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Background Peripheral iridectomy (PI), routinely performed during glaucoma filtration surgery, may contribute to scarring. This study aims to determine whether PI alters the concentrations of VEGF-A and TGF-β isoforms in the rabbit aqueous humour. Methods Anterior chamber paracentesis (ACP) was performed in both eyes of six New Zealand white rabbits, with additional surgical PI performed in the right eyes. Eyes were examined on postoperative days (PODs) 1, 7, 30 and 60 by means of the tonopen, slit-lamp biomicroscopy, and bead-based cytokine assays for TGF-β and VEGF-A concentrations in the aqueous humor. Results ACP caused a significant reduction in intraocular pressure (IOP) from mean preoperative 11.47 ± 1.01 mmHg to 5.67 ± 1.63 mmHg on POD 1 while PI did not cause further IOP reduction. Limbal conjunctival vasculature appeared slightly increased on POD 1 in both ACP and PI eyes with PI also causing mild bleeding from damaged iris vessels. Two PI eyes developed fibrinous anterior chamber reaction and/ or peripheral anterior synechiae. Aqueous VEGF-A levels were not significantly different between eyes treated with ACP and PI. Aqueous TGF-β concentrations distributed in the ratio of 4:800:1 for TGF-β1:TGF-β2:TGF-β3 respectively. While aqueous TGF-β2 was not significantly induced by either procedure at any time point, TGF-β1 and TGF-β3 were significantly induced above baseline levels by PI on POD 1. Conclusion PI increases the risk of inflammation. The combined induction of aqueous TGF-β1 and TGF-β3 by PI in glaucoma surgery may impact surgery success in glaucoma subtypes sensitive to these isoforms.

We examined the safety and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) of the right orbitofrontal cortex (OFC) in patients with refractory obsessive-compulsive disorder (OCD) and comorbid Major Depressive Disorder. All participants (n = 26) received excitatory stimulation of the left dorsolateral prefrontal cortex followed by inhibitory stimulation of bilateral supplementary motor area for 10 sessions. In 18 patients with poor early OCD response, treatment was augmented with OFC inhibitory stimulation after the tenth treatment session. Augmentation with OFC stimulation was well-tolerated, and associated with further alleviation of both OCD and depression symptoms, particularly in individuals with more severe illnesses.

ObjectiveMAPT mutations typically cause behavioral variant frontotemporal dementia with or without parkinsonism. Previous studies have shown that symptomatic MAPT mutation carriers have frontotemporal atrophy, yet studies have shown mixed results as to whether presymptomatic carriers have low gray matter volumes. To elucidate whether presymptomatic carriers have lower structural brain volumes within regions atrophied during the symptomatic phase, we studied a large cohort of MAPT mutation carriers using a voxelwise approach.MethodsWe studied 22 symptomatic carriers (age 54.7±9.1, 13 female) and 43 presymptomatic carriers (age 39.2±10.4, 21 female). Symptomatic carriers' clinical syndromes included: behavioral variant frontotemporal dementia (18), an amnestic dementia syndrome (2), Parkinson's disease (1), and mild cognitive impairment (1). We performed voxel-based morphometry on T1 images and assessed brain volumetrics by clinical subgroup, age, and mutation subtype.ResultsSymptomatic carriers showed gray matter atrophy in bilateral frontotemporal cortex, insula, and striatum, and white matter atrophy in bilateral corpus callosum and uncinate fasciculus. Approximately 20% of presymptomatic carriers had low gray matter volumes in bilateral hippocampus, amygdala, and lateral temporal cortex. Within these regions, low gray matter volumes emerged in a subset of presymptomatic carriers as early as their thirties. Low white matter volumes arose infrequently among presymptomatic carriers.InterpretationA subset of presymptomatic MAPT mutation carriers showed low volumes in mesial temporal lobe, the region ubiquitously atrophied in all symptomatic carriers. With each decade of age, an increasing percentage of presymptomatic carriers showed low mesial temporal volume, suggestive of early neurodegeneration.

Supplemental material, Supplemental material1 for Elevation of cerebrospinal fluid cytokine/chemokines involved in innate, T cell, and granulocyte inflammation in pediatric focal cerebral arteriopathy by Kavitha Kothur, Christopher Troedson, Richard Webster, Sushil Bandodkar, Stephanie Chu, Louise Wienholt, Alun Pope, Mark T Mackay and Russell C Dale in International Journal of Stroke

Supplemental material, Supplemental material2 for Elevation of cerebrospinal fluid cytokine/chemokines involved in innate, T cell, and granulocyte inflammation in pediatric focal cerebral arteriopathy by Kavitha Kothur, Christopher Troedson, Richard Webster, Sushil Bandodkar, Stephanie Chu, Louise Wienholt, Alun Pope, Mark T Mackay and Russell C Dale in International Journal of Stroke

PurposeOur aim was to test the feasibility of a set of quality of care indicators for urinary incontinence and at the same time measure the care provided to women with urinary incontinence in 2 clinical settings.Materials and methodsThis was a pilot test of a set of quality of care indicators. A total of 20 quality of care indicators were previously developed using the RAND Appropriateness Method. These quality of care indicators were used to measure care received for 137 women with a urinary incontinence diagnosis in a 120-physician hospital based multispecialty medical group. We also performed an abstraction of 146 patient records from primary care offices in Southern California. These charts were previously used as part of ACOVE (Assessing Care of Vulnerable Elders Project). As a post-hoc secondary analysis, the 2 populations were compared with respect to quality, as measured by compliance with the quality of care indicators.ResultsIn the ACOVE population, 37.7% of patients with urinary incontinence underwent a pelvic examination vs 97.8% in the multispecialty medical group. Only 15.6% of cases in the multispecialty medical group and 14.2% in ACOVE (p= 0.86) had documentation that pelvic floor exercises were offered. Relatively few women with a body mass index of greater than 25 kg/m(2) were counseled about weight loss in either population (20.9% multispecialty medical group vs 26.1% ACOVE, p = 0.76). For women undergoing sling surgery, documentation of counseling about risks was lacking and only 9.3% of eligible cases (multispecialty medical group only) had documentation of the risks of mesh.ConclusionsQuality of care indicators are a feasible means to measure the care provided to women with urinary incontinence. Care varied by population studied and yet deficiencies in care were prevalent in both patient populations studied.

Paclitaxel (PTX) is an effective anti-mitotic drug. It stops cancer from spreading by interfering with the microtubule dynamics which in turn leads to cell cycle arrest and eventually cell death. Despite the clinical success in treating different types of cancers, resistance to PTX remains a major hurdle for successful treatment in relapse patients. Albendazole (ABZ) is a popular anthelmintic used world-wide for the treatment of various types of helmintic infections. In helminthes, ABZ binds to β-tubulin and inhibits microtubule polymerisation. It was subsequently found that ABZ has anti-cancer activity. This study was carried out to study the effects of ABZ on PTX sensitive and PTX resistant human ovarian carcinoma cells. Cell growth assays revealed that the anti-proliferative activity of ABZ was not only effective on the PTX-sensitive human ovarian carcinoma cell line lA9, but also on its PTX-resistant sub-line, lA9PTX22. The ICso values of ABZ in lA9 and lA9PTX22 were 205 nM and 322 nM, respectively. Confocal images demonstrated that ABZ disrupted the microtubule network and caused formation of short microtubule bundles in both cell lines. Further analysis using tubulin polymerisation assay showed that the percentage of polymerised tubulin in lA9 and lA9PTX22 was increased by 58.9 % and 20.6 % respectively. Together, these results revealed for the first time that ABZ interacts with microtubules in human cancer cells and causes their polymerisation. It was also demonstrated that ABZ increased the release of cytochrome c, an important component of the intrinsic pathway in apoptosis. It was found that the expression of Bim, a BH-3 only pro-apoptotic protein was not elevated after ABZ treatment. The results presented in this study provide some information on the effect of ABZ on the microtubule network which could relate to its apoptotic effect in human ovarian carcinoma cells.