Treadmill training in Parkinson's disease:possible role of prefrontal modifications in the improved cortical-subcortical network function

Parkinson’s disease(PD)is a complex neurodegenerative disorder characterized by a range of motor symptoms such as bradykinesia,resting tremor,rigidity,and postural instability,as well as non-motor symptoms,such as depression,anxiety,sleep disturbances,and fatigue(Bloem et al.,2021).

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.

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.

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.

Effect of patient COVID-19 vaccine hesitancy on hospital care team perceptions

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic posed new challenges in patient care worldwide.Vaccinations,which have proven efficacious in lowering the COVID-19 hospital burden,are still avoided by large populations.We,therefore,hypothesized that hospital care teams would have worse perceptions regarding the characteristics and care of patients with vaccine hesitancy.AIM To evaluate whether patient vaccine hesitancy affected the hospital care team(HCT)perceptions.METHODS We performed a prospective clinical study using structured questionnaires.We approached physicians and nurses with previous experience caring for COVID-19patients from 11 medical centers across Israel during the fourth COVID-19 surge(September and October 2021).The participants completed a questionnaire with the following parts:(1)Sociodemographic characteristics;(2)Assessment of anger(STAXI instrument)and chronic workplace stress(Shirom-Melamed burnout measure);and(3)Three tools to assess the effect of patient vaccine hesitancy on the HCT perceptions(the difficult doctor-patient relation questionnaire,the medical staff perception of patient’s responsibility questionnaire and the characterological derogation questionnaire).Results were evaluated according to each part of the questionnaire and the questionnaire as a whole.Associations between HCT perceptions and their baseline characteristics,anger or chronic workplace stress were assessed.RESULTS The HCT experienced their relationship with unvaccinated patients as more difficult(P<0.001,Cohen’s d=0.85),perceived unvaccinated patients as responsible for their medical condition(P<0.001,d=1.39)and perceived vaccinated patients as having a higher character value(P<0.001,d=1.03).Unvaccinated patients were considered selfish(P<0.001),less mature(P<0.001)and less satisfying to care for(P<0.001).The relationship with unvaccinated patients was more difficult among HCT with higher burnout(r=0.37,n=66,P=0.002).No correlations with baseline characteristics were found.All three study tools showed high internal consistency(αbetween 0.72 and 0.845).CONCLUSION Our results should raise awareness of the possible effects of vaccine hesitancy on HCT perceptions regarding unvaccinated patients.In order to minimize the potential negative impact on patient care,designated departments should promote specific patient-centered preparations.Further investigations should assess whether vaccine hesitancy directly affects patient quality of care.

Transdiagnostic considerations of mental health for the post-COVID era:Lessons from the first surge of the pandemic

BACKGROUND The Coronavirus disease 19(COVID-19)-related psychiatric burden partly results from prolonged social stress world-wide.Studies have examined the psychiatric impact of COVID-19 on Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM 5)and International Classification of Diseases 11th Revision(ICD-11)categories,implicating multiple diagnoses,complicating clinical management.AIM To verify whether COVID-19-related psychopathology spans multiple DSM-5 and ICD-11 diagnoses,but not in a random pattern.Consequently,empirical analysis of the multiple associated symptoms will better describe COVID-19-related psychopathology.METHODS We conducted a bi-national study during the first surge of the pandemic:an Italian sample(n=21217,studied March-April 2020);and three representative longitudinal samples from Israel(n=1276,1189,and 1432 respectively,studied May-July 2020).Data in Italy were collected by a national internet-based survey with an initially approached sample of about one million persons and in Israel by the Israeli Central Bureau of Statistics using probability-based national representative sampling.Data analysis focused on the frequency and patterns of reported multiple mental health symptoms.RESULTS Combinations with all symptoms were more prevalent than combinations with fewer symptoms,with no majorities-minorities differences in both countries,demonstrating the generalizability of the transdiagnostic pattern of mental health issues in both nations.A history of previous mental disorder(Italian study)and an increase in symptom prevalence over time(Israel study)were associated with an increased number of symptoms.Conclusions:Based on finding correlated symptom diversity spanning conventional diagnostic categories,we suggest that the pattern of mental health issues associated with the COVID-19 pandemic is transdiagnostic.CONCLUSION The findings have implications for improving prevention and treatment of COVID-19 related psychopathology and for post-pandemic times in conditions resulting from multiplicity of stressors with mixed symptomatology in the clinical picture.

