Relative impacts of morphological alteration to shorelines and eutrophication on littoral macroinvertebrates in Mediterranean lakes

Development of effective methods for assessing the ecological status of lakes based on littoral benthic fauna has been hampered by the lack of quantitative data on the relative impacts of key pressures on the benthic community. We used variance partitioning at 126 sites belonging to 14 natural Mediterranean lakes to analyze the pure and shared effects of eutrophication, morphological alterations, microhabitat type, lake morphometry and geographic position on the littoral macroinvertebrate community. The spatial arrangement of the sampling sites was responsible for 9.1% of the total variance in littoral benthic community composition, lake morphometry accounted for 4.3% of variation, and microhabitat type accounted for 3.9%. Communities appeared to be affected primarily by morphological alterations to lake shorelines, and their impact was 2.5 times as important as that of eutrophication. The structure of littoral benthic communities was governed by processes acting at several spatial scales from region to lake scale. Thus, several pressures and the various spatial scales at which these act should be taken into account when implementing methods of assessing lake ecological condition based on littoral benthic invertebrates. Region-specific methods for subalpine and volcanic lakes might enhance the validity of assessment of results of morphological alterations and improve management of those water resources

Polymyxins and quinazolines are LSD1/KDM1A inhibitors with unusual structural features

Because of its involvement in the progression of several malignant tumors, the histone lysine-specific demethylase 1 (LSD1) has become a prominent drug target in modern medicinal chemistry research. We report on the discovery of two classes of noncovalent inhibitors displaying unique structural features. The antibiotics polymyxins bind at the entrance of the substrate cleft, where their highly charged cyclic moiety interacts with a cluster of positively charged amino acids. The same site is occupied by quinazoline-based compounds, which were found to inhibit the enzyme through a most peculiar mode because they form a pile of five to seven molecules that obstruct access to the active center. These data significantly indicate unpredictable strategies for the development of epigenetic inhibitors

Histone deacetylase 6 controls Notch3 trafficking and degradation in T-cell acute lymphoblastic leukemia cells

Several studies have revealed that endosomal sorting controls the steady-state levels of Notch at the cell surface in normal cells and prevents its inappropriate activation in the absence of ligands. However, whether this highly dynamic physiologic process can be exploited to counteract dysregulated Notch signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by aberrant Notch signaling, sustained by activating mutations in Notch1 as well as overexpression of Notch3, a Notch paralog physiologically subjected to lysosome-dependent degradation in human cancer cells. Here we show that treatment with the pan-HDAC inhibitor Trichostatin A (TSA) strongly decreases Notch3 full-length protein levels in T-ALL cell lines and primary human T-ALL cells xenografted in mice without substantially reducing NOTCH3 mRNA levels. Moreover, TSA markedly reduced the levels of Notch target genes, including pT alpha, CR2, and DTX-1, and induced apoptosis of T-ALL cells. We further observed that Notch3 was post-translationally regulated following TSA treatment, with reduced Notch3 surface levels and increased accumulation of Notch3 protein in the lysosomal compartment. Surface Notch3 levels were rescued by inhibition of dynein with ciliobrevin D. Pharmacologic studies with HDAC1, 6, and 8-specific inhibitors disclosed that these effects were largely due to inhibition of HDAC6 in TALL cells. HDAC6 silencing by specific shRNA was followed by reduced Notch3 expression and increased apoptosis of TALL cells. Finally, HDAC6 silencing impaired leukemia outgrowth in mice, associated with reduction of Notch3 full-length protein in vivo. These results connect HDAC6 activity to regulation of total and surface Notch3 levels and suggest HDAC6 as a potential novel therapeutic target to lower Notch signaling in T-ALL and other Notch3-addicted tumor

Objective Evidence of Gastro-Esophageal Reflux Disease is Rare in Patients with Autoimmune Gastritis.

Background and Aims: Patients with autoimmune atrophic gastritis (AAG) often complain of acid reflux symptoms, despite the evidence of hypo-achlorhydria. Rome IV criteria are used to define functional esophageal disorders. Our aim was to characterize gastroesophageal reflux disease (GERD) phenotypes in patients with AAG. Methods: Between 2017-2018, 172 AAG patients were evaluated at Gastro-Oncology outpatient clinic of University of Padua. Of them, 38 patients with reflux symptoms underwent high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH). Seventy-six AAG consecutive patients asymptomatic for gastroesophageal reflux were selected as age and gender matched controls. Serum biomarkers (pepsinogens, gastrin-17 and Helicobacter pylori antibodies), upper endoscopy, histology and clinical data were compared. Results: Out of 38/172 (22%) AAG patients with reflux symptoms, 2/38 had a GERD diagnosis based on abnormal esophageal acid exposure and 6/38 had a major motility disorder (i.e. outflow obstruction). Among the 30/38 patients with normal endoscopic findings, 9/30 had reflux hypersensitivity, 19 functional heartburn, 1 functional globus, 1 functional chest pain according to the Rome IV criteria. Antral atrophy, advanced corpus atrophy and OLGA stage were more frequent in controls than in reflux patients (p=0.01, p=0.031, p=0.01, respectively). No differences were found for serum biomarkers and symptom presentation. Most of the patients received proton pump inhibitors (PPIs) treatment (87%), with a minority (34%) reporting clinical benefit. Conclusions: Reflux symptoms are relatively common in AAG patients, but a firm diagnosis of GERD is rare (5%), whereas most of the patients have a functional disorder. PPI treatment is mostly clinical ineffective and should not be largely indicated

Autoimmune Atrophic Gastritis: The Role of miRNA in Relation to Helicobacter Pylori Infection

IntroductionMicroRNAs (miRNAs) have been proposed as diagnostic markers, biomarkers of neoplastic progression, and possible therapeutic targets in several immune-mediated diseases. We aimed to analyze the expression profile of selected miRNAs (miR21, miR142, miR223, miR155) in patients with autoimmune atrophic gastritis (AAG), patients with non-autoimmune multifocal atrophic gastritis (MAG), and healthy control subjects (HC).Materials and methodsA total of 103 patients with AAG were consecutively recruited for this study among those attending our gastroenterology outpatient clinic. Participating patients were divided into two groups: primary, not Helicobacter pylori (HP)-associated related AAG (n=57, P-AAG) and HP-associated AAG (n=46, HP-AAG); this subgroup included HP-positive patients, patients with previously reported HP infection, and patients harboring antral atrophy, considered as a stigma of HP infection. We also included 20 sex-age-matched MAG patients and 10 HC. Upper endoscopy with gastric biopsies were performed on each AAG and MAG patient. Circulating levels of miR21-5p, miR142-3p, miR223-3p, and miR155-5p were measured by RT-PCR in all groups.ResultsMiR-21 was over-expressed in P-AAG (p=0.02), HP-AAG (p = 0.04), and MAG (p=0.03) compared with HC. By contrast, miR-142 was more expressed in HC than in HP-AAG (p=0.04) and MAG (p=0.03). MiR-155 showed no significant differences among the four subgroups, while, unexpectedly, miR-223 was overexpressed in HC compared to P-AAG (p=0.01), HP-AAG (p=0.003), and MAG (p<0.001), and was higher in P-AAG than in MAG (p=0.05).ConclusionsMiR-21 was over-expressed in patients with gastric precancerous conditions irrespective of etiology, while in the same subgroups miR-142 and miR-223 were under-expressed compared to healthy controls. Controlling miRNAs up- or downregulation could lead to a breakthrough in treating chronic autoimmune diseases and potentially interfere with the progression to cancer

Kinesiology Students' Perception Regarding Exercise Oncology: A Cross-Sectional Study

none13noDelivering physical activity in cancer care requires knowledge, competence, and specific skills to adapt the exercise program to the patients' specific needs. Kinesiology students could be one of the main stakeholders involved in the promotion of physical activity. This study aims to investigate the knowledge, perception, and competence about exercise in patients with oncological disease in a sample of students attending the Sports Science University. A total of 854 students (13% response rate) from four Italian universities completed the online survey between May and June 2021. About half of the study participants identified the correct amount of aerobic (44%) and strength (54%) activities proposed by the American College of Sports Medicine for patients with cancer. Almost all the students recognized the importance of physical activity in cancer prevention (96%), in the management of cancer before surgery (96%), during anticancer treatments (84%), and after therapies completion (98%). On the contrary, they reported a lack of university courses dedicated to cancer diseases, psychological implications, and prescription of physical activity in all types of cancer prevention. Overall, few students felt qualified in delivered counseling about physical activity and individual or group-based exercise programs in patients with cancer. Logistic regression revealed that the students attending the Master's Degree in Preventive and Adapted Physical Activity were more likely to have knowledge and competence than other students. The present study suggests that kinesiology universities should increase the classes and internships about exercise oncology to train experts with specific skills who are able to adequately support patients in their lifestyle modification.Avancini, Alice; Ferri Marini, Carlo; Sperduti, Isabella; Natalucci, Valentina; Borsati, Anita; Pilotto, Sara; Cerulli, Claudia; Barbieri, Elena; Lucertini, Francesco; Lanza, Massimo; Parisi, Attilio; Grazioli, Elisa; Di Blasio, AndreaAvancini, Alice; Ferri Marini, Carlo; Sperduti, Isabella; Natalucci, Valentina; Borsati, Anita; Pilotto, Sara; Cerulli, Claudia; Barbieri, Elena; Lucertini, Francesco; Lanza, Massimo; Parisi, Attilio; Grazioli, Elisa; Di Blasio, Andre

Kinesiology students' perception regarding exercise oncology: a cross-sectional study

Delivering physical activity in cancer care requires knowledge, competence, and specific skills to adapt the exercise program to the patients' specific needs. Kinesiology students could be one of the main stakeholders involved in the promotion of physical activity. This study aims to investigate the knowledge, perception, and competence about exercise in patients with oncological disease in a sample of students attending the Sports Science University. A total of 854 students (13% response rate) from four Italian universities completed the online survey between May and June 2021. About half of the study participants identified the correct amount of aerobic (44%) and strength (54%) activities proposed by the American College of Sports Medicine for patients with cancer. Almost all the students recognized the importance of physical activity in cancer prevention (96%), in the management of cancer before surgery (96%), during anticancer treatments (84%), and after therapies completion (98%). On the contrary, they reported a lack of university courses dedicated to cancer diseases, psychological implications, and prescription of physical activity in all types of cancer prevention. Overall, few students felt qualified in delivered counseling about physical activity and individual or group-based exercise programs in patients with cancer. Logistic regression revealed that the students attending the Master's Degree in Preventive and Adapted Physical Activity were more likely to have knowledge and competence than other students. The present study suggests that kinesiology universities should increase the classes and internships about exercise oncology to train experts with specific skills who are able to adequately support patients in their lifestyle modification

Clinical prognostic factors for older people: A systematic review and meta-analysis

Objective: To explore the accuracy and precision of prognostic tools used in older people in predicting mortality, hospitalization, and nursing home admission across different settings and timings. Design: Systematic review and meta-analysis of prospective and retrospective studies. Data sources: A systematic search from database inception until 01st February 2023 was run in Medline, Embase, Cinhal, Cochrane Library. Eligibility criteria: Studies were eligible if they reported accuracy (area under the curve [AUC]) and/or precision (C-index) for the prognostic index in relation to any of the following outcomes: mortality, hospitalization, and nursing home admission. Data extraction and synthesis: Two independent reviewers extracted data. Data were pooled using a random effects model. The risk of bias was assessed with the Quality in Prognosis Studies (QUIPS) tool. If more than three studies for the same setting and time were available, a meta-analysis was performed and evaluated using the GRADE tool; other data were reported descriptively. Results: Among 16,082 studies initially considered, 159 studies with a total of 2398856 older people (mean age: 78 years) were included. The majority of the studies was carried out in hospital or medical wards. In the community setting, only two tools (Health Assessment Tool and the Multidimensional Prognostic Index, MPI) had good precision for long-term mortality. In emergency department setting, Barthel Index had an excellent accuracy in predicting short-term mortality. In medical wards, the MPI had a moderate certainty of the evidence in predicting short-term mortality (13 studies; 11,787 patients; AUC=0.79 and 4 studies; 3915 patients; C-index=0.82). Similar findings were available for MPI when considering longer follow-up periods. When considering nursing home and surgical wards, the literature was limited. The risk of bias was generally acceptable; observed bias was mainly owing to attrition and confounding. Conclusions: Several tools are used to predict poor prognosis in geriatric patients, but only those derived from a multidimensional evaluation have the characteristics of precision and accuracy

Cross-sectional survey evaluating the psychological impact of the COVID-19 vaccination campaign in patients with cancer: The VACCINATE study

The COVID-19 pandemic has profoundly impacted on cancer patients' psychological well-being and clinical status. We assessed the levels of anxiety, depression, and distress and the attitude towards COVID-19 vaccination in cancer patients, accepting vaccination at the Verona University Hospital and Camposampiero Hospital in the Veneto region. Self-reported questionnaires were administered to patients undergoing COVID-19 vaccination between March and May 2021 (first and second dose). Twenty-seven items were investigated: i) demographics/clinical characteristics; ii) anxiety, depression, and distress (Hospital Anxiety and Depression Scale-HADS-and Distress Thermometer-DT); iii) four specific items regarding awareness about infection risks, interference with anticancer treatments, and vaccine side effects. Sixty-two and 57% of the patients who accepted to be vaccinated responded to the survey in the two participating Hospitals, respectively. Mean age was 63 years (SD: 12 years; range 19-94 years), women were slightly more prevalent (57.6%), most participants were married (70%), and either worker or retired (60%). Borderline and clinical levels of anxiety were recorded in 14% and 10% of respondents; borderline and clinical levels of depression in 14% and 8%; and moderate and severe distress levels in 33% and 9%. Overall, there was high confidence that vaccination would reduce the risk of contracting COVID-19 (70%), which would make patients feel less worried about contracting the infection (60%). Fear that vaccine-related side effects would interfere with anticancer treatment and/or global health status was low (10% and 9% for items 3 and 4, respectively) and significantly associated with baseline levels of anxiety, depression, and distress at multivariate analysis. Results did not differ between the Verona and Camposampiero cohorts. During the COVID-19 vaccination campaign, adult cancer patients demonstrated high levels of confidence towards vaccination; baseline levels of anxiety, depression, and distress were the only significant predictors of reduced confidence

Evidence-based tailored nutrition educational intervention improves adherence to dietary guidelines, anthropometric measures and serum metabolic biomarkers in early-stage breast cancer patients: A prospective interventional study

Purpose: The impact of the adherence to dietary guidelines of early-stage breast cancer (EBC) patients on body composition changes during treatment is not entirely defined. This study aimed to evaluate the role of an evidence-based nutrition educational intervention, according to adherence to dietary guidelines, in EBC patients. Methods: This prospective study included EBC patients, candidates for neoadjuvant/adjuvant therapy. Patients received an evidence-based tailored nutrition educational intervention. The adherence to dietary guidelines, anthropometric and dietary assessments, and blood glucose and lipid profile tests were evaluated at baseline and after a 12-months nutritional intervention. Results: Two hundred and forty-three patients were enrolled. At baseline, 38.3% and 23.9% of patients were overweight and obese, weight gain ≥5% (compared to 6-months before enrollment) and central obesity were observed in 47.3% and 52.7% of patients, respectively. Adherence to dietary guidelines was low (median Med-Diet score: 6 [IQR 4-8]). After the nutritional intervention (median follow-up: 22 months [range 12-45]), adherence to dietary guidelines significantly increased (median Med-Diet score: 12 [IQR 8-13]), p < 0.0001). High adherence to dietary guidelines (defines as Med-Diet score ≥10) significantly correlated with: 1) overall weight loss ≥5% (21.8% vs. 2.5%, p = 0.003); 2) median BMI drop (from 25.6 kg/m2 to 24.4 kg/m2, p = 0.003); 3) lower prevalence of central obesity (38.2% vs. 7.2%, p = 0.01); 4) improvement in blood glucose levels and lipid profile. Conclusion: This study suggests that an evidence-based tailored nutrition educational intervention during treatment for EBC significantly increases overall adherence to dietary guidelines, and it improves both anthropometric measures and serum metabolic biomarkers in patients with high adherence