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The demand of social skills interventions for people with ASD has grown in recent years. The main goal of this research was to study social skills: "responding to interaction" and "initiating interaction", and to capture whether there were differences between an initial and a final session in a program for children with ASD. Additionally, we aimed to compare social skills patterns according to the VIQ level. The sample (N = 20) was divided into 2 subgroups depending on whether the VIQ was > 90 or < 90. We employed a mixed methods approach based on a systematic observation of social behaviors. The observational design was nomothetic, follow-up, and multidimensional. Once we confirmed inter-observer reliability for the ad hoc observational instrument we performed descriptive statistics and polar coordinate analysis using LINCE software. The results show high intragroup and intergroup variability. In general, participants with VIQ < 90 showed a better improvement in responding to interaction, whereas participants with VIQ > 90 showed more complex patterns to initiate interactions. The polar coordinate technique was useful for detecting significant relationships between autism's social micro-behaviors. Results and information obtained through observational methodology could allow professionals to understand communication and interaction of participants.

In vivo pharmacological inhibition of soluble epoxide hydrolase (sEH) reduces inflammatory diseases, including acute pancreatitis (AP). Adamantyl ureas are very potent sEH inhibitors, but the lipophilicity and metabolism of the adamantane group compromise their overall usefulness. Herein, we report that the replacement of a methylene unit of the adamantane group by an oxygen atom increases the solubility, permeability, and stability of three series of urea-based sEH inhibitors. Most of these oxa-analogues are nanomolar inhibitors of both the human and murine sEH. Molecular dynamics simulations rationalize the molecular basis for their activity and suggest that the presence of the oxygen atom on the adamantane scaffold results in active site rearrangements to establish a weak hydrogen bond. The 2-oxaadamantane 22, which has a good solubility, microsomal stability, and selectivity for sEH, was selected for further in vitro and in vivo studies in models of cerulein-induced AP. Both in prophylactic and treatment studies, 22 diminished the overexpression of inflammatory and endoplasmic reticulum stress markers induced by cerulein and reduced the pancreatic damage.

BackgroundThe proportion of older people has dramatically increased in recent decades. Moreover, social and demographic trends show a global increase of older people at risk of loneliness and lack of social relationships. The objective of this study was to evaluate the process, the effectiveness and the cost-effectiveness of a planned 22 weekly group sessions called School of Health for Older People to reduce social isolation.MethodsThis is a mixed methods multi-approach evaluation that includes: 1) A qualitative evaluation among coordinators and participants taking part in the intervention, through in depth-interviews and focus groups, respectively. The main topics covered will be positive and negative aspects of the intervention, suggestions for its improvement, opinions on different aspects of the intervention, and perceived benefits; 2) A quantitative quasi-experimental design, comparing a group of individuals taking part in the intervention with another group with similar characteristics not receiving the intervention. Data will be collected at the beginning and at the end of the intervention. Social support will be measured through questions drawn from the Medical Outcomes Study and the National Social Life, Health, and Aging Project questionnaires. Psychological morbidity will be measured through Goldberg's General Health Questionnaire, and Health-related Quality of Life will be measured through the EuroQoL questionnaire. Information on visits to the primary care center in the years before and after the intervention will be obtained from the electronic records of the primary care centers; 3) A cost-utility analysis, which will be conducted from a health system (primary care) perspective, including direct costs of the program and the primary care health services used. The effects of the intervention will be measured on quality-adjusted life years.DiscussionThere is an urgent need for studies assessing the effectiveness and the efficiency of potential interventions to reduce social isolation among older persons. The results of this study will help to fill the knowledge gap in this area and might be especially useful for the development of social and public health policies and programs for older people in disadvantaged neighborhoods in urban areas.Trial registrationNCT03142048 retrospectively registered (April 11, 2017).

BACKGROUND AND PURPOSE: FGF21 has emerged as a therapeutic strategy for treating type 2 diabetes mellitus due to its antidiabetic effects, and this has led to the development of long-acting analogues of FGF21. However, these compounds have some limitations, including a need to be administered by s.c. injection and their prolonged pharmacodynamic effect compared with native FGF21, which might be responsible for their reported side effects. EXPERIMENTAL APPROACH: We have previously demonstrated that i.p. administration of haem-regulated eukaryotic translation initiation factor 2a kinase (HRI) activators increases hepatic and circulating levels of FGF21. In this study, we examined the effects of p.o. administration of a new HRI activator, EPB-53, on high-fat diet (HFD)-induced glucose intolerance, hepatic steatosis, and hypertriglyceridaemia, and compared them with those of metformin. KEY RESULTS: EPB-53 administration for the last 2 weeks, to mice fed a HFD for 10 weeks, reduced body weight gain, improved glucose intolerance, and prevented hepatic steatosis and hypertriglyceridaemia, whereas metformin only ameliorated glucose intolerance. Moreover, EPB-53, similar to the reported effects of FGF21, reduced lipogenesis in cultured human hepatocytes and in the liver of mice fed a HFD. Administration of EPB-53 to Fgf21-knockout mice had no effects, demonstrating that its efficacy is dependent on this hormone. CONCLUSIONS AND IMPLICATIONS: Overall, the findings of this study demonstrate that p.o. administration of HRI activators, by increasing FGF21, is a promising strategy for the treatment of type 2 diabetes mellitus and non-alcoholic fatty liver disease.

Over the last 20 years, researchers have been mixing qualitative and quantitative approaches, but mixed methods research represents a new movement that arose in response to the currents of qualitative and quantitative research, considered separately. Little has been published on the use of polar coordinate analysis in psychotherapy. This type of analysis can provide detailed information and integrate the qualitative-quantitative analysis. Even less has been published on the analysis of ASD children's behavior. The main aim of this study was to implement this mixed methods methodology to analyze patterns of social behaviors in a group of adolescents with ASD during a group social competence intervention program. Moreover, we wanted to see whether an observational scale could be combined fruitfully with polar coordinate analysis and to investigate whether typical ASD behaviors show similar interrelations (prospective and retrospective sequentialities) as behaviors observed in psychotherapy. We used an adaptation from the Social Skills Training Program (UC Davis, California). We observed that each participant took a unique course, increasing or decreasing the number and quality of their social behaviors. In accordance with previous literature, results suggest some increment in the amount of appropriate social conduct. We did not detect a generalized progress pattern but agreed that there were changes between the beginning and end of the intervention. Therefore, we consider that observational methodology is useful in the field of psychotherapy and ASD, offering detailed information about changes and development that cannot be obtained with other traditional measures, such as questionnaires.

Cancer-associated pain has traditionally been treated with opioid analgesics, often in escalating doses. Opioid-induced constipation (OIC) is a common problem associated with chronic use of opioid analgesics. Typical treatment strategies to alleviate constipation are based on dietary changes, exercise, and laxatives. However, laxatives have a nonspecific action and do not target underlying mechanisms of OIC. This article will review prevalent, clinical presentation and recommendations for the treatment of OIC. An independent literature search was carried out by the authors. We reviewed the literature for randomized controlled trials that studied the efficacy of laxatives, naloxone, and naloxegol in treating OIC. Newer strategies addressing the causal pathophysiology of OIC are needed for a more effective assessment and management of OIC. Finally, traditional recommended therapies are appraised and compared with the latest pharmacological developments. Future research should address whether naloxegol is more efficacious by its comparison directly with first-line treatments, including laxatives.

Objective: The very low-density lipoprotein receptor (VLDLR) plays an important role in the development of hepatic steatosis. In this study, we investigated the role of Peroxisome Proliferator-Activated Receptor (PPAR)beta/delta and fibroblast growth factor 21 (FGF21) in hepatic VLDLR regulation. Methods: Studies were conducted in wild-type and Ppar beta/delta-null mice, primary mouse hepatocytes, human Huh-7 hepatocytes, and liver biopsies from control subjects and patients with moderate and severe hepatic steatosis. Results: Increased VLDLR levels were observed in liver of Ppar beta/delta-null mice and in Ppar beta/delta-knocked down mouse primary hepatocytes through mechanisms involving the heme-regulated eukaryotic translation initiation factor 2 alpha (e1F2 alpha) kinase (HRI), activating transcription factor (ATF) 4 and the oxidative stress-induced nuclear factor (erythroid-derived2)-like 2 (Nrf2) pathways. Moreover, by using a neutralizing antibody against FGF21, Fgf21-null mice and by treating mice with recombinant FGF21, we show that FGF21 may protect against hepatic steatosis by attenuating endoplasmic reticulum (ER) stress-induced VLDLR upregulation. Finally, in liver biopsies from patients with moderate and severe hepatic steatosis, we observed an increase in VLDLR levels that was accompanied by a reduction in PPAR beta/delta mRNA abundance and DNA-binding activity compared with control subjects. Conclusions: Overall, these findings provide new mechanisms by which PPAR beta/delta and FGF21 regulate VLDLR levels and influence hepatic steatosis development. 2017 The Authors. Published by Elsevier GmbH.

Fibroblast growth factor 21 (FGF21), a peptide hormone with pleiotropic effects on carbohydrate and lipid metabolism, is considered a target for the treatment of diabetes. We investigated the role of peroxisome proliferator-activated receptor (PPAR) ß/d deficiency in hepatic FGF21 regulation. Increased Fgf21 expression was observed in the livers of PPARß/d-null mice and in mouse primary hepatocytes when this receptor was knocked down by small interfering RNA (siRNA). Increased Fgf21 was associated with enhanced protein levels in the heme-regulated eukaryotic translation initiation factor 2a (eIF2a) kinase (HRI). This increase caused enhanced levels of phosphorylated eIF2a and activating transcription factor (ATF) 4, which is essential for Fgf21-induced expression. siRNA analysis demonstrated that HRI regulates Fgf21 expression in primary hepatocytes. Enhanced Fgf21 expression attenuated tunicamycin-induced endoplasmic reticulum stress, as demonstrated by using a neutralizing antibody against FGF21. Of note, increased Fgf21 expression in mice fed a high-fat diet or hepatocytes exposed to palmitate was accompanied by reduced PPARß/d and activation of the HRI-eIF2a-ATF4 pathway. Moreover, pharmacological activation of HRI increased Fgf21 expression and reduced lipid-induced hepatic steatosis and glucose intolerance, but these effects were not observed in Fgf21-null mice. Overall, these findings suggest that HRI is a potential target for regulating hepatic FGF21 levels.

BACKGROUND: smoking. The purpose of the study was to use Conversational Analysis to enhance understanding of the process in Motivational Interviewing sessions carried out by primary care doctors and nurses to motivate their patients to quit smoking. The present study is a substudy of the Systematic Intervention on Smoking Habits in Primary Health Care Project (Spanish acronym: ISTAPS). interview sessions were conducted with two of the nine) in the ISTAPS study who were current smokers and scored fewer than 5 points on the Richmond test that measures motivation to quit smoking were videotaped and transcribed. A total of 11 interviews conducted by five primary health care professionals in Barcelona, Spain, were analysed. Qualitative Content Analysis was used to develop an analytical guide for coding transcriptions. Conversation Analysis allowed detailed study of the exchange of words during the interaction. on readiness to change, and summary. The interaction was constructed during an office visit, where interactional dilemmas arise and can be resolved in various ways. Some actions by professionals (use of reiterations, declarations, open-ended questions) helped to construct a framework of shared relationship; others inhibited this relationship (focusing on risks of smoking, clinging to the protocol, and prematurely emphasizing change). Some professionals tended to resolve interactional dilemmas (e.g., resistance) through a confrontational or directive style. Interactions that did not follow Motivational Interviewing principles predominated in seven of the interviews analysed. increases when a health professional encounters individuals with low motivation for change, and interactional dilemmas may occur that make it difficult to follow Motivational Interview principles. Incorporating different forms of expression during the Motivational Interviewing could help to build patient-centred health care relationships and, for patients with low motivation to stop smoking, offer an opportunity to reflect on tobacco use during the office visit. The study findings could be included in professional training to improve the quality of motivational interviewing. DDEUIT

Hamilton & Orians (1965) stated that the non-parasitic ancestor of cowbirds accelerated its incubation period and nestling growth. Later, by comparing cowbirds with nesting birds, it was suggested that those characteristics, together with small eggs with thicker eggshell, were adaptations. When these hypotheses were tested considering the characteristics of the group in which cowbirds evolved, i.e. the "grackles and allies", it was found that only the thicker eggshell was a plausible adaptation. Moreover, nesting grackles and allies showed the same reproductive patterns as cowbirds (shorter incubation periods, faster nestling growth, and smaller eggs than those predicted by general allometric equations). In the present study, we tested whether small eggs with short incubation periods and nestlings with accelerated growth evolved in the ancestor of grackles and allies. For all the traits tested, we reconstructed ancestral states and built prediction intervals generated with independent variables that were allometrically related to them. Except for accelerated growth, we applied two evolutionary models incorporating outgroups in three steps. We found that the short incubation period and the faster nestling growth never evolved in the ancestor of grackles and allies. In most ancestor reconstructions, neither egg mass nor female body mass changed. However, when it changed, it increased both egg and female masses. The prediction intervals indicated that those increases did not imply an allometric change in size. Consequently, neither a decrease in egg mass nor an acceleration in nestling development and incubation period are considered characteristics that predisposed cowbirds to become brood parasites. © The Neotropical Ornithological Society. Fil:Mermoz, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.