Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B.

Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung. Increased CSL levels enhanced the proliferative potential of HKCs and SCC cells, while silencing of CSL induced growth arrest and apoptosis. In vivo, SCC cells with increased CSL levels gave rise to rapidly expanding tumors, while cells with silenced CSL formed smaller and more differentiated tumors with enhanced inflammatory infiltrate. Global transcriptomic analysis of HKCs and SCC cells with silenced CSL revealed major modulation of apoptotic, cell-cycle, and proinflammatory genes. We also show that the histone demethylase KDM6B is a direct CSL-negative target, with inverse roles of CSL in HKC and SCC proliferative capacity, tumorigenesis, and tumor-associated inflammatory reaction. CSL/KDM6B protein expression could be used as a biomarker of SCC development and indicator of cancer treatment

Examining maternal and paternal involvement as promotive factors of competence in African American children in informal kinship care

Grandparents or other relatives are raising over 2.7 million children in the United States; and research suggests that the birth parents of these children maintain varying levels of involvement with them and their relative caregivers. However, the impact of parental involvement on children's developmental outcomes remains largely unexplored. This study sought to understand the role of maternal and paternal involvement (each parent's contact with the caregiver, contact with the child, friendliness to the caregiver, and quality of relationship with the child) on competence levels of African American children in informal kinship care. Exploring these relationships are pivotal, especially given the various psychosocial benefits associated with social and academic competence. Findings from the SEM analysis suggest that paternal involvement in informal kinship care is a significant predictor of competence among this sample of African American children. Maternal involvement only revealed a positive trend with competence; however the quality of the mothers' relationship with children was associated with children's competence levels. Implications for future research and social work practice are discussed

Pattern of Young and Old Onset Rheumatoid Arthritis (YORA and EORA) Among a Group of Egyptian Patients with Rheumatoid Arthritis

Objective Rheumatoid arthritis (RA) differs depending on the age of disease onset. The differences between EORA and YORA are important because they have clinical and therapeutic implications. Method 1185 patients were ranked after classification according to age at onset of the disease into YORA I (16–40 years), YORA II (41–60 years) and EORA >60 years. All patients groups were compared, based on disease duration, disease activity, severity parameters and drug history. Results YORA I included 298 patients, 28.85% were males, with mean age of 29.4 ± 6 years and disease duration 4 ± 3.3 y, YORA II included 539 patients, 33.77% males, age 49.7 ± 6.1 y and disease duration 6.5 ± 5.6 y. EORA included 348 RA patients 40.5% males, age 67.1 ± 6.6 y, disease duration 9.95 ± 7.2 y. Activity was increased in EORA compared to YORA I and YORA II, while severity decreased in EORA. ESR, CRP and degree of anemia were higher in EORA. RF titer was higher in YORA. Small joints of the hands and feet were more involved in YORA, while, large joints in EORA. Rheumatoid nodules were increased in YORA I than EORA P = 0.04. Polymyalgia rheumatica was exclusively present in EORA group 25 patients 7.2%. Methotrexate was used in both YORA and EORA, with a higher mean of dosage in YORA than EORA. Multiple DMARDs in EORA was 57.9%, and biologics in 0.8% was which was significantly lower compared with YORA I, 86.3% and 1.7%, with P = 0.001. Conclusion EORA has more active and less disabling and affects more males than YORA. The use of biologic therapy and combination DMARD therapy was less in EORA

Psychosocial predictors of primiparous breastfeeding initiation and duration

Background: Many US women fall short of meeting the recommendations on breastfeeding.Whereas prenatal demographic factors have been well researched in relation to breastfeeding,psychosocial maternal characteristics are less understood but could be important predictors ofbreastfeeding initiation and duration.Objective: This study examined primiparous maternal psychosocial characteristics andtemperamentally based negative infant affect as predictors of breastfeeding initiation andduration while accounting for depression and sociodemographic covariates.Methods: Prenatally, 237 primiparous women were administered the Adult AttachmentInterview and completed a measure of beliefs related to infant crying. At 6 months postpartum,negative infant affect was assessed via mother report. Breastfeeding was assessed at 6 monthsand 1 year postpartum via mother report.Results: Results indicated that younger, low income, less educated, single, ethnic minoritymothers and mothers with elevated depressive symptoms were less likely to initiate breastfeedingand breastfed for a shorter period than other women. Women who initiated breastfeeding tendedto have higher adult attachment coherence scores (more secure attachment) than those who didnot initiate breastfeeding (median score of 6.00 vs 4.00). An interaction was observed betweennegative infant affect and beliefs about crying related to spoiling, such that earlier cessation ofbreastfeeding was observed among mothers who reported high levels of negative infant affectand strongly endorsed the belief that responding to cries spoils infants (hazard ratio = 1.71, P Conclusion: Although these psychosocial variables predicted relatively little variation inbreastfeeding over and above covariates, the results suggest some novel approaches to promotebreastfeeding

First Generation Amperometric Biosensing of Galactose with Xerogel-Carbon Nanotube Layer-By-Layer Assemblies

A first-generation amperometric galactose biosensor has been systematically developed utilizing layer-by-layer (LbL) construction of xerogels, polymers, and carbon nanotubes toward a greater fundamental understanding of sensor design with these materials and the potential development of a more efficient galactosemia diagnostic tool for clinical application. The effect of several parameters (xerogel silane precursor, buffer pH, enzyme concentration, drying time and the inclusion of a polyurethane (PU) outer layer) on galactose sensitivity were investigated with the critical nature of xerogel selection being demonstrated. Xerogels formed from silanes with medium, aliphatic side chains were shown to exhibit significant enhancements in sensitivity with the addition of PU due to decreased enzyme leaching. Semi-permeable membranes of diaminobenzene and resorcinol copolymer and Nafion were used for selective discrimination against interferent species and the accompanying loss of sensitivity with adding layers was countered using functionalized, single-walled carbon nanotubes (CNTs). Optimized sensor performance included effective galactose sensitivity (0.037 μA/mM) across a useful diagnostic concentration range (0.5 mM to 7 mM), fast response time (~30 s), and low limits of detection (~80 μM) comparable to literature reports on galactose sensors. Additional modification with anionic polymer layers and/or nanoparticles allowed for galactose detection in blood serum samples and additional selectivity effectiveness

Examination of the Cameroon DHS data to investigate how water access and sanitation services are related to diarrhea and nutrition among infants and toddlers in rural households

Undernutrition among children is a significant issue in rural areas in Cameroon, with diarrhea being one of the major contributing risk factors. To gain a better understanding of the risk factors of diarrhea, the main objective of this epidemiological study was to examine associations between water access and sanitation service with diarrhea, diet diversity, and anemia among infants and toddlers in rural households in Cameroon. The study involved household- and individual-level data of 2,129 rural-dwelling infants and toddlers from the Demographic and Health Survey database. About one-third of infants and toddlers were experiencing diarrhea, with higher odds among those who lived in households with limited water service (p = 0.028). The odds of having diarrhea were 50% higher among infants and toddlers when households did not have sanitation facilities (p = 0.007). The lack of improved water and sanitation was also associated with a low intake of various food groups among older infants and toddlers. The prevalence of anemia was high, but no significant differences were seen by water and sanitation services. The achievement of SDG #6 will help address undernutrition and achieve other SDGs, including improving health and wellbeing

Correlation of in Vitro Cytokine Responses with the Chemical Composition of Soil-Derived Particulate Matter

We treated human lung epithelial cells, type BEAS-2B, with 10–80 μg/cm(2) of dust from soils and road surfaces in the western United States that contained particulate matter (PM) < 2.5 μm aerodynamic diameter. Cell viability and cytokine secretion responses were measured at 24 hr. Each dust sample is a complex mixture containing particles from different minerals mixed with biogenic and anthropogenic materials. We determined the particle chemical composition using methods based on the U.S. Environmental Protection Agency Speciation Trends Network (STN) and the National Park Service Interagency Monitoring of Protected Visual Environments (IMPROVE) network. The functionally defined carbon fractions reported by the ambient monitoring networks have not been widely used for toxicology studies. The soil-derived PM(2.5) from different sites showed a wide range of potency for inducing the release of the proinflammatory cytokines interleukin-6 (IL-6) and IL-8 in vitro. Univariate regression and multivariate redundancy analysis were used to test for correlation of viability and cytokine release with the concentrations of 40 elements, 7 ions, and 8 carbon fractions. The particles showed positive correlation between IL-6 release and the elemental and pyrolyzable carbon fractions, and the strongest correlation involving crustal elements was between IL-6 release and the aluminum:silicon ratio. The observed correlations between low-volatility organic components of soil- and road-derived dusts and the cytokine release by BEAS-2B cells are relevant for investigation of mechanisms linking specific air pollution particle types with the initiating events leading to airway inflammation in sensitive populations

Promoting the use of the PI-QUAL score for prostate MRI quality: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant's ability to apply PI-QUAL. METHODS: Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. RESULTS: There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50-0.66]) to post-teaching (0.96 [0.92-0.98]), an improvement of 0.37 [0.21-0.41] (p < 0.001). CONCLUSIONS: A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. KEY POINTS: • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations

COVID-19 Pandemic Driven Knowledge, Attitude, Clinical Practice, Distress Reactions, and Post-Traumatic Growth of Dental Care Providers in Riyadh City, Saudi Arabia: A Cross-Sectional Study

Objective: The present study aimed to assess knowledge, attitude, clinical practices, distress reactions, and post-traumatic growth of dentists during the COVID-19 pandemic in Riyadh City. Methodology: An online questionnaire was developed to assess various dental professionals from both governmental and private sectors during the early COVID-19 outbreak in Riyadh City, Saudi Arabia. The questionnaire was framed to assess the demographic variables, knowledge, attitude, and clinical practices towards handling the COVID-19 pandemic. Furthermore, the general anxiety disorder-7 (GAD-7), worry questionnaire items, short form of post-traumatic growth inventory (PTGI-SF), and life satisfaction questionnaire items were developed to assess the anxiety, worries, post-traumatic growth, and life satisfaction of dental care providers following the traumatic events. Data were analysed using SPSS 22.0 and R environment ver.3.2.2. Continuous measurement results were presented as mean ± SD, and categorical measurements results were presented in number (%). Results: Our study's significant findings revealed that a majority of the dentists were in the age group of 21-30 and practiced general dentistry. The study participants in age groups 51–60 and 41–50 years old showed more liability in perceiving COVID-19 as an extremely dangerous disease than 31–40 and 21–30 age groups. The majority of respondents (63.4%) had an anxiety scale score of greater than 40, followed by 22.8% with scores 20-40 and 13.9% with scores less than 20, respectively. The mean scores for the GAD-7 and the worry items were 8.24 ± 3.21 and 13.92 ± 4.77, respectively. The data showed that most survey participants had adopted moderate post-traumatic changes during the pandemic, as evident by their mean score of 34.17 ± 3.40. The life satisfaction of the participants was neutral, as demonstrated by their mean score of 20.16 ± 4.03. Conclusion: This study’s findings delineated that the COVID-19 pandemic situation has influenced dentists' mental health, with a moderate level of anxiety, and worries among other psychological symptoms. Furthermore, there was adequate knowledge regarding the COVID-19 among dentists; however, the pandemic affected the financial conditions of the respondents. There was a moderate level of post-traumatic growth and neutral life satisfaction of the dental providers