Recommended Resting-State fMRI Acquisition and Preprocessing Steps for Preoperative Mapping of Language and Motor and Visual Areas in Adult and Pediatric Patients with Brain Tumors and Epilepsy.

Resting-state (rs) fMRI has been shown to be useful for preoperative mapping of functional areas in patients with brain tumors and epilepsy. However, its lack of standardization limits its widespread use and hinders multicenter collaboration. The American Society of Functional Neuroradiology, American Society of Pediatric Neuroradiology, and the American Society of Neuroradiology Functional and Diffusion MR Imaging Study Group recommend specific rs-fMRI acquisition approaches and preprocessing steps that will further support rs-fMRI for future clinical use. A task force with expertise in fMRI from multiple institutions provided recommendations on the rs-fMRI steps needed for mapping of language, motor, and visual areas in adult and pediatric patients with brain tumor and epilepsy. These were based on an extensive literature review and expert consensus.Following rs-fMRI acquisition parameters are recommended: minimum 6-minute acquisition time; scan with eyes open with fixation; obtain rs-fMRI before both task-based fMRI and contrast administration; temporal resolution of ≤2 seconds; scanner field strength of 3T or higher. The following rs-fMRI preprocessing steps and parameters are recommended: motion correction (seed-based correlation analysis [SBC], independent component analysis [ICA]); despiking (SBC); volume censoring (SBC, ICA); nuisance regression of CSF and white matter signals (SBC); head motion regression (SBC, ICA); bandpass filtering (SBC, ICA); and spatial smoothing with a kernel size that is twice the effective voxel size (SBC, ICA).The consensus recommendations put forth for rs-fMRI acquisition and preprocessing steps will aid in standardization of practice and guide rs-fMRI program development across institutions. Standardized rs-fMRI protocols and processing pipelines are essential for multicenter trials and to implement rs-fMRI as part of standard clinical practice.

Comprehensive Update and Review of Clinical and Imaging Features of SMART Syndrome.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a delayed complication of cranial irradiation, with subacute onset of stroke-like symptoms including seizures, visual disturbance, speech impairment, unilateral hemianopsia, facial droop, and aphasia, often associated with migraine-type headache. The diagnostic criteria were initially proposed in 2006. However, the diagnosis of SMART syndrome is challenging because clinical symptoms and imaging features of SMART syndrome are indeterminate and overlap with tumor recurrence and other neurologic diseases, which may result in inappropriate clinical management and unnecessary invasive diagnostic procedures. Recently, various imaging features and treatment recommendations for SMART syndrome have been reported. Radiologists and clinicians should be familiar with updates on clinical and imaging features of this delayed radiation complication because recognition of this entity can facilitate proper clinical work-up and management. This review provides current updates and a comprehensive overview of the clinical and imaging features of SMART syndrome.

Human C1q Tumor Necrosis Factor 8 (CTRP8) defines a novel tryptase+ mast cell subpopulation in the prostate cancer microenvironment.

The adipokine C1q Tumor Necrosis Factor 8 (CTRP8) is the least known member of the 15 CTRP proteins and a ligand of the relaxin receptor RXFP1. We previously demonstrated the ability of the CTRP8-RXFP1 interaction to promote motility, matrix invasion, and drug resistance. The lack of specific tools to detect CTRP8 protein severely limits our knowledge on CTRP8 biological functions in normal and tumor tissues. Here, we have generated and characterized the first specific antiserum to human CTRP8 which identified CTRP8 as a novel marker of tryptase+ mast cells (MCT) in normal human tissues and in the prostate cancer (PC) microenvironment. Using human PC tissue microarrays composed of neoplastic and corresponding tumor-adjacent prostate tissues, we have identified a significantly higher number of CTRP8+ MCT in the peritumor versus intratumor compartment of PC tissues of Gleason scores 6 and 7. Higher numbers of CTRP8+ MCT correlated with the clinical parameter of biochemical recurrence. We showed that the human MC line ROSAKIT WT expressed RXFP1 transcripts and responded to CTRP8 treatment with a small but significant increase in cell proliferation. Like the cognate RXFP1 ligand RLN-2 and the small molecule RXFP1 agonist ML-290, CTRP8 reduced degranulation of ROSAKIT WT MC stimulated by the Ca2+-ionophore A14187. In conclusion, this is the first report to identify the RXFP1 agonist CTRP8 as a novel marker of MCT and autocrine/paracrine oncogenic factor within the PC microenvironment.

Ulnar nerve morphology on magnetic resonance imaging predicts nerve recovery after surgery for cubital tunnel syndrome.

