Miracle-dz/UniFAR-FTUs huggingface dataset:
Leucine Supplementation Differently Modulates Branched-Chain Amino Acid Catabolism, Mitochondrial Function and Metabolic Profiles at the Different Stage of Insulin Resistance in Rats on High-Fat Diet

The available findings concerning the association between branched-chain amino acids (BCAAs)—particularly leucine—and insulin resistance are conflicting. BCAAs have been proposed to elicit different or even opposite effects, depending on the prevalence of catabolic and anabolic states. We tested the hypothesis that leucine supplementation may exert different effects at different stages of insulin resistance, to provide mechanistic insights into the role of leucine in the progression of insulin resistance. Male Sprague-Dawley rats were fed a normal chow diet, high-fat diet (HFD), HFD supplemented with 1.5% leucine, or HFD with a 20% calorie restriction for 24 or 32 weeks. Leucine supplementation led to abnormal catabolism of BCAA and the incompletely oxidized lipid species that contributed to mitochondrial dysfunction in skeletal muscle in HFD-fed rats in the early stage of insulin resistance (24 weeks). However, leucine supplementation induced no remarkable alternations in BCAA catabolism, but did enhance mitochondrial biogenesis with a concomitant improvement in lipid oxidation and mitochondrial function during the hyperglycaemia stage (32 weeks). These findings suggest that leucine trigger different effects on metabolic signatures at different stages of insulin resistance, and the overall metabolic status of the organisms should be carefully considered to potentiate the benefits of leucine.
A Case Study on the Implementation of a Positive Youth Development Program (Project P.A.T.H.S.) in a Changing Education Policy Environment

This investigation of the implementation of a positive youth development program (Project P.A.T.H.S.) was part of a large study undertaken comprehensively to explore how effective the Tier 1 Program was in practice and how the results can shed light on future developments. Case studies on randomly selected schools were conducted in order to examine the factors that influence the process and quality of implementation of the Tier 1 Program of the Project P.A. T.H. S. Through interviews with the school contact person and focus group interviews with the teachers, an integration of the findings of these studies showed that five factors related to the program, people, process, policy, and place (5 “P”s) facilitated the implementation process of the Tier 1 Program in the school. Based on the integrated findings of a randomly selected school, it was found that the school made use of the changes in the educational policy environment to facilitate school policy and structural changes, to pave the way for the success of the implementation of a new and “unfamiliar” curriculum. Overall, the quality of program implementation in the school was good and the program was well received by the program implementers. Implications of the present findings for future program implementation with reference to school administrative arrangements and implementation issues are also discussed.
Temporal trends in the treatment and outcomes of elderly patients with acute coronary syndrome.

AIMS To determine whether treatment and outcomes of older acute coronary syndrome (ACS) patients changed over time. METHODS AND RESULTS We analysed the use of guideline-recommended therapies and in-hospital outcomes of 13 662 ACS patients ≥70 years enrolled in the prospective Acute Myocardial Infarction in Switzerland (AMIS) cohort between 2001 and 2012 according to 4-year periods (2001-2004, 2005-2008, and 2009-2012). Between first and last 4-year period, percutaneous coronary intervention (PCI) use increased from 43.8 to 69.6% of older ACS patients ( ITALIC! P < 0.001). Use of guideline-recommended drugs as well increased. At the same time, in-hospital mortality of the overall population decreased from 11.6% in the first to 10.0% in the last 4-year period ( ITALIC! P = 0.020), and in-hospital major adverse cardiac and cerebrovascular events from 14.4 to 11.3% ( ITALIC! P < 0.001). Percutaneous coronary intervention was used in increasingly older and co-morbid patients over time (mean age of patients treated with PCI 76.2 years in 2001-2004 and 78.1 years in 2009-2012, ITALIC! P < 0.001; Charlson score ≥2 was found for 27.6% of patients treated with PCI in 2001-2004 and for 32.1% in 2009-2012, ITALIC! P = 0.003). Percutaneous coronary intervention use was associated with similar odds ratios (ORs) of in-hospital mortality over time (adjusted OR 0.29, 95% confidence interval, CI, 0.22-0.40, in 2001-2004; and, adjusted OR 0.26, 95% CI 0.20-0.35, in 2009-2012). CONCLUSION Use of guideline-recommended therapies for ACS increased and in-hospital outcomes improved over the observed 12-year period. Though PCI was used in increasingly older and co-morbid patients, PCI use was associated with similar ORs of in-hospital mortality over time. This study suggests that increasing use of guideline-recommended therapies was appropriate. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01305785.
Youth’s Adjustment to Cancer: Examination of Patterns of Adjustment and the Role of Peer Relations

Objective Examine unique forms of peer relations (i.e., peer group vs. friendships) in relation to patterns of youth's resilience and challenge-related growth in the context of cancer. Methods In all, 279 youth (cancer, n = 156; control, n = 123) completed measures of posttraumatic stress, depression, anxiety, posttraumatic growth (PTG), and perceived positive changes. Youth also reported on their peer relations. Latent profile analysis (LPA) was used to examine patterns of youth's adjustment. Peer relations were examined as predictors of youth's adjustment. Results LPA revealed three profiles (42.1% resilient high growth, 21.4% resilient low growth, and 36.5% mild distress with growth). Youth's peer relations, demographic factors, and disease-related factors predicted assignment to profiles. Differences in adjustment emerged depending on youth's connection with their peers versus their friends. Summary Peer relations serve an important role in youth's adjustment to stressful life events. Assessment of peer and friend support may provide a more nuanced understanding of adjustment processes.
Oligonucleotide-Lipid Conjugates Forming G-Quadruplex Structures Are Potent and Pangenotypic Hepatitis C Virus Entry Inhibitors In Vitro and Ex Vivo

ABSTRACT A hepatitis C virus (HCV) epidemic affecting HIV-infected men who have sex with men (MSM) is expanding worldwide. In spite of the improved cure rates obtained with the new direct-acting antiviral drug (DAA) combinations, the high rate of reinfection within this population calls urgently for novel preventive interventions. In this study, we determined in cell culture and ex vivo experiments with human colorectal tissue that lipoquads, G-quadruplex DNA structures fused to cholesterol, are efficient HCV pangenotypic entry and cell-to-cell transmission inhibitors. Thus, lipoquads may be promising candidates for the development of rectally applied gels to prevent HCV transmission.
Barriers to Combined-Modality Therapy for Limited-Stage Small Cell Lung Cancer

Importance Combined-modality therapy with chemotherapy and radiation therapy plays a crucial role in the upfront treatment of patients with limited-stage small cell lung cancer (SCLC), but there may be barriers to utilization in the United States. Objective To estimate utilization rates and factors associated with chemotherapy and radiation therapy delivery for limited-stage SCLC using the National Cancer Database. Design, Setting, and Participants Analysis of initial management of all limited-stage SCLC cases from 2004 through 2013 in the National Cancer Database. Main Outcomes and Measures Utilization rates of chemotherapy and radiation therapy at time of initial treatment. Multivariable analysis identified independent clinical and socioeconomic factors associated with utilization and overall survival. Results A total of 70 247 cases met inclusion criteria (55.3% female; median age, 68 y [range, 19-90 y]). Initial treatment was 55.5% chemotherapy and radiation therapy, 20.5% chemotherapy alone, 3.5% radiation therapy alone, and 20.0% neither (0.5% not reported). Median survival was 18.2 (95% CI, 17.9-18.4), 10.5 (95% CI, 10.3-10.7), 8.3 (95% CI, 7.7-8.8), and 3.7 (95% CI, 3.5-3.8) months, respectively. Being uninsured was associated with a lower likelihood of both chemotherapy (odds ratio [OR], 0.65; 95% CI, 0.56-0.75; P < .001) and radiation therapy (OR, 0.75; 95% CI, 0.67-0.85; P < .001) administration on multivariable analysis. Medicare/Medicaid insurance had no impact on chemotherapy use, whereas Medicaid (OR, 0.79; 95% CI, 0.72-0.87; P < .001) and Medicare (OR, 0.86; 95% CI, 0.82-0.91; P < .001) were independently associated with a lower likelihood of radiation therapy delivery. Lack of health insurance (HR, 1.19; 95% CI, 1.13-1.26; P < .001), Medicaid (HR, 1.27; 95% CI, 1.21-1.32; P < .001), and Medicare (HR, 1.12; 95% CI, 1.09-1.15; P < .001) coverage were independently associated with shorter survival on adjusted analysis, while chemotherapy (HR, 0.55; 95% CI, 0.54-0.57; P < .001) and radiation therapy (HR, 0.62; 95% CI, 0.60-0.63; P < .001) were associated with a survival benefit. Conclusions and Relevance Substantial proportions of patients documented in a major US cancer registry did not receive radiation therapy or chemotherapy as part of initial treatment for limited-stage SCLC, which, in turn, was associated with poor survival. Lack of radiation therapy delivery was uniquely associated with government insurance coverage, suggesting a need for targeted access improvement in this population. Additional work will be necessary to conclusively define exact population patterns, specific treatment deficiencies, and causative factors leading to heterogeneous care delivery.
The use of leucocyte and platelet-rich fibrin in socket management and ridge preservation: a split-mouth, randomized, controlled clinical trial.

AIM To investigate the influence of the use L-PRF as a socket filling material and its ridge preservation properties. MATERIALS AND METHODS Twenty-two patients in need of single bilateral and closely symmetrical tooth extractions in the maxilla or mandible were included in a split-mouth RCT. Treatments were randomly assigned (L-PRF socket filling versus natural healing). CBCT scans were obtained after tooth extraction and three months. Scans were evaluated by superimposition using the original DICOM data. Mean ridge width differences between timepoints were measured at three levels below the crest on both the buccal and lingual sides (crest -1 mm (primary outcome variable), -3 mm and -5 mm). RESULTS Mean vertical height changes at the buccal were -1.5 mm (±1.3) for control sites and 0.5 mm (±2.3) for test sites (p < 0.005). At the buccal side, control sites values were, respectively, -2.1 (±2.5), -0.3 mm (±0.3) (p < 0.005) and -0.1 mm (±0.0), and test sites values were, respectively, -0.6 mm (±2.2) (p < 0.005), -0.1 mm (±0.3) and 0.0 mm (±0.1). Significant differences (p < 0.005) were found for total width reduction between test (-22.84%) and control sites (-51.92%) at 1 mm below crest level. Significant differences were found for socket fill (visible mineralized bone) between test (94.7%) and control sites (63.3%). CONCLUSION The use of L-PRF as a socket filling material to achieve preservation of horizontal and vertical ridge dimension at three months after tooth extraction is beneficial.
A controlled‐release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice

Lipodystrophy is a rare disorder characterized by complete or partial loss of adipose tissue. Patients with lipodystrophy exhibit hypertriglyceridemia, severe insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). Efforts to ameliorate NASH in lipodystrophies with pharmacologic agents have met with limited success. We examined whether a controlled‐release mitochondrial protonophore (CRMP) that produces mild liver‐targeted mitochondrial uncoupling could decrease hypertriglyceridemia and reverse NASH and diabetes in a mouse model (fatless AZIP/F‐1 mice) of severe lipodystrophy and diabetes. After 4 wk of oral CRMP (2 mg/kg body weight per day) or vehicle treatment, mice underwent hyperinsulinemic‐euglycemic clamps combined with radiolabeled glucose to assess liver and muscle insulin responsiveness and tissue lipid measurements. CRMP treatment reversed hypertriglyceridemia and insulin resistance in liver and skeletal muscle. Reversal of insulin resistance could be attributed to reductions in diacylglycerol content and reduced PKC‐ε and PKC‐θ activity in liver and muscle respectively. CRMP treatment also reversed NASH as reflected by reductions in plasma aspartate aminotransferase and alanine aminotransferase concentrations; hepatic steatosis; and hepatic expression of IL‐1α, ‐β, ‐2, ‐4, ‐6, ‐10, ‐12, CD69, and caspase 3 and attenuated activation of the IRE‐1α branch of the unfolded protein response. Taken together, these results provide proof of concept for the development of liver‐targeted mitochondrial uncoupling agents as a potential novel therapy for lipodystrophy‐associated hypertriglyceridemia, NASH and diabetes. —Abulizi, A. , Perry, R. J., Camporez, J. P. G. , Jurczak, M. J., Petersen, K. F. , Aspichueta, P., Shulman, G. I. A controlled‐release mitochondrial protonophore reverses hypertriglyceridemia, nonalcoholic steatohepatitis, and diabetes in lipodystrophic mice. FASEB J. 31, 2916–2924 (2017). www.fasebj. org
Breastfeeding preterm infants - a randomized controlled trial of the effectiveness of an Internet-based peer-support group.

AIMS The aim of this study was to examine whether an Internet-based peer-support intervention has an effect on the duration of breastfeeding or breast milk expression or maternal breastfeeding attitude compared with routine care in the mothers of preterm infants. In addition, the feasibility of the intervention was examined. BACKGROUND A few peer-support interventions conducted face-to-face or by telephone have given promising results in promoting breastfeeding in preterm infants. DESIGN A randomized controlled trial with a 1-year follow-up was conducted in one hospital in Finland in 2011-2015. METHODS Altogether 124 mothers of preterm (<35 weeks) infants were recruited; 60 in an experimental and 64 in a control group. The intervention was a closed peer-support group in social media. Data were collected by structured questionnaires. Neonatal and breastfeeding data were collected from patient records. RESULTS The duration of overall breastfeeding was on average 3·0 and 4·3 months, in the experimental and control groups respectively. The intervention had no effect on breastfeeding or expressing the breast milk or maternal breastfeeding attitude. A breastfeeding-favourable attitude and at least two previous children predicted longer duration of breastfeeding. Attitude-score decreased during the follow-up. The mothers in the experimental group enjoyed peer support, but only a few reported it as having some impact on breastfeeding. CONCLUSION Although the Internet-based peer-support intervention had no effect, the importance of breastfeeding attitude for the duration of breastfeeding in mothers of preterm infants was shown. In future, interventions in social media should be studied more and attitude-focused interventions be developed.
A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease

In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease.
Best Practice in Provider/Parent Interaction

In this 3-year prospective grounded theory study in three pediatric settings, we aimed to develop a conceptualization of best practice health care providers (BPHCPs) in interaction with parents of children with complex, chronic, life-threatening conditions. Analysis of semistructured interviews with 34 parents and 80 health care professionals (HCPs) and 88 observation periods of HCP/parent interactions indicated that BPHCPs shared a broad worldview; values of equity, family-centered care, and integrity; and a commitment to authentic engagement. BPHCPs engaged in direct care activities, in connecting behaviors, and in exquisitely attuning to particularities of the situation in the moment, resulting in positive outcomes for parents and HCPs. By focusing on what HCPs do well, findings showed that not only is it possible for HCPs to practice in this way, but those who do so are also recognized as being the best at what they do. We provide recommendations for practice and initial and ongoing professional education.
Using a situation awareness approach to determine decision-making behaviour in squash

ABSTRACT Situation awareness (SA) refers to the awareness of all relevant sources of information, an ability to synthesise this information using domain knowledge gained from past experiences and the ability to physically respond to a situation. Expert-novice differences have been widely reported in decision-making in complex situations although determining the small differences in expert behaviour are more elusive. This study considered how expert squash players use SA to decide on what shot to play. Matches at the 2010 (n = 14) and 2011 (n = 27) Rowe British Grand Prix were recorded and processed using Tracker software. Shot type, ball location, players’ positions on court and movement parameters between the time an opponent played a shot prior to the player’s shot to the time of the opponent’s following shot were captured 25 times per second. Six SA clusters were named to relate to the outcome of a shot ranging from a defensive shot played under pressure to create time to an attempted winner played under no pressure with the opponent out of position. This new methodology found fine-grained SA differences in expert behaviour, even for the same shot type played from the same court area, beyond the usual expert-novice differences.
Curcumin Anti-Apoptotic Action in a Model of Intestinal Epithelial Inflammatory Damage

The purpose of this study is to determine if a preventive treatment with curcumin can protect intestinal epithelial cells from inflammatory damage induced by IFNγ. To achieve this goal we have used a human intestinal epithelial cell line (HT29) treated with IFNγ to undergo apoptotic changes that can reproduce the damage of intestinal epithelia exposed to inflammatory cytokines. In this model, we measured the effect of curcumin (curcuminoid from Curcuma Longa) added as a pre-treatment at different time intervals before stimulation with IFNγ. Curcumin administration to HT29 culture before the inflammatory stimulus IFNγ reduced the cell apoptosis rate. This effect gradually declined with the reduction of the curcumin pre-incubation time. This anti-apoptotic action by curcumin pre-treatment was paralleled by a reduction of secreted IL7 in the HT29 culture media, while there was no relevant change in the other cytokine levels. Even though curcumin pre-administration did not impact the activation of the NF-κB pathway, a slight effect on the phosphorylation of proteins in this inflammatory signaling pathway was observed. In conclusion, curcumin pre-treatment can protect intestinal cells from inflammatory damage. These results can be the basis for studying the preventive role of curcumin in inflammatory bowel diseases.
Nurse practitioner‐led transitional care interventions: An integrative review

Background and purpose: Chronically ill patients 65 and above have an increased risk of preventable readmission within 30 days of discharge from the hospital. The Transitional Care Model (TCM) introduced by Naylor and colleagues was implemented to improve the transition between hospital and home while decreasing readmissions. This article examines whether nurse practitioner (NP)‐led TCM interventions as compared to standard care decrease hospital readmission rates in older adults. Methods: A literature review was conducted from June 2016 to March 2017 using Cochrane Library, PubMed, Cumulative Index to Nursing and Health Literature (CINAHL) PLUS, Joanna Briggs Institute, and ProQuest Central to seek out the highest level of evidence. Search results were refined to focus on randomized control trials (RTCs) containing NP‐led TCM interventions with older adults. Conclusions: Synthesis of three RTCs, one meta‐analysis, and four nonrandomized studies reviewed TCM interventions that included these interventions: follow‐up phone calls post discharge, home visits, and handoff of information to the patient's primary care provider. These interventions, although not exclusively led by NPs, decreased hospital readmission rates. Implications for practice: NP‐led TCM interventions have the potential to decrease readmissions, but the level of evidence is insufficiently high to allow for generalizability, warranting further study.
‘Suddenly the first fifty years of my life made sense’: Experiences of older people with autism

Research on the experience of growing older with autism is very limited. In this study, 13 people with autism aged over 50 years participated in semi-structured interviews about their experiences of diagnosis, social support and getting older. Interviews were analysed using thematic analysis. Three overarching themes were generated: difference, life review and longing for connection. Prior to diagnosis, individuals had awareness of their difficulties, attributed these to intrinsic difference and engaged in a deliberate process of reducing the visibility of this difference. Diagnosis prompted a process of life review and externalisation, whereby past negative experiences were reattributed to autism as opposed to the self. Loneliness, isolation and yearning for interpersonal connection were ubiquitous and longstanding. Autism support and social groups were highly valued, offering opportunities for belonging, acceptance and social comparison. Results highlight the similarity to younger age groups in terms of lived experience and need for greater support, particularly with respect to reducing isolation and improving access to diagnosis.