From Deep Learning to the Discovery of Promising VEGFR-2 Inhibitors.

Vascular endothelial growth factor receptor 2 (VEGFR-2) stands as a prominent therapeutic target in oncology, playing a critical role in angiogenesis, tumor growth, and metastasis. FDA-approved VEGFR-2 inhibitors are associated with diverse side effects. Thus, finding novel and more effective inhibitors is of utmost importance. In this study, a deep learning (DL) classification model was first developed and then employed to select putative active VEGFR-2 inhibitors from an in-house chemical library including 187 druglike compounds. A pool of 18 promising candidates was shortlisted and screened against VEGFR-2 by using molecular docking. Finally, two compounds, RHE-334 and EA-11, were prioritized as promising VEGFR-2 inhibitors by employing PLATO, our target fishing and bioactivity prediction platform. Based on this rationale, we prepared RHE-334 and EA-11 and successfully tested their anti-proliferative potential against MCF-7 human breast cancer cells with IC50 values of 26.78±4.02 and 38.73±3.84 µM, respectively. Their toxicities were instead challenged against the WI-38. Interestingly, expression studies indicated that, in the presence of RHE-334, VEGFR-2 was equal to 0.52±0.03, thus comparable to imatinib equal to 0.63±0.03. In conclusion, this workflow based on theoretical and experimental approaches demonstrates effective in identifying VEGFR-2 inhibitors and can be easily adapted to other medicinal chemistry goals.

UAV-based RGB and TIR imaging for geothermal monitoring: a case study at Kestanbol geothermal field, Northwestern Turkey.

Kestanbol is one of the most important geothermal fields in NW Turkey. This study conducted the first-ever surveys over a 10 ha reach of the Kestanbol geothermal field using an unmanned aerial vehicle (UAV) equipped with visible (RGB) and thermal infrared (TIR) cameras. Low-altitude flights below 40 m above the ground were operated above the Kestanbol geothermal field. Approximately 3500 RGB and TIR images were captured using the UAV. We recorded high-resolution RGB and TIR data of the Kestanbol geothermal field and applied the structure from motion (SfM) algorithm to identify the distribution of geothermal springs and seeps. The Kestanbol geothermal field was monitored to create a georeferenced RGB orthophoto, RGB 3D surface model, thermal anomaly map, and digital surface model (DSM) of the area with centimeter-level accuracy. In the TIR orthophoto, the surface temperature in the geothermal field was found to be between 15 and 75 °C. All the thermal anomalies revealed by the survey were verified by field observations. The geothermal springs and seeps were parallel to the NE-SW regional tectonic trends. The results of this study demonstrate an effective technique for monitoring and assessing geothermal water using UAV-based RGB and TIR imaging and provide an accurate basis for geothermal development projects. RGB and TIR imaging using UAVs are considered promising methods for improving the assessment of the effects of geothermal water on the environment.

Machine learning study: from the toxicity studies to tetrahydrocannabinol effects on Parkinson's disease.

Aim: Investigating molecules having toxicity and chemical similarity to find hit molecules. Methods: The machine learning (ML) model was developed to predict the arylhydrocarbon receptor activity of anti-Parkinson's and US FDA-approved drugs. The ML algorithm was a support vector machine, and the dataset was Tox21. Results: The ML model predicted apomorphine in anti-Parkinson's drugs and 73 molecules in FDA-approved drugs as active. The authors were curious if there is any molecule like apomorphine in these 73 molecules. A fingerprint similarity analysis of these molecules was conducted and found tetrahydrocannabinol (THC). Molecular docking studies of THC for dopamine receptor 1 (affinity = -8.2 kcal/mol) were performed. Conclusion: THC may affect dopamine receptors directly and could be useful for Parkinson's disease.

Arylhydrocarbon receptor has tissue-specific roles in xenobiotic metabolism, the immune system, inflammation and cancer. Studies showed that carbidopa and dopamine are agonists of arylhydrocarbon receptor. Parkinson's disease is a neurodegenerative disease and depends on the dopamine system's dysregulation. There is a strong relationship between the dopamine system and cannabinoids. In this study, the possibility of the agonist effect of tetrahydrocannabinol on dopamine receptors was investigated by a machine learning method.

SYNTHETIC CANNABINOID BONZAI RELATED CREATINE KINASE ENZYME ELEVATION: A TURKISH CENTER STUDY.

Synthetic cannabinoid (locally named 'Bonzai' in Turkey) use is increasing worldwide (especially among people with low income). One of its harmful adverse effects is an increase in serum levels of muscle enzymes (i.e., creatine kinase [CK]). The aim of this study was to determine the prevalence of Bonzai use in patients admitted with elevated CK levels and to compare the 1-month survival status of Bonzai users with that of non-Bonzai users. This retrospective study was conducted on a total of 468 patients, median (min-max) age 48±22 (18-93) years. It was found that 10.68% (n=50) of the patients presenting with elevated CK levels were using Bonzai (group 1), while the remaining 418 (89.32%) patients were non-Bonzai users (group 2). Median age was higher in group 2 as compared with group 1 (p=0.001). In group 1, the predominance of male (M) over female (F) patients was interestingly high, yielding a F:M ratio of 1/49 (χ2=110.03, p<0.001). The prevalence of Bonzai use among patients admitted to our center with elevated CK levels was 10.68%. The Bonzai group patients were younger and mostly males, and none of them died at 1 month of admission. These findings may help in the management of such clinical conditions and could be a pathfinder for further studies in this field.

Is there a relationship between causative microorganisms and hearing loss in neonatal sepsis?

BACKGROUND: The aim of the present study was to determine the possible relationship between cultured microorganisms and hearing loss in infants admitted to the neonatal intensive care unit (NICU) who could not pass a standard hearing test. METHOD: The medical records of infants treated at the NICU were retrospectively evaluated. The patients were first divided into two groups, and group 1 was divided into two subgroups: Group 1 included patients with hearing loss accompanied by proven sepsis caused by either gram-negative (group 1A) or gram-positive (group 1B) bacteria, and group 2 included patients with clinical sepsis. The groups were compared with potential risk factors related to hearing loss. RESULTS: Between January 2014 and January 2019, the cases of 3,800 infants admitted to the NICU were reviewed. Of 3,548 living babies, the Auditory Brainstem Response (ABR) test showed that 35 infants (0.98%) were diagnosed with hearing loss. In 12 infants with hearing loss, microbial growth in the blood cultures was detected, whereas in the remaining 23, the blood cultures were negative. Of the cases with microbial growth, five were gram negative and seven were gram positive. In the comparison of groups 1A, 1B, and 2, there were statistically significant differences in terms of risk factors such as low birth weight (p = .048), neonatal hospitalization time (p = .001), free oxygen support (p = .001), intraventricular bleeding (p = .001), loop diuretic use (p = .001), and blood transfusion (p = .048). CONCLUSION: The relationship between hearing loss and microorganisms causing sepsis could not be determined in this research.

Design, synthesis and biological evaluation of 3,5-diaryl isoxazole derivatives as potential anticancer agents.

The present study was carried out in the attempt to synthesize a new class of potential anticancer agents comprising eleven compounds (24-34) sharing the 3,5-diarylisoxazole as a core. The chemical structure of the new synthesized compounds was established by IR, 1H NMR, 13C NMR and elemental analysis. Their biological potential towards prostate cancer was evaluated by using cancer PC3 cells and non-tumorigenic PNT1a cells. Interestingly, compound 26 distinguished from others with a quite high selectivity value that is comparable to 5-FU. The binding mode of 26 towards Ribosomal protein S6 kinase beta-1 (S6K1) was investigated at a molecular level of detail by employing docking simulations based on GLIDE standard precision as well as MM-GBSA calculations.

Clinical characteristics and neonatal outcomes of liveborn newborns with hydrops fetalis treated in a tertiary level neonatal intensive care unit.

BACKGROUND: This study was performed for examining the neonatal results and aetiological factors of neonates with hydrops fetalis (HF) and determining the factors affecting mortality. METHODS: The medical records of liveborn neonates with HF who were admitted to a tertiary Neonatal Intensive Care Unit (NICU) in Konya, Turkey, between 2013 and 2019 were reviewed retrospectively. The demographic data, prenatal intervention, clinical findings, and results of the patients were recorded. RESULTS: A total of 32.6% of the 46 liveborn HF infants had immune HF (IHF), while 67.4% had nonimmune HF (NIHF); there was prenatal diagnoses in 39 (84.7%) cases. Cordocentesis and blood transfusion (n = 14; 30.4%) were the prenatal diagnosis and treatment interventions with the highest rate. A total of 16 patients (34.7%) received in utero interventional treatment. It was determined that the mean gestational age was not associated with mortality; moreover, birthweight (BW), Apgar score and the need for mechanical ventilation affected mortality. CONCLUSION: The prognosis changes according to different etiologies of HF. However, despite the developments in neonatal care, mortality is still high in HF infants.

Prediction of the development of pulmonary arterial hypertension with Tei Index in congenital heart diseases with left-to-right shunt.

OBJECTIVE: The aim of this study was to determine the usefulness of the Tei Index, an echocardiographic parameter, in the early determination of pulmonary artery pressure (PAP) in congenital heart disease (CHD) with a left-to-right shunt. METHODS: Right and left ventricular functions were evaluated using Tei Index values determined with tissue Doppler echocardiography. Cardiac catheterization was performed in all cases. The presence of pulmonary arterial hypertension (PAH) was defined as a mean PAP of ≥25 mm Hg and a pulmonary vascular resistance index of >3 WU/m2. Patients with a pulmonary/systemic blood flow ratio of ≥2 were considered candidates for surgery. RESULTS: The Tei Index values measured from the left ventricular posterior wall and the right ventricular anterior wall were found to be significantly higher in the patients with PAH (0.68±0.18, 0.67±0.16, respectively) compared with the patients without PAH (0.56±0.16, p=0.027; 0.51±0.12 p=0.001). A significant correlation was detected between the Tei Index value measured from the left ventricular posterior wall and the mean PAP (correlation coefficient: 0.491). CONCLUSION: The right ventricular Tei Index values in children with CHD and a left-to-right shunt can be used as a parameter to follow up on the potential development of PAH, to make a diagnosis in the early period, and to make a timely decision about surgery.

A Prediction Model of Operation Efficacy Using Protruding Prostate Lobe Volume in Patients Who Are Candidates for Transurethral Resection of Prostate.

PURPOSE: To create a prediction model that could preoperatively measure the success of the transurethral prostate resection (TURP) because of bladder outlet obstruction. METHODS: Patients aged 50-80 years applied with TURP were examined prospectively and evaluated in respect of the preoperative and postoperative values of maximum flow rate (Qmax), international prostate symptom score (IPSS), quality of life (QoL) score and post-voiding residual (PVR) urine amount. On the preoperative transabdominal ultrasonography, total prostate volume (TPV), and protruding prostate lobe volume (PPLV) were measured and the protruding ratio (PR), as the ratio of PPLV to TPV, was calculated. Based on the mean of the preoperative and postoperative Qmax difference (Qmax-D) value, Group 1 (n = 33) was defined as "low efficacy" and Group 2 (n = 30) as "high efficacy". RESULTS: A correlation was determined between the QMax-D, IPSS difference, PVR difference, and QoL difference measured for the efficacy of the operation, and TPV, PPLV and PR. The results of multivariate analysis showed the main effect to be created by PR (p = 0.000; OR 1.596). In the evaluation with receiver operating characteristic curve analysis of high efficacy obtained in the TURP, a significantly powerful effect of the measurements of PPLV area under curve (AUC 0.922 [0.855-0.989] p= 0.000) and PR (AUC 0.954 [0.982-1.000] p = 0.000) was determined. The cutoff value of 11.5 was detected for PR. Efficacy sensitivity and the positive predictive values were recorded as 93.3%, and specificity and negative predictive value as 93.9%. CONCLUSION: When determining candidate patients for TURP surgery, measurements of the PPLV and especially the PR should be taken into consideration in the preoperative prediction of efficacy.

Hepatitis D reactivation in a patient with metastatic renal cell carcinoma receiving sunitinib therapy.

BACKGROUND: Cytotoxic and immunosuppressive therapies for cancer treatment may allow hepatitis reactivation. Hepatitis due to viral hepatitis reactivation is detected in 14%-25% of hepatitis B surface antigen (HBsAg)-positive cancer patients undergoing anticancer treatments. Drug toxicity may be confused with hepatitis reactivation, which may cause a delay in diagnosis. CASE REPORT: A 60-year-old man with metastatic renal cell carcinoma was treated with sunitinib. Sixteen months after sunitinib inception, liver enzymes were elevated and viral hepatitis reactivation was detected as hepatitis delta virus infection in the HBsAg-positive patient. CONCLUSION: Cancer patients should be screened for viral hepatitis prior to immunosuppressive therapy or chemotherapy.

Imidacloprid induced alterations in oxidative stress, biochemical, genotoxic, and immunotoxic biomarkers in non-mammalian model organism Galleria mellonella L. (Lepidoptera: Pyralidae).

Imidacloprid (IMI), a neonicotinoid insecticide, is widely used to control pests in agriculture. We investigated the changes in antioxidant enzyme activities, lipid peroxidation levels, biochemical effects, genotoxic effect, and immunotoxic effect of sublethal doses (0.25, 0.50, 0.75, and 1.00 µg) of IMI at different time periods (24, 48, 72, and 96 h) on a model organism, Galleria mellonella L. The results indicated that there were dose-dependent increases in both antioxidant enzyme activities (SOD and CAT) and MDA levels. Protein content was not affected by IMI at 24th and 48th, whereas it was decreased by the highest dose of IMI (1.00 µg) at 72nd and 96th h. Lipid and carbohydrate contents were reduced with increasing doses of IMI. Micronucleus frequency significantly increased in all IMI doses. All IMI doses caused a significant decrease in THC at 24th, 48th, and 72nd h. Our results can help to illustrate the effects of IMI in target organisms and indirectly may aid to discover potential risk of it on nontarget organisms. Future studies, at molecular levels, will be helpful in understanding the mechanism of action of IMI on these biomarkers.

Comparison of inflammatory markers between brucella and non-brucella epididymo-orchitis

ABSTRACT Objectives: Brucellosis is a multi-system infectious disease that is associated with inflammation, which causes an increase in acute phase reactants. Hematological inflammatory markers of brucellosis include mean platelet volume (MPV), red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). In this study, we aimed to evaluate the diagnostic value of hematological inflammatory markers in Brucella epididymo-orchitis (BEO), and to investigate the utility of these markers for differential diagnosis from non-Brucella epididymo-orchitis (non-BEO). Materials and Methods: We retrospectively reviewed the records of 22 BEO and 50 non-BEO patients. Hematological parameters were recorded and compared between the two groups. The main diagnostic criteria for BEO were positive clinical findings (i.e., testicular pain, tenderness and scrotal swelling), a positive Rose Bengal test result, standard tube agglutination (STA) titer ≥ 1/160, and/or a positive blood culture. Results: The most decisive factors in discriminating between BEO and non-BEO were NLR, RDW, and MPV, in decreasing order of their strength. Regardless of other factors, NLR values < 2.3 significantly increased the odds of BEO (OR=8.080, 95% CI: 1.929-33.843, p=0.004). After adjusting for other factors, RDW values >14.45% significantly increased the odds of BEO (OR=7.020, 95% CI: 1.749-28.176, p=0.006). Independent of the other factors, patients with MPV < 7.65 fL had a 6.336 times higher risk for BEO (95% CI: 1.393 - 28.822, p=0.017). Conclusion: Hematological inflammatory markers such as NLR, RDW, and MPV can aid in the differential diagnosis of BEO and non-BEO.

Outcomes of microsurgical subinguinal varicocelectomy to treat painful recurrent varicocele.

In this study, was evaluated the outcomes of patients undergoing microsurgical varicocelectomy to treat scrotal pain due to recurrent varicocele were evaluated. A total of 27 patients who underwent microsurgical varicocele ligation for recurrent varicocele and scrotal and/or testicular pain were included in this retrospective study. Recurrent varicocele in all patients was diagnosed with by physical examination and coloured Doppler ultrasonography (CDUSG). All patients underwent pre-operative follow-up and post-operative follow-up at 3 and 6 months by physical examination, assessment of using the Visual Analog Scale (VAS) score, and CDUSG. The rRecurrent varicocele was grade 3 in 24 patients (88.9%) and grade 2 in 3 patients (11.1%). In all cases, the varicocele was on the left side. The mean VAS score was 6.5 (range 5-8) pre-operatively, 0.7 (range 0-5) at 3 months post-operatively, and 0.3 (range 0-4) at 6 months post-operatively (p < 0.001). Post-operative complete responseresolution, partial resolutionponse, and non-responsiveness rates were 85.2%, 11.1%, and 3.7% at the 3rd month post-operatively, respectively, and 88.8%, 7.5%, and 3.7% at the 6th month post-operatively, respectively. During follow-up, there was recurrence in 1 patient (3.7%) and hydrocele in 1 patient (3.7%). Microsurgical subinguinal varicocelectomy is an effective treatment for patients with scrotal pain caused by recurrent varicocele.

Comparison of inflammatory markers between brucella and non-brucella epididymo-orchitis.

OBJECTIVES: Brucellosis is a multi-system infectious disease that is associated with inflammation, which causes an increase in acute phase reactants. Hematological inflammatory markers of brucellosis include mean platelet volume (MPV), red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). In this study, we aimed to evaluate the diagnostic value of hematological inflammatory markers in Brucella epididymo-orchitis (BEO), and to investigate the utility of these markers for differential diagnosis from non-Brucella epididymo-orchitis (non-BEO). MATERIALS AND METHODS: We retrospectively reviewed the records of 22 BEO and 50 non-BEO patients. Hematological parameters were recorded and compared between the two groups. The main diagnostic criteria for BEO were positive clinical findings (i.e., testicular pain, tenderness and scrotal swelling), a positive Rose Bengal test result, standard tube agglutination (STA) titer ≥ 1/160, and/or a positive blood culture. RESULTS: The most decisive factors in discriminating between BEO and non-BEO were NLR, RDW, and MPV, in decreasing order of their strength. Regardless of other factors, NLR values < 2.3 significantly increased the odds of BEO (OR=8.080, 95% CI: 1.929- 33.843, p=0.004). After adjusting for other factors, RDW values >14.45% significantly increased the odds of BEO (OR=7.020, 95% CI: 1.749-28.176, p=0.006). Independent of the other factors, patients with MPV < 7.65 fL had a 6.336 times higher risk for BEO (95% CI: 1.393 - 28.822, p=0.017). CONCLUSION: Hematological inflammatory markers such as NLR, RDW, and MPV can aid in the differential diagnosis of BEO and non-BEO.

The Respiratory Induced Kidney Motion: Does It Really Effect the Shock Wave Lithotripsy?

PURPOSE: To investigate the effect of respiratory induced kidney mobility on success of shock wave lithotripsy (SWL) with an electrohydraulic lithotripter. MATERIALS AND METHODS: Between May 2013 and April 2015, 158 patients underwent SWL treatment for kidney stones with an electrohydraulic lithotripter. The exclusion criteria were presence of a known metabolic disease (such as cystinuria), non-opaque stones, need for focusing with ultrasonography, abnormal habitus, urinary tract abnormalities, and inability to tolerate SWL until the end of the procedure. Stones greater than 20 mm, and lower pole stones were also excluded. The movement of the kidneys were measured with fluoroscopy guidance. RESULTS: The procedure was successful in 66.7% of the males, and 56.9% of the females. The mean stone size was 11 ± 3 mm in the successful group, and it was 14 ± 4 mm in the unsuccessful group. The mean stone mobility rate was 32 ± 10 in the successful group and 40 ± 11 in the unsuccessful group. Multivariate analysis showed that stone size and kidney mobility affected the success rate significantly, however Hounsfield Unit (HU) did not. CONCLUSION: The current study shows the significant effect of kidney motion on the success of SWL. Further studies with different lithotripters are needed to determine the significance of kidney mobility.

Complete penile skin necrosis.

Superficial penile skin infections may be presented in different clinical situations that vary from simple infection to organ loss and serious morbidity and mortality. Antibiotic treatment and, if necessary, urgent debridement is required. A 46-year-old male patient with the complaints of urethral discharge and pain admitted to our outpatient clinic. He declared that there were midpenil tenderness and erythema 14 days ago which occurred after sexual intercourse. Complete penile skin necrosis with purulent discharge was detected in physical examination. After wound debridement and 14-days of intravenous antibiotic treatment, wound site culture was negative and then full-thickness skin grafting was performed. Urgent antibiotic treatment should be given, especially for the skin infections of the genital area. Despite the rapid spread of antibiotic treatment, clinical presentation may worsen within hours. It should be noted that especially in diabetics and elderly patients with poor hygiene, the infection may spread to anogenital region and may lead to fulminant necrotizing fasciitis which can present with severe morbidity and mortality. Reconstructive surgery is planned after the control of infection and according to the amount of tissue loss.

Management of Forgotten Ureteral Stents: Relationship Between Indwelling Time and Required Treatment Approaches.

BACKGROUND: Double-J stents are widely used in urology practice, and removal of these stents can sometimes be forgotten. AIMS: To investigate whether indwelling time of double-J stent can predict which treatment modality is required for removal of the stent from the body. STUDY DESIGN: A multicentre, retrospective observational study. METHODS: The data of 57 patients who were treated for forgotten ureteral stents between January 2007 and December 2014 were evaluated retrospectively. Patients were classified into four groups according to indwelling time of the stents: 6-12 months, 13-24 months, 25-36 months, and <36 months. Encrustation and associated stone burden of the stents were evaluated with non-contrast stone protocol computerised tomography. RESULTS: Patients were classified according to their duration of the stent indwelling time. Simple cystoscopic stent retrieval was performed in 71.4% of patients in the 6-12 months group, 44% of patients in the 13-24 months group, 6.2% of patients in the 25-36 months group, and 11.1% of patients in the <36 months group. A percutaneous or open surgery was required in no patients with an indwelling time of double-J stent shorter than 30 months. CONCLUSION: Transurethral and/or percutaneous combined endo-urological approaches are usually sufficient for the removal of forgotten double-J stents. Transurethral procedures are sufficient for the treatment of patients with double-J stent indwelling times less than 30 months.

Decreased cerebral vasomotor reactivity in patients with obstructive sleep apnea syndrome.

OBJECTIVE: In obstructive sleep apnea syndrome (OSAS), any of the activated neural, vascular, hemodynamic, metabolic, inflammatory, and thrombotic mechanisms may be related to increased cerebrovascular disease and risk of death; however, the possible pathophysiological process between obstructive sleep apnea syndrome and stroke has not been clearly explained. We hypothesize that alterations in vasomotor reactivity in patients may be responsible for their altered cerebral blood flow, and may contribute to the increased risk of ischemic stroke. METHODS: A total of 30 untreated patients with severe obstructive sleep apnea and 26 control subjects were included in the study. The mean blood flow velocity and breath holding index were measured in middle cerebral artery bilaterally in both patient and control groups by using transcranial Doppler ultrasound. We compared the values between two groups. RESULTS: The mean blood flow velocity and breath holding indexes were significantly decreased in the patient group when compared with the control group. There were no correlations between cerebral hemodynamic parameters and polysomnographic findings in patients. CONCLUSION: Our findings suggest that there was a deteriorated vasodilator response to hypercapnia in patients with OSAS. This deterioration may stem from chemoreceptors or endothelial damages that lead to vascular relaxation and vasodilatation in cerebrovascular circulation. This impaired cerebral vascular regulation may contribute to the increased risk of stroke in patients with OSAS.

Transcallosal conduction in paroxysmal kinesigenic dyskinesia.

OBJECTIVES: Detecting whether a possible disequilibrium between the excitatory and inhibitory interhemispheric interactions in paroxysmal kinesigenic dyskinesia (PKD) exists. METHODS: This study assessed measures of motor threshold, motor evoked potential latency, the cortical silent period, the ipsilateral silent period and the transcallosal conduction time (TCT) in PKD patients. Data were compared between the clinically affected hemisphere (aH) and the fellow hemisphere (fH). RESULTS: The transcallosal conduction time from the aH to the fH was 11.8 ms (range = 2.3-20.7) and 13.6 ms (range = 2.8-67.7) from the fH to the aH. The difference in TCT in the affected side was significant (p = .019). CONCLUSION: The findings demonstrated that, although inhibitory interneurons act normally and symmetrically between the motor cortices and transcallosal inhibition was normal and symmetrical between both sides, the onset of transcallosal inhibition was asymmetrical. The affected hemisphere's inhibition toward the unaffected hemisphere is faster compared to the inhibition provided by the fellow hemisphere. These results are consistent with an inhibitory deficit in the level of interhemispheric interactions. SIGNIFICANCE: This study revealed a defect in inhibition of the motor axis could be responsible in the pathological mechanisms of kinesigenic dyskinesia.