Assessing the Attitudes and Perceptions of the Old Order Amish toward Genetic Testing for Familial Defective Apolipoprotein B-100

Through a founder effect, one in eight Lancaster County, PA, Amish harbors the pathogenic APOB variant R3527Q, causing Familial Defective Apolipoprotein B-100 (FDB) that is rare in the general population. Affected individuals are at increased risk for high low density lipoprotein (LDL) cholesterol levels and cardiovascular disease and may benefit from early screening and treatment. A qualitative interview approach was used to investigate the genetic risk perceptions of the Amish and their attitudes towards genetic testing for FDB. The goal was to identify elements necessary for a successful program that would identify high risk individuals in the Lancaster County Amish community and provide them with potentially lifesaving education and interventions. Thirty interviews were conducted. Collected data were analyzed and coded for common themes. Participants perceived a great deal of importance in genetic risk and were aware of the significant impact genetics have on health. Most individuals perceived genetic risk as more significant than family history. Twenty-four of 30 individuals would consider testing; of these, all 24 reported they would take proactive measures to reduce risks if given a positive result. Most would prefer diet modification and natural health remedies, with prescription medication only as a last resort. Several participants stated that most Amish people would be unlikely to test if they were feeling healthy. Cost was the most significant barrier to pursuing testing. Implementing a successful screening program would require community outreach and awareness, risk reduction education and support, and minimal out-of-pocket expenses. The program’s success provides insights into the efficacy of predictive genetic screening for the general population. [Abstract by authors.

Short and long-term clinical outcomes of use of beta-interferon or glatiramer acetate for people with clinically isolated syndrome : a systematic review of randomised controlled trials and network meta-analysis

Source of funding: This work is part of a larger report commissioned by the NIHR HTA Programme as project number ID809. A.C. and G.J.M.T. are partly supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care West Midlands at the University Hospitals Birmingham NHS Foundation Trust.Peer reviewedPublisher PD

Randomised controlled trial of early frenotomy in breastfed infants with mild-moderate tongue-tie

TRIAL DESIGN: A randomised, parallel group, pragmatic trial. SETTING: A large UK maternity hospital. PARTICIPANTS: Term infants <2 weeks old with a mild or moderate degree of tongue-tie, and their mothers who were having difficulties breastfeeding. OBJECTIVES: To determine if immediate frenotomy was better than standard breastfeeding support. INTERVENTIONS: Participants were randomised to an early frenotomy intervention group or a ‘standard care’ comparison group. OUTCOMES: Primary outcome was breastfeeding at 5 days, with secondary outcomes of breastfeeding self-efficacy and pain on feeding. Final assessment was at 8 weeks; 20 also had qualitative interviews. Researchers assessing outcomes, but not participants, were blinded to group assignment. RESULTS: 107 infants were randomised, 55 to the intervention group and 52 to the comparison group. Five-day outcome measures were available for 53 (96%) of the intervention group and 52 (100%) of the comparison group, and intention-to-treat analysis showed no difference in the primary outcome—Latch, Audible swallowing, nipple Type, Comfort, Hold score. Frenotomy did improve the tongue-tie and increased maternal breastfeeding self-efficacy. At 5 days, there was a 15.5% increase in bottle feeding in the comparison group compared with a 7.5% increase in the intervention group. After the 5-day clinic, 44 of the comparison group had requested a frenotomy; by 8 weeks only 6 (12%) were breastfeeding without a frenotomy. At 8 weeks, there were no differences between groups in the breastfeeding measures or in the infant weight. No adverse events were observed. CONCLUSIONS: Early frenotomy did not result in an objective improvement in breastfeeding but was associated with improved self-efficacy. The majority in the comparison arm opted for the intervention after 5 days

Inflammation in benign prostate tissue and prostate cancer in the finasteride arm of the Prostate Cancer Prevention Trial

BACKGROUND: A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here we studied these associations in the PCPT finasteride arm. METHODS: Prostate cancer cases (N=197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N=248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of H&E stained sections. Logistic regression was used for statistical analysis. RESULTS: In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas; p < 0.001 for difference compared to placebo arm. Overall, the odds of prostate cancer did not differ by prevalence (OR=0.90, 95% CI 0.44-1.84) or extent (P-trend=0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR=1.07, 95% CI 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammationin either cases or controls. CONCLUSION: The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. IMPACT: Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation

PTEN protein loss by immunostaining: Analytic validation and prognostic indicator for a high risk surgical cohort of prostate cancer patients

PURPOSE: Analytically validated assays to interrogate biomarker status in clinical samples are crucial for personalized medicine. PTEN is a tumor suppressor commonly inactivated in prostate cancer that has been mechanistically linked to disease aggressiveness. Though deletion of PTEN, as detected by cumbersome fluorescence in situ hybridization (FISH) spot counting assays, is associated with poor prognosis, few studies have validated immunohistochemical (IHC) assays to determine whether loss of PTEN protein is associated with unfavorable disease. EXPERIMENTAL DESIGN: PTEN IHC was validated by employing formalin fixed and paraffin embedded isogenic human cell lines containing or lacking intact PTEN alleles. PTEN IHC was 100% sensitive and 97.8% specific for detecting genomic alterations in 58 additional cell lines. PTEN protein loss was then assessed on 376 prostate tumor samples, and PTEN FISH or high resolution SNP microarray analysis was performed on a subset of these cases. RESULTS: PTEN protein loss, as assessed as a dichotomous IHC variable, was highly reproducible, correlated strongly with adverse pathologic features (e.g. Gleason score and pathological stage), detected between 75% and 86% of cases with PTEN genomic loss, and was found at times in the absence of apparent genomic loss. In a cohort of 217 high risk surgically treated patients, PTEN protein loss was associated with decreased time to metastasis. CONCLUSIONS: These studies validate a simple method to interrogate PTEN status in clinical specimens and support the utility of this test in future multi-center studies, clinical trials and ultimately perhaps for routine clinical care

Surgery for rheumatic heart disease in the Northern Territory, Australia, 1997-2016: what have we gained?

Background: Between 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival. Methods: A retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016. Survival was examined using Kaplan-Meier and Cox regression analysis. Findings: The cohort included 281 adults and 61 children. The median (IQR) age at first surgery was 31 (18-42) years; 173/342 (51%) had a valve replacement, 113/342 (33%) had a valve repair and 56/342 (16%) had a commissurotomy. There were 93/342 (27%) deaths during a median (IQR) follow-up of 8 (4-12) years. The overall 10-year survival was 70% (95% CI: 64% to 76%). It was 62% (95% CI: 53% to 70%) in those having valve replacement. There were 204/281 (73%) adults with at least 1 preoperative comorbidity. Preoperative comorbidity was associated with earlier death, the risk of death increasing with each comorbidity (HR: 1.3 (95% CI: 1.2 to 1.5), p50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death. Interpretation: Survival after valve replacement for RHD in this region of Australia has not improved. Although the patients were young, many had multiple comorbidities, which influenced long-term outcomes. The increasing prevalence of complex comorbidity in the region is a barrier to achieving optimal health outcomes

Blastococcus atacamensis sp. nov., a novel strain adapted to life in the Yungay core region of the Atacama Desert

A polyphasic study was undertaken to establish the taxonomic status of a Blastococcus strain isolated from an extreme hyper-arid Atacama Desert soil. The isolate, strain P6T, was found to have chemotaxonomic and morphological properties consistent with its classification in the genus Blastococcus . It was shown to form a well-supported branch in the Blastococcus 16S rRNA gene tree together with the type strains of Blastococcus capsensis and Blastococcus saxobsidens and was distinguished from the latter, its close phylogenetic neighbour, by a broad range of phenotypic properties. The draft genome sequence of isolate P6T showed 84.6?% average nucleotide identity, 83.0?% average amino acid identity and a digital DNA–DNA hybridisation value of 27.8?% in comparison with the genome sequence of B. saxobsidens DSM 44509T, values consistent with its assignment to a separate species. Based on these data it is proposed that isolate P6T (NCIMB 15090T=NRRL B-65468T) be assigned to the genus Blastococcus as Blastococcus atacamensis sp. nov. Analysis of the whole genome sequence of B. atacamensis P6T, with 3778 open reading frames and a genome size of 3.9?Mb showed the presence of genes and gene clusters that encode for properties that reflect its adaptation to the extreme environmental conditions that prevail in Atacama Desert soils

The Emergence and Development of Association Football: Influential Sociocultural Factors in Victorian Birmingham

This article explores the interdependent, complex sociocultural factors that facilitated the emergence and diffusion of football in Birmingham. The focus is the development of football in the city, against the backdrop of the numerous social changes in Victorian Birmingham. The aim is to fill a gap in the existing literature which seemingly overlooked Birmingham as a significant footballing centre, and the ‘ordinary and everyday’ aspects of the game’s early progression. Among other aspects, particular heed is paid to the working classes’ involvement in football, as previous literature has often focused on the middle classes and their influence on and participation in organized sport. As the agency of the working classes along with their mass participation and central role in the game’s development is unfolded, it is argued that far from being passive cultural beings, the working classes, from the beginnings, actively negotiated the development of their own emergent football culture