Factors determining the integration of nutritional genomics into clinical practice by registered dietitians

YesPersonalized nutrition has the potential to improve health, prevent disease and reduce healthcare expenditure. Whilst research hints at positive consumer attitudes towards personalized nutrition that draws upon lifestyle, phenotypic and genotypic data, little is known about the degree to which registered dietitians (RD) are engaged in the delivery of such services. This review sought to determine possible factors associated with the integration of the emerging science of Nutritional Genomics (NGx) into the clinical practice setting by practicing registered dietitians. Scope Search of online databases (Pubmed; National Library of Medicine; Cochrane Library; Ovid Medline) was conducted on material published from January 2000 to December 2014. Studies that sampled practicing dietitians and investigated integration or application of NGx and genetics knowledge into practice were eligible. Articles were assessed according to the American Dietetic Association Quality Criteria Checklist. Key findings Application of nutritional genomics in practice has been limited. Reluctance to integrate NGx into practice is associated with low awareness of NGx, a lack of confidence in the science surrounding NGx and skepticism toward Direct to consumer (DTC) products. Successful application to practice was associated with knowledge about NGx, having confidence in the science, a positive attitude toward NGx, access to DTC products, a supportive working environment, working in the clinical setting rather than the public health domain and being in private rather than public practice. Conclusions There is a need to provide RGs with a supportive working environment that provides ongoing training in NGx and which is integrated with clinical practice

Perceptions and experiences of early-adopting registered dietitians in integrating nutrigenomics into practice

yesPurpose - This research explores the perceptions and experiences of early adopters of the technology. Design/Method/Approach - Registered Dietitians (RD´s) (N=14) were recruited from the UK, Canada, South-Africa, Australia, Mexico and Israel. Six qualitative interviews and two focus groups were conducted online using a conference calling platform. Data were recorded, transcribed and thematically analysed. Findings - Early adopters of Nutrigenomics (NGx) were experienced, self-efficacious RD’s who actively sought knowledge of NGx through communication with one another and the broader scientific community. They considered NGx an extension of current practice and believed RD’s had the skills to deliver it. Perceived barriers to widening the application of NGx were linked to skepticism among the wider dietetics community. Proliferation of unregulated websites offering tests and diets was considered ‘pseudoscience’ and detrimental to dietetics fully embracing NGx. The lack of a sustainable public health model for the delivery of NGx was also perceived to hinder progress. Results are discussed with reference to ‘diffusion of innovation theory’. Originality/Value - The views of RD’s who practice NGx have not been previously studied. These data highlight requirements for future dietetic training provision and more inclusive service delivery models. Regulation of NGx services and formal recognition by professional bodies is needed to address the research/practice translation gap

Cognitive-behavioural longitudinal assessment in ALS:The Italian Edinburgh Cognitive and Behavioural ALS Screen (ECAS)

<p><i>Objective</i>: The study presents data on the longitudinal administration of the Italian Edinburgh Cognitive and Behavioral ALS Screen (ECAS). We investigated cognitive-behavioral performance in a group of ALS patients over time and the feasibility of repeating the ECAS longitudinally compared with standard neuropsychological tests. Finally, correlations between clinical/genetic and cognitive/behavioral data were considered. <i>Methods</i>: One hundred and sixty-eight ALS patients were tested at baseline (T₀). Among these, 48 patients performed the ECAS after 6 months (T₁), 18 patients performed it at T₂ (12 months), and five patients were assessed after 24 months (T₃). Participants were also administered two cognitive test (FAB; MoCA) and psychological questionnaires (BDI; STAI/Y). The FBI was carried out with caregivers. <i>Results</i>: No cognitive deterioration was found across follow-ups. In contrast, although scores did not change between T₀ and T₁, scores improved significantly for ECAS Total/ALS Non-specific and Memory domains when the ECAS was repeated on three occasions (T₀, T₁, T₂). Apathy/Inertia was the most common behavioral symptom, but no worsening of behavioral scores was detected over time. After 12–24 months, patients were still able to perform the ECAS in total, in contrast to FAB and MoCA, which were only partially administrable. <i>Conclusions</i>: The significant improvement of some ECAS scores over time supports the presence of possible practice effects, particularly in the memory domain, highlighting the need to accommodate for these in longitudinal assessments, through healthy controls groups or alternate versions. This work represents the first Italian ECAS follow-up study and confirms ECAS feasibility in patients with increasing physical disability.</p

Sexual assault, sexual abuse, and harassment: Understanding the mental health impact and providing care for survivors: An International Society for Traumatic Stress Studies Briefing Paper

Recent events including revelations of the systematic cover-up of widespread childhood sexual abuse in the Catholic Church, sexual assault and harassment accusations involving many prominent individuals in the entertainment and other industries in the U.S., Canada, Europe, Australia, and Japan, global coverage of cases of violent rape and rape-murder of girls and young women in India, and the #metoo movement, have served to increase public consciousness internationally regarding the pervasiveness of various forms of sexual victimization worldwide. In response, the International Society for Traumatic Stress Studies (ISTSS) commissioned this briefing paper to inform its membership, policymakers, and global stakeholders about the prevalence, impact, and barriers faced by survivors of various forms of sexual victimization including attempted and completed rape, sexual abuse in childhood, and sexual harassment in workplace and educational settings. This paper outlines the research evidence regarding (1) the prevalence of different forms of sexual victimization worldwide including childhood sexual abuse, various forms of sexual assault in adulthood, and sexual harassment in workplace and educational settings, (2) the prevalence of various forms of sexual victimization among several marginalized groups, (3) the psychological, behavioral, and physical health impacts of sexual victimization in childhood and adulthood, (4) evidence-based interventions for survivors of sexual victimization, and (5) barriers to treatment seeking commonly faced by survivors of different forms of sexual victimization. Recommendations are also made in the areas of policy, practice, research, and for professional organizations. Research conducted throughout the world continues to document the alarmingly high prevalence of various forms of sexual victimization throughout the lifespan, including the sexual abuse of children, sexual assault of adults, and sexual harassment within individuals’ place of employment and in educational settings. Although all individuals are vulnerable to experiences of sexual victimization, sexual assault, abuse, and harassment are gendered crimes, such that women and girls are more likely to be victims of these forms of sexual violence. In addition, members of a number of marginalized groups face substantially increased vulnerability to sexual victimization. These include individuals with disabilities, sexual and gender minorities, homeless individuals, individuals engaging in various kinds of sex work, and members of indigenous populations. Further, the impact of sexual victimization is both broad and targeted, with various forms of sexual victimization, including experiences of childhood sexual abuse and sexual assault in adulthood, associated with a host of negative outcomes including the development of posttraumatic stress disorder, depression, anxiety, substance use disorders, eating disordered pathology, suicidality, dissociation, and high risk sexual behaviors. Further, sexual victimization is associated with risk for a number of negative physical health outcomes including obesity, gastrointestinal disorders, chronic pelvic pain, and reproductive health issues. There exists a robust evidence base supporting the efficacy of psychological treatment for PTSD symptomology among adult survivors of childhood sexual abuse and sexual assault. Of extant treatments, cognitive-behavioral based treatments have the strongest evidence for their efficacy. Similarly, cognitive-behavioral treatments, such as trauma-focused CBT, have demonstrated efficacy in treating PTSD and depressive symptomology among children and adolescents who have experienced sexual abuse. There is also some evidence supporting the efficacy of psychopharmacological treatment in reducing PTSD symptomology among adult survivors of sexual abuse or assault. Conversely, there is far more limited research examining the efficacy of psychological treatments for PTSD in other cultural contexts, with the vast majority of research involving United States samples. There is also much less evidence regarding the impact of trauma-focused treatments on other outcomes besides PTSD symptomology and depression, or examining how to treat additional behavioral and mental health issues among survivors of sexual victimization. Finally, almost no research has evaluated the efficacy of psychological treatments for individuals who have experienced sexual harassment in their workplace. Further, research documents that survivors of various forms of sexual victimization often face substantial barriers to disclosing their experience or seeking formal help. These barriers include issues related to defining the experience as a victimization, concerns about not being believed or taken seriously, and feelings of stigma, shame, or embarrassment. Other barriers include concerns about whether the experience will be reported to authorities, mistrust of formal support systems, and prior negative experiences following disclosure of a sexual victimization experience. Many survivors also may be unaware of services that are available to them, may believe that available services are not appropriate for them, and may also face substantial barriers to accessing the care that is available, and available care may be inadequate for addressing their needs in many parts of the world. Finally, it is important to note that many individuals who experience sexual victimization face ongoing issues related to poverty, socioeconomic disadvantage, ongoing personal and community violence, and belong to marginalized groups. Given the prevalence, impact, and substantial barriers to care faced by individuals who experience sexual victimization, including childhood sexual abuse, sexual assault, and sexual harassment, it is clear that concerted, international, and collaborative efforts involving policymakers, researchers, clinicians, professional organizations, and other global stakeholders is imperative

Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells

The goal of targeted cancer therapies is to specifically block oncogenic signalling, thus maximising efficacy, while reducing side-effects to patients. The gamma-secretase (GS) complex is an attractive therapeutic target in haematological malignancies and solid tumours with major pharmaceutical activity to identify optimal inhibitors. Within GS, nicastrin (NCSTN) offers an opportunity for therapeutic intervention using blocking monoclonal antibodies (mAbs). Here we explore the role of anti-nicastrin monoclonal antibodies, which we have developed as specific, multi-faceted inhibitors of proliferation and invasive traits of triple-negative breast cancer cells. We use 3D in vitro proliferation and invasion assays as well as an orthotopic and tail vail injection triple-negative breast cancer in vivo xenograft model systems. RNAScope assessed nicastrin in patient samples. Anti-NCSTN mAb clone-2H6 demonstrated a superior anti-tumour efficacy than clone-10C11 and the RO4929097 small molecule GS inhibitor, acting by inhibiting GS enzymatic activity and Notch signalling in vitro and in vivo. Confirming clinical relevance of nicastrin as a target, we report evidence of increased NCSTN mRNA levels by RNA in situ hybridization (RNAScope) in a large cohort of oestrogen receptor negative breast cancers, conferring independent prognostic significance for disease-free survival, in multivariate analysis. We demonstrate here that targeting NCSTN using specific mAbs may represent a novel mode of treatment for invasive triple-negative breast cancer, for which there are few targeted therapeutic options. Furthermore, we propose that measuring NCSTN in patient samples using RNAScope technology may serve as companion diagnostic for anti-NCSTN therapy in the clinic

High-Throughput Sequencing of mGluR Signaling Pathway Genes Reveals Enrichment of Rare Variants in Autism

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism

African multi-site 2-year neuropsychological study of school-age children perinatally infected, exposed, and unexposed to human immunodeficiency virus

CITATION: Boivin, M. J. et al. 2020. African Multi-Site 2-Year Neuropsychological Study of School-Age Children Perinatally Infected, Exposed, and Unexposed to Human Immunodeficiency Virus. Clinical infectious diseases, 71(7): e105–e114. doi:10.1093/cid/ciz1088The original publication is available at https://academic.oup.com/cid/Background Children living with human immunodeficiency virus (HIV) are at neuropsychological risk for cognitive and motor dysfunction. However, few prospective, multi-site studies have evaluated neuropsychological outcomes longitudinally among perinatally infected African children who received early antiretroviral treatment (ART). Methods We enrolled 611 children aged 5 to 11 years at 6 sites (South Africa [3], Zimbabwe, Malawi, Uganda). Of these, there were 246 children living with HIV (HIV+) who were initiated on ART before 3 years of age in a prior clinical trial comparing nevirapine to lopinavir/ritonavir (International Maternal Pediatric Adolescent Acquired Immunodeficiency Syndrome Clinical Trials [IMPAACT] P1060); 183 age-matched, exposed but uninfected (HEU) children; and 182 unexposed and uninfected (HUU) children. They were compared across 3 assessment time points (Weeks 0, 48, and 96) on cognitive ability (Kaufman Assessment Battery for Children, second edition [KABC-II]), attention/impulsivity (Tests of Variables of Attention [TOVA]), motor proficiency (Bruininks-Oseretsky Test, second edition [BOT-2]), and on the Behavior Rating Inventory of Executive Function (BRIEF). The cohorts were compared using linear mixed models, adjusting for site, child’s age and sex, and selected personal/family control variables. Results The HIV+ cohort performed significantly worse than the HEU and HUU cohorts for all KABC-II, TOVA, and BOT-2 performance outcomes across all 3 time points (P values < .001). The HUU and HEU cohorts were comparable. For the KABC-II planning/reasoning subtests, the HIV+ children showed less improvement over time than the HUU and HEU groups. The groups did not differ significantly on the BRIEF. Conclusions Despite initiation of ART in early childhood and good viral suppression at the time of enrollment, the HIV+ group had poorer neuropsychological performance over time, with the gap progressively worsening in planning/reasoning. This can be debilitating for self-management in adolescence.https://academic.oup.com/cid/article/71/7/e105/5649306?login=truePublishers versio