In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.

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Although the most common front‐line therapies for immune thrombocytopenia (ITP) have been in use for decades, it is still not possible to predict an individual patient's clinical course and response to therapy. Patients are managed with a trial‐and‐error approach and often suffer side effects of therapies which could have been avoided if response prediction were possible. Corticosteroids are the most frequently used upfront therapy for adults and children with ITP. Our group performed whole exome sequencing on a cohort of pediatric ITP patients, and identified two missense single nucleotide variants (SNV) in Toll‐like receptor 4 (TLR4). These coding variants in TLR4 had an increased frequency in Caucasian patients with poor response to upfront steroid therapy. Both TLR4 (D299G; rs4986790) and TLR4 (T399I; rs4986791) had a minor allele frequency (MAF) of 20.7% in those patients unresponsive to steroids, but were present at lower allele frequencies of 2.3% and 3.4% in responders respectively (P < .001). These findings were consistent with the trend identified in an independent cohort of pediatric ITP patients treated with corticosteroids who underwent direct genotyping for both SNVs. This study identified two candidate genetic variants in two unique cohorts of ITP patients which may contribute to steroid response and have prognostic implications for treatment response in ITP.

Dyskinesia refers to any involuntary movement, such as chorea, dystonia, ballism that affect any part of the body. Levodopa-induced dyskinesia is a neurological disorder that afflicts many patients with Parkinson disease usually 5 years after the onset of levodopa therapy and can cause severe disability. The pathophysiology of this dyskinesia is complex and not fully understood. However, the association between vitamin D and Parkinson disease is interesting. The present study was conducted to evaluate the effect of vitamin D on levodopa induced dyskinesia in patients with Parkinson’s disease .In this Double blind clinical trial, 120 patients with PD divided into two groups randomly, vitamin D and placebo group. A dose of 1000 IU/d was selected, Demographic information is registered. In the first visit, three variables have been measured which were the duration, severity of dyskinesia and unified Parkinson’s disease rating scale (UPDRS). These variables were measured again after 3 months and the data was analyzed using SPSS 22. There are no differences between two groups after 3 months. This study revealed, vitamin D has no effects on improvement of levodopa induced dyskinesia.

Background:In patients undergoing septorhinoplasty, control of bleeding and hemodynamic variables is of great importance and laryngoscopy and tracheal intubation could be followed by a specific and transient increase in systemic blood pressure and heart rate.Objectives:This study aimed to examine the effects of oral gabapentin on hemodynamic changes, during direct laryngoscopy, and the amount of bleeding in the patients undergoing septorhinoplasty.Patients and Methods:In a double-blind clinical trial, 103 patients (American society of anesthesiologists class I, II) aged 18 - 45 years old, who were septorhinoplasty candidates, were randomly assigned into two groups, a 900 mg gabapentin group and placebo, in Amir-Al-Momenin academic hospital. The drug was prescribed to the patients orally, 2 hours before the operation. Anesthetic technique was similar for all the patients. Heart rate (HR), systolic (SBP) and diastolic blood pressures (DBP), mean arterial blood pressure (MAP), oxygen saturation percentage of arterial blood (SaO2), before induction of anesthesia, 3, 5, 10, and 15 minutes after the intubation and tracheal extubation, and the amount of bleeding during operation were measured. Statistical analysis was performed with the SPSS (v. 16) software.Results:Variations in the HR, DBP and SaO2, in the specified time intervals, did not show any statistically significant difference, although variations in SBP were statistically significant (higher in gabapentin group). Regarding the average amount of bleeding volume, although there was a lower amount of bleeding in the gabapentin group, the difference was not statistically significant. Also, regarding the pain, there was no significant difference between the two groups in terms of visual analog scale (VAS) average and the received analgesic.Conclusions:The present study showed that premedication with 900 mg gabapentin did not affect the hemodynamic changes induced by laryngoscopy and the amount of bleeding. However, the decreased amount of bleeding was observed in the gabapentin group.

Intellectual disability (ID), which presents itself during childhood, belongs to a group of neurodevelopmental disorders (NDDs) that are clinically widely heterogeneous and highly heritable, often being caused by single gene defects. Indeed, NDDs can be attributed to mutations at over 1000 loci, and all type of mutations, ranging from single nucleotide variations (SNVs) to large, complex copy number variations (CNVs), have been reported in patients with ID and other related NDDs. In this study, we recruited seven different recessive NDD families with comorbidities to perform a detailed clinical characterization and a complete genomic analysis that consisted of a combination of high throughput SNP-based genotyping and whole-genome sequencing (WGS). Different disease-associated loci and pathogenic gene mutations were identified in each family, including known (n = 4) and novel (n = 2) mutations in known genes (NAGLU, SLC5A2, POLR3B, VPS13A, SYN1, SPG11), and the identification of a novel disease gene (n = 1; NSL1). Functional analyses were additionally performed in a gene associated with autism-like symptoms and epileptic seizures for further proof of pathogenicity. Lastly, detailed genotype-phenotype correlations were carried out to assist with the diagnosis of prospective families and to determine genomic variation with clinical relevance. We concluded that the combination of linkage analyses and WGS to search for disease genes still remains a fruitful strategy for complex

The true influence of the perioperative intravenous lidocaine on the development of postoperative cognitive deficit (POCD) in coronary artery bypass grafting (CABG) remains controversial. The principal aim is to undertake a meta-regression to determine whether moderator variables mediate the relationship between lidocaine and POCD. Areas covered: We searched the Web of Science, PubMed database, Scopus and the Cochrane Library database (up to June 2017) and systematically reviewed a list of retrieved articles. Our final review includes only randomized controlled trials (RCTs) that compared infusion of lidocaine and placebo during cardiopulmonary bypass (CPB). Mantel-Haenszel risk ratio (MH RR) and corresponding 95% confidence interval (CI) was used to report the overall effect and meta-regression analysis. A total of 688 patients in five RCTs were included. POCD occurred in 34% of all cases. Perioperative lidocaine reduces POCD (MH RR 0.702 (95% CI: 0.541-0.909). Younger age, male gender, longer CPB and higher concentration of lidocaine significantly mediate the relationship between lidocaine and POCD in favour of the neuroprotective effect of lidocaine. Expert commentary: The neuroprotective effect of lidocaine on POCD is consistent in spite of longer CPB time. A higher concentration of lidocaine strengthened the neuroprotective effect of lidocaine.

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