advances in our knowledge,the improved survival rate of HNSCC patients over the last 40 years has been limited.Failure to identify the molecular origins of development of HNSCC and the genetic basis of the disease and its biological heterogeneity impedes the development of new therapeutic methods.These results indicate a need to identify more genetic factors underlying this complex disease,which can be better used in early detection and prevention strategies.The lack of reliable animal models to investigate the underlying molecular processes is one of the most significant barriers to understanding HNSCC tumors.In this report,we explore and discuss potential research prospects utilizing the Collaborative Cross mouse model and crossing it to mice carrying single or double knockout genes(e.g.Smad 4 and P53 genes)to identify genetic factors affecting the development of this complex disease using genome-wide association studies,epigenetics,micro RNA,long noncoding RNA,lnc RNA,histone modifications,methylation,phosphorylation,and proteomics.

The clinical impact of bacterial biofilms

Bacteria survive in nature by forming biofilms on surfaces and probably most, if not all, bacteria （and fungi） are capable of forming biofilms. A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and extracellular DNA. Bacterial biofilms are resistant to antibiotics, disinfectant chemicals and to phagocytosis and other components of the innate and adaptive inflammatory defense system of the body. It is known, for example, that persistence of staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infections in cystic fibrosis patients are caused by biofilm growing mucoid strains. Gradients of nutrients and oxygen exist from the top to the bottom of biofilms and the bacterial cells located in nutrient poor areas have decreased metabolic activity and increased doubling times. These more or less dormant cells are therefore responsible for some of the tolerance to antibiotics. Biofilm growth is associated with an increased level of mutations. Bacteria in biofilms communicate by means of molecules, which activates certain genes responsible for production of virulence factors and, to some extent, biofilm structure. This phenomenon is called quorum sensing and depends upon the concentration of the quorum sensing molecules in a certain niche, which depends on the number of the bacteria. Biofilms can be prevented by antibiotic prophylaxis or early aggressive antibiotic therapy and they can be treated by chronic suppressive antibiotic therapy. Promising strategies may include the use of compounds which can dissolve the biofilm matrix and quorum sensing inhibitors, which increases biofilm susceptibility to antibiotics and phagocytosis.

Hypermucoviscosity in Clinical Isolates of Klebsiella pneumoniae Correlates with High Multiple Antibiotic Resistance (MAR) Index

Klebsiella pneumoniae is an opportunistic pathogen of medical importance and the capsule and mucoid phenotype in this organism are considered as requisite virulence determinants. A total of 62 clinical samples from ATBUTH were collected and screened for K. pneumoniae. The isolates were identified using standard tests for this organism. The string test was used to detect the mucoid (hypermucoviscous) phenotype and the antimicrobial susceptibility test to 10 antibiotics was carried out with the disk diffusion technique after standardizing inoculum. A K. pneumoniae prevalence of 24% (15/62) was obtained of which 47% (7/15) were mucoid (hypermucoviscous) and 53% (8/15) were non-mucoid. Colonial sizes of the two strains do not reveal any significant differences in growth fitness of the strains. On blood agar, the mucoid and non-mucoid strains had a mean colonial size ± standard deviations of 4.41 ± 0.58 mm and 4.27 ± 0.42 mm respectively. The antibiotic susceptibility rate showed that the mucoid strains compared to the non-mucoid were more resistant to nine out of 10 antibiotics. The mucoid strains were outrightly resistant to augmentin, amoxicillin, septrin, sparfloxacin and perfloxacin. The non-mucoid strains showed no complete resistant to any antibiotic tested but had a higher resistant rate to chloramphenicol only. The Multiple Antibiotic Resistance (MAR) index shows the themucoid strains with a high MAR index range of 0.7 - 1.0 with a median MAR index of 0.8, while the non-mucoid strains had a MAR index of 0.2 - 0.8 with a median MAR index of 0.35. The data suggest that the mucoid phenotype could be associated with extrachromsomal element(s) carrying resistance genes to antibiotics and that these extrachromosomal elements may not harbour resistance determinants to chloramphenicol. Furthermore, the extrachromosomal elements bearing the mucoid phenotype and the resistance elements in the mucoid strains do not significantly impact on the fitness of the cognate strain. Whether these phenotype and resistances that had no fitness cost to the bacterium could significantly affect the virulence of the bacteria in vivo remains to be investigated.

