Core outcome set for diabetes after pregnancy prevention across the life span: international Delphi study

Introduction: Mothers with gestational diabetes mellitus (GDM) are at high risk of future diabetes. An active area of research examines health behavior change strategies in women within 5 years of a GDM pregnancy to prevent diabetes after pregnancy. We aimed to develop a core outcome set (COS) to facilitate synthesis and comparison across trials. Research: design and methods Candidate outcomes were identified through systematic review and scored for importance (1–9) by healthcare professionals, researchers, and women with prior GDM through an international two-round electronic-Delphi survey. Outcomes retained required round two scores above prespecified thresholds (≥70% scoring 7–9) or expert panel endorsement when scores were indeterminate. The panel organized the COS by domain. Results: 115 stakeholders participated in the survey and 56 completed both rounds. SD of scores decreased by 0.24 (95%CI 0.21 to 0.27) by round 2, signaling convergence. The final COS includes 19 domains (50 outcomes): diabetes (n=3 outcomes), other related diseases (n=3), complications in subsequent pregnancy (n=2), offspring outcomes (n=3), adiposity (n=4), cardiometabolic measures (n=5), glycemia (n=3), physical activity (n=2), diet (n=4), breast feeding (n=2), behavior change theory (n=5), diabetes-related knowledge (n=2), health literacy (n=1), social support (n=1), sleep (n=1), quality of life (n=1), program delivery (n=4), health economic evaluation (n=2), and diabetes risk screening (n=2). The seven outcomes endorsed by ≥90% were diabetes development and GDM recurrence, attending the postpartum diabetes screening and completing oral glucose tolerance testing and/or other glycemia measures, weight and total energy intake, and health behaviors in general. Among the 15 at the 80%–90% endorsement level, approximately half were specific elements related to the top 7, while the remainder related to diabetes knowledge, personal risk perception, motivation for change, program element completion, and health service use and cost. Conclusion: Researchers should collect and report outcomes from the breadth of domains in the COS

Modeling drying kinetics of thyme (thymus vulgaris l.): theoretical and empirical models, and neural networks

[EN] The drying kinetics of thyme was analyzed by considering different conditions: air temperature of between 40 C and 70 C, and air velocity of 1 m/s. A theoretical diffusion model and eight different empirical models were fitted to the experimental data. From the theoretical model application, the effective diffusivity per unit area of the thyme was estimated (between 3.68 10 5 and 2.12 10 4 s 1). The temperature dependence of the effective diffusivity was described by the Arrhenius relationship with activation energy of 49.42 kJ/mol. Eight different empirical models were fitted to the experimental data. Additionally, the dependence of the parameters of each model on the drying temperature was determined, obtaining equations that allow estimating the evolution of the moisture content at any temperature in the established range. Furthermore, artificial neural networks were developed and compared with the theoretical and empirical models using the percentage of the relative errors and the explained variance. The artificial neural networks were found to be more accurate predictors of moisture evolution with VAR 99.3% and ER 8.7%.The authors acknowledge the financial support from the 'Ministerio de Educacion y Ciencia' in Spain, CONSOLIDER INGENIO 2010 (CSD2007-00016).Rodríguez Cortina, J.; Clemente Polo, G.; Sanjuán Pellicer, MN.; Bon Corbín, J. (2014). Modeling drying kinetics of thyme (thymus vulgaris l.): theoretical and empirical models, and neural networks. Food Science and Technology International. 20(1):13-22. https://doi.org/10.1177/1082013212469614S132220

Does the road to happiness depend on the retirement decision? Evidence from Italy

This study estimates the causal effect of retirement decision on well-being in Italy. To do so, the authors exploit the exogenous variation provided by the changes in the eligibility criteria for pensions that were enacted in Italy in 1995 (Dini’s law) and in 1997 (Prodi’s law, from the names of the prime ministers at the time of their introduction). A sizeable and positive impact of retirement decision is found on satisfaction with leisure time and on frequency of meeting friends. Furthermore, the results are generalized, allowing for the estimation of different moments from different data sources

