Effects of Transcranial Direct Current Stimulation on Clinical Outcomes, Calcitonin Gene-Related Peptide, and Pituitary Adenylate Cyclase-Activating Polypeptide-38 Levels in Menstrual Migraine.

OBJECTIVES: Transcranial direct current stimulation (tDCS) has been suggested as an alternative treatment option for migraine. The present study aimed to evaluate the efficacy of tDCS on clinical outcomes in addition to calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating peptide 38 (PACAP-38) levels in individuals with menstrual-related migraine (MRM) for the first time. MATERIALS AND METHODS: In this parallel study, 58 female patients between the ages of 18 and 45 years, including 36 with MRM and 22 with nonmenstrual migraines (nMM), were recruited. Sessions of 2-mA 20-minute anodal tDCS were administered over the left dorsolateral prefrontal cortex within three consecutive days (1:1 active and sham stimulation). Migraine attack frequency, severity, analgesic usage, CGRP, and PACAP-38 levels of the patients were evaluated before and one month after tDCS. RESULTS: After tDCS, in the active group compared with the sham group, the frequency (p = 0.031), the severity of attacks (p = 0.003), the number of days with headache (p = 0.004), and the analgesic usage (p = 0.024) were all decreased. In both MRM and nMM groups, the frequency and severity of attacks and analgesic usage were decreased in those receiving active stimulation (p < 0.001 for each). CGRP and PACAP-38 levels were no different in the active group and the sham group after tDCS. CONCLUSIONS: tDCS was shown to be efficacious in migraine prophylaxis and a valuable option for migraine and MRM treatment. The absence of changes in serum CGRP and PACAP-38 levels suggests that tDCS efficacy may stem from distinct cerebral electrophysiological mechanisms.

Acute effect of transcranial direct current stimulation on photoparoxysmal response.

INTRODUCTION: Transcranial direct current stimulation (tDCS) is a non-invasive technique, used to modify the excitability of the central nervous system. The main mechanism of tDCS is to change the excitability by subthreshold modulation by affecting neuronal membrane potentials in the direction of depolarization or repolarization. tDCS was previously investigated as an alternative adjunctive therapy in patients with epilepsy. We aimed here to investigate the acute effect of tDCS on the photoparoxysmal response (PPR) in EEG. METHODS: We enrolled 11 consecutive patients diagnosed with idiopathic generalized epilepsy who had PPR on at least 2 EEGs. Three different procedures, including sham, anodal, and cathodal tDCS were applied to the patients at intervals of one week by placing the active electrode over Oz, for 2 mA, 20 minutes. Spike-wave indices (SWI) were counted by two researchers independently and were compared during intermittent photic stimulation (IPS) on EEGs both before and after the application. RESULTS: After cathodal tDCS, SWI increased compared to baseline EEG and sham EEG in 3 patients, and after anodal tDCS, SWI increased in 2 patients. Although the SWI values did not change significantly, 8 patients reported subjectively that the applications were beneficial for them and that they experienced less discomfort during photic stimulation after the sessions. There were no side effects except transient skin rash in one patient, only. CONCLUSIONS: In our sham controlled tDCS study with both cathodal and anodal stimulation, our data showed that there was no significant change in SWI during IPS, despite subjective well-being. tDCS' modulatory effect does not seem to act in the acute phase on EEG parameters after photic stimulation.

Long-Term Prophylactic Transcranial Direct Current Stimulation Ameliorates Allodynia and Improves Clinical Outcomes in Individuals With Migraine.

