Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026: 06/28/17

Τετάρτη 28 Ιουνίου 2017

Impact of HSCT Conditioning and Glucocorticoid Dose on Exercise Adherence and Response.

Purpose: Evidence from randomized controlled trials (RCT) is growing that exercise interventions have beneficial effects in patients undergoing allogeneic stem cell transplantation (allo-HSCT). However, intensive chemotherapy conditioning as well as glucocorticoid (GC) treatment is always part of an allo-HSCT and possibly impact exercise adherence and training response. Therefore, we aimed to examine whether various conditioning protocols or different doses of GC treatment affect exercise adherence and/or training response during the inpatient period. Methods: We analyzed inpatient data from intervention groups of two large RCTs in allo-HSCT patients (n=113). The intervention incorporated partly supervised endurance and resistance exercise 3-5x/week. According to the potentially interfering factors patients were divided into groups depending on intensity of conditioning (myeloablative conditioning (MAC), reduced-intensity conditioning (RIC) and nonmyeloablative conditioning (NMC)) and cumulative dose of GC treatment (GC LOW 9 mg/kg prednisone) and were compared. Results: Median exercise adherence (target value 5 sessions weekly) during the inpatient period was 64% in MAC, 54% in RIC and 63% in NMC. The proportion of prematurely terminated training sessions ranged from 11% to 15%. Tiredness was the most frequent cause of exercise termination in all groups. Exercise adherence, duration (minutes/week) and type of training was significantly associated with GC dose. With regard to training response, results suggest GC LOW patients tend to respond better in knee extensor muscle strength. Conclusions: Exercise adherence during inpatient period is significantly impacted by dose of GC treatment but not by condition regimen. However, given the reasonable adherence rates also in the GC HIGH group data supports the feasibility and importance of exercising for all allo-HSCT patients during the inpatient period. (C) 2017 American College of Sports Medicine

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The Influence of External Load on Quadriceps Muscle and Tendon Dynamics during Jumping.

Tendons possess both viscous (rate-dependent) and elastic (rate-independent) properties that determine tendon function. During high-speed movements external loading increases both the magnitude (FT) and rate (RFDT) of tendon loading. PURPOSE: The influence of external loading on muscle and tendon dynamics during maximal vertical jumping was explored. METHODS: Ten resistance-trained men performed parallel-depth, countermovement vertical jumps with and without additional load (0%, 30%, 60% and 90% of maximum squat lift strength), while joint kinetics and kinematics, quadriceps tendon length (LT) and patellar tendon FT and RFDT were estimated using integrated ultrasound, motion analysis and force platform data and muscle-tendon modelling. RESULTS: Estimated FT and RFDT, but not peak LT, increased with external loading. Temporal comparisons between 0% and 90% loads revealed that FT was greater with 90% loading throughout the majority of the movement (11-81% & 87-95% movement duration). However, RFDT was greater with 90% load only during the early movement initiation phase (8-15% movement duration) but was greater in the 0% load condition later in the eccentric phase (27-38% movement duration). LT was longer during the early movement (12-23% movement duration) but shorter in the late eccentric and early concentric phases (48-55% movement duration) with 90% load. DISCUSSION: External loading positively influenced peak FT and RFDT but tendon strain appeared unaffected, suggesting no additive effect of external loading on patellar tendon lengthening during human jumping. Temporal analysis revealed that external loading resulted in a large initial RFDT that may have caused dynamic stiffening of the tendon and attenuated tendon strain throughout the movement. These results suggest that external loading influences tendon lengthening in both a load- and movement-dependent manner. (C) 2017 American College of Sports Medicine

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Mild Traumatic Brain Injury Leads to Decreased Inhibition and a Differential Response of Calretinin Positive Interneurons in the Injured Cortex

Journal of Neurotrauma , Vol. 0, No. 0.

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Prevalence of Fatigue and Associated Factors in a Spinal Cord Injury Population: Data from an Internet-Based and Face-to-Face Surveys

Journal of Neurotrauma , Vol. 0, No. 0.

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Should Young Children with Traumatic Brain Injury Be Compared with Community or Orthopedic Control Participants?

Journal of Neurotrauma , Vol. 0, No. 0.

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Paroxysmal freezing of gait in a patient with mesial frontal transient ischemic attacks

Rare patients have been reported who developed a mixture of gait disturbances following a focal lesion in the frontal lobe. Thus, the exact location of frontal lesion responsible for a specific gait disturbanc...

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Update on afatinib-based combination regimens for the treatment of EGFR mutation-positive non-small-cell lung cancer

Future Oncology Ahead of Print.

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The Influence of Intraoperative Testing on Surgical Decision-making During Cochlear Implantation.

Objective: To review our use of intraoperative testing during cochlear implantation (CI) and determine its impact on surgical decision-making. Study Design: Retrospective chart review. Setting: Tertiary referral center. Patients: A total of 197 children and adults who underwent a total of 266 primary and/or revision CI by a single surgeon from 2010 to 2015. Intervention: Intraoperative electrophysiologic monitoring including evoked compound action potentials and electrical impedances. Main Outcome Measures: Whether surgical management was changed based on intraoperative testing. Results: In only 2 of 266 patients (0.8%), the back-up device was used due to findings on intraoperative testing. In three patients (1.1%), X-ray was performed intraoperatively to confirm intracochlear electrode placement, which was found to be normal in all patients. Conclusion: Our data suggest that with respect to CI in children and adults in straightforward cases (e.g., normal anatomy, nondifficult insertion, etc.), routine intraoperative evoked compound action potentials, impedances, and imaging rarely influence surgical decision-making in our clinic and may have limited usefulness in these patients. The implications of this are discussed and a review of the literature is presented. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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Outcomes and Time to Emergence of Auditory Skills After Cochlear Implantation of Children With Charge Syndrome.

Objective: Review perioperative complications, benefits, and the timeframe over which auditory skills develop in children with CHARGE syndrome who receive a cochlear implant (CI). Study Design: IRB-approved retrospective chart review of children with CHARGE syndrome who had at least 12 months of cochlear implant use. Setting: Tertiary care children's hospital. Patients: Twelve children, seven males and five females. Mean age implant = 3.5 years (1.7-8.2 yr); mean duration follow-up = 4.7 years (1.5-10.1 yr). Intervention: Cochlear implantation. Main Outcome Measures: Auditory skills categorized into four levels, temporal bone imaging findings, perioperative complications, time to emergence of speech perception, expressive communication mode. Results: All children imaged with magnetic resonance imaging had cochlear nerve deficiency in at least one ear. Speech awareness threshold improved with the CI compared with aided preoperative in 83% of children, with means of 51.7 dB SAT preoperative and 27.1 dB with the CI (p

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The Hannover Coupler: Controlled Static Prestress in Round Window Stimulation With the Floating Mass Transducer.

Introduction: Stimulation of the cochlear round window (RW) with the floating mass transducer (FMT) still suffers from large variation in clinical outcomes. Beside the geometric mismatch between RW and FMT diameter that is a known limiting factor in achieving optimal coupling between actuator and RW membrane, the applied static force between FMT and RW is usually undefined. In this study, the feasibility and efficacy of a specially designed FMT coupler permitting application of static preloads to the RW membrane to optimize FMT-RW coupling was investigated. Methods: Experiments were performed in fresh human cadaveric temporal bones. The "Hannover Coupler" FMT-prosthesis has a spherical tip (d=0.5 mm) at the front end and a spring at the prosthesis back that enables the application of static preloads and mobility of the FMT at the same time. Stapes footplate (SFP) displacements in response to acoustic stimulation of the tympanic membrane and to RW stimulation by the FMT were measured by a Laser-Doppler vibrometer. Results: Average SFP displacement responses of ASTM standard F2504-05 compliant temporal bones to RW stimulation by the "Hannover Coupler" were dependent on the applied force (~0-100 mN) and increased by up to 25 dB at frequencies >= 1 kHz. When averaged at speech relevant frequencies (0.5, 1, 2, 4 kHz) SFP displacements showed a global maximum at RW preloads of ~4 mN. Conclusion: The coupling between FMT and RW membrane was improved by the application of static RW preloads as indicated by increased SFP amplitudes to RW stimulation. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

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From Japan to Europe: the importance to assess excessive daytime sleepiness in adults with ADHD symptoms

We read with great interest the article [1] by Ito, which presents the findings of a web-based study on the prevalence of excessive daytime sleepiness (EDS) and ADHD symptoms in adults with possible ADHD. Their findings show that the prevalence and severity of EDS in Japanese adults with ADHD symptoms are higher compared to those individuals classified as non-ADHD (9822 subjects). This study suggests that EDS and inattentive symptoms share a common underlying mechanism. We thank the authors for highlighting the importance of EDS in ADHD patients.

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Are we reproducible in measurement of NET liver metastasis?

Accurate measurement of well-differentiated neuroendocrine tumours (NET) liver metastases is critical to determine tumour slope and to assess treatment efficacy.Our objectives were to determine which CT or MRI sequence is the most reproducible to measure NET liver metastases and to assess the percentage of variability of measurements.Intra and inter-observer variability were studied on triphasic abdominal CT or liver MRI in 22 and 32 NET patients respectively. Patients were treatment-naïve or under somatostatin analogues.

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Critical Ischemia Times and The Effect of Novel Preservation Solutions HTK-N and TiPROTEC on Tissues of a Vascularized Tissue Isograft.

Background: We herein investigate critical ischemia times and the effect of novel preservation solutions HTK-N and TiProtec on the individual tissues of a rat limb isograft. Methods: Orthotopic hind-limb transplantations were performed in male Lewis rats following 2h, 6h or 10h of cold ischemia. Limbs were flushed and stored in either HTK-N, TiProtec, HTK or saline solution. Muscle, nerve, vessel, skin and bone samples were procured on day 10 for histology, immunohistochemistry, confocal and electron microscopy and RTqPCR analysis. Results: Histomorphology of the muscle showed a mainly perivascular inflammatory infiltrate, fibrotic degeneration and neovascularization after 6h and 10h of cold ischemia. However, centrally aligned nuclei observed in muscle fibers suggest for muscle regeneration in these samples. In addition to Wallerian degeneration, nerve injury was significantly (p=0.032) aggravated after prolonged cold ischemia. Proinflammatory and regulatory cytokines were most significantly upregulated after 2h cold ischemia. Our data suggest no superiority of novel perfusates HTK-N and TiProtec in terms of tissue preservation, compared to HTK and saline. Conclusions: Limiting cold ischemia time below 6h is the most significant factor to reduce tissue damage in vascularized tissue transplantation. Signs of muscle regeneration give rise that ischemic muscle damage in limb transplantation might be reversible to a certain extent. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Targeted Next-generation Sequencing in Brazilian Children With Nephrotic Syndrome Submitted to Renal Transplant.

Background: The aims of this study were to identify the genetic mutations profile in Brazilian children with nephrotic syndrome and to determine a genotype-phenotype correlation in this disease. Methods: Next generation sequencing (NGS) and mutation analysis were performed on 24 genes related to nephrotic syndrome in a cross-sectional study involving 95 children who underwent kidney transplantation due to nephrotic syndrome, excluding congenital cases. Results: A total of 149 variants were identified in 22 out of 24 sequenced genes. The mutations were classified as pathogenic, likely pathogenic, likely benign and benign per the chance of causing the disease. NPHS2 was the most common mutated gene. We identified 8 patients (8.4%) with hereditary NS and 5 patients (5%) with probably genetically caused NS. COL4A3-5 variants were found as well, but it is not clear whether they should be considered isolated FSGS or simply a misdiagnosed type of the Alport spectrum. Considering the clinical results, hereditary NS patients presented a tendency to early disease onset when compared to the other groups (p=0.06) and time to end stage renal disease (ESRD) was longer in this group (p=0.03). No patients from hereditary NS group had NS recurrence after transplantation. Conclusions: This is the first study in children with steroid resistant nephrotic syndrome who underwent kidney transplantation using NGS. Considering our results, we believe this study has shed some light to the uncertainties of genotype-phenotype correlation in NS, where several genes cooperate to produce or even to modify the course of the disease. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Pharmacokinetics and Clinical Outcomes of Generic Tacrolimus (Hexal) Versus Branded Tacrolimus in De Novo Kidney Transplant Patients: A Multicenter, Randomized Trial.

Background: Scrupulous comparison of the pharmacokinetic and clinical characteristics of generic tacrolimus formulations versus the reference drug (Prograf) is essential. Pharmacokinetics of the TacHexal formulation are similar to Prograf in stable renal transplant patients but data in de novo patients is lacking. Methods: De novo kidney transplant patients were randomized to generic tacrolimus (Tacrolimus Hexal [TacHexal]) or Prograf in a 6-month open-label study. Results: The primary endpoint, the dose-normalized AUC0-12h ratio at month 1 posttransplant, was similar with TacHexal or Prograf: back-transformed geometric means of adjusted log-transformed values (ANOVA) were 18.99 ng*h/L (TacHexal) and 20.48 ng*h/L (Prograf) (ratio 1.08 [90% CI 0.84; 1.38]; p=0.605). The dose-normalized peak concentration (Cmax) geometric means at month 1 was also comparable between treatments (ratio 1.16 [90% CI 0.88; 1.54], p=0.377). There were no relevant differences in other pharmacokinetic parameters at month 1, or in AUC0-4 and trough concentration when measured at months 3 and 6. The adjusted change in mean estimated GFR from baseline to month 6 (Nankivell) was noninferior for TacHexal versus Prograf using observed values (47.7 versus 38.6mL/min/1.73m2, p

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Tacrolimus Trough Concentration Variability and Disparities in African American Kidney Transplantation.

Background: Low tacrolimus concentrations have been associated with higher risk of acute rejection, particularly within African-American (AA) kidney transplant recipients; little is known about intrapatient tacrolimus variabilities impact on racial disparities. Methods: Ten year, single-center, longitudinal cohort study of kidney recipients. Intrapatient tacrolimus variability was assessed using the coefficient of variation (CV) measured between 1 month posttransplant and the clinical event, with a comparable period assessed in those without events. Pediatrics, nontacrolimus/mycophenolate regimens and nonrenal transplants were excluded. Multivariable Cox regression models were used to analyze data. Results: 1411 recipients were included (54.4% AA) with 39 521 concentrations utilized to assess intrapatient tacrolimus CV. Overall, intrapatient tacrolimus CV was higher in AAs vs non-AAs (39.9+/-19.8 % vs. 34.8+/-15.8% p40%) was a significant explanatory variable for disparities in AAs; the crude relative risk of acute rejection in AAs was reduced by 46% when including tacrolimus variability in modeling and reduced by 40% for graft loss. Conclusions: These data demonstrate that intrapatient tacrolimus variability is strongly associated with acute rejection in AAs and graft loss in all patients. Tacrolimus variability is a significant explanatory variable for disparities in AA recipients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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New and cost-effective way of retracting orbital contents during repair of the orbital floor

Publication date: Available online 28 June 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): N. Bhatti, S. Ali, S. Holmes

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Effects of phylogeny and locomotor style on the allometry of body mass and pelvic dimensions in birds

Abstract

The pelvic girdle provides physical support and attachment for the hind limb musculature. In birds there is variability in pelvic morphology across different orders and this has been used as evidence for various types of locomotion. However, the morphological variation of pelvic bones has yet to be studied systematically in birds. Therefore, we investigated basic allometric relationships among female body mass (as a size proxy) and various pelvic measurements in a phylogenetic context. We also examined in detail the inter-relationships among various pelvic measurements. Also considered were the effects of broader taxonomic relationships at the level of order, with further examination of the influence of style of terrestrial locomotion on the allometric relationships. Positive relationships were initially found among all pelvic linear measurements and female body mass (FBM). The relationships among measures of pelvic width and FBM were isometric, whereas those between pelvic length and FBM showed positive allometry. Also, FBM explained more of the variance in pelvic length than in width. Similarly, the angle of the pelvis had a significant negative relationship, but FBM only explained a very low proportion of the variation in pelvic angles. In general terms, ancova showed that the effect of FBM was smaller than the effect of locomotor style in this species set. Both the synsacrum and pelvic girdle play roles in weight support and therefore scale in proportion to body weight accordingly. All three parts of the pelvis (ilium, ischium and pubis) are attached around the acetabulum and also provide muscle attachment points, so it might be expected for them to scale in a similar manner. Increased angulation of the pelvis is linked to orders which employ their hind limbs in feeding, perching and running, although FBM also explains a very low proportion of the variation in pelvic angle. Muscle attachment and the confines on morphology presented by locomotion explain much of the variation exhibited by the relationships among pelvic measurements.

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Cost analysis of microtia treatment in the Netherlands

Ear reconstruction for microtia is a challenging procedure. Although analyzing aesthetic outcome is crucial, there is a paucity of information with regard to financial aspects of microtia reconstruction. This study was conducted to analyze the costs associated with ear reconstruction with costal cartilage in patients with microtia.

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Sustained attention ability in schizophrenia: investigation of conflict monitoring mechanisms

Amongst the main cognitive deficits in schizophrenia, impairments in sustained attention have been considered to be characteristic since the first descriptions and definition of the disorder (Kraepelin, 1919; Bleuler, 1950; Shakow, 1962; Nuechterlein et al., 1984). Nowadays, they are still considered as a hallmark of schizophrenia (Green, 1996; Green et al., 2000; Nuechterlein et al., 2004) and recognized as a probable causal explanation of multiple impairments observed in these patients (Green, 1996; Green et al., 2000; Green et al., 2004).

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Celiac disease and a novel association with a multifocal acquired motor axonopathy (MAMA)

Human rights

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Propriospinal cutaneous-induced EMG suppression is unaltered by anodal tDCS of healthy motor cortex

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique with potential application as an adjuvant to neuro-rehabilitation of the upper limb. Anodal tDCS (a-tDCS) is expected to increase corticomotor excitability and cathodal tDCS (c-tDCS) decrease corticomotor excitability (Nitsche et al., 2000; Nitsche et al., 2008; Stagg et al., 2011). The exact mechanisms of tDCS are yet to be elucidated, however corticomotor excitability may be modulated via acute subthreshold shifts in the membrane potential that mediates polarity-specific changes in synaptic plasticity (Stagg et al., 2011).

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Temporal-spatial characteristics of phase-amplitude coupling in electrocorticogram for human temporal lobe epilepsy

Abnormal discharge of neurons in the epileptic human brain causes the specificity of the neural oscillations of the cerebral cortex. The low-frequency and high-frequency neural oscillations of some frequency bands have been known as the essential biomarkers of the epileptogenicity and epileptic seizure-onset zones. The dynamic process of very low frequency oscillations (LFOs) in the intracranial electroencephalographic recordings has been found to occur during the preictal state in the refractory epilepsy patients (Ren et al., 2011).

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The long-term impact of oncoplastic breast conserving surgery using Latissimus Dorsi miniflaps on mammographic surveillance and the detection of local recurrence

Latissimus Dorsi Miniflap is a breast-conserving volume replacement technique for reconstruction of large breast defects. While mammographic features of Mini Flap reconstruction have been described, little is known about the incidence, mode of presentation and size of local recurrence after this procedure. The aim of this study was to investigate the impact of Latissimus Dorsi Miniflap reconstruction on frequency, presentation and detection of local recurrence.

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Safety and effectiveness of eribulin in Japanese patients with locally advanced or metastatic breast cancer: a post-marketing observational study

Summary

Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m²) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs). Secondary endpoints included overall response rate (ORR) and time to treatment failure (TTF). Results Of 968 patients registered at 325 institutions, 951 and 671 were included in the safety and effectiveness analyses, respectively. In the safety population, ADRs were observed in 841 patients (88.4%). The most common (≥15% incidence) were neutropenia (66.6%), leukopenia (62.4%), lymphopenia (18.4%), and peripheral neuropathy (16.8%). The most common grade ≥ 3 ADRs (>5% incidence) were neutropenia (59.8%), leukopenia (50.5%), lymphopenia (16.1%), and febrile neutropenia (7.7%). In the effectiveness population, ORR was 16.5% (95% confidence interval: 13.7, 19.4). The median TTF was 127 days (95% confidence interval: 120, 134). Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings.

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Update on afatinib-based combination regimens for the treatment of EGFR mutation-positive non-small-cell lung cancer

Future Oncology Ahead of Print.

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Primary Squamous Cell Carcinoma of the Pancreas: a Case Report and Literature Review

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Posterior Reversible Encephalopathy Syndrome During Treatment with Aflibercept, 5-Fluorouracil, Leucovorin, and Irinotecan for Metastatic Colorectal Cancer

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Colon Metastasis, 8 years after Gastrectomy, for Stage I Gastric Cancer

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Rectal Cancer Surveillance—Recurrence Patterns and Survival Outcomes from a Cohort Followed up Beyond 10 Years

Abstract

Aim

The intensity and duration of surveillance for rectal cancer after surgical resection remain contentious. We evaluated the pattern of recurrences in a rectal cancer cohort followed up beyond 10 years.

Methods

An analysis was performed on a retrospective database of 326 patients with rectal cancer who underwent curative surgical resection from 1999 to 2007. The above study duration was chosen to ensure at least 10 years of follow-up. Data on patient demographics, peri-operative details, and follow-up outcomes were extracted from the database. The pattern of recurrences and investigative modality that detected recurrences was identified. Patients were followed up until either year 2016 or the day of their demise.

Results

Two hundred seventeen patients (66.6%) were male and 109 patients (33.3%) female. Median age was 64 years old. Close to a third of the patients received adjuvant therapy (34%). Among the 326 patients studied, 29.8% of (97/326) patients developed recurrence. 7.7% (25/326) had loco-regional recurrence while 22.1% (72/326) had distant metastasis. Median time to recurrence was 16 months (4–83) and 18 months (3–81), respectively. Computed tomography scan was the best modality to detect both loco-regional and distant recurrences (48% in loco-regional and 41.7% in distant metastasis). The most common site of distant metastasis is the lung (34.7%). The salvage rate for loco-regional and distant recurrences was 52 and 12.5%, respectively.

Conclusion

The predominant pattern of recurrence in rectal cancer is distant disease. Surveillance regimes may need to be altered to increase early detection of distant metastases.

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Prevalence of Fatigue and Associated Factors in a Spinal Cord Injury Population: Data from an Internet-Based and Face-to-Face Surveys

Journal of Neurotrauma , Vol. 0, No. 0.

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Should Young Children with Traumatic Brain Injury Be Compared with Community or Orthopedic Control Participants?

Journal of Neurotrauma , Vol. 0, No. 0.

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Upregulation of circulating myomiR following short-term energy restriction is inversely associated with whole-body protein synthesis

The objective of the present investigation was to determine whether energy restriction (ER) influences expression of skeletal muscle specific microRNA in circulation (c-myomiR), and if changes in c-myomiR are associated with rates of whole-body protein synthesis. Sixteen older (64 ± 2 yrs) overweight (28.5 ± 1.2 kg·m^-2) males enrolled in this 35-day controlled feeding trial. A 7-day weight maintenance (WM) period was followed by 28 days of 30% ER. Whole-body protein turnover was determined from ¹⁵N-glycine enrichments in 24-hr urine collections, and c-myomiR (miR-1-3p, miR-133a-3p, miR-133b, and miR-206) expressions were assessed from serum samples using RT-qPCR at the conclusions of WM and ER. Participants lost 4.4 ± 0.3 kg body mass during ER (P < 0.05). Following 28 days of ER miR-133a and miR-133b expression was upregulated (P < 0.05) compared to WM. When all four c-myomiR were grouped as a c-myomiR Score (sum of the median fold change of all myomiR), overall expression of c-myomiR was higher (P < 0.05) at ER versus WM. Backward linear regression analysis of whole-body protein synthesis, breakdown, and carbohydrate, fat and protein oxidation determined protein synthesis to be the strongest predictor of c-myomiR Score. An inverse association (P < 0.05) was observed with ER c-myomiR Scores and whole-body protein synthesis (r = -0.729, r² = -0.530). Findings from the present investigation provide evidence that upregulation in c-myomiR expression profiles in response to short-term ER are associated with lower rates of whole-body protein synthesis.

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Renal Vascular and Glomerular Pathologies Associated with Spontaneous Hypertension in the Nonhuman Primate Chlorocebus aethiops sabaeus

Hypertension is a complex disease affecting 78 million adults in the United States. The etiology of essential hypertension is unknown and current experimental models do not recapitulate all behavioral and physiological characteristics of the pathology. Researchers should assess the translational capacity of these models and look to other animal models for the discovery of new therapies. Chlorocebus aethiops sabaeus, the African Green Monkey (AGM), is a nonhuman primate that develops spontaneous hypertension and is a novel translational model for the study of hypertension and associated diseases. In a group of 424 adult AGMs, 37% (157/424) exhibited systolic blood pressures (SBP) >140 mmHg (SBP: 172.0±2.2 mmHg) and were characterized as hypertensive (HT). 44% (187/424) were characterized as normotensive with SBP <120 mmHg (NT, SBP: 99.6±1.0 mmHg) and the remaining 18% (80/424) as borderline hypertensive (BHT, SBP: 130.6±0.6 mmHg). Compared to NT animals, HT AGMs are older (8.7±0.6 vs 12.4±0.7 years, p<0.05) with elevated heart rates (121.3±1.91 vs 34.3±2.1 BPM, p<0.05). BHT animals had average heart rates of 138.2±3.1 BPM (p<0.05 vs. NT) and were 11.00±0.9 years old. NT and HT animals had similar levels of angiotensinogen gene expression, plasma renin activity, and renal cortical renin content (p>0.05). HT monkeys exhibit renal vascular remodeling (wall/lumen ratio NT 0.11±0.01 vs HT 0.15±0.02, p<0.05) and altered glomerular morphology (Bowman's capsular space: NT 30.9±1.9% vs HT 44.4±3.1%, p<0.05). The hypertensive AGM is an animal model that is highly similar to humans and may help identify novel, effective targets for the treatment of hypertension.

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MEMORY T CELLS EXPRESSING AN NKG2D-CAR EFFICIENTLY TARGET OSTEOSARCOMA CELLS

Purpose: NKG2D ligands (NKG2DL) are expressed on various tumor types and immunosuppressