Reduction of intractable seizures using cerebellar stimulation

Of the 32 patients with active intractable seizures, 27 had spastic cerebral palsy (CP) and 5 had epilepsy (EP), and all underwent chronic cerebellar stimulation (CCS) (amplitude 1-2 microC/cm2/phase, rate 10-180 pps, duration of implantation 0.5-7 years, average 4.5 years). Grand mal seizures occurred in 23 patients (19 CP, 4 EP); with CCS 17 patients stopped, 4 had a reduction, 3 were unchanged. Petit mal occurred in 9 patients (8 CP, 1 EP); with CCS 4 patients ceased seizuring, 3 reduced and 2 were unchanged. Myoclonic seizures were present in 6 patients (5 CP, 1 EP); with CCS 1 patient stopped, 3 had a reduction while 2 patients were unaffected. Severe psychomotor seizuring affected 2 EP patients, 1 had a marked behavioral improvement and finally stopped seizuring for the past 9 months. Overall, CCS stopped 18 (57%) of the patients seizuring, reduced a further 9 (28%), with no effect in 5 patients (15%).     

Cerebellar stimulation for spastic cerebral palsy--double-blind quantitative study

Thirty spastic cerebral palsy (CP) patients were involved in a double-blind quantitative study to determine the effectiveness of chronic cerebellar stimulation, (CCS) and 19 patients completed the testing. Of the 12 patients undergoing the five motor performance tests, 8 (66%) showed improvements with the stimulation. Of the 16 patients tested for active motion in seven bilateral joints, 10 (63%) showed increases with CCS. Profiles of six mood states were tested in 15 patients, and CCS produced an overall 15% improvement.     

Role of obesity in differences in cervical cancer screening rates by migration history. The CONSTANCES survey

BackgroundImmigrant women often have lower cervical cancer screening (CCS) rates, tend to have a higher body mass index (BMI) and may be more vulnerable to BMI-related stigmatization. Our aim was to assess the role of BMI in differences in CCS rates by migration history.MethodsAnalyses were based on the 2012–2015 inclusion data (n = 27,226) for the population-based CONSTANCES cohort, including detailed, self-reported information on demographics and socioeconomic characteristics, migration history, health behaviours, health, and health care use. Measured BMI (underweight (<18.5), normal-weight (18.5–25), overweight (25–30), obese (>30)) was collected. Poisson regression models with robust variance were conducted to assess the contribution of BMI to differences in CCS rates by migration history, and analyses stratified by BMI were done. Multiple imputations were performed.ResultsThe CCS rates ranged from 87% among French-born women with two French parents to 86% among French-born women with at least one parent of foreign origin, 82% among naturalized immigrants and 74% among non-naturalized immigrants. After adjusting for covariates, non-naturalized immigrants showed an 11% (95% CI: 8%–14%) lower CCS rate than French-born women with two French parents. Adjusting for BMI did not change the estimates. When stratifying by BMI category, non-naturalized immigrants showed an 11% (7%–14%) lower CCS rate then French-born with two French parents when normal weight, a 9% (2%–16%) lower CCS rate when overweight, and an 18% (5%–30%) lower CCS rate when obese.ConclusionMigration history and BMI jointly impact CCS rates. They were lower among all non-naturalized immigrants, particularly those who were obese.     

Outcomes and indications of corpus callosum section for intractable seizure control

Callosotomy (CCS) was performed in 9 cases of rigorously classified drug-refractory epilepsy not eligible for focal cortical resection. Complete CCS was carried out in two stages in 8 patients. 1 case had an anterior CCS only. None of the 9 patients has become seizure free. In 7, seizure frequency has diminished by a factor of 3-60 for at least one seizure type. Drop attacks in 2 cases have ceased. Clinical seizure patterns appeared more helpful in predicting outcome than preoperative EEG and stereoelectroencephalographic studies. Complete CCS may result in prolonged behavioral disturbances in the areas of language, hemisphere competition and attention-memory sequencing with impact on the sphere of daily living.     

