(J Am Vet Med Assoc 2011;239:992-997)”
“Karyomegalic interst

(J Am Vet Med Assoc 2011;239:992-997)”
“Karyomegalic interstitial nephritis (KIN) is a rare and certainly underdiagnosed nephropathy. selleck kinase inhibitor It is characterized by a peculiar histological picture of interstitial nephritis associated with the presence of hyperchromatic, abnormally enlarged nuclei of tubular epithelial cells. KIN has an uncertain etiology, but should be suspected in young patients in the second or third decade of life presenting with progressive renal failure, proteinuria and/or hematuria and a history of recurrent respiratory infections. In these cases, the diagnosis should

be suspected and confirmed by a renal biopsy. Herein, we report a case of KIN with atypical clinical presentation in a young patient with progressive kidney failure without proteinuria or hematuria or history of recurrent respiratory infections.”
“Study Design. Biomechanical evaluation of

occipitocervical instrumentation techniques.

Objective. Compare methods of occipital instrumentation by quantifying load sharing of occipital screws and measuring motion across instrumented occipitocervical PCI32765 spines.

Summary of Background Data. Newer occipitocervical plate/screw systems that attach to longitudinal rods have been developed to improve fixation. These devices place screws in the center of occipital bone or off- midline. Midline plates offer screw purchase in thicker bone. Off-midline systems may increase the effective moment arm for torsional and lateral bending control. Measurement of screw loads within occipital plates is useful for determining optimal plate configuration.

Methods. Ten cadaveric specimens (occiput-C4) were tested in flexion/extension (FE),

lateral bending (LAT), and axial rotation (ROT) over +/- 3 Nm pure moment. After intact testing, 4 occipitocervical fixation constructs were tested using washer load cells to assess loading across screws used to fix the plates to the occiput. Parasagittal occipital plates were positioned either convex or concave side facing medially. Each plate was first fixed using 3 screws (rostral, middle, caudal), then with the caudal screw eliminated (simulated failure). Range of motion (ROM) and peak screw loads are reported.

Results. ROM decreased from intact to any GW786034 of the 4 fusion plate configurations in FE, LAT, and ROT (P << 0.05), but not between plate configurations. Screw load significantly decreased from medially convex to medially concave configurations in LAT, but no significant changes were observed in FE or ROT. With caudal screws removed, middle screws peak loads significantly increased in FE and LAT (P << 0.05), but not ROT.

Conclusion. Occipital screw placement off- midline improves screw loads under lateral bending forces on occipitocervical constructs, though loads for FE and ROT are unchanged. As screws pullout, the loads may be redistributed, resulting in increased screw pullout forces above.

The centroid method is most reliable

and least influenced

The centroid method is most reliable

and least influenced by experience. The EP method is easy to perform and very reliable. Spine surgeons should pick their preferred method and apply it consistently. Changes >= 3-mm suggest RS progression. RS may be a useful measure in addition to Cobb angle in AS. Having defined measurement reliability, the role of RS progression in surgical indications and Cell Cycle inhibitor patient outcomes can be evaluated.”
“The chromosomal translocation (11;14)(q13;q32) rearranging the locus for cyclin D1 (CCND1) to that of the immunoglobulin heavy chain (IGH) can be found in virtually all cases of mantle cell lymphoma (MCL), while other CCND1 translocations are extremely rare. As CCND1 overexpression and activation is a hallmark of MCL it is regarded as a central biological mechanism in the development and maintenance of this disease. Here we present a patient initially diagnosed with chronic lymphocytic leukemia (CLL) where chromosome banding analysis revealed, among other aberrations, a translocation (11;22)(q13;q11.2). We show by fluorescence in situ

hybridization (FISH) analysis that on chromosome 22 the immunoglobulin light chain lambda (IGL) is involved in this cytogenetic aberration. Additionally, we demonstrate the resulting overexpression of CCND1 on the RNA and protein level, thereby consolidating the new diagnosis of a MCL-like B-cell neoplasia. Summing up, we described a rare case of t(11;22)(q13;q11.2) in a MCL-like neoplasia and showed click here that this aberration leads to an overexpression of CCND1 which is regarded as a key biological feature in MCL. This case underlines the importance of cytogenetic analyses especially in atypical cases of B cell lymphomas.”
“Background Impregnation of activated carbon or oxidized activated carbon was carried out using iron(III) nitrate as starting solution and ammonia as the precipitating agent, intending the removal from aqueous solution of arsenates a priority pollutant. The high affinity of

