7 research outputs found
Cervico-mandibular muscle activity in females with chronic cervical pain a descriptive, cross-sectional, correctional study
No full textIncludes abstract.Includes bibliographical references.Chronic musculoskeletal conditions of the spine and periphery are a burden both internationally and in South Africa. There is a socio-economic burden as a consequence of the severity, duration and recurrence of chronic cervical musculoskeletal conditions among information technology and sedentary office workers. However, the precise mechanisms behind chronic cervical disorders remain unclear. It is theorised that the pathophysiological mechanisms in chronic cervical musculoskeletal conditions share a similar theoretical framework to chronic pain itself. The biopsychosocial model of chronic pain accepts the dynamic nature of pain. This model accepts the dual biological and psychosocial components that enhance the experience and maintenance of chronic pain, through central sensitisation. There appears to be a neurophysiological, biomechanical and psychological link between the cervical area and the temporomandibular area. Although numerous studies have implied that individuals with temporomandibular disorders have concurrent cervical dysfunction, there is currently no evidence that individuals with cervical dysfunction exhibit altered muscle activity in the masseter and cervical erector spinae muscles or report teeth clenching habits. Consequently, identification of factors that may contribute to chronic cervical musculoskeletal conditions, stemming from the temporomandibular area, may potentially be lost. The aim of the present study was to explore the activity levels of the cervicomandibular muscles in females with chronic cervical musculoskeletal conditions, who showed no symptoms of temporomandibular disorders. This study had a descriptive cross-sectional correlational design with single-blinding. The telephonic screening process was followed by the signing of informed consent forms. Validated questionnaires were used for categorisation and comparison of the socio-demographic and biopsychosocial profiles of the pain group (n = 20) and the no pain group (n = 22). The screening, informed consent and questionnaires were completed by an assistant. The first of five questionnaires, the adapted Research Diagnostic Criteria History questionnaire, was used as an instrument for exclusion of temporomandibular disorders and the recording of a daytime parafunctional teeth clenching habit. The remaining four questionnaires, listed as the Neck Disability Index, the Computer Usage Questionnaire, the Brief Pain Inventory, and the EuroQol-5D were used for determining levels of cervical disability for categorisation and comparison between groups, as well as for determining levels of pain-related disability, occupational and sporting activity, and health related quality of life
Clinical, splicing and functional analysis to classify BRCA2 exon 3 variants: application of a points-based ACMG/AMP approach
No full textSkipping of BRCA2 exon 3 (∆E3) is a naturally occurring splicing event, complicating clinical classification of variants that may alter ∆E3 expression. This study used multiple evidence types to assess pathogenicity of 85 variants in/near BRCA2 exon 3. Bioinformatically predicted spliceogenic variants underwent mRNA splicing analysis using minigenes and/or patient samples. ∆E3 was measured using quantitative analysis. A mouse embryonic stem cell (mESC) based assay was used to determine the impact of 18 variants on mRNA splicing and protein function. For each variant, population frequency, bioinformatic predictions, clinical data, and existing mRNA splicing and functional results were collated. Variant class was assigned using a gene-specific adaptation of ACMG/AMP guidelines, following a recently proposed points-based system. mRNA and mESC analysis combined identified six variants with transcript and/or functional profiles interpreted as loss of function. Cryptic splice site use for acceptor site variants generated a transcript encoding a shorter protein that retains activity. Overall, 69/85 (81%) variants were classified using the points-based approach. Our analysis shows the value of applying gene-specific ACMG/AMP guidelines using a points-based approach and highlights the consideration of cryptic splice site usage to appropriately assign PVS1 code strength.</p
Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes
No full textBACKGROUND: Higher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, whether these associations are causal remains unclear.METHODS: We explored the relation of maternal pre-/early-pregnancy BMI with 20 pregnancy and perinatal outcomes by integrating evidence from three different approaches (i.e. multivariable regression, Mendelian randomisation, and paternal negative control analyses), including data from over 400,000 women.RESULTS: All three analytical approaches supported associations of higher maternal BMI with lower odds of maternal anaemia, delivering a small-for-gestational-age baby and initiating breastfeeding, but higher odds of hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, caesarean section, large-for-gestational age, high birthweight, low Apgar score at 1 min, and neonatal intensive care unit admission. For example, higher maternal BMI was associated with higher risk of gestational hypertension in multivariable regression (OR = 1.67; 95% CI = 1.63, 1.70 per standard unit in BMI) and Mendelian randomisation (OR = 1.59; 95% CI = 1.38, 1.83), which was not seen for paternal BMI (OR = 1.01; 95% CI = 0.98, 1.04). Findings did not support a relation between maternal BMI and perinatal depression. For other outcomes, evidence was inconclusive due to inconsistencies across the applied approaches or substantial imprecision in effect estimates from Mendelian randomisation.CONCLUSIONS: Our findings support a causal role for maternal pre-/early-pregnancy BMI on 14 out of 20 adverse pregnancy and perinatal outcomes. Pre-conception interventions to support women maintaining a healthy BMI may reduce the burden of obstetric and neonatal complications.FUNDING: Medical Research Council, British Heart Foundation, European Research Council, National Institutes of Health, National Institute for Health Research, Research Council of Norway, Wellcome Trust.</p
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BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
No full textBreast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR
BRCA2 Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer.
No full textBreast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case-control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; P = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; P = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; P = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; P = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. Cancer Res; 77(11); 2789-99. ©2017 AACR
