Psychosocial and mental profile of children with sickle cell disease and their caregivers.

Sickle cell disease (SCD), a chronic debilitating disorder that may negatively affect health-related quality-of-life (HRQoL). In this observational, case-control study, we aim to assess the prevalence of impaired psychosocial profile and poor HRQoL among SCD patients and their caregivers as well as to determine the association of such impairment with parameters of disease severity. Sixty-five children and adolescents with SCD and 65 age- and sex-matched healthy controls and their caregivers were recruited. Demographic and clinical characteristics were collected, and a thorough clinical and psychiatric assessments and HR QoL were conducted. Recruited children and adolescents with SCD were 34 (52.3%) boys and 31 (47.7%) girls, and their mean age was 11.40 ± 3.55. Most of them (n = 44, 67.7%) had sickle HbSß+, and vaso-occlusive crises were the most common causes for hospital admission (n = 24, 36.9%). Children with SCD and their caregivers had depression and anxiety symptoms scores higher than reported in the control group. Children with SCD had significantly less self-esteem and less QoL scores with the least scores were in the communication domain. This adverse psychological profile was significantly negatively correlated with the age of the child, duration of illness, number and duration of hospitalizations, disease severity score, and occurrence of complications. We conclude that HRQoL of children suffering from SCD, and their caregivers are adversely affected necessitating implementation of interventions which focus on reducing depressive symptoms, enhancing self-esteem and QoL.

ERß mediates sex-specific protection in the App-NL-G-F mouse model of Alzheimer's disease.

Menopausal loss of neuroprotective estrogen is thought to contribute to the sex differences in Alzheimer's disease (AD). Activation of estrogen receptor beta (ERß) can be clinically relevant since it avoids the negative systemic effects of ERα activation. However, very few studies have explored ERß-mediated neuroprotection in AD, and no information on its contribution to the sex differences in AD exists. In the present study we specifically explored the role of ERß in mediating sex-specific protection against AD pathology in the clinically relevant App NL-G-F knock-in mouse model of amyloidosis, and if surgical menopause (ovariectomy) modulates pathology in this model. We treated male and female App NL-G-F mice with the selective ERß agonist LY500307 and subset of the females was ovariectomized prior to treatment. Memory performance was assessed and a battery of biochemical assays were used to evaluate amyloid pathology and neuroinflammation. Primary microglial cultures from male and female wild-type and ERß-knockout mice were used to assess ERß's effect on microglial activation and phagocytosis. We find that ERß activation protects against amyloid pathology and cognitive decline in male and female App NL-G-F mice. Ovariectomy increased soluble amyloid beta (Aß) in cortex and insoluble Aß in hippocampus, but had otherwise limited effects on pathology. We further identify that ERß does not alter APP processing, but rather exerts its protection through amyloid scavenging that at least in part is mediated via microglia in a sex-specific manner. Combined, we provide new understanding to the sex differences in AD by demonstrating that ERß protects against AD pathology differently in males and females, warranting reassessment of ERß in combating AD.

Hemophagocytic lymphohistiocytosis in Egyptian children: diagnosis, treatment challenges, and outcome.

BACKGROUND: Hemophagocyticlymphohistiocytosis (HLH) is a spectrum of immune activation which could be genetically determined, or secondary to an underlying illness. Our aim was to present the clinico-genetic aspects of HLH among Egyptian children and to evaluate the patterns of reactivation and outcome with illustrations of overlap manifestations. RESEARCH DESIGNAND METHODS: We retrospectively collected the data of 55 patients with HLH, registered at Ain Shams University Children's Hospital,Cairo, Egypt. RESULTS: Median age at diagnosis was 19 months (range 2-180), 33 patients (60%) fulfilled the diagnostic HLH criteria at presentation. Fourteen (25.45%) patients had secondary HLH, 15 (27.27%) patients had genetically documented familial HLH (11 had variants in UNC13D gene and one in PRF1 gene), 3 had Griscelli and Chediak-Higashi syndromes. Sixteen patients (29.1%) had reactivations, 8 (50%) of them had molecularly confirmed HLH. We report the death of 40 patients, the median duration from the diagnosis to death of 5 months mostly due to disease activity. CONCLUSIONS: This study confirms that the nonspecific signs and symptoms of HLH are challenging. Genetic testing, though expensive and sophisticated, is integral for the diagnosis. The difficulty in finding non-related donors for stem cell transplantation and the early reactivations are the causes of the inferior outcome.

BCL11A Polymorphism in Egyptian Children with ß-Thalassemia: Relation to Phenotypic Heterogeneity.

Fetal hemoglobin (HbF) is a potent genetic modifier of ß-thalassemia phenotype. B-cell lymphoma 11A ( BCL11A ) gene results in significant silencing of HbF. The aim of this study was to assess the prevalence of different BCL11A genotypes among a cohort of Egyptian children with ß-thalassemia and to correlate them to HbF and clinical severity score. Eighty-two children with ß-thalassemia (aged 12.95 ± 3.63 years) were recruited from the Pediatric Hematology Clinic, Ain Shams University. They were divided based on the clinical severity of ß-thalassemia into three subgroups: 20 mild (24.4%), 24 moderate (29.3%), and 38 severe (46.3%). Age, gender, age of diagnosis, initial HbF level, transfusion history, and history of splenectomy were assessed. Anthropometric measures, signs of anemia and hemosiderosis, and the severity score were determined. Laboratory investigations such as complete blood picture, ferritin, and single gene polymorphism genotyping of the rs11886868 were also performed. Our findings showed that 16 children had CC genotype (19.5%), 38 had TC genotype (46.3%), and 28 had TT genotype (34.1%) of the rs#. ß-thalassemia children with TT genotype had significantly higher severity scoring than the other two groups ( p < 0.001). Moreover, mean initial HbF was found to be lower in children with TT genotype followed by TC and CC genotypes ( p < 0.001). Increased γ-globin expression associated with BCL11A gene polymorphism is associated with better clinical severity of ß-thalassemia.

Novel Single-Nucleotide Variants for Morpho-Physiological Traits Involved in Enhancing Drought Stress Tolerance in Barley.

Barley (Hordeum vulgare L.) thrives in the arid and semi-arid regions of the world; nevertheless, it suffers large grain yield losses due to drought stress. A panel of 426 lines of barley was evaluated in Egypt under deficit (DI) and full irrigation (FI) during the 2019 and 2020 growing seasons. Observations were recorded on the number of days to flowering (NDF), total chlorophyll content (CH), canopy temperature (CAN), grain filling duration (GFD), plant height (PH), and grain yield (Yield) under DI and FI. The lines were genotyped using the 9K Infinium iSelect single nucleotide polymorphisms (SNP) genotyping platform, which resulted in 6913 high-quality SNPs. In conjunction with the SNP markers, the phenotypic data were subjected to a genome-wide association scan (GWAS) using Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK). The GWAS results indicated that 36 SNPs were significantly associated with the studied traits under DI and FI. Furthermore, eight markers were significant and common across DI and FI water regimes, while 14 markers were uniquely associated with the studied traits under DI. Under DI and FI, three (11_10326, 11_20042, and 11_20170) and five (11_20099, 11_10326, 11_20840, 12_30298, and 11_20605) markers, respectively, had pleiotropic effect on at least two traits. Among the significant markers, 24 were annotated to known barley genes. Most of these genes were involved in plant responses to environmental stimuli such as drought. Overall, nine of the significant markers were previously reported, and 27 markers might be considered novel. Several markers identified in this study could enable the prediction of barley accessions with optimal agronomic performance under DI and FI.