Lowering fasting blood glucose with non-dialyzable material of cranberry extract is dependent on host genetic background,sex and diet

Background:Type 2 diabetes(T2D)is a polygenic metabolic disease,character-ized by high fasting blood glucose(FBG).The ability of cranberry(CRN)fruit to regulate glycemia in T2D patients is well known.Here,a cohort of 13 lines of the genetically diverse Collaborative Cross(CC)mouse model was assessed for the effect of non-dialyzable material(NDM)of cranberry extract in lowering fasting blood glucose.Methods:Eight-week-old mice were maintained on either a standard chow diet(con-trol group)or a high-fat diet(HFD)for 12 weeks,followed by injections of intraperi-toneal(IP)NDM(50 mg/kg)per mouse,three times a week for the next 6 weeks.Absolute FBG(mg/dl)was measured bi-weekly and percentage changes in FBG(%FBG)between weeks 0 and 12 were calculated.Results:Statistical analysis showed a significant decrease in FBG between weeks 0 and 12 in male and female mice maintained on CHD.However,a non-significant in-crease in FBG values was observed in male and female mice maintained on HFD dur-ing the same period.Following administration of NDM during the following 6 weeks,the results show a variation in significant levels of FBG lowering between lines,male and female mice and under the different diets.Conclusion:The results suggest that the efficacy of NDM treatment in lowering FGB depends on host genetic background(pharmacogenetics),sex of the mouse(phar-macosex),and diet(pharmacodiet).All these results support the need for follow-up research to better understand and implement a personalized medicine approach/uti-lization of NDM for reducing FBG.

Fecal microbiota transplantation for the treatment of irritable bowel syndrome:A systematic review and meta-analysis

BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS,also known as‘gut dysbiosis’.Fecal microbiota transplantation(FMT)has been suggested as a treatment for IBS.AIM To assess the efficacy and safety of FMT for the treatment of IBS.METHODS We searched Cochrane Central,MEDLINE,EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials(RCTs)investigating the effectiveness of FMT compared to placebo(including autologous FMT)in treating IBS.The primary outcome was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms score.Secondary outcomes were changes in quality-of-life scores,non-serious and serious adverse events.Risk ratios(RR)and corresponding 95%CI were calculated for dichotomous outcomes,as were the mean differences(MD)and 95%CI for continuous outcomes.The Cochrane risk of bias tool was used to assess the quality of the trials.GRADE criteria were used to assess the overall quality of the evidence.RESULTS Eight RCTs(484 participants)were included in the review.FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo(RR 1.19,95%CI:0.68-2.10).Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group(RR 1.17,95%CI:0.63-2.15).One serious adverse event occurred in the FMT group and two in the placebo group(RR 0.42,95%CI:0.07-2.60).Endoscopic FMT delivery resulted in a significant improvement in symptoms,while capsules did not.FMT did not improve the quality of life of IBS patients but,instead,appeared to reduce it,albeit non significantly(MD-6.30,95%CI:-13.39-0.79).The overall quality of the evidence was low due to moderate-high inconsistency,the small number of patients in the studies,and imprecision.CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS.Larger trials are needed.

Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases

BACKGROUND Helicobacter pylori(H.pylori)is a significant human pathogen that is responsible for a variety of illnesses,including mucosa-associated lymphoid tissue lymphoma,gastric cancer,peptic ulcers,and gastritis.AIM To investigate the frequency of H.pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H.pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen.METHODS H.pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H.pylori infection.The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction.The patients underwent 14 d of triple-therapy treatment.The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation.RESULTS The intention-to-treat eradication rate was 59.2%(95%CI:48.2%-70.3%).Rates of H.pylori resistance to clarithromycin,amoxicillin,and metronidazole were 52.8%,81.9%,and 100%,respectively.Successful eradication of H.pylori was more significantly associated with vacA s1-positive strains[adjusted odds ratio(aOR)=0.507,95%CI:0.175-0.822].A significant association was found between failed eradication rate and H.pylori strains resistant to clarithromycin(aOR=0.204,95%CI:-0.005 to 0.412)and amoxicillin(aOR=0.223,95%CI:0.026-0.537).CONCLUSION This study’s low H.pylori eradication rate following 14-d triple therapy is concerning and worrying.H.pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin,amoxicillin,and clarithromycin in this research is challenging and of great concern.