iron oxyhydroxide Trichostatin A nanocrystals toward inorganic arsenic species is known. Activated carbon, on the other hand, can provide a high surface area for adsorption. The initial materials and those after adsorption of arsenate were characterized, in order to explain the adsorption enhancing effect found, when using this precipitating agent. Results The role of carbon surface chemistry and structural heterogeneity on iron oxyhydroxide and thus, on the adsorption of arsenate were investigated. The study of the materials was carried out by adsorption of nitrogen, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and thermal analysis.

The objective of this paper is to describe the development of an

The objective of this paper is to describe the development of an analytic process to organize and synthesize data from a realist review.

Methods: Clinical practice guidelines have had an inconsistent and modest impact on clinical practice, which may in part be due to limitations in their design. This study illustrates the development of a transparent method for organizing and analyzing a complex data set informed by a Realist Review on guideline

implementability to better understand the characteristics of guidelines that affect their uptake in practice (e.g., clarity, format). The data organization method consisted of 4 levels of refinement: 1) extraction and 2) organization of data; 3) creation of a conceptual map of guideline implementability; and 4) the development of a codebook of definitions.

Results: SCH772984 research buy This new method is comprised of four steps: data extraction, data organization, development of a conceptual map, and operationalization vis-a-vis a codebook. Applying this method, we extracted 1736

guideline attributes from 278 articles into a consensus-based set of categories, and collapsed them into 5 core conceptual domains for our selleckchem guideline implementability map: Language, Format, Rigor of development, Feasibility, Decision-making.

Conclusions: This study advances analysis methods by offering a systematic approach to analyzing complex data sets where the goals are to condense, organize and identify relationships.”
“Objective-To estimate the relative risk of paratuberculosis (Johne’s disease [JD]) in calves fed a plasma-derived colostrum-replacement (CR) product versus raw bovine maternal colostrum Mdivi1 (MC).

Study Design-Randomized controlled clinical trial.

Animals-497 heifer calves born in 12 JD-endemic commercial Holstein dairy farms located in Minnesota and Wisconsin.

Procedures-Every calf was separated from its dam

within 30 to 60 minutes after birth and systematically assigned to be fed raw bovine MC (control group, n = 261 calves) or CR (treatment group, 236 calves). The calves were monitored to adulthood and tested for Mycobacterium avium subsp paratuberculosis (MAP) infection by use of an ELISA to detect serum antibodies against MAP and bacterial culture for MAP in feces at approximately 30, 42, and 54 months of age. Weibull regression models were used to evaluate the effect of feeding CR (vs raw bovine MC) on the risk of developing JD infection.

Results-Calves fed CR at birth were less likely (hazard ratio = 0.559) to become infected with MAP (as determined by use of an ELISA, bacterial culture, or both diagnostic tests), compared with the likelihood for calves fed MC at birth.

Conclusions and Clinical Relevance-This study revealed that feeding CB reduced the risk of developing MAP infection in Holstein calves born in JD-endemic herds, which implied that feeding raw bovine MC may be a source of MAP for calves.

Identifying effective strategies for identifying and treating the

Identifying effective strategies for identifying and treating these obesity related co-morbidities in children are crucial to the prevention of future cardiovascular disease and poor health outcomes. This review discusses the pathophysiologic connections between obesity, metabolic disease and cardiovascular risk. Current evidence and recommendations for screening and treatment for the metabolic consequences of pediatric obesity are reviewed.”
“Non-alcoholic fatty liver disease click here (NAFLD) is a very common condition among obese patients that may lead to the enlargement of the liver, that in turn impairs the access to the gastro-esophageal

junction during laparoscopic bariatric surgery. Omega-3

polyunsaturated fatty acids (Omega-3 PUFAs) supplementation has been shown to reduce nutritional hepatic steatosis. The aim of this study was to assess the effects of a 4-week course of oral Omega-3 PUFAs supplementation on the volume of the liver.

20 morbidly obese patients were administered oral Omega-3 PUFAs (1,500 mg daily) for 4 weeks before undergoing the laparoscopic Roux-en-Y gastric bypass (LRYGBP) without any dietary restriction. The volume of the left hepatic MK-2206 lobe was estimated by liver ultrasonography at baseline and at the end of treatment. The degree of difficulty to access the gastro-esophageal junction was appreciated subjectively by the operating surgeon.

All patients completed the study and no side effect was reported. The mean volume of the left hepatic lobe decreased by 20 % from 598 +/- 97 to 484 +/- 118 cm(3) after the treatment (p = 0.002). The access to the gastro-esophageal junction was reported as simple, with easy retraction of

the left hepatic Stem Cell Compound Library in vitro lobe by the operating surgeon in all cases.

This study demonstrates that a 4-week course of oral Omega-3 PUFAs supplementation results in a significant reduction in liver size that facilitates the LRYGBP.”
“Hydroxychloroquine (HCQ) is used as the first-line systemic treatment for severe, widespread or refractory cutaneous lupus erythematosus (CLE) in many countries. However HCQ is not an approved drug in Japan. For the establishment of HCQ therapy as the alternative treatment for CLE in Japan, we conducted a pilot study in Japanese patients with refractory CLE by administrating HCQ, and evaluated the improvements in the skin lesions using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). We administrated HCQ to seven CLE cases, including four systemic lupus erythematosus (SLE) cases. The skin lesions of the four cases improved dramatically, and their mean CLASI activity index decreased significantly following HCQ treatment.

Although it is well known that CAs are particularly

Although it is well known that CAs are particularly this website relevant to adult cardiac surgery with hypothermic cardiopulmonary bypass (CPB), paediatric cardiac surgery with congenital heart disease and with CAs has been reported very rarely. We present here a case of paediatric cardiac surgery to repair atrial septal defect with pulmonary stenosis in an 11-month old infant with a family history of CAs. She was detected to have a high titre of CAs preoperatively, and underwent an intracardiac repair with normothermic CPB using temporary electrical fibrillation for added safety. Her post-operative course was uneventful without any

complications.”
“Semen preparation and cryopreservation require finely adjusted procedures. Gametes are sensitive to environmental stresses, so in vitro procedures aim to minimize the inevitable harmful conditions. Applying stress to precondition cells has only

been investigated recently. Studies demonstrated that by utilizing a well defined and properly applied hydrostatic pressure (HP) stress treatment to spermatozoa before in vitro GSK1210151A order storage, cryopreservation or insemination, cell survival and fertility improved compared with untreated controls. The birth of healthy piglets from treated fresh or frozen-thawed semen demonstrates the in vivo safety of the procedure. Although the biological mechanism is still unclear, several processes incorporating cellular stress response might explain the observations. This paper summarizes results, background, aspects and considerations of HP treatment for porcine semen. The new principle, i.e. to improve the stress tolerance by a defined sublethal stress

may outline a new strategy in assisted reproductive technologies with unique theoretical and practical consequences.”
“Background-Social gradients in cardiovascular mortality across the United Kingdom may reflect differences in incidence, disease severity, or treatment. It is unknown whether a universal healthcare system delivers equitable lifesaving medical therapy for coronary heart disease. We therefore examined secular trends in the use of key medical therapies stratified by socioeconomic circumstances across a broad Adriamycin spectrum of coronary disease presentations, including acute coronary syndromes, secondary prevention, and clinical angina.

Methods and Results-This was a cross-sectional observational analysis of nationally representative primary and secondary care data from the United Kingdom. Data on treatments for all myocardial infarction patients in 2003 and 2007 were derived from the Myocardial Ischemia National Audit Project (n=51 755). Data on treatments for patients with chronic angina (n=33 211) or requiring secondary prevention (n=32 976) in 1999 and 2007 were extracted from the General Practice Research Database.

