Anal signs of child sexual abuse: a case–control study

Background: There is uncertainty about the nature and specificity of physical signs following anal child sexual abuse. The study investigates the extent to which physical findings discriminate between children with and without a history of anal abuse.<p></p> Methods: Retrospective case note review in a paediatric forensic unit.<p></p> Cases: all eligible cases from 1990 to 2007 alleging anal abuse.<p></p> Controls: all children examined anally from 1998 to 2007 with possible physical abuse or neglect with no identified concern regarding sexual abuse. Fisher’s exact test (two-tailed) was performed to ascertain the significance of differences for individual signs between cases and controls. To explore the potential role of confounding, logistic regression was used to produce odds ratios adjusted for age and gender.<p></p> Results: A total of 184 cases (105 boys, 79 girls), average age 98.5 months (range 26 to 179) were compared with 179 controls (94 boys, 85 girls) average age 83.7 months (range 35–193). Of the cases 136 (74%) had one or more signs described in anal abuse, compared to 29 (16%) controls. 79 (43%) cases and 2 (1.1%) controls had >1 sign. Reflex anal dilatation (RAD) and venous congestion were seen in 22% and 36% of cases but <1% of controls (likelihood ratios (LR) 40, 60 respectively), anal fissure in 14% cases and 1.1% controls (LR 13), anal laxity in 27% cases and 3% controls (LR 10).<p></p> Novel signs seen significantly more commonly in cases were anal fold changes, swelling and twitching. Erythema, swelling and fold changes were seen most commonly within 7 days of last reported contact; RAD, laxity, venous congestion, fissure and twitching were observed up to 6 months after the alleged assault.<p></p> Conclusions: Anal findings are more common in children alleging anal abuse than in those presenting with physical abuse or neglect with no concern about sexual abuse. Multiple signs are rare in controls and support disclosed anal abuse

Correspondence from Charlotte E. Hobbs to Fannie Hardy Eckstorm ca. 1935 and 1939

Manuscript letters from Charlotte E. Hobbs regarding the Indians on the Arnold expedition, and the Indian named Paugus. Digitized from Box 1, Folder 55 of the Fannie Hardy Eckstorm Papers. Transcription produced by the DigitalMaine Transcription Project.https://digitalcommons.library.umaine.edu/eckstorm_papers/1048/thumbnail.jp

The Ser82 RAGE variant affects lung function and serum RAGE in smokers and sRAGE production in vitro

Introduction: Genome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model. Methods: Immunohistochemistry was used to identify RAGE protein expression in 26 human tissues and qPCR was used to quantify AGER mRNA in lung cells. Gene expression array data was used to identify AGER expression during lung development in 38 fetal lung samples. RNA-Seq was used to identify AGER transcripts in lung cells. sRAGE levels were assessed in cells and patient serum by ELISA. BEAS2B-R1 cells were transfected to overexpress RAGE protein with either the Gly82 or Ser82 variant and sRAGE levels identified. Results: Immunohistochemical assessment of 6 adult lung samples identified high RAGE expression in the alveoli of healthy adults and individuals with COPD. AGER/RAGE expression increased across developmental stages in human fetal lung at both the mRNA (38 samples) and protein levels (20 samples). Extensive AGER splicing was identified. The rs2070600T (Ser82) allele is associated with higher FEV1, FEV1/FVC and lower serum sRAGE levels in UK smokers. Using an airway epithelium model overexpressing the Gly82 or Ser82 variants we found that HMGB1 activation of the RAGE-Ser82 receptor results in lower sRAGE production. Conclusions: This study provides new information regarding the expression profile and potential role of RAGE in the human lung and shows a functional role of the Gly82Ser variant. These findings advance our understanding of the potential mechanisms underlying COPD particularly for carriers of this AGER polymorphism

A gene-based association test of interactions for maternal-fetal genotypes identifies genes associated with nonsyndromic congenital heart defects.

The risk of congenital heart defects (CHDs) may be influenced by maternal genes, fetal genes, and their interactions. Existing methods commonly test the effects of maternal and fetal variants one-at-a-time and may have reduced statistical power to detect genetic variants with low minor allele frequencies. In this article, we propose a gene-based association test of interactions for maternal-fetal genotypes (GATI-MFG) using a case-mother and control-mother design. GATI-MFG can integrate the effects of multiple variants within a gene or genomic region and evaluate the joint effect of maternal and fetal genotypes while allowing for their interactions. In simulation studies, GATI-MFG had improved statistical power over alternative methods, such as the single-variant test and functional data analysis (FDA) under various disease scenarios. We further applied GATI-MFG to a two-phase genome-wide association study of CHDs for the testing of both common variants and rare variants using 947 CHD case mother-infant pairs and 1306 control mother-infant pairs from the National Birth Defects Prevention Study (NBDPS). After Bonferroni adjustment for 23,035 genes, two genes on chromosome 17, TMEM107 (p = 1.64e-06) and CTC1 (p = 2.0e-06), were identified for significant association with CHD in common variants analysis. Gene TMEM107 regulates ciliogenesis and ciliary protein composition and was found to be associated with heterotaxy. Gene CTC1 plays an essential role in protecting telomeres from degradation, which was suggested to be associated with cardiogenesis. Overall, GATI-MFG outperformed the single-variant test and FDA in the simulations, and the results of application to NBDPS samples are consistent with existing literature supporting the association of TMEM107 and CTC1 with CHDs