Magnetic resonance imaging (MRI) can evaluate nerve morphology in cubital tunnel syndrome (CuTS), but its value in predicting surgical outcome is unclear. The purpose of this study was to determine whether ulnar nerve morphology on MRI correlated with outcome after CuTS surgery. We reviewed 40 patients who had preoperative MRI and electrodiagnostic (EDX) examinations for CuTS and outcome evaluation 6 months and 2 years postoperatively. Using MRI, ulnar nerve cross-sectional area (UNCSA), changes in signal intensity, and any space-occupying lesion were evaluated. Other factors assessed were age, symptom duration and severity, type-2 diabetes and EDX parameters. Factors associated with unfavorable surgical outcome were identified. At 6 months postoperatively, 12 patients (30%) had excellent, 19 (47.5%) good, 8 (20%) fair and 1 (2.5%) poor results on modified Wilson-Krout criteria. On univariate analysis, unfavorable outcomes were associated with increased UNCSA, space-occupying lesion, and decreased motor nerve conduction velocity (mNCV), and on multivariate analysis with increased UNCSA 1 cm distal from the epicondyle only (model 1) or increased UNCSA 1 cm proximal from the epicondyle and decreased mNCV (model 2). At 2 years, 15 patients (37.5%) had excellent, 21 (52.5%) good, 3 (7.5%) fair and 1 (2.5%) poor results, and no factors correlated with unfavorable outcome. Increased UNCSA on MRI was associated with unfavorable outcome at 6 months but not at 2 years. This study suggests that morphologic ulnar nerve changes can predict delayed nerve recovery after surgery for CuTS.

Isolated idiopathic aortitis with an unusually thickened aortic wall: case report.

Aortitis includes a broad range of disorders involving inflammation of the aorta. While most forms of aortitis can be linked to a specific cause, patients with idiopathic aortitis (IDA), are asymptomatic and usually diagnosed after surgical removal. The specific pathophysiology is not well understood, but can be strongly associated with tobacco smoking, young age at presentation, and family history of aortic aneurysm. Wall thickening is the most common physical characteristic of aortitis, and the inflammation can affect any layer of the aorta. The normal wall thickness of the aorta is less than 4 mm and can be as thick as 9 mm. Few studies document a correlation between wall thickness and the severity of aortitis. This paper presents a unique case of severe aortic aneurysm associated with an abnormal thickening of the ascending aorta.

Chemical composition and antibacterial activity of essential oil of Nepeta graciliflora Benth. (Lamiaceae).

The chemical composition of the essential oil obtained from aerial parts of Nepeta graciliflora was analysed, for the first time, by GC-FID and GC-MS. A total of 27 compounds were identified, constituting over 91.44% of oil composition. The oil was strongly characterised by sesquiterpenes (86.72%), with ß-sesquiphellandrene (28.75%), caryophyllene oxide (12.15%), α-bisabolol (8.97%), α-bergamotene (8.51%), ß-bisabolene (6.33%) and ß-Caryophyllene (5.34%) as the main constituents. The in vitro activity of the essential oil was determined against four micro-organisms in comparison with chloramphenicol by the agar well diffusion and broth dilution method. The oil exhibited good activity against all tested organisms.

A multicentre UK study of GVHD following DLI: rates of GVHD are high but mortality from GVHD is infrequent.

DLIs are frequently used following haematopoietic SCT (HSCT) in patients with risk of relapse but data on GVHD following DLI are scarce. We report on 68 patients who received DLI following HSCT. Most patients developed GVHD following DLI (71%), which was acute in 22 patients (32%) almost half of whom had grade III-IV acute GVHD (aGVHD). Thirty patients (44%) developed cGVHD which followed aGVHD in four patients and was graded severe in nine patients. Corticosteroids were the most common first-line therapy for both acute and chronic GVHD. A wide range of second/third-line agents included cyclosporin, mycophenolate, tacrolimus, imatinib, infliximab and ECP. Relapse of initial malignancy occurred in 37%. Relapse was significantly less frequent in those receiving pre-emptive DLI. Relapse rates were also lower in those with GVHD (31%) than those without GVHD (50%), but this did not reach statistical significance. At 55 months post DLI, 34% of patients had died most commonly from relapse and 22% had on-going GVHD. Although GVHD was an important cause of morbidity post DLI (71%), only 6% died from GVHD. Although most patients develop GVHD post DLI and may require consecutive therapies, mortality from GVHD is infrequent. DLI remains an important option for relapse post transplant and manipulation of the GVT effect needs to be optimised to induce remission without morbidity from GVHD.

Posterolateral corner injuries of the knee--a review.

Posterolateral corner injuries of the knee are usually associated with injuries to other structures of the knee. It is not unusual to miss this injury during the initial assessment. Undiagnosed and untreated posterolateral corner knee injury leads to significant morbidity including early osteo-arthritis of the knee. Failure to recognise and reconstruct posterolateral corner injuries is one of the important reasons for the failure of cruciate ligament reconstruction surgery. In this article we have reviewed the literature regarding anatomy, biomechanics, clinical features and treatment of the posterolateral corner injuries of the knee.

