Women’s experiences of the diagnostic journey in uterine adenomyosis:A scoping review protocol

Introduction Uterine adenomyosis is a benign gynaecological disease that causes physical and psychological problems, impacting on relationships. It is poorly understood and consequently may be diagnosed late. This protocol describes the process of conducting a systematic scoping review to retrieve and describe literature examining the daily experience and impact of living with uterine adenomyosis. It will explore the journey to diagnosis (and perceptions of what this process is like); identify the main concepts currently used in the literature and highlight gaps in knowledge for future research in relevant populations. Methods and analysis Using the Joanna Briggs Institute methodology, the population-concept-context approach is used to form clear review questions. A three-phase search strategy will locate published and unpublished evidence from multiple sources. All articles reporting on the personal experiences of women diagnosed with uterine adenomyosis will be considered. Findings from qualitative, quantitative and mixed-method study designs from all settings will be included, not limited by geography but restricted to English. Documents will be screened by the primary researcher, supported by university supervisors. Search outputs will be presented using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 flow diagram. No formal quality appraisal will be conducted. Review findings will be descriptively collated and reported consistent with the Scoping Review Extension of the PRISMA checklist. Patient and public involvement engagement reflected a positive response for the project that this protocol supports. Ethics and dissemination As primary data will not be collected, formal ethical approval is not required. Prepared as part of a professional doctorate thesis, the findings of this study will be disseminated via peer-reviewed publications, conference presentations, support groups and social media networks.</p

Fishmeal supplementation during ovine pregnancy and lactation protects against maternal stress-induced programming of the offspring immune system

Background: Prenatally stressed offspring exhibit increased susceptibility to inflammatory disorders due to in utero programming. Research into the effects of n-3 PUFAs shows promising results for the treatment and prevention of these disorders. The purpose of this study was to investigate whether maternal fishmeal supplementation during pregnancy and lactation protects against programming of the offspring\u27s immune response following simulated maternal infection. Methods: In order to accomplish this, 53 ewes were fed a diet supplemented with fishmeal (FM; rich in n-3 PUFA) or soybean meal (SM; rich in n-6 PUFAs) from day 100 of gestation (gd 100) through lactation. On gd135, half the ewes from each dietary group were challenged with either 1.2 μg/kg Escherichia coli lipopolysaccharide (LPS) endotoxin to simulate a bacterial infection, or saline as the control. At 4.5 months of age the offspring\u27s dermal immune response was assessed by cutaneous hypersensitivity testing with ovalbumin (OVA) and candida albicans (CAA) 21 days after sensitization. Skinfold measurements were taken and serum blood samples were also collected to assess the primary and secondary antibody immune response. Results: Offspring born to SM + LPS mothers had a significantly greater change in skinfold thickness in response to both antigens as well as a greater secondary antibody response to OVA compared to all treatments. Conclusions: Supplementation during pregnancy with FM appears to protect against adverse fetal programming that may occur during maternal infection and this may reduce the risk of atopic disease later in life

Vertical integration and firm boundaries : the evidence

Since Ronald H. Coase's (1937) seminal paper, a rich set of theories has been developed that deal with firm boundaries in vertical or input–output structures. In the last twenty-five years, empirical evidence that can shed light on those theories also has been accumulating. We review the findings of empirical studies that have addressed two main interrelated questions: First, what types of transactions are best brought within the firm and, second, what are the consequences of vertical integration decisions for economic outcomes such as prices, quantities, investment, and profits. Throughout, we highlight areas of potential cross-fertilization and promising areas for future work

The Lantern Vol. 3, No. 2, March 1935

• Puppets of Propaganda • Reluctance • Reflections From My Diary • Reverie • Bash Turner Enters the Limelight • The College Students\u27 Obligation • The Schwenkfelders • Love\u27s Desire • Verse • On the Squirt of a Grapefruit • Pioneers! • Whither Fraternities? • Mary Peters: A Book Review • Different as Night and Day • Ode to an Alley Cathttps://digitalcommons.ursinus.edu/lantern/1005/thumbnail.jp

Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood–Onset Retinal Dystrophy

PurposeTo provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations.DesignNonrandomized, multicenter clinical trial.ParticipantsEight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood–onset retinal degeneration (SECORD).MethodsPatients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment.Main Outcome MeasuresThe primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire.ResultsAll patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area.ConclusionsTreatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns

Maize Cultivar Performance under Diverse Organic Production Systems

Maize (Zea mays L.) performance can vary widely between different production systems. The need for high-performing hybrids for organic systems with wide adaptation to various macroenvironments is becoming increasingly important. The goal of this study was to characterize inbred lines developed by distinct breeding programs for their combining ability and hybrid yield performance across diverse organic environments. Parent lines were selected from five different breeding programs to give a sample of publically available germplasm with potential for use in organic production systems with expired plant variety protection (Ex-PVP) and current commercial inbreds as benchmarks. A North Carolina Design II mating design was used to produce all possible cross combinations between seven lines designated as males and seven lines designated as females. A significantly positive general combining ability for the female inbred UHF134 suggests that it performs well in hybrid combination. Significant general combining ability was not observed for any male inbred line in this study. Several significantly positive specific combining abilities suggest that nonadditive genetic effects play an important role in determining yield in this germplasm. Further analysis revealed that hybrids containing either an Ex-PVP line or a commercial inbred line were on average superior to hybrids containing only inbreds developed by the cooperators of this study. This demonstrates the utility of testing inbreds from diverse sources when developing hybrids for organic production systems

Smooth muscle enriched long non-coding RNA (SMILR) regulates cell proliferation

Background—Phenotypic switching of vascular smooth muscle cells from a contractile to a synthetic state is implicated in diverse vascular pathologies, including atherogenesis, plaque stabilization, and neointimal hyperplasia. However, very little is known about the role of long noncoding RNA (lncRNA) during this process. Here, we investigated a role for lncRNAs in vascular smooth muscle cell biology and pathology. Methods and Results—Using RNA sequencing, we identified &gt;300 lncRNAs whose expression was altered in human saphenous vein vascular smooth muscle cells following stimulation with interleukin-1α and platelet-derived growth factor. We focused on a novel lncRNA (Ensembl: RP11-94A24.1), which we termed smooth muscle–induced lncRNA enhances replication (SMILR). Following stimulation, SMILR expression was increased in both the nucleus and cytoplasm, and was detected in conditioned media. Furthermore, knockdown of SMILR markedly reduced cell proliferation. Mechanistically, we noted that expression of genes proximal to SMILR was also altered by interleukin-1α/platelet-derived growth factor treatment, and HAS2 expression was reduced by SMILR knockdown. In human samples, we observed increased expression of SMILR in unstable atherosclerotic plaques and detected increased levels in plasma from patients with high plasma C-reactive protein. Conclusions—These results identify SMILR as a driver of vascular smooth muscle cell proliferation and suggest that modulation of SMILR may be a novel therapeutic strategy to reduce vascular pathologies

Differential antibody responses to Plasmodium falciparum merozoite proteins in Malawian children with severe malaria

Cerebral malaria (CM) and severe malarial anemia (SMA) are 2 major causes of death in African children infected with Plasmodium falciparum. We investigated levels of naturally acquired antibody to conserved and variable regions of merozoite surface protein (MSP)-1 and MSP-2, apical membrane antigen (AMA)-1, and rhoptry-associated protein 1 in plasma samples from 126 children admitted to the hospital with CM, 59 with SMA, and 84 with uncomplicated malaria (UM) in Malawi. Children with SMA were distinguished by very low levels of immunoglobulin (Ig) G to the conserved C-terminus of MSP-1 and MSP-2 and to full-length AMA-1. Conversely, children with CM had significantly higher levels of IgG to the conserved regions of all antigens examined than did children with UM (for MSP-1 and AMA-1, P&lt; .005; for MSP-2, P&lt; .05) or SMA (for MSP-1 and MSP-2, P&lt;.001; for AMA-1, P&lt; .005). These distinct IgG patterns might reflect differences in age, exposure to P. falciparum, and/or genetic factors affecting immune responses

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer