Intraosseous Synovial Sarcoma of the Proximal Tibia

Synovial Sarcoma is a malignant mesenchymal tumor that comprises 5–10% of all soft tissue sarcomas. The mean age of onset is thirty years old. Intraosseous presentation is very rare and has only been documented a few times. We report herein a case of a 53-year-old man with synovial sarcoma arising in the left proximal tibia. The patient underwent a wide surgical resection and reconstruction, followed by adjuvant chemotherapy. Three years later, the patient developed a local recurrence that resulted in an above-the-knee amputation. Eight months later, the patient has completed chemotherapy and is without signs of recurrence. The current recommended treatment for synovial sarcoma is wide surgical resection followed by chemotherapy as well as long-term followup. Despite improved surgical techniques, long-term survival rates remain low

A Scoping Review of the Roles, Training, and Impact of Community Health Workers in Oral Health Supplemental Tables

Objective: To synthesize English or Spanish-language literature on community health workers’ (CHWs’) roles, training, and impact in oral health. Basic research design: A scoping review conducted in accordance with the Arksey and O’Malley (2005) methodological framework. Method: Electronic literature searches were conducted in Medline (Ovid), Embase (Ovid), DOSS, CINAHL, Web of Science, and Global Health CAB from inception of the databases to April 2020. Three reviewers independently conducted the title and abstract and full-text reviews. This was followed by data charting by three reviewers and data summarizing by two reviewers. Results: Out of the 36 articles that met the inclusion criteria, most took place in the United States (n=15) with most published between 2012 and 2019 (12). CHWs were incorporated in programs that focused on access to dental care (n=10), oral health promotion only (9), early childhood caries (8), oral health promotion and services (5), and oral cancer screening (4). Common roles included providing oral health education and behavior change motivation to community members, facilitating utilization of dental services, and the delivery of diagnostic and dental services to community members. Training and outcomes were not consistently described across studies. Conclusion: CHWs have been used in oral health programs and interventions across a wide range of locations and contexts. The implementation and scaling-up of oral health CHW programs requires appropriate provision of training as well as community embedded monitoring and evaluation structures based on rigorous methods with clearly defined outcomes

Chemical characterisation and the anti-inflammatory, anti-angiogenic and antibacterial properties of date fruit (Phoenix dactylifera L.)

Ethnopharmacological relevance: Date fruit, Phoenix dactylifera L. has traditionally been used as a medicine in many cultures for the treatment of a range of ailments such as stomach and intestinal disorders, fever, oedema, bronchitis and wound healing. Aim of the review: The present review aims to summarise the traditional use and application of Phoenix dactylifera date fruit in different ethnomedical systems, additionally the botany and phytochemistry are identified. Critical evaluation of in vitro and in vitro studies examining date fruit in relation to anti-inflammatory, anti-angiogenic and antimicrobial activities are outlined. Key Findings: The ethnomedical use of Phoenix dactylifera in the treatment of inflammatory disease has been previously identified and reported. Furthermore, date fruit and date fruit co-products such as date syrup are rich sources of polyphenols, anthocyanins, sterols and carotenoids. In vitro studies have demonstrated that date fruit exhibits antibacterial, anti-inflammatory and anti-angiogenic activity. The recent interest in the identification of the numerous health benefits of dates using in vitro and in vivo studies have confirmed that date fruit and date syrup have beneficial health effects that can be attributed to the presence of natural bioactive compounds. Conclusions: Date fruit and date syrup have therapeutic properties, which have the potential to be beneficial to health. However, more investigations are needed to quantify and validate these effects

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, <scp>genotype–phenotype</scp> correlations and common mechanisms

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (&gt;60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS‐like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or “DTRs”). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype–phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

Novel Common Genetic Susceptibility Loci for Colorectal Cancer

BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screenin

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Decayed, missing, and filled: Subjectivity and the dental safety net in central Appalachia

Dental caries, popularly known as tooth decay or cavities, is among the world’s most common health problems. When caught early, it is also one of the most easily resolvable. Yet, advanced decay is a trenchant marker of social inequality and a major contributor to the maldistribution of physical pain and psychosocial suffering. Why? Access to dental care within the U.S. model of fee-for-service dental private practice follows existing lines of social stratification. Dental disparities, a term that calls attention to the relationships between maldistributed disease and maldistributed care, reflect deep ontological, moral, and political differences about responsibility for the prevention and treatment of dental disease, the quality and distribution of dental care, and even what constitutes health and well-being. What kinds of sociopolitical and moral negotiations constitute and transpire around dental disparities? How do these negotiations shape the experiences of patients and providers, and how do their experiences shape these negotiations? What can an ethnography of the dental safety net – a complex, fragile, and unpredictable network of treatment opportunities for low-income families – tell us about health governance more broadly? These are some of the questions that drive my research. In this dissertation, I explore how the sociopolitical relations of dental disparities are enacted through the dental safety net. Drawing on fifteen months of ethnographic research in clinical and community settings in central Appalachia, a region that has come to symbolize the dental crisis in the popular imagination, I show how the dental safety net exemplifies health governance in a neoliberal milieu. A fragmented system characterized by a discontinuity that starkly contrasts the model of health care generally advocated in both private and public medical systems, I argue that the dental safety net in far southwest Virginia does not merely fail to relieve the suffering of marginalized people but also can produce it. For example, the constitution of publicly-funded and charitable dental care can serve to routinize and even incentivize excess extractions among low-income adults while exempting preventive or restorative care. In addition to its effects on underserved patients, the dental safety net is a site through the fraught and contradictory relationships of dental providers and the sociopolitical stakes of the pursuit of oral health equity can be understood. For example, the flexible teamwork arrangements prized in private practice, when posited for the dental safety net, are often interpreted by dentists as risks of pluralization and threats to professional hierarchy that must be contained through legislative means. Borrowing from the crude classificatory scheme used to screen teeth quickly, I show how the dental safety net is decayed, as it bears the wear of overuse beyond maintenance; missing, or better described as an absence than a presence; and filled, like a cavitated tooth or a canaled dental root, with manufactured solutions of variable standards and longevity