The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance.

Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohort of 89 families with the clinical sign of arthrogryposis. Additional molecular techniques including array comparative genomic hybridization (aCGH) and Droplet Digital PCR (ddPCR) were performed on individuals who were found to have pathogenic copy number variants (CNVs) and mosaicism, respectively. A molecular diagnosis was established in 65.2% (58/89) of families. Eleven out of 58 families (19.0%) showed evidence for potential involvement of pathogenic variation at more than one locus, probably driven by absence of heterozygosity (AOH) burden due to identity-by-descent (IBD). RYR3, MYOM2, ERGIC1, SPTBN4, and ABCA7 represent genes, identified in two or more families, for which mutations are probably causative for arthrogryposis. We also provide evidence for the involvement of CNVs in the etiology of arthrogryposis and for the idea that both mono-allelic and bi-allelic variants in the same gene cause either similar or distinct syndromes. We were able to identify the molecular etiology in nine out of 20 families who underwent reanalysis. In summary, our data from family-based ES further delineate the molecular etiology of arthrogryposis, yielded several candidate disease-associated genes, and provide evidence for mutational burden in a biological pathway or network. Our study also highlights the importance of reanalysis of individuals with unsolved diagnoses in conjunction with sequencing extended family members.

Multicenter Validation of Individual Preoperative Motor Outcome Prediction for Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for Parkinson's disease (PD) patients suffering from motor response fluctuations despite optimal medical treatment, or severe dopaminergic side effects. Despite careful clinical selection and surgical procedures, some patients do not benefit from STN DBS. Preoperative prediction models are suggested to better predict individual motor response after STN DBS. We validate a preregistered model, DBS-PREDICT, in an external multicenter validation cohort. METHODS: DBS-PREDICT considered eleven, solely preoperative, clinical characteristics and applied a logistic regression to differentiate between weak and strong motor responders. Weak motor response was defined as no clinically relevant improvement on the Unified Parkinson's Disease Rating Scale (UPDRS) II, III, or IV, 1 year after surgery, defined as, respectively, 3, 5, and 3 points or more. Lower UPDRS III and IV scores and higher age at disease onset contributed most to weak response predictions. Individual predictions were compared with actual clinical outcomes. RESULTS: 322 PD patients treated with STN DBS from 6 different centers were included. DBS-PREDICT differentiated between weak and strong motor responders with an area under the receiver operator curve of 0.76 and an accuracy up to 77%. CONCLUSION: Proving generalizability and feasibility of preoperative STN DBS outcome prediction in an external multicenter cohort is an important step in creating clinical impact in DBS with data-driven tools. Future prospective studies are required to overcome several inherent practical and statistical limitations of including clinical decision support systems in DBS care.

Copy number variations in patients with idiopathic recurrent pregnancy loss: an arrayCGH approach.

BACKGROUND: It is not always possible to determine the causative basis of pregnancy losses and even today it has been reported that 50% of cases with recurrent pregnancy loss (RPL) have no reason to be detected. In our study, it is aimed to reveal the copy number variations (CNVs) of the genes which presumably have a potential effect in individuals with RPL and contribute to subsequent functional studies in the follow-up. METHODS: We retrospectively evaluated the array-comparative genomic hybridization (aCGH) data of cytogenetically 64 normal individuals (21 couples, 11 unrelated women, and 11 unrelated men) who had applied to our outpatient clinic from January 2016 to December 2017, for the history of idiopathic two or more RPL. RESULTS: A total of 83 CNVs were detected in 56 different chromosomal regions [36% (20/56) is deletion and 64% (36/56) is duplication] in 40/64 (62.5%) of the cases. Two detected deleterious CNVs encompassing 1p36.22-p36.21 and 10q11.22 chromosomal locus have been reported as pathogenic according to the Database of Genomic Variants (DGV). DISCUSSION: CNVs that may play a role in the genetic etiology of idiopathic RPL were revealed in our study and potential chromosomal loci were introduced to the literature for further analysis. The detection of CNVs and their association with reproduction such as RPL, infertility, and even other diseases will allow us to have more information about the clinical consequences and will make it possible to provide more accurate and comprehensive genetic counseling.

Identification of a novel pathogenic variant in CKAP2L and literature review in a child with Filippi syndrome and congenital talipes equinovarus.

Filippi syndrome (MIM #272440), one of the craniodigital syndromes, is a rare genetic entity with autosomal recessive inheritance and characterized by pre- and postnatal growth retardation, microcephaly, distinctive facial appearance, developmental delay/intellectual disability, and variable syndactylies of the fingers and toes. In this report, a further female patient of Filippi syndrome who additionally had a unilateral congenital talipes equinovarus (CTEV), a feature not previously recorded, is described. Genetic testing revealed a novel homozygous frameshift pathogenic variant (c.552_555delCAAA, p.Asn184Lysfs*8) in CKAP2L and thus confirmed the diagnosis of Filippi syndrome. We hope that the newly recognized feature (CTEV) will contribute to expand the clinical spectrum of this extremely rare condition. In view of the paucity of reported cases, the full spectrum of clinical findings of Filippi syndrome necessitates obviously further affected individuals/pedigrees delineation in order to elucidate the etiological and phenotypic aspects of this orphan disease appropriately.

A socio-ecological approach to improve industrial zones towards eco-industrial parks.

One of the concrete examples of industrial symbiosis development is eco-industrial parks, which improves resource efficiency and minimizes environmental impacts by adopting models for waste exchanges between industries. Despite past efforts, many industrial zones around the world are not yet considered as eco-industrial parks because of the low number (or total lack) of symbiotic relationships among industries. A promising strategy is to develop those existing industrial zones into eco-industrial parks. However, there is a lack of studies addressing how to assess environmental improvement in relation to network sustainability. This study demonstrates such an assessment approach using an integration of food web analysis and social network analysis. These two methods can assist in assessing differences in network configurations with respect to potential implementations of industrial symbiosis, and in analysing the resilience, redundancy, connectance, and cyclicity of eco-parks. The use of the methods is illustrated in a case study of an industrial zone in Turkey. Four potential future scenarios are proposed, including potential future co-location of companies in the industrial zone in order to foster industrial symbiotic network formation. These scenarios are compared with the current configuration. The results indicate the method's ability to assess the resilience of an industrial network. Moreover, the case shows an improvement of network sustainability and follows some sustainable properties of natural ecosystems as a result of implementing the industrial symbiosis.

Protective effect of 2-APB on testicular ischemia-reperfusion injury in rats.

PURPOSE: We performed biochemical and histopathological evaluations to assess the effects of 2-APB on ischemia-reperfusion induced testicular damage. MATERIALS AND METHODS: A total of 28 rats were randomly divided into 4 groups, including sham treated, ischemia-reperfusion, ischemia-reperfusion plus 2 mg/kg 2-APB and ischemia-reperfusion plus 4 mg/kg 2-APB. Testicular tissue superoxide dismutase, glutathione, malondialdehyde, total antioxidant capacity and DNA fragmentation levels were determined. Testicular tissue samples were examined by histopathology and TUNEL staining. RESULTS: Mean superoxide dismutase, total antioxidant capacity and glutathione were significantly higher in the sham treated group than in the ischemia-perfusion group (p <0.05). Mean malondialdehyde and DNA fragmentation levels were significantly lower in the sham treated group than in the ischemia-reperfusion group (p <0.05). After 2-APB treatment superoxide dismutase, total antioxidant capacity and glutathione were significantly increased but malondialdehyde and DNA fragmentation levels were significantly decreased compared to the ischemia-reperfusion group (p <0.05). The number of TUNEL positive cells was significantly lower in the 2-APB treatment groups than in the ischemia-reperfusion group (p <0.05). CONCLUSIONS: In rats 2-APB reduced the oxidative stress and apoptosis caused by testicular ischemia-reperfusion injury. The testicular protective effect of 2-APB appears to be mediated through its antiapoptotic and antioxidative effects.

Volumetric analysis of the subthalamic and red nuclei based on magnetic resonance imaging in patients with Parkinson's disease.

Parkinson's disease (PD) is associated with degeneration of the dopaminergic neurons in the substantia nigra. The subthalamic nucleus (STN) plays a pivotal role in the pathogenesis. However, there is not much known about the morphological changes in the STN. The red nucleus (RN) has many connections with the motor coordinating pathways although it is not primarily involved in the pathogenesis. In this study we aimed to compare the volumes of the STN and RN measured by magnetic resonance imaging in PD patients and controls to investigate how these structures are affected at the morphological level. Twenty patients with PD and twenty age/sex matched controls were enrolled in this study. Severity score was determined by Hoehn & Yahr staging: 6 at stage II and 14 at stage III in med-off state. Imaging was performed by a 1.5 Tesla (T) MR scanner. Measurements of total brain and normalized STN and RN volumes were performed by manual planimetry using Image J software. No statistically significant differences were observed between two groups based on age or gender and disease stage and nuclei volumes. The total estimated brain volumes were not different between PD patients and controls. However, normalized volumes of the STN and RN were 14% and 16% larger, respectively, in PD patients compared to the controls (p < 0.05). Our findings suggest that the volumes of the STN and RN are increased in patients with PD. These changes possibly reflect the altered metabolic activity of these regions demonstrated by neurophysiological studies.

The protective effect of selenium in cisplatin-related retinotoxicity.

PURPOSE: The aim of this study is to evaluate the retinal toxicity of cisplatin and neuroprotective effect of selenium in cisplatin-related retinal toxicity. METHODS: Eighteen adult Wistar-Albino rats were divided into three groups. Group 1 (n = 6) received intraperitoneal (i.p.) injection of 2.5 ml physiologic saline for three days, group 2 (n = 6) received i.p. 16 mg/kg cisplatin for three days and group 3 (n = 6) received i.p. 16 mg/kg cisplatin for three days and 1.5 mg/kg twice daily selenium via gavage five days prior to cisplatin injection and for three days concomitantly with cisplatin injections. The total retinal thickness, outer nuclear layer (ONL), inner nuclear layer (INL) and inner plexiform layer (IPL) thicknesses were measured in hematoxylin/eosin and apoptotic index (AI) of ganglion cell layer (GCL) and INL was evaluated in TdT-mediated dUTP-biotin nick end labeling (TUNEL)-stained retina sections. RESULTS: Selenium statistically succeeded to reduce total retinal thickness in cisplatin-toxicated retinas: from 210.17 ± 23.40 to 173.55 ± 20.43, ONL: 49.79 ± 5.32 to 41.87 ± 6.30, INL: 33.72 ± 7.93 to 25.06 ± 5.73 and IPL: 53.61 ± 8.63 to 45.61 ± 6.92 µm in hematoxylin/eosin-stained retina sections. The AI was also reduced in INL (30.10 ± 12.02 to 19.48 ± 12.99) and in GCL (37.59 ± 17.70 to 33.15 ± 13.78). However, statistical significance was present in only AI values of INL. CONCLUSIONS: Selenium limited edema due to the toxicity and reduced the retinal thickness and showed neuroprotection in cisplatin-induced retinotoxicity.

Visual Evoked Potentials in Patients With Vitamin B12 Deficiency.

PURPOSE: The aim of this study was to investigate the subclinical involvement of the optic nerve in asymptomatic patients with vitamin B12 deficiency using visual evoked potentials. METHODS: This study included 40 asymptomatic patients diagnosed with vitamin B12 deficiency (considered as serum levels below 150 pg/mL) and a control group of 40 healthy individuals. All participants underwent a visual evoked potential examination. Routine screening for homocysteine was performed for patients with vitamin B12 deficiency. The levels of vitamin B12 and homocysteine and the presence of megaloblastic anemia were analyzed statistically compared with P100, N75, and N135 latencies and amplitudes. RESULTS: The mean vitamin B12 level was 96 pg/mL in the patient group and 374 pg/mL in the control group. In the patient group, 24 (60%) patients had hyperhomocysteinemia and 8 (20%) patients had megaloblastic anemia. The P100 wave latency of patients with vitamin B12 deficiency was significantly prolonged compared with the control group ( P < 0.01). There was no significant difference in the P100 amplitude between the patient group and the control group. P100 latencies were significantly longer in patients with hyperhomocysteinemia ( P = 0.002). CONCLUSIONS: Our study showed that patients with vitamin B12 deficiency may have visual evoked potential abnormalities without visual symptoms or examination findings. In addition, high homocysteine levels led to a prolonged P100 latency in the patient group independent of vitamin B12 levels.

Subthalamic Nucleus Deep Brain Stimulation in a Patient with Severe Axial Symptoms and Suboptimal Levodopa Responsive Parkinson's Disease.

AIM: Deep brain stimulation (DBS) is a well-established treatment option for improving function and quality of life (QoL) in carefully selected patients with Parkinson?s disease (PD). Patient selection is a crucial step that should be performed by an experienced multidisciplinary team according to the proposed inclusion and exclusion criteria to increase the QoL of patients. CASE REPORT: A 47-year-old bedridden woman with a 20-year history of PD presented with levodopa-unresponsive tremor and severe axial symptoms. Despite various antiparkinsonian medications, a suboptimal improvement was observed with the levodopa challenge test. After detailed evaluations, she underwent bilateral subthalamic nucleus DBS. During the 2-year follow-up, her axial symptoms improved significantly leading to a better QoL. CONCLUSION: Although levodopa-resistant axial symptoms are considered a relative contraindication to DBS surgery, this case report demonstrates that with an interdisciplinary approach and an accurate assessment of symptoms, even bedridden and latestage selected PD cases may benefit from DBS.

Electrode Fixation with Bone Cement or Stimloc® in Deep Brain Stimulation Surgery: A Comparative Study.

AIM: To examine the postoperative outcomes of electrode fixation using bone cement and Stimloc® in patients with Parkinson?s disease (PD) who underwent subthalamic nucleus (STN) deep brain stimulation (DBS). MATERIAL AND METHODS: Between 2016 and 2018, permanent electrode fixation was performed in 30 patients with PD, of which 15 received bone cement and the remaining 15 received Stimloc®. Data regarding preoperative Unified Parkinson?s Disease Rating Scale (UPDRS) III scores, levodopa equivalent daily dose (LEDD) values, surgery duration, and the fixation technique used were recorded. Brain computed tomography was performed for early postoperative evaluation of pneumocephalus and possible hematoma as well as for the determination of migration 1 year postoperatively. UPDRS III scores and LEDD values were re-evaluated 1 year postoperatively; surgery duration, clinical effectiveness, and complication rates were compared between the two fixation techniques. RESULTS: A statistically significant difference in application time was observed between the two techniques (bone cement: 21 min, Stimloc®: 6 min). After 1 year from surgery, 0.92- and 0.88-mm migrations were observed in the bone cement and Stimloc® groups, respectively. A significant correlation between migration and the pneumocephalus volume was observed in both groups. No differences were observed between the groups regarding infection, migration, pneumocephalus volume, wound erosion, and clinical outcomes. CONCLUSION: Stimloc® is preferred over bone cement for electrode fixation in DBS surgeries as it is associated with shorter application duration; this increases patient comfort and tolerance during awake surgery. Clinical efficacy and complication rates associated with both techniques are similar.

Effects of Deep Brain Stimulation of the Subthalamic Nucleus on the Postoperative Levodopa Response: One Year Follow Up.

AIM: To investigate the effect of preoperative levodopa responsiveness to clinical outcomes in the first postoperative year, and to evaluate the changes in the postoperative levodopa responsiveness in patients undergoing subthalamic nucleus (STN) deep brain stimulation (DBS). MATERIAL AND METHODS: Forty-nine Parkinson?s Disease (PD) patients undergoing bilateral DBS of the STN were included in this study. Their clinical motor symptoms were assessed preoperatively by UPDRS Part III score in both OFF and ON medication states. Postoperatively, the assessments were obtained in three consecutive conditions. Preoperatively and postoperatively, the percentage difference between these two scores was evaluated as levodopa response. RESULTS: Mean age was 54.6 ± 9 years (27?70). Levodopa response significantly decreased postoperatively by 56% a year. Compared with preoperative med on and postoperative stim on / med on scores, the clinical results of the first year were obtained and an improvement of 25% on the UPDRS 3 score was observed. Compared with preoperative levodopa response and clinical outcomes, better clinical results were obtained in patients with higher preoperative levodopa response (p < 0.05). CONCLUSION: In this study, we confirm that the response of L-dopa decreases after DBS of the STN. The reasons for this finding are not clear. However, DBS of the STN allows for the reduction of PD medications and improvement of daily life activities, motor function, motor fluctuations, and dyskinesia.

The Effect of Bitter Melon (Momordica charantia) Extract on the Uptake of 99mTc Labeled Paclitaxel: In Vitro Monitoring in Breast Cancer Cells.

BACKGROUND: Bitter Melon Extract (BME) is widely used for the treatment of various diseases worldwide due to its rich phytochemical and antioxidant content. The well-known anti-cancer drug Paclitaxel (PAC) plays a major role in the treatment of various cancer types such as ovarian, breast, and lung cancer. Technetium-99m (99mTc) radiolabeled paclitaxel is emerging as an imaging probe for breast cancer in vivo. 99mTc labeled compounds have been attracting more scientific attention since the achievement of earlier researches in Nuclear Medicine. People consume several types of diets of plant origin without knowing the interaction with radiolabeled compounds or radiopharmaceuticals. Objective: In the current study, we aimed to monitor the potential effects of the BME on the uptake of 99mTc labeled Paclitaxel (99mTc-PAC) against MCF-7 (ER+) and MDA-MB-231 (ER-) cell lines by using in vitro methods. METHODS: BME was obtained by the extraction of BM seeds by 80% ethanol. PAC was labeled with 99mTc by stannous chloride (SnCl2) as a reducing agent. Cytotoxicity and incorporation assays were performed on MCF-7 and MDA-MB-231 cells within the cell culture studies. RESULTS: The uptake value of 99mTc-PAC on MCF-7 cells at 240 minutes was 6.20% and BME treated 99mTc- PAC value was 17.39%. Conclusion: It is observed that BME treatment has a significant effect on the uptake of 99mTc-PAC on MCF-7 cells which is a known estrogen receptor-positive breast carcinoma cell line. It is concluded that this effect could be due to the estrogen receptor-dependent interaction of BME.

Microelectrode Recording for Deep Brain Stimulation of the Subthalamic Nucleus in Patients with Advanced Parkinson's Disease: Advantage or Loss of Time?

AIM: To investigate the effect of using microelectrode recording (MER) on the length of time required to carry out a deep brain stimulation (DBS) procedure of the subthalamic nucleus in patients with Parkinson's disease (PD). MATERIAL AND METHODS: The time required to include MER in the DBS operation was calculated for the first and second sides in 24 patients with PD. The number of microelectrodes used on each trajectory for the first and second sides, and the percentage of permanent electrodes implanted on each trajectory for the first and second sides, were quantified. RESULTS: The average times taken to use MER were 23.4 ± 6.2 minutes, 17.4 ± 6.5 minutes, and 41.2 ± 6.3 minutes for the first side, second side and total procedure, respectively. In 75% of patients, the permanent electrode was implanted at the planned target site for the first side, and in 61% of patients for the second side. CONCLUSION: MER extends the time required to carry out the DBS procedure. However, during surgery, it provides real-time information on the electrodes' neurophysiological locations and helps the surgical team choose an alternative target if the planned target does not produce satisfying results.

Characterizing the Intraoperative Microelectrode Recording-Induced Microlesion Effect on Motor Symptoms in Patients with Parkinson's Disease Undergoing Deep Brain Stimulation of the Subthalamic Nucleus.

AIM: To investigate microelectrode recording (MER)-induced microlesion effect (MLE) on the motor symptoms of 30 patients with Parkinson’s disease (PD) who underwent deep brain stimulation of the subthalamic nucleus. MATERIAL AND METHODS: MER-induced MLE was evaluated based on the difference between tremor, rigidity, and bradykinesia scores in the preoperative off-state and intraoperative state following MER and before test stimulation. RESULTS: MLE scores improved by 21.7% [left (L) side] and by 13.6% [right (R) side] from baseline (p < 0.05). Tremor scores improved by 31.5% (L) and by 14.2% (R) (p < 0.05), rigidity scores improved by 17.3% (L) and by 14.2% (R) (p < 0.05) and bradykinesia scores improved by 20.6% (L) and by 11.5% (R) (p < 0.05) from baseline. There was no significant difference between MLE and the number of microelectrodes used (p > 0.05). CONCLUSION: MER-induced MLE improved motor symptoms and was not correlated with the number of microelectrodes used during the procedure.

Selenium Protects Retinal Cells from Cisplatin-Induced Alterations in Carbohydrate Residues.

BACKGROUND: Investigate alterations in the expression and localization of carbohydrate units in rat retinal cells exposed to cisplatin toxicity. AIMS: The aim of the study was to evaluate putative protective effects of selenium on retinal cells subjected to cisplatin. STUDY DESIGN: Animal experiment. METHODS: Eighteen healthy Wistar rats were divided into three equal groups: 1. Control, 2. Cisplatin and 3. Cisplatin+selenium groups. After anesthesia, the right eye of each rat was enucleated. RESULTS: Histochemically, retinal cells of control groups reacted with α-2,3-bound sialic acid-specific Maackia amurensis lectin (MAA) strongly, while cisplatin reduced the staining intensity for MAA. However, selenium administration alleviated the reducing effect of cisplatin on the binding sites for MAA in retinal cells. The staining intensity for N-acetylgalactosamine (GalNAc residues) specific Griffonia simplicifolia-1 (GSL-1) was relatively slight in control animals and cisplatin reduced this slight staining for GSL-1 further. Selenium administration mitigated the reducing effect of cisplatin on the binding sites for GSL-1. A diffuse staining for N-acetylglucosamine (GlcNAc) specific wheat germ agglutinin (WGA) was observed throughout the retina of the control animals. In particular, cells localized in the inner plexiform and photoreceptor layers are reacted strongly with WGA. Compared to the control animals, binding sites for WGA in the retina of rats given cisplatin were remarkably decreased. However, the retinal cells of rats given selenium reacted strongly with WGA. CONCLUSION: Cisplatin reduces α-2,3-bound sialic acid, GlcNAc and GalNAc residues in certain retinal cells. However, selenium alleviates the reducing effect of cisplatin on carbohydrate residues in retinal cells.

Ultrasonographic findings in hereditary neuropathy with liability to pressure palsies.

OBJECTIVES: The aims of this study were to evaluate the sonographic findings of patients with hereditary neuropathy with liability to pressure palsies (HNPP) and to examine the correlation between sonographic and electrophysiological findings. METHODS: Nine patients whose electrophysiological findings indicated HNPP and whose diagnosis was confirmed by genetic analysis were enrolled in the study. The median, ulnar, peroneal, and tibial nerves were evaluated by ultrasonography. RESULTS: We ultrasonographically evaluated 18 median, ulnar, peroneal, and tibial nerves. Nerve enlargement was identified in the median, ulnar, and peroneal nerves at the typical sites of compression. None of the patients had nerve enlargement at a site of noncompression. None of the tibial nerves had increased cross-sectional area (CSA) values. There were no significant differences in median, ulnar, and peroneal nerve distal motor latencies (DMLs) between the patients with an increased CSA and those with a normal CSA. In most cases, there was no correlation between electrophysiological abnormalities and clinical or sonographic findings. DISCUSSION: Although multiple nerve enlargements at typical entrapment sites on sonographic evaluation can suggest HNPP, ultrasonography cannot be used as a diagnostic tool for HNPP. Ultrasonography may contribute to the differential diagnosis of HNPP and other demyelinating polyneuropathies or compression neuropathies; however, further studies are required.

Inhibitory effect of sub-conjunctival tocilizumab on alkali burn induced corneal neovascularization in rats.

BACKGROUND: To evaluate the effects of sub-conjunctivally applied interleukin-6 receptor (IL-6R) antibody (tocilizumab) on alkali burn induced corneal neovascularization (CNV) in rats. METHODS: Alkali burn induced corneal neovascularization was created in 24 right eyes of 24 rats. The rats were then randomized into 2 groups. Group 1 received sub-conjunctival injection of 4 mg/0.2 ml tocilizumab and Group 2 received sub-conjunctival injection of 0.2 ml normal saline at the 5th day of alkali burn. The corneal surface area invaded with neovascular vessels were calculated on photographs. The rats were sacrificed and the corneas were excised at the15th day. The corneal specimens were stained with hemotoxylin-eosin to evaluate tissue morphology and with Willebrand factor (vWF) to evaluate microvascular structures immunohistochemically. Vascular endothelial growth factor (VEGF) expression was analyzed by ELISA. RESULTS: The percent area of CNV was 26.9% in Group 1 and 56.5% in Group 2 (p < 0.001). The histological evaluation showed that the corneal structures were not visibly altered by sub-conjuntival tocilizumab injection. Group 1 showed significantly lower corneal inflammation score than Group 2 (p < 0.001). The number of vessels stained with vWF were significantly higher in Group 2 than Group 1 (15.23 and 5.46, respectively; p < 0.001). ELISA analyses showed that corneal VEGF levels were significantly lower in Group 1 compared to Group 2 (p = 0.013) CONCLUSION: The present data demonstrated first time the beneficial effects of sub-conjunctival tocilizumab on decreasing CNV in alkali burn model of the rat cornea. Further studies are warranted to confirm these findings for the clinical application.

Syncope associated with subthalamic nucleus deep brain stimulation in a patient with Parkinson's disease.

In advanced Parkinson's disease (PD), deep brain stimulation (DBS) may be an alternative option for the treatment of motor symptoms. Side effects associated with subthalamic nucleus (STN) DBS in patients with PD are emerging as the most frequent sensory and motor symptoms. DBS-related syncope is reported as extremely rare. We wanted to discuss the mechanisms of syncope associated with STN DBS in a patient with Parkinson's disease. Case report. Sixty-three-year-old female patient is followed up with diagnosis of idiopathic Parkinson's disease for 6 years in our clinic. The patient has undergone STN DBS due to painful dystonia and drug resistant tremor. During the operation, when the left STN was stimulated at 5 milliampere (mAmp), the patient developed presyncopal symptoms. However, when the stimulation was stopped symptoms improved. During the early period after the operation, when the right STN was stimulated at 1.3 millivolts (mV), she developed the pre-yncopal symptoms and then syncope. Our case shows that STN DBS may lead to directly autonomic symptoms resulting in syncope during stimulation-on (stim-on).