Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, Cochrane Library, and grey literature up to 2 February 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials in non-pregnant outpatients with type 1 diabetes that compared the use of any artificial pancreas system with any type of insulin based treatment. Primary outcome was proportion (%) of time that sensor glucose level was within the near normoglycaemic range (3.9-10 mmol/L). Secondary outcomes included proportion (%) of time that sensor glucose level was above 10 mmol/L or below 3.9 mmol/L, low blood glucose index overnight, mean sensor glucose level, total daily insulin needs, and glycated haemoglobin. The Cochrane Collaboration risk of bias tool was used to assess study quality. RESULTS: 40 studies (1027 participants with data for 44 comparisons) were included in the meta-analysis. 35 comparisons assessed a single hormone artificial pancreas system, whereas nine comparisons assessed a dual hormone system. Only nine studies were at low risk of bias. Proportion of time in the near normoglycaemic range (3.9-10.0 mmol/L) was significantly higher with artificial pancreas use, both overnight (weighted mean difference 15.15%, 95% confidence interval 12.21% to 18.09%) and over a 24 hour period (9.62%, 7.54% to 11.7%). Artificial pancreas systems had a favourable effect on the proportion of time with sensor glucose level above 10 mmol/L (-8.52%, -11.14% to -5.9%) or below 3.9 mmol/L (-1.49%, -1.86% to -1.11%) over 24 hours, compared with control treatment. Robustness of findings for the primary outcome was verified in sensitivity analyses, by including only trials at low risk of bias (11.64%, 9.1% to 14.18%) or trials under unsupervised, normal living conditions (10.42%, 8.63% to 12.2%). Results were consistent in a subgroup analysis both for single hormone and dual hormone artificial pancreas systems. CONCLUSIONS: Artificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes. The main limitations of current research evidence on artificial pancreas systems are related to inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials

Non-Invasive Assessment of Micro- and Macrovascular Function after Initiation of JAK Inhibitors in Patients with Rheumatoid Arthritis

Background: Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients. Methods: Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima–media thickness was assessed with ultrasound. Results: Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities. Conclusions: Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA

Η αξιοποίηση του σχεδίου δράσης (project) ως δυναμικού εργαλείου για την ανάπτυξη δεξιοτήτων σε μαθητές Α’ Λυκείου

Η εν λόγω ποιοτική έρευνα πραγματεύεται τη συμβολή του project ως δυναμικού μεθοδολογικού εργαλείου στην ανάπτυξη δεξιοτήτων σε μαθητές και μαθήτριες Α΄ Λυκείου. Αφού προηγηθεί σύντομη εννοιολογική αποσαφήνιση των κεντρικών εννοιών της έρευνας και βιβλιογραφική ανασκόπηση συναφών ερευνών, τα Ερευνητικά Ερωτήματα που διατυπώνονται, αφορούν τη διερεύνηση της στάσης των εκπαιδευτικών του δείγματος απέναντι στη χρήση της μεθόδου project στην εκπαιδευτική διαδικασία και των απόψεών τους σχετικά με τις δεξιότητες που καλλιεργούνται σε μαθητές και μαθήτριες μέσω αυτής. Τα ερευνητικά ερωτήματα διατυπώθηκαν μετά από Παρατήρηση (συμμετοχική και μη), είκοσι μίας διδακτικών ωρών, σε πραγματικό χρόνο, του σχολικού περιβάλλοντος δύο σχολικών μονάδων (ενός Γενικού Λυκείου επαρχιακής περιοχής και ενός Πρότυπο Λυκείου αστικής περιοχής). Τα ερευνητικά ερωτήματα διερευνώνται μέσω δέκα ημιδομημένων συνεντεύξεων με εκπαιδευτικούς (γυναίκες και άνδρες) των παραπάνω σχολικών μονάδων. Το εμπειρικό υλικό της εργασίας αποτελούν τα απομαγνητοφωνημένα κείμενα των παραπάνω συνεντεύξεων. Τα ερευνητικά ευρήματα αναδεικνύουν τη θετική στάση των εκπαιδευτικών του δείγματος απέναντι στη χρήση του project στο σχολικό πλαίσιο, με την πλειονότητα των εκπαιδευτικών να αναγνωρίζουν σημαντικά μαθησιακά αποτελέσματα από τη χρήση του. Ως προς τις δεξιότητες που καλλιεργούνται μέσω του project, εστιάζουν κυρίως στις εργαλειακές (γνωστικές, μεθοδολογικές, τεχνολογικές και γλωσσικές), και στις διαπροσωπικές (ατομικές και κοινωνικές) και λιγότερο στις συστημικές (οργάνωση, επιχειρησιακό πνεύμα, ηγεσία). Καταλήγοντας, η μελέτη περιλαμβάνει τα συμπεράσματα της ερευνήτριας σε σχέση με τη συμβολή του πρότζεκτ σε εναλλακτικές μορφές διδασκαλίας και αξιολόγησης σε σύγχρονα εκπαιδευτικά περιβάλλοντα και αναδεικνύει το εκπαιδευτικό αίτημα για μαθητοκεντρικές εκπαιδευτικές διαδικασίες.This qualitative research reports on the contribution of project-based learning as a dynamic methodological tool for the development of students’ skills in the first grade of senior high school. After a short definition of the terms, as well as looking at the retrospective bibliography, the research questions that were articulated, concern to the investigation of the attitude of teachers sampled regarding the use of project in the educative process, as well as their beliefs about the competences which students are fostering through this method. The research questions were structured through observation (participant and non-participant) of twenty-two hours in real time in two school environments (one standard provincial high school and one exemplify high school in urban area). The research questions are examined through ten semi-structured interviews from secondary teachers (women and men) of the schools that mentioned above. The empirical material of the thesis consists of the transcriptions of the aforementioned interviews. The research findings point out the positive attitude of the sampled teachers concerning the use of the project method in school environment, with the majority of them acknowledging that important learning outcomes can arise from its use. Regarding the skills which are fostered through the project, it has been proved that they are mostly instrumental (cognitive, methodological, technological, language), interpersonal (individual, social) and less systemic competences (organization, enterprising spirit, leadership). In conclusion, this study includes the investigator’s conclusions regarding the contribution of the project in alternative forms of teaching and assessment in contemporary teaching environments and brings out the educators’ request for student-centered educative processes

