Vaccination Exemptions for School-Aged Children in Delaware

Background: Current awareness around childhood vaccinations and associated requirements for school entry has been heightened both nationally and internationally as governments work to find a balance between protecting their residents’ health and personal freedoms. Scant research exists examining the characteristics of these vaccine exemptors, but as the percentage of students seeking these exemptions increases yearly, this yields an opportunity to identify trends and inform future policy. Question: What are the associations between reason for exemption from mandated vaccinations and the demographics of race and gender for school-aged children in the state of Delaware? Results: Drawing from school nurse vaccine exemption record data, we looked at student’s reason for vaccine exemption and used chi square analyses to study the association with race, disease(s) of vaccine, and gender. White race and male gender were significantly associated with having a religious vaccine exemption, X2 (1, N = 154) = 22.75, p = .000 and X2 (1, N = 154) = 8.71, p = .003, respectively. The varicella vaccine was the most common disease when the reason for exemption was having had the disease, while the Tdap vaccine was the most common vaccine exemption for religious reasons. Conclusion: The significant association of white race and religious vaccination exemptions implicates future policy that focuses on this proportion of exemptions, rather than prior exposure exemptions that do not impact herd immunity. While data was available for only one school district within the state of Delaware, the significance of the findings suggests further and broader inquiry is imperative in the on-going efforts to keep our populations safe from vaccine preventable diseases

Health Care Providers’ Experience with a Protocol for the Identification, Treatment, and Referral of Human-Trafficking Victims

Abstract The healthcare setting is thought to be one of the most promising places to identify victims of human trafficking. The present study was designed to relay the experiences of a sample of 10 healthcare providers and hospital administrators who developed and have used a protocol to identify victims of human trafficking since February 2014. To our knowledge, the protocol was one of the first to be adopted by any healthcare system in the U.S. Three primary themes emerged from the participant interviews. First, developing the protocol was challenging because at the time there were no predecessor examples. Second, providers reported that the protocol is simple to use and victim identification is easier because of it. Third, identifying and serving victims of human trafficking remains challenging, because there is still a deficit of trained providers and a lack of community resources for survivors. The field needs evidence that this and similar protocols improve users’ knowledge and skills, result in the better identification and treatment of trafficking victims, and ultimately improve public safety and public health

A Two-dimensional Map of Color Excess in NGC 3603

Using archival HST/WFC3 images centered on the young HD 97950 star cluster in the giant HII region NGC 3603, we computed the pixel-to-pixel distribution of the color excess, E(B-V)g, of the gas associated with this cluster from its H_alpha/Pa_beta flux ratio. At the assumed distance of 6.9 kpc, the resulting median color excess within 1 pc from the cluster center is E(B-V)g =1.51 \pm 0.04 mag. Outside the cluster (at r > 1 pc), the color excess is seen to increase with cluster-centric distance towards both North and South, reaching a value of about 2.2 mag at r = 2 pc from the cluster center. The radial dependence of E(B-V)g westward of the cluster appears rather flat at about 1.55 mag over the distance range 1.2 pc < r < 3 pc. In the eastern direction, E(B-V)g steadily increases from 1.5 mag at r = 1 pc to 1.7 mag at r = 2 pc, and stays nearly constant at 1.7 mag for 2 pc < r < 3 pc. The different radial profiles and the pixel-to-pixel variations of E(B-V)g clearly indicate the presence of significant differential reddening across the 4.9 pc \times 4.3 pc area centered on the HD 97950 star cluster. We interpret the variations of E(B-V)g as the result of stellar radiation and stellar winds interacting with an inhomogeneous dusty local interstellar medium (ISM) whose density varies spatially. From the E(B-V)g values measured along the rims of the prominent pillars MM1 and MM2 in the southwest and southeast of the HD 97950 cluster we estimate an H2 column density of log10(N(H2))=21.7 and extrapolate it to log10(N(H2))=23 in the pillars' interior. We find the pillars to be closer to us than the central ionizing cluster and suggest that star formation may be occurring in the pillar heads.Comment: 14 pages, 6 figures, 2 tables, accepted for publication in A

Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells

SummaryOncogene-induced DNA methylation-mediated transcriptional silencing of tumor suppressors frequently occurs in cancer, but the mechanism and functional role of this silencing in oncogenesis are not fully understood. Here, we show that oncogenic epidermal growth factor receptor (EGFR) induces silencing of multiple unrelated tumor suppressors in lung adenocarcinomas and glioblastomas by inhibiting the DNA demethylase TET oncogene family member 1 (TET1) via the C/EBPα transcription factor. After oncogenic EGFR inhibition, TET1 binds to tumor suppressor promoters and induces their re-expression through active DNA demethylation. Ectopic expression of TET1 potently inhibits lung and glioblastoma tumor growth, and TET1 knockdown confers resistance to EGFR inhibitors in lung cancer cells. Lung cancer samples exhibited reduced TET1 expression or TET1 cytoplasmic localization in the majority of cases. Collectively, these results identify a conserved pathway of oncogenic EGFR-induced DNA methylation-mediated transcriptional silencing of tumor suppressors that may have therapeutic benefits for oncogenic EGFR-mediated lung cancers and glioblastomas

Osteopoikilosis and multiple exostoses caused by novel mutations in LEMD3 and EXT1 genes respectively - coincidence within one family

<p>Abstract</p> <p>Background</p> <p>Osteopoikilosis is a rare autosomal dominant genetic disorder, characterised by the occurrence of the hyperostotic spots preferentially localized in the epiphyses and metaphyses of the long bones, and in the carpal and tarsal bones <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Heterozygous <it>LEMD3 </it>gene mutations were shown to be the primary cause of the disease <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>. Association of the primarily asymptomatic osteopokilosis with connective tissue nevi of the skin is categorized as Buschke-Ollendorff syndrome (BOS) <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. Additionally, osteopoikilosis can coincide with melorheostosis (MRO), a more severe bone disease characterised by the ectopic bone formation on the periosteal and endosteal surface of the long bones <abbrgrp><abbr bid="B4">4</abbr><abbr bid="B5">5</abbr><abbr bid="B6">6</abbr></abbrgrp>. However, not all MRO affected individuals carry germ-line <it>LEMD3 </it>mutations <abbrgrp><abbr bid="B7">7</abbr></abbrgrp>. Thus, the genetic cause of MRO remains unknown. Here we describe a familial case of osteopoikilosis in which a novel heterozygous <it>LEMD3 </it>mutation coincides with a novel mutation in <it>EXT1</it>, a gene involved in aetiology of multiple exostosis syndrome. The patients affected with both <it>LEMD3 </it>and <it>EXT1 </it>gene mutations displayed typical features of the osteopoikilosis. There were no additional skeletal manifestations detected however, various non-skeletal pathologies coincided in this group.</p> <p>Methods</p> <p>We investigated <it>LEMD3 </it>and <it>EXT1 </it>in the three-generation family from Poland, with 5 patients affected with osteopoikilosis and one child affected with multiple exostoses.</p> <p>Results</p> <p>We found a novel c.2203C > T (p.R735X) mutation in exon 9 of <it>LEMD3</it>, resulting in a premature stop codon at amino acid position 735. The mutation co-segregates with the osteopoikilosis phenotype and was not found in 200 ethnically matched controls. Another new substitution G > A was found in <it>EXT1 </it>gene at position 1732 (cDNA) in Exon 9 (p.A578T) in three out of five osteopoikilosis affected family members. Evolutionary conservation of the affected amino acid suggested possible functional relevance, however no additional skeletal manifestations were observed other then those specific for osteopoikilosis. Finally in one member of the family we found a splice site mutation in the <it>EXT1 </it>gene intron 5 (IVS5-2 A > G) resulting in the deletion of 9 bp of cDNA encoding three evolutionarily conserved amino acid residues. This child patient suffered from a severe form of exostoses, thus a causal relationship can be postulated.</p> <p>Conclusions</p> <p>We identified a new mutation in <it>LEMD3 </it>gene, accounting for the familial case of osteopoikilosis. In the same family we identified two novel <it>EXT1 </it>gene mutations. One of them A598T co-incided with the <it>LEMD3 </it>mutation. Co-incidence of <it>LEMD3 </it>and <it>EXT1 </it>gene mutations was not associated with a more severe skeletal phenotype in those patients.</p

Promiscuous Binding of Invariant Chain-Derived CLIP Peptide to Distinct HLA-I Molecules Revealed in Leukemic Cells

Antigen presentation by HLA class I (HLA-I) and HLA class II (HLA-II) complexes is achieved by proteins that are specific for their respective processing pathway. The invariant chain (Ii)-derived peptide CLIP is required for HLA-II-mediated antigen presentation by stabilizing HLA-II molecules before antigen loading through transient and promiscuous binding to different HLA-II peptide grooves. Here, we demonstrate alternative binding of CLIP to surface HLA-I molecules on leukemic cells. In HLA-II-negative AML cells, we found plasma membrane display of the CLIP peptide. Silencing Ii in AML cells resulted in reduced HLA-I cell surface display, which indicated a direct role of CLIP in the HLA-I antigen presentation pathway. In HLA-I-specific peptide eluates from B-LCLs, five Ii-derived peptides were identified, of which two were from the CLIP region. In vitro peptide binding assays strikingly revealed that the eluted CLIP peptide RMATPLLMQALPM efficiently bound to four distinct HLA-I supertypes (-A2, -B7, -A3, -B40). Furthermore, shorter length variants of this CLIP peptide also bound to these four supertypes, although in silico algorithms only predicted binding to HLA-A2 or -B7. Immunization of HLA-A2 transgenic mice with these peptides did not induce CTL responses. Together these data show a remarkable promiscuity of CLIP for binding to a wide variety of HLA-I molecules. The found participation of CLIP in the HLA-I antigen presentation pathway could reflect an aberrant mechanism in leukemic cells, but might also lead to elucidation of novel processing pathways or immune escape mechanisms

Milk Lacking α-Casein Leads to Permanent Reduction in Body Size in Mice

The major physiological function of milk is the transport of amino acids, carbohydrates, lipids and minerals to mammalian offspring. Caseins, the major milk proteins, are secreted in the form of a micelle consisting of protein and calcium-phosphate

A novel, integrated in vitro carcinogenicity test to identify genotoxic and non-genotoxic carcinogens using human lymphoblastoid cells

Human exposure to carcinogens occurs via a plethora of environmental sources, with 70–90% of cancers caused by extrinsic factors. Aberrant phenotypes induced by such carcinogenic agents may provide universal biomarkers for cancer causation. Both current in vitro genotoxicity tests and the animal-testing paradigm in human cancer risk assessment fail to accurately represent and predict whether a chemical causes human carcinogenesis. The study aimed to establish whether the integrated analysis of multiple cellular endpoints related to the Hallmarks of Cancer could advance in vitro carcinogenicity assessment. Human lymphoblastoid cells (TK6, MCL-5) were treated for either 4 or 23 h with 8 known in vivo carcinogens, with doses up to 50% Relative Population Doubling (maximum 66.6 mM). The adverse effects of carcinogens on wide-ranging aspects of cellular health were quantified using several approaches; these included chromosome damage, cell signalling, cell morphology, cell-cycle dynamics and bioenergetic perturbations. Cell morphology and gene expression alterations proved particularly sensitive for environmental carcinogen identification. Composite scores for the carcinogens’ adverse effects revealed that this approach could identify both DNA-reactive and non-DNA reactive carcinogens in vitro. The richer datasets generated proved that the holistic evaluation of integrated phenotypic alterations is valuable for effective in vitro risk assessment, while also supporting animal test replacement. Crucially, the study offers valuable insights into the mechanisms of human carcinogenesis resulting from exposure to chemicals that humans are likely to encounter in their environment. Such an understanding of cancer induction via environmental agents is essential for cancer prevention