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Background: The initial inflammatory reaction starts following occlusion in ischemic stroke (IS). Interleukin-1β (IL-1β) is a pro-inflammatory cytokine with a crucial role in the pathogenesis of neurodegenerative disorders.Objective: To investigate the levels of IL-1β and vitamin D (VitD) in patients with IS compared with controls and their correlation.Methods: The serum level of 25-OH VitD and IL-1β was assessed in 102 IS patients (0-24 h after stroke) and 102 controls with an enzyme-linked immunosorbent assay (ELISA) kit.Results: We found a significant increase in IL-1β (80.14±6.8 vs. 60.32±4.1 pg/ml, p

Background: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system characterized by infiltration of inflammatory leukocytes to the CNS followed by oligodendrocyte cell death, myelin sheath destruction, and axonal injury. A logical incidence occurring after demyelination is remyelination. G-protein coupled receptors (GPCRs) activate internal signal transduction cascades through binding to different ligands. This family of receptors are targeted by more than 40% of currently marketed drugs. GPCRs can be successfully targeted for induction of remyelination. GPCRs highly enriched in oligodendrocyte progenitor cells compared to oligodendrocytes are proposed to hamper oligodendrocyte differentiation and therefore their inhibition might induce remyelination. This study aimed to investigate the expression of GPCRs in silico and in vitro. Methods: We performed gene expression analysis using DAVID and Panther websites on a RNA-seq dataset (GSE52564 accession number). Primary embryonic neural stem/progenitor cell isolation and culture were performed and subsequently NSPCs were characterized by Immunocytochemistry with Anti-Nestin antibody. Expression of GPR37L1, EDNRB, PDGFRα, CNPase and GFAP were assessed using real-time PCR. All the experiments were conducted at Shiraz University of Medical Sciences (SUMS), Shiraz, Iran, in the year 2018. Results: The 14 most highly expressed GPCRs in oligodendrocyte progenitor cells (OPCs) compared to Oligodendrocytes were presented in our study. Conclusion: The investigation of the most highly expressed GPCRs in OPCs compared to oligodendrocyte in silico and in vitro presents the significant role of GPCRs in remyelination induction. Among the 14 GPCRs mentioned in this study, GPR37L1 is a potential remyelinating drug target and is suggested for further studies.

Objective(s): Diabetes mellitus (DM) is a major worldwide public health challenge, for which gene therapy offers a potential therapeutic approach. To date, no systematic review or meta-analysis has been published in this area, so we examined all relevant published studies on rodents to elucidate the overall effects of gene therapy on bodyweight, intraperitoneal glucose tolerance test (IPGTT), fasting blood glucose, and insulin in animals with type 1 DM. Materials and Methods: The Cochrane Library, PubMed, Embase, ISI Web of Science, SCOPUS, and Google Scholar were systematically searched for potentially relevant studies. Mean±standard deviation (SD) was pooled using a random-effects model.Results: After the primary search, out of 528 studies identified, 16 studies were in concordance with predefined criteria and selected for the final assessment. Of these, 12 studies used viral manipulation, and 4 employed non-viral vectors for gene delivery. The meta-analysis showed gene therapy with a viral vector decreased mean IPGTT (-12.69 mmol/l, PConclusion: Gene therapy has favorable effects on alleviating type 1 DM related factors in diabetic rodents.

The present study was aimed at preparation of transdermal patches of tizanidine HCl, evaluation of the effect of polymers on in vitro release pattern of the drug, and the effect of permeation enhancers on the penetration of the drug through the rabbit skin. Various proportions of hydrophilic (HPMC) and hydrophobic (Eudragit L-100) polymers were used with PEG 400 as film-forming agent, and Span 20 or DMSO as permeation enhancer. The formulations were assessed for physicochemical characteristics and in vitro drug release studies using USP paddle over disc method in phosphate buffered saline (pH 7.4) at 32.0±1°C. On the basis of in vitro studies and physicochemical evaluations, S03-A and S04-A were selected at Eudragit : HPMC ratios of 8 : 2 and 7 : 3, respectively, for further ex vivo analysis. The effects of different concentrations of Span 20 and DMSO were evaluated on excised rabbit skin using Franz diffusion cell. Cumulative drug permeation, flux, permeability coefficient, target flux, and enhancement ratio were calculated and compared with the control formulations. Kinetic models and Tukey’s multiple comparison test were applied to evaluate the drug release patterns. Formulation SB03-PE containing Eudragit L-100:HPMC (7:3) with Span 20 (15% w/w) produced the highest enhancement in drug permeation, and followed zero order kinetic model with super case-II drug release mechanism.

