Examining the perspectives of Massachusetts' highs school coaches concerning sports-related concussions and state mandated concussion education

Thesis (Ed.D.)--Boston UniversityBackground: The primary purpose of this study was to explore the knowledge, attitudes, and perceptions of Massachusetts' high school coaches who have completed mandated training relating to concussion recognition, management, and legislation. The second purpose was to examine their opinions on the effectiveness of state approved concussion education. Participants: High school coaches from Massachusetts' Interscholastic Athletic Association (MIAA) schools who have completed at least one season of coaching. Coaches from various sports were recruited for quantitative survey data (n = 104) and coaches from high concussion risk sports were recruited for qualitative interviews (n = 12). Methods: This study utilized a mixed methods research design, with an emphasis on qualitative methods. Interviews were conducted for qualitative data collection about the attitudes towards sports-related concussions and current concussion management practices of MIAA high school coaches. A survey was used to collect quantitative data about MIAA high school coaches' knowledge regarding concussions, concussion legislation, awareness about the risks of concussions, and perceived self-efficacy in managing concussion scenarios. Results: Major findings indicate that participants demonstrate only average levels of concussion knowledge and lack a sufficient understanding of how to practically apply that knowledge. Most participants report prudent attitudes towards player safety, but also acknowledge a "winning-oriented" youth sport culture. Many participants perceived themselves as knowledgeable and confident when handling concussions, but at the same time they believe athletic trainers or healthcare professionals should bear the primary responsibility for managing concussions. Remarkably, very few participants perceived current concussion education to be effective in changing coaching practices regarding concussions. Instead they report the most influential sources of information are personal or coaching experiences, the media, or in-person trainings. Conclusions: High school coaches are not qualified to make concussion management decisions due to their partial understanding of proper concussion care and several conflicts of interest that exist in current sport culture exposed by this study. Therefore, coaches' appropriate responsibility should be to establish and maintain a safe sporting environment. Additionally, the design and delivery of concussion education must be improved so that all coaches will possess the critical skills necessary to effectively implement appropriate concussion management protocols

Olaparib-induced Adaptive Response Is Disrupted by FOXM1 Targeting that Enhances Sensitivity to PARP Inhibition

FOXM1 transcription factor network is activated in over 84% of cases in high-grade serous ovarian cancer (HGSOC), and FOXM1 upregulates the expression of genes involved in the homologous recombination (HR) DNA damage and repair (DDR) pathway. However, the role of FOXM1 in PARP inhibitor response has not yet been studied. This study demonstrates that PARP inhibitor (PARPi), olaparib, induces the expression and nuclear localization of FOXM1. On the basis of ChIP-qPCR, olaparib enhances the binding of FOXM1 to genes involved in HR repair. FOXM1 knockdown by RNAi or inhibition by thiostrepton decreases FOXM1 expression, decreases the expression of HR repair genes, such as BRCA1 and RAD51, and enhances sensitivity to olaparib. Comet and PARP trapping assays revealed increases in DNA damage and PARP trapping in FOXM1-inhibited cells treated with olaparib. Finally, thiostrepton decreases the expression of BRCA1 in rucaparib-resistant cells and enhances sensitivity to rucaparib. Collectively, these results identify that FOXM1 plays an important role in the adaptive response induced by olaparib and FOXM1 inhibition by thiostrepton induces “BRCAness” and enhances sensitivity to PARP inhibitors

Intergenerational transmission of parenting: findings from a UK longitudinal study.

BACKGROUND: The quality of parenting is associated with a wide range of child and adult outcomes, and there is evidence to suggest that some aspects of parenting show patterns of intergenerational transmission. This study aimed to determine whether such intergenerational transmission occurs in mothers and fathers in a UK birth cohort. METHODS: The study sample consisted of 146 mothers and 146 fathers who were recruited from maternity wards in England and followed up for 24 months ['Generation 2' (G2)]. Perceptions of their own parenting [by 'Generation1' (G1)] were assessed from G2 parents at 12 months using the Parental Bonding Instrument (PBI). G2 parents were filmed interacting with their 'Generation 3' (G3) children at 24 months. RESULTS: We found that G1 mothers' 'affection' was associated with positive parenting behaviour in the G2 fathers ('positive responsiveness' β = 0.19, P = 0.04 and 'cognitive stimulation' β = 0.26, P < 0.01). G1 mothers' 'control' was associated with negative parenting behaviour in G2 mothers (decreased 'engagement' β = -0.19, P = 0.04), and negative parenting behaviour in G2 fathers (increased 'control' β = 0.18, P = 0.05). None of the G1 fathers' parenting variables were significantly associated with G2 parenting. CONCLUSIONS: There is evidence of intergenerational transmission of parenting behaviour in this highly educated UK cohort, with reported parenting of grandmothers associated with observed parenting in both mothers and fathers. No association was seen with reported parenting of grandfathers. This raises the possibility that parenting interventions may have benefits that are realised across generations

Glutathione S-transferase class mu regulation of apoptosis signal-regulating kinase 1 protein during VCD-induced ovotoxicity in neonatal rat ovaries

4-vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-related kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also studied. Postnatal day (PND) 4 rat ovaries were cultured in control media ±: 1) VCD (30 μM) for 2–8d; 2) VCD (30 μM) for 2d, followed by incubation in control media for 4d (acute VCD exposure); or 3) LY294002 (20 μM) for 6d. VCD exposure did not alter Gstm mRNA expression, however, GSTM protein increased (P \u3c 0.05) after 6d of both the acute and chronic treatments. Ask1 mRNA increased (0.33-fold; P \u3c 0.05) relative to control after 6d of VCD exposure. Ovarian GSTM:ASK1 protein complex formation was confirmed and, relative to control, the amount of GSTM bound to ASK1 increased 33% (P \u3c 0.05) by chronic but with no effect of acute VCD exposure. PI3K inhibition increased (P \u3c 0.05) GSTM protein by 40% and 71% on d4 and d6, respectively. These findings support involvement of GSTM in the ovarian response to VCD exposure, through regulation of pro-apoptotic ASK1

The P72R Polymorphism in R248Q/W p53 Mutants Modifies the Mutant Effect on Epithelial to Mesenchymal Transition Phenotype and Cell Invasion via CXCL1 Expression

High-grade serous carcinoma (HGSC), the most lethal subtype of epithelial ovarian cancer (EOC), is characterized by widespread TP53 mutations (\u3e90%), most of which are missense mutations (\u3e70%). The objective of this study was to investigate differential transcriptional targets affected by a common germline P72R SNP (rs1042522) in two p53 hotspot mutants, R248Q and R248W, and identify the mechanism through which the P72R SNP affects the neomorphic properties of these mutants. Using isogenic cell line models, transcriptomic analysis, xenografts, and patient data, we found that the P72R SNP modifies the effect of p53 hotspot mutants on cellular morphology and invasion properties. Most importantly, RNA sequencing studies identified CXCL1 a critical factor that is differentially affected by P72R SNP in R248Q and R248W mutants and is responsible for differences in cellular morphology and functional properties observed in these p53 mutants. We show that the mutants with the P72 SNP promote a reversion of the EMT phenotype to epithelial characteristics, whereas its R72 counterpart promotes a mesenchymal transition via the chemokine CXCL1. These studies reveal a new role of the P72R SNP in modulating the neomorphic properties of p53 mutants via CXCL1, which has significant implications for tumor invasion and metastasis

Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity

ADP ribosylation factor guanine nucleotide exchange factors (ARFGEFs) are a family of proteins implicated in cellular trafficking between the Golgi apparatus and the plasma membrane through vesicle formation. Among them is ARFGEF1/BIG1, a protein involved in axon elongation, neurite development, and polarization processes. ARFGEF1 has been previously suggested as a candidate gene for different types of epilepsies, although its implication in human disease has not been well characterized. International data sharing, in silico predictions, and in vitro assays with minigene study, western blot analyses, and RNA sequencing. We identified 13 individuals with heterozygous likely pathogenic variants in ARFGEF1. These individuals displayed congruent clinical features of developmental delay, behavioral problems, abnormal findings on brain magnetic resonance image (MRI), and epilepsy for almost half of them. While nearly half of the cohort carried de novo variants, at least 40% of variants were inherited from mildly affected parents who were clinically re-evaluated by reverse phenotyping. Our in silico predictions and in vitro assays support the contention that ARFGEF1-related conditions are caused by haploinsufficiency, and are transmitted in an autosomal dominant fashion with variable expressivity. We provide evidence that loss-of-function variants in ARFGEF1 are implicated in sporadic and familial cases of developmental delay with or without epilepsy

IQuaD dental trial; improving the quality of dentistry : a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

Peer reviewedPublisher PD

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

Peer reviewe