Nurses' preparedness to care for women exposed to Intimate Partner Violence: a quantitative study in primary health care

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence (IPV) has a deep impact on women's health. Nurses working in primary health care need to be prepared to identify victims and offer appropriate interventions, since IPV is often seen in primary health care. The aim of the study was to assess nurses' preparedness to identify and provide nursing care to women exposed to IPV who attend primary health care.</p> <p>Method</p> <p>Data was collected using a questionnaire to nurses at the primary health care centres. The response rate was 69.3%. Logistic regression analysis was used to test relationships among variables.</p> <p>Results</p> <p>Shortcomings were found regarding preparedness among nurses. They lacked organisational support e.g. guidelines, collaboration with others and knowledge regarding the extensiveness of IPV. Only half of them always asked women about violence and mostly when a woman was physically injured. They felt difficulties to know how to ask and if they identified violence they mostly offered the women a doctor's appointment. Feeling prepared was connected to obtaining knowledge by themselves and also to identifying women exposed to IPV.</p> <p>Conclusion</p> <p>The majority of the nurses were found to be quiet unprepared to provide nursing care to women exposed to IPV. Consequences might be treatment of symptoms but unidentified abuse and more and unnecessary suffering for these women. Improvements are needed on both at the level of the organisation and individual.</p

Common founder effects of hereditary hemochromatosis, Wilson´s disease, the long QT syndrome and autosomal recessive deafness caused by two novel mutations in the WHRN and TMC1 genes.

BACKGROUND: Genealogy and molecular genetic studies of a Swedish river valley population resulted in a large pedigree, showing that the hereditary hemochromatosis (HH) HFE/p.C282Y mutation is inherited with other recessive disorders such as Wilson´s disease (WND), a rare recessive disorder of copper overload. The population also contain individuals with the Swedish long QT syndrome (LQTS1) founder mutation (KCNQ1/p.Y111C) which in homozygotes causes the Jervell & Lange Nielsen syndrome (JLNS) and hearing loss (HL).Aims of the study were to test whether the Swedish long QT founder mutation originated in an ancestral HFE family and if carriers had an increased risk for hemochromatosis (HH), a treatable disorder. We also aimed to identify the pathogenic mutation causing the hearing loss disorder segregating in the pedigree. METHODS: LQTS patients were asked about their ancestry and possible origin in a HH family. They were also offered a predictive testing for the HFE genotype. Church books were screened for families with hearing loss. One HH family had two members with hearing loss, who underwent molecular genetic analysis of the LQTS founder mutation, connexin 26 and thereafter exome sequencing. Another family with hearing loss in repeat generations was also analyzed for connexin 26 and underwent exome sequencing. RESULTS: Of nine LQTS patients studied, four carried a HFE mutation (two p.C282Y, two p.H63D), none was homozygous. Three LQTS patients confirmed origin in a female founder ( b 1694, identical to AJ b 1694, a HFE pedigree member from the Fax river. Her descent of 44 HH families, included also 29 families with hearing loss (HL) suggesting JLNS. Eleven LQTS probands confirmed origin in a second founder couple (b 1614/1605) in which the woman b 1605 was identical to a HFE pedigree member from the Fjällsjö river. In her descent there were not only 64 HH, six WND families, one JLNS, but also 48 hearing loss families. Most hearing loss was non syndromic and caused by founder effects of the late 16th century. One was of Swedish origin carrying the WHRN, c.1977delC, (p.S660Afs*30) mutation, the other was a TMC1(NM_138691),c.1814T>C,(p.L605P) mutation, possibly of Finnish origin. CONCLUSIONS: Deep human HFE genealogies show HFE to be associated with other genetic disorders like Wilson´s disease, LQTS, JLNS, and autosomal recessive hearing loss. Two new homozygous HL mutations in WHRN/p.S660Afs*30 and TMC1/p.L605P were identified,none of them previously reported from Scandinavia. The rarity of JLNS was possibly caused by miscarriage or intrauterine death. Most hearing loss (81.7%) was seen after 1844 when first cousin marriages were permitted. However, only 10 (10.3%) came from 1st cousin unions and only 2 (2.0 %) was born out of wedlock

SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts

Acknowledgements We sincerely thank the patients and family members who participated in this study. We would also like to thank Stefan Esher, Umeå University, for help with genealogy, and Anna Westerlund for excellent technical assistance. This work was supported by grants from the FOU, at the Umeå university hospital, and the Medical Faculty at Umeå University. The work at University of Gothenburg was supported by grants from The Swedish Research Council, the Swedish Rheumatism Association, the Royal 80-Year Fund of King Gustav V, ALF/LUA research grant from Sahlgrenska University Hospital in Gothenburg and the Lundberg Foundation. The work at the University of Gothenburg and the University of Aberdeen was supported by Euroclast, a Marie Curie FP7-People-2013-ITN: # 607446.Peer reviewedPublisher PD

Novel MYH11 and ACTA2 mutations reveal a role for enhanced TGFβ signaling in FTAAD

BACKGROUND: Thoracic aortic aneurysm / dissection (TAAD) is a common phenotype that may occur as an isolated manifestation or within the constellation of a defined syndrome. In contrast to syndromic TAAD, the elucidation of the genetic basis of isolated TAAD has only recently started. To date, defects have been found in genes encoding extracellular matrix proteins (fibrillin-1, FBN1; collagen type III alpha 1, COL3A1), proteins involved in transforming growth factor beta (TGFβ) signaling (TGFβ receptor 1 and 2, TGFBR1/2; and SMAD3) or proteins that build up the contractile apparatus of aortic smooth muscle cells (myosin heavy chain 11, MYH11; smooth muscle actin alpha 2, ACTA2; and MYLK). METHODS AND RESULTS: In 110 non-syndromic TAAD patients that previously tested negative for FBN1 or TGFBR1/2 mutations, we identified 7 ACTA2 mutations in a cohort of 43 familial TAAD patients, including 2 premature truncating mutations. Sequencing of MYH11 revealed an in frame splice-site alteration in one out of two probands with TAA(D) associated with PDA but none in the series of 22 probands from the cohort of 110 patients with non-syndromic TAAD. Interestingly, immunohistochemical staining of aortic biopsies of a patient and a family member with MYH11 and patients with ACTA2 missense mutations showed upregulation of the TGFβ signaling pathway. CONCLUSIONS: MYH11 mutations are rare and typically identified in patients with TAAD associated with PDA. ACTA2 mutations were identified in 16% of a cohort presenting familial TAAD. Different molecular defects in TAAD may account for a different pathogenic mechanism of enhanced TGFβ signaling

Exome sequencing in Crisponi/CISS-like individuals reveals unpredicted alternative diagnoses

Crisponi/cold‐induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder characterized by a complex phenotype (hyperthermia and feeding difficulties in the neonatal period, followed by scoliosis and paradoxical sweating induced by cold since early childhood) and a high neonatal lethality. CS/CISS is a genetically heterogeneous disorder caused by mutations in CRLF1 (CS/CISS1), CLCF1 (CS/CISS2) and KLHL7 (CS/CISS‐like). Here, a whole exome sequencing approach in individuals with CS/CISS‐like phenotype with unknown molecular defect revealed unpredicted alternative diagnoses. This approach identified putative pathogenic variations in NALCN, MAGEL2 and SCN2A. They were already found implicated in the pathogenesis of other syndromes, respectively the congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome, the Schaaf‐Yang syndrome, and the early infantile epileptic encephalopathy‐11 syndrome. These results suggest a high neonatal phenotypic overlap among these disorders and will be very helpful for clinicians. Genetic analysis of these genes should be considered for those cases with a suspected CS/CISS during neonatal period who were tested as mutation negative in the known CS/CISS genes, because an expedited and corrected diagnosis can improve patient management and can provide a specific clinical follow‐up

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Clinical and genetic studies of three inherited skeletal disorders

Mutations in genes of importance for cartilage development may lead to skeletal malformations, chondroskeletal dysfunction and increased susceptibility to degenerative joint disease. Characterization of these mutations and identification of molecular pathways for the corresponding gene products have contributed to our understanding of mechanisms regulating skeletal patterning, endochondral ossification and joint formation. A five generation family segregating autosomal dominant osteochondritis dissecans (OCD) was identified. Affected family members presented with OCD in knees, hips and elbows, short stature, and early osteoarthritis. A genome wide scan and a multipoint linkage analysis identified aggrecan (ACAN) as a prime candidate gene. DNA sequence analysis of the ACAN-gene revealed heterozygosity for a missense mutation (c.6907G&gt;A) in affected subjects, resulting in a p.V2303M substitution in the aggrecan G3 domain C-type lectin. This domain is important for the interaction with other proteins in the cartilage extracellular matrix. To determine the effect of the V2303M substitution on secretion and interaction, we performed binding studies with recombinant mutated and wild type G3 proteins. We found decreased affinity or complete loss of interaction between V2303M aggrecan and fibulin1, fibulin2 and tenascin-R. Analysis of articular cartilage from an affected family member confirmed that V2303M aggrecan is produced and present. In search for gene mutations associated with multiple epiphyseal dysplasia (MED) we considered the ACAN-gene a likely candidate. The ACAN-gene was analysed in 39 individuals with MED and screened negative for mutations in six previously known MED genes. Sequence analysis revealed a heterozygous missense mutation (c.1448G&gt;T) in one adult male and compound heterozygous missense mutations (c.1366T&gt;C and c.836G&gt;A) in a five year old boy with healthy parents, each of them carrier for one of the mutations. A large family segregating autosomal dominant brachymesophalangia and OCD in finger joints was characterised. The clinical presentation in six affected family members was consistent with the diagnosis Brachydactyly type A1, in this family characterized by shortening of the middle phalanges, short ulnar styloid process, flattening of the metacarpal heads and mild osteoarthritis. The condition may be caused by mutations in the Indian hedgehog gene (IHH) or a yet unidentified gene on chromosome 5p13. Sequence analysis of the IHH-gene in affected individuals revealed a novel C to T transition (c.472C&gt;T) leading to a p.158Arg&gt;Cys substitution. Residue 158 in IHH is highly conserved throughout evolution and molecular structure modelling of IHH suggests that the R158C substitution leads to a conformational change at the site of interaction with the IHH-receptor. This supports that the substitution causes Brachydactyly type A1 in this family. In summary, we report on the clinical, radiological and molecular genetic characteristics of the three skeletal disorders OCD, MED and BDA1. Our results provide a novel molecular mechanism in the pathophysiology of familial osteochondritis dissecans confirming the importance of aggrecan C-type lectin for cartilage function. We also show that ACAN-gene mutations may be associated with MED extending the spectrum of skeletal dysplasias associated with the aggrecan gene. Finally, we report on a novel missense mutation in a conserved region of the IHH-gene associated with BDA1

Sudden cardiac death among the young in Sweden from 2000 to 2010 : An autopsy-based study

Aims To study the incidence and aetiology of sudden cardiac death (SCD) in 1- to 35-year-olds in Sweden from 2000 to 2010. Methods and results We used the database of the Swedish National Board of Forensic Medicine and the Swedish Cause of Death Registry and identified SCD cases by review of forensic files and death certificates. We identified 552 individuals with SCD in 1- to 35-year-olds; 156 (28%) were women. In 393 (71%), a forensic autopsy had been performed; in 131 (24%), a clinical autopsy had been performed; in 28 (5%) with no autopsy, a cardiac disease was diagnosed before death. The incidence of SCD per 100 000 person-years was 1.3 in 1- to 35-year-olds and 1.8 in 15- to 35-year-olds. In women, the incidence rates yearly decreased during the study period by 11% (95% confidence interval 6.6-14.2). The most common aetiology in 1- to 35-year-olds was sudden arrhythmic death syndrome (31%) and coronary artery disease (15%). In cases with forensic autopsy, death occurred during daily activity (48%), sleep (38%), and physical activity (14%); death was unwitnessed in 60%. Co-morbidity in 15- to 35-year-olds, e.g. psychiatric disorder, obesity, or diabetes, was present in 93/340 (27%) (73 men). Conclusion The incidence of SCD among 1- to 35-year-olds in Sweden during 2000-10 was 1.3 per 100 000 person-years (28% women); incidence was decreasing in women. Sudden arrhythmic death syndrome was the most common diagnosis. Co-morbidity such as psychiatric disorders and obesity was common among men