Prevalence and intensity of urinary schistosomiasis and soil-transmitted helminths among women of reproductive age in Mwaluphamba,Kwale

Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba location.Stool specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine specimens.Participants’sociodemographic details were obtained using a standardized questionnaire.Results:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 mL.The patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,respectively.Women without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a latrine.Similarly,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary schistosomiasis.In bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.

Hepatocellular carcinoma: Therapeutic advances in signaling,epigenetic and immune targets

Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besides first and second generation tyrosine kinase inhibitors,immune checkpoint inhibitors have become central for the treatment of HCC.New modalities like epigenetic therapy using histone deacetylase inhibitors(HDACi)and cell therapy approaches with chimeric antigen receptor T cells(CAR-T cells)are currently under investigation in clinical trials.Development of such novel drugs is closely linked to the availability and improvement of novel preclinical and animal models and the identification of predictive biomarkers.The current status of treatment options for advanced HCC,emerging novel therapeutic approaches and different preclinical models for HCC drug discovery and development are reviewed here.

Biomarkers for hepatocellular carcinoma: What's new on the horizon?

Treatment of advanced hepatocellular carcinoma remains unsatisfying and so far only prognostic biomarkers like α-fetoprotein have been established. No clear predictive biomarker is currently available for standard of care therapies, including targeted therapies like sorafenib. Novel therapeutic options like immune checkpoint inhibitors may pose new challenges to identification and validation of such markers. Currently, PD-L1 expression via immunohistochemistry and tumor mutational burden via next-generation sequencing are explored as predictive biomarkers for these novel treatments. Limited tissue availability due to lack of biopsies still restricts the use of tissue based approaches. Novel methods exploring circulating or cell free nucleic acids(DNA, RNA or miRNAcontaining exosomes) could provide a new opportunity to establish predictive biomarkers. Epigenetic profiling and next-generation sequencing approaches from liquid biopsies are under development. Sample size, etiologic and geographical background need to be carefully addressed in such studies to achieve meaningful results that could be translated into clinical practice. Proteomics, metabolomics and molecular imaging are further emerging technologies.

Biliary tract cancer stem cells-translational options and challenges

Management of biliary tract cancer remains challenging. Tumors show high recurrence rates and therapeutic resistance, leading to dismal prognosis and short survival. The cancer stem cell model states that a tumor is a heterogeneous conglomerate of cells, in which a certain subpopulation of cells-the cancer stem cells-possesses stem cell properties. Cancer stem cells have high clinical relevance due to their potential contributions to development, progression and aggressiveness as well as recurrence and metastasis of malignant tumors. Consequently, reliable identification of as well as pharmacological intervention with cancer stem cells is an intensively investigated and promising research field. The involvement of cancer stem cells in biliary tract cancer is likely as a number of studies demonstrated their existence and the obvious clinical relevance of several established cancer stem cell markers in biliary tract cancer models and tissues. In the present article, we review and discuss the currently available literature addressing the role of putative cancer stem cells in biliary tract cancer as well as the connection between known contributors of biliary tract tumorigenesis such as oncogenic signaling pathways, micro-RNAs and the tumor microenvironment with cancer stem cells.

Dynamics and cytokinic regulation of immune cell infiltration in genetically engineered mouse models of pancreatic cancer dictate the sensitivity to immunotherapy

Dear Editor,Targeting the immune compartment in pancreatic duc-tal adenocarcinoma(PDAC)holds promise for prognostic improvement,yet our knowledge on the spatial and tem-poral dynamics and the molecular modulators of the PDAC-associated immunophenotype is scarce.

Liver Fat Scores for Noninvasive Diagnosis and Monitoring of Nonalcoholic Fatty Liver Disease in Epidemiological and Clinical Studies

Nonalcoholic fatty liver disease(NAFLD)is strongly associated with the metabolic syndrome and type 2 diabetes and independently contributes to long-term complications.Being often asymptomatic but reversible,it would require population-wide screening,but direct diagnostics are either too invasive(liver biopsy),costly(MRI)or depending on the examiner’s expertise(ultrasonography).Hepatosteatosis is usually accommodated by features of the metabolic syndrome(e.g.obesity,disturbances in triglyceride and glucose metabolism),and signs of hepatocellular damage,all of which are reflected by biomarkers,which poorly predict NAFLD as single item,but provide a cheap diagnostic alternative when integrated into composite liver fat indices.Fatty liver index,NAFLD LFS,and hepatic steatosis index are common and accurate indices for NAFLD prediction,but show limited accuracy for liver fat quantification.Other indices are rarely used.Hepatic fibrosis scores are commonly used in clinical practice,but their mandatory reflection of fibrotic reorganization,hepatic injury or systemic sequelae reduces sensitivity for the diagnosis of simple steatosis.Diet-induced liver fat changes are poorly reflected by liver fat indices,depending on the intervention and its specific impact of weight loss on NAFLD.This limited validity in longitudinal settings stimulates research for new equations.Adipokines,hepatokines,markers of cellular integrity,genetic variants but also simple and inexpensive routine parameters might be potential components.Currently,liver fat indices lack precision for NAFLD prediction or monitoring in individual patients,but in large cohorts they may substitute nonexistent imaging data and serve as a compound biomarker of metabolic syndrome and its cardiometabolic sequelae.

The socioeconomic aspects of nonalcoholic fatty liver disease:food insecurity as a novel risk factor for steatosis and liver fibrosis

Over the last decade,the global prevalence of nonalcoholic fatty liver disease(NAFLD)in both adults and children was rapidly increasing and has become the most common cause of chronic liver disease in many parts of the world.It is predicted to become also the most frequent indication for liver transplantation by 2030 and fueling the rising incidence and prevalence of primary liver cancer in western countries(1,2).