Supportive evidence for 11 loci from genome-wide association studies in Parkinson's disease

Genome-wide association studies have identified a number of susceptibility loci in sporadic Parkinson's disease (PD). Recent larger studies and meta-analyses have greatly expanded the list of proposed association signals. We performed a case-control replication study in a Scandinavian population, analyzing samples from 1345 unrelated PD patients and 1225 control subjects collected by collaborating centers in Norway and Sweden. Single-nucleotide polymorphisms representing 18 loci previously reported at genome-wide significance levels were genotyped, as well as 4 near-significant, suggestive, loci. We replicated 11 association signals at p < 0.05 (SNCA, STK39, MAPT, GPNMB, CCDC62/HIP1R, SYT11, GAK, STX1B, MCCC1/LAMP3, ACMSD, and FGF20). The more recently nominated susceptibility loci were well represented among our positive findings, including 3 which have not previously been validated in independent studies. Conversely, some of the more well-established loci failed to replicate. While future meta-analyses should corroborate disease associations further on the level of common markers, efforts to pinpoint functional variants and understand the biological implications of each risk locus in PD are also warranted.     

Evaluation of Epstein-Barr Virus,Human Herpesvirus 6 (HHV-6), and HHV-8 Antiviral Drug Susceptibilities by Use of Real-Time-PCR-Based Assays

Evaluation of candidate antiviral drugs against Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and HHV-8 is hampered by the lack of convenient laboratory assays. We developed real-time quantitative PCR assays performed on supernatants of lymphoma cell lines and determined the 50% inhibitory concentrations (IC₅₀s) of nucleoside, nucleotide, and pyrophosphate analogues against these herpesviruses.     

Evaluation of Estrogen,Progesterone, and GCDFP-15 Expression in Uterine Leiomyomas

Approximately, one fourth of women have leiomyomas. Leiomyomas are benign tumors that originated from smooth muscle cells. Estrogen is claimed to relate as a cause but exact mechanism has not fully understood. In this study, 95 leiomyoma cases that have been diagnosed by our department in years between 2010 and 2012 were examined. Age ranges of patients, sizes, locations, and numbers of leiomyomas were identified. Immunohistochemically ER (estrogen), PR (progesterone), and Gross cystic disease fluid protein-15 stains were performed to the paraffin blocks and their percentages of staining were noted. Statistically, submucosal and intramural locations were significantly related to ER and PR (p < 0,001). There were significant relationship between ER and PR in 30–50 years age group (p < 0,001). There were significant relationship between ER, PR and locations (p < 0,001), numbers (p < 0,001), sizes of leiomyomas (below 5 cm; p < 0,001), (between 5 and 10 cm; p = 0,037), larger than 10 cm; p = 0,002). Consequently, relationship between leiomyoma and ER, PR were revealed in this study. Also, relationship between leiomyoma locations and patient ages were identified statistically. There was no immunoreactivity with GCDFP-15 in leiomyomas.     

Effects of 2-Hydroxypropyl-Beta-Cyclodextrin on Cardiovascular Signs of Amitriptyline Poisoning in a Rat Model

The aim of this study was to investigate the efficacy of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as an antidotal treatment for the in vivo cardiovascular effects of amitriptyline poisoning. Experiments were carried out on 33 Wistar rats. To evaluate cardiovascular effects of HPBCD, rats were infused with dextrose or HPBCD. In the poisoning model, amitriptyline (0.94 mg/kg/min) was infused until the mean arterial blood pressure (MAP) dropped to 50 % of the baseline. Following amitriptyline infusion, dextrose, low-dose HPBCD (4.19 mg/kg/min), or high-dose HPBCD (16.76 mg/kg/min) was infused, and MAP, heart rate (HR), and electrocardiogram were recorded for 60 min. Hearts were examined for tissue damage and apoptosis. HPBCD infusion alone did not yield significant difference for MAP, HR, QRS duration, QT interval, and cardiac tissue damage when compared to dextrose (p > 0.05). In the poisoning model, MAP and HR decreased, while QRS duration and QT interval prolonged significantly following amitriptyline infusion (p < 0.0167). Dextrose, low-dose HPBCD, and high-dose HPBCD infusion similarly corrected MAP, HR, QRS duration, and QT interval values at the end-experiment time point (p > 0.05). Histological scores for tissue damage and apoptosis showed no significant difference between the groups (p > 0.05). Based on our results, HPBCD did not show cardiovascular toxicity, while it was not more effective than dextrose for the treatment of amitriptyline poisoning. Further antidotal studies of cyclodextrins with higher doses and/or binding affinities are needed for poisonings.     

New microsatellite markers for multi-scale genetic studies on Phlebotomus ariasi Tonnoir,vector of Leishmania infantum in the Mediterranean area

The population structure of Phlebotomus ariasi, a proven vector of Leishmania infantum in the Mediterranean area, is still poorly understood. Previously, only two microsatellite loci had been developed to study the population genetics of this species. Herein we use these loci and determined fourteen novel microsatellite loci, useful for the characterization of P. ariasi populations. These loci were tested on three populations of P. ariasi, two from France and one from Portugal. In addition, the usefulness of these markers was also evaluated on seven other sandfly species.     

Differential diagnosis of a rare case of upper limb pain: Paget-Schroetter syndrome in a doner kebab chef

[Purpose] Paget-Schroetter syndrome (PSS) is an uncommon deep vein thrombosis of the axillary and subclavian veins which may occur spontaneously, but is usually caused by excessive upper limb activity. PSS is clinically similar to other upper limb musculoskeletal disorders and soft tissue infections, and this may lead to delay in correct diagnosis in its early stages. The aim of our case report is to discuss this rare condition with reference to the available literature. [Subjects and Methods] Here we report the case of a doner kebab chef who complained of swelling and pain in his right arm around the biceps muscle. The initial diagnosis was biceps tendon rupture, for which the patient underwent magnetic resonance imaging (MRI) of the right arm and shoulder. Since the MRI revealed no pathological findings, right upper limb venous Doppler ultrasound analysis was performed. Subacute thrombosis materials were detected in the subclavian, axillary, and brachial veins. [Results] With rapid anticoagulant therapy, the patient’s symptoms quickly improved. [Conclusion] Early diagnosis and treatment of PSS is critical for preventing potentially fatal complications such as pulmonary embolism. Prophylaxis is important for preventing recurrent thrombosis and for avoiding the development of post-thrombotic syndrome. PSS should be considered a possible cause of painful swelling of the upper limbs, especially in young, active patients who use their arms excessively.Key words: Doner kebab chef, Effort thrombosis, Paget-Schroetter syndrome     

Novel Growth Hormone-Releasing Hormone Receptor Gene Mutations in Turkish Children with Isolated Growth Hormone Deficiency

Objective: Isolated growth hormone deficiency (IGHD) is defined as a medical condition associated with growth failure due to insufficient production of GH or lack of GH action. Mutations in the gene encoding for GH-releasing hormone receptor (GHRHR) have been detected in patients with IGHD type IB. However, genetic defects on GHRHR causing IGHD in the Turkish population have not yet been reported. To identify mutations on GHRHR gene in a population of Turkish children with IGHD.Methods: Ninety-six Turkish children with IGHD were included in this study. Exon1-13 and exon/intron boundaries of GHRHR were amplified by suitable primers. The polymerase chain reaction products for GHRHR gene were sequenced with primers.Results: We analyzed the GHRHR gene for mutations in ninety-six patients with IGHD based on sequence results. We identified novel p.K264E, p.S317T, p.S330L, p.G369V, p.T257A and C base insertion on position 380 (c.380inserC) mutations. In 5 of the patients, the mutation was homozygote and in 1-heterozygote (p.S317T).Conclusion: Six new missense mutations and one first case of insertion mutations for the GHRHR gene are reported.     

Laughter as a social rejection cue: Gelotophobia and transient cardiac responses to other persons' laughter and insult

Other persons' laughter, normally perceived as a signal that persons are friendly and inviting others to approach, can also be perceived as a cue of social rejection. In this study, prerecorded laughter was placed in a realistic and personally relevant context, and participants' responses were related to gelotophobia, a trait predisposing to perceiving laughter as a cue of social rejection. Individuals with gelotophobia showed marked heart rate deceleration in response to the laughter stimulus, possibly indicating a “freezing‐like” response. Moreover, cardiac responses to anger provocation by overtly insulting statements indicated heightened aggressive anger in response to cumulated social threat. The study adds to recent research showing specific cardiac responses to social rejection and to the literature on social rejection sensitivity by demonstrating the value of using well interpretable physiological measures in this research context.     

Home-based exercise therapy in patients with ankylosing spondylitis: effects on pain, mobility, disease activity, quality of life, and respiratory functions

The home-based exercise therapy recommended to the patients with ankylosing spondylitis (AS) is a simply applicable and cheap method. The aim of this study was to investigate the effects of home-based exercise therapy on pain, mobility, function, disease activity, quality of life, and respiratory functions in patients with AS. Eighty patients diagnosed with AS according to the modified New York criteria were included in the study. Home-based exercise program including range of motion, stretching, strengthening, posture, and respiratory exercises was practically demonstrated by a physiotherapist. A training and exercise manual booklet was given to all patients. Patients following home-based exercise program five times a week at least 30 min per session (exercise group) for 3 months were compared with those exercising less than five times a week (control group). Visual analog scale pain (VASp) values at baseline were significantly higher in the exercise group. The exercise group showed improvements in VASp, tragus–wall distance, morning stiffness, finger–floor distance, modified Schober's test, chest expansion, the Bath Ankylosing Spondylitis Disease Activity Index, the Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL), forced expiratory volume in first second, and forced vital capacity at third month. There was significant difference in ASQoL scores between the two groups in favor of the exercise group at third month. Regular home-based exercise therapy should be a part of main therapy in patients with AS. Physicians should recommend that patients with AS do exercise at least five times a week at least 30 min per session.