In silico analyses of metagenomes from human atherosclerotic plaque samples

Background Through several observational and mechanistic studies, microbial infection is known to promote cardiovascular disease. Direct infection of the vessel wall, along with the cardiovascular risk factors, is hypothesized to play a key role in the atherogenesis by promoting an inflammatory response leading to endothelial dysfunction and generating a proatherogenic and prothrombotic environment ultimately leading to clinical manifestations of cardiovascular disease, e.g., acute myocardial infarction or stroke. There are many reports of microbial DNA isolation and even a few studies of viable microbes isolated from human atherosclerotic vessels. However, high-resolution investigation of microbial infectious agents from human vessels that may contribute to atherosclerosis is very limited. In spite of the progress in recent sequencing technologies, analyzing host-associated metagenomes remain a challenge. Results To investigate microbiome diversity within human atherosclerotic tissue samples, we employed high-throughput metagenomic analysis on: (1) atherosclerotic plaques obtained from a group of patients who underwent endarterectomy due to recent transient cerebral ischemia or stroke. (2) Presumed stabile atherosclerotic plaques obtained from autopsy from a control group of patients who all died from causes not related to cardiovascular disease. Our data provides evidence that suggest a wide range of microbial agents in atherosclerotic plaques, and an intriguing new observation that shows these microbiota displayed differences between symptomatic and asymptomatic plaques as judged from the taxonomic profiles in these two groups of patients. Additionally, functional annotations reveal significant differences in basic metabolic and disease pathway signatures between these groups. Conclusions We demonstrate the feasibility of novel high-resolution techniques aimed at identification and characterization of microbial genomes in human atherosclerotic tissue samples. Our analysis suggests that distinct groups of microbial agents might play different roles during the development of atherosclerotic plaques. These findings may serve as a reference point for future studies in this area of research

Ten-year audit of Lichtenstein hernioplasty under local anaesthesia performed by surgical residents

<p>Abstract</p> <p>Background</p> <p>To analyse in a prospective trial the long-term results of Lichtenstein hernioplasty performed by surgical trainees.</p> <p>Methods</p> <p>Training of tension-free Lichtenstein hernia operation was started in our ambulatory unit as an outpatient procedure under local anaesthesia in 1996. After performing 36 teaching operations together with residents and their supervising specialist, 281 patients were operated during 1996-2000 either by one senior consultant (n = 141) or by 12 surgical trainees (n = 140). After 10 years, 247 (88%) patients were available for the long-term assessment.</p> <p>Results</p> <p>After one month postoperatively, the rate of wound infections (consultant 1.1%, residents 0.7%) and hematomas (consultant 1.1%, residents 3.0%) were low and not related to surgeon's training level (ns). Only 6 (2.1%) clinically evident recurrences were found after 10 years: two after specialist repair and four after trainee repair (ns). Although one third of the patients reported some discomfort after 3 and 10 years, 93-95% of the patients were very satisfied with the operation, with no statistical difference between the surgeons.</p> <p>Conclusion</p> <p>Ambulatory open mesh repair under local anaesthesia was a safe operation and the long-term results were acceptable among the patients operated by surgical trainees.</p

Neoantigen-reactive CD8+ T cells affect clinical outcome of adoptive transfer with tumor-infiltrating lymphocytes in melanoma

BACKGROUND: Neoantigen-driven recognition and T cell-mediated killing contribute to tumor clearance following adoptive cell therapy (ACT) with Tumor-Infiltrating Lymphocytes (TILs). Yet, how diversity, frequency, and persistence of expanded neoepitope-specific CD8+ T cells derived from TIL infusion products affect patient outcome is not fully determined. METHODS: Using barcoded pMHC multimers, we provide a comprehensive mapping of CD8+ T cells recognizing neoepitopes in TIL infusion products and blood samples from 26 metastatic mela-noma patients who received ACT. RESULTS: We identified 106 neoepitopes within TIL infusion products corresponding to 1.8% of all predicted neoepitopes. We observed neoepitope-specific recognition to be virtually devoid in TIL infusion products given to patients with progressive disease outcome. Moreover, we found that the frequency of neoepitope-specific CD8+ T cells in TIL infusion products correlated with in-creased survival, and that detection of engrafted CD8+ T cells in post-treatment (i.e. originating from the TIL infusion product) were unique to responders of TIL-ACT. Finally, we found that a transcriptional signature for lymphocyte activity within the tumor microenvironment was associated with a higher frequency of neoepitope-specific CD8+ T cells in the infusion product. CONCLUSIONS: These data support previous case studies of neoepitope-specific CD8+ T cells in melanoma, and indicate that successful TIL-ACT is associated with an expansion of neoepitope-specific CD8+ T cells. FUNDING: NEYE Foundation; European Research Council; Lundbeck Foundation Fellowship; Carlsberg Foundation

A Comparative Exploration of Community Pharmacists' Views on the Nature and Management of Over-the-Counter (OTC) and Prescription Codeine Misuse in Three Regulatory Regimes: Ireland, South Africa and the United Kingdom

Misuse of codeine containing preparations is a public health concern given the potential for associated harms and dependence. This study explores the perspectives of community pharmacists in three regulatory regimes on issues of customer misuse of over-the-counter (OTC) and prescribed codeine. A qualitative design comprising six focus groups (n = 45) was conducted in Ireland, United Kingdom, South Africa. Transcripts were analysed using the constant comparative method of content analysis. Pharmacists described popular codeine-containing products and the need for improved medicine information and warning labels. Issues around legitimate availability of codeine and regulatory status; presence of therapeutic need; difficulties in customer–pharmacist communication; business environments and retail focus were raised. Participants also discussed how they identified customers potentially misusing codeine and difficulties in relationships between pharmacists and prescribers. A number of recommendations were put forward as ways to manage the issues. The study highlights the difficulties encountered by community pharmacists operating under various regulatory regimes when supplying codeine containing preparations in negotiating patient awareness and compliance and potential ways to deal with misuse and dependence

Mutations in Arabidopsis YCF20-like genes affect thermal dissipation of excess absorbed light energy

Plants dissipate excess absorbed light energy as heat to protect themselves from photo-oxidative stress. The Arabidopsis thaliananpq6 mutant affected in thermal dissipation was identified by its partial defect in the induction of nonphotochemical quenching of chlorophyll fluorescence (NPQ) by excess light. Positional cloning revealed that npq6 contains a frameshift mutation caused by a single base-pair deletion in the At5g43050 gene, which encodes a member of the hypothetical chloroplast open reading frame 20 (YCF20) family of proteins with unknown function(s). The YCF20 protein family is mostly conserved in oxygenic photosynthetic organisms including cyanobacteria, eukaryotic algae, and plants. Amino acid sequence comparison identified two other genes in Arabidopsis that encode similar proteins to NPQ6: At1g65420 and At3g56830. These three Arabidopsis proteins have functional chloroplast-targeting transit peptides. Using reverse genetics, a mutant with a T-DNA insertion within the At1g65420 gene was identified and shown to exhibit a low NPQ phenotype similar to that of npq6; therefore, At1g65420 was named NPQ7. In contrast, a knockdown mutant in the At3g56830 gene with lower transcript levels showed wild-type levels of NPQ. The npq6 npq7 double mutant had an additive NPQ defect, indicating that the YCF20 family members in Arabidopsis have overlapping functions affecting thermal dissipation

Secretion of Hepatitis C Virus Envelope Glycoproteins Depends on Assembly of Apolipoprotein B Positive Lipoproteins

The density of circulating hepatitis C virus (HCV) particles in the blood of chronically infected patients is very heterogeneous. The very low density of some particles has been attributed to an association of the virus with apolipoprotein B (apoB) positive and triglyceride rich lipoproteins (TRL) likely resulting in hybrid lipoproteins known as lipo-viro-particles (LVP) containing the viral envelope glycoproteins E1 and E2, capsid and viral RNA. The specific infectivity of these particles has been shown to be higher than the infectivity of particles of higher density. The nature of the association of HCV particles with lipoproteins remains elusive and the role of apolipoproteins in the synthesis and assembly of the viral particles is unknown. The human intestinal Caco-2 cell line differentiates in vitro into polarized and apoB secreting cells during asymmetric culture on porous filters. By using this cell culture system, cells stably expressing E1 and E2 secreted the glycoproteins into the basal culture medium after one week of differentiation concomitantly with TRL secretion. Secreted glycoproteins were only detected in apoB containing density fractions. The E1–E2 and apoB containing particles were unique complexes bearing the envelope glycoproteins at their surface since apoB could be co-immunoprecipitated with E2-specific antibodies. Envelope protein secretion was reduced by inhibiting the lipidation of apoB with an inhibitor of the microsomal triglyceride transfer protein. HCV glycoproteins were similarly secreted in association with TRL from the human liver cell line HepG2 but not by Huh-7 and Huh-7.5 hepatoma cells that proved deficient for lipoprotein assembly. These data indicate that HCV envelope glycoproteins have the intrinsic capacity to utilize apoB synthesis and lipoprotein assembly machinery even in the absence of the other HCV proteins. A model for LVP assembly is proposed