Role of prior immunity in binding to spike of "future" Omicron subvariants.

BACKGROUND: Throughout the COVID-19 pandemic, virus evolution and large-scale vaccination programs have caused multiple exposures to SARS CoV-2 spike protein, resulting in complex antibody profiles. The binding of these to spike protein of "future" variants in the context of such heterogeneous exposure has not been studied. METHODS: We tested archival sera (Delta and Omicron period) stratified by anti-spike antibody (including IgG) levels for reactivity to Omicron-subvariants(BA.1, BA.2,BA.2.12.1, BA.2.75, BA.4/5 and BF.7) spike protein. Assessed antigenic distance between groups using Antigenic Cartography and performed hierarchical clustering of antibody data in a Euclidean distance framework. RESULTS: Antibody (including IgG) antibody reactivity to Wild-type (CLIA) and subvariants (ELISA) spike protein were similar between periods (p > 0.05). Both 'High S' and 'Low S' of Delta and Omicron periods were closely related to "future" subvariants by Antigenic Cartography. Sera from different S groups clustered together with 'Low S' interspersed between 'High S' on hierarchical clustering, suggesting common binding sites. Further, anti-spike antibodies (including IgG) to Wild-type (S1/S2 and Trimeric S) clustered with Omicron-subvariant binding antibodies. CONCLUSIONS: Hybrid immunity caused by cumulative virus exposure in Delta or Omicron periods resulted in equivalent binding to "future" variants, which might be due to binding to conserved regions of spike protein of future variants. A prominent finding is that the 'Low S' antibody demonstrates similar binding.

Enhancing skin lesion classification with advanced deep learning ensemble models: a path towards accurate medical diagnostics.

Skin cancer, including the highly lethal malignant melanoma, poses a significant global health challenge with a rising incidence rate. Early detection plays a pivotal role in improving survival rates. This study aims to develop an advanced deep learning-based approach for accurate skin lesion classification, addressing challenges such as limited data availability, class imbalance, and noise. Modern deep neural network designs, such as ResNeXt101, SeResNeXt101, ResNet152V2, DenseNet201, GoogLeNet, and Xception, which are used in the study and ze optimised using the SGD technique. The dataset comprises diverse skin lesion images from the HAM10000 and ISIC datasets. Noise and artifacts are tackled using image inpainting, and data augmentation techniques enhance training sample diversity. The ensemble technique is utilized, creating both average and weighted average ensemble models. Grid search optimizes model weight distribution. The individual models exhibit varying performance, with metrics including recall, precision, F1 score, and MCC. The "Average ensemble model" achieves harmonious balance, emphasizing precision, F1 score, and recall, yielding high performance. The "Weighted ensemble model" capitalizes on individual models' strengths, showcasing heightened precision and MCC, yielding outstanding performance. The ensemble models consistently outperform individual models, with the average ensemble model attaining a macro-average ROC-AUC score of 96 % and the weighted ensemble model achieving a macro-average ROC-AUC score of 97 %. This research demonstrates the efficacy of ensemble techniques in significantly improving skin lesion classification accuracy. By harnessing the strengths of individual models and addressing their limitations, the ensemble models exhibit robust and reliable performance across various metrics. The findings underscore the potential of ensemble techniques in enhancing medical diagnostics and contributing to improved patient outcomes in skin lesion diagnosis.

Parent Perspectives on Adverse Childhood Experiences & Unmet Social Needs Screening in the Medical Home: A Qualitative Study.

OBJECTIVES: To explore parental perspectives regarding disclosure of child and parental adverse childhood experiences (ACE) and family unmet social needs (USN) and to elicit parental recommendations for screening in the pediatric medical home. METHODS: We conducted a qualitative study using a purposive sample of English- and Spanish-speaking parents in our urban academic community clinic. Between January 2018 and March 2019, each parent underwent one semistructured interview that was audiotaped, transcribed, and independently coded in Atlas.ti by 2 study team members. Data analysis was based in constructivist grounded theory methodology to identify common themes and subthemes. RESULTS: We interviewed 25 English-speaking and 15 Spanish-speaking parents who were mostly female, racial/ethnic minorities with ≥1 ACE. English-speaking subjects were more likely to have a high school degree and be single parents. Four themes were identified: 1) Pediatricians should ask about ACE and USN. 2) Disclosure is a longitudinal process, not a discrete event. 3) Barriers to disclosure are significant, involving concrete and emotional risks for the family. 4) Trauma-informed providers and practices support disclosure. CONCLUSIONS: Families support pediatricians addressing ACE and USN in the medical home despite significant barriers. Even if providers screen using trauma-informed principles, parents may prefer not to disclose ACE initially because they regard disclosure as a stepwise process. These findings contribute to a new conceptual framework for thinking of ACE screening not merely as a way to generate information, but as an interactive, therapeutic relationship-building activity irrespective of whether or when it produces disclosure.

