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The hydrogeological regime covering a section passing from Anamaduwa to the Kalpitiya peninsula in northwest Sri Lanka was examined to understand the groundwater flow across the metamorphic and sedimentary rock terrains. The study was conducted as a hydrogeological survey based on a structured questionnaire (n = 82) on the consumption, water level fluctuation, and water supply, supplemented by field examination of shallow dug (n = 20) and tube wells (n = 62). In Kalpitiya the average water level fluctuation was 3.44 m (vary from 2.95 to 6.39 m) while it was 6.27 m (vary from 2.25 to 8.52 m) in the Anamaduwa-Puttalam area. The drinking water supply in Kalpitiya was 24 hours per day irrespective of the dry or wet climate. However, in the Anamaduwa-Puttalam area, it was 14 hours during the dry period while it may extend up to 21 hours during the wet period. The average daily per capita domestic water consumption in the Kalpitiya area was 72.4 L while in the Anamaduwa-Puttalam area, it was 81.5 L. The EC of groundwater in the Anamaduwa-Puttalam area varies from 0.479 to 35.42 dS/m (average 3.336 dS/m) whereas the TDS varies from 319 to 23360 mg/L (average 2190 mg/L). However, in Kalpitiya peninsula EC varies from 0.339 to 5.980 dS/m (average 1.457 dS/m) whereas the TDS varies from 223 to 3847 mg/L (average 962 mg/L). Barring of groundwater flow through faulted basins in Andigama-Anamaduwa area and near the unconformity between Wanni complex and limestone belt are hydro-geologically responsible for the higher EC (>2.500 dS/m) and TDS (>2000 mg/L). Seawater intrusions along with sandy aquifers in the Kalpitiya peninsula are responsible for the EC/TDS variations. Moreover, Kalpitiya indicates better prospects compared to landward areas. The outcome highlighted future water sector challenges in support of achieving the Sustainable Development Goal (SDG) target 6 in the study area.

Although liquid electrolyte based dye-sensitized solar cells (DSCs) have shown higher photovoltaic performance in their class, they still suffer from some practical limitations such as solvent evaporation, leakage, and sealing imperfections. These problems can be circumvented to a certain extent by replacing the liquid electrolytes with quasi-solid-state electrolytes. Even though SnO2 shows high election mobility when compared to the semiconductor material commonly used in DSCs, the cell performance of SnO2-based DSCs is considerably low due to high electron recombination. This recombination effect can be reduced through the use of ultrathin coating layer of ZnO on SnO2 nanoparticles surface. ZnO-based DSCs also showed lower performance due to its amphoteric nature which help dissolve in slightly acidic dye solution. In this study, the effect of the composite SnO2/ZnO system was investigated. SnO2/ZnO composite DSCs showed 100% and 38% increase of efficiency compared to the pure SnO2-based and ZnO-based devices, respectively, with the gel electrolyte consisting of LiI salt.

Abstract  Toxocariasis is a worldwide zoonotic disease caused by the ascarid nematode Toxocara canis. The most common method available for serodiagnosis of toxocariasis is an enzyme-linked immunosorbent assay (ELISA) test using Toxocara excretory-secretory antigen (TES). The present study describes the development of IgG-ELISA based on antiserum prepared against the recombinant arginine kinase of Toxocara canis. Antiserum was prepared against the purified recombinant arginine kinase (AK) using 6-week-old female Japanese white rabbits. Serum samples were collected from experimentally infected BALB/c and C57BL/6 mice at different time periods. The IgG-ELISA was performed using serum samples from mice (infected/uninfected) and TES antigen with antiserum prepared against the recombinant-AK. The optical density (OD450) was measured at 450 nm using a micro-plate ELISA reader. There were significant differences (P T. canis-infected mice. Therefore, it is suggested that the recombinant-AK based IgG-ELISA could be applied for immunodiagnosis of human toxocariasis. However, it is necessary to evaluate the specificity of this recombinant antigen with similar geohelminth infections. [ABSTRACT FROM AUTHOR]

Abstract  Adult flukes of Paragonimus species were obtained from lungs of experimental animals infected with metacercariae found in field-collected freshwater crabs in Sri Lanka. Morphological studies of adult worms under a scanning electron microscope as well as a ordinary microscope were performed in the present study. All of morphological features observed clearly indicated that this species is P. westermani. On the other hand, the shapes of metacercariae were found to be mainly oval, but semioval and spherical ones also coexisted. In spite of the variety of their morphology of the metacercariae, there is no correlation between their shapes of metacercariae and the deoxyribonucleic acid (DNA) sequences. Molecular phylogenetic analyses using two DNA regions (partial mitochondrial cytochrome c oxidase subunit 1 and second internal transcribed spacer of the nuclear ribosomal gene repeat) placed the adult flukes of P. westermani from Sri Lanka basal in a tree including all specimens of P. westermani from various areas in Asia and P. siamensis from Thailand. The present study showed that P. westermani from Sri Lanka is an ancestral form. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC). The pathogenesis of CRC in IBD differs from sporadic cancer, with the burden of inflammation being an important contributing factor. Other risk factors for developing CRC in patients with Crohn's disease (CD) or ulcerative colitis (UC) includes a family history of CRC, personal history of dysplasia, history of strictures, or primary sclerosing cholangitis (PSC). Dysplasia is the precursor of cancer and ensuring effective surveillance strategies is vital for early detection and intervention. In the past, dysplasia detection relied on random biopsies, but recent studies have shown that, with the adaptation of high-definition white light endoscopy (HD-WLE), dye sprayed chromoendoscopy (DCE) and virtual chromoendoscopy (VCE), dysplasia detection has improved. While there exists a certain degree of consensus amongst experts regarding the management of dysplasia, it is important to implement a personalized approach to each patient's care. Our review focuses on advancements in the past two decades, specifically highlighting the modifications that have been implemented since the SCENIC guidelines. It also explores future directions, including the potential implementation of stool studies as a non-invasive tool for surveillance and the emerging role of artificial intelligence (AI) in dysplasia detection., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-36/coif). The series “Controversies and Updates in Inflammatory Bowel Disease” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2024 Translational Gastroenterology and Hepatology. All rights reserved.)

Background: Patients with inflammatory bowel disease (IBD) and substance use disorder (SUD) may have worse clinical outcomes. However, data specific to the hospital admission and mortality rates among IBD patients with SUD are scarce. Our objective was to assess trends in admission, healthcare expenses, and mortality for IBD patients with SUD., Methods: We conducted a retrospective study using the National Inpatient Sample database to analyze SUD (alcohol, opioids, cocaine, and cannabis) among IBD hospitalizations from 2009 to 2019., Results: A total of 132,894 hospitalizations for IBD had a secondary diagnosis of SUD. Of these patients, 75,172 (57%) were men and 57,696 (43%) were women. The IBD-SUD cohort had a longer length of stay than the non-SUD cohort ( P  < 0.001). The mean inpatient charges for IBD hospitalizations with SUD increased from $48,699 ± $1374 in 2009 to $62,672 ± $1528 in 2019 ( P  < 0.001). We found a 159.5% increase in IBD hospitalizations with SUD. The hospitalization rate increased from 3492 per 100,000 IBD hospitalizations in 2009 to 9063 per 100,000 in 2019 ( P  < 0.001). In-hospital mortality for IBD hospitalizations with SUD increased by 129.6% (from 250 deaths per 100,000 IBD hospitalizations in 2009 to 574 deaths per 100,000 IBD hospitalizations in 2019) ( P  < 0.001)., Conclusions: Over the last decade, there has been a rise in IBD hospitalizations with SUD. This has resulted in a longer length of stay, higher inpatient charges, and higher mortality rates. Identifying IBD patients potentially at risk for SUD by screening for anxiety, depression, pain, or other factors has become crucial., Competing Interests: The authors report no funding or conflicts of interests., (Copyright © 2023 Baylor University Medical Center.)

