Population genetics of Hyphaene thebaica Mart., in Rabigh province, Saudi Arabia: Implications for conservation

Hyphaene thebaica is a perennial plant distributed in desert and subtropical regions of the world. In Rabigh Province, western Saudi Arabia, the few persisting populations of this species are exposed to many threats, including overcutting and, recently, human habitation. These threats are predicted to be exacerbated with the advancement of aridification caused by climate change. The conservation and revival of the diminished populations of H. thebaica requires an assessment of their genetic diversity and genetic differentiation. To accomplish this objective, we applied 10 simple sequence repeat (SSR) primer pairs, with which all are polymorphic loci. These polymorphic loci were used to determine the population genetics of 60 plant accessions sampled from 5 populations of H. thebaica located in five sites in Rabigh Province: Wadi EL Khaneg, Wadi Al Johfa, Wadi Al Hakak and Wadi Khurieba and Wadi Kuliayah . Low to moderate levels of genetic diversity were found in all populations (the values of the PPL% ranged between 52.5% and 22.5%) along with a decreased value of HT (0.388) and a considerable inbreeding value (F= 0.4552), which verified an obvious shortage of heterozygotes. High genetic differentiation among the populations and a low level of gene flow suggest isolation among the H. thebaica populations, which caused a severe deficiency in gene migration. The data obtained herein will inspire several recommendations for conservation the existing populations, including seed preservation, and management of human activities. All of these actions are urgently needed to prevent imminent extinction.

Neuron Navigator 3 (NAV3) is Required for Heart Development in Zebrafish

As a tightly controlled biological process, cardiogenesis requires the specification and migration of a suite of cell types to form a particular three-dimensional configuration of the heart. Many genetic factors are involved in the formation and maturation of the heart, and any genetic mutations may result in severe cardiac failures. The neuron navigator (NAV) family consists of three vertebrate homologs (NAV1, NAV2, and NAV3) of the neural guidance molecule Uncoordinated-53 (UNC-53) in Caenorhabditis elegans. Although they are recognized as neural regulators, their expressions are also detected in many organs, including the heart, kidney, and liver. However, the functions of NAVs, regardless of neural guidance, remain largely unexplored. In our study, we found that nav3 gene was expressed in the cardiac region of zebrafish embryos from 24 to 48 hours post-fertilization (hpf) by means of in situ hybridization (ISH) assay. A CRISPR/Cas9-based genome editing method was utilized to delete the nav3 gene in zebrafish and loss-of-function of Nav3 resulted in a severe deficiency in its cardiac morphology and structure. The similar phenotypic defects of the knockout mutants could recur by nav3 morpholino injection and be rescued by nav3 mRNA injection. Dual-color fluorescence imaging of ventricle and atrium markers further confirmed the disruption of the heart development in nav3-deleted mutants. Although the heart rate was not affected by the deletion of nav3, the heartbeat intensity was decreased in the mutants. All these findings indicate that Nav3 was required for cardiogenesis in developing zebrafish embryos.

Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes

Background: Several studies suggest an association between serum 25-hydroxyvitamin D (25OHD) and the outcomes of Severe Acute Respiratory Syndrome Corona-Virus-2 (SARS-CoV-2) infection, in particular Coronavirus Disease-2019 (COVID-19) related severity and mortality. The aim of the present meta-analysis was to investigate whether vitamin D status is associated with the COVID-19 severity, defined as ARDS requiring admission to intensive care unit (ICU) or mortality (primary endpoints) and with the susceptibility to SARS-CoV-2 and COVID-19-related hospitalization (secondary endpoints).Methods: A search in PubMed, ScienceDirect, Web of Science, Google Scholar, Scopus, and preprints repositories was performed until March 31th 2021 to identify all original observational studies reporting association measures, or enough data to calculate them, between Vitamin D status (insufficiency <75, deficiency <50, or severe deficiency <25 nmol/L) and risk of SARS-CoV-2 infection, COVID-19 hospitalization, ICU admission, or death during COVID-19 hospitalization.Findings: Fifty-four studies (49 as fully-printed and 5 as pre-print publications) were included for a total of 1,403,715 individuals. The association between vitamin D status and SARS-CoV2 infection, COVID-19 related hospitalization, COVID-19 related ICU admission, and COVID-19 related mortality was reported in 17, 9, 27, and 35 studies, respectively. Severe deficiency, deficiency and insufficiency of vitamin D were all associated with ICU admission (odds ratio [OR], 95% confidence intervals [95%CIs]: 2.63, 1.45–4.77; 2.16, 1.43–3.26; 2.83, 1.74–4.61, respectively), mortality (OR, 95%CIs: 2.60, 1.93–3.49; 1.84, 1.26–2.69; 4.15, 1.76–9.77, respectively), SARS-CoV-2 infection (OR, 95%CIs: 1.68, 1.32–2.13; 1.83, 1.43–2.33; 1.49, 1.16–1.91, respectively) and COVID-19 hospitalization (OR, 95%CIs 2.51, 1.63–3.85; 2.38, 1.56–3.63; 1.82, 1.43–2.33). Considering specific subgroups (i.e., Caucasian patients, high quality studies, and studies reporting adjusted association estimates) the results of primary endpoints did not change.Interpretations: Patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 infection and related hospitalization.

