Relation of testosterone level and other factors with bone mineral density in male kidney transplant recipients: a cross-sectional study.

BACKGROUND: Although testosterone has a pivotal role in bone health, its correlation with bone mineral density (BMD) is understudied in kidney transplant recipients who are at high risk of osteoporosis. This study aimed to elucidate if there is any correlation between serum free testosterone and BMD in this population. PATIENTS AND METHODS: Sixty male kidney transplant recipients were enrolled in this cross-sectional study, and they were subjected to history taking, clinical examination, and laboratory investigations (including total and free testosterone). BMD was assessed in three regions (forearm, hip, and lumbar spine) using DEXA scan. RESULTS: The mean age of the included patients was 45.55 ± 13.58 years. Serum total and free testosterone had mean values of 5.17 ± 1.4 ng/ml and 95.46 ± 28.24 pg/ml, respectively, with all levels within the normal range. DEXA scan detected osteoporosis and osteopenia in 9 (15%) and 30 (50%) patients in the lumbar region, 3 (5%) and 36 (60%) in the hip region, as well as 21 (35%) and 33 (55%) in the forearm region, respectively. BMD of the lumbar region had a significant positive correlation with free testosterone, phosphorus, and eGFR, while it had a significant negative correlation with platelets and patient age. BMD of the hip region was positively correlated with serum phosphorus, parathyroid hormone, and duration since the transplant, whereas it was negatively correlated with platelets and total testosterone level. BMD of the forearm had a significant positive correlation with eGFR, whereas it had a significant negative correlation with age and duration since transplantation. In addition, forearm BMD was significantly lower in patients with a radiocephalic AVF. CONCLUSION: Even within the normal range, free testosterone has a significant positive correlation with lumbar spine BMD with no significant association with the forearm or hip BMD.

The anti-HCV, Sofosbuvir, versus the anti-EBOV Remdesivir against SARS-CoV-2 RNA dependent RNA polymerase in silico.

Coronavirus diseases 2019 (COVID-19) are seriously affecting human health all over the world. Nucleotide inhibitors have promising results in terms of its efficacy against different viral polymerases. In this study, detailed molecular docking and dynamics simulations are used to evaluate the binding affinity of a clinically approved drug, sofosbuvir, with the solved structure of the viral protein RNA-dependent RNA polymerase (RdRp) and compare it to the clinically approved drug, Remdesivir. These drugs are docked onto the three-dimensional structure of the nsp12 protein of SARS-CoV-2, which controls the polymerization process. Hence, it is considered one of the primary therapeutic targets for coronaviruses. Sofosbuvir is a drug that is currently used for HCV treatment; therefore, HCV RdRp is used as a positive control protein target. The protein dynamics are simulated for 100 ns, while the binding is tested during different dynamics states of the SARS-CoV-2 RdRp. Additionally, the drug-protein complexes are further simulated for 20 ns to explore the binding mechanism. The interaction of SARS-CoV-2 RdRp as a target with the active form of sofosbuvir as a ligand demonstrates binding effectiveness. One of the FDA-approved antiviral drugs, such as sofosbuvir, can help us in this mission, aiming to limit the danger of COVID-19. Sofosbuvir was found to bind nsp12 with comparable binding energies to that of Remdesivir, which has been reported for its potential against COVID-19 RdRp and is currently approved by the FDA.

A Review of Human Coronaviruses' Receptors: The Host-Cell Targets for the Crown Bearing Viruses.

A novel human coronavirus prompted considerable worry at the end of the year 2019. Now, it represents a significant global health and economic burden. The newly emerged coronavirus disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the primary reason for the COVID-19 global pandemic. According to recent global figures, COVID-19 has caused approximately 243.3 million illnesses and 4.9 million deaths. Several human cell receptors are involved in the virus identification of the host cells and entering them. Hence, understanding how the virus binds to host-cell receptors is crucial for developing antiviral treatments and vaccines. The current work aimed to determine the multiple host-cell receptors that bind with SARS-CoV-2 and other human coronaviruses for the purpose of cell entry. Extensive research is needed using neutralizing antibodies, natural chemicals, and therapeutic peptides to target those host-cell receptors in extremely susceptible individuals. More research is needed to map SARS-CoV-2 cell entry pathways in order to identify potential viral inhibitors.

Cholelithiasis after bariatric surgery, incidence, and prophylaxis: randomized controlled trial.

BACKGROUND: Rapid weight loss is associated with a high incidence of cholelithiasis. OBJECTIVES: To identify the incidence of gallstone formation after weight loss surgery and to detect the efficacy of 6 months regimen of prophylactic Ursodeoxycholic acid (UDCA). METHODS: RCT included a total of 1530 morbid obese patients who were subjected to either laparoscopic one anastomosis gastric bypass (OAGB), sleeve gastrectomy (SG), or greater curve plication (GCP). Patients with previous or concomitant cholecystectomy and missed follow-up were excluded, leaving 1432 patients to analyze. They were randomly allocated into two groups receiving either UDCA or placebo with a minimum follow-up of one year for assessment of cholelithiasis and weight loss. RESULTS: The overall incidence of cholelithiasis after surgery was 9.7%. There was a significant decrease in the incidence of gallstone formation from 22% in placebo to 6.5% in treated group with UDCA. The mean percentage of excess weight loss (%EWL) was significantly higher in those who develop gallstones than others. Of those developing gallstones, there was 64.7 % with SG versus 28.1% and 7.2% in OAGB and GCP, respectively, which is statistically significant. NNT to prevent cholelithiasis is six, AR% is 70.4%, and RR is 3.4%. CONCLUSIONS: Cholelithiasis after SG and OAGB was higher than GCP. %EWL was rapid and higher in OAGB and SG contributing to the higher rate of symptomatic cholelithiasis and could be predictive for post-bariatric cholelithiasis. A 6-month use of UDCA is an effective prophylaxis decreasing gallstone formation after bariatric surgery at short-term follow-up.

The mesenchymal stem cell marker CD248 (endosialin) is a negative regulator of bone formation in mice.

OBJECTIVE: CD248 (tumor endothelial marker 1/endosialin) is found on stromal cells and is highly expressed during malignancy and inflammation. Studies have shown a reduction in inflammatory arthritis in CD248-knockout (CD248(-/-) ) mice. The aim of the present study was to investigate the functional effect of genetic deletion of CD248 on bone mass. METHODS: Western blotting, polymerase chain reaction, and immunofluorescence were used to investigate the expression of CD248 in humans and mice. Micro-computed tomography and the 3-point bending test were used to measure bone parameters and mechanical properties of the tibiae of 10-week-old wild-type (WT) or CD248(-/-) mice. Human and mouse primary osteoblasts were cultured in medium containing 10 mM ß-glycerophosphate and 50 µg/ml ascorbic acid to induce mineralization, and then treated with platelet-derived growth factor BB (PDGF-BB). The mineral apposition rate in vivo was calculated by identifying newly formed bone via calcein labeling. RESULTS: Expression of CD248 was seen in human and mouse osteoblasts, but not osteoclasts. CD248(-/-) mouse tibiae had higher bone mass and superior mechanical properties (increased load required to cause fracture) compared to WT mice. Primary osteoblasts from CD248(-/-) mice induced increased mineralization in vitro and produced increased bone over 7 days in vivo. There was no decrease in bone mineralization and no increase in proliferation of osteoblasts in response to stimulation with PDGF-BB, which could be attributed to a defect in PDGF signal transduction in the CD248(-/-) mice. CONCLUSION: There is an unmet clinical need to address rheumatoid arthritis-associated bone loss. Genetic deletion of CD248 in mice results in high bone mass due to increased osteoblast-mediated bone formation, suggesting that targeting CD248 in rheumatoid arthritis may have the effect of increasing bone mass in addition to the previously reported effect of reducing inflammation.

Novel guanosine derivatives against MERS CoV polymerase: An in silico perspective.

The Middle East Respiratory Syndrome Coronavirus (MERS CoV), also termed camel flu, is a new viral infection that first reported in the year 2012 in the Middle East region and further spread during the last seven years. MERS CoV is characterized by its high mortality rate among different human coronaviruses. MERS CoV polymerase shares more than 20% sequence identity with the Hepatitis C Virus (HCV) Non-structural 5b (NS5b) RNA dependent RNA polymerase (RdRp). Despite the low sequence identity, the active site is conserved between the two proteins, with two consecutive aspartates that are crucial in the nucleotide transfer reaction. In this study, seven nucleotide inhibitors have been tested against MERS CoV RdRp using molecular modeling and docking simulations, from which four are novel compounds. Molecular Dynamics Simulation for 260 nanoseconds is performed on the MERS CoV RdRp model to test the effect of protein dynamics on the binding affinities to the tested nucleotide inhibitors. Results support the hypothesis of using the anti-polymerases (Anti-HCV drugs) against MERS CoV RdRp as a potent candidates. Besides four novel compounds are suggested as a seed for high performance inhibitors against MERS CoV RdRp.Communicated by Ramaswamy H. Sarma.

Relation between vitamin D and geriatric syndrome.

BACKGROUND: Vitamin D level is a common health problem for elderly persons and it is associated with a decrease in physical performance, furthermore, it has been demonstrated that those with low serum vitamin D level has more risk of cognitive impairment, depression and anxiety. AIM: The aim of the study was to estimate relation of vitamin D and geriatric syndrome. METHODS: A prospective study was done on 50 subjects who were normal elderly persons above 65 years. All the participants were subjected to full history taking, complete physical examination, laboratory assessment including serum 25-hydroxyvitamin D (OH)D by enzyme linked immunosorbent assay (ELISA) and geriatric syndrome assessment using 5 methods namely fall risk assessment using timed up &go test, mini-mental state examination (MMSE), geriatric depressive scale, mini nutritional assessment and Tinetti performance - oriented mobility assessment (POMA). RESULTS: The number of patients who were vitamin D deficient (<12 ng/ml), insufficient (12-20 ng/ml) and sufficient (>20 ng/ml) were 11, 24 and 15 respectively. There was significant p association between low vitamin D level and female gender (p = 0.024), advanced age (p = 0.026), no-sun exposure jobs (p = 0.001) and nursing home residency. Mini mental state examination (p = 0.006) and geriatric depressive scale (p = 0.002) had a significant positive correlation with low vitamin D level while mini nutritional assessment (p = 1.000), timed up and go test (p = 0.225) and POMA score (p = 0.133) had no significant correlation with low vitamin D level. CONCLUSION: There is correlation finding between vitamin D deficiency and advanced age, cognitive dysfunction, and depression.

Severe retinitis pigmentosa phenotype associated with novel CNGB1 variants.

PURPOSE: To report a severe phenotype of retinitis pigmentosa associated with novel mutations in CNGB1. OBSERVATIONS: Six siblings, age range 50-75 years old, were examined using optical coherence tomography and fundus autofluorescene, electroretinogram testing, Goldman visual field testing, and genetic testing using next generation sequencing.In four affected siblings, two novel compound heterozygous variants in CNGB1 were detected: in exon 26 the missense variant c.2603G > A (p.(Gly868Asp)), and in exon 21, the in-frame 12-bp duplication c.2093_2104dupGCGACCTCATCT (p.(Cys698_lle701dup)). One sibling was unaffected and carried neither of the variants, while another sibling had mild macular degeneration changes and carried the latter variant in heterozygous status. The affected siblings presented with a phenotype showing markedly constricted visual field, flat scotopic and photopic electroretinogram responses and generalized retinal atrophy. CONCLUSIONS AND IMPORTANCE: This is the first report of a 12bp in-frame duplication and a missense variant (in compound heterozygous status) in CNGB1, being associated with a severe form of retinitis pigmentosa featuring extensive peripheral and central retinal degeneration. This study expands the molecular genetic basis of CNGB1-related disease.

Studying the relation between vitamin D deficiency and glycemic state among pregnant women with gestational diabetes.

AIM: This study was conducted to illustrate the relation between vitamin D deficiency and glycemic parameters. MATERIALS AND METHODS: The study was carried out on 80 pregnant females who were attending obstetrics and gynecology out-patient clinic in el-Shatby hospital in Alexandria university, Egypt. They were divided into 2 groups: group 1 (n = 40) pregnant females diagnosed with gestational diabetes de novo at week 24-28 and group 2 (n = 40) pregnant females of the same age group who were not suffering from any glucose intolerance (control group). Each patient was subjected to detailed history taking, complete physical examination, One step 75 gm Oral glucose tolerance test, insulin, glycated hemoglobin(HbA1c),homeostatic model assessment of insulin resistance(HOMA-IR), 25 hydroxy-vitamin D, serum calcium, phosphorous and parathormone were assessed. RESULTS: A statistically significant higher fasting blood glucose (FBG), HbA1c%, fasting insulin and HOMA-IR was observed in patients with Gestational diabetes mellitus (GDM) versus control (p < 0.001). However, no significant difference was observed as regards Vitamin D levels in patients with GDM and control group. Among patients with GDM, vitamin D was found to correlate negatively with HbA1c (p < 0.001), insulin(p = 0.019) and HOMA-IR(p = 0.034). CONCLUSION: No definite causal relationship was observed between low vitamin D and subsequent occurrence of GDM.however, a significant correlation was found between the degree of vitamin D deficiency and the insulin resistance in patients with GDM.

DObesity: Relationship between vitamin D deficiency, obesity and sclerostin as a novel biomarker of bone metabolism.

AIM: To study the relationship between obesity, insulin resistance, vitamin D deficiency and sclerostin as a bone biomarker. MATERIALS AND METHODS: Cross-section study of 75 subjects grouped into 3 groups; obese (n = 31), overweight (n = 23) and normal (n = 21) subjects. Sclerostin, fasting insulin, fasting plasma glucose and 25(OH)D were measured and anthropometric measures were taken. RESULTS: 25(OH)D was lower in obese subjects than overweight and control groups (mean ±â€¯SD 5.27 ±â€¯5.14 vs. 12.55 ±â€¯6.99 vs.17.65 ±â€¯4.07 ng/L, p < 0.001). Sclerostin was significantly lower in obese subjects versus the control (mean ±â€¯SD 1.02 ±â€¯0.45 vs 1.58 ±â€¯0.83 ng/mL, p = 0.014). CONCLUSION: These results lead us to hypothesize that the relationship between sclerostin and Vitamin D levels has an important role in the link between obesity and bone metabolism. DObesity could be an active focus of research in the coming years.

Prevalence of newly detected diabetes in pregnancy in Qatar, using universal screening.

BACKGROUND: Diabetes first detected during pregnancy is currently divided into gestational diabetes mellitus (GDM) and diabetes mellitus (DM)- most of which are type 2 DM (T2DM). This study aims to define the prevalence and outcomes of diabetes first detected in pregnancy based on 75-gram oral glucose tolerance test (OGTT)using the recent WHO/IADPSG guidelines in a high-risk population. METHODS: This is a retrospective study that included all patients who underwent a 75 g (OGTT) between Jan 2016 and Apr 2016 and excluded patients with known pre-conception diabetes. RESULTS: The overall prevalence of newly detected diabetes in pregnancy among the 2000 patients who fulfilled the inclusion/exclusion criteria was 24.0% (95% CI 22.1-25.9) of which T2DM was 2.5% (95% CI 1.9-3.3), and GDM was 21.5% (95% CI 19.7-23.3). The prevalence of newly detected diabetes in pregnancy was similar among the different ethnic groups. The T2DM group was older (mean age in years was 34 ±5.7 vs 31.7±5.7 vs 29.7 ±5.7, p<0.001); and has a higher mean BMI (32.4±6.4 kg/m2 vs 31.7±6.2 kg/m2 vs 29.7± 6.2 kg/m2, p< 0.01) than the GDM and the non-DM groups, respectively. The frequency of pre-eclampsia, pre-term delivery, Caesarean-section, macrosomia, LGA and neonatal ICU admissions were significantly higher in the T2DM group compared to GDM and non-DM groups. CONCLUSION: Diabetes first detected in pregnancy is equally prevalent among the various ethnic groups residing in Qatar. Newly detected T2DM carries a higher risk of poor pregnancy outcomes; stressing the importance of proper classification of cases of newly detected diabetes in pregnancy.