These VLPs may represent a novel vaccine strategy for the control

These VLPs may represent a novel vaccine strategy for the control of EMCV infection

on pig farms. (C) 2010 Elsevier Ltd. All rights reserved.”
“A bidirectional relationship exists between diabetes mellitus (DM) and major depressive disorder (MDD), with depression commonly reported in both type 1 DM (T1DM) and type 2 DM (T2DM), and depressive symptoms associated with a higher incidence of diabetes. However, how the two conditions are pathologically connected is not completely understood. Similar neurophysiological abnormalities have been reported in both DM and MDD, including elevated electroencephalographic Nutlin-3a clinical trial (EEG) activity in low-frequency slow waves and increased latency and/or reduced amplitude of event-related potentials. Elacridar mouse It is possible that this association reflects some common underlying pathology, and it has been proposed that diabetes may place patients at risk for depression through a biological mechanism linking the metabolic changes

of DM to changes in the central nervous system. In this review we will discuss EEG abnormalities in DM, as well as the biological mechanisms underlying various EEG parameters, in order to evaluate whether or not a common EEG biosignature exists between DM and MDD. Identifying such commonalities could significantly inform the current understanding of the mechanisms that subserve the development of the two conditions. Moreover, this new insight may provide the basis for informing new drug discovery capable of mitigating and possibly even preventing both conditions.”
“Porcine circovirus type 2 (PCV2) is the essential Acalabrutinib inhibitor infectious agent of postweaning multisystemic wasting syndrome

(PMWS) considered as one of the most important swine diseases worldwide. One of the main risk factors reported for the development of PMWS is the PCV2 genotype. The presence of PCV2 in Cuban swine herds has been reported recently. However, genetic information about these viruses is not available yet. Hence, the objectives of this study were to classify the Cuban porcine circovirus type 2 sequences as well as to investigate the genetic diversity and the putative origins of the virus circulating in Cuban swine herds. PCV2 Cuban sequences appeared to be close related when an analysis of the entire viral genome sequences was performed. The main variations on amino acid sequences of the capsid protein were found within the immunoreactive areas. All the Cuban PCV2 sequences analyzed belonged to genotype 1 and were located within the same Cluster (1A). Interestingly, five of them were clustered with high confident values with those described as the PCV2 variants associated with severe porcine circovirus diseases reported in Canada from the late 2004 to 2006. Pigs imported from this source appeared to be the most probable origin of the viruses circulating in Cuban swine herds currently.

Conclusion Radial tears and herniation are significant predictor

Conclusion. Radial tears and herniation are significant predictors of progressive nuclear degeneration, which was not seen in the absence of radial tears. End plate defects also frequently occur before nuclear degeneration but rarely in the absence of anular tears.”
“Semi and full interpenetrating network (IPN) hydrogels were synthesized by allowing free radical copolymerization of acrylic acid (AA) and hydroxyethyl methacrylate (HEMA) in the matrix of polyvinyl alcohol (PVOH). Accordingly, Givinostat chemical structure four different semi IPN hydrogels

were prepared with PVOH: copolymer mass ratio of 1 : 1, 1 : 0.75, 1 : 0.5, and 1 : 0.25. These hydrogels were designated as SEMIIPN1, Z VAD FMK SEMIIPN2, SEMIIPN3, and SEMIIPN4, respectively. In all of these SEMIIPN, after polymerization PVOH was crosslinked with 2 mass % glutaraldehyde to form the semi IPN structure. In a similar way, sequential full IPN were prepared from PVOH and copolymer of AA and HEMA (designated as PAAHEMA) with same composition except in this case apart from crosslinking of PVOH by 2 mass % glutaraldehyde the PAAHEMA copolymer was

further crosslinked with N,N’-methylenebisacrylamide (NMBA) to produce four full IPN hydrogels designated as FULLIPN1, FULLIPN2, FULLIPN3, and FULLIPN4. All of these semi and full IPN type hydrogels were characterized by carboxylic %, FTIR, UV, DTA-TGA, XRD, SEM, and mechanical properties. The network parameters, swelling

and diffusion characteristics buy Talazoparib of these hydrogels were also studied. The performance of these semi and full IPNs were compared in terms of their relative abilities for removing varied concentration of rhodamine B (RB) and methyl Violet (MV) dyes from water. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012″
“The brittle culm (bc) mutants of Gramineae plants having brittle skeletal structures are valuable materials for studying secondary cell walls. In contrast to other recessive bc mutants, rice Bc6 is a semi-dominant bc mutant with easily breakable plant bodies. In this study, the Bc6 gene was cloned by positional cloning. Bc6 encodes a cellulose synthase catalytic subunit, OsCesA9, and has a missense mutation in its highly conserved region. In culms of the Bc6 mutant, the proportion of cellulose was reduced by 38%, while that of hemicellulose was increased by 34%. Introduction of the semi-dominant Bc6 mutant gene into wild-type rice significantly reduced the percentage of cellulose, causing brittle phenotypes. Transmission electron microscopy analysis revealed that Bc6 mutation reduced the cell wall thickness of sclerenchymal cells in culms. In rice expressing a reporter construct, BC6 promoter activity was detected in the culms, nodes, and flowers, and was localized primarily in xylem tissues.

7-14 0 mg/kg per d) Five patients developed self-injurious and v

7-14.0 mg/kg per d). Five patients developed self-injurious and violent behaviors. Two patients developed severe insomnia. The most affected patient was a 6-year-old boy whose mood and affect became extremely volatile. He also experienced threatening visual and

auditory hallucinations and insomnia. All 9 patients had dramatic improvement and/or resolution of the adverse neurobehavioral Milciclib supplier effects following discontinuation or reduction of lamotrigine. Reversible, severe neurobehavioral disturbances associated with lamotrigine therapy have not been reported in the literature. While idiosyncratic and uncommon, this is a potentially significant, clinical side effect. Further studies are necessary to clarify the population at risk.”
“Viral infections of the pediatric central nervous system (CNS) encompass a broad spectrum of both perinatally and postnatally acquired diseases with potentially devastating effects on the developing brain. In children, viral infections have been associated with chronic encephalopathy, encephalitis, demyelinating disease, tumors, and epilepsy. Older diagnostic techniques of biopsy, viral culture, electron microscopy, gel-based polymerase chain reaction (PCR), and viral titer quantification are being replaced with more rapid, sensitive, and specific real-time and microarray-based PCR technologies. Advances in neuroimaging technologies have provided

for earlier recognition of CNS injury without elucidation of specific viral etiology. Although the mainstay therapy of many pediatric neurovirologic diseases, JNK-IN-8 molecular weight aside from HIV, includes intravenous acyclovir, much work is being done to develop novel antiviral immunotherapies aimed at both treating and preventing pediatric CNS viral disease.”
“Flavonoids are low molecular weight secondary plant metabolites with a myriad of

functions. As flavonoids affect auxin transport (an important growth-controlling hormone) and are biologically active in eukaryotes, flavonoid mutants were expected to have undescribed architectural phenotypes. The Arabidopsis thaliana transparent testa (tt) mutants are compromised in the enzymatic steps or transcriptional regulators affecting flavonoid synthesis. tt mutant seedlings were grown on hard-slanted GW2580 agar (a stress condition), under varying light conditions, and in soil to examine the resulting growth patterns. These tt mutants revealed a wide variety of architectural phenotypes in root and aerial tissues. Mutants with increased inflorescences, siliques, and lateral root density or reduced stature are traits that could affect plant yield or performance under certain environmental conditions. The regulatory genes affected in architectural traits may provide useful molecular targets for examination in other plants.”
“Pancreatic ductal adenocarcinoma is known as one of the most fatal malignant diseases in gastrointestinal system.

We investigated whether the capacity of serum to induce cholester

We investigated whether the capacity of serum to induce cholesterol efflux was associated with endothelial dysfunction in type 2 diabetes. Methods: Endothelium-dependent and-independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound

and serum cholesterol efflux capacity was determined by measuring the transfer of [3H] cholesterol selleck screening library from Fu5AH cells to serum in 137 patients with type 2 diabetes and 75 controls. Results: Serum cholesterol efflux capacity was lower in diabetic patients than in the controls (13.6+/-2.5% vs. 14.6+/-3.4%, respectively, p=0.02), and both endothelium-dependent vasodilation (4.9+/-2.2% vs. 8.8+/-4.1%, respectively, p<0.01) and endothelium-independent vasodilation were impaired (13.4+/-4.3% vs. 16.3+/-5.5%. respectively, p<0.01). Endothelium-dependent vasodilation correlated with serum cholesterol efflux capacity (r=0.26, p=0.003) in diabetic patients and controls (r=0.24, p=0.037). On general linear model analysis, the presence of diabetes, brachial artery diameter and serum cholesterol efflux capacity were significant independent determinants of endothelium-dependent vasodilation. Conclusion: Impaired serum cholesterol efflux capacity was associated with endothelial dysfunction independent of other cardiovascular risk

factors.”
“To improve the interaction between syndiotactic polypropylene (SPP) and fibrous cellulose (FC), the effects of the addition of maleated polypropylene (MAPP) and FC surface modification with 3-aminopropyltriethoxysilane (APTES) on SPP/FC composites were studied with respect to the morphology and the tensile properties. CH5183284 purchase The

addition of MAPP brought about an improvement in the interfacial adhesion between SPP and FC according to scanning electron microscopy observations and tensile testing. This improvement was, however, less effective than the improvement in the interfacial adhesion between isotactic polypropylene (IPP) and FC. SPP and MAPP partially or microscopically phase-separated because of the IPP-like polymer chain structure of MAPP. With respect selleck kinase inhibitor to the compatibility between SPP and FC, FC surface modification with APTES was more suitable. The increase in Young’s modulus was remarkable in the SPP/silanized FC composite with APTES. The tensile strength of the SPP/silanized FC composite with APTES was, however, considerably lower than that of the SPP/FC/MAPP composite. These results suggest that interfacial improvement between SPP and FC requires a compatibilizer or a surface modifier with a suitable primary structure. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 113: 2022-2029, 2009″
“Alterations of elastic properties may contribute to the accelerated atherosclerosis in patients with T2D. Little is known, however, about radial artery distensibility in this patient group. A total of 19 patients with T2D and 19 controls were investigated.


“Opinion statement

Headache and migraine are co


“Opinion statement

Headache and migraine are common symptoms of the menopause, often associated with irregular periods, hot. ashes, and night sweats. Perimenopausal women should routinely be asked about headache and migraine, so that they can be offered appropriate advice. If attacks are infrequent, it may be sufficient to optimize acute treatment strategies. Lifestyle

changes, alone or combined with a nonprescription treatment such as isoflavones, may be considered, although evidence of efficacy is limited. In women with migraine and more severe menopause symptoms, continuous hormone replacement therapy should be considered, using a nonoral route and the lowest dose effective in controlling symptoms. For women who have contraindications to estrogen therapy or do not wish to use it, compounds that inhibit serotonin buy ABT-263 reuptake, such as venlafaxine,fluoxetine,

and paroxetine, have all shown efficacy for the control of hot. ashes and prevention of migraine. Gabapentin is another nonhormonal option that has clinical trial evidence of effectiveness in treating hot. ashes and reducing the frequency and severity of migraine attacks. Although clonidine is licensed in several countries for migraine prophylaxis and treatment of vasomotor symptoms, any benefit Temsirolimus mouse from treatment is often offset by adverse events. There is evidence that hysterectomy can increase the frequency of migraine and menopause symptoms, with added morbidity and risk of mortality. Therapy should regularly be evaluated to assess its ongoing need, as hormonal triggers are self-limiting and abate after menopause.”
“In this study, antioxidant and anti-photoaging activities of 2-methoxy-5-(2-methyl propyl) pyrazine

(MMPP) isolated from peach (Prunus persica (L.) Batsch) were investigated in terms of matrix metalloproteinase (MMP)-1 and type-1 procollagen expression in ultraviolet (UV)-irradiated human skin fibroblasts. MMPP was obtained from the butanol fraction of a 95% ethanol extract of peach. The antioxidant and anti-photoaging activity of MMPP were assessed by 1,1-diphenyl-2-picrylhydrazy (DPPH), Western blot, and Ilomastat reverse trans-cription-polymerase chain reaction (RT-PCR) analyses. MMPP displayed radical scavenging activity, suppressed MMP-1 expression, and increased type-1 procollagen expression. These results support the use of MMPP from peach as an anti-photoaging compound.”
“Opinion statement

Recent scientific data support an effect of botulinum neurotoxin (BoNT) on pain and headache. BoNT was shown to affect the release of neurotransmitters that are important in pain transmission and in migraine pathogenesis. Data from both animal and clinical studies suggest that the toxin may have an analgesic effect that is independent from its effect on muscle tone. The high tolerability and long duration of action of the drug make it appealing as a potential prophylactic treatment for headache patients.