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.

Ophthalmic exam and ophthalmology residents’ subspecialty preference

AIM:To evaluate residents’perceptions and attitudes toward the various aspects of a comprehensive ophthalmic examination,and to determine if these factors correlate with their choices for fellowship and future career plans.METHODS:This is a cross-sectional study.A questionnaire on the perception of the ophthalmic exam was sent via SurveyMonkey to ophthalmology residents throughout Israel.Eighty of them(one-half of all ophthalmology residents in 2019)completed it.The first part related to how they perceived each component of the ophthalmic evaluation.The second part related to their future fellowship plans.The Chi-squared test was used to compare categorical variables and Student’s t-test and One-way ANOVA were used to compare continuous variables.Multivariate logistic regression analysis was applied as needed to detect interactions between variables and to exclude confounder effects.RESULTS:Slit-lamp examination of the anterior and posterior segments ranked as the most likeable aspects,whereas gonioscopy,ocular motility examination and visual acuity assessment were least likeable.Anterior segment and retina subspecialties were the ones most sought after.Forty-nine respondents(61.3%)noted a direct correlation between their preferred parts of comprehensive ophthalmic evaluations and their choice of subspecialty.Perceptions of selected components of those evaluations were significantly associated with responders’intentions to pursue anterior segment,retina,or oculoplastic fellowships(P<0.05).CONCLUSION:Perspectives of residents toward the ophthalmic examination,and most specifically its individual components,play an important role in their choice of subspecialty training.

Nutrition and physical activity in NAFLD:An overview of the epidemiological evidence

Nonalcoholic fatty liver disease(NAFLD)has been recognized as a major health burden.The high prevalence of NAFLD is probably due to the contemporary epidemics of obesity,unhealthy dietary pattern,and sedentary lifestyle.The efficacy and safety profile of pharmacotherapy in the treatment of NAFLD remains uncertain and obesity is strongly associated with hepatic steatosis;therefore,the first line of treatment is lifestyle modification.The usual management of NAFLD includes gradual weight reduction and increased physical activity(PA)leading to an improvement in serum liver enzymes,reduced hepatic fatty infiltration,and,in some cases,a reduced degree of hepatic inflammation and fibrosis.Nutrition has been demonstrated to be associated with NAFLD and Non-alcoholic steatohepatitis(NASH)in both animals and humans,and thus serves as a major route of prevention and treatment.However,most human studies are observational and retrospective,allowing limited inference about causal associations.Large prospective studies and clinical trials are now needed to establish a causal relationship.Based on available data,patients should optimally achieve a 5%-10%weight reduction.Setting realistic goals is essential for long-term successful lifestyle modification and more effort must be devoted to informing NAFLD patients of the health benefits of even a modest weight reduction.Furthermore,all NAFLD patients,whether obese or of normal weight,should be informed that a healthy diet has benefits beyond weight reduction.They should be advised to reduce saturated/trans fat and increase polyunsaturated fat,with special emphasize on omega-3 fatty acids.They should reduce added sugar to its minimum,try to avoid soft drinks containing sugar,including fruit juices that contain a lot of fructose,and increase their fiber intake.For the heavy meat eaters,especially those of red and processed meats,less meat and increased fish intake should be recommended.Minimizing fast food intake will also help maintain a healthy diet.PA should be integrated into behavioral therapy in NAFLD,as even small gains in PA and fitness may have significant health benefits.Potentially therapeutic dietary supplements are vitamin E and vitamin D,but both warrant further research.Unbalanced nutrition is not only strongly associated with NAFLD,but is also a risk factor that a large portion of the population is exposed to.Therefore,it is important to identify dietary patterns that will serve as modifiable risk factors for the prevention of NAFLD and its complications.

Treatment of hepatocellular carcinoma: Steps forward but still a long way to go

Hepatocellular carcinoma(HCC) is the fifth most common malignancy and the third cause of tumor associated deaths worldwide. HCC incidence rates are increasing in many parts of the world including developing and developed countries. Potentially curative treatments for HCC are resection and liver transplantation, but these are only suitable for patients with small tumors, meeting strict pre-defined criteria, or well-compensated liver disease. Early diagnosis of HCCcan be achieved by surveillance of at-risk populations. For patients with non-resectable disease treatments modalities include loco-ablative and systemic therapies. In this review we focus on treatment options in HCC and their allocation. Although significant research is in progress, to this date, the results are unsatisfactory with limited long-term survival. In the fight against this deadly disease, there is still a long way to go.

Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial

AIM: To evaluate the effect of resistance training (RT) on non alcoholic liver disease (NAFLD) patients.

Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification

AIM:To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease(NAFLD).METHODS:Cross-sectional study of subjects from the general population,a subgroup from the First Israeli National Health Survey,without excessive alcohol consumption or viral hepatitis.All subjects underwent anthropometric measurements and fasting blood tests.Evaluation of liver fat was performed using four noninvasive methods:the SteatoTest;the fatty liver index(FLI);regular abdominal ultrasound(AUS);and the hepatorenal ultrasound index(HRI).Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods:the HRI,the ratio between the median brightness level of the liver and right kidney cortex;and the SteatoTest,a biochemical surrogate marker of liver steatosis.The FLI is calculated by an algorithm based on triglycerides,body mass index,γ-glutamyl-transpeptidase and waist circumference,that has been validated only vs AUS.FLI < 30 rules out and FLI ≥ 60 rules in fatty liver.RESULTS:Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests.The prevalence rate of NAFLD was 31.1% according to AUS.The FLI was very strongly correlated with SteatoTest(r = 0.91,P < 0.001) and to a lesser but significant degree with HRI(r = 0.55,P < 0.001).HRI and SteatoTest were significantly correlated(r = 0.52,P < 0.001).The κ between diagnosis of fatty liver by SteatoTest(≥ S2) and by FLI(≥ 60) was 0.74,which represented good agreement.The sensitivity of FLI vs SteatoTest was 85.5%,specificity 92.6%,positive predictive value(PPV) 74.7%,and negative predictive value(NPV) 96.1%.Most subjects(84.2%) with FLI < 60 had S0 and none had S3-S4.The κ between diagnosis of fatty liver by HRI(≥ 1.5) and by FLI(≥ 60) was 0.43,which represented only moderate agreement.The sensitivity of FLI vs HRI was 56.3%,specificity 86.5%,PPV 57.0%,and NPV 86.1%.The diagnostic accuracy of FLI for steatosis > 5%,as predicted by SteatoTest,yielded an area under the receiver operating characteristic curve(AUROC) of 0.97(95% CI:0.95-0.98).The diagnostic accuracy of FLI for steatosis> 5%,as predicted by HRI,yielded an AUROC of 0.82(95% CI:0.77-0.87).The κ between diagnosis of fatty liver by AUS and by FLI(≥ 60) was 0.48 for the entire sample.However,after exclusion of all subjects with an intermediate FLI score of 30-60,the κ between diagnosis of fatty liver by AUS and by FLI either ≥ 60 or < 30 was 0.65,representing good agreement.Excluding all the subjects with an intermediate FLI score,the sensitivity of FLI was 80.3% and the specificity 87.3%.Only 8.5% of those with FLI < 30 had fatty liver on AUS,but 27.8% of those with FLI ≥ 60 had normal liver on AUS.CONCLUSION:FLI has striking agreement with SteatoTest and moderate agreements with AUS or HRI.However,if intermediate values are excluded FLI has high diagnostic value vs AUS.

Incidence and management of colonoscopic perforations: 8 years' experience

AIM： To review the experience of a major medical teaching center with diagnostic and therapeutic colonoscopies and to assess the incidence and management of related colonic perforations. METHODS： All colonoscopies performed between January 1994 and December 2001 were studied. Data on patients, colonoscopic reports and procedure-related complications were collected from the departmental computerized database. The medical records of the patients with post procedural colonic perforation were reviewed. RESULTS： A total of 12 067 colonoscopies were performed during the 8 years of the study. Seven colonoscopic perforations （4 females, 3 males） were diagnosed （0.058%）. Five occurred during diagnostic and two during therapeutic colonoscopy. Six were suspected during or immediately after colonoscopy. All except one had signs of diffuse tenderness and underwent immediate operation with primary repair done in 4 patients. No deaths were reported. CONCLUSION： Perforation rate during colonoscopy is low. Nevertheless, it is a serious complication and its early recognition and treatment are essential to optimize outcome. In patients with diffuse peritonitis early operative intervention makes primary repair a safe option.

