Free-living use of artificial pancreas for children with type 1 diabetes: systematic review

BACKGRAUND: A closed-loop glucose control system or artificial pancreas consists of three components a Continuous Glucose Monitor (CGM), infusion pumps to deliver hormone(s) and a sophisticated dosing algorithm to control hormone delivery. In the past years, numerous studies with closed-loop system devices were conducted with gradual shift to out-of-hospital environment and with lengthening study duration. AIMS: To compare efficacy and safety of closed-loop insulin pump use in children with type 1 diabetes mellitus in compare with conventional insulin treatment (continuous subcutaneous insulin infusion (CSII) with our without CGM) based on randomized control trials data (RCT). METHODS: In the systematic review we have include 28 randomized controlled trials results indexed in PubMed, Medline databases published till 15 June 2017. The efficacy on metabolic control in this study evaluated by the proportion of time within target range (preferably 70 to 180 mg/dl if reported) and mean (median) glucose based on sensor measurements, and the safety evaluated by time in hypoglycemia (below 70 mg/dl if reported). RESULTS: Increased time in range in the night period was observed in all RCT. Only 3 RCT showed decrease of the time in range within 24 h evaluation period. In one RCT the significant positive differences have been shown in the time in range for dual hormone closed-loop glucose control system in compare with insulin-only artificial pancreas. Mean glycaemia and glucose variability changes were not in the same manner in different RCT, both in the night only and in 24 h estimation period. Night hypoglycemia duration decreased in most RCT with closed-loop control in compare with CSII, and increased only in 2 RCT. When all-day estimation period the time in hypoglycemia changed not in the same manner in different RCT. Valuable methodology differences of the glycaemic control estimation within observed RCT brought significant complications in the data analysis and made impossible the results quantitative estimation to prepare a metaanalysis. CONCLUSIONS: Much work has been done to develop effective and safe artificial pancreas, but not all RCTs confirmed advantages of closed-loop glucose control in compare with CSII in children and adolescents in real life. More research with prospective randomized control design required to prove benefits of closed-loop glucose control. Further RCTs should have an uniform methodology for glycemic control assessment and long duration that will allow to use cumulative measures in a closed-loop efficacy estimation (HbA1c)

Circadian tumor infiltration and function of CD8+ T cells dictate immunotherapy efficacy.

The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8 <sup>+</sup> T cells, are important parameters for the control of tumor growth and response to immunotherapy. Here, we show in murine and human cancers that these parameters exhibit circadian oscillations, driven by both the endogenous circadian clock of leukocytes and rhythmic leukocyte infiltration, which depends on the circadian clock of endothelial cells in the tumor microenvironment. To harness these rhythms therapeutically, we demonstrate that efficacy of chimeric antigen receptor T cell therapy and immune checkpoint blockade can be improved by adjusting the time of treatment during the day. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in patients with melanoma and correlate with response to anti-PD-1 therapy. Our data demonstrate the functional significance of circadian dynamics in the tumor microenvironment and suggest the importance of leveraging these features for improving future clinical trial design and patient care

Adaptation and Validation of QUick, Easy, New, CHEap, and Reproducible (QUENCHER) Antioxidant Capacity Assays in Model Products Obtained from Residual Wine Pomace

Evaluation of the total antioxidant capacity of solid matrices without extraction steps is a very interesting alternative for food researchers and also for food industries. These methodologies have been denominated QUENCHER from QUick, Easy, New, CHEap, and Reproducible assays. To demonstrate and highlight the validity of QUENCHER (Q) methods, values of Q-method validation were showed for the first time, and they were tested with products of well-known different chemical properties. Furthermore, new QUENCHER assays to measure scavenging capacity against superoxide, hydroxyl, and lipid peroxyl radicals were developed. Calibration models showed good linearity (R2 > 0.995), proportionality and precision (CV < 6.5%), and acceptable detection limits (<20.4 nmol Trolox equiv). The presence of ethanol in the reaction medium gave antioxidant capacity values significantly different from those obtained with water. The dilution of samples with powdered cellulose was discouraged because possible interferences with some of the matrices analyzed may take place.The autonomous government of Castilla y León (Project BU268A11-2

Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility

Technical aspects and clinical limitations of sperm DNA fragmentation testing in male infertility: a global survey, current guidelines, and expert recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial