Genetic polymorphisms of twelve X-STRs of the investigator Argus X-12 kit and additional six X-STR centromere region loci in an Egyptian population sample

Recently, many researchers have focused on analysis of different X-chromosomal STRs as they bear the potential to efficiently complement the analysis of autosomal and Y-chromosomal STRs in solving special complex kinship deficiency cases. In the current study we examined a sample of 250 unrelated Egyptian males with the Investigator Argus X-12 kit (Qiagen GmbH, Hilden, Germany) which detects 12 X-STR markers distributed over the entire X-chromosome as four closely linked clusters. Microvariant off ladder alleles as well as null alleles have been detected in some loci. Furthermore, discordant results were observed between the Investigator Argus X-12 and the Mentype^® Argus X-8 kits (Biotype AG, Dresden, Germany). New primers were designed for loci DXS10101, DXS10146 and DXS10148 to correct the allele drop outs observed in these loci with the Investigator Argus X-12 kit. Additionally, DNA sequence analysis revealed the polymorphisms responsible for the allele drop outs. Furthermore, six additional X-STRs (DXS10161, DXS10159, DXS10162, DXS10163, DXS10164 and DXS10165) located in the centromere region at Xp11.21–Xq11.1 were examined in a single multiplex reaction. Allele and haplotype frequencies as well as different forensic statistical parameters of the 18 X-STR loci tested indicated that they are highly informative in different forensic applications in the Egyptian population. However, some modifications still need to be performed on the Investigator Argus X-12 kit before its use in forensic casework is validated.     

Clinical outcome in patients with venous thromboembolism receiving concomitant anticoagulant and antiplatelet therapy

IntroductionPatients with arterial disease receiving antiplatelet agents may develop venous thromboembolism (VTE) and need anticoagulant therapy, although concomitant use of these drugs may increase bleeding risk. We analyzed RIETE data and compared clinical outcomes depending on decision to discontinue or maintain antiplatelet therapy at VTE diagnosis.MethodsConsecutive patients with acute VTE were enrolled in RIETE. Only patients receiving antiplatelet therapy at baseline were included in this analysis. Primary outcomes were: rate of subsequent ischemic events, major bleeding or death during anticoagulation course.Results1178 patients who received antiplatelet drugs at VTE diagnosis were included. Antiplatelet therapy was discontinued in 62% of patients. During anticoagulation course, patients also receiving antiplatelet therapy had higher rates of lower limb amputations (2.28 vs. 0.21 events per 100 patients-years; p < 0.01), any ischemic events (5.7 vs. 2.28 events per 100 patients-years; p < 0.05) or death (23.6 vs. 13.9 deaths per 100 patients-years; p < 0.01). No differences in the rate of major bleeding or recurrent VTE were revealed. In matched analysis, patients on antiplatelet therapy were found to have a significantly higher rate of limb amputations (odds ratio: 15.3; 95% CI: 1.02–229) and an increased number of composite outcomes including all-cause deaths, arterial and VTE events (odds ratio: 1.46; CI: 1.03–2.06), with no differences in major bleeding rate.ConclusionConcomitant anticoagulant and antiplatelet therapy in patients with VTE and arterial disease is not associated with increased risk for bleeding, recurrent VTE or death. The worse outcome observed in patients who continued antiplatelet therapy requires further investigations.     

Staphylococcal Scalded Skin Syndrome in Neonates: An 8‐Year Retrospective Study in a Single Institution

Staphylococcal scalded skin syndrome (SSSS) is a rare disorder in children. Complications may occur without timely treatment. Mortality in children with SSSS is approximately 4%. Other than a limited number of case reports, data on SSSS in neonates are limited. The objective of the current study was to investigate SSSS in neonates. A retrospective review of neonates with a diagnosis of SSSS from January 2004 to January 2012 was performed. Population distribution, historical features, physical examination findings including laboratory tests, antibiotic therapies, and outcomes were evaluated. Thirty‐nine cases were included, 31 (79.5%) in the last 4 years. The mean patient age was 17.4 ± 7.7 days. Boys (25 cases) were more commonly affected, and occurrence during summer and autumn months was more frequent. The face was the most common body part affected and the area most commonly initially affected. Fever, high white blood cell count, and high C‐reactive protein levels were uncommon. Pneumonia was the most frequent complication (74.4%). The positive rate of Staphylococcus aureus isolation was low (23.5%). Drug susceptibility tests showed that amoxicillin with clavulanic acid and cephalosporins were effective in practice. The median length of hospitalization was 9.0 days. All of the 39 neonates were cured without scarring. This study established basic epidemiologic characteristics of a group of neonates diagnosed with SSSS. In the presence of a clinical suspicion of SSSS, even with apparently normal laboratory tests, immediate treatment with cephalosporins, β‐lactamase‐resistant semisynthetic penicillin, or both is advocated.     

A multimodal approach using TMS and EEG reveals neurophysiological changes in Parkinson's disease

IntroductionAlterations in large scale neural networks leading to neurophysiological changes have been described in Parkinson's disease (PD). The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been suggested as a promising tool to identify and quantify neurophysiological mechanisms. The aim of this study was to investigate specific changes in electrical brain activity in response to stimulation of four brain areas in patients with PD.Methods21 healthy controls and 32 patients with PD underwent a combined TMS-EEG assessment that included stimulation of four brain areas: left M1, right M1, left dorso-lateral prefrontal cortex (DLPFC), and right DLPFC. Six measures were calculated to characterize the TMS evoked potentials (TEP) using EEG: (1) wave form adherence (WFA), (2) late phase deflection (LPD), (3) early phase deflection (EPD), (4) short-term plasticity (STP), (5) inter-trial adherence, and (6) connectivity between right and left M1 and DLPFC. A Linear mixed-model was used to compare these measures between groups and areas stimulated.ResultsPatients with PD showed lower WFA (p = 0.052), lower EPD (p = 0.009), lower inter-trial adherence (p < 0.001), and lower connectivity between homologs areas (p = 0.050), compared to healthy controls. LPD and STP measures were not different between the groups. In addition, lower inter-trial adherence correlated with longer disease duration (r = −0.355, p = 0.050).ConclusionsOur findings provide evidence to various alterations in neurophysiological measures in patients with PD. The higher cortical excitability along with increased variability and lower widespread of the evoked potentials in PD can elucidate different aspects related to the pathophysiology of the disease.     

Predictive role of the overexpression for CXCR4, C-Met,and VEGF-C among breast cancer patients: A meta-analysis

BackgroundThe overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients.MethodsPubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided.ResultsA total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34–4.91, P = 0.005; and HR = 1.63 95% CI = 1.20–2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52–4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69–1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64–1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43–1.33, P = 0.333].ConclusionsOur meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients.     

Inhibiting effect of Radix Hedysari Polysaccharide (HPS) on endotoxin-induced uveitis in rats

PurposeThe aim of this study is to investigate the anti-inflammatory effect of Radix Hedysari Polysaccharide (HPS) on clinical indicators, the expression of Toll-like receptor-4 (TLR4) and its downstream transduction molecules during endotoxin-induced uveitis in rats.MethodsEIU was induced through the intraperitoneal injection of male Wistar rats with lipopolysaccharide (LPS 200 μg). HPS (400 mg/kg), DXM (1 mg/kg) or an equivalent volume of normal saline was injected intraperitoneally 1 h before the LPS induction. The clinical manifestation was observed and scored at 2-h intervals using a slit microscope. The degree of inflammatory reaction was determined by routine histological examinations, and the expression of TLR4 and MyD88 in the iris-ciliary body complex was detected through a double-labeled immunofluorescence study. Real-time RT-PCR was used to assess the effects of HPS on the expression of the TLR4 complex, MyD88 and NF-κB p65 mRNA. The protein expression levels of TLR4, MyD88 and NF-κB p65 were examined by western blot.ResultsHPS treatment produced similar therapeutic results with dexamethasone by significantly reducing the clinical severity of EIU as well as fibrin exudations and inflammatory cell infiltration in the eye. Correspondingly, according to the immunofluorescence results, HPS treatment significantly suppressed the expression of TLR4 and MyD88 in the iris–ciliary body complex. HPS treatment could also remarkably reduce the mRNA and protein expression of the TLR4 complex, MyD88 and NF-κB p65.ConclusionHPS can suppress the intraocular inflammation observed in EIU by inhibiting TLR4 and its downstream signal transduction pathway.     

Effect of hesperidin and neohesperidin from bittersweet orange (Citrus aurantium var. bigaradia) peel on indomethacin-induced peptic ulcers in rats

Hesperidin and neohesperidin are the major flavanones isolated from bittersweet orange. It was recently reported that they have potent anti-inflammatory effects in various inflammatory models. In the present study, the effects of hesperidin and neohesperidin on indomethacin-induced ulcers in rats and the underlying mechanisms were investigated. Gastric ulcers were induced in rats with a single dose of indomethacin. The effects of pretreatment with hesperidin and neohesperidin were assessed in comparison with omeprazole as reference standard. Ulcer index, gene expression of gastric cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), lipid peroxidation product, malondialdhyde (MDA), and reduced glutathione (GSH) content in stomach were measured. Furthermore, gross and histopathological examination was performed. Our results indicated that both hesperidin and neohesperidin significantly aggravated gastric damage caused by indomethacin administration as evidenced by increased ulcer index and histopathological changes of stomach.