Background: Wound healing is an active, complex, integrated series of cellular, physiological, and biochemical changes initiated by the stimulus of injury in a tissue. The present study was performed to investigate the potential wound healing abilities of Sargassum ilicifolium crude extracts (CE) that were characterized by 1 H NMR and FTIR Spectrometric measurements., Materials and Methods: Seaweed samples were collected from southern coastal sites of Sri Lanka. To determine the cytotoxicity and proliferation of S. ilicifolium CE were used for the MTT and alamarBlue assays respectively. The scratch and exclusion wound models were used to HaCaT and HDF cells to assess the cell proliferation and migration. RAW 264.7 cells (macrophages) were used to evaluate Nitric Oxide (NO) production and phagocytosis activities. Moreover, Fifteen, 8-week-old, female, New Zealand rabbits were selected and divided into five groups: excision skin wounds (10.40 ± 0.60 mm) were induced in groups I, II, and III. Rabbits in groups I and IV were given S. ilicifolium CE (orally, 100 mg/kg day, two weeks), whereas groups II and V were given equal amounts of distilled water. Wound healing properties were measured and wound tissue samples were collated, formalin-fixed, wax-embedded, stained (Hematoxylin and Eosin; Van Gieson) and examined for the healing process., Results: Anti-inflammatory and wound healing activities were observed in RAW 264.7, HDF and HaCaT cells treated with S. ilicifolium aqueous extracts when compared to the control groups. S. ilicifolium extracts concentration 8 - 4 μg/μL, (P<0.05) had remarkable the highest proliferative and migratory effects on RAW 264.7, HDF and HaCaT cells when compared with the control. RAW 264.7 cell proliferation and/or migration were higher in S. ilicifolium extracts (4 μg/μL, 232.8 ± 10.07%) compared with the control (100 %). Scratch wound healing were remarkably enhanced in 24 h, 48 h (P<0.05) when treated with S. ilicifolium on HaCaT cells. Rabbits treated with the CE of S. ilicifolium showed a significantly increased wound healing activities (P<0.05) within three days with a close wound area of 57.21 ± 0.77 % compared with control group (26.63 ± 1.09 %). Histopathology, aspartate aminotransferase and alanine aminotransferase levels evidenced no toxic effects on seaweed treated groups. Histopathological results also revealed that the healing process was significantly faster in the rabbit groups which were as treated with CE of S. ilicifolium orally with the evidence of enhanced early granulation tissue (connective tissue and angiogenesis) and significant epithelization compared to the control., Conclusions: Cell proliferation and migration are significantly faster when treated with S. ilicifolium aqueous extracts. Moreover, there are no toxic effect of S. ilicifolium aqueous extracts on RAW 264.7, HDF and HaCaT cell lines. In this study, it is revealed that S. ilicifolium has potential remedial agent; D-Mannitol for skin wound healing properties that by promote keratinocyte and fibroblast proliferation and migration. These findings show that S. ilicifolium have promising wound healing properties., (© 2023. The Author(s).)

Background: Inflammatory bowel disease (IBD) is a chronic intestinal inflammation resulting in a genetically susceptible population. The present study aimed to look at the effect of substance abuse on IBD hospitalizations in the United States., Methods: We identified primary IBD hospitalizations with substance abuse using the National Inpatient Sample database (2016-2019). A matched comparison cohort of IBD hospitalizations without substance abuse was identified by 1:N propensity score matching using the nearest-neighbor method, based on demographics, hospital-level factors, and comorbidities., Results: We matched 4437 IBD hospitalizations with a diagnosis of substance abuse to 4528 hospitalizations without abuse. The median age was higher in the substance abuse group than no abuse (44 vs. 38 years, P<0.001). There was a higher prevalence of discharge to care facilities (2.9% vs. 2.2%) and against medical advice (4.9% vs. 1.8%) in the substance abuse group compared to the no abuse (P<0.001). The median length of hospital stays (LOS) (P=0.74) and hospitalization charge did not differ significantly (P=0.57). There was no significant difference in 30-day inpatient mortality among cohorts (adjusted hazard ratio 0.74, 95% confidence interval 0.32-1.81; P=0.54). There was a higher prevalence of psychoses (2.5% vs. 1.3%) and depression (18.8% vs. 15.7%) in IBD hospitalizations with substance abuse compared to those without abuse (P<0.001)., Conclusions: This study reports no difference in median LOS, hospitalization charge, or mortality risk in IBD hospitalizations based on substance abuse. There is a higher prevalence of psychoses and depression in IBD patients, requiring screening for substance abuse to improve overall outcomes., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Objectives: To describe the clinical spectrum and the cytokine response of leptospirosis patients in an endemic setting of Sri Lanka., Methods: Patients presenting to the university teaching hospital, Anuradhapura, Sri Lanka with a leptospirosis-compatible illness were recruited over a period of 12 months starting from June 2012. Daily clinical and biochemical parameters of the patients were prospectively assessed with a follow-up of 14 days after discharge. A magnetic bead-based multiplex cytokine kit was used to detect 17 cytokines., Results: Of the 142 clinically suspected leptospirosis patients recruited, 47 were confirmed and, 29 cases were labeled as "probable." Thrombocytopenia and leukocytosis were observed at least once during the hospital stay among 76(54%) and 39(28%) patients, respectively. Acute kidney injury was observed in 31 patients (22%) and it was significantly higher among confirmed and probable cases. Hu TNF-α and IL-1β were detected only in patients without complications. Hu MIP-1b levels were significantly higher among patients with complications. During the convalescence period, all tested serum cytokine levels were lower compared to the acute sample, except for IL-8. The cytokine response during the acute phase clustered in four different groups. High serum creatinine was associated GM-CSF, high IL-5 and IL-6 level were correlates with lung involvement and saturation drop. The patients with high billirubin (direct)>7 mmol/l had high IL-13 levels., Conclusions: Results of this study confirms that the knowledge on cytokine response in leptospirosis could be more complex than other similar tropical disease, and biosignatures that provide diagnostic and prognostic information for human leptospirosis remain to be discovered., Competing Interests: No authors have competing interests.

Background: The management of inflammatory bowel disease (IBD) has become much more complex as our understanding of the disease pathology has improved and as new novel therapeutic options come into play. A factor that has not been studied in the management of this disease is the role that Direct-To-Consumer Advertisement (DTCA) plays in patients' decisions regarding their treatment options. Here we investigate the very role this mode of television advertisement has on influencing our patients., Methods: Following formal institutional review board approval, we devised a prospective, single institution, survey-based study in our university-based outpatient gastroenterology clinic. Surveys included major demographic features along with questions pertaining to patients' interactions with various advertisements. Surveys were collected over a 3-month period., Results: Overall, 103 surveys were collected. The data were not normally distributed. Fifty-three patients were female, and 40 patients were male. Eighty-one percent of patients with IBD were not affected in any way by advertisements with regard to influencing their decision to start new therapies. A subgroup analysis revealed that various parameters including age, sex, and marital status played a role in how DTCA influences patients with regard to their IBD treatments., Discussion: This study demonstrates that overall patients are not significantly influenced by DTCAs; however, some cohorts are influenced in more ways than others. This study highlights the importance of understanding the role DTCA plays in influencing our patients with IBD and sets the foundation for further inquiry into this very interesting relationship., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background/aims: Optimal management of inflammatory bowel disease (IBD) with concomitant Clostridium difficile infection (CDI) is controversial, especially when CDI diagnosis is made by polymerase chain reaction (PCR) testing, which may reflect colonization without infection., Methods: We performed a multicenter review of all inpatients with IBD and PCR diagnosed CDI. Outcomes included length of stay, 30- and 90-day readmission, colectomy during admission and within 3 months, intensive care unit (ICU) admission, CDI relapse and death for patients who received corticosteroid (CS) after CDI diagnosis versus those that did not. Propensity-adjusted regression analysis of outcomes based on CS usage was performed., Results: We identified 177 IBD patients with CDI, 112 ulcerative colitis and 65 Crohn's disease. For IBD overall, CS after CDI diagnosis was associated with prolonged hospitalization (5.5 days: 95% confidence interval [CI], 1.5-9.6 days; P=0.008), higher colectomy rate within 3 months (odds ratio [OR], 5.5; 95% CI, 1.1-28.2; P=0.042) and more frequent ICU admissions (OR, 7.8; 95% CI, 1.5-41.6; P=0.017) versus no CS. CS use post-CDI diagnosis in UC patients was associated with prolonged hospitalization (6.2 days: 95% CI, 0.4- 12.0 days; P=0.036) and more frequent ICU admissions (OR, 7.4; 95% CI, 1.1-48.7; P=0.036)., Conclusions: CS use among IBD inpatients with CDI diagnosed by PCR is associated with poorer outcomes and would seem to reinforce the importance of C. difficile toxin assay to help distinguish colonization from infection. This adverse effect appears more prominent among those with UC.

Facial soft tissue thickness (FSTT), together with the osteological characteristics of the skull, is one of the important factors for facial reconstruction in both forensic anthropology and plastic surgeries. Even though a number of countries around the world have analysed the FSTT data of their own populations and are having a FSTT database, no such dataset or analysis is available in Sri Lanka. In this study, FSTT was measured at 23 standard anthropological landmarks using magnetic resonance images (MRIs) of 243 adult individuals (male - 121, female - 122) of the Sri Lankan population, which were collected from clinical data from the National Hospital of Sri Lanka. For each landmark, basic descriptive statistics were calculated. The FSTT values which were classified according to the gender and age, were analysed to assess the variation of FSTT with those categories. The results of this study indicate that there are certain FSTT attributes which are related to specific landmarks and age groups. For example, data in this study depict that men have higher FSTT than women, in the area along the midline. However, the area around the cheeks shows comparatively large tissue thickness in young women (within 20-39 age range) than in men. Some landmarks indicate a significant variation in values with aging. Finally the results of this study were compared with that of a North West Indian study to evaluate whether a significant difference is present among the two geographically close countries., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only)., Method: V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group., Results: Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT., Conclusion: The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.

Background/objectives: The reported risk of chronic kidney disease (CKD) in patients with Helicobacter pylori infection is conflicting. This meta-analysis was conducted to summarize all available data and to estimate the prevalence and association between H. pylori and kidney disease and CKD., Methods: Comprehensive literature review was conducted using MEDLINE and EMBASE database through October 2016 to identify studies that reported the prevalence or the association between H. pylori infection and non-dialysis-dependent kidney diseases or CKD. Effect estimates from the individual study were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird., Results: Of 4546 studies, nine cross-sectional studies met the eligibility criteria and were included in the meta-analysis. The estimated prevalence of H. pylori infection among subjects with kidney disease was 53% (95% CI 45-61%). The pooled OR of H. pylori in patients with non-dialysis-dependent kidney diseases was 1.20 (95% CI 0.73-1.97) when compared with the patients without kidney diseases. The meta-analysis was then limited to only studies evaluating the risk of H. pylori in CKD; the pooled OR of H. pylori in patients with CKD was 1.00 (95% CI 0.58-1.71)., Conclusions: The estimated prevalence of H. pylori in patients with non-dialysis-dependent kidney diseases is 53%. This study does not support the association between H. pylori infection and non-dialysis-dependent kidney diseases nor CKD.

Aim: To investigate the prevalence and association of Helicobacter pylori ( H. pylori ) with end-stage renal disease (ESRD)., Methods: SA comprehensive literature search was completed from inception until October 2016. Studies that reported prevalence, relative risks, odd ratios, hazard ratios or standardized incidence ratio of H. pylori among ESRD patients were included. Participants without H. pylori were used as comparators to assess the association between H. pylori infection and ESRD. Pooled risk ratios and 95%CI was calculated using a random-effect model. Adjusted point estimates from each study were combined by the generic inverse variance method of DerSimonian and Laird., Results: Of 4546 relevant studies, thirty-seven observational studies met all inclusion criteria. Thirty-five cross-sectional studies were included in the analyses to assess the prevalence and association of H. pylori with ESRD. The estimated prevalence of H. pylori among ESRD patients was 44% (95%CI: 40%-49%). The pooled RR of H. pylori in patients with ESRD was 0.77 (95%CI: 0.59-1.00) when compared with the patients without ESRD. Subgroup analysis showed significantly reduced risk of H. pylori in adult ESRD patients with pooled RR of 0.71 (95%CI: 0.55-0.94). The data on the risk of ESRD in patients with H. pylori were limited. Two cohort studies were included to assess the risk of ESRD in patients with H. pylori . The pooled risk RR of ESRD in patients with H. pylori was 0.61 (95%CI: 0.03-12.20)., Conclusion: The estimated prevalence of H. pylori in ESRD patients is 44%. Our meta-analysis demonstrates a decreased risk of H. pylori in adult ESRD patients., Competing Interests: Conflict-of-interest statement: The authors deny any conflict of interest.