Recurrent retinal detachment: does initial treatment matter?

BACKGROUND/AIMS: To evaluate the treatment course of patients with primary rhegmatogenous retinal detachment (RRD) that re-detach after initial retinal detachment surgery. METHODS: Patients were divided into three groups based on initial surgical treatment: scleral buckle procedure (SBP) (63 eyes), pars plana vitrectomy (PPV) (88 eyes) and combined SBP/PPV (135 eyes). Charts were reviewed for a mean follow-up of 12 months. RESULTS: Average number of secondary procedures to achieve anatomical success was lowest in the SBP group (1.1), compared with the PPV group (1.47) and the SBP/PPV group (1.5) (p<0.05). Patients that re-detached after initial PPV/SBP, PPV or SBP required silicone oil injection in 83%, 60% and 22% of the cases and had final best-corrected visual acuity better than or equal to 20/50 in 21%, 33% and 45% of the cases, respectively. Phakic patients that re-detached after initial treatment with PPV/SBP, PPV and SBP required pars plana lensectomy (PPL) in 42%, 25% and 12.5% of the cases, respectively. CONCLUSION: Patients with primary RRD that re-detach after initial treatment with SBP require fewer number of secondary operations and silicone oil injections, show a trend for better visual outcomes and are less likely to develop dense cataract or to require PPL compared to patients that re-detach after initial PPV or PPV/SBP.

Rituximab (Rituxan).

Rituximab is a monoclonal antibody that was first approved by the FDA as an antineoplastic agent designed to treat B-cell malignancies. This article will review the mechanism of action and clinical role of this anti-B-cell agent.

Pharmacological inhibition of poly(ADP-ribose) polymerase (PARP) activity in PARP-1 silenced tumour cells increases chemosensitivity to temozolomide and to a N3-adenine selective methylating agent.

We recently demonstrated that poly(ADP-ribose) polymerase (PARP)-1 is involved in angiogenesis and tumour aggressiveness. In this study we have compared the influence of abrogation of PARP-1 expression by stable gene silencing to that of the pharmacological inhibition of cellular PARP activity using PARP-1/-2 inhibitors on the chemosensitivity of tumour cells to the wide spectrum methylating agent temozolomide (TMZ) and to the N3-adenine selective methylating agent {1-methyl-4-[1-methyl-4-(3-methoxysulfonylpropanamido)pyrrole-2-carboxamido]-pyrrole-2-carboxamido}propane (Me-Lex). Silencing of PARP-1 in melanoma or cervical carcinoma lines enhanced in vitro sensitivity to TMZ and Me- Lex, and induced a higher level of cell accumulation at the G2/M phase of cell cycle with respect to controls. GPI 15427, which inhibits both PARP-1 and PARP-2, increased sensitivity to TMZ and Me-Lex both in PARP-1-proficient and - deficient cells. However, it induced different cell cycle modulations depending on PARP-1 expression, provoking a G2/M arrest only in PARP-1 silenced cells. Treatment of PARP-1 silenced cells with TMZ or Me-Lex resulted in a more extensive phosphorylation of Chk-1 and p53 as compared to PARP-1 proficient cells. The combination of the methylating agents with GPI 15427 increased Chk-1 and p53 phosphorylation both in PARP-1 proficient or deficient cells. When mice challenged with PARP-1 silenced melanoma cells were treated with the TMZ and PARP inhibitor combination there was an additional reduction in tumour growth with respect to treatment with TMZ alone. These results suggest the involvement of PARP-2 or other PARPs, in the repair of DNA damage provoked by methylating agents, highlighting the importance of targeting both PARP-1 and PARP-2 for cancer therapy.

Phase II trial of neoadjuvant temozolomide in resectable melanoma patients.

BACKGROUND: We treated melanoma patients with temozolomide (TMZ) in the neoadjuvant setting and collected cryopreserved tumor samples before and after treatment. The primary objective was to determine whether the response proportion was higher than previously reported in widely metastatic patients. A secondary objective was to test the feasibility of obtaining adequate tissue before and after treatment for genetic testing. MATERIALS AND METHODS: Chemotherapy-naive melanoma patients who were candidates for surgical resection were eligible. TMZ was administered orally at 75 mg/m(2)/day for 6 weeks of every 8-week cycle. Cycles were repeated until complete response (CR), progression, or stable disease (SD) for two cycles. RESULTS: Of 19 assessable patients, 2 had CRs and 1 had partial response. Four patients had SD; 12 progressed. Tumor O-6-methylguanine-DNA methyltransferase (MGMT) promoter was unmethylated in all nine patients analyzed including from the two CR patients. Pretreatment tumor microarray results were obtained in 16 of 19 patients. CONCLUSIONS: The response proportion to TMZ in the neoadjuvant setting was 16%, not different than in the metastatic setting. Responses were seen even in tumors with a methylated MGMT promoter. Pretreatment cryopreserved tumor adequate for microarray analysis could be obtained in most, but not all, patients. Post-treatment tumor was unavailable in complete responders.

