The psoriatic great toe or the psoriatic onycho-pachydermo-periostitis of great toe (OP3gt)

The onycho-pachydermo-periostitis of the great toe is a characteristic feature of psoriatic arthritis first described by Fournie in 1980. In the affected patients, the great toe involvement is characterised by a relevant osteo-periostitis of the distal phalanx, a thickening of the distal soft tissues associated with a psoriatic onychopathy. In most cases, the distal interphalangeal joint is spared. Radiographic and scintigraphic osteo-periostitis of distal phalanx of the great toe are frequent, being found in about 44% of patients with psoriatic arthritis. However, clinical manifestations, with inflammatory inflammation of the great toe, are rare

Subclinical atherosclerosis in patients with psoriatic arthritis: a case-control study. Preliminary data

Objective: The aim of this study was to evaluate the prevalence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA), correlated with some traditional risk factors of atherosclerosis and with PsA-related disease factors. Methods: Forty-one patients and 41 healthy subjects were evaluated for intima-media thickness (IMT) and flow-mediated dilation (FMD), using carotid duplex scanning. IMT values were expressed like IMT mean (cumulative mean of all the IMT mean) and M-MAX (cumulative mean of all the higher IMT). Subclinical atherosclerosis markers were correlated with age, body mass index (BMI) and blood pressure in both groups, with duration of arthritis, duration of psoriasis, tender and swollen joints, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), BASFI (Bath Ankylosing Spondylitis Functional Index), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients. Results: IMT mean and M-MAX were both higher in PsA patients compared with controls (0.7±0.15 vs 0.62±0.09 mm; p<0.01 and 0.86±0.21 vs. 0.74±0.13 mm; p<0.01 respectively). FMD was smaller in patients than in controls (5.9±2 vs 7.5±2.8%; p<0.01). Univariate analysis showed a correlation between IMT mean and SBP (r=0.217; p=0.05) and a correlation between M-MAX and age (r=0.392; p<0.001), BMI (r=0.252; p<0.05), SBP (r=0.446; p<0.001) in both groups. In PsA patients M-MAX resulted correlated with ESR (r=0.338; p<0.05) and BASDAI (r=0.322; p<0.05). Conclusions: PsA patients exhibited endothelial dysfunctions which is an early marker of subclinical atherosclerosis, as well as an higher IMT. An interesting correlation between M-MAX and PsA activity index (ESR and BASDAI) was found

A contemporary dose selection algorithm for stereotactic radiosurgery in the treatment of brain metastases - An initial report.

Indications and treatment goals for SRS have changed since the publication of RTOG 90-05. We present initial retrospective outcomes from a new dose selection algorithm in use at our institution felt to be more contemporary with doses being used in the radiosurgery community today and report our local control and toxicity outcomes. This dose selection algorithm will be subject to a forthcoming prospective phase 2 trial.To evaluate safety and efficacy of an institutional dose selection algorithm in the treatment of brain metastases (BM) with single fraction radio-surgery (SRS).The medical records of 65 patients with ≤10 BM treated with GK at our institution between April 2012 and October 2012 were reviewed retrospectively. The prescription doses used in this study ranged from 16-22Gy and were based upon RTOG 90-05 guideline doses subsequently modified at our institution depending on lesion number, lesion volume, institutional experience and prior history of whole brain radiation therapy (WBRT). Primary endpoint was local recurrence (LR) with additional outcomes measured including distant intracranial recurrence (DIR), death without local recurrence (DWLR) and alive and disease free (ADF). Fine Gray competing risk analysis was used to examine factors affecting local recurrence.Median follow up was 8.9 months (range 1.0-29.6months) and 12 month overall survival was 37% (95% CI 24.9-49.1%). Overall local recurrence rate was 7.7%. On competing risks regression analysis, no variable was significantly associated with local recurrence, including previous whole brain radiotherapy (WBRT), (SHR 1.21 [95%CI 0.13-11.5], p=0.87 and radioresistant versus radiosensitive histology (SHR 0.51 [95% CI 0.06-7.73], p=0.55). No patient developed grade 3 or higher neurotoxicity at 12 months following GK.Initial local control and toxicity results from our institutional dose selection algorithm are reported here. Comparison of our results with RTOG 90-05 is difficult due to significant differences in the patient population and their treatments. The applicability of this algorithm merits further investigation across multiple centers for the purpose of treatment and clinical trial standardization in single fraction SRS and will be the subject of a forthcoming phase 2 prospective study within our own institution

Ability-Based Methods for Personalized Keyboard Generation

This study introduces an ability-based method for personalized keyboard generation, wherein an individual's own movement and human-computer interaction data are used to automatically compute a personalized virtual keyboard layout. Our approach integrates a multidirectional point-select task to characterize cursor control over time, distance, and direction. The characterization is automatically employed to develop a computationally efficient keyboard layout that prioritizes each user's movement abilities through capturing directional constraints and preferences. We evaluated our approach in a study involving 16 participants using inertial sensing and facial electromyography as an access method, resulting in significantly increased communication rates using the personalized keyboard (52.0 bits/min) when compared to a generically optimized keyboard (47.9 bits/min). Our results demonstrate the ability to effectively characterize an individual's movement abilities to design a personalized keyboard for improved communication. This work underscores the importance of integrating a user's motor abilities when designing virtual interfaces.Comment: 20 pages, 7 figure

Assessing the Cultural Appropriateness of UPLIFT for African Americans With Epilepsy: A Community Engaged Approach

Background: In trials of Project UPLIFT, a distance-delivered, mindfulness-based cognitive therapy intervention, there was improvement in the mental health of people with epilepsy/seizure disorder. In these trials, however, African Americans have been few. Thus, as this program is disseminated, it is desirable to ensure that it is culturally appropriate for minority populations. Methods: To determine the appropriateness of Project UPLIFT for African Americans, we engaged in three main research activities: 1) the formation and involvement of an epilepsy community advisory board; 2) qualitative interviews with healthcare providers who serve this community; and 3) focus groups with African American adults living with epilepsy or seizure disorder and main support persons of African American adults living with epilepsy or seizure disorder. Results: The epilepsy community advisory board provided recommendations for the most appropriate language to use when engaging and recruiting the target population. Healthcare providers indicated that psychosocial concerns of African American persons living with epilepsy seemed to be different from those among patients of other racial groups. They indicated that Project UPLIFT might be useful for this group. Focus groups revealed experiences of living with and supporting someone with epilepsy and provided favorable feedback on the UPLIFT intervention. Conclusions: Formative feedback indicates that Project UPLIFT may be useful for African Americans with epilepsy. These data will be used to guide a forthcoming randomized, controlled trial to assess the acceptability and feasibility of the intervention with this group

Inhibition of N-linked glycosylation impairs ALK phosphorylation and disrupts pro-survival signaling in neuroblastoma cell lines

<p>Abstract</p> <p>Background</p> <p>The Anaplastic Lymphoma Kinase (ALK) is an orphan receptor tyrosine kinase, which undergoes post-translational N-linked glycosylation. The catalytic domain of ALK was originally identified in the t(2;5) translocation that produces the unglycosylated oncogenic protein NPM-ALK, which occurs in Anaplastic Large Cell Lymphoma (ALCL). Recently, both germline and somatic activating missense mutations of ALK have been identified in neuroblastoma (NB), a pediatric cancer arising from neural crest cells. Moreover, we previously reported that ALK expression is significantly upregulated in advanced/metastatic NB. We hypothesized that ALK function may depend on N-linked glycosylation and that disruption of this post-translational modification would impair ALK activation, regardless the presence of either gene mutations or overexpression.</p> <p>Methods</p> <p>We employed tunicamycin to inhibit N-linked glycosylation. The following ALK-positive NB cell lines were used: SH-SY5Y and KELLY (ALK mutation F1174L), UKF-NB3 (ALK mutation R1275Q) and NB1 (ALK amplification). As a control, we used the NB cell lines LA1-5S and NB5 (no ALK expression), and the ALCL cell line SU-DHL1 (NPM-ALK).</p> <p>Results</p> <p>Tunicamycin treatment of ALK-positive NB cells resulted in a hypoglycosylated ALK band and in decreased amounts of mature full size receptor. Concomitantly, we observed a marked reduction of mature ALK phosphorylation. On the contrary, tunicamycin had no effects on NPM-ALK phosphorylation in SU-DHL1 cells. Moreover, phosphorylation levels of ALK downstream effectors (AKT, ERK1/2, STAT3) were clearly impaired only in ALK mutated/amplified NB cell lines, whereas no significant reduction was observed in both ALK-negative and NPM-ALK-positive cell lines. Furthermore, inhibition of N-linked glycosylation considerably impaired cell viability only of ALK mutated/amplified NB cells. Finally, the cleavage of the Poly-ADP-ribose-polymerase (PARP) suggested that apoptotic pathways may be involved in cell death.</p> <p>Conclusions</p> <p>In this study we showed that inhibition of N-linked glycosylation affects ALK phosphorylation and disrupts downstream pro-survival signaling, indicating that inhibition of this post-translational modification may be a promising therapeutic approach. However, as tunicamycin is not a likely candidate for clinical use other approaches to alter N-linked glycosylation need to be explored. Future studies will assess whether the efficacy in inhibiting ALK activity might be enhanced by the combination of ALK specific small molecule and N-linked glycosylation inhibitors.</p