Pump-controlled hydraulic circuits offer an energy-efficient solution for many applications. They combine the high power to weight ratio of hydraulic technology with the ease of control of electric technology. Pump-controlled circuits for double-rod cylinders are well developed as compared to those of single-rod cylinders. In spite of many initiatives, certain common pump-controlled single-rod cylinder solutions present stability issues during specific modes of operation. Common examples of the solutions are circuits that utilize pilot-operated check valves and circuits that use shuttle valves. In these circuits, velocity oscillations have been reported during actuator retraction at low assistive loads. In this paper, we study the area on the load-velocity graph of the available circuits where oscillatory behavior is experienced. We then propose a solution that shifts this critical zone towards lower loading values. This in turn reduces system response oscillations. Shifting the critical zone is accomplished by utilizing two charge pressures and asymmetric flow compensating valves. The concept is evaluated via simulations and experiments. Our results clearly show the enhanced performance of the circuits incorporating the proposed solution.

Context: Candida species are opportunistic yeasts that cause infections ranging from simple dermatosis to potentially life-threatening fungemia. The emergence of resistance to antifungal drugs has been increased in the past two decades. Aim: the present study we determined to find out the susceptibility profiles of clinical isolates of Candida species against four antifungal drugs, including amphotericin B, ketoconazole, fluconazole and itraconazole. Materials and Methods: Antifungal susceptibility testing of the yeasts was done in accordance with the proposed guidelines for antifungal disk diffusion susceptibility testing of yeasts based on the CLSI document M44-A. Results: A total of 206 yeast isolates were assessed. Among the evaluated Candida species, the highest rates of resistance to ketoconazole were seen in Candida glabrata (16.6%) and Candida albicans (3.2%). Susceptibility and intermediate response to fluconazole were seen in 96.6% and 3.4% of the Candida isolates, respectively. A total of 19 (9.2%) yeast isolates showed petite phenomenon including 11 C. glabrata, 3 C. albicans, 2 Candida dubliniensis and one isolate of each Candida krusei and Candida parapsilosis. Conclusion: The high number of petite mutation in the isolated yeasts should be seriously considered since it may be one of the reasons of antifungal treatment failure.

Valve-controlled hydraulic actuation systems are favored in many applications due to their fast response, high power-to-weight ratio, and stability under variable working conditions. Efficiency, however, is the main disadvantage of these systems. Pump-controlled hydraulic actuations, on the other hand, eliminate energy losses in throttling valves and require less cooling. Furthermore, they inherently hold the ability to recover energy from assistive loads. Pump-controlled circuits for double-rod cylinders are well developed and are implemented in many industrial applications, including aviation. However, pump-controlled circuits for single-rod cylinders usually experience performance issues during specific modes of operation. In this paper, a new circuit using two valves to compensate for the differential flow of single-rod actuators is proposed. The compensating valves provide limited throttling over the differential flow only in critical operating regions to alleviate unwanted velocity oscillations. They have a minimum throttling effect in all other operating regions to preserve the efficiency. The new circuit has been experimentally evaluated. Its performance has also been compared with three other previously proposed circuits. The proposed circuit displays an improved performance, besides being capable of energy regeneration.

Background: Sulfonylureas are important drugs of choice for treatment of type 2 diabetes mellitus (T2DM). It is suggested that differential response to sulfonylureas from T2DM patients is under influence of single nucleotide polymorphisms in some of the target genes. In spite of favorable therapeutic effects, sulfonylureas are associated with some adverse side effects such as microvascular complications and stroke, especially in older patients. Therefore, for T2DM patients who are getting less benefit, sulfonylureas should be avoided. Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like (CDKAL1) gene variation is reported to be associated with sulfonylureas effectiveness. Due to the inconsistency of available data regarding association of rs7754840 in CDKAL1 gene with sulfonylureas response in T2DM patients, the present study is conducted. Materials and Methods: Fifty-one diabetic patients sensitive to sulfonylureas and 51 patients resistant to sulfonylureas treatment were recruited to this study. After extraction of DNA from patients' peripheral blood samples, rs7754840 single-nucleotide polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism assay using MaeII (Tail) restriction enzyme. Results: Frequency of G allele in resistant group was more than sensitive group (71, 6% vs. 57, 8%). Regression analysis was shown significant association between GG genotype and higher risk of resistance to sulfonylureas treatment (odds ratio = 2.250 [95% confidential intervals: 1.010–5.012]; P = 0.046). Conclusion: Our data confirmed that genotypes of rs7754840 are significantly associated with sulfonylureas treatment response. rs7754840 in CDKAL1 gene in combination with other clinicopathological findings would help to move towards personalized therapy of T2DM patients.

Background: Grape exosome-like nanovesicles (GELNs) have the advantage of inherent biocompatibility and biodegradability, the potential to be used as oral delivery vehicles. The objective of this research was to evaluate the efficiency of Syrah GELN purification and their effects on the intestinal stem cells when orally administrated to the rats. Materials and Methods: In this experimental study, Syrah GELN isolated by differential centrifugation and sucrose gradient ultracentrifugation method, then the concentration of protein, size, and zeta potential were measured as well as nanoparticles morphology. The stability of nanoparticles was investigated in the solution that mimicked the condition encountered in the stomach and intestine. To demonstrate transfection efficiency of intestinal stem cells, real-time PCR was carried out using rat leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5)-specific primers on cDNA derived from total RNA extracted from the upper part of the small intestine of GELN-treated rats and their controls. Results: The mean size, zeta potential, and concentration of nanoparticles were 205.1 nm, −12.5 mV, and 250 μg/ml, respectively. The result of stability test demonstrated that Syrah GELN were resistant to the harsh environment of the stomach. Lgr5 gene expression was increased by tenfold in GELN-treated rats compared with the controls. Conclusions: As intestinal stem cells are poorly accessible by common exogenous agents in vivo, oral delivery of GELNs provides a new approach to modulate the stem cell microenvironment for intestinal remodeling. This novel and effective method would help to overcome conditions such as inflammatory bowel disease, colorectal cancer, and applicable in regenerative medicine.

Pump-controlled hydraulic circuits are more efficient than valve-controlled circuits, as they eliminate the energy losses due to flow throttling in valves and require less cooling effort. Presently existing pump-controlled solutions for single rod cylinders encounter an undesirable performance during certain operating conditions. This paper investigates the performance issues in common pump-controlled circuits for the single rod actuators. Detailed analysis is conducted that identifies these regions in a load-velocity plane and the factors affecting them. The findings are validated by experimental results. A new design is then proposed that employs a limited throttling valve alongside two pilot operated check valves for differential flow compensation to improve the performance. The valve is of the flow control type and is chosen to have a throttling effect over critical regions; it has the least throttling over other operating regions, thus maintaining efficiency. Experimental work demonstrates improved performance in a full operating range of the actuator as compared to a circuit that uses only the pilot-operated check valves. This circuit is energy efficient and capable of recuperating energy.

Objective: In recent years, an overwhelming association between Pediatric Type 1 Diabetes Mellitus (T1DM) and autoimmune diseases has been largely reported. The current study was designed to determine a possible association between autoimmune thyroiditis (AIT), celiac disease (CD) - associated autoantibodies, and Parvovirus B19 infection among pediatric T1DM cases in the southwestern region of Saudi Arabia., Patients and Methods: Blood samples from age groups 1-18 years attending the Diabetic Clinic were collected over a period of 12 months. Serum anti-thyroid peroxidase (TPO), anti-thyroglobulin (TG), anti-tissue transglutaminase immunoglobulin A (TG-IgA), endomysial IgA (EMA-IgA), Parvovirus B19-IgG and IgM antibodies were detected by standard methods., Results: The results showed the prevalence of autoantibodies against thyroid and CD among pediatric T1DM patients to be 44 (25%) and 25 (14.4%), respectively. The prevalence of antibodies against B19 was 70 (40%). Further determination of the prevalence of Parvovirus B19-IgG antibodies and thyroid antibodies among T1DM pediatric patients revealed that there was a significant association between them with a p<0.0491., Conclusions: The prevalence of autoantibodies against the thyroid was higher among the seropositive Parvovirus B19 children with T1DM. A positive association between the prevalence of autoantibodies against thyroid disease and the increase in the duration of diabetes was also noted. Hence, periodic screening of T1DM patients for B19 antibodies and autoantibodies for thyroid is crucial.

Human toxocariasis is a zoonotic infection with global and regional impacts. Worldwide it is underestimated and clinically overlooked. Medical practitioners are generally unaware of the extent of the resulting disease spectrum. The objective of the study was to assess knowledge and disease awareness among medical practitioners in Aseer, south-western Saudi Arabia. A questionnaire addressing knowledge about the parasite, its visceral larva migrans and the disease spectrum generated was used to interview participants. The study included 285 participants. In answer to the question what is toxocara, only 27%, answered correctly that it is a nematode, paediatricians being the majority. With regard to years of experience among participants, 56.8% of those who answered correctly had less than 5-year experience, as opposed to 35.4% for those with more than 10-year experience. The cumulative awareness about the disease manifestations and spectrum, i.e. those who knew, was less than 30% across specialties and years of experiences. Lack of awareness regarding Toxocara infection and the disease spectrum it can generate is evident. The consequence for such lack of knowledge within our practising medical community is simply unacceptable as it might translate into misdiagnosis and consequently misguided treatment., (© 2021. EcoHealth Alliance.)

Objectives: To investigate the presence of toxoplasmosis, rubella, cytomegalovirus, and herpes (TORCH) infections in women attending at the antenatal care clinic in Abha, Kingdom of Saudi Arabia (KSA). Methods: A total of 190 blood samples were collected from Abha maternity hospital in Aseer region, KSA, from February 2018 to May 2019 and screened with the TORCH panel (toxoplasmagondii [IgG/IgM], cytomegalovirus [CMV] [IgG/IgM], rubella [IgG/IgM], and herpes simplex type 1 and 2 [IgG/IgM])., Results: The mean age was 31.42±6.514 years and gestational age was 32.48±6.168 weeks. Serum IgG was positive for Toxoplasma gondii (T. gondii) (27.4%), herpes simplex type 1 (HSV-1) (94.7%), herpes simplex type 2 (HSV-2) (0.5%), CMV (100%), and rubella (88.9%). Serum IgM was positive only for CMV (9.5%). Though, there was an association between abortions from previous pregnancies (26.5%), intrauterine death (5.8%), premature labor (3.2%), microcephaly (1.6%), other congenital diseases (1.6%) and low birth weight (0.5%) with current IgG positivity for TORCH infections, the results were not statistically significant., Conclusion: Seropositivity for IgG antibodies correlate with TORCH-associated pregnancy complications in Abha, KSA; however, IgM positive CMV pregnant cases warrant further systematic investigation to understand the implications of CMV on outcomes during pregnancy.

Objective: Vascular endothelial growth factor (VEGF) is regulated by hypoxia that is essential for placental development. It is antagonized by a soluble form of its receptor (sFlt-1). The purpose of this study was to measure these factors in the maternal and the cord bloods, at low and high altitude., Methods: Samples were collected from full term births normal pregnant women. Free (unbound) VEGF and sFlt-1 levels were measured in plasma samples from cord and maternal blood for each subject by enzyme-linked immunosorbent assay (ELISA) using commercially available kits from R&D systems, UK (Cat # DVE00 and Cat # SVR100B, respectively)., Results: At high altitude, the average maternal free VEGF in pg/ml was significantly (p < 0.001) lower than that of the cord level (71.30 ± 282.14 and 431.35 ± 424.31, respectively). On the other hand, the average maternal sFlt-1 was significantly (p < 0.001) higher than that of the cord level (8205.41 ± 6244.72 and 1811.74 + 3469.30, respectively). At low altitude, the average maternal free VEGF was significantly lower than that of the cord level (0.47 ± 0.89 and 483.44 ± 457.31, respectively, p < 0.001). On the other hand, the average maternal sFlt-1 was significantly higher than that of the cord level (9267.82 ± 6345.68 and 958.66 ± 1359.92, respectively, p < 0.001). There were no significant differences by altitude., Conclusion: Secretion of sFlt-1 appears to be polarized, in that concentrations are higher in the maternal compartment than on the fetal side at both high and low altitudes. This may be a normal physiological phenomenon to permit angiogenesis in the placenta and fetus while protecting the mother. Chronic exposure to hypobaric hypoxia at high altitude does not affect these distributions.

Background: To find out whether preterm labor is associated with raised maternal serum concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) and whether the measurement of these cytokines can be used to detect early intrauterine infection in preterm labor., Methods: Cross-sectional study: 77 women in preterm labor, 47 controls of healthy preterm women not in labor and 19 women in term labor. The serum cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). The newborns of women who were in labor were followed up for evidence of infection. Differences between groups were tested using analysis of variance, Student's t-test and chi2-test., Results: There was no significant difference in the concentration of all the cytokines measured between the different groups. No statistical difference was found in the concentration of the cytokines between women in preterm labor with ruptured membranes and those with intact membranes. There was also no difference found in the concentration of cytokines between women whose newborns had positive bacterial culture and those with negative culture. There was a positive correlation between the concentrations of IL-6, IL-8 and TNF-alpha., Conclusion: Serum levels of interleukin-6, interleukin-8 and tumor necrosis factor-alpha were not increased in preterm labor compared to normal control women. There is doubt regarding the usefulness of maternal serum measurement of these cytokines for the detection of early fetal infection in preterm labor, but this needs further evaluation.

Objective: Laparoscopic cholecystectomy, a minimal access surgery, is fast replacing open cholecystectomy and is being associated with less trauma. The objective of this study was to compare the proinflammatory cytokine levels in both laparoscopic cholecystectomy and open cholecystectomy., Methods: This study was carried out at Aseer Central Hospital, Aseer region, Abha Private Hospital and the College of Medicine and Medical Sciences, King Khalid University, Abha, Kingdom of Saudi Arabia, during the time period October 1998 through to November 2000. Sixty-one patients were included in the study, 27 of them had laparoscopic cholecystectomy and 34 had open cholecystectomy. Cytokines [Interleukin-6 Interleukin-1b, Tumor necrosis factor -a and Interleukin- 8] were measured in blood samples collected from the patients before, at and 24 hours post surgery, using commercially available kits., Results: Interleukin-6 levels were significantly increased at 24 hours post surgery in the open cholecystectomy group of patients compared to the laparoscopic cholecystectomy group (P<0.04). No differences were found in the other cytokines levels (Interleukin-1b, tumor necrosis factor -a and Interleukin-8) between the open cholecystectomy and laparoscopic cholecystectomy groups., Conclusion: Laparoscopic cholecystectomy, a minimal access surgery, is associated with lower levels of the proinflammatory interleukin-6 cytokine compared to open cholecystectomy.

A total of 2182 serum samples from 38 patients with surgically confirmed unilocular hydatidosis, 19 clinically assessed patients, 15 patients with parasitic infections other than hydatidosis, 104 hospital outpatients, and 2006 normal Jordanians were serodiagnosed for the presence of IgG antibodies against hydatid fluid, circulating immune complexes (CIC), and/or hydatid circulating antigen (CA). Anti-hydatid IgG antibodies were detected in the sera of 77.4% of patients with hydatid disease and persist for very long periods postsurgery. As many as 54.1% of patients with hydatidosis had positive levels of CIC, and 16.1% had circulating antigen in their sera. The search for circulating antigen and CIC decreased the number of false-negative hydatid cases from seven to three, and the combined sensitivity of the assays thus increased from 77.4% to 90.3%. Using the immunoblot technique, 16- and < 14.4-kDa Echinococcus granulosus-specific bands were detected in sera from 54.1% and 61.5% of patients with hydatid disease who were tested before and after surgery, respectively. The seropositivity rate for anti-hydatid IgG antibodies was 2.4% for the general Jordanian population and 5.8% for hospital outpatients.