Clinical Features and Haematological Indices of Neonatal Septicaemia in Poor Resource Setting

Background: The burden of neonatal septicaemia has remained high worldwide and even more severe in the developing countries like ours. Clinical manifestation is variable and non-specific thereby resulting in delay in diagnosis. Blood culture which is the gold standard for diagnosis of neonatal septicaemia (NNS) has many drawbacks due to long waiting time for culture process, low yield, improper inoculation adding to the problem of late diagnosis. Haematological parameters have been utilized in rapid and early diagnosis of NNS and prompt treatment thus circumventing problems associated with drawbacks in blood culture. Objective: The study was to identify the common clinical features of neonatal septicaemia and haematological indices that were commonly utilized in rapid diagnosis of NNS, and also to determine their sensitivity, specificity, positive predictive and negative predictive value. Materials and Methods: The study was prospective and neonates that had clinical features suggestive of neonatal septicaemia were enrolled consecutively into the study. The patients were appropriately investigated including blood cultures, CSF cultures and urine among others, also blood sample for packed cell volume (PCV), total white cell count (TWBC), absolute neutrophil count (ANC), absolute platelet count (APC). Immature to mature neutrophil ratio (I/MNR), immature to total neutrophil ratio (I/TNR) and micro-ESR (erythrocyte sedimentation rate) was also done and analyzed. Results: The common clinical symptoms were fever 39.5%, poor feeding 33.6%, excessive cry 38.7%, difficulty in breathing 50.0%, yellowish skin 26.9%, while the common physical signs were hyper/hypothermia 41.1%, tachypnoea 41.2%, septic umbilical stump 64.0%, hepatomegally 37.3% and convulsions 42.0%. Blood culture yield was positive in 41.82% and mortality was as high as 28.00%, the incidence of NNS was 5.9/1000 live births. The haematological parameters as marker of NNS PCV, TWBC, ANC, APC, I/MNR, I/TNR and micro-ESR individually were statistically significant (P < 0.05), also their individual sensitivity, specificity, positive and negative predictive values were highly associated with neonatal septicaemia. However, when they were tested in combinations these markers of neonatal septicaemia had low sensitivity, specificity and their predictive values were weak in excluding NNS. Conclusions: The need for early and rapid diagnosis of NNS is pertinent, culturing of the appropriate specimens remains the only way to identify the aetiological organisms, but is associated with delay. Haematological indices are excellent markers of NNS and analysis is rapid and can easily be done in our laboratory settings, and when utilized efficiently, it would circumvent the delay associated with blood culture for long waiting period for the result, thereby reducing morbidity and mortality.

Clinical application of combined detection of SARS-CoV-2-specific antibody and nucleic acid