New Variants of the Cytochrome P450 2R1 (CYP2R1) Gene in Individuals with Severe Vitamin D-Activating Enzyme 25(OH)D Deficiency

Background: Vitamin D is a fat-soluble cholesterol derivative found in two forms, vitamin D2, and vitamin D3. Cytochrome P450 2R1 (CYP2R1) encoded by the CYP2R1 gene is the major hydroxylase that activates vitamin D by catalyzing the formation of 25-hydroxyvitamin D (25(OH)D). Methods: We collected 89 (100%) subjects, 46 of which (51.69%) had a documented severe deficiency of 25(OH)D (<10 ng/mL) and 43 (48.31%) in the control group with documented optimum levels of 25(OH)D (>30 ng/mL). We performed Sanger sequencing of three selected fragments of the CYP2R1 gene (Ch11: 14878000–14878499; Ch11: 14880058–14880883 and Ch11: 14885321–14886113) that affect the binding of substrates to this enzyme and analyzed the possible involvement of genetic variation in these regions with an increased risk of vitamin D deficiency in healthy Polish individuals. Results: Two substitutions were found within the three fragments. Bioinformatic analysis suggested that one of these (NC_000011.10: g.14878291G>A) may influence the structure and function of CYP2R1. Conclusions: Variant NC_000011.10: g.14878291G>A may have a perturbing effect on heme binding in the active site of CYP2R1 and on the function of 25-hydroxylase and probably affects the concentration of 25(OH)D in vivo. We intend to perform functional verification in a larger patient population to confirm and extend these results.

Devastating Salt-wasting Crisis in a Four-month-old Male Child with Congenital Adrenal Hyperplasia, Highlighting the Essence of Neonatal Screening

Classic Congenital Adrenal Hyperplasia in males usually presents late until before puberty, but rarely at birth. In cases of undiagnosed CAH, severe deficiency of cortisol may lead to life threatening situation in an infant with acute salt losing crisis. Screening for CAH at birth can lead to better outcomes.

Vitamin D Deficiency and Adverse Results in COVID-19

Aim: The goal of this study is to find out how common vitamin D deficiency is in patients with corona virus disease and what the consequences are. Study Design: Observational /Prospective Place and Duration: Institute of Basic medical sciences, Khyber Medical University (KMU), Jan 2021-Oct 2021. Materials & Methods: This study included 120 patients of both genders who had been diagnosed with covid-19. Patients ranged in age from 15 to 75 years. After receiving written agreement, demographically detailed such as age, sex, and BMI were recorded. All of the patients had a 5 mL blood sample obtained to check their vitamin D levels. 25(OH)D < 25 nmol/L (10 ng/dL) was considered severe Vitamin D insufficiency. The prevalence of vitamin D insufficiency as well as negative effects were investigated. SPSS 23.0 was used to analyse the data. Results: The mean age of the 120 patients was 40.11±8.64 years, with 68 (56.7%) males and 52 (43.3%) females. There were 52 patients (43.3%) with severe vitamin D insufficiency. There were 17 deaths of the total number of patients in the study. Vitamin D deficiency was associated with a higher mortality rate in patients with covid-19 disease than in those who had normal levels of vitamin D, a finding that was statistically significant at the 0.05 level. Conclusion: It was found that severe deficiency of vitamin D and death in individuals with covid-19 illness had a strong association. Keywords: Mortality, Vitamin D Deficiency, Covid-19,

Vitamin D status and obesity in children from Chile

Background Vitamin D [25(OH)D] is essential for normal bone development and maintenance. Furthermore, its deficiency has been associated with obesity, cardiovascular diseases, insulin resistance, autoimmune diseases, and certain cancers. Objective To determine the incidence of serum 25(OH)D deficiency (<20 ng/ml) among apparently healthy Chilean children (4–14 years old) from three Chilean geographic areas during May–September 2018. Materials and methods Serum 25(OH)D levels were measured by a competitive protein-binding ELISA assay in 1134 children, and correlations between serum 25(OH)D levels, BMI, and geographic area were calculated. Individuals were grouped according to their serum 25-hydroxyvitamin D levels (ng/ml): severe deficiency: <5; moderate deficiency: 5–10.9; mild deficiency: 11–20.9; insufficiency: 21–29.9 and sufficiency: 30–100. Results We found 80.4% of children had serum 25(OH)D deficiency, with 1.7% severe, 24.6% moderate, and 54.1% mild. In the three cities, the percentage of serum 25(OH)D deficit was increased when comparing overweight or obesity with a healthy weight. Additionally, an interaction effect was observed between geographic area, nutritional status, and serum 25(OH)D levels using the factorial ANOVA test (p = 0.038). In Antofagasta, there were more overweight children and also a higher percentage of children with VitD deficiency (<30 ng/ml) compared to Santiago or Concepción. Conclusion This study revealed a high prevalence of serum 25(OH)D deficiency in children between 4 and 14 years old in Chile (80.4%) during May–September 2018. Obese and overweight children had the highest prevalence of serum 25(OH)D deficiency.

Bone Deformity due to Rickets and Osteomalacia in Children and Adolescents

Rickets is a worldwide bone disease that is associated with disorders of calcium and phosphate homeostasis and can lead to short stature and joint deformities. Osteomalacia is a major metabolic bone disease that results from a chronic and severe deficiency of vitamin D or phosphate from any cause after growth has stopped. A deficiency of vitamin D or phosphate leads to defective bone mineralization and generalized or localized vague bone pain in various parts of the skeleton and / or proximal muscle weakness. Rickets and osteomalacia are two different clinical diseases with impaired bone mineralization. Rickets occurs throughout the growing skeleton in infants and children, while osteomalacia occurs in adults after fusion of the growth plates. Rickets and osteomalacia are increasingly common in Saudi Arabia, with vitamin D deficiency being the most common etiological cause. Early skeletal deformities can occur in infants, such as soft, thin skull bones, a condition known as craniotabes. In adults, as a result of demineralization, the bones become less rigid (soft bone) with pathological fractures. The diagnosis of both diseases is based on the medical history and physical examination, radiological characteristics, and biochemical tests. Management depends on the underlying etiology.

Evaluation of Maternal and Infantile Levels of Vitamin D in Preterm Infants

Introduction: Vitamin D deficiency is highly prevalent during pregnancy and in premature infants. This study was done to investigate the maternal and infantile levels of vitamin D in preterm infants. Methods: Using available sampling during 2018-2020 the maternal and umbilical cord serum levels of vitamin D were measured in 294 premature infants in Ghaem Hospital, Mashhad, Iran. A researcher-made questionnaire containing neonatal demographic and clinical characteristics was used as data collection tool. Both maternal and placental vitamin D levels were categorized into four classes: severe deficiency (vitamin D<10 ng/ml), moderate deficiency (10.1≤vitamin D≤20 ng/ml), mild deficiency (20.1≤vitamin D≤30 ng/ml) and normal (vitamin D >30.1ng ml). Results: Vitamin D deficiency was seen in 89% of premature infants (46.6% severe, 30.6% moderate, and 11.9% mild). Serum levels of vitamin D were 18.28±13.94 ng/ml and 14.10±9.70 ng/ml in mothers and infants, respectively. The infants below and above 32 weeks had vitamin D values of: 10.97±6.31 ng/ml and 18.05±11.64 ng/ml, respectively. The difference in vitamin D levels between boys (12.59±8.40 ng/ml) and girls (16.05±11.45 ng/ml) was significant (P=0.009). Moderate and severe vitamin D deficiency were more common at earlier pregnancy ages (P=0.001). Conclusion: Vitamin D deficiency is more common and severe in preterm infants and their mothers. Controlling vitamin D level during pregnancy, especially in women at risk of preterm labor and preterm infants may help reduce prematurity problems.