Involvement of smad7 in inflammatory diseases of the gut and colon cancer

In physiological conditions, the human intestinal mucosa is massively infiltrated with various subsets of immune cells, the activity of which is tightly regulated by several counter-regulatory factors. One of these factors is transforming growth factor-beta 1 (TGF-beta 1), a cytokine produced by multiple cell types and targeting virtually all the intestinal mucosal cells. Binding of TGF-beta 1 to its receptors triggers Smad2/3 signaling, thus culminating in the attenuation/suppression of immune-inflammatory responses. In patients with Crohn's disease and patients with ulcerative colitis, the major human inflammatory bowel diseases (IBD), and in mice with IBD-like colitis, there is defective TGF-beta 1/Smad signaling due to high levels of the intracellular inhibitor Smad7. Pharmacological inhibition of Smad7 restores TGF-beta 1 function, thereby reducing inflammatory pathways in patients with IBD and colitic mice. On the other hand, transgenic over-expression of Smad7 in T cells exacerbates colitis in various mouse models of IBD. Smad7 is also over-expressed in other inflammatory disorders of the gut, such as refractory celiac disease, necrotizing enterocolitis and cytomegalovirus-induced colitis, even though evidence is still scarce and mainly descriptive. Furthermore, Smad7 has been involved in colon carcinogenesis through complex and heterogeneous mechanisms, and Smad7 polymorphisms could influence cancer prognosis. In this article, we review the data about the expression and role of Smad7 in intestinal inflammation and cancer

KRAS testing in metastatic colorectal carcinoma: challenges, controversies, breakthroughs, and beyond

Metastatic colorectal cancer harboring a mutation in codon 12 or 13 of the KRAS gene does not benefit from therapy with antibodies targeting the epidermal growth factor receptor (EGFR). The implementation of community KRAS testing is generating a rapid flow of new data that have implications for the pathologist and testing guidelines, besides the physician. Therefore, it seems timely to draw together the threads of this large body of information in order that pathologists can be knowledgeable partners in the multidisciplinary process of targeted cancer therapy, and to help refine current testing guidelines. This review addresses: (1) the most relevant methodological and technical aspects of KRAS testing in terms of sample site (primary/metastatic), test specimens (resection/biopsy/cytology), and the diverse molecular methods available; (2) issues related to daily practice, namely the timing of the test, its turnaround time and the quality control procedures; and (3) the evidence related to the relationship between KRAS genetic intratumoral heterogeneity, clinical sensitivity of mutational detection tools and anti-EGFR treatment outcome. Hopefully, in the near future, elucidation of the potential of biomarker panels, and of the mechanisms underlying primary and acquired resistance to anti-EGFR therapy will refine even further personalized treatment regimes for patients with metastatic colorectal cancer

Psychological Outcomes in Children and Early Adolescents With Type 1 Diabetes Following Pediatric Diabetes Summer Camp: A 3-Month Follow-Up Study

Objective: The aim of this study was to assess general psychosocial adjustment to diabetes and perceived disease management among patients with type 1 diabetes (T1D) and their parents before and after patients' participation in a diabetes summer camp. Methods: In this follow-up study, 20 children and adolescents with T1D (eight boys; mean age = 11.01 ± 0.94 years; mean diabetes duration = 3.02 ± 2.27) attending a southern Italian diabetic center, along with their parents, were assessed prior to and 3 months after the youths participated in a 1 week camp-based intervention involving didactic and interactive child-centered education and recreational activities. Patients and their parents completed measures assessing patients' quality of life and strategies employed by patients to cope with pain. Patients also completed measures evaluating their diabetes psychosocial adjustment, diabetes self-efficacy management, and illness perception; also, their parents completed measures of caregivers' perceived diabetes burden and treatment satisfaction. Youths' glycated hemoglobin (HbA1c) and standardized body mass index (z-BMI) values were also assessed. Within-subjects repeated-measures analyses of variance evaluated pre- and post-camp changes. Results: Camp attendance showed no beneficial effects on glycemic control, as indicated by HbA1c values both before (7.02%) and after (7.28%) camp being lower than 7.5%. HbA1c values were found to have increased after camp (pre-camp = 7.02%, post-camp = 7.28%; p = 0.010), but since they still fell within an acceptable range, they did not reveal clinically relevant changes in glycemic control. No substantial significant improvement in psychosocial measures was observed in children or parents (all p > 0.05). According to the parents' evaluation, social support-seeking as a patient pain-coping strategy was slightly increased (p = 0.044) after attending the camp. Conclusions: This study does not provide empirical evidence of benefits of participating in a diabetes camp for either patients or their parents. These findings suggest that healthcare providers rethink such camps as an experience for youths with T1D that actively involves parents and that includes both youth- and parent-focused psychological interventions

Body Image Problems in Individuals with Type 1 Diabetes: A Review of the Literature

Despite type 1 diabetes' (T1D) potential influence on adolescents' physical development, the occurrence of body image problems of adolescents with diabetes remains unclear. No research synthesis has yet addressed this issue. This study aims to systematically evaluate the empirical evidence concerning body image in individuals with T1D in order to provide an overview of the existing literature. Using PRISMA methodology, 51 relevant studies that fulfilled the eligibility criteria were found, the majority of them (N = 48) involving youth. The findings varied across studies: 17 studies indicated that in youth with T1D, body dissatisfaction was common and that body concerns were generally greater in youth with T1D than in controls; nine studies did not find any differences in body image problems between participants with and without T1D; three studies described higher body satisfaction in youth with diabetes than in controls; and three studies reported mixed results. Body concerns in individuals with T1D were often found to be associated with negative medical and psychological functioning. The variability and limits in assessment tools across studies, the overrepresentation of female subjects, and the fact that most research in this field is based on cross-sectional data are stressed in the interpretation of these mixed findings. Future research directions that could improve the understanding of body image concerns and clinical implications are discussed

Lesions associated with mineral deposition in the lymph nodes and lungs of cattle: a case-control study of environmental health hazard.

This report focuses on the state of health of the cattle raised in the district of Taranto - city of Italy rated as environmentally at risk. Representative samples of lungs, bronchial and mediastinal lymph nodes of cattle from district of Taranto's slaughterhouses were collected. After a macroscopic examination, samples with marked lesions were processed for light microscopy. Samples were also observed with polarized light microscopy, scanning electron microscopy and with microanalysis. The macroscopic examination revealed that 60 out of 183 samples showed marked lesions. Lung alterations were characterized by thickening of the alveolar septa and by the latter's modifying action on the alveolar spaces, foci of fibrosis and bronchopulmonary inflammation. For 51 out of the 60 samples observed, the histological examination confirmed the presence of pneumoconiosis and lymph nodal anthracosis. Energy-dispersive X-ray microanalysis of lung samples identified a wide range of elements including silicon, aluminium, titanium, iron, carbon and small amount of the other metals. In the lymph-nodes the same kind of metals with a different levels of distribution was observed. Our survey on cattle farmed in areas at high risk of pollution may be helpful to the estimation of the exposure risk for man to environmental contaminants and to the evaluation of the occurrence of the pathological manifestations as well

Prevalence of disordered eating behaviors in adolescents with type 1 diabetes: Results of multicenter Italian Nationwide study

Objective: To assess the prevalence of disordered eating behaviors (DEBs) in a large sample of Italian adolescents with type 1 diabetes and to explore potential demographic, clinical, and psychological differences (understood as emotional and behavioral problems) among adolescents with and without DEBs. Method: Adolescents (11–19 years) with type 1 diabetes completed the Diabetes Eating Problems Survey-revised (DEPS-r) and the Youth Self Report (YSR). Demographic and clinical data were also collected. Results: Of 690 adolescents with type 1 diabetes (mean age 14.97 ± 1.81, n = 337 girls) assessed in this study, 28.1% (21% boys, 35% girls) were DEPS-r positive (score ≥ 20). Girls had higher DEPS-r total scores (p <.0001, d =.42) than boys, although no age differences were found in mean DEPS-r total scores (p =.961). In both genders, adolescents with DEBs had significantly higher zBMI (p <.0001, d =.52) and HbA1c values (p <.0001, d =.54) and showed more emotional and behavioral problems (both as internalizing and externalizing problems) than those without DEBs (all p <.0001). These differences were largely confirmed in all age groups. Adolescents reporting insulin misuse had higher HbA1c values (p =.001, d =.26), higher DEPS-r mean scores (p <.0001, d = 1.07), and greater psychological problems (all p <.001) than those who did not. Discussion: DEBs are prevalent among adolescents with type 1 diabetes, and those with eating problems showed adverse clinical and psychological conditions. Routine screening for DEBs and of general psychological condition should be a fundamental part of diabetes care, especially during adolescence. Public significance statement: This nationwide study indicated that DEBs are common in adolescents with T1D, and those suffering from them show poorer clinical conditions and higher emotional and behavioral problems. As such, it offers important contributions for those working with EDs and in the T1D field, as it provides a deeper understanding of the co-occurring DEBs–emotional/behavioral problems in youths with T1D and highlights the importance of continuous monitoring of their psychological condition by a multidisciplinary team

Eating Problems in Youths with Type 1 Diabetes During and After Lockdown in Italy: An 8-Month Follow-Up Study

Eighty-five youths with T1D and 176 controls aged 8–19 years were asked to complete online questionnaires (ChEAT and EAT-26) measuring disordered eating behaviors (DEBs) during (baseline) and after (8-month follow-up) the lockdown. DEB symptoms in all participants (especially younger than 13 years), glycemic control, and zBMI were found unchanged from baseline to follow-up (all p >.05). After 8 months, the ChEAT/EAT-26 critical score frequency decreased significantly in controls (p =.004), as was the score for the ChEAT/EAT-26’s Oral Control subscale in both groups (T1D: p =.005; controls: p =.01). Participants with T1D, especially those older than 13 years, had higher ChEAT/EAT-26 Dieting scores (p =.037) and lower ChEAT/EAT-26 Oral Control scores (p =.046) than controls. Unchanged DEB symptoms suggest that the COVID-19 restrictions did not significantly affect participants’ eating behaviors and that a general adaptation to the challenges of lockdown and other pandemic containment measures occurred in both T1D and control participants

Approach to cytological indeterminate thyroid nodules.

The indeterminate thyroid nodules diagnosed by fine-needle aspiration cytology (FNAC)represents a problem for both cytopathologists and clinicians. The former sometimes use this diagnostic category as a sort of basket, putting in cases that they do not know exactly how to classify. The latter are faced with a highly variable risk of malignancy and consequently the management remains a challenge. On the histopathological side, the new WHO classification of tumors of the thyroid introduced the concept of tumors with uncertain and low malignant potential, and the concept of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), whose prognosis and management are still to be completely elucidated. While the risk of malignancy of the indeterminate diagnostic category has decreased due to the re-classification of certain types of papillary thyroid carcinomas of the follicular variant into a low malignant potential form (the NIFTP), cases diagnosed cytologically as indeterminate will probably increase in the future to avoid false positive diagnosis. Thus, the indeterminate thyroid diagnostic category still remains a challenge, both at the diagnostic level and for its management. The new version of the Bethesda system for reporting thyroid cytopathology suggests managing these patients with a repeat FNA, diagnostic lobectomy and/or molecular testing

Disordered eating behaviors in youths with type 1 diabetes during COVID-19 lockdown: an exploratory study

Background: Recent research indicates that patients with type 1 diabetes (T1D) are at higher risk for disordered eating behaviors (DEBs) than their peers without diabetes. The present study aimed to explore the prevalence of DEBs in a sample of Italian children and adolescents with T1D and in matched-pair healthy controls during the COVID-19 lockdown. Methods: In a cross-sectional study, 138 children and adolescents with T1D (aged 8.01–19.11 years, 65 boys) attending a Southern Italian diabetic service and 276 age- and gender-matched healthy peers voluntarily completed an online survey about eating behaviors (ChEAT and EAT-26), anthropometric characteristics, and clinical characteristics. Results: 8.69% (N = 12) of participants with T1D and 13.4% (N = 37) of controls had ChEAT/EAT-26 scores indicating presence of DEBs, with no differences between patients—whether children (total ChEAT score F(1, 157) =.104, p =.748) or adolescents (total EAT-26 score F(1, 255) =.135, p =.731)—and healthy peers. zBMI values were lower than those measured in the latest diabetes visit (p <.0001), while HbA1c values remained unchanged (p =.110). In both groups, adolescents had lower Oral Control scores than children (T1D: F(1, 138) = 20.411, p <.0001, η2 =.132, controls: F(1, 276) = 18.271, p <.0001, η2 =.063); additionally, gender (female) and age were found to be significant predictors of several ChEAT/EAT-26 scores. Conclusions: This exploratory study suggested that children and adolescents with T1D did not experience more DEB symptoms during the COVID-19 lockdown compared to healthy controls. Results revealed DEBs as more of a female adolescent developmental issue rather than a result of the challenges of living with a chronic illness under quarantine measures. Possible effects of parental pressure on their children’s eating behaviors in the context of home confinement and of using a non-diabetes-specific measure to assess DEBs are discussed