Outcomes in 125 individuals with adrenal incidentalomas from a single centre. a retrospective assessment of the 1 mg overnight and low dose dexamethasone suppression tests

Adrenal masses discovered incidentally during imaging studies - adrenal incidentalomas (AIs) - are common and prompt investigations to exclude secretory lesions and malignancy. Their best management strategy is unknown. Our objectives were to identify all outcomes of AI investigation in a UK centre and to assess the performance of the 2?mg low dose (LDDST) and 1?mg overnight dexamethasone (ODST) suppression tests in this setting. Out of 125 patients referred to our centre between 2005 and 2009 with AIs, 16 (12.8%) were diagnosed with secretory adrenal adenomas. 24 patients (23%) failed to suppress on LDDST or ODST using a serum cortisol cut-off of 50?nmol/l for both tests; in 12 this was due to false positive results. 5 patients were diagnosed with adrenal Cushing's syndrome and 7 with subclinical hypercortisolism. The use of a higher post LDDST (83?nmol/l) or ODST (138?nmol/l) cortisol cut-off would have resulted in missing 1 patient with Cushing's syndrome and 4 with subclinical hypercortisolism or 2 patients with Cushing's syndrome and 1 with subclinical hypercortisolism, respectively. In patients who had both tests, the ODST systematically resulted in higher post-test cortisol values compared with the LDDST. The adenoma diameter correlated with and was predictive of the post LDDST cortisol. Our results indicate that altering the post dexamethasone cut-off in accordance to published guidelines changes the performance of the suppression tests. The ODST may result in higher post-test cortisol levels compared to LDDST when used in patients with AIs.     

Modification of the standing long jump test enhances ability to predict anaerobic performance

The purpose of this study was to investigate whether modifying the standing long jump test would enhance its ability to be a better predictor of anaerobic performance compared to other common anaerobic power tests. Three modified box long jump (MBLJ) tests were performed using 1, 2, or 3 boxes. Subjects consisted of 38 healthy males (age, 21.7 +/- 1.7 years) who performed all the testing procedures. All 3 variations of the MBLJ test showed significant correlations (p < 0.05) with the vertical jump (VJ); standing long jump (SLJ); 50-, 100-, 200-, 400-m runs; long jump; triple jump; and shot put ability (r = 0.362-0.891). All 3 variations of the MBLJ test also showed significant correlations with isokinetic peak torque knee extension and flexion, Wingate mean power (W), and Wingate mean power per kilogram (W/kg) (r = 0.357-0.504). Generally, correlations of the 3 MBLJ tests were stronger than correlations between VJ and SLJ ability to the same measure of power. Generally, the 3-box MBLJ tests showed stronger correlations with measures of power than the 1- and 2-box MBLJ tests. Multiple linear regression models indicated that the 3-box MBLJ test is a major predictor of the track and field performances compared to the other tests of anaerobic power. Along with other independent variables, the 3-box MBLJ test explained 55%, 44%, 51%, 61%, 52%, and 72% of the variance of 50-, 100-, 200-, and 400-m runs; long jump; and triple jump performance, respectively. In conclusion, due to the significant correlations between the MBLJ tests, especially the 3-box version, and other measures of power, these tests are appropriate for testing lower body power.     

Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers

The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer), owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67-80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease.     

When Do We Really Need Coronary Calcium Scoring Prior to Contrast-Enhanced Coronary Computed Tomography Angiography? Analysis by Age,Gender and Coronary Risk Factors

Aims

To investigate the value of coronary calcium scoring (CCS) as a filter scan prior to coronary computed tomography angiography (CCTA).

Methods and Results

Between February 2008 and April 2011, 732 consecutive patients underwent clinically indicated CCTA. During this ‘control phase’, CCS was performed in all patients. In patients with CCS≥800, CCTA was not performed. During a subsequent ‘CCTA phase’ (May 2011–May 2012) another 200 consecutive patients underwent CCTA, and CCS was performed only in patients with increased probability for severe calcification according to age, gender and atherogenic risk factors. In patients where CCS was not performed, calcium scoring was performed in contrast-enhanced CCTA images. Significant associations were noted between CCS and age (r = 0.30, p<0.001) and coronary risk factors (χ² = 37.9; HR = 2.2; 95%CI = 1.7–2.9, p<0.001). Based on these associations, a ≤3% pre-test probability for CCS≥800 was observed for males <61 yrs. and females <79 yrs. According to these criteria, CCS was not performed in 106 of 200 (53%) patients during the ‘CCTA phase’, including 47 (42%) males and 59 (67%) females. This resulted in absolute radiation saving of ∼1 mSv in 75% of patients younger than 60 yrs. Of 106 patients where CCS was not performed, estimated calcium scoring was indeed <800 in 101 (95%) cases. Non-diagnostic image quality due to calcification was similar between the ‘control phase’ and the ‘CCTA’ group (0.25% versus 0.40%, p = NS).

Conclusion

The value of CCS as a filter for identification of a high calcium score is limited in younger patients with intermediate risk profile. Omitting CCS in such patients can contribute to further dose reduction with cardiac CT studies.     

Different value of coronary calcium score to predict obstructive coronary artery disease in patients with and without moderate chronic kidney disease

Purpose

The coronary calcium score (CCS) predicts significant coronary artery disease (CAD) in the general population. While moderate chronic kidney disease (CKD) is associated with high CCS, the use of CCS to predict significant CAD in these patients is unknown.

Methods

A total of 704 patients underwent computed tomography coronary angiography for the assessment of CCS and CAD. Sixty-nine (10 %) patients had moderate CKD, defined by an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73m², and the remaining patients were considered to be without significant CKD (eGFR?≥?60 mL/min/1.73m²).

Results

Patients with moderate CKD were older, had a higher CCS, and a higher prevalence of obstructive CAD than patients without significant CKD. Receiver-operator curve analysis showed that CCS predicted the presence of obstructive CAD in both patients with moderate CKD and those without significant CKD. In patients with moderate CKD, the optimal cut-off value of CCS to diagnose obstructive CAD was 140 (sensitivity 73 % and specificity of 70 %), and is 2.8 fold higher than in patients without significant CKD (cut-off value?=?50; sensitivity 75 % and specificity 75 %).

Conclusion

The present results demonstrate that CCS can predict obstructive CAD in patients with moderate CKD, although the optimal cut-off value is higher than in patients without significant CKD.     

Endurance training of older men: responses to submaximal exercise.

The purpose of this study was to quantify the exercise response of older subjects on a time-to-fatigue (TTF) submaximal performance test before and after a training program. Eight older men (67.4 +/- 4.8 yr) performed two maximal treadmill tests to determine maximum oxygen uptake (VO2max) and ventilation threshold (TVE) and a constant-load submaximal exercise treadmill test that required an oxygen uptake (VO2) between TVE and VO2max. The submaximal test, performed at the same absolute work rate before and after the training program, was performed to volitional fatigue to measure endurance time. The men trained under supervision at an individualized pace representing approximately 70% of VO2max (80% maximum heart rate) for 1 h, four times per week for 9 wk. Significant increases were demonstrated for VO2max (ml.kg-1.min-1; 10.6%); maximal ventilation (VE, l/min; 11.6%), and TVE (l/min; 9.8%). Weight decreased 2.1%. Performance time on the TTF test increased by 180% (7.3 +/- 3.0 to 20.4 +/- 13.5 min). The similar end points for VO2, VE, and heart rate during the TTF and maximal treadmill tests established that the TTF test was stopped because of physiological limitations. The increase in performance time among the subjects was significantly correlated with improvements in VO2max and TVE, with the submaximal work rate representing a VO2 above TVE by 88% of the difference between TVE and VO2max pretraining and 73% of this difference on posttraining values.     

Increased alkali stability in Trichoderma reesei endo-1, 4-beta-xylanase II by site directed mutagenesis

A number of engineered Trichoderma reesei endo-beta-1,4-xylanase (Xyn II) mutants were created and activity tests were performed for increased stability. The stability of the earlier characterized mutant Y5 (T2C, T28C, K58R, +191D) was further increased by the mutations creating the constructs P9 (N97R+F93W+H144K), P12 (H144C+N92C), P15 (F180Q+H144C+N92C) and P21 (H22K+F180Q+H144C+N92C). The resistance towards thermal inactivation at alkaline pH was increased in all of the mutants. Residual activity T(50%) was increased 4-5 degrees C for P9 at pH 9. The performance of the P9 mutant in sulphate pulp bleaching was also tested and was shown to increase brightness markedly compared to the reference. The bleaching results showed the industrial potential of the obtained mutant.     

Measurement of the Effect of Physical Exercise on the Concentration of Individuals with ADHD

Attention Deficit Hyperactivity Disorder (ADHD) mainly affects the academic performance of children and adolescents. In addition to bringing physical and mental health benefits, physical activity has been used to prevent and improve ADHD comorbidities; however, its effectiveness has not been quantified. In this study, the effect of physical activity on children''s attention was measured using a computer game. Intense physical activity was promoted by a relay race, which requires a 5-min run without a rest interval. The proposed physical stimulus was performed with 28 volunteers: 14 with ADHD (GE-EF) and 14 without ADHD symptoms (GC-EF). After 5 min of rest, these volunteers accessed the computer game to accomplish the tasks in the shortest time possible. The computer game was also accessed by another 28 volunteers: 14 with ADHD (GE) and 14 without these symptoms (GC). The response time to solve the tasks that require attention was recorded. The results of the four groups were analyzed using D''Agostino statistical tests of normality, Kruskal-Wallis analyses of variance and post-hoc Dunn tests. The groups of volunteers with ADHD who performed exercise (GE-EF) showed improved performance for the tasks that require attention with a difference of 30.52% compared with the volunteers with ADHD who did not perform the exercise (GE). The (GE-EF) group showed similar performance (2.5% difference) with the volunteers in the (GC) group who have no ADHD symptoms and did not exercise. This study shows that intense exercise can improve the attention of children with ADHD and may help their school performance.     