BACKGROUND The global outbreak of human severe acute respiratory syndrome coronavirus(SARS-CoV)-2 infection represents an urgent need for readily available,accurate and rapid diagnostic tests.Nucleic acid testing of respiratory tract specimens for SARS-CoV-2 is the current gold standard for diagnosis of coronavirus disease 2019(COVID-19).However,the diagnostic accuracy of reverse transcription polymerase chain reaction(RT-PCR)tests for detecting SARS-CoV-2 nucleic acid may be lower than optimal.The detection of SARS-CoV-2-specific antibodies should be used as a serological non-invasive tool for the diagnosis and management of SARS-CoV-2 infection.AIM To investigate the diagnostic value of SARS-CoV-2 IgM/IgG and nucleic acid detection in COVID-19.METHODS We retrospectively analyzed 652 suspected COVID-19 patients,and 206 non-COVID-19 patients in Wuhan Integrated TCM and Western Medicine Hospital.Data on SARS-CoV-2 nucleic acid tests and serum antibody tests were collected to investigate the diagnostic value of nucleic acid RT-PCR test kits and immunoglobulin(Ig)M/IgG antibody test kits.The j2 test was used to compare differences between categorical variables.A 95%confidence interval(CI)was provided by the Wilson score method.All analyses were performed with IBM SPSS Statistics version 22.0(IBM Corp.,Armonk,NY,United States).RESULTS Of the 652 suspected COVID-19 patients,237(36.3%)had positive nucleic acid tests,311(47.7%)were positive for IgM,and 592(90.8%)were positive for IgG.There was a significant difference in the positive detection rate between the IgM and IgG test groups(P<0.001).Using the RT-PCR results as a reference,the specificity,sensitivity,and accuracy of IgM/IgG combined tests for SARS-CoV-2 infection were 98.5%,95.8%,and 97.1%,respectively.Of the 415 suspected COVID-19 patients with negative nucleic acid test results,366 had positive IgM/IgG tests with a positive detection rate of 88.2%.CONCLUSION Our data indicate that serological IgM/IgG antibody combined test had high sensitivity and specificity for the diagnosis of SARS-CoV-2 infection,and can be used in combination with RT-PCR for the diagnosis of SARS-CoV-2 infection.

A study of the influence of genetic variance and sex on the density and thickness of the calvarial bone in collaborative cross mice

Background:Bone microarchitecture is affected by multiple genes,each having a small effect on the external appearance.It is thus challenging to characterize the genes and their specific effect on bone thickness and porosity.The purpose of this study was to assess the heritability and the genetic variation effect,as well as the sex effect on the calvarial bone thickness(Ca.Th)and calvarial porosity(%PoV)using the Collaborative Cross(CC)mouse population.Methods:In the study we examined the parietal bones of 56 mice from 9 lines of CC mice.Morphometric parameters were evaluated using microcomputed tomography(μCT)and included Ca.Th and%PoV.We then evaluated heritability,genetic versus environmental variance and the sex effect for these parameters.Results:Our morphometric analysis showed that Ca.Th and%PoV are both significantly different among the CC lines with a broad sense heritability of 0.78 and 0.90,respectively.The sex effect within the lines was significant in line IL111 and showed higher values of Ca.Th and%PoV in females compared to males.In line IL19 there was a borderline sex effect in Ca.Th in which males showed higher values than females.Conclusions:These results stress the complexity of sex and genotype interactions controlling Ca.Th and%PoV,as the skeletal sexual dimorphism was dependent on the genetic background.This study also shows that the CC population is a powerful tool for establishing the genetic effect on these traits.

Prevalence of Antimicrobial Resistance of ESKAPE Pathogens before and during Pandemic COVID-19 Pandemic in a University Affiliated Hospital in Tangerang, Indonesia

Introduction: Antimicrobial resistance is the most important health problems currently. Antibiotic prophylaxis to prevent bacterial co-infections in hospitalized COVID-19 patients, and lack of surveillance were associated with antimicrobial resistance. ESKAPE pathogens consisting of E. faecium, S. aureus, K. pneumoniae, A. baumanii, P. aeruginosa and Enterobacter spp. are associated with healthcare-associated infections. Patients and Methods: This descriptive, retrospective, longitudinal study aims to describe the resistance rates of bloodstream infection due to ESKAPE pathogens from patients admitted in Siloam Hospital Karawaci, before and during COVID-19 pandemic (January 1st, 2019 until December 31st, 2022). Out of 296 ESKAPE pathogens collected from blood samples, S. aureus was the most frequent species, followed by K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp., and E. faecium. Results: Resistance rates of E. faecium were alarmingly high from 2019 until 2021, but in 2022 no sample was found. Resistance rates of S. aureus and MRSA decreased from 2019 until 2021 and then increased again in 2022 while for K. pneumoniae it peaked in 2020 and reached the lowest in 2022. Resistance pattern of A. baumanii was not favorable from 2019 until 2021, but decreased dramatically in 2022. Resistance pattern of P. aeruginosa was quite variable in 2021 and 2022 while for Enterobacter spp. it was variable in 2020 to 2022. Conclusion: The COVID-19 pandemic affected the antimicrobial resistance pattern of ESKAPE pathogens in Banten province, Indonesia. Resistance rates increased as the pandemic peaked in 2020 to 2021, and decreased as the pandemic resolves in 2022.

