Mifepristone pretreatment overcomes resistance of prostate cancer cells to tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)

Examination of the effects of TRAIL (tumor necrosis factor alpha-related apoptosis-inducing ligand) showed higher apoptotic response in LNCaP C4-2, whereas LNCaP were resistant. However, treatment of LNCaP with Mifepristone, an antiprogestin, before TRAIL induced significant apoptosis, similar to the levels observed in LNCaP C4-2. Experiments to determine the reasons for altered response of the cell lines showed no significant differences in death/decoy receptors and caspase-8 activity. However, treatment induced increased truncation of Bid and activation of caspases -9, -7, and -3 in LNCaP C4-2. Time course experiments showed that caspase-8 was activated before the involvement of mitochondrial pathway, and caspase-9 was responsible for activation of caspases -7 and -3. Use of specific caspase inhibitors demonstrated the presence of a short-loop feedback activation of Bid. Published reports suggested that increased phosphorylation of Akt was responsible for resistance of LNCaP to TRAIL. However, no significant differences were noticed in the levels of phosphorylated Akt in TRAIL-resistant LNCaP and TRAIL-sensitive LNCaP C4-2. On the basis of our results, it is suggested that the differences in response of the two cell lines to TRAIL is at the mitochondrial level.     

Esomeprazole vs pantoprazole effects on cyclosporine levels in kidney transplantation: A randomized clinical trial

Renal allograft survival requires multiple immunosuppressive drugs. This strategy may lead to gastric complications that necessitate gastro‐protective medications, notably, proton pump inhibitors (PPI). This study aimed to compare the influence of pantoprazole and esomeprazole on serum cyclosporine trough levels (C₀) in renal transplant recipients (RTR). A prospective, parallel, open‐label trial was conducted on 47 adult RTR receiving cyclosporine doses adjusted to attain trough concentrations of 100 to 150 μg/L, mycophenolate mofetil (MMF) 750 mg q12 hour and prednisolone at 5 mg daily at Nasser Institute, Cairo, Egypt from January to September 2016. Patients were randomized into the esomeprazole group (25) or pantoprazole group (22) receiving the same dose (40 mg once daily). The study outcomes included clinical signs of rejection and renal function decline, assessed by elevations in serum creatinine, caused by cyclosporine level variations in either of the two study groups. Renal function, C₀ and CBC measurements were measured at baseline and monthly for 6 months. The mean C₀ values were higher in the pantoprazole group than in the esomeprazole group in the sixth month only (P = .007). Serum creatinine level was lower in the sixth month than at baseline in the esomeprazole group (P = .004). There were no signs of rejection biochemical or clinical in any of the study groups. In conclusion, PPIs should be used with caution and doses should be titrated to reach the C₀ targets in RTR, which is of more importance in pantoprazole than esomeprazole to avoid C₀ level elevation or decline affecting the allograft function.     

Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT-ND3 and MT-ND4L) and male infertility

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.     

Comparing the efficacy of mandibular implant-retained overdentures and conventional dentures among middle-aged edentulous patients: satisfaction and functional assessment

PURPOSE: The aim of this randomized clinical trial was to compare the relative efficacy of mandibular overdentures retained by only two implants and a bar attachment with conventional dentures. MATERIALS AND METHODS: Edentulous adults, aged 35 to 65 years, were randomly assigned to two groups that received either a mandibular conventional denture (n = 48) or an overdenture supported by two endosseous implants with a connecting bar (n = 54). All subjects rated their general satisfaction and other features of their original dentures and their new prostheses (comfort, stability, ability to chew, speech, esthetics, and cleaning ability) on 100-mm visual analogue scales prior to treatment and 2 months postdelivery. Oral health-related quality of life was also evaluated pre- and posttreatment. RESULTS: Multiple regression analysis revealed that the mean general satisfaction was significantly higher in the overdenture group than in the conventional denture group (P = .0001). Age, gender, marital status, and income were not significantly associated with ratings of general satisfaction. Furthermore, the implant group gave significantly higher ratings on three additional measures of the prostheses (comfort, stability, and ease of chewing; P < .05). CONCLUSION: A mandibular two-implant overdenture opposed by a maxillary conventional denture is a more satisfactory treatment than conventional dentures for edentulous middle-aged adults.     

Risk factors associated with hospitalization owing to COVID-19: a cross-sectional study in Palestine

ObjectivesWe aimed to identify the risk factors for coronavirus disease 2019 (COVID-19)-associated hospitalization to provide evidence for improved clinical care of patients with COVID-19 infection.MethodsWe conducted a cross-sectional study among 300 participants. The collected data comprised sociodemographic data, lifestyle habits, physical activity, medical history, anthropometric measurements, COVID-19-related symptoms, dietary habits prior to and after COVID-19 infection, and psychological status.ResultsFifty-nine participants were hospitalized. Fever, dry cough, joint pain, chills, diarrhea, and shortness of breath were significantly associated with hospitalization owing to COVID-19. Adults with obesity, diabetes mellitus, hypertension, respiratory diseases, and cardiovascular diseases had higher rates of hospitalization. The findings also showed that residential area and age were related to COVID-19 hospitalization. Furthermore, our analysis revealed that certain dietary habits were associated with hospitalization rates.ConclusionOur study confirmed that older age, urban residence, illiteracy, obesity, hypertension, diabetes mellitus, respiratory diseases, cardiovascular diseases, and symptoms of loss of smell and sneezing elevated the risk of hospitalization among patients with COVID-19 infection. Patients with a higher risk of hospitalization may benefit from targeted therapeutic and preventive interventions.     

Protective effect of Fragaria ananassa methanolic extract on cadmium chloride (CdCl2)-induced hepatotoxicity in rats

This study investigated the protective effect of Fragaria ananassa methanolic extract on cadmium chloride (CdCl₂)-induced hepatotoxicity in rats. CdCl₂ was intraperitoneally injected at a dose of 6.5?mg/kg of body weight for 5 d with or without methanol extract of Fragaria ananassa (250?mg/kg). The hepatic cadmium concentration, lipid peroxidation, nitric oxide, glutathione (GSH) content, and antioxidant enzyme activities, including superoxide dismutase, catalase (CAT), GSH peroxidase, and GSH reductase, were estimated. CdCl₂ injection induced a significant elevation in cadmium concentration, lipid peroxidation, and nitric oxide and caused a significant depletion in GSH content compared to controls, along with a remarkable decrease in antioxidant enzymes. Oxidative stress induction and cadmium accumulation in the liver were successfully ameliorated by F. ananassa (strawberry) pre-administration. In addition, the pre-administration of strawberry decreased the elevated gene expression of the pro-apoptotic Bax gene as well as the protein expression of caspases-3 in the liver of CdCl₂-injected rats. In addition, the reduced gene expression of anti-apoptotic Bcl-2 was increased. Our results show an increase in the expression of tumor necrosis factor α in the liver of rats treated with cadmium. In sum, our results suggested that F. ananassa successfully prevented deleterious effects on liver function by reinforcing the antioxidant defense system, inhibiting oxidative stress and reducing apoptosis.     

An enzyme-linked immunosorbent assay for detection of IgG1 antibodies specific to human cystic echinococcosis in Egypt

Human cystic hydatidosis (cystic echinococcosis) is a chronic zoonotic disease that results from infection with the dog tapeworm Echinococcus granulosus. In Egypt, cystic echinococcosis (CE) is recognized in slaughtered livestock by veterinarians, however, there is little information about human CE infection rates. We describe an immunological assay useful for the diagnosis of human cystic hydatidosis. Sera were collected from surgically confirmed hydatid cases (34), nonendemic subjects free from parasitic infection (20) and from subjects (109) infected with other helminths (Hymenolepis nana, Schistosoma mansoni, Fasciola hepatica and Ancylostoma duodenale). Hydatid cyst fluid (HCF) of camel origin was used as antigen in an ELISA format to measure total E. granulosus specific IgG antibodies and IgG subclasses. Sensitivity measurements of total IgG, and IgG1-4 were 100, 100, 79.4, 61.8 and 55.9%, respectively, whereas respective specificity reached 65.1, 97.7, 98.4, 96.1 and 83. 7%. The diagnostic value of measuring IgG1 (97.7%), as assessed by a rating index (J) for combined sensitivity and specificity, was superior to total IgG (65.1%) and IgG2-4 (77.8, 57.9 and 39.6%, respectively). These findings set the stage for field evaluation of the IgG1 assay in areas endemic with human cystic hydatidosis.     

A real-time EMG-driven virtual arm.

An EMG-driven virtual arm is being developed in our laboratories for the purposes of studying neuromuscular control of arm movements. The virtual arm incorporates the major muscles spanning the elbow joint and is used to estimate tension developed by individual muscles based on recorded electromyograms (EMGs). It is able to estimate joint moments and the corresponding virtual movements, which are displayed in real-time on a computer screen. In addition, the virtual arm offers artificial control over a variety of physiological and environmental conditions. The virtual arm can be used to examine how the neuromuscular system compensates for the partial or total loss of a muscle's ability to generate force as might result from trauma or pathology. The purpose of this paper is to describe the design objectives, fundamental components and implementation of our real-time, EMG-driven virtual arm.     

A novel knock-in prostate cancer model demonstrates biology similar to that of human prostate cancer and suitable for preclinical studies.

Preclinical studies of prostate cancer (CaP) have employed a genetically engineered mouse model, since there is no naturally occurring CaP in rodents. We have previously reported a new knock-in mouse adenocarcinoma prostate (KIMAP) model. In this study, we demonstrate that the new model possesses a tumor architecture of heterogeneity and multifocality similar to that of human CaP, by utilizing a new compound scoring system to compare with the PSP94 (approved gene symbol Msmb) gene-directed transgenic mouse CaP model (TGMAP). KIMAP mice showed a balanced distribution of tumor extent, which penetrated the prostate gland. Comparative studies on cDNA microarrays demonstrated that KIMAP tumors were upregulated with higher contents of immunoresponse genes, whereas PSP-TGMAP tumors had neuroendocrine (NE) differentiation. The majority of KIMAP mice did not progress to NE CaP, which was observed only at a very late stage and a low frequency. Several tumor marker genes characteristic of human CaP were uniquely identified in KIMAP tumors, including hepsin, maspin, Nkx3.1, CD10 and PSP94 (similar to PSA), etc. The differences between these two CaP models are attributed to the introduction of a single endogenous knock-in mutation. Due to the similarities between human CaP tumors and the PSP-KIMAP tumors, this preclinical model may supplement the current transgenic models to study CaP more accurately.