Cyclosporine A in the long-term management of systemic lupus erythematosus

To retrospectively evaluate safety and efficacy of long-term treatment with Cyclosporine A (CSA) in patients with systemic lupus erythematosus (SLE) poorly responsive to treatment with corticosteroids (CCS) and/or conventional disease-modifying anti-rheumatic drugs (DMARDs), SLE patients who had received CSA-based induction and maintenance regimens according to disease activity were recorded. Efficacy was assessed using the SLE Disease Activity Index (SLEDAI) and laboratory analyses. Forty SLE patients (including 18 with lupus nephritis, 11 with neurological involvement and 7 with overlap syndromes (4 Sj?gren's syndrome, 2 myasthenia gravis and 1 Beh?et's disease) were recorded. According to baseline SLEDAI, 30 patients had severe and 10 moderate SLE. Mean SLEDAI scores and relevant laboratory values significantly reduced from baseline (22?10 vs 5?6; P < 0.002) during the follow-up period (8?2 years; range 1-15). Twenty-three (57.5 percent) patients achieved excellent (improvement in the range 70-100 percent) response to treatment (10 of whom were subsequently maintained on CSA monotherapy), 14 (35 percent) had good-fair (improvement in the range 25-69 percent) response and 3 (7.5 percent) had to interrupt therapy (including CSA) for disease worsening. Mild and transient adverse events occurred in 15 (37 percent) patients, including hypertrichosis (17.5 percent), gum hypertrophy (17.5 percent) hypertension (12.5 percent), abdominal pain (7.5 percent), and dyslipidemia (5 percent), but treatment interruption was not required. Low-dose CSA together with other drugs is effective to induce, or as monotherapy to maintain, long-term (at least 2 years) remission, and is generally well tolerated in patients with moderate or severe SLE poorly responsive to CCS and/or conventional DMARDs. Furthermore, the favourable effect of CSA treatment may allow to spare more cytotoxic drugs.     

Outcome in colorectal adenocarcinoma: two seven-year studies of a population.

OBJECTIVE--To record every patient with proved colorectal adenocarcinoma presenting from a defined population over two years in 1968-9 and during 1980-2, and to compare treatment and outcome over seven years. DESIGN--Retrospective in 1968-9 and prospective in 1980-2. SETTING--Aberdeen general hospitals. SUBJECTS--Every patient presenting to the four general surgical units with histological proof of colorectal adenocarcinoma. MAIN FINDINGS--On average, one new patient presented each week per 100,000 population. The proportion of patients aged 65 and over rose from 67% to 71%. An operation was performed on 385 patients in 1968-9 and on 399 during 1980-2. At laparotomy the proportion of patients who seemed to be curable and had a radical operation rose slightly, from 56% to 61%, and operative mortality fell from 9% to 5%. In all there were 421 survivors of curative surgery, and seven years later three quarters were either alive (51%) or had died without recurrence (25%). In both studies some 40% of patients were considered incurable when they presented, but the number who had a palliative resection rose from 59% to 85%. CONCLUSIONS--The contribution of radical surgery to the treatment of colorectal adenocarcinoma is substantial, with three quarters of patients so treated showing no evidence of recurrence after seven years. Operative mortality in an elderly population is now low, and improvement in late outcome is more likely to come from developments in adjuvant therapy than in operative technique. A continuing problem is that 40% of patients are not curable when they present, although palliative resection can now be offered to over 80%.     

Malignant cerebral glioma--I: Survival,disability, and morbidity after radiotherapy.