Ascorbic acid levels in leukocytes in patients with myelodysplastic syndrome

[…] Aim of this study was to determine ascorbic acid (AA) levels in plasma and white blood cells (WBC) in subjects with MDS, and to investigate possible correlation between AA levels/response upon AA supplementation and MDS features. This could help in clarifying the pathogenesis of MDS and establish a role for AA as a functional and reliable prognostic factor in the treatment and follow-up of subjects with MDS. MDS are a heterogeneous group of haematologic malignancies. The basic defect is a clonal mutation of the stem cell which leads to the evolution of a pathologic clone. The main features of MDS are ineffective haematopoiesis and peripheral cytopenia, although the bone marrow is mostly hypercellular. This is probably mediated through a significant increase of programmed cell death (apoptosis) of blood cells.We studied 50 patients with MDS and 20 control subjects. By means of highperformance liquid chromatography (HPLC) we assayed in plasma and WBC cells(granulocytes and mononuclear) ascorbic acid, total ascorbic acid and percentage of dehydroascorbic acid (DHA) upon total ascorbic acid. Moreover, to study the effect of AA upon a stem cell population, we performed bone marrow cultures in ten patients with MDS and two control subjects. Cultures were supplemented with 0 (control culture), 25 and 50 μΜ ascorbic acid solutions (similar to those observed in plasma) and dithiothreitol (DTT). […][…] Σκοπός της παρούσας μελέτης ήταν ο προσδιορισμός των επιπέδων του ΑΑ στο πλάσμα και τα λευκά αιμοσφαίρια ασθενών με ΜΔΣ, και η ανεύρεση πιθανών συσχετίσεων μεταξύ των επιπέδων του ΑΑ, της απόκρισης στη χορήγηση ΑΑ και των ΜΔΣ, ώστε να καταστεί δυνατή η χρησιμοποίησή του στην περαιτέρω διευκρίνιση του παθογενετικού μοντέλου των ΜΔΣ, στην κλινική πράξη ως εύχρηστος και αξιόπιστος προγνωστικός δείκτης για την παρακολούθηση των ΜΔΣ ή/και στη θεραπεία των ΜΔΣ. Αρχικά μελετήθηκαν τα επίπεδα του ασκορβικού οξέος του πλάσματος και των λευκών αιμοσφαιρίων ασθενών με μυελοδυσπλαστικά σύνδρομα. Με τη μέθοδο της υγρής χρωματογραφίας υψηλής πίεσης (HPLC) διενεργήθηκε προσδιορισμός των επιπέδων του ΑΑ, του ολικού ΑΑ και του ποσοστού δεϋδροασκορβικού οξέος (DHA) επί του ολικού ΑΑ, στο πλάσμα και στα λευκά αιμοσφαίρια (πολυμορφοπύρηνα και μονοπυρηνικά κύτταρα) 50 ασθενών με ΜΔΣ, καθώς και σε 20 υγιείς μάρτυρες. Επίσης, διενεργήθηκαν καλλιέργειες μυελού των οστών σε 10 ασθενείς με ΜΔΣ και 2 υγιείς μάρτυρες, με τις οποίες μελετήθηκε η επίδραση του ΑΑ στη συμπεριφορά των προγονικών αιμοποιητικών κυττάρων. Καλλιέργειες διενεργήθηκαν τόσο χωρίς ασκορβικό οξύ (controls) όσο και μετά την προσθήκη ασκορβικού οξέος σε διάφορες συγκεντρώσεις (25μΜ, 50μΜ, δηλ. συγκεντρώσεις αντίστοιχες του πλάσματος), συνοδεία πάντα της αναγωγικής ουσίας διθειοθρεϊτόλη (DTT). […

Central banks and climate-related disclosures: applying the TCFD’s recommendations

Central banks are increasingly exploring how climate-related financial risks and opportunities impact their price and financial stability mandates, as well as their own operations. They are also beginning to consider how their own actions, and those of the financial institutions they supervise, may contribute to and exacerbate climate change risks and opportunities. Measuring and reporting – or disclosing – climate-related risks and opportunities is a key step in addressing these issues, for both individual institutions and thefinancial system as a whole. With this recognition, the Task Force on Climate-related Financial Disclosures (TCFD) was established, to guide financial institutions to make effective climate disclosures. The development of high quality, reliable, comparable and transparent climate disclosures can support decision-making and enable better understanding of the implications of climate change for central banks. Further, central banks can lead by example by demonstrating lessons learned from their own climate-related disclosures to other financial institutions and by using their influence over the financial rulebook to build the broader system architecture. This paper reviews key elements of the recommendations made by the TCFD – first released in 2017 – and their application by central banks to date. The paper also considers potential enhancements for central banks’ climate disclosures and their possible implications for the wider financial system. The fact that definitions, data, and methodologies for assessing climate-related issues are constantly evolving means that efforts to develop climate-related disclosures will need to follow a progressive approach, with the quantity and quality of disclosures improving in parallel with the progress made in these areas. A flexible framework also suits the distinct operational models and different mandates of central banks. The recommendations made in this paper can be applied to the different central bank portfolios, including monetary and non-monetary and credit facilities, as well as financial stability and physical operations. They are designed to support a wider and more practical application of the TCFD recommendations by central banks

Erythrocytosis Secondary to Testosterone Therapy in a Male with Cryptorchidism: A Case Report

Hypogonadism is association with aging (andropause) can now be recognized earlier and treated with testosterone, thus resulting in the relief of symptoms and better quality of life. However, any patients that are treated with testosterone must be closely monitored in order to avoid the development of sleep apnea, cardiovascular diseases, hepatic dysfunction, plasma lipid disorders, or erythrocytosis, all of which are potential side effects of treatment. Herein, we present a case of erythrocytosis secondary to testosterone treatment in a patient with cryptorchidism. Hemoglobin levels returned to normal soon after phlebotomy and discontinuation of testosterone therapy. Physicians should be aware of the side effects of testosterone replacement therapy and cautiously monitor patients in order to avoid these side effects and cumbersome and expensive laboratory tests

