Sheep α-globin gene sequences: Implications for their concerted evolution and for the down-regulation of the 3' genes

In sheep as in man and most other mammals, there are two α-globin genes (Iα and IIα), which are expressed at different levels, the upstream gene being the most efficient. In α-globin gene triplication and quadruplication, this trend is confirmed, i.e., the α-chain output of the downstream genes progressively decreases. In this study, we have determined the complete sequence of the cDNAs and of both the introns in a triple-α haplotype in which each gene could be recognized for the presence of distinct alleles. The sequence analysis reveals that the bodies of the three α-globin genes are essentially identical (99.9% homology) and moreover indicates that the down-regulation of additional α-globin genes in sheep is not the effect of sequence variation from the Cap to the Poly(A) addition sites. This striking similarity among α-genes is higher than that seen in other mammals and is probably sustained by particularly efficient mechanisms of gene conversion and cross-over fixation

Recurrence of gastrointestinal and extra-intestinal symptoms in celiac patients affected by nickel allergic contact mucositis: when proper gluten-free diet is not enough

BACKGROUND AND AIM: Nickel (Ni) is a metal widely present in nature and the prevalence of Ni allergy is increasing. Allergic contact mucositis (MAC) induced by Ni-rich foods is often responsible for IBS-like disorders and it can be diagnosed by means of a Ni oral mucosa patch test (omPT). It has been observed that, after several months of correct gluten-free diet (GFD), many celiac disease (CD) patients show a recrudescence of gastrointestinal and extra-intestinal symptoms, although serological and histological remission has been achieved. This can be due to a Ni load induced by GFD: a greater consumption of Ni-rich foods (e.g. corn) would lead to a consequent intestinal sensitization to Ni in predisposed subjects. Our study aimed to assess the role played by Ni in the recurrence of symptoms in CD subjects after strict GFD. MATERIAL AND METHODS: Twenty celiac patients (all female, age 23-65 yrs) in serological and histological remission after at least 12 months of GFD have been consecutively included: they all were complaining recurrence gastrointestinal and extra-intestinal symptoms. Subjects with organic gastrointestinal pathologies were excluded. A symptom questionnaire (GSRS modified according to the Salerno Experts' Criteria) has been administered to all patients in 4 stages: T0 (during free diet - active CD); T1 (after 12 months of GFD - CD remission); T2 (during GFD - recurrence of symptoms); T3 (during GFD and after 3 months of low-Ni diet). Ni omPT was performed at T2. Statistical analysis was performed using Wilcoxon signed rank test. RESULTS: All 20 patients showed positive Ni omPT, with local and/or systemic alterations confirming Ni ACM diagnosis. The analysis obtained by comparing T2-T3 showed p-value <0.01 for: abdominal pain, bloating, swelling, increased number of evacuations, dermatitis, asthenia; p-value values <0.05 for: heartburn, acid regurgitation, borborygmus, flatulence, loose stools, urgent need for defecation, headache. The other variables were statistically not significant. CONCLUSIONS: Our data suggest that gastrointestinal and extra-intestinal symptoms observed in CD subjects after prolonged and correct GFD may be due to the necessary dietary change and an increased Ni intake. Specifically, these patients developed Ni MAC, diagnosed by specific Ni omPT. We also observed that regression of symptoms may occur after a proper low-Ni diet. We can conclude that GFD may lead to an increased consumption of Ni-rich foods and this could explain the recurrence of apparently gluten-dependent symptoms

Impact of prior antibiotic use in primary care on escherichia coli resistance to third generation cephalosporins. A case-control study

Research is lacking on the reversibility of antimicrobial resistance (AMR). Thus, we aimed to determine the influence of previous antibiotic use on the development and decay over time of third generation cephalosporin (3GC)-resistance of E. coli. Using the database of hospital laboratories of the Autonomous Province of Bolzano/Bozen (Italy), anonymously linked to the database of outpatient pharmaceutical prescriptions and the hospital discharge record database, this matched case-control study was conducted including as cases all those who have had a positive culture from any site for 3GC resistant E. coli (3GCREC) during a 2016 hospital stay. Data were analyzed by conditional logistic regression. 244 cases were matched to 1553 controls by the date of the first isolate. Male sex (OR 1.49, 95% CI 1.10–2.01), older age (OR 1.11, 95% CI 1.02–1.21), the number of different antibiotics taken in the previous five years (OR 1.20, 95% CI 1.08–1.33), at least one antibiotic prescription in the previous year (OR 1.92, 95% CI 1.36–2.71), and the diagnosis of diabetes (OR 1.57, 95% CI 1.08–2.30) were independent risk factors for 3GCREC colonization/infection. Patients who last received an antibiotic prescription two years or three to five years before hospitalization showed non-significant differences with controls (OR 0.97, 95% CI 0.68–1.38 and OR 0.85, 95% CI 0.59–1.24), compared to an OR of 1.92 (95% CI 1.36–2.71) in those receiving antibiotics in the year preceding hospitalization. The effect of previous antibiotic use on 3GC-resistance of E. coli is highest after greater cumulative exposure to any antibiotic as well as to 3GCs and in the first 12 months after antibiotics are taken and then decreases progressively

