Childhood Inflammatory Bowel Disease in Libya: Epidemiological and Clinical features

Background & Aims: Inflammatory bowel disease is thought to be rare in Libya. The aim is to determine the prevalence of juvenile onset inflammatory bowel disease in Libya. Setting: Al-Fateh childrens' hospital, Benghazi, Libya. Methods: This is a retrospective study of all cases diagnosed over 10 years (1997–2006) with either ulcerative colitis, Crohn's disease or indeterminate colitis. Inclusion criteria were age <15 years at time of presentation who were resident in the eastern part of the country and who diagnosed with inflammatory bowel disease. Clinical features were outlined using a proforma. Results: Sixteen cases were diagnosed with inflammatory bowel disease, of whom 11 were males (M:F ratio of 1.5:1). The prevalence and incidence rates in the year 2006 were 3.6 and 0.9 per 100,000 children, respectively. The incidence rate increased from 0.2 in 2002 to 0.9 in 2006 (Z score of 39.87, p= 0.00). The age at presentation ranged from 5 months to 14 years. Nine had Crohn's disease (6 males) and 6 had ulcerative colitis (4 males). One patient had indeterminate colitis. The most common clinical features were diarrhea in 10 (62.5%), abdominal pain, anorexia and weight loss in 9 (56.2%), anemia in 7 (43.75%) and vomiting in 6 (37%). Ileopancolitis was found in 3 patients whereas 6 patients had ileocecal disease. Conclusions: Childhood inflammatory bowel disease in this population is not so rare and it is increasing. The clinical pattern is similar to that reported by others

Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-Fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963)

Circadian clocks control cellular proliferation and drug metabolism over the 24 h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N = 556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p < .0001), and G3-4 were 7% and 25%, respectively (p < .0001). Neutropenia was significantly more frequent in women than men on either schedule (FOLFOX2, p = .003; chronoFLO4, p = .04). Median survival was 20.7 mo in patients with G3-4 neutropenia versus 12.5 mo in neutropenia-free patients on FOLFOX2 (p < .0001). Corresponding figures were 13.7 and 19.4 mo, respectively, on chronoFLO4 (p = .36). Multivariate analysis confirmed occurrence of severe neutropenia independently predicted for better overall survival on FOLFOX2 (HR = 0.56; p = .015), and worse survival on chronoFLO4 (HR = 1.77, p = .06), with a significant interaction test (p < .0001). Prediction of better survival in neutropenic patients on FOLFOX2 supports the administration of conventional chemotherapy near maximum tolerated dose. The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through personalized circadian-timed therapy.info:eu-repo/semantics/publishedVersio

Targeting the tumor microenvironment: An unexplored strategy for mutant KRAS tumors

Current evidence strongly suggests that cancer cells depend on the microenvironment in order to thrive. In fact, signals from the surrounding tumor microenvironment are crucial for cancer cells´ aggressiveness, altering their expression profile and favoring their metastatic potential. As such, targeting the tumor microenvironment to impair cancer progression became an attractive therapeutic option. Interestingly, it has been shown that oncogenic KRAS signaling promotes a pro-tumorigenic microenvironment, and the associated crosstalk alters the expression profile of cancer cells. These findings award KRAS a key role in controlling the interactions between cancer cells and the microenvironment, granting cancer a poor prognosis. Given the lack of effective approaches to target KRAS itself or its downstream effectors in the clinic, exploring such interactions may open new perspectives on possible therapeutic strategies to hinder mutant KRAS tumors. This review highlights those communications and their implications for the development of effective therapies or to provide insights regarding response to existing regimens.This work was supported through FEDER funds through the Operational Programme for Competitiveness Factors (COMPETE 2020), Programa Operacional de Competitividade e Internacionalização (POCI), Programa Operacional Regional do Norte (Norte 2020), European Regional Development Fund (ERDF), and by National Funds through the Portuguese Foundation for Science and Technology (FCT) (PTDC/MED-ONC/31354/2017). PDC is a PhD student from Doctoral Program in Pathology and Molecular Genetics from the Institute of Biomedical Sciences Abel Salazar (ICBAS) and she is funded through a PhD fellowship (SFRH/BD/131156/2017) awarded by Portuguese Foundation for Science and Technology (FCT). FM is a PhD student from Doctoral Programme in Biomedicine from the Faculty of Medicine of the University of Porto and she is funded through NORTE-01-0145-FEDER-000029. ALM is funded through NORTE-01-0145-FEDER-000012. SV is hired by IPATIMUP under norma transitória do DL n.º 57/2016 alterada pela lei n.º 57/2017. This work was supported through FEDER funds through the Operational Programme for Competitiveness Factors (COMPETE 2020), Programa Operacional de Competitividade e Internacionaliza??o (POCI), Programa Operacional Regional do Norte (Norte 2020), European Regional Development Fund (ERDF), and by National Funds through the Portuguese Foundation for Science and Technology (FCT) (PTDC/MED-ONC/31354/2017). PDC is a PhD student from Doctoral Program in Pathology and Molecular Genetics from the Institute of Biomedical Sciences Abel Salazar (ICBAS) and she is funded through a PhD fellowship (SFRH/BD/131156/2017) awarded by Portuguese Foundation for Science and Technology (FCT). FM is a PhD student from Doctoral Programme in Biomedicine from the Faculty of Medicine of the University of Porto and she is funded through NORTE-01-0145-FEDER-000029. ALM is funded through NORTE-01-0145-FEDER-000012. SV is hired by IPATIMUP under norma transitória do DL n.° 57/2016 alterada pela lei n.° 57/2017

Analysis of risk factors for canine mast cell tumors based on the Kiupel and Patnaik grading system among dogs with skin tumors

Background: Skin tumors are the most frequently diagnosed lesions, of which 7%-21% are mast cell tumors (MCTs). There is a great effort to identify factors that can influence the prospective course of MCTs. Although, the histological grade is considering an important predictor helping to determine the malignancy and metastatic potential of MCTs. Aim: In this study, an epidemiological analysis of risk factors (breed, age, sex, and anatomical site) for dogs having MCTs was evaluated considering the respective MCTs histological grade in comparison to other skin tumors. Methods: The study included 244 dogs affected by cutaneous MCTs from a universe of 1,185 dogs diagnosed with skin tumors. A univariable analysis with Fisher exact test was performed to determine the odds ratios (ORs) with 95% confidence intervals (CIs). Results: Boxers had a higher predisposition to Patnaik's grade I (OR = 5.9, 95% CI 2.648-13.152) and to Kiupel's low-grade MCTs (OR = 2.6, 95% CI 1.539-4.447). Labrador retrievers (OR = 2.1, 95% CI 1.423-3.184), and pugs (OR = 12.9, 95% CI 2.336-70.931) had a predisposition for Patnaik's grade II MCTs and Kiupel's low-grade lesions (OR = 2.3, 95% CI 1.478-3.597; OR = 17.1, 95% CI 3.093-94.377, respectively). French bulldogs had a higher risk to grade III MCTs (OR = 7.9, 95% CI 2.381-26.072). Pit bulls had a predisposition to grade III MCTs and Kiupel's high-grade tumors (OR = 4.4, 95% CI 1.221-16.1 and OR = 4.962, 95% CI 1.362-18.077, respectively). Bull terriers (OR = 12.7, 95% CI 2.098-76.818) presented higher risk for having low-grade MCTs. The perigenital area and trunk exhibit a greater risk for high grading lesion (OR = 6.6, 95% CI 2.679-16.334; OR = 1.9, 95% CI 1.028-3.395, respectively) and the limbs had a predisposition to grade II tumor (OR = 1.6, 95% CI 1.134-2.395). A decreased risk of having MCT was seen in older dogs (from 7-10 years to 11-18 years) compared to that in the reference group (4-6 years). Conclusion: When comparing to canine skin tumors, this study showed a relationship between MCT histological grading and the risk factors, age, breed, and topography of canine MCTs. The variations noted in the clinical presentation of MCTs amongst predisposed dog breeds reinforces the relevance of the genetic background in MCTs carcinogenesis

Características físicas e químicas de frutos de pupunheira no estado do Pará.

O objetivo deste estudo foi caracterizar física e físico-quimicamente frutos de 21 matrizes de pupunheira (Bactris gasipaes Kunth), visando a obter subsídios que permitam avançar com o programa de melhoramento genético, em especial para características da polpa do fruto. Os frutos provenientes de diferentes genótipos foram caracterizados quanto à dimensão dos frutos e caroço, umidade, proteínas, lipídeos, cinzas, fibras e carotenoides totais. Os resultados obtidos para as diferentes variáveis analisadas demonstraram diferenças entre os frutos obtidos de diferentes genótipos. A análise de proteínas apresentou valores que variaram de 4,20 a 6,79%, com destaque para a matriz B04-P20, que apresentou o maior valor. Para lipídeos, os teores variaram bastante, com valores entre 8,25 e 40,83%, destacando-se a matriz B02-P30 com o maior teor de lipídeos. Os teores de carotenoides totais das matrizes de pupunheira variaram de 8,02 a 124,90µg/g, com destaque para as matrizes B02-P30 (124,90µg/g) e B05-P45 (123,04µg/g), indicando que a pupunha pode contribuir de maneira importante na ingestão de antioxidantes na dieta. De maneira geral, as análises físicas e físico-químicas dos frutos mostraram diferenças significativas entre as matrizes para os caracteres estudados, evidenciando ser um conjunto geneticamente promissor para a prática da seleçã

Zebrafish xenografts as a fast screening platform for bevacizumab cancer therapy

Cancer is the second leading cause of death in the world. Given that cancer is a highly individualized disease, predicting the best chemotherapeutic treatment for individual patients can be difficult. Ex vivo models such as mouse patient-derived xenografts (PDX) and organoids are being developed to predict patient-specific chemosensitivity profiles before treatment in the clinic. Although promising, these models have significant disadvantages including long growth times that introduce genetic and epigenetic changes to the tumor. The zebrafish xenograft assay is ideal for personalized medicine. Imaging of the small, transparent fry is unparalleled among vertebrate organisms. In addition, the speed (5-7 days) and small patient tissue requirements (100-200 cells per animal) are unique features of the zebrafish xenograft model that enable patient-specific chemosensitivity analyses.info:eu-repo/semantics/publishedVersio

Latent cluster analysis of ALS phenotypes identifies prognostically differing groups

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001). CONCLUSION The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research

Less Minimal Flavour Violation

We consider the approximate U(2)^3 flavour symmetry exhibited by the quark sector of the Standard Model and all its possible breaking terms appearing in the quark Yukawa couplings. Taking an Effective Field Theory point of view, we determine the current bounds on these parameters, assumed to control the breaking of flavour in a generic extension of the Standard Model at a reference scale Lambda. In particular, a significant bound from epsilon'/epsilon is derived, which is relevant to Minimal Flavour Violation as well. In the up-quark sector, the recently observed CP violation in D -> pi+ pi-, K+ K- decays might be accounted for in this generic framework, consistently with any other constraint.Comment: 15 pages, 1 figur