Cardiovascular disease risk factor profiles in children with celiac disease on gluten-free diets

AIM:To describe the cardiovascular disease(CVD)risk factors in a population of children with celiac disease(CD)on a gluten-free diet(GFD).METHODS:This cross-sectional multicenter study was performed at Schneider Children’s Medical Center of Israel(Petach Tiqva,Israel),and San Paolo Hospital(Milan,Italy).We enrolled 114 CD children in serologic remission,who were on a GFD for at least one year.At enrollment,anthropometric measurements,blood lipids and glucose were assessed,and compared to values at diagnosis.The homeostasis model assessment-estimated insulin resistance was calculated as a measure of insulin resistance.RESULTS:Three or more concomitant CVD risk factors[body mass index,waist circumference,low density lipoprotein(LDL)cholesterol,triglycerides,blood pressure and insulin resistance]were identified in 14%of CD subjects on a GFD.The most common CVD risk factors were high fasting triglycerides(34.8%),elevated blood pressure(29.4%),and high concentrations of calculated LDL cholesterol(24.1%).On a GFD,four children(3.5%)had insulin resistance.Fasting insulin and HOMA-IR were significantly higher in the Italian cohort compared to the Israeli cohort(P<0.001).Children on a GFD had an increased prevalence of borderline LDL cholesterol(24%)when compared to values(10%)at diagnosis(P=0.090).Trends towards increases in overweight(from 8.8%to 11.5%)and obesity(from 5.3%to 8.8%)were seen on a GFD.CONCLUSION:This report of insulin resistance and CVD risk factors in celiac children highlights the importance of CVD screening,and the need for dietary counseling targeting CVD prevention.

Role of IL-10 in the progression of kidney disease

Interleukin-10(IL-10), a cytokine with anti-inflammatory and immunomodulatory functions, regulates the biology of B and T cells. The present review describes the role of IL-10 in normal renal physiology, during acute kidney injury and in the development of chronic renal failure. We further discuss IL-10-induced cellular and molecular pathways and their link to the progression of kidney injury.

Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients

To describe the relationships between non-alcoholic fatty-liver disease (NAFLD) patient’s disease consequences and treatment perceptions, self-efficacy, and healthy lifestyle maintenance.METHODSA cross-sectional study among 146 ultrasound diagnosed NAFLD patients who visited the fatty liver clinic at the Tel-Aviv Medical Center. Eighty-seven of these individuals, participated in a clinical trial of physical activity and underwent fasting blood tests, analyzed at the same lab. Exclusion criteria included positivity for serum HBsAg or anti-HCV antibodies; fatty liver suspected to be secondary to hepatotoxic drugs; excessive alcohol consumption (≥ 30 g/d in men or ≥ 20 g/d in women) and positive markers of genetic or immune-mediated liver diseases. Patients were asked to complete a self-report structured questionnaire, assembled by the Israeli Center for Disease Control. Nutrition habits were measured using six yes/no questions (0 = no, 1 = yes) adopted from the national survey questionnaire. Participants in the clinical trial completed a detailed semi-quantitative food frequency questionnaire (FFQ) reporting their habitual nutritional intake during the past year. Self-efficacy was assessed by the Self-Efficacy Scale questionnaire, emotional representation, degree of illness understanding, timeline perception, treatment perception and symptoms were measured by the Brief Illness Perception questionnaire. Illness consequences were measured by the Personal Models of Diabetes Interview questionnaire. A path analysis was performed to describe the interrelationships between the patients’ illness perceptions, and assess the extent to which the data fit a prediction of nutritional habits.RESULTSThe study sample included 54.1% men, with a mean age of 47.76 ± 11.68 years (range: 20-60) and mean body mass index of 31.56 ± 4.6. The average perceived nutrition habits score was 4.73 ± 1.45 on a scale between 0-6, where 6 represents the healthiest eating habits. Most of the study participants (57.2%) did not feel they fully understood what NAFLD is. Better nutritional habits were positively predicted by the degree of illness understanding (β = 0.26; P = 0.002) and self-efficacy (β = 0.25; P = 0.003). Perceptions of more severe illness consequences were related with higher emotional representation (β = 0.55; P < 0.001), which was related with lower self-efficacy (β = -0.17; P = 0.034). The perception of treatment effectiveness was positively related with self-efficacy (β = 0.32; P < 0.001). In accordance with the correlation between self-efficacy and the perceived nutrition habits score, self-efficacy was also correlated with nutrient intake evaluated by the FFQ; negatively with saturated fat (percent of saturated fat calories from total calories) (r = -0.28, P = 0.010) and positively with fiber (r = 0.22, P = 0.047) and vitamin C intake (r = 0.34, P = 0.002). In a sub analysis of the clinical trial participants, objectively measured compliance to physical activity regimen was positively correlated with the self-efficacy level (r = 0.34, P = 0.046).CONCLUSIONSelf-efficacy and illness understanding are major determinants of lifestyle-modification among NAFLD patients. This information can assist clinicians in improving compliance with lifestyle changes among these patients.

Longitudinal decrease in platelet counts as a surrogate marker of liver fibrosis

BACKGROUND Liver cirrhosis is a significant source of morbidity and mortality worldwide.The disease is usually indolent and asymptomatic early in its course while many cirrhotic patients are diagnosed late when severe complications occur.A major challenge is to diagnose advanced fibrosis as early as possible,using simple and non-invasive diagnostics tools.Thrombocytopenia represents advanced fibrosis and portal hypertension(HTN)and most non-invasive scores that predict liver fibrosis incorporate platelets as a strong risk factor.However,little is known about the association between longitudinal changes in platelet counts(PTC),when still within the normal range,and the risk of cirrhosis.AIM To explore whether platelet counts trajectories over time,can predict advanced liver fibrosis across the different etiologies of liver diseases.METHODS A nested case-control study utilizing a large computerized database.Cirrhosis cases(n=5258)were compared to controls(n=15744)matched for age and sex at a ratio of 1:3.All participants had multiple laboratory measurements prior to enrollment.We calculated the trends of PTC,liver enzymes,bilirubin,international normalized ratio,albumin and fibrosis scores(fibrosis-4 and aspartate transaminase-to-platelet ratio index)throughout the preceding 20 years prior to cirrhosis diagnosis compared to healthy controls.The association between PTC,cirrhosis complications and fibrosis scores prior to cirrhosis diagnosis was investigated.RESULTS The mean age in both groups was 56(SD 15.8).Cirrhotic patients were more likely to be smokers,diabetic with chronic kidney disease and had a higher prevalence of HTN.The leading cirrhosis etiologies were viral,alcoholic and fatty liver disease.The mean PTC decreased from 240000/μL to 190000/μL up to 15 years prior to cirrhosis diagnosis compared to controls who’s PTC remained stable around the values of 240000/μL.This trend was consistent regardless of sex,cirrhosis etiology and was more pronounced in patients who developed varices and ascites.Compared to controls whose values remained in the normal range,in the cirrhosis group aspartate aminotransferase and alanine aminotransferase,increased from 40 U/L to 75 U/L and FIB-4 increased gradually from 1.3 to 3 prior to cirrhosis diagnosis.In multivariable regression analysis,a decrease of 50 units in PTC was associated with 1.3 times odds of cirrhosis(95%CI 1.25-1.35).CONCLUSION In the preceding years before the diagnosis of cirrhosis,there is a progressive decline in PTC,within the normal range,matched to a gradual increase in fibrosis scores.

Preservation of sperm of cancer patients： extent of use and pregnancy outcome in a tertiary infertility center

Sperm cryopreservation is the best modality to ensure future fertility for males diagnosed with cancer. The extent to which cryopreserved sperm is actually used for impregnation, the fertility treatment options that are available and the success rates of these treatments have not been investigated in depth. The medical records of 682 patients who cryopreserved sperm cells due to cancer treatment were analyzed. Seventy of these patients withdrew their frozen sperm for fertility treatments over a 20-year period （most within the first 4 years after cryopreservation）. Sperm quality of different malignancies and outcomes of assisted reproduction treatment （ART） for pregnancy achievement in relation to the type of treatment and the type of malignancy were evaluated. The results showed that the rate of using cryo-thawed sperm from cancer patients for fertility treatments in our unit was 10.3%. Sperm quality indices differed between different types of malignancies, with the poorest quality measured in testicular cancer. Conception was achieved in 46 of the 184 ART cycles （25%）, and resulted in 36 deliveries. The use of intracytoplasmic sperm injection （ICSI） methodology yielded a significantly higher pregnancy rate （37.4%） than intrauterine insemination （IUI; 11.5%） and was similar to other groups of infertile couples using these modalities. In vitro fertilization （IVF） failed to produce pregnancies. In conclusion, the rate of use of cryopresseved sperm in cancer patients is relatively low （10.3%）. Achievement of pregnancies by ICSI presents the best option but when there are enough stored sperm samples and adequate quality, I UI can be employed. Cryopreservation is nevertheless the best option to preserve future fertility potential and hope for cancer patients.