Anti-TNFα therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNFα therapy, we investigated if patients treated with anti-TNFα antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNFα therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNFα therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNFα antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNFα antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNFα antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNFα therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise., (© 2015 Wiley Periodicals, Inc.)

Acute mesenteric ischemia (AMI) is a rare vascular emergency associated with a high mortality rate. The most common cause of AMI is cardiac emboli from thrombi associated with atrial fibrillation or following myocardial infarction. We present a case of AMI caused by a unique source of emboli, confirmed as an embolization of a cardiac sarcoma to the small bowel by matching biopsies obtained from the superior mesenteric artery (SMA) and the embolic source.

Aim: In a case of cardiac arrest lay people in Republic of Slovenia rarely start basic life support procedures. The aim of this study was to determine the extent of knowledge about and attitude towards cardiopulmonary resuscitation in lay population., Method: A cross-sectional telephone survey using computer-assisted telephone interview method was performed in August and September 2006. Questionnaire contained sections regarding participant demographics, knowledge of cardiac arrest signs and of cardiopulmonary resuscitation procedures (CPR), previous courses of CPR training, and the awareness of emergency phone contact number., Results: We interviewed 500 subjects. Nearly 70% of subjects had attended courses on CPR, but nearly 80% of them did so more than 10 years ago. Less than half of the subjects knew that CPR include rescue breathing (47%) and chest compressions (44.6%). Subjects who passed training on CPR knew that twice more often (p < 0.001). Knowledge on resuscitation skills was generally poor. Only 1.2% knew the rate of chest compressions, 2.2% knew the correct compressions-to-ventilations ratio in adult CPR, and only 3 out of 500 subjects (0.6%) knew both. Correct site and correct strength for chest compressions were stated in 37.6% and 13.0%, respectively. Both the correct site and the correct strength were stated more often in CPR-trained group (p = 0.002 and p = 0.02, respectively)., Conclusion: Lay public in Republic of Slovenia has poor knowledge on CPR. Knowledge is better in trained versus untrained individuals. Educational campaign in the community would improve response to cardiac emergencies.

Background: Recent guidelines from the American College of Gastroenterology for screening for colorectal cancer have included obesity as an important risk factor. The recommendation for screening obese people at earlier age was tempered by the need for more data regarding obesity and colorectal neoplasia., Aims: We designed a cross-sectional study to further examine the predictive value of obesity for colorectal adenomas in asymptomatic patients., Methods: We prospectively collected demographic, medical, lifestyle, and dietary history from asymptomatic patients presenting for screening colonoscopy. Patients underwent complete colonoscopy using high-definition colonoscope to detect colorectal adenomas. We defined advanced neoplasia as large (≥ 1 cm) adenoma, villous adenoma, high-grade dysplasia or cancer., Results: Six hundred patients with median age of 56 years completed the study. Over 40% of these patients did not consider themselves Caucasian, and less than 5% had a first-degree relative with colorectal cancer. Overall, 40 patients (6.7%) had advanced neoplasia and 216 (36.3%) had any adenoma. There were 185 obese patients (30.8%), who had a prevalence of 44.3% for any adenoma and 13.0% for advanced neoplasia. After multivariate analysis, obesity [body mass index (BMI) ≥ 30 kg/m(2)] was significantly associated with increased risk of advanced neoplasia [odds ratio (OR) = 3.83; 95% confidence interval (CI): 1.94-7.55]., Conclusions: Obesity was associated with advanced neoplasia in this screening population. Our data regarding the association of colorectal neoplasia with this modifiable risk factor has implications for screening and prevention of colorectal cancer.

Background: Flat adenomas represent a morphologically distinct class of polyps that may be difficult to detect, and little is known regarding risk factors for these lesions. Identification of risk factors for these lesions may aid in colorectal cancer (CRC) screening, because patients at risk for these lesions may require special imaging techniques. Smoking, an important risk factor for CRC, may be associated with molecular changes that increase the risk for flat adenomas., Objective: The aim of this study was to examine the association between smoking and flat adenomas., Design: Prospective cross-sectional study., Setting: University hospital endoscopy center., Patients: We enrolled asymptomatic patients presenting for CRC screening., Interventions: We screened patients with a high-definition (1080i signal) wide-angle (170 degrees field of view) Olympus 180-series colonoscope. We collected demographics, medication use, family history of CRC, diet history, and smoking history., Main Outcome Measurements: Polyp morphology, assessed by using the Japanese Research Society Classification (JRSC)., Results: A total of 600 patients were enrolled. We observed that smoking was associated with having a flat adenoma of any size (adjusted odds ratio [OR], 2.53; 95% CI, 1.60-4.00), having only flat adenomas that were > or = 6 mm in diameter (adjusted OR, 3.84; 95% CI, 2.02-7.32), as well as flat advanced adenomas (adjusted OR, 2.81; 95% CI, 1.08-7.30)., Limitations: The study design may not account for some confounding variables and provides no information regarding smoking status at the time of initiation of flat adenomas., Conclusion: Smoking was associated with flat adenomas in our population. Our findings may explain the earlier onset of CRC in smokers as well as the advanced stage with which they present, with compared with nonsmokers. Smokers may require screening with high-definition colonoscopes to detect flat adenomas., (Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

The stimulation of DC by CD4(+) T cells is known to condition DC to activate naïve CD8(+) T cells, predominantly via CD40-CD40L interactions. It has been proposed that a critical consequence of DC conditioning is the induction of CD70 expression. Whether and how CD70 induction contributes to CD8(+) T cell responses in the absence of CD40-CD40L interactions are unknown. CD8(+) T cell responses to adenoviral- or DC-based immunization of CD40-deficient mice revealed a CD40-independent, CD4(+) T cell-dependent pathway for CD70 induction on conventional DC. This pathway and subsequent CD8(+) T cell responses were enhanced by, but not dependent on, concomitant activation of TLR and in part, used TRANCE and LIGHT/LTalphabeta stimulation. Blocking TRANCE and LIGHT/LTalphabeta during stimulation reduced the immunogenicity of CD40-deficient DC. These data support the hypothesis that induction of CD70 expression on DC after an encounter with activated CD4(+) T cells is a major component of CD4(+) T cell-mediated licensing of DC. Further, multiple pathways exist for CD4(+) T cells to elicit CD70 expression on DC. These data in part explain the capacity of CD40-deficient mice to mount CD8(+) T cell responses and may provide additional targets for immunotherapy in situations when CD40-mediated licensing is compromised.

Novel bi-functional compounds with a nitric oxide (NO)-releasing moiety bound to a dorzolamide scaffold were investigated. Several compounds were synthesized and their activity as selective carbonic anhydrase inhibitors (CAI) evaluated in vitro on recombinant hCA type I, II and IV enzyme isoforms where they showed different degrees of potency and selectivity to hCA II. A high resolution X-ray crystal structure for the CA II adduct with 8 confirmed the high affinity of this class of compounds for the enzyme. Compounds 4, 6, and 8 showed highly potent and efficacious NO-mediated properties as assessed by their vascular relaxant effect on methoxamine-precontracted rabbit aortic rings. Finally, compounds 4 and 6 exerted potent intraocular pressure (IOP) lowering effects in vivo in normotensive rabbits thereby anticipating their potential for the treatment of hypertensive glaucoma.

Background: 5-Aminosalicylate (5-ASA) agents are the mainstay of oral therapy for ulcerative colitis (UC). Balsalazide, a prodrug of 5-ASA, has recently been approved for the treatment of UC., Objective: To summarize current data on balsalazide and to discuss its impact on management of UC., Methods: A systematic review of published literature was performed on PubMed using the search terms 'Balsalazide' and 'Colazal(TM)'. The Cochrane database was also reviewed., Results: Balsalzide, a 5-ASA prodrug, ulilizes azoreduction by colonic bacteria to achieve a sustained release of active 5-ASA throughout the colon. A recent clinical trial has demonstrated balsalazide 6.7 g/day to be superior to placebo in inducing remission in symptomatic UC. The drug is well tolerated with a safety profile comparable to other oral 5-ASA agents. The current data suggests that symptomatic remission occurs with both greater swiftness and greater frequency when compared with mesalamine., Conclusion: Balsalazide is approved for the treatment of mild-to-moderate active UC. It is efficacious for the induction of remission in mild to moderate UC and has a favorable safety profile, with the added advantages of greater efficacy of remission induction and rapidity of onset.

The hormonal form of vitamin D, 1,25-dyhydroxyvitamin D3 (1,25(OH)2D3), is implicated in a wide range of functions other than its classical role in calcium and phosphorous homeostasis. When Toxoplasma gondii-infected BALB/c mice were treated with 1,25(OH)2D3, they succumb to death sooner than their counterparts. But they showed less parasite burden in tissues which was further supported by mild pathological lesions. As an effort to understand the physiological mechanism for the above observation an in vitro study was performed. Fewer parasites were observed when 1,25(OH)2D3 pre-treated murine intestinal epithelial cells were challenged with parasites. Moreover, the observed inhibition was dose-dependent and had a maximum effect with 10(-7)M of 1,25(OH)2D3. However, no observable difference was observed, when pre-incubated parasites were added to cells suggesting that the observed inhibition was a result of an effect from 1,25(OH)2D3 on Toxoplasma intracellular growth. Our data support the notion that 1,25(OH)2D3 may inhibit intra cellular T. gondii parasite proliferation in vivo and in vitro.

Gonadotropin releasing hormone (GnRH) plays an important role in the biology of reproduction. The use of GnRH receptor antagonists has been reported in the literature for the treatment of breast, ovarian, and prostate cancers. In this article, we report the synthesis, in vitro characterization, pharmacokinetics, and pharmacodynamics of an orally bioavailable, potent, small molecule GnRH receptor antagonist N-{4,6-dimethoxy-2-[(3-morpholin-4-ylpropyl)amino]pyrimidin-5-yl}-5-[3,3,6-trimthyl-2,3-dihydro-1H-inden-5-yl)oxy]-2-furamide (compound 1).

Bidirectional associative memories (BAMs) are shown to be capable of precisely learning concept lattice structures by Radim Belohlávek. The focus of this letter is to show that the BAM, when set up with a concept lattice by setting up connection weights according to the rule proposed by Belohlávek, always returns the most specific or most generic concept containing the given set of objects or attributes when a set of objects or attributes is presented as input to the object or attribute layer. A proof of this property is given here, together with an example, and a brief application of the property is provided.

The hormonal form of Vitamin D, 1,25-dihydroxyvitamin D3, is well known for its immunosuppressive, anti-proliferative and pro-apoptotic activities. In the present work, we studied the effect of 1,25-dihydroxyvitamin D3 on Toxoplasma gondii-infected mice. We observed that 1,25-dihydroxyvitamin D3 reduces the survival rate of infected mice by up to 37% at day 10 post-infection compared to untreated infected mice (P < 0.0001). IFN-gamma and IL-12p40 levels were significantly reduced by 1,25-dihydroxyvitamin D3 in infected mice sera indicating an inhibition of Th-1-type cytokines. CD4+ T lymphocyte and splenocyte counts were also reduced following 1,25-dihydroxyvitamin D3 treatment and a marked induction of apoptosis, accompanied with down-regulation of the anti-apoptotic proteins Bcl-2 and Bcl-X(L), was observed. The above results indicate that 1,25-dihydroxyvitamin D3 induces splenocyte apoptosis and enhances host susceptibility to toxoplasmosis.

In the BALB/c mouse model, primary infection with Toxoplasma gondii during the second third of gestation leads to a high percentage of infected foetuses. However, immunity induced by infection contracted before pregnancy prevents parasites from crossing the placenta and completely protects the foetuses, as well as the pregnant women. In order to clarify the roles of CD4+, CD8+ T lymphocytes and IFN-gamma in this protection, pregnant BALB/c mice were treated with depleting monoclonal antibodies against CD4, CD8, IFN-gamma, or control antibody. Only the foetuses of the groups treated with anti-CD8 and anti-IFN-gamma antibodies developed congenital toxoplasmosis. The maternal production of IFN-gamma was depressed in the mice depleted of CD4 and CD8 cells (P < 0.001). Determination of the blood parasite load demonstrated that materno-foetal transmission of T. gondii correlates with maternal parasitaemia. Together, these results show that CD8+ T lymphocytes and IFN-gamma play an important role in protection against congenital toxoplasmosis during reinfection.