OBJECTIVE: To describe survival, disability, and morbidity after radiotherapy for malignant glioma. DESIGN: Two year prospective study with home interviews with patients and relatives. SETTING: Seven neurosurgical and radiotherapy centres in London. SUBJECTS: 105 patients aged 21 to 75: 59 had biopsy; 46 had partial macroscopic resection; 92 received radiotherapy; and 13 received steroids alone. MAIN OUTCOME MEASURES: Survival, time free from disability, and changes in disability after treatment. RESULTS: Six and 12 month survival for radiotherapy patients was 70% and 39%, respectively. Age, World Health Organisation clinical performance status, extent of surgery, and history of seizures before diagnosis each influenced survival. The Medical Research Council prognostic index was also significantly related to survival. Multivariate analysis showed that initial clinical performance status was the most important component of the index. Most (80%; 49/61) patients with a clinical performance status of 0, 1, or 2 lived at least six months before becoming permanently disabled. Most patients who had initially had a good clinical performance status (0-2) and who were alive six months after radiotherapy (68%; 36/52), however, had experienced either clinical deterioration or severe tiredness after treatment. In 17% (9/52) of these some permanent loss of function remained. These adverse effects were associated with increasing radiotherapy dose. Severely disabled patients (clinical performance status 3 or 4) gained little benefit. CONCLUSION: Severely disabled patients gain little physical benefit from radiotherapy, whereas those not so disabled may experience considerable adverse effects.     

Accuracy and Feasibility of Point-Of-Care White Blood Cell Count and C-Reactive Protein Measurements at the Pediatric Emergency Department

Background

Several point-of-care (POC) tests are available for evaluation of febrile patients, but the data about their performance in acute care setting is sparse. We investigated the analytical accuracy and feasibility of POC tests for white blood cell (WBC) count and C-reactive protein (CRP) at the pediatric emergency department (ED).

Methods

In the first part of the study, HemoCue WBC and Afinion AS100 CRP POC analyzers were compared with laboratory’s routine WBC (Sysmex XE-2100) and CRP (Modular P) analyzers in the hospital central laboratory in 77 and 48 clinical blood samples, respectively. The POC tests were then adopted in use at the pediatric ED. In the second part of the study, we compared WBC and CRP levels measured by POC and routine methods during 171 ED patient visits by 168 febrile children and adolescents. Attending physicians performed POC tests in capillary fingerprick samples.

Results

In parallel measurements in the laboratory both WBC and CRP POC analyzers showed good agreement with the reference methods. In febrile children at the emergency department (median age 2.4 years), physician performed POC determinations in capillary blood gave comparable results with those in venous blood analyzed in the laboratory. The mean difference between POC and reference test result was 1.1 E9/L (95% limits of agreement from -6.5 to 8.8 E9/L) for WBC and -1.2 mg/L (95% limits of agreement from -29.6 to 27.2 mg/L) for CRP.

Conclusions

POC tests are feasible and relatively accurate methods to assess CRP level and WBC count among febrile children at the ED.     

Impact of training intensity distribution on performance in endurance athletes

The purpose of this study was to compare the effect of 2 training programs differing in the relative contribution of training volume, clearly below vs. within the lactate threshold/maximal lactate steady state region on performance in endurance runners. Twelve subelite endurance runners (who are specialists in track events, mostly the 5,000-m race usually held during spring-summer months and who also participate in cross-country races [9-12 km] during fall and winter months) were randomly assigned to a training program emphasizing low-intensity (subthreshold) (Z1) or moderately high-intensity (between thresholds) (Z2) training intensities. At the start of the study, the subjects performed a maximal exercise test to determine ventilatory (VT) and respiratory compensation thresholds (RCT), which allowed training to be controlled based on heart rate during each training session over a 5-month training period. Subjects performed a simulated 10.4-km cross-country race before and after the training period. Training was quantified based on the cumulative time spent in 3 intensity zones: zone 1 (low intensity; RCT). The contribution of total training time spent in zones 1 and 2 was controlled to have relatively more low-intensity training in Z1 (80.5 +/- 1.8% and 11.8 +/- 2.0%, respectively) than in Z2 (66.8 +/- 1.1% and 24.7 +/- 1.5%, respectively), whereas the contribution of high-intensity (zone 3) training was similar (8.3 +/- 0.7% [Z1] and 8.5 +/- 1.0% [Z2]). The magnitude of the improvement in running performance was significantly greater (p = 0.03) in Z1 (-157 +/- 13 seconds) than in Z2 (-121.5 +/- 7.1 seconds). These results provide experimental evidence supporting the value of a relatively large percentage of low-intensity training over a long period ( approximately 5 months), provided that the contribution of high-intensity training remains sufficient.     

Neurocognitive Function in HIV-Infected Patients: Comparison of Two Methods to Define Impairment

Objective

To compare two definitions of neurocognitive impairment (NCI) in a large clinical trial of effectively-treated HIV-infected adults at baseline.

Methods

Hopkins Verbal Learning test-Revised (HVLT-R), Colour Trail (CTT) and Grooved Pegboard (GPT) tests were applied exploring five cognitive domains. Raw scores were transformed into Z-scores and NCI defined as summary NPZ-5 score one standard deviation below the mean of the normative dataset (i.e. <−1SD) or Z-scores <−1SD in at least two individual domains (categorical scale). Principal component analysis (PCA) was performed to explore the contribution of individual tests to the total variance.

Results

Mean NPZ-5 score was −0.72 (SD 0.98) and 178/548 (32%) participants had NPZ-5 scores <−1SD. When impairment was defined as <−1SD in at least two individual tests, 283 (52%) patients were impaired. Strong correlations between the two components of the HVLT-R test (learning/recall) (r = 0.73), and the CTT and (attention/executive functioning) (r = 0.66) were observed. PCA showed a clustering with three components accounting for 88% of the total variance. When patients who scored <−1SD only in two correlated tests were considered as not impaired, prevalence of NCI was 43%. When correlated test scores were averaged, 36% of participants had NPZ-3 scores <−1SD and 32% underperformed in at least two individual tests.

Conclusion

Controlling for differential contribution of individual test-scores on the overall performance and the level of correlation between components of the test battery used appear to be important when testing cognitive function. These two factors are likely to affect both summary scores and categorical scales in defining cognitive impairment.

Trial registration

EUDRACT: 2007-006448-23 and ISRCTN04857074.     

Down-regulation of miR-199b associated with imatinib drug resistance in 9q34.1 deleted BCR/ABL positive CML patients

Chronic myeloid leukemia (CML) occurs due to t(9,22) (q34;q11) and molecularly BCR/ABL gene fusion. About 15–18% Philadelphia positive CML patients have gene deletions around the translocation breakpoints on 9q34.1. The microRNAs (miRNAs), namely miR-219-2 and miR-199b, centromeric to the ABL1 gene are frequently lost in CML patients. We have designed a study to determine miR-219-2 and miR-199b expression levels which would help to understand the prognosis of imatinib therapy. A total of 150 CML patients were analyzed to identify 9q deletion. Fluorescent in-situ hybridization (FISH) was performed using BCR/ABL dual color, dual fusion probe to study the signal pattern and BAC probes for miR-199b and miR-219-2 (RP11-339B21 and RP11-395P17) to study the miRNA deletions. The expression level of miRNA was analyzed by real-time polymerase chain reaction (RT-PCR). FISH analysis revealed 9q34.1 deletion in 34 (23%) CML patients. The deletions were not detected using BAC probes for miRNAs in 9q deleted patients. The expression analysis showed down-regulation of miR-199b and miR-219-2 in the 9q deleted patients (34 CML) as compared to a pool of patients without deletion. However, miR-199b (9q34.11) was significantly (p = 0.001) down-regulated compared to miR-219-2. The follow-up study showed that the miR-199b was found to be strongly associated with imatinib resistance, as 44.11% patients showed resistance to imatinib therapy. Hence, the deletion in 9q34.1 region (ABL) plays an important role in disease pathogenesis. Eventually, miRNAs can provide new therapeutic strategies and can be used as a prognostic indicator.     

Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS

This study aims at substituting the essential functions of photoreceptors in patients who are blind owing to untreatable forms of hereditary retinal degenerations. A microelectronic neuroprosthetic device, powered via transdermal inductive transmission, carrying 1500 independent microphotodiode-amplifier-electrode elements on a 9 mm² chip, was subretinally implanted in nine blind patients. Light perception (8/9), light localization (7/9), motion detection (5/9, angular speed up to 35 deg s⁻¹), grating acuity measurement (6/9, up to 3.3 cycles per degree) and visual acuity measurement with Landolt C-rings (2/9) up to Snellen visual acuity of 20/546 (corresponding to decimal 0.037 or corresponding to 1.43 logMAR (minimum angle of resolution)) were restored via the subretinal implant. Additionally, the identification, localization and discrimination of objects improved significantly (n = 8; p < 0.05 for each subtest) in repeated tests over a nine-month period. Three subjects were able to read letters spontaneously and one subject was able to read letters after training in an alternative-force choice test. Five subjects reported implant-mediated visual perceptions in daily life within a field of 15° of visual angle. Control tests were performed each time with the implant''s power source switched off. These data show that subretinal implants can restore visual functions that are useful for daily life.