Identifying genetic susceptibility to Aspergillus fumigatus infection using collaborative cross mice and RNA-Seq approach

Background:Aspergillus fumigatus(Af)is one of the most ubiquitous fungi and its infection potency is suggested to be strongly controlled by the host genetic back-ground.The aim of this study was to search for candidate genes associated with host susceptibility to Aspergillus fumigatus(Af)using an RNAseq approach in CC lines and hepatic gene expression.Methods:We studied 31 male mice from 25 CC lines at 8 weeks old;the mice were infected with Af.Liver tissues were extracted from these mice 5 days post-infection,and next-generation RNA-sequencing(RNAseq)was performed.The GENE-E analysis platform was used to generate a clustered heat map matrix.Results:Significant variation in body weight changes between CC lines was ob-served.Hepatic gene expression revealed 12 top prioritized candidate genes differ-entially expressed in resistant versus susceptible mice based on body weight changes.Interestingly,three candidate genes are located within genomic intervals of the previ-ously mapped quantitative trait loci(QTL),including Gm16270 and Stox1 on chromo-some 10 and Gm11033 on chromosome 8.Conclusions:Our findings emphasize the CC mouse model's power in fine mapping the genetic components underlying susceptibility towards Af.As a next step,eQTL analysis will be performed for our RNA-Seq data.Suggested candidate genes from our study will be further assessed with a human cohort with aspergillosis.

Individualized anti-thrombotic therapy for acute myocardial infarction complicated with left ventricular thrombus: A case report

BACKGROUND Presently,there is no established standard anti-blood clot therapy for patients facing acute myocardial infarction(AMI)complicated by left ventricular thrombus(LVT).While vitamin K antagonists are the preferred choice for oral blood thinning,determining the best course of blood-thinning medication remains challenging.It is unclear if non-vitamin K antagonist oral blood thinners have different effectiveness in treating LVT.This study significantly contributes to the medical community.CASE SUMMARY The blood-thinning treatment of a patient with AMI and LVT was analyzed.Triple blood-thinning therapy included daily enteric-coated aspirin tablets at 0.1 g,daily clopidogrel hydrogen sulfate at 75 mg,and dabigatran etexilate at 110 mg twice daily.After 15 d,the patient’s LVT did not decrease but instead increased.Clinical pharmacists comprehensively analyzed the cases from the perspective of the patient’s disease status and drug interaction.The drug regimen was reformulated for the patient,replacing dabigatran etexilate with warfarin,and was administered for six months.The clinical pharmacist provided the patient with professional and standardized pharmaceutical services.The patient’s condition was discharged after meeting the international normalized ratio value(2-3)criteria.The patient fully complied with the follow-up,and the time in the therapeutic range was 78.57%,with no serious adverse effects during pharmaceutical monitoring.CONCLUSION Warfarin proves to be an effective drug for patients with AMI complicated by LVT,and its blood-thinning course lasts for six months.

Strategies for combating bacterial biofilm infections

Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.

Microbial profile and antibiotic sensitivity pattern in bile cultures from endoscopic retrograde cholangiography patients

AIM:To identify the frequency of bacterial growth,the most commonly grown bacteria and their antibiotic susceptibility,and risk factors for bacterial colonization in bile collected from patients with different biliary diseases.METHODS:This prospective study was conducted between April 2010 and August 2011.Patients with various biliary disorders were included.Bile was aspirated by placing a single-use,5F,standard sphincterotome catheter into the bile duct before the injection of contrast agent during endoscopic retrograde cholangiopancreaticography (ERCP).Bile specimens were transported to the microbiology laboratory in blood culture bottles within an anaerobic transport system.Bacteria were cultured and identified according to the standard protocol used in our clinical microbiology laboratory.The susceptibilities of the organisms recovered were identified using antimicrobial disks,chosen according to the initial gram stain of the positive cultures.RESULTS:Ninety-one patients (27% male,mean age 53.7 ± 17.5 years,range:17-86 years) were included in the study.The main indication for ERCP was benign biliary disease in 79 patients and malignant disease in 12 patients.The bile culture was positive for bacterial growth in 46 out of 91 (50.5%) patients.The most frequently encountered organisms were Gram-negative bacteria including Escherichia coli (28.2%),Pseudomonas (17.3%) and Stenotrophomonas maltophilia (15.2%).There were no significant differences between patients with malignant and benign disease (58% vs 49%,P = 0.474),patients with acute cholangitis and without acute cholangitis (52.9% vs 50%,P = 0.827),patients who were empirically administered antibiotics before intervention and not administered (51.4% vs 60.7%,P = 0.384),with regard to the bacteriobilia.We observed a large covering spectrum or low resistance to meropenem,amikacin and imipenem.CONCLUSION:We did not find a significant risk factor for bacteriobilia in patients with biliary obstruction.A bile sample for microbiological analysis may become a valuable diagnostic tool as it leads to more accurate selection of antibiotics for the treatment of cholangitis.

High prevalence of viable Mycobacterium avium subspecies paratuberculosis in Crohn's disease

AIM:To examine the detection rate of viable Mycobacterium avium subspecies paratuberculosis(MAP) in patients with inflammatory bowel disease [Crohn's disease(CD) and ulcerative colitis(UC)].METHODS:Thirty patients with CD(15 with at least one NOD2/CARD15 mutation),29 with UC,and 10 with no inflammatory bowel disease(IBD).were tested for MAP by polymerase chain reaction(specific IS900 fragment) and blood culture.RESULTS:MAP DNA was detected in all original blood samples and 8-wk blood cultures(CD,UC and non-IBD).Positive MAP DNA status was confirmed by dot blot assays.All 69 cultures were negative by acid-fast Ziehl-Neelsen staining.Viable MAP,in spheroplast form,was isolated from the 18-mo blood cultures of all 30 CD patients,one UC patient,and none of the non-IBD controls.No association was found between positive MAP cultures and use of immunosuppressive drugs or CDassociated single nucleotide polymorphisms.CONCLUSION:MAP is widely present in our area and MAP DNA can be recovered from the blood of CD,UC and non-IBD patients.However,MAP spheroplasts were only found in CD patients.

Current understanding of multi-species biofilms

Direct observation of a wide range of natural microorganisms has revealed the fact that the majority of microbes persist as surface-attached communities surrounded by matrix materials, called biofilms. Biofilms can be formed by a single bacterial strain. However, most natural biofilms are actually formed by multiple bacterial species. Conventional methods for bacterial cleaning, such as applications of antibiotics and/or disinfectants are often ineffective for biofilm populations due to their special physiology and physical matrix barrier. It has been estimated that billions of dollars are spent every year worldwide to deal with damage to equipment, contamina- tions of products, energy losses, and infections in human beings resulted from microbial biofilms. Microorganisms compete, cooperate, and communicate with each other in multi-species biofilms. Understanding the mechanisms of multi-species hiofilm formation will facilitate the development of methods for combating bacterial hiofilms in clinical, environmental, industrial, and agricultural areas. The most recent advances in the understanding of multi-species biofilms are summarized and discussed in the review.

Efficacy and safety of pegylated-interferon α-2a in hemodialysis patients with chronic hepatitis C

AIM: To evaluate the efficacy and safety of pegylated-interferon alpha-2a in hemodialysis patients with chronichepatitis C.METHODS: Thirty-six hemodialysis patients with chronichepatitis C were enrolled in a controlled and prospectivestudy. All patients were treatment naive, positivetested for anti-HCV antibodies, and positive tested forserum HCV-RNA. Twenty-two patients received 135 μgpeglyated-interferon a-2a weekly for 48 wk (group A).The remaining patients were left untreated, elevenrefused therapy, and three were not candidates forkidney transplantation and were allocated to the controlgroup (group B). At the end of the treatment biochemicaland virological response was evaluated, and 24 wk aftercompletetion of therapy sustained virological response(SVR) was assessed. Side effects were monitored.RESULTS: Of 22 hemodialysis patients, 12 were maleand 10 female, with a mean age of 35.2 ± 12.1 years.Virological end-of-treatment response was observed in14 patients (82.4%) in group A and in one patient (7.1%)in group B (P = 0.001). Sustained virological responsewas observed in 11 patients (64.7%) in group A and inone patient in group B (7.1%). Biochemical responseparameters normalized in 10/14 patients (71.4%) at theend of the treatment. ALT levels in group B were initiallyhigh in six patients and normalized in one of them (25%)at the end of the 48 wk. In five patients (22.7%) therapyhad to be stopped at mo 4 due to complications ofweakness, anemia, and bleeding.CONCLUSION: SVR could be achieved in 64.7% ofpatients on hemodialysis with chronic hepatitis C by atreatment with peglyated-interferon a-2a. Group A hada significantly better efficacy compared to the controlgroup B, but the side effects need to be concerned.

Effectiveness of Saccharomyces boulardii in a rat model of colitis

AIM:To investigate the effects of Saccharomyces boulardii(S.boulardii) in an experimental rat model of trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:Thirty-two Wistar albino female rats were categorized into five groups.On the first day of the study,50 mg TNBS was administered via a rectal catheter in order to induce colitis in all rats,except those in the control group.For 14 d,the rats were fed a standard diet,without the administration of any additional supplements to either the control or TNBS groups,in addition to 1 mg/kg per day S.boulardii to the S.boulardii group,1 mg/kg per day methyl prednisolone(MP) to the MP group.The animals in the S.boulardii + MP group were coadministered these doses of S.boulardii and MP.During the study,weight loss,stool consistency,and the presence of obvious blood in the stool were evaluated,and the disease activity index(DAI) for colitis was recorded.The intestines were examined and colitis was macro-and microscopically scored.The serum and tissue levels of tumor necrosis factor-α(TNF-α) and nitric oxide(NO) were determined,and fungemia was evaluated in the blood samples.RESULTS:The mean DAI scores for the MP and S.boulardii + MP groups was significantly lower than the TNBS group(3.69 ± 0.61 vs 4.46 ± 0.34,P = 0.018 and 3.77 ± 0.73 vs 4.46 ± 0.34,P = 0.025,respectively).While no significant differences between the TNBS and the S.boulardii or MP groups could be determined in terms of serum NO levels,the level of serum NO in the S.boulardii + MP group was significantly higher than in the TNBS and S.boulardii groups(8.12 ± 4.25 μmol/L vs 3.18 ± 1.19 μmol/L,P = 0.013;8.12 ± 4.25 μmol/L vs 3.47 ± 1.66 μmol/L,P = 0.012,respectively).The tissue NO levels in the S.boulardii,MP and S.boulardii + MP groups were significantly lower than the TNBS group(16.62 ± 2.27 μmol/L vs 29.72 ± 6.10 μmol/L,P = 0.002;14.66 ± 5.18 μmol/Lvs 29.72 ± 6.10 μmol/L,P = 0.003;11.95 ± 2.34 μmol/Lvs 29.72 ± 6.10 μmol/L,P = 0.002,respectively).The tissue NO levels in the S.boulardii,MP and S.boulardii + MP groups were similar.The mean serum and tissue TNF-α levels were determined to be 12.97 ± 18.90 pg/mL and 21.75 ± 15.04 pg/mL in the control group,18.25 ± 15.44 pg/mL and 25.27 ± 11.95 pg/mL in the TNBS group,20.59 ± 16.15 pg/mL and 24.39 ± 13.06 pg/mL in the S.boulardii group,9.05 ± 5.13 pg/mL and 24.46 ± 10.85 pg/mL in the MP group,and 13.95 ± 10.17 pg/mL and 24.26 ± 10.37 pg/mL in the S.boulardii + MP group.Significant differences in terms of the levels of serum and tissue TNF-α and the macroscopic and microscopic scores were not found between the groups.S.boulardii fungemia was not observed in any of the rats.However,Candida fungemia was detected in one rat(14%) in the TNBS group,two rats(28%) in the S.boulardii group,three rats(50%) in the MP group,and three rats(42%) in S.boulardii + MP group.CONCLUSION:S.boulardii does not demonstrate considerable effects on the DAI,pathological scores,or cytokine levels but does decrease the tissue NO levels.

Seroprevalence and genotyping of hepatitis B,hepatitis C and HIV among healthy population and Turkish soldiers in Northern Cyprus

AIM: To compare the prevalence of hepatitis viral markers among soldiers from Turkey, blood donors from Northern Cyprus, and soldiers from Northern Cyprus. METHODS: Hepatitis B surface antigen (HBsAg), anti- HCV and anti-human immunodeficiency virus (HIV) seroprevalence, HBV DNA, HCV RNA and HCV genotyping among soldiers from Turkey (groupⅠ), civil blood donors from Northern Cyprus (group Ⅱ), and soldier candidates from Northern Cyprus (group Ⅲ) were studied and compared to one another. In total, 17 545 cases (13 546 males and 3999 females with a mean age of 34.5 ± 10.3 year, groupⅠ= 11 234, group Ⅱ = 5057, and group Ⅲ = 1254) were included into the study. RESULTS: Among all cases, HBsAg positivity rates were 2.46%, anti-HCV was 0.46% and anti-HIV was 0.00%. HBV DNA was 2.25%, HCV RNA was 0.33% in all groups. HBsAg positivity rates were 2.16% in groupⅠ, 3.00% in group Ⅱ and 2.71% in group Ⅲ. There was a significant difference between groupⅠand group Ⅱ (χ2 = 6.11, P = 0.047 < 0.05). Anti-HCV positivity rates were 0.45% in groupⅠ, 0.45% in group Ⅱ, and 0.56% in group Ⅲ. Genotypes of HCV were 1b and 1a in groupⅠ, 1b, 1a and 2 in group Ⅱ, and 1b, 1a in group Ⅲ. HBsAg carrier rates were 2.20% in females and 2.53% in males. Anti- HCV prevalence was 0.38% in females and 0.48% in males. HBsAg positivity rates were 2.53% in individuals younger than 50, and 1.47% in older than 50. There was a significant difference between the two groups (χ2 =23.48, P = 0.001). CONCLUSION: Prevalences of HBsAg, HCV and HIV infections in Northern Cyprus population are similar to those of Turkey.

Randomised controlled trial of triclosan coated vs uncoated sutures in primary hip and knee arthroplasty

BACKGROUND Triclosan-coated vicryl plus suture(Ethicon, Inc.) was developed to reduce microbial colonisation during surgical procedures. However, its effect on wound healing and surgical site infections remain unclear after hip and knee arthroplasty surgery.AIM To determine the effect of triclosan-coated sutures(TCS) vs non-coated sutures on wound healing, following primary hip and knee arthroplasties.METHODS A single-centred, double-blind randomised controlled trial(RCT) was undertaken. We randomly allocated patients to receive either the triclosan-coated sutures(TCS vicryl plus) or non-coated sutures(NCS vicryl) during the closure of unilateral primary hip and knee arthroplasties. We utilised the ASEPSIS wound scoring system to evaluate wound healing for the first 6 weeks post-operatively.RESULTS One hundred and fifty patients undergoing primary total hip or knee arthroplasty over a one-year period were included. Eighty-one were randomised to the TCS group and 69 to the NCS group. Despite no statistically significant difference in the ASEPSIS scores among the study groups(P = 0.75), sensitivity analysis using the Mann Whitney test(P = 0.036) as well as assessment of the wound complications at 6 weeks follow up, demonstrated significantly higher wound complication rates in the TCS group(8 vs 1, P = 0.03).CONCLUSION No clear advantage was demonstrated for using the TCS. However, larger multicentred RCTs are required to validate their use in hip and knee arthroplasty surgery.