Gene-by-gene interactions associated with the risk of conotruncal heart defects

BACKGROUND: The development of conotruncal heart defects (CTDs) involves a complex relationship among genetic variants and maternal lifestyle factors. In this article, we focused on the interactions between 13 candidate genes within folate, homocysteine, and transsulfuration pathways for potential association with CTD risk. METHODS: Targeted sequencing was used for 328 case-parental triads enrolled in the National Birth Defects Prevention Study (NBDPS). To evaluate the interaction of two genes, we applied a conditional logistic regression model for all possible SNP pairs within two respective genes by contrasting the affected infants with their pseudo-controls. The findings were replicated in an independent sample of 86 NBDPS case-parental triads genotyped by DNA microarrays. The results of two studies were further integrated by a fixed-effect meta-analysis. RESULTS: One SNP pair (i.e., rs4764267 and rs6556883) located in gene MGST1 and GLRX, respectively, was found to be associated with CTD risk after multiple testing adjustment using simpleM, a modified Bonferroni correction approach (nominal p-value of 4.62e-06; adjusted p-value of .04). Another SNP pair (i.e., rs11892646 and rs56219526) located in gene DNMT3A and MTRR, respectively, achieved marginal significance after multiple testing adjustment (adjusted p-value of .06). CONCLUSION: Further studies with larger sample sizes are needed to confirm and elucidate these potential interactions

Ensuring an Essential Supply of Allied Health Professions (AHP) Placements: Using Crowdsourcing to Develop a National Call to Action

Sustainable growth in the Allied Health Professions (AHP) workforce is an ambition of the United Kingdom’s NHS Long Term Plan. However historically, access to good quality placements has been a barrier to increasing pre-registration training numbers. This article focuses on work carried out by Health Education England (HEE) to gain insights on the impact of the COVID-19 pandemic on capacity. Using a pragmatic, embedded mixed-methods approach, insights were gathered using an online workshop, crowdsourcing, open for two weeks in the summer of 2020. AHP placement stakeholders could vote, share ideas or comment. Descriptive data were extracted, and comments made were analysed using inductive thematic analysis. Participants (N = 1,800) made over 8,500 comments. The themes identified included: diversity of placement opportunity, improved placement coordination, a more joined-up system, supervision models and educator capacity. Alongside considering the challenges to placement capacity, several areas of innovative practice owing to the pandemic were highlighted. Generated insights have shaped the aims and objectives of the Health Education (HEE) pre-registration AHP student practice learning programme for 2020/2021 and beyond. The COVID-19 pandemic has disrupted the delivery of AHP placements. In the absence of face-to-face activities, crowdsourcing provided an online data collection tool offering stakeholders an opportunity to engage with the placement capacity agenda and share learning. Findings have shaped the HEE approach to short-term placement recovery and long-term growth

Case Report: Ocular Toxocariasis: A Report of Three Cases from the Mississippi Delta

Ocular toxocariasis can be vision threatening, and is commonly reported from tropical or subtropical regions. Knowledge of clinical manifestations from the United States, particularly in underserved areas such as the American South, is lacking. We report three cases of ocular toxocariasis in individuals from the Mississippi Delta, a rural community with prevalent poverty. Visual acuity was severely affected in two of the three cases. Increased awareness of ocular toxocariasis, which may have under-recognized frequency, will contribute to prompt diagnosis and treatment, which will ultimately improve patient health in the region

COVID-19 in Children: A Review and Parallels to Other Hyperinflammatory Syndromes

During the COVID-19 pandemic, children have had markedly different clinical presentations and outcomes compared to adults. In the acute phase of infection, younger children are relatively spared the severe consequences reported in adults. Yet, they are uniquely susceptible to the newly described Multisystem Inflammatory Syndrome in Children (MIS-C). This may result from the developmental "immunodeficiency" resulting from a Th2 polarization that starts in utero and is maintained for most of the first decade of life. MIS-C may be due to IgA complexes in a Th2 environment or a Th1-like response to COVID-19 antigens that developed slowly. Alternatively, MIS-C may occur in vulnerable hosts with genetic susceptibilities in other immune and non-immune pathways. Herein, we present a brief overview of the host immune response, virologic and genetic factors, and comparable inflammatory syndromes that may explain the pathophysiology leading to drastic differences in clinical presentation and outcomes of COVID-19 between children and adults