Does the length of uniportal video-assisted thoracoscopic lobectomy affect postoperative pain? Results of a randomized controlled trial

Background: Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy has become a common approach for the treatment of early stage lung cancer. Here, we aimed to establish whether the length of uniportal incision could affect postoperative pain and surgical outcomes in consecutive patients undergoing uniportal VATS lobectomy for early stage lung cancer. Methods: This was a unicenter Randomized Control Trial (NCT 03218098). Consecutive patients undergoing uniportal VATS lobectomy for Stage I lung cancer were randomly assigned to a Small Incision group or Long Incision group in 1:1 ratio based on whether patients received a 4 cm or 8 cm incision. The endpoints were to compare the intergroup difference regarding (i) postoperative pain measured by brief pain inventory (BPI) questionnaire (first endpoint); (ii) operative time; (iii) length of chest drainage; (iv) length of hospital stay; (v) postoperative complications; and (vi) pulmonary functional status (secondary endpoints). Results: A total of 48 patients were eligible for the study. Four patients were excluded; the study population included 44 patients: 23 within the Small Incision group, and 21 within the Long Incision group. The 11 BPI scores between the two groups showed no significant difference. Small Incision group presented higher operative time than Long Incision group (138.69 vs. 112.14 minutes; P = 0.0001) while no significant differences were found regarding length of hospital stay (P = 0.95); respiratory complications (P = 0.92); FEV1% (P = 0.63), and 6-Minute Walking Test (P = 0.77). Conclusions: A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. Key points: A larger incision for uniportal VATS lobectomy significantly reduced the operative time due to better exposure of the anatomical structures without increasing postoperative pain or affecting the surgical outcome. To perform a larger incision could be a valuable strategy, particularly in nonexpert hands or when the patient's anatomy or tumor size make exposure of anatomic structures through smaller incisions difficult

Regulatory T cells with multiple suppressive and potentially pro-tumor activities accumulate in human colorectal cancer

Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor. Ex vivo, those Tregs suppressed the proliferation of tumor-infiltrating CD8(+) and CD4(+) T cells. A differential compartmentalization was detected between Helioshigh and Helios(low) Treg subsets (thymus-derived versus peripherally induced): while Helios(low) Tregs were enriched in both sites, only Helios(high) Tregs accumulated significantly and specifically in tumors, displayed a highly demethylated TSDR region and contained high proportions of cells expressing CD39 and OX40, markers of activation and suppression. Besides the suppression of T cells, Tregs may contribute to CRC progression also through releasing IL-17, or differentiating into Tfr cells that potentially antagonize a protective Tfh response, events that were both detected in tumor-associated Tregs. Overall, our data indicate that Treg accumulation may contribute through multiple mechanisms to CRC establishment and progression

Etude d'un épisode photochimique à l'alde d'un modèle méso-échelle et de mesures intensives sur la région de Grenoble

La ville de Grenob le, située au carrefour de trois vallées, est systématiquement soumise à des périodes de smog estival avec de fortes concentrations en ozone (0 3), Au cours de l'été 1999, l'Association pour le contrôle et la préservation de l'air dans la région grenobloise (ASCOPARG) et l'École Polytechnique Fédérale de Lausanne (EPFL) ont mené conjointement -une campagne de mesures en déployant, durant un mois, un réseau de mesures au sol renforcé par des moyens de mesures à la vertical e. Deux périodes d'observations intensives (POl) ont eu lieu, la première fin juillet, et la deuxième dé but août. Les simulations ont été réa lisées pour la première POl (24-27 juill et) avec le modèle METeorological PHOtochem istry MODel (METPHOMOD) utilisant le mécanisme chimique Regional Atmospheric Chemistry Mechanism (RACM). Une technique de nesting one-way est utilisée avec une grande grille de 198 km de côté et une résolution de 6 x 6 km et une petite grille de 78 x 68 km avec une résolution de 2 x 2 km. À la verticale, 24 niveaux sont pris en compte jusqu'à 8 000 m. Au sol, les champs de vents, les concentrations d'03 et de dioxyde d'azote (NOx) sont bien reproduits par le modèle et mettent en évidence le déplacement horizontal du panache d'03 vers le sud avec un maximum d'03 de 95 ppb. Pour la verticale, les mesures et les simulations montrent une couche de mélange convective (CMC) supérieure à 2 000 rn, le transport horizontal du panache dans la CMC et la formation de la couche réservoir d'03' La CMC est donc plus haute en terrain de montagne qu'en plaine. Une stratification verticale spécifique de l'atmosphère, suivant trois couches, a été mise en évidence lors de cet épisode photoch imique sur Grenoble. Une simulation sans émissions sur le petit domaine de calcul a permis d'évaluer la production locale d'03de la ville à 32 ppb, soit un tiers de la concentration maximale mesurée et simulée dans le sud de l'agglomération

Sex and Gender Differences in Ischemic Heart Disease: Endocrine Vascular Disease Approach (EVA) Study Design

Improvements in ischemic heart disease (IHD) management have been unbalanced between sexes, with coronary microvascular dysfunction considered the likely underlying reason. The Endocrine Vascular disease Approach (EVA) is an observational study (Clinicaltrial.gov NCT02737982) aiming to assess sex and gender interactions between coronary circulation, sexual hormones, and platelet function. Consecutive patients with IHD undergoing coronary angiography will be recruited: (1) to assess sex and gender differences in angiographic reperfusion indexes; (2) to evaluate the effects of estrogen/androgen on sex-related differences in myocardial ischemia; (3) to investigate the platelet biology differences between men and women with IHD; (4) to verify sex- and gender-driven interplay between response to percutaneous coronary intervention, platelets, sex hormones, and myocardial damage at baseline and its impact on 12-month outcomes. The integration of sex and gender in this translational project on IHD will contribute to the identification of new targets for further innovative clinical interventions

Relationship between low Ankle-Brachial Index and rapid renal function decline in patients with atrial fibrillation: A prospective multicentre cohort study

OBJECTIVE: To investigate the relationship between Ankle-Brachial Index (ABI) and renal function progression in patients with atrial fibrillation (AF). DESIGN: Observational prospective multicentre cohort study. SETTING:Atherothrombosis Center of I Clinica Medica of 'Sapienza' University of Rome; Department of Medical and Surgical Sciences of University Magna Græcia of Catanzaro; Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study. PARTICIPANTS: 897 AF patients on treatment with vitamin K antagonists. MAIN OUTCOME MEASURES: The relationship between basal ABI and renal function progression, assessed by the estimated Glomerular Filtration Rate (eGFR) calculated with the CKD-EPI formula at baseline and after 2 years of follow-up. The rapid decline in eGFR, defined as a decline in eGFR >5 mL/min/1.73 m(2)/year, and incident eGFR<60 mL/min/1.73 m(2) were primary and secondary end points, respectively. RESULTS: Mean age was 71.8±9.0 years and 41.8% were women. Low ABI (ie, ≤0.90) was present in 194 (21.6%) patients. Baseline median eGFR was 72.7 mL/min/1.73 m(2), and 28.7% patients had an eGFR60 mL/min/1.73 m(2), 153 (23.9%) had a reduction of the eGFR <60 mL/min/1.73 m(2). ABI ≤0.90 was also an independent predictor for incident eGFR<60 mL/min/1.73 m(2) (HR 1.851, 95% CI 1.205 to 2.845, p=0.005). CONCLUSIONS: In patients with AF, an ABI ≤0.90 is independently associated with a rapid decline in renal function and incident eGFR<60 mL/min/1.73 m(2). ABI measurement may help identify patients with AF at risk of renal function deterioration

Placing the library at the heart of plagiarism prevention: The University of Bradford experience.

yesPlagiarism is a vexed issue for Higher Education, affecting student transition, retention and attainment. This paper reports on two initiatives from the University of Bradford library aimed at reducing student plagiarism. The first initiative is an intensive course for students who have contravened plagiarism regulations. The second course introduces new students to the concepts surrounding plagiarism with the aim to prevent plagiarism breaches. Since the Plagiarism Avoidance for New Students course was introduced there has been a significant drop in students referred to the disciplinary programme. This paper discusses the background to both courses and the challenges of implementation

Effect of Canagliflozin on Renal Threshold for Glucose, Glycemia, and Body Weight in Normal and Diabetic Animal Models

Background: Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM). Methods: 14 C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; 3 H-2-deoxy-D-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RTG) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity. Results: Treatment with canagliflozin 1 mg/kg lowered RT G from 415612 mg/dl to 94610 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RTG. Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c) and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio