Age-related macular degeneration: a disease of systemic or local complement dysregulation?

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries. The role of complement in the development of AMD is now well-established. While some studies show evidence of complement dysregulation within the eye, others have demonstrated elevated systemic complement activation in association with AMD. It is unclear which one is the primary driver of disease. This has important implications for designing novel complement-based AMD therapies. We present a summary of the current literature and suggest that intraocular rather than systemic modulation of complement may prove more effective

Birth and After Birth and Painting Churches: Tina Howe\u27s Examination of Love and Savagery in the American Family

Playwright Tina Howe has been quoted as saying that family life has been over-romanticized; the savagery has not been seen enough in the theatre and in movies . . . (Moore 101). In two of her plays, Birth and After Birth (1973) and Painting Churches (1983), that savagery appears in the form of name-calling, jealousy, apathy, disregard, and physical and mental abuse. A juxtaposition of the similarities in Birth and After Birth and Painting Churches will explain the savagery Howe is examining. The earlier play is written in the surrealistic style of lonesco and Beckett, playwrights who have been a major influence on Howe. The later work is a much more realistic, conventional play. Both center around three-member families (a set of parents and an only child) and take place at a time of significant change. The main focus is Painting Churches and the abuse that lies at the heart of the play. Mags Church (short for Margaret) has come home to help her parents, Fanny and Gardner, pack their things; they are moving from Boston to their summer cottage in Concuit. A promising young artist on the rise, she is also going to paint a portrait of them. But the painting of this portrait will be much more than the creating of a new piece of art for Mags; it will be a very personal and very trying test. Throughout the play, Howe reveals Mags\u27 multifaceted mental and emotional problems and how her mother, while essentially a loving parent, contributed greatly to her daughter\u27s lack of self-esteem and need to mask herself behind her work. She may even be responsible, and this thesis proves that Fanny Church subjected her only child to continuous psychological abuse, creating in her a deep-rooted psychosis. Birth and After Birth, written a decade earlier, examines some of the issues addressed in Painting Churches, and is basically used as backup evidence to help prove my theory

Med Moth: A Storytelling Platform for Improving Wellness in Medical Education

Background: Burnout is a major issue amongst medical students and professionals that demands a solution. Mindfulness has been shown to decrease burnout. Storytelling, as a form of mindfulness, leads to reflection. Few publications have studied the effect of storytelling on student and clinician wellness. To address wellness within their medical community and utilize the underexplored method of narrative medicine as a curricular enhancement, the authors designed and implemented a novel storytelling platform, Med Moth, at the University of Massachusetts Medical School (UMMS) and associated hospital (UMass Memorial Medical Center). Methods: Members of the community were invited to storytelling events to listen to and share stories about formative medical experiences. Four events were held between 2017 and 2018. After each event, participants received a survey inquiring how attendance benefitted them personally and professionally. Results: Clinicians, students, and faculty comprised the 104 first-time attendees surveyed. Med Moth produced a strong perceived benefit to surrogate measures including emotional exhaustion and depersonalization, defining characteristics of burnout, and professional development. Among these three measures, 66% of participants rated 4-5 (out of 5). Nearly all attendees (96%) rated 4-5 for the overall experience. Lastly, medical students reported a higher benefit regarding professional development than clinicians (p=0.002). Conclusions: This pilot study of a novel storytelling platform demonstrates positive personal and professional development outcomes, both during and after medical school training. Medical schools, residency programs, and medical institutions should strongly consider the implementation of such a wellness platform to build resiliency and to mitigate burnout through reflection

Progressive myoclonic epilepsy with Fanconi syndrome

This report illustrates the difficulties in diagnosing complex cases and demonstrates how whole exome sequencing can resolve complex phenotypes

AMMECR1: a single point mutation causes developmental delay, midface hypoplasia and elliptocytosis

Background: Deletions in the Xq22.3–Xq23 region, inclusive of COL4A5, have been associated with a contiguous gene deletion syndrome characterised by Alport syndrome with intellectual disability (Mental retardation), Midface hypoplasia and Elliptocytosis (AMME). The extrarenal biological and clinical significance of neighbouring genes to the Alport locus has been largely speculative. We sought to discover a genetic cause for two half-brothers presenting with nephrocalcinosis, early speech and language delay and midface hypoplasia with submucous cleft palate and bifid uvula.Methods: Whole exome sequencing was undertaken on maternal half-siblings. In-house genomic analysis included extraction of all shared variants on the X chromosome in keeping with X-linked inheritance. Patient-specific mutants were transfected into three cell lines and microscopically visualised to assess the nuclear expression pattern of the mutant protein.Results: In the affected half-brothers, we identified a hemizygous novel non-synonymous variant of unknown significance in AMMECR1 (c.G530A; p.G177D), a gene residing in the AMME disease locus. Transfected cell lines with the p.G177D mutation showed aberrant nuclear localisation patterns when compared with the wild type. Blood films revealed the presence of elliptocytes in the older brother.Conclusions: Our study shows that a single missense mutation in AMMECR1 causes a phenotype of midface hypoplasia, mild intellectual disability and the presence of elliptocytes, previously reported as part of a contiguous gene deletion syndrome. Functional analysis confirms mutant-specific protein dysfunction. We conclude that AMMECR1 is a critical gene in the pathogenesis of AMME, causing midface hypoplasia and elliptocytosis and contributing to early speech and language delay, infantile hypotonia and hearing loss, and may play a role in dysmorphism, nephrocalcinosis and submucous cleft palate.<br/

Variation in colorectal cancer treatment and outcomes in Scotland:real world evidence from national linked administrative health data

Background: Colorectal cancer (CRC) is the fourth most common type of cancer in the United Kingdom and the second leading cause of cancer death. Despite improvements in CRC survival over time, Scotland lags behind its UK and European counterparts. In this study, we carry out an exploratory analysis which aims to provide contemporary, population level evidence on CRC treatment and survival in Scotland. Methods: We conducted a retrospective population-based analysis of adults with incident CRC registered on the Scottish Cancer Registry (Scottish Morbidity Record 06 (SMR06)) between January 2006 and December 2018. The CRC cohort was linked to hospital inpatient (SMR01) and National Records of Scotland (NRS) deaths records allowing a description of their demographic, diagnostic and treatment characteristics. Cox proportional hazards regression models were used to explore the demographic and clinical factors associated with all-cause mortality and CRC specific mortality after adjusting for patient and tumour characteristics among people identified as early-stage and treated with surgery. Results: Overall, 32,691 (73%) and 12,184 (27%) patients had a diagnosis of colon and rectal cancer respectively, of whom 55% and 53% were early-stage and treated with surgery. Five year overall survival (CRC specific survival) within this cohort was 72% (82%) and 76% (84%) for patients with colon and rectal cancer respectively. Cox proportional hazards models revealed significant variation in mortality by sex, area-based deprivation and geographic location.Conclusions: In a Scottish population of patients with early-stage CRC treated with surgery, there was significant variation in risk of death, even after accounting for clinical factors and patient characteristics.<br/

Empowering Teachers with Low Intensity Strategies to Support Instruction: A Self-Monitoring Illustration

The purpose of “Empowering Teachers with Low-Intensity Strategies to Support Instruction,” a creative inquiry at Clemson University, was to equip teachers with low-intensity strategies that can be implemented within the classroom to boost the academic engagement of their students

Mechanisms of Fetal Programming in Hypertension

Events that occur in the early fetal environment have been linked to long-term health and lifespan consequences in the adult. Intrauterine growth restriction (IUGR), which may occur as a result of nutrient insufficiency, exposure to hormones, or disruptions in placental structure or function, may induce the fetus to alter its developmental program in order to adapt to the new conditions. IUGR may result in a decrease in the expression of genes that are responsible for nephrogenesis as nutrients are rerouted to the development of more essential organs. Fetal survival under these conditions often results in low birth weight and a deficit in nephron endowment, which are associated with hypertension in adults. Interestingly, male IUGR offspring appear to be more severely affected than females, suggesting that sex hormones may be involved. The processes of fetal programming of hypertension are complex, and we are only beginning to understand the underlying mechanisms

Deleterious coding variants in multi-case families with non-syndromic cleft lip and/or palate phenotypes

Nonsyndromic Cleft Lip and/or Palate (NSCLP) is regarded as a multifactorial condition in which clefting is an isolated phenotype, distinguished from the largely monogenic, syndromic forms which include clefts among a spectrum of phenotypes. Nonsyndromic clefting has been shown to arise through complex interactions between genetic and environmental factors. However, there is increasing evidence that the broad NSCLP classification may include a proportion of cases showing familial patterns of inheritance and contain highly penetrant deleterious variation in specific genes. Through exome sequencing of multi-case families ascertained in Bogota, Colombia, we identify 28 non-synonymous single nucleotide variants that are considered damaging by at least one predictive score. We discuss the functional impact of candidate variants identified. In one family we find a coding variant in the MSX1 gene which is predicted damaging by multiple scores. This variant is in exon 2, a highly conserved region of the gene. Previous sequencing has suggested that mutations in MSX1 may account for ~2% of NSCLP. Our analysis further supports evidence that a proportion of NSCLP cases arise through monogenic coding mutations, though further work is required to unravel the complex interplay of genetics and environment involved in facial clefting