Anatomical identification of active contacts in subthalamic deep brain stimulation

BACKGROUND: Subthalamic Deep Brain Stimulation is a valid surgical procedure for the treatment of idiopathic PD, although its precise mechanism of action is still unclear; moreover, there are no conclusive data about the functional anatomy of the human subthalamic region. Identifying the location of active contacts for StnDBS can yield interesting insights on the mechanisms of action of DBS and the different role played by the anatomical structures of the subthalamic region. METHODS: Twenty-five patients operated on for bilateral StnDBS were considered. During the surgical procedure, a complete intraoperative neurophysiological study was obtained by means of semimicrorecordings and stimulations. After surgery, an MRI study confirmed the position of the electrodes; MR images were subsequently superimposed onto a stereotactic atlas by using a dedicated workstation. The coordinates relative to the tip of the electrodes and active contacts were then calculated. RESULTS: Most of the electrode tips are located inside the subthalamus or immediately ventrally to it. Of the active contacts used for chronic stimulation, 96.5% are located in a well-defined anatomical region, which includes subthalamus, zona incerta, and FF. CONCLUSIONS: Our findings seem to suggest that other structures beyond the subthalamus itself play a clinical role in symptoms control after DBS for PD.     

Identification of 14-3-3 theta as an antigen that induces a humoral response in lung cancer

We have implemented a strategy to identify tumor antigens that induce a humoral immune response in lung cancer based on the analysis of tumor cell proteins. Chromatographically fractionated protein extracts from three lung cancer cell lines were subjected to Western blotting and hybridization with individual sera to determine serum antibody binding. Two sets of sera were initially investigated. One set consisted of sera from 19 newly diagnosed subjects with lung adenocarcinoma and 19 matched controls. A second independent set consisted of sera from 26 newly diagnosed subjects with lung adenocarcinoma and 24 controls matched for age, gender, and smoking history. One protein that exhibited significant reactivity with both sets of cancer sera (P = 0.0008) was confidently identified by mass spectrometry as 14-3-3 theta. Remarkably, significant autoantibody reactivity against 14-3-3 theta was also observed in an analysis of a third set consisting of 18 prediagnostic lung cancer sera collected as part of the Beta-Carotene and Retinol Efficacy Trial cohort study, relative to 19 matched controls (P = 0.0042). A receiver operating characteristic curve constructed with a panel of three proteins consisting of 14-3-3 theta identified in this study, plus annexin 1 and protein gene product 9.5 proteins previously identified as associated with autoantibodies in lung cancer, gave a sensitivity of 55% at 95% specificity (area under the curve, 0.838) in discriminating lung cancer at the preclinical stage from matched controls.     

A multi-feature and multi-channel univariate selection process for seizure prediction.

OBJECTIVE: To develop a prospective method for optimizing seizure prediction, given an array of implanted electrodes and a set of candidate quantitative features computed at each contact location. METHODS: The method employs a genetic-based selection process, and then tunes a probabilistic neural network classifier to predict seizures within a 10 min prediction horizon. Initial seizure and interictal data were used for training, and the remaining IEEG data were used for testing. The method continues to train and learn over time. RESULTS: Validation of these results over two workshop patients demonstrated a sensitivity of 100%, and 1.1 false positives per hour for Patient E, using a 2.4s block predictor, and a failure of the method on Patient B. CONCLUSIONS: This study demonstrates a prospective, exploratory implementation of a seizure prediction method designed to adapt to individual patients with a wide variety of pre-ictal patterns, implanted electrodes and seizure types. Its current performance is limited likely by the small number of input channels and quantitative features employed in this study, and segmentation of the data set into training and testing sets rather than using all continuous data available. SIGNIFICANCE: This technique theoretically has the potential to address the challenge presented by the heterogeneity of EEG patterns seen in medication-resistant epilepsy. A more comprehensive implementation utilizing all electrode sites, a broader feature library, and automated multi-feature fusion will be required to fully judge the method's potential for predicting seizures.     

Physical activity prevented functional decline among frail community-living elderly subjects in an international observational study

ObjectivesThe aims of the study were to describe the prevalence of physical activity in a sample of older adults in home care in Europe and to examine the relationship between physical activity and incident disability.Study Design and SettingStudy population consisted of a random sample of 2,005 subjects aged 65 or older admitted to home care programs in 11 European Home Health Agencies who participated in AgeD in HOme Care project. Participants who reported spending 2 or more hours of physical activities in last 3 days were defined physically active. Disability performing activities of daily living was defined as the need of assistance in one or more of the following ADL: eating, dressing, transferring, mobility in bed, personal hygiene, and toileting.ResultsMore than 50% of participants were physically active. During a median follow-up of 12 months, 370 subjects (15%) became disabled. After adjusting for age, gender, and other possible confounding variables, active subjects were significantly less likely to become disabled compared to those reporting no or very low-intensity physical activity (OR, 0.67; 95% CI 0.53–0.84).ConclusionsThese findings support the possibility that physical activity has an independent effect on functional autonomy among frail and old people.     

Defining a standard and weighted mathematical index for maturation of dendritic cells

The concept of dendritic cell (DC) maturation generally refers to the changes in morphology and function of DCs. Conventionally, DC maturity is based on three criteria: loss of endocytic ability, gain of high‐level capacity to present antigens and induce proliferation of T cells, and mobility of DCs toward high concentrations of CCL19. Impairment of DC maturation has been suggested as the main reason for infectivity or chronicity of several infectious agents. In the case of hepatitis C virus, this has been a matter of controversy for the last two decades. However, insufficient attention has been paid to the method of ex vivo maturation as the possible source of such controversies. We previously reported striking differences between DCs matured with different methods, so we propose the use of a standard quantitative index to determine the level of maturity in DCs as an approach to compare results from different studies. We designed and formulated a mathematically calculated index to numerically define the level of maturity based on experimental data from ex vivo assays. This introduces a standard maturation index (SMI) and weighted maturation index (WMI) based on strictly standardized mean differences between different methods of generating mature DCs. By calculating an SMI and a WMI, numerical values were assigned to the level of maturity achieved by DCs matured with different methods. SMI and WMI could be used as a standard tool to compare diversely generated mature DCs and so better interpret outcomes of ex vivo and in vivo studies with mature DCs.     

Diagnostic yield of push-type enteroscopy in relation to indication

Background—Push-type enteroscopy, a recent methodfor investigating the small intestine, is currently undergoingassessment. Its diagnostic yield varies in the studies reported to date.
Aim—To assess the diagnostic value of push-typeenteroscopy according to indication.
Patients and methods—From January 1994 toSeptember 1995, 152 consecutive patients (mean age 34 years) underwentpush-type enteroscopy (jejunoscopy, n=93; retrograde ileoscopy, n=17;and double way enteroscopy, n=42). The indications were: unexplained iron deficiency anaemia or macroscopic gastrointestinal bleeding (n=76), radiological abnormalities of the small intestine (n=23), chronic diarrhoea and/or malabsorption syndrome (n=18), abdominal pain(n=12), and miscellaneous (n=23). All patients had undergone previousnegative aetiological investigations.
Results—The jejunum and ileum were exploredthrough 120 cm (30-160 cm) and 60 cm (20-120 cm). Digestivebleeding: lesions of the small bowel were found in 6% of the patientswith isolated iron deficiency anaemia and 20% of patients with patentdigestive haemorrhage. Radiological abnormalities of the smallintestine: push-type enteroscopy provided a diagnosis or modified theinterpretation of radiological findings in 18/23 cases (78%). Chronicdiarrhoea and/or malabsorption: push-type enteroscopy yieldedexplanatory findings in four cases (22%). Abdominal pain: push-typeenteroscopy provided no diagnosis.
Conclusion—In this series, push-type enteroscopywas of particular value in investigating patients with radiologicalabnormalities of the small intestine. It was of some value in theexploration of patent digestive haemorrhage or chronic diarrhoea, butnot of abdominal pain. Its value was limited in the exploration of irondeficiency anaemia.

Keywords:enteroscopy; gastrointestinal bleeding

     

Managements of recurrent hepatocellular carcinoma after liver transplantation: A systematic review

AIM: To investigate the efficacy(survival) and safety of treatments for recurrent hepatocellular carcinoma(HCC) in liver transplantation(LT) patients.METHODS: Literature search was performed on available online databases without a time limit until January 2015. Clinical studies describing survival after HCC recurrence in LT patients were retrieved for a fulltext evaluation. A total of 61 studies were selected: 13 case reports, 41 retrospective case series, and 7 retrospective comparative studies.RESULTS: Based on all included studies, the mean HCC recurrence rate was 16% of all LTs for HCC. A total of 1021 LT patients experienced HCC recurrence. The median time from LT to HCC recurrence was 13 mo(range 2-132 mo). The majority of patients(67%) presented with HCC extra-hepatic recurrences, involving lung, bone, adrenal gland, peritoneal lymph nodes, and rarely the brain. Overall survival after HCC recurrence was 12.97 mo. Surgical resection of localized HCC recurrence and Sorafenib for controlling systemic spread of HCC recurrence were associated with the higher survival rates(42 and 18 mo, res-pectively). However, Sorafenib, especially when combined with m TOR, was frequently associated with severe side effects that required dose reduction or discontinuation CONCLUSION: Management of recurrent HCC in LT patients is challenging and associated with poor prognosis independently of the type of treatment.     

MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project

Background:

The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics.

Methods:

Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses.

Results:

Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24–1.76), 1.39 (1.15–1.69) and 1.61 (1.35–1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19–1.70) for V60L to 2.66 (1.06–6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair.

Conclusions:

Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype.