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

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

Starch/Poly(glycerol-adipate) Nanocomposites: A Novel Oral Drug Delivery Device

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Biocompatible and bio-based materials are an appealing resource for the pharmaceutical industry. Poly(glycerol-adipate) (PGA) is a biocompatible and biodegradable polymer that can be used to produce self-assembled nanoparticles (NPs) able to encapsulate active ingredients, with encouraging perspectives for drug delivery purposes. Starch is a versatile, inexpensive, and abundant polysaccharide that can be effectively applied as a bio-scaffold for other molecules in order to enrich it with new appealing properties. In this work, the combination of PGA NPs and starch films proved to be a suitable biopolymeric matrix carrier for the controlled release preparation of hydrophobic drugs. Dynamic Light Scattering (DLS) was used to determine the size of drug-loaded PGA NPs, while the improvement of the apparent drug water solubility was assessed by UV-vis spectroscopy. In vitro biological assays were performed against cancer cell lines and bacteria strains to confirm that drug-loaded PGA NPs maintained the effective activity of the therapeutic agents. Dye-conjugated PGA was then exploited to track the NP release profile during the starch/PGA nanocomposite film digestion, which was assessed using digestion models mimicking physiological conditions. The collected data provide a clear indication of the suitability of our biodegradable carrier system for oral drug delivery.Peer reviewedFinal Published versio

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

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

The relationship between chronic type III acromioclavicular joint dislocation and cervical spine pain

<p>Abstract</p> <p>Background</p> <p>This study was aimed at evaluating whether or not patients with chronic type III acromioclavicular dislocation develop cervical spine pain and degenerative changes more frequently than normal subjects.</p> <p>Methods</p> <p>The cervical spine of 34 patients with chronic type III AC dislocation was radiographically evaluated. Osteophytosis presence was registered and the narrowing of the intervertebral disc and cervical lordosis were evaluated. Subjective cervical symptoms were investigated using the Northwick Park Neck Pain Questionnaire (NPQ). One-hundred healthy volunteers were recruited as a control group.</p> <p>Results</p> <p>The rate and distribution of osteophytosis and narrowed intervertebral disc were similar in both of the groups. Patients with chronic AC dislocation had a lower value of cervical lordosis. NPQ score was 17.3% in patients with AC separation (100% = the worst result) and 2.2% in the control group (p < 0.05). An inverse significant nonparametric correlation was found between the NPQ value and the lordosis degree in the AC dislocation group (p = 0.001) wheras results were not correlated (p = 0.27) in the control group.</p> <p>Conclusions</p> <p>Our study shows that chronic type III AC dislocation does not interfere with osteophytes formation or intervertebral disc narrowing, but that it may predispose cervical hypolordosis. The higher average NPQ values were observed in patients with chronic AC dislocation, especially in those that developed cervical hypolordosis.</p

Carotid plaque detection improves the predictive value of CHA2DS2-VASc score in patients with non-valvular atrial fibrillation::The ARAPACIS Study

BACKGROUND AND AIMS: Vascular disease (VD), as assessed by history of myocardial infarction or peripheral artery disease or aortic plaque, increases stroke risk in atrial fibrillation (AF), and is a component of risk assessment using the CHA2DS2-VASc score. We investigated if systemic atherosclerosis as detected by ultrasound carotid plaque (CP) could improve the predictive value of the CHA2DS2-VASc score. METHODS: We analysed data from the ARAPACIS study, an observational study including 2027 Italian patients with non-valvular AF, in whom CP was detected using Doppler Ultrasonography. RESULTS: VD was reported in 351 (17.3%) patients while CP was detected in 16.6% patients. Adding CP to the VD definition leaded to higher VD prevalence (30.9%). During a median [IQR] follow-up time of 36months, 56 (2.8%) stroke/TIA events were recorded. Survival analysis showed that conventional VD alone did not increase the risk of stroke (Log-Rank: 0.009, p=0.924), while addition of CP to conventional VD was significantly associated to an increased risk of stroke (LR: 5.730, p=0.017). Cox regression analysis showed that VD+CP was independently associated with stroke (HR: 1.78, 95% CI: 1.05-3.01, p=0.0318). Reclassification analysis showed that VD+CP allowed a significant risk reclassification when compared to VD alone in predicting stroke at 36months (NRI: 0.192, 95% CI: 0.028-0.323, p=0.032). CONCLUSIONS: In non-valvular AF patients the addition of ultrasound detection of carotid plaque to conventional VD significantly increases the predictive value of CHA2DS2-VASc score for stroke

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