OBJECTIVES: Migraine is a common and substantially debilitating disorder that may associate with allodynia, a marker of central sensitization in the pain circuits. Several unmet needs, like limited adherence to drugs due to adverse events and cost-effectivity, still occur in the prophylactic treatment of migraine. Transcranial direct current stimulation (tDCS) has recently been indicated to be beneficial in individuals with migraine with and without allodynia. However, to our knowledge, there are no studies evaluating the efficacy of six-month tDCS in migraine. MATERIALS AND METHODS: This study was a randomized double-blind parallel-group sham-controlled five-month extension study after a one-month lead-in trial of tDCS in individuals with migraine. A total of 23 individuals with migraine with allodynia who completed the lead-in trial were recruited after their consent and were administered three consecutive sessions of 2-mA anodal 20-minute tDCS over the left primary motor cortex every month for an additional five months. Pain-related outcomes were determined using monthly headache diaries. Allodynia, depression, anxiety, and disability because of migraine also were assessed throughout the study. RESULTS: Improvements in allodynia levels, attack frequency, number of rescue medications, and attack duration were higher, and mostly gradual during the trial, in the active group. Migraine Disability Scale grades also were lower in the active group, whereas no between-group differences were found in depression and anxiety scores. Higher responder rates of migraine attack frequency (56.8% vs 25%), number of headache days (56% vs 16.7%), and migraine attack duration (90.9% vs 8.3%) were observed after six-month tDCS in the active group than in the sham group. CONCLUSIONS: Long-term extended tDCS is shown to be a safe, efficacious, and plausible modality for prophylactic treatment in individuals with migraine with allodynia. SIGNIFICANCE: Long-term extended tDCS can alleviate allodynia, which is an indicator of drug resistance and chronicity, and meet the goals of prophylactic treatment in individuals with migraine with allodynia.

Synthesis, characterization and thermal degradation kinetics of a new pyrazole derived methacrylate polymer, poly(1,3-diphenyl-1H-pyrazol-5-yl methacrylate).

A new pyrazole derived methacrylate monomer, 1,3-diphenyl-1H-pyrazol-5-yl methacrylate, was synthesized from the reaction of 1,3-diphenyl-5-pyrazolone with methacryloyl chloride in the presence of triethylamine. After that, its homopolymerization was carried out by free radical polymerization method at 60 °C initiated with benzoyl peroxide. Spectral characterizations were achieved by 1H-NMR and FTIR spectroscopies. The kinetics of thermal degradation of the new polymer, poly(1,3-diphenyl-1H-pyrazol-5-yl methacrylate), poly(DFPMA), were investigated by thermogravimetric analysis (TGA) at different heating rates. The initial decomposition temperature of the polymer changed from 216.3 °C to 243.5 °C depending on the increasing heating rate. The thermal decomposition activation energies in a conversion range of 7-19% were 79.45 kJ/mol and 81.56 kJ/mol by the Flynn-Wall-Ozawa and Kissinger methods, respectively. Thermodegradation mechanism of the poly(DFPMA) were investigated in detail by using different kinetic methods available in the literature such as Coats-Redfern, Tang, Madhusudanan and Van Krevelen. Among all these methods, the best result was obtained for Coats-Redfern method (E =90.93 kJ/mol) at the optimum heating rate of 15 °C/min for D1 mechanism. That means the thermodegradation mechanism of poly(DFPMA) proceeds over a one-dimensional diffusion type deceleration mechanism.

Is Allodynia a Determinant Factor in the Effectiveness of Transcranial Direct Current Stimulation in the Prophylaxis of Migraine?