Mucin gene expression in bile of patients with and without gallstone disease,collected by endoscopic retrograde cholangiography

AIM： To investigate the pattern of mucin expression and concentration in bile obtained during endoscopic retrograde cholangiography （ERC） in relation to gallstone disease.METHODS： Bile samples obtained at ERC from 29 consecutive patients, 17 with and 12 without gallstone disease were evaluated for mucin content by gel filtration on a Sepharose CL-4B column. Dot blot analysis for bile mucin apoproteins was performed with antibodies to Mucin 1 （MUC1）, MUC2, MUC3, MUC5AC, MUC5B and MUC6. Staining intensity score （0-3） was used as a measure of antigen expression.RESULTS： MUCl, MUC2, MUC3, MUCSAC, MUC5B and MUC6 were demonstrated in 34.4%, 34.4%, 51.7%, 51.7%, 55.1% and 27.5% of bile samples, respectively.The staining intensity scores were 0.62 ± 0.94, 0.58 ± 0.90, 0.79 ± 0.97, 1.06 ± 1.22, 1.20 ± 2.26 and 0.41 ± 0.73, respectively. Mean mucin concentration measured in bile by the Sepharose CL-4B method was 22.8 ± 24.0 mg/mL （range 3.4-89.0 mg/mL）. Mean protein concentration was 8.1 ± 4.8 mg/mL （range 1.7-23.2 mg/mL）.CONCLUSION： High levels of MUC3, MUC5AC and MUC5B are expressed in bile aspirated during ERC examination. A specific pattern of mucin gene expression or change in mucin concentration was not found in gallstone disease.

Etiology and long-term outcome of extrahepatic portal vein obstruction in children

AIM:To study the management and outcome of children with extrahepatic portal vein obstruction(EHPVO) in a whole country population.METHODS:A nationwide multicenter retrospective case series of children with EHPVO was conducted.Data on demographics,radiographic studies,laboratory workup,endoscopic and surgical procedures,growth and development,were extracted from the patients' charts.Characteristics of clinical presentation,etiology of EHPVO,management and outcome were analyzed.RESULTS:Thirty patients,13 males and 17 females,19(63.3%) Israeli and 11(36.7%) Palestinians,were included in the analysis.Age at presentation was 4.8± 4.6 years,and mean follow-up was 4.9±4.3 years.Associated anomalies were found in 4 patients.The incidence of EHPVO in Israeli children aged 0-14 years was 0.72/million.Risk factors for EHPVO were detected in 13(43.3%)patients,including 9 patients(30%) with perinatal risk factors,and 4 patients(13.3%) with prothrombotic states:two had low levels of protein S and C,one had lupus anticoagulant,and one was homozygous for methyltetrahydrofolate reductase mutations.In 56.6% of patients,no predisposing factors were found.The most common presenting symptoms were an incidental finding of splenomegaly(43.3%),and upper gastrointestinal bleeding(40%).No differences were found between Israeli and Palestinian children with regard to age at presentation,etiology and clinical symptoms.Bleeding occurred in 18 patients(60%),at a median age of 3 years.Sclerotherapy or esophageal banding was performed in 20 patients.No sclerotherapy complications were reported.Portosystemic shunts were performed in 11 patients(36.6%),at a median age of 11(range 3-17)years:splenorenal in 9,mesocaval in 1,and a meso-Rex shunt in 1 patient.One patient underwent splenectomy due to severe pancytopenia.Patients were followed up for a median of 3(range 0.5-15)years.One patient died aged 3 years due to mucopolysaccharidase deficiency type Ⅲ.None of the patients died due to gastrointestinal bleeding.CONCLUSION:EHPVO is a rare disorder.The etiological factors are still mostly unknown,and the endoscopic and surgical treatment options ensure a good long-term prognosis.