Nailfold Videocapillaroscopy for the Evaluation of Peripheral Microangiopathy in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic and refractory autoimmune joint disease that affects multiple organs. Several methods have been applied for the study of microvascular endothelial dysfunction, which is considered an important component of vascular disease in RA. Implementation of nailfold videocapillaroscopy (NVC) represents a viable choice, as the skin is an easily accessible window for the non-invasive, real-time assessment of subtle microcirculation abnormalities. Although NVC is routinely used in the rheumatology field, especially for the diagnostic workout of Raynaud’s phenomenon, accumulating evidence suggests a role in the evaluation of systemic vasculopathy associated with autoimmune rheumatic disorders. The current paper aims to provide an overview of NVC as a valuable clinical aid for the assessment of peripheral microcirculation in RA. Previous studies characterizing the capillaroscopic pattern in RA are summarized, along with associations with disease-related characteristics. Most available reports have mainly focused on the descriptions of non-specific morphological alterations that may reflect endothelial injury over the course of the disease. Still, the exact pattern of structural and functional capillaroscopic alterations and their clinical significance in RA remains a subject of ongoing research

pH-Sensitive Gold Nanorods for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Delivery and DNA-Binding Studies

A facile experimental protocol for the synthesis of poly(ethylene glycol)-modified (PEGylated) gold nanorods (AuNRs@PEG) is presented as well as an effective drug loading procedure using the non-steroidal anti-inflammatory drug (NSAID) naproxen (NAP). The interaction of AuNRs@PEG and drug-loaded AuNRs (AuNRs@PEG@NAP) with calf-thymus DNA was studied at a diverse temperature revealing different interaction modes; AuNRs@PEG may interact via groove-binding and AuNRs@PEG@NAP may intercalate to DNA-bases. The cleavage activity of the gold nanoparticles for supercoiled circular pBR322 plasmid DNA was studied by gel electrophoresis while their affinity for human and bovine serum albumins was also evaluated. Drug-release studies revealed a pH-sensitive behavior with a release up to a maximum of 24% and 33% NAP within the first 180 min at pH = 4.2 and 6.8, respectively. The cytotoxicity of AuNRs@PEG and AuNRs@PEG@NAP was evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines. The development of AuNRs as an efficient non-steroidal anti-inflammatory drugs (NSAIDs) delivery system for chemotherapy is still in its infancy. The present work can shed light and inspire other research groups to work in this direction

A simple plaster for screening for diabetic neuropathy: A diagnostic test accuracy systematic review and meta-analysis

Objective. Neuropad is an adhesive indicator test applied at the plantar surface of the foot that detects sweating through color change. We examined the diagnostic accuracy of this simple plaster as triage test for screening for clinically relevant diabetic sensorimotor polyneuropathy in adult outpatients with type 1 or type 2 diabetes. Materials/Methods. Systematic review and meta-analysis of diagnostic accuracy studies. We searched Medline, Embase, Cochrane Library, Biosis Previews, Web of Science, Scopus and gray literature without date or language restrictions. We pooled estimates of sensitivity and specificity, and fitted hierarchical models to produce summary receiver operating characteristic curves. We assessed methodological quality of included studies utilizing the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Results. Eighteen studies with 3470 participants met the inclusion criteria. Average sensitivity and specificity were 86% (95% CI 79 to 91) and 65% (95% CI 51 to 76) respectively. Likelihood ratios (LRs) were LR+ = 2.44 and LR- = 0.22. Subgroup analyses per reference standard utilized provided similar estimates. Most studies were at risk of bias for patient selection and use of index or reference test, and had concerns regarding applicability due to patient selection. Conclusion. The adhesive indicator test has reasonable sensitivity and could be used for triage of diabetic neuropathy to rule out foot at risk. Patients who tested positive should be referred to specialized care to establish a definite diagnosis. There is insufficient evidence for effectiveness on patient-important outcomes and cost-effectiveness of implementation in the diagnostic pathway compared with the standard clinical examination. (C) 2014 Elsevier Inc. All rights reserved