Oral fatty acid sensitivity and dietary fat consumption

Lisa investigated the taste of fat and its influence on excess fat consumption and obesity. This research established that taste sensitivity to fat can be modulated by fat intake and may be used as an obesity prevention tool in the future

Dietary fat restriction increases fat taste sensitivity in people with obesity

OBJECTIVE: Individuals with obesity may be less sensitive to the taste of fat, and it is hypothesized that this is due to excess dietary fat intake. This study assessed the effect of a 6-week low-fat (LF) or portion control (PC) diet matched for weight loss on fat taste thresholds, fat perception, and preference in people with overweight/obesity. METHODS: Participants (n = 53) completed a randomized dietary intervention and consumed either a LF diet (25% fat) or PC diet (33% fat) for 6 weeks. Fat taste thresholds (lowest detectable fat concentration), fat perception (discrimination ability), preference, and anthropometry were assessed at baseline and week 6. RESULTS: Consumption of a LF diet (n = 26) and PC diet (n = 27) reduced participants\u27 weight (P < 0.001), with no significant differences between groups (LF, -2.9%, PC, -2.7%). Both diets resulted in a decrease in fat taste thresholds (P = 0.014), and the effect tended to be stronger in the LF diet vs. the PC diet (P = 0.060). The ability to perceive different fat concentrations in foods was increased after the LF diet only (P = 0.017); however, food preference did not change on either diet. CONCLUSIONS: A PC and LF diet both increase fat taste sensitivity in people with overweight/obesity, with the strongest effect after the LF diet

Impaired Effective Connectivity During a Cerebellar-Mediated Sensorimotor Synchronization Task in Schizophrenia

Prominent conceptual models characterize schizophrenia as a dysconnectivity syndrome, with recent research focusing on the contributions of the cerebellum in this framework. The present study examined the role of the cerebellum and its effective connectivity to the cerebrum during sensorimotor synchronization in schizophrenia. Specifically, the role of the cerebellum in temporally coordinating cerebral motor activity was examined through path analysis. Thirty-one individuals diagnosed with schizophrenia and 40 healthy controls completed a finger-tapping fMRI task including tone-paced synchronization and self-paced continuation tapping at a 500 ms intertap interval (ITI). Behavioral data revealed shorter and more variable ITIs during self-paced continuation, greater clock (vs motor) variance, and greater force of tapping in the schizophrenia group. In a whole-brain analysis, groups showed robust activation of the cerebellum during self-paced continuation but not during tone-paced synchronization. However, effective connectivity analysis revealed decreased connectivity in individuals with schizophrenia between the cerebellum and primary motor cortex but increased connectivity between cerebellum and thalamus during self-paced continuation compared with healthy controls. These findings in schizophrenia indicate diminished temporal coordination of cerebral motor activity by cerebellum during the continuation tapping portion of sensorimotor synchronization. Taken together with the behavioral finding of greater temporal variability in schizophrenia, these effective connectivity results are consistent with structural and temporal models of dysconnectivity in the disorder

Do Children\u27s Advocacy Centers improve families’ experiences of child sexual abuse investigations?

Abstract Objective The Children\u27s Advocacy Center (CAC) model of child abuse investigation is designed to be more child and family-friendly than traditional methods, but there have been no rigorous studies of their effect on children\u27s and caregivers’ experience. Data collected as part of the Multi-Site Evaluation of Children\u27s Advocacy Centers were used to examine whether CACs improve caregivers’ and children\u27s satisfaction with investigations. Methods Nonoffending caregiver and child satisfaction were assessed during research interviews, including the administration of a 14-item Investigation Satisfaction Scale (ISS) for caregivers. Two hundred and twenty-nine sexual abuse cases investigated through a CAC were compared to 55 cases investigated in communities with no CAC. Results Hierarchical linear regression results indicated that caregivers in CAC cases were more satisfied with the investigation than those from comparison sites, even after controlling for a number of relevant variables. There were few differences between CAC and comparison samples on children\u27s satisfaction. Children described moderate to high satisfaction with the investigation, while a minority expressed concerns about their experience. Conclusions The CAC model shows promise for improving families’ experiences, but to build upon this promise, agencies will need to systematize procedures for refining and adapting the model as new research becomes available

High-Dose Ipilimumab and High-Dose Interleukin-2 for Patients With Advanced Melanoma.

High-dose ipilimumab (IPI) and high-dose interleukin-2 (IL-2) are approved agents for metastatic melanoma, but the efficacy and safety of the combination are unknown. The objective of this study was to evaluate the feasibility, safety, and efficacy of combination high-dose IPI and high-dose IL-2 in patients with histologically confirmed advanced unresectable stage III and IV melanoma. This Phase II, multicenter, open-label, single-arm trial was conducted in nine patients enrolled between 12/2014 and 12/2015. Subjects were treated with high-dose IPI 10 mg/kg intravenous (IV) every 3 weeks for four doses starting at week 1 and high-dose IL-2 (600,000 IU/kg IV bolus every 8 h for up to 14 doses) concurrently with IPI at weeks 4 and 7. After the first 12 weeks of combination therapy, maintenance IPI (10 mg/kg IV) monotherapy was administered every 12 weeks for up to 1 year. No patient had received prior PD-1 blockade, and only one received prior vemurafenib. Confirmed partial response was achieved in one (11%), stable disease in four (44%), and progressive disease in four (44%) of nine patients. Two patients achieved durable disease control of 44+ and 50+ months at the most recent follow-up without subsequent therapy. The median overall survival was not reached after a minimum 24 months of follow-up time. One-year and 2-year survival rates were 89 and 67%, respectively. Seven patients (78%) experienced grade 3 or 4 adverse events related to the study therapy, three of which were attributed to both agents. One patient discontinued the treatment due to liver and kidney toxicity. While toxicity was significant, all events were reversible, and there was no treatment-related mortality. In peripheral blood of patients with decreasing tumor burden, the ratio of the non-classical MHC-II proteins HLA-DM to HLA-DO increased 2-fold, raising the possibility of the ratio of HLA-DM:HLA-DO as a novel biomarker of response to treatment. Although the sample size was limited, combination therapy with high-dose IPI and high-dose IL-2 was feasible and associated with clinical benefit. IL-2-based compounds in combination with CTLA-4 blockade should be studied in advanced melanoma patients who fail to benefit from first-line PD-1 blockade

Cigarette smoking, cytochrome P4501A1 polymorphisms, and breast cancer among African-American and white women

INTRODUCTION: Previous epidemiologic studies suggest that women with variant cytochrome P4501A1 (CYP1A1) genotypes who smoke cigarettes are at increased risk for breast cancer. METHODS: We evaluated the association of breast cancer with CYP1A1 polymorphisms and cigarette smoking in a population-based, case–control study of invasive breast cancer in North Carolina. The study population consisted of 688 cases (271 African Americans and 417 whites) and 702 controls (285 African Americans and 417 whites). Four polymorphisms in CYP1A1 were genotyped using PCR/restriction fragment length polymorphism analysis: M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4) RESULTS: No associations were observed for CYP1A1 variant alleles and breast cancer, ignoring smoking. Among women who smoked for longer than 20 years, a modest positive association was found among women with one or more M1 alleles (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.2–3.5) but not among women with non-M1 alleles (OR = 1.2, 95% CI = 0.9–1.6). Odds ratios for smoking longer than 20 years were higher among African-American women with one or more M3 alleles (OR = 2.5, 95% CI = 0.9–7.1) compared with women with non-M3 alleles (OR = 1.3, 95% CI = 0.8–2.2). ORs for smoking in white women did not differ appreciably based upon M2 or M4 genotypes. CONCLUSIONS: Cigarette smoking increases breast cancer risk in women with CYP1A1 M1 variant genotypes and in African-American women with CYP1A1 M3 variant genotypes, but the modifying effects of the CYP1A1 genotype are quite weak

Abandoned Acid? Understanding Adherence to Bisphosphonate Medications for the Prevention of Osteoporosis among Older Women: A Qualitative Longitudinal Study

Background There is significant morbidity and mortality caused by the complications of osteoporosis, for which ageing is the greatest epidemiological risk factor. Preventive medications to delay osteoporosis are available, but little is known about motivators to adhere to these in the context of a symptomless condition with evidence based on screening results. Aim To describe key perceptions that influence older women's adherence and persistence with prescribed medication when identified to be at a higher than average risk of fracture. Design of Study A longitudinal qualitative study embedded within a multi-centre trial exploring the effectiveness of screening for prevention of fractures. Setting Primary care, Norfolk. United Kingdom Methods Thirty older women aged 70–85 years of age who were offered preventive medication for osteoporosis and agreed to undertake two interviews at 6 and 24 months post-first prescription. Results There were no overall predictors of adherence which varied markedly over time. Participants' perceptions and motivations to persist with medication were influenced by six core themes: understanding adherence and non-adherence, motivations and self-care, appraising and prioritising risk, anticipating and managing side effects, problems of understanding, and decision making around medication. Those engaged with supportive professionals could better tolerate and overcome barriers such as side-effects. Conclusions Many issues are raised following screening in a cohort of women who have not previously sought advice about their bone health. Adherence to preventive medication for osteoporosis is complex and multifaceted. Individual participant understanding, choice, risk and perceived need all interact to produce unpredictable patterns of usage and acceptability. There are clear implications for practice and health professionals should not assume adherence in any older women prescribed medication for the prevention of osteoporosis. The beliefs and motivations of participants and their healthcare providers regarding the need to establish acceptable medication regimes is key to promoting and sustaining adherence

Parental perceptions of barriers and facilitators to preventing child unintentional injuries within the home: a qualitative study

Background Childhood unintentional injury represents an important global health problem. Most of these injuries occur at home, and many are preventable. The main aim of this study was to identify key facilitators and barriers for parents in keeping their children safe from unintentional injury within their homes. A further aim was to develop an understanding of parents’ perceptions of what might help them to implement injury prevention activities. Methods Semi-structured interviews were conducted with sixty-four parents with a child aged less than five years at parent’s homes. Interview data was transcribed verbatim, and thematic analysis was undertaken. This was a Multi-centre qualitative study conducted in four study centres in England (Nottingham, Bristol, Norwich and Newcastle). Results Barriers to injury prevention included parents’ not anticipating injury risks nor the consequences of some risk-taking behaviours, a perception that some injuries were an inevitable part of child development, interrupted supervision due to distractions, maternal fatigue and the presence of older siblings, difficulties in adapting homes, unreliability and cost of safety equipment and provision of safety information later than needed in relation to child age and development. Facilitators for injury prevention included parental supervision and teaching children about injury risks. This included parents’ allowing children to learn about injury risks through controlled risk taking, using “safety rules” and supervising children to ensure that safety rules were adhered to. Adapting the home by installing safety equipment or removing hazards were also key facilitators. Some parents felt that learning about injury events through other parents’ experiences may help parents anticipate injury risks. Conclusions There are a range of barriers to, and facilitators for parents undertaking injury prevention that would be addressable during the design of home safety interventions. Addressing these in future studies may increase the effectiveness of interventions

Beryllium increases the CD14^dimCD16+ subset in the lung of chronic beryllium disease

CD14dimCD16+ and CD14brightCD16+ cells, which compose a minor population of monocytes in human peripheral blood mononuclear cells (PBMC), have been implicated in several inflammatory diseases. The aim of this study was to investigate whether this phenotype was present as a subset of lung infiltrative alveolar macrophages (AMs) in the granulomatous lung disease, chronic beryllium disease (CBD). The monocytes subsets was determined from PBMC cells and bronchoalveolar lavage (BAL) cells from CBD, beryllium sensitized Non-smoker (BeS-NS) and healthy subjects (HS) using flow cytometry. The impact of smoking on the AMs cell phenotype was determined by using BAL cells from BeS smokers (BeS-S). In comparison with the other monocyte subpopulations, CD14dimCD16+ cells were at decreased frequency in PBMCs of both BeS-NS and CBD and showed higher HLA-DR expression, compared to HS. The AMs from CBD and BeS-NS demonstrated a CD14dimCD16+phenotype, while CD14brightCD16+ cells were found at increased frequency in AMs of BeS, compared to HS. Fresh AMs from BeS-NS and CBD demonstrated significantly greater CD16, CD40, CD86 and HLA-DR than HS and BeS-S. The expression of CD16 on AMs from both CBD and BeS-NS was downregulated significantly after 10μM BeSO4 stimulation. The phagocytic activity of AMs decreased after 10μM BeSO4 treatment in both BeS-NS and CBD, although was altered or reduced in HS and BeS-S. These results suggest that Be increases the CD14dimCD16+ subsets in the lung of CBD subjects. We speculate that Be-stimulates the compartmentalization of a more mature CD16+ macrophage phenotype and that in turn these macrophages are a source of Th1 cytokines and chemokines that perpetuate the Be immune response in CBD. The protective effect of cigarette smoking in BeS-S may be due to the low expression of co-stimulatory markers on AMs from smokers as well as the decreased phagocytic function