Comparison of a chemiluminescence immunoassay and an enzyme immunoassay for detection of IgM antibodies against measles, mumps, rubella, cytomegalovirus (CMV), Epstein Barr virus (EBV), and human herpes virus (HHV) -1 and -2 infections.

PURPOSE: Outbreaks of vaccine-preventable viral diseases have been increasingly reported globally over the past few years. The burden of congenital viral infections, their impact on physical and mental development and the resulting economic loss to the family and the community are also well known. IgM antibody detection has been convenient in the diagnosis of acute viral infections, particularly in settings with limited resources where molecular tests are not feasible. METHODS: This is a comparative study between a chemiluminescence immunoassay (Liaison, DiaSorin, Saluggia, Italy) and an enzyme linked immunosorbent assay (ELISA) (Euroimmun, Lubeck, Germany) for the detection of IgM antibody against measles, mumps, rubella, CMV, EBV and HHV-1 and -2 viruses using a total of 345 samples. Results are expressed as agreement using kappa statistics. RESULTS: In this study, CLIA is perfectly comparable to ELISA for the detection of IgM antibodies against measles (0.86) and mumps (0.92) with a moderate agreement for rubella (0.52), CMV (0.57), EBV (0.50), and HHV-1 and -2 (0.47) assays. However, a PABAK (prevalence-adjusted bias-adjusted kappa) showed improved agreement for rubella (0.64), CMV (0.65), EBV (0.60), and HHV-1 and -2 (0.88) assays. CONCLUSIONS: IgM antibody assays (CLIA and ELISA) against measles and mumps virus can be comparably used depending on the laboratory setup, throughput and expertise.

Testing for rare genetic causes of obesity: findings and experiences from a pediatric weight management program.

BACKGROUND: Genetic screening for youth with obesity in the absence of syndromic findings has not been part of obesity management. For children with early onset obesity, genetic screening is recommended for those having clinical features of genetic obesity syndromes (including hyperphagia). OBJECTIVES: The overarching goal of this work is to report the findings and experiences from one pediatric weight management program that implemented targeted sequencing analysis for genes known to cause rare genetic disorders of obesity. SUBJECTS/METHODS: This exploratory study evaluated youth tested over an 18-month period using a panel of 40-genes in the melanocortin 4 receptor pathway. Medical records were reviewed for demographic and visit information, including body mass index (BMI) percent of 95th percentile (%BMIp95) and two eating behaviors. RESULTS: Of 117 subjects: 51.3% were male; 53.8% Hispanic; mean age 10.2 years (SD 3.8); mean %BMIp95 157% (SD 29%). Most subjects were self- or caregiver-reported to have overeating to excess or binge eating (80.3%) and sneaking food or eating in secret (59.0%). Among analyzed genes, 72 subjects (61.5%) had at least one variant reported; 50 (42.7%) had a single variant reported; 22 (18.8%) had 2-4 variants reported; most variants were rare (<0.05% minor allele frequency [MAF]), and of uncertain significance; all variants were heterozygous. Nine subjects (7.7%) had a variant reported as PSCK1 "risk" or MC4R "likely pathogenic"; 39 (33.3%) had a Bardet-Biedl Syndrome (BBS) gene variant (4 with "pathogenic" or "likely pathogenic" variants). Therefore, 9 youth (7.7%) had gene variants previously identified as increasing risk for obesity and 4 youth (3.4%) had BBS carrier status. CONCLUSIONS: Panel testing identified rare variants of uncertain significance in most youth tested, and infrequently identified variants previously reported to increase the risk for obesity. Further research in larger cohorts is needed to understand how genetic variants influence the expression of non-syndromic obesity.

A Novel Subset of Triple-Negative Breast Cancers with Unique Histology and Immunohistochemical Expression.

Background & Objective: Triple-Negative Breast Carcinoma (TNBC) is characterized by an absence of estrogen receptor, progesterone receptor and HER2 neu expression, with distinct molecular, histological and clinical features, aggressive clinical course and a poor prognosis. The objective was to evaluate the expression of Cytokeratin5/6 (CK 5/6), Epidermal Growth Factor Receptor 1 (EGFR 1), E-cadherin and Androgen receptor in tissue sections of TNBC. Methods: All modified radical mastectomy samples received negative for the three markers were subjected to further studies with CK5/6, EGFR 1, E- cadherin and Androgen receptor staining. The clinical and pathological data were tabulated and statistically analysed using the Chi-square test, and cross-tabulation was done to assess the correlation between these markers. Results: Of 94 samples classified as TNBC, 31 (33%) were positive for CK 5/6, 47 (50%) for EGFR, 32 (34%) for E Cadherin and Androgen receptor, respectively. We had one positive patient for all four markers, 13 patients were negative for all four. Thirty-five cases were positive for only one marker, 32 were positive for two markers, and 13 were positive for three markers. Analysis revealed certain interesting patterns, namely - E cadherin was the most common isolated marker expressed in our cohort of TNBC with 15 of 35 positives. Conclusion: This study highlights the presence of a unique subtype of TNBC, which are negative for all the four markers studied here, with unique histomorphology of absent tumour necrosis and stromal lymphocytic infiltration being unique.

Characteristics of Children Referred to a Lipid Clinic Before and After the Universal Screening Guidelines.

In 2011, universal lipid screening was recommended for children aged 9 to 11 years; the impact of this recommendation on the lipid clinic setting is unknown. We examined the rate of primary and secondary dyslipidemia diagnoses in a lipid clinic before (2010-2011) and after (2012-2015) the guideline recommendation. We conducted a retrospective study of new clinic patients aged 0 to 20 years seen between April 2010 and April 2015. Chi-square testing was applied. The 345 subjects were 58% males; 48% ≥13 years; 56% Hispanic; and 59% obese. There was no difference in the rate of dyslipidemia diagnoses between periods (before: primary 23%, secondary 73%, no dyslipidemia 4% vs after: 22%, 72%, 6%, respectively; P = .616). There was no significant difference between periods in subject demographics for the total sample, but among those with primary dyslipidemia, pre- to post-guideline percentage of subjects with public insurance decreased (71% to 39%; P = .006). Additional strategies to increase identification of children with dyslipidemia are needed.

Screening for Toxic Stress Risk Factors at Well-Child Visits: The Addressing Social Key Questions for Health Study.

OBJECTIVES: To determine the prevalence of and demographic characteristics associated with toxic stress risk factors by universal screening, the impact of screening on referral rates to community resources, and the feasibility and acceptability of screening in a medical home setting. STUDY DESIGN: We developed the Addressing Social Key Questions for Health Questionnaire, a 13-question screen of adverse childhood experiences (ACEs) and unmet social needs. Parents/guardians of children 0-17 years of age received this questionnaire at well-child visits at 4 academic clinics from August 1, 2016 to February 28, 2017. Providers reviewed the tool and referred to community resources as needed. A subset of families completed demographic and satisfaction surveys. Prevalence of ACEs and unmet social needs, community referral rates at 1 site with available data, and family acceptability data were collected. Analyses included frequency distributions, χ2 tests, and Poisson regression. RESULTS: Of 2569 families completing an Addressing Social Key Questions for Health Questionnaire, 49% reported ≥1 stressor; 6% had ≥1 ACE; 47% had ≥1 unmet social need. At 1 site, community referral rates increased from 2.0% to 13.3% (P < .0001) after screening implementation. Risk factors for having a stressor include male sex and African American or Hispanic race. 86% of 446 families want clinics to continue screening. CONCLUSIONS: Universal screening for toxic stress risk factors in pediatric primary care improved identification and management of family needs. Screening was feasible and acceptable to families. Prevalence of unmet social needs but not ACEs was comparable with prior studies. Further evaluation and modification of the screening protocol is needed to increase screening and identification.

Percent Body Fat Measurement in the Medical Management of Children with Obesity.

Sustaining weight loss can be challenging, as physiological responses to weight loss, including metabolic and hormonal adaptations and decreased energy expenditure, promote weight regain. Paired with sustained dietary changes, physical activity can promote weight maintenance after successful weight loss, as physical activity can help maintain fat-free mass. We present several illustrative cases to highlight the potential use of body composition measurement using a bioelectrical impedance analysis (BIA) scale to augment obesity management counseling in a tertiary care pediatric weight-management clinic. BIA does require some interpretation, as it can be affected by hydration status and time of day, as well as patient age, sex, and body mass index. Nonetheless, BIA can be a helpful aid to obesity counseling. More research is needed to better understand how to use change in percent body fat over time as a motivational tool for management of children with obesity. [Pediatr Ann. 2018;47(12):e487-e493.].

Virological investigation of hand, foot, and mouth disease in a tertiary care center in South India.

CONTEXT: Hand, foot, and mouth disease (HFMD) remains a common problem in India, yet its etiology is largely unknown as diagnosis is based on clinical characteristics. There are very few laboratory-based molecular studies on HFMD outbreaks. AIM: The aim of this study was to characterize HFMD-related isolates by molecular techniques. SETTINGS AND DESIGN: Between 2005 and 2008, during two documented HFMD outbreaks, 30 suspected HFMD cases presented at the Outpatient Unit of the Department of Dermatology, Christian Medical College (CMC), Vellore. Seventy-eight clinical specimens (swabs from throat, mouth, rectum, anus, buttocks, tongue, forearm, sole, and foot) were received from these patients at the Department of Clinical Virology, CMC, for routine diagnosis of hand, foot, and mouth disease. MATERIALS AND METHODS: Samples from these patients were cultured in Vero and rhabdomyosarcoma (RD) cell lines. Isolates producing enterovirus-like cytopathogenic effect (CPE) in cell culture were identified by a nested reverse transcription-based polymerase chain reaction (RT-PCR) and sequenced. The nucleotide sequences were analyzed using the BioEdit sequence program. Homology searches were performed using the Basic Local Alignment Search Tool (BLAST) algorithm. STATISTICAL ANALYSIS USED: The statistical analysis was performed using Epi Info version 6.04b and Microsoft Excel 2002 (Microsoft Office XP). RESULTS: Of the 30 suspected HFMD cases, only 17 (57%) were laboratory confirmed and Coxsackievirus A16 (CVA16) was identified as the etiological agent in all these cases. CONCLUSIONS: Coxsackievirus A16 (CVA16) was identified as the virus that caused the HFMD outbreaks in Vellore between 2005 and 2008. Early confirmation of HFMD helps to initiate control measures to interrupt virus transmission. In the laboratory, classical diagnostic methods, culture and serological tests are being replaced by molecular techniques. Routine surveillance systems will help understand the epidemiology of HFMD in India.

Power-up: a collaborative after-school program to prevent obesity in African American children.

BACKGROUND: Schools represent a key potential venue for addressing childhood obesity. OBJECTIVE: To assess the feasibility of Power-Up, an after-school program to decrease obesity risk among African American children, using community-based participatory research (CBPR) principles. METHODS: Teachers led 14 weekly nutrition and physical activity sessions during afterschool care at the Woodlawn Community School on Chicago's South Side. Forty African American children ages 5 to 12 participated; their 28 parents discussed similar topics weekly at pickup time, and families practiced relevant skills at home. Pre- and post-intervention anthropometrics, blood pressure, dietary measures, and health knowledge and beliefs for children and parents were compared in univariate analysis. RESULTS: At baseline, 26% of children were overweight; 28% were obese. Post-intervention, mean body mass index (BMI) z scores decreased from 1.05 to 0.81 (p<.0001). Changes were more pronounced for overweight (-0.206 z-score units) than for obese children (-0.062 z-score units; p=.01). Girls decreased their combined prevalence of overweight/obesity from 52% to 46%; prevalence across these categories did not change for boys. The prevalence of healthful attitudes rose, including plans to "eat more foods that are good for you" (77% to 90%; p=.027) and "planning to try some new sports" (80% to 88%; p=.007). CONCLUSION: Children in the Power-Up program reduced mean BMI z scores significantly. The after-school venue proved feasible. The use of CBPR principles helped to integrate Power-Up into school activities and contributed to likelihood of sustainability. Engaging parents effectively in the afterschool time frame proved challenging; additional strategies to engage parents are under development. Plans are underway to evaluate this intervention through a randomized study.

Performance of a rapid immunochromatographic screening test for detection of antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2: experience at a tertiary care hospital in South India.

The performance characteristics of a rapid immunochromatographic-screening test, SD Bioline HIV-1/2 3.0 (Standard Diagnostics Inc., Kyonggi-do, South Korea) on 23,754 sera and 30 plasma samples are reported. The sensitivity and specificity for the assay on serum samples are 100% and 99.4%, respectively. The assay detected antibodies in individuals infected with human immunodeficiency virus type 1 (HIV-1) genotypes A and C and HIV-2. This straightforward assay is a reliable diagnostic tool for screening HIV in resource-poor settings.