Lymphatic malformation in adult patient: a rare case.

Lymphatic malformation is an uncommon anomaly that commonly occurs in the posterior triangles of infants. The case presented here was an adult male patient with swelling in submental region. This site often leads to misdiagnosis of other common pathology including plunging ranula or lipoma. However, USG and MRI were done for diagnosis of the lesion by which final diagnosis of lymphatic malformation was made. Surgical excision was carried out and histopathology confirmed the primary diagnosis. No recurrence is seen in one and half year follow-up period.

Extraskeletal ossifying chondroma in Hoffa's fat pad: an unusual cause of anterior knee pain.

Hoffa's disease is an obscure cause of anterior knee pain. A misconception about its rarity is very common among clinicians, and hence it is often misdiagnosed and treated as meniscal pathology. Increased awareness is required to diagnose and treat the condition appropriately. These diagnostic uncertainties commonly result in increased patient morbidity and mismanagement. In spite of a widely-accepted common occurrence of Hoffa's disease, ossification of the Hoffa's fat pad is seldom reported. We report a giant extraskeletal ossifying chondroma in a 55-year-old man, presented as chronic knee pain and successfully treated by excision. The anatomy, pathology, histology, radiological features and management of the disease are described, to increase awareness in the orthopaedic community of this common, interesting but rarely discussed condition.

Abrogation of DNA vector-based RNAi during apoptosis in mammalian cells due to caspase-mediated cleavage and inactivation of Dicer-1.

RNA interference (RNAi) is used as a reverse-genetic tool to examine functions of a gene in different cellular processes including apoptosis. As key cellular proteins are inactivated during apoptosis, and as RNAi requires cooperation of many cellular proteins, we examined whether DNA vector-based RNAi would continue to function during apoptosis. The short hairpin RNA transcribed from the DNA vector is processed by Dicer-1 to form small interfering RNA that is incorporated in the RNA-induced silencing complex (RISC) to guide a sequence-specific silencing of the target mRNA. We report here that DNA vector-based RNAi of three different genes, namely poly(ADP-ribose) polymerase-1, p14(ARF) and lamin A/C are abrogated during apoptosis. The failure of DNA vector-based RNAi was not at the level of Ago-2 or RISC-mediated step of RNAi but due to catalytic inactivation of Dicer-1 on specific cleavage at the STTD(1476) and CGVD(1538) sites within its RNase IIIa domain. Using multiple approaches, caspase-3 was identified as the major caspase responsible for the cleavage and inactivation of Dicer-1. As Dicer-1 is also the common endonuclease required for formation of microRNA (miRNA) in mammalian cells, we observed decreased levels of mature forms of miR-16, miR-21 and let-7a. Our results suggest a role for apoptotic cleavage and inactivation of Dicer-1 in controlling apoptotic events through altered availability of miRNA.

Impact of anterior capsule polishing on anterior capsule opacification after cataract surgery: a randomized clinical trial.

AIMS: To evaluate the effect of anterior capsule polishing on the development of anterior capsule opacification (ACO) in patients undergoing cataract surgery. METHODS: This prospective randomized observational double-masked clinical trial comprised 120 eyes of 60 consecutive patients with bilateral age-related cataract who underwent phacoemulsification. The patients were randomly assigned to one of the two groups: One eye received a 360 degree anterior capsule polishing (group 1 (cases)) and the fellow eye was without anterior capsule polishing (group 2 (controls)) The primary observation was to observe the development of ACO between the 2 groups, whereas the secondary observation was to measure uveal inflammation. ACO was evaluated at 1 week, 1 month, and 6 months. RESULTS: At the 1-week follow-up, there was no significant difference in the development of ACO between the two groups. At 1 month, 54 (90%) eyes developed ACO in controls and 26 (43.3%) eyes in cases (P<0.001). However, at 6 months, there was no significant difference in the development of ACO between controls and cases (P=0.500). The odds of having cells and flare were significantly more in cases compared with controls at first postoperative day (cells: OR, 39.27; 95% CI, 13.49-114.26 and flare: OR, 48.0; 95% CI, 15.57-147.97). CONCLUSIONS: ACO was significantly lower at 1 month in cases compared with controls. However, the difference in ACO between the two groups was insignificant at 6 months. A significant difference in anterior segment inflammation was documented in cases on the first postoperative day. There was no detectable benefit of performing scraping on the anterior capsule to avoid opacification after phacoemulsification.E