OBJECTIVES: Allodynia, the clinical marker of central sensitization, affects even simple daily living activities and increases the tendency for migraine to be more resistant to treatment and have a chronic course. Migraine that impairs quality of life can often be treated with variable pharmaceutical agents, but with various side effects. Transcranial direct current stimulation (tDCS) is a potential alternative treatment for migraine prophylaxis. MATERIALS AND METHODS: Seventy-seven patients diagnosed with migraine (48 with allodynia and 29 without allodynia) were included in the study. Randomly, 41 of the 77 patients received sham stimulation and 36 patients underwent three sessions of anodal left primary motor cortex stimulation for 2 mA, 20 min. Migraine attack characteristics (frequency, severity, and duration) and analgesic drug use were followed with headache diaries for one month after the stimulation. RESULTS: After tDCS, migraine attack frequency (p = 0.021), the number of headache days (p = 0.005), duration of attacks (p = 0.008), and symptomatic analgesic drug use (p = 0.007) decreased in patients receiving active tDCS, compared to the sham group. The therapeutic gain of tDCS was calculated as 44% (95% confidence interval [CI]: 22-60%) for headache days and 76% (95% CI: 55-86) for headache duration. Response to tDCS treatment was higher in patients without allodynia (60% vs. 24%; p = 0.028) and allodynia came out as an independent predictor of response to tDCS with logistic regression analysis. Side effects were rare and similar to the sham group. CONCLUSIONS: tDCS is a safe, efficacious, and fast method for migraine prophylaxis. However, the administration of tDCS before allodynia occurs, that is, before central sensitization develops, will provide increased responsiveness to the treatment. SIGNIFICANCE: tDCS is more effective before the development of allodynia, but it also improves the quality of life even after the development of allodynia.

The effect of transcranial direct current stimulation on seizure frequency of patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is a non-invasive and safe method tried in drug-resistant epilepsies, in recent years. Our aim was to evaluate the effect of tDCS in patients diagnosed with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) which is a well-known drug-resistant focal epilepsy syndrome. PATIENTS AND METHODS: Twelve MTLE-HS patients diagnosed with their typical clinical, EEG and MRI findings fulfilling the criteria for drug-resistance as suggested by the ILAE commission were included after Ethics Committee approval and their signed consent. All patients received modulated cathodal stimulation; 2mA for 30min on 3 consecutive days. All patients also received sham stimulation with the same electrode positions; designed as 60s stimulation gradually decreasing in 15s with placement of the electrodes for 30min over the stimulation side. They were followed up by standard seizure diaries and their medical treatment was not changed during the study period. Their seizure frequencies both before and after cathodal tDCS and sham stimulation were compared statistically. Adverse effects were also questioned. RESULTS: Mean age of our study group was 35.42±6.96 (6 males; median: 35.50). The mean seizure frequency was 10.58±9.91 (median=8; min-max=2-30) at the baseline and significantly decreased to 1.67±2.50 (median=0.5; min-max=0-8) after cathodal tDCS application (p=0.003). Ten patients (83.33%) had more than 50% decrease in their seizure frequencies after cathodal tDCS. Two patients (16.67%) also showed positive sham effect. Six patients (50%) were seizure-free in the post-cathodal tDCS period of one month. No adverse effect has been reported except tingling sensation during cathodal stimulation. CONCLUSION: Our small series suggested that cathodal tDCS may be used as an additional treatment option in MTLE-HS. It may be tried in TLE-HS patients waiting for or rejecting epilepsy surgery or even with ineffective surgery results. More studies are needed with large series of patients to investigate the effects of tDCS in drug resistant epilepsies.

Transcranial direct current stimulation improves seizure control in patients with Rasmussen encephalitis.

Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t-DCS) is a non-invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t-DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t-DCS on seizures in Rasmussen encephalitis and to clarify its safety. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non-sham stimulations), and finally sham stimulation with two-month intervals, respectively. Three patients received classic (DC) cathodal t-DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60-second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm x 50 mm wet sponge electrodes with 2-mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30-minute stimulation period. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t-DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Both classic and modulated cathodal t-DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients.

Synthesis, Characterization and Thermal Decomposition Kinetics of a Novel Benzofuran Ketoxime Derived Polymer.

A novel benzofuran ketoxime derived polymer, poly(benzofuran-2-yl-methylketoxime-O-methacrylate) [poly(BMKMA], was firstly synthesized by free radical polymerization method. Its thermal degradation studies were performed by thermogravimetric analysis (TGA) in order to determine the actual reaction mechanisms of the decomposition process. The activation energy of the solid-state process was determined using Flynn-Wall-Ozawa method, which resulted to be 235.94 kJ/mol. The activation energies of different mechanism models were determined by Coats-Redfern, Madhusudanan and Van Krevelen kinetic methods. Compared with the Ozawa method, the actual reaction mechanism obeyed deceleration type, phase boundary controlled reaction (R1).

Injection-seeded, gain-switched tunable Cr:ZnSe laser.

We report a narrow-linewidth, tunable, gain-switched Cr:ZnSe laser operating between 2255 and 2455 nm. The spectral width of the laser was reduced from 125 nm to 0.3 nm by using injection seeding. Seeding was achieved with a second tunable CW Cr:ZnSe laser. The output wavelength was varied by tuning the wavelength of the seed laser. The seeded oscillator produced as high as 157 µJ pulses with 598 µJ incident pump pulse energy at a repetition rate of 1 kHz. The slope efficiency was determined to be 26%.

Thermal degradation behavior of methyl methacrylate derived copolymer.

A novel copolymer of 2-hydroxy-3-menthyloxy-1-(4-methoxyphenyl)-3-oxopropyl methacrylate (HMOPMA) and methyl methacrylate (MMA), [poly(HMOPMA-co-MMA)], was synthesized by free radical polymerization. The percentages of HMOPMA and MMA units obtained in the copolymer composition were 19% and 81%, respectively. The solubility parameter of poly(HMOPMA-co-MMA) was found to be 10.3 cal(1/2) cm(-3/2) by turbidimetric titration method. Thermal degradation mechanism and activation energies for initial decomposition process under non-isothermal conditions were determined by integral approximation methods from the thermogravimetric study. The decomposition activation energies of poly(HMOPMA-co-MMA) using Kissinger and Flyn-Wall-Ozawa methods were calculated as 119.99 kJ/mol and 125.34 kJ/mol, respectively. The study of kinetic equations showed that the reaction mechanism of decomposition process in the conversion range studied progressed with D1 mechanism, one-dimensional diffusion of deceleration type of solid state mechanism.

Development of a thulium (Tm:YAP) laser system for brain tissue ablation.

In this study, a thulium (Tm:YAP) laser system was developed for brain surgery applications. As the Tm:YAP laser is a continuous-wave laser delivered via silica fibers, it would have great potential for stereotaxic neurosurgery with highest local absorption in the IR region. The laser system developed in this study allowed the user to set the power level, exposure time, and modulation parameters (pulse width and on-off cycles). The Tm:YAP laser beam (200-600 mW, 69-208 W/cm(2)) was delivered from a distance of 2 mm to cortical and subcortical regions of ex-vivo Wistar rat brain tissue samples via a 200-µm-core optical fiber. The system performance, dosimetry study, and ablation characteristics of the Tm:YAP laser were tested at different power levels by maximizing the therapeutic effects and minimizing unwanted thermal side-effects. The coagulation and ablation diameters were measured under microscope. The maximum ablation efficiency (100 × ablation diameter/coagulation diameter) was obtained when the Tm:YAP laser system was operated at 200 mW for 10 s. At this laser dose, the ablation efficiency was found to be 71.4% and 58.7% for cortical and subcortical regions, respectively. The fiber-coupled Tm:YAP laser system in hence proposed for the delivery of photothermal therapies in medical applications.

Fluence of thulium laser system in skin ablation.

Tm:YAP laser system at power levels up to 1.2 W at 1980 nm was established in both continuous-wave and modulated modes of operation. The fluence effect of the laser system for skin ablation was analyzed by histology analysis with Wistar rat skin tissues. Thermally altered length, thermally altered area, ablation area, and ablation depth parameters were measured on histology images of skin samples just after the laser operation and after four-day healing period. Continuous-wave mode of operation provided higher thermal effects on the skin samples. Lower fluence levels were found for efficient ablation effect.

Modulated and continuous-wave operations of low-power thulium (Tm:YAP) laser in tissue welding.

Our aim is to explore the welding capabilities of a thulium (Tm:YAP) laser in modulated and continuous-wave (CW) modes of operation. The Tm:YAP laser system developed for this study includes a Tm:YAP laser resonator, diode laser driver, water chiller, modulation controller unit, and acquisition/control software. Full-thickness incisions on Wistar rat skin were welded by the Tm:YAP laser system at 100 mW and 5 s in both modulated and CW modes of operation (34.66 Wcm(2)). The skin samples were examined during a 21-day healing period by histology and tensile tests. The results were compared with the samples closed by conventional suture technique. For the laser groups, immediate closure at the surface layers of the incisions was observed. Full closures were observed for both modulated and CW modes of operation at day 4. The tensile forces for both modulated and CW modes of operation were found to be significantly higher than the values found by conventional suture technique. The 1980-nm Tm:YAP laser system operating in both modulated and CW modes maximizes the therapeutic effect while minimizing undesired side effects of laser tissue welding. Hence, it is a potentially important alternative tool to the conventional suturing technique.

Corneal tissue welding with infrared laser irradiation after clear corneal incision.

PURPOSE: The aim of this study was to investigate the potential of infrared lasers for corneal welding to seal corneal cuts done in an experimental animal model. MATERIALS AND METHODS: Full-thickness corneal cuts on freshly enucleated bovine eyes were irradiated with infrared (809-nm diode, 980-nm diode, 1070-nm YLF, and 1980-nm Tm:YAP) lasers to get immediate laser welding. An 809-nm laser was used with the topical application of indocyanine green to enhance the photothermal interaction at the weld site. In total, 60 bovine eyes were used in this study; 40 eyes were used in the first part of the study for the determination of optimal welding parameters (15 eyes were excluded because of macroscopic carbonization, opacification, or corneal shrinkage; 2 eyes were used for control), and 20 eyes were used for further investigation of more promising lasers (YLF and Tm:YAP). Laser wavelength, irradiating power, exposure time, and spot size were the dose parameters, and optimal dose for immediate closure with minimal thermal damage was estimated through histological examination of welded samples. RESULTS: In the first part of the study, results showed that none of the applications was satisfactory. Full-thickness success rates were 28% (2 of 7) for 809-nm and for 980-nm diode lasers and 67% (2 of 3) for 1070-nm YLF and (4 of 6) for 1980-nm Tm:YAP lasers. In the second part of the study, YLF and Tm:YAP lasers were investigated with bigger sample size. Results were not conclusive but promising again. Five corneal incisions were full-thickness welded out of 10 corneas with 1070-nm laser, and 4 corneal incisions were partially welded out of 10 corneas with 1980-nm laser in the second part of the study. CONCLUSIONS: Results showed that noteworthy corneal welding could be obtained with 1070-nm YLF laser and 1980-nm Tm:YAP laser wavelengths. Furthermore, in vitro and in vivo studies will shed light on the potential usage of corneal laser welding technique.

Kerr-lens mode-locked femtosecond Cr(2+):ZnSe laser at 2420 nm.

We describe a cw Kerr-lens mode-locked Cr(2+):ZnSe laser pumped by a 1800 nm thulium fiber laser. The astigmatically compensated asymmetric x cavity contained a 2.4-mm-long Cr(2+):ZnSe sample with a pump absorption coefficient of 11.6 cm(-1) and was operated with a 1% output coupler. The dispersion compensation was achieved by using a MgF(2) prism pair. During Kerr-lens mode-locked operation, we could generate 95 fs pulses at a pulse repetition rate of 94.3 MHz and with 40 mW of output power. The center wavelength of the pulses was 2420 nm. The pulses had a spectral width of 69 nm and a time-bandwidth product of 0.335, which is close to the transform limit for hyperbolic secant pulses.

Synthesis and characterization of poly(acrylic acid) stabilized cadmium sulfide quantum dots.

Cadmium sulfide (CdS) nanoparticles (NPs) capped with poly(acrylic acid) (PAA) were prepared in aqueous solutions from Cd(NO3)2 and Na2S. Influence of the COOH/Cd ratio (0.8-12.5), reaction pH (5.5 and 7.5), and PAA molecular weight (2100 and 5100 g/mol) on the particle size, colloidal stability, and photoluminescence were investigated. A Cd/S ratio of <1 causes ineffective passivization of the surface with the carboxylate and therefore results in a red shift of the absorption band and a significant drop in photoluminescence. Therefore, the Cd/S ratio was fixed at 1.1 for all experiments studying the mentioned variables. PAA coating provided excellent colloidal stability at a COOH/Cd ratio above 1. Absorption edges of PAA-coated CdS NPs are in the range of 460-508 nm. The size of the NPs increases slightly with increasing PAA molecular weight and COOH/Cd ratio at pH 7.5. It is demonstrated that there is a critical COOH/Cd ratio (1.5-2) that maximizes the photoluminescence intensity and quantum yield (QY, 17%). Above this critical ratio, which corresponds to smaller crystal sizes (3.7-4.1 nm) for each reaction set, the quantum yield decreases and the crystal size increases. Moreover, CdS NPs prepared at pH 7.5 have significantly higher QY and absorb at lower wavelengths in comparison with those prepared at pH 5.5. Luminescence quenching has not been observed over 8 months.

Development of a surgical diode-laser system: controlling the mode of operation.

OBJECTIVE: The aim of this study was to develop a microcontroller based surgical diode laser system and to test it at two different modes (continuous [CW] and modulated) in vitro on lamb liver tissue. BACKGROUND DATA: In laser surgery, depending on the properties of laser source (wavelength, power, application time, and mode of operation), the effects observed on the tissue may change from carbonization to hyperthermia. The aim is to remove the target tissue without giving any thermal damage to the surrounding tissue. Carbonization should be avoided, thus controlling the mode of operation is very crucial. METHODS: The system consisted of a microcontroller based control unit, 980-nm high-power diode laser source, and fiber delivery unit. This system has the capability of delivering different modes of laser energy to the target tissue ranging from CW to 20-Hz modulated beams. The surgical diode laser system was tested on liver tissue in vitro. Efficiency of laser-tissue interaction was quantified in terms of thermal alteration per unit energy and corresponding carbonization level. RESULTS: Modulated mode resulted in larger coagulated area with minimum carbonizations. Carbonized area/thermally altered area (CarbA/TAA) ratio for CW mode of operation at 16 J is 0.35; however, this ratio was found to be 0.05 at modulated mode, when even 10 times higher energy (160 J) was delivered to the target tissue. CONCLUSION: Results emphasized the significance of mode of operation as well as the other laser parameters. Modulated mode was found to be a promising regime for safer laser surgery.

An animal model of fetishism.

An animal model of sexual fetishism was developed with male Japanese quail based on persistence of conditioned sexual responding during extinction to an inanimate object made of terrycloth (Experiments 1 and 3). This persistent responding occurred only in subjects that came to copulate with the terrycloth object, suggesting that the copulatory behavior served to maintain the fetishistic behavior. Sexual conditioning was carried out by pairing a conditioned stimulus (CS) with the opportunity to copulate with a female (the unconditioned stimulus or US). Copulation with the CS object and persistent responding did not develop if the CS was a light (Experiment 1) or if conditioning was carried out with a food US (Experiment 2). In addition, subjects that showed persistence in responding to the terrycloth CS did not persist in their responding to a light CS (Experiment 3). The results are consistent with the hypothesis that conditioned copulatory behavior creates a form of self-maintenance that leads to persistent responding to an inanimate object. The development of an animal model of such fetishistic behavior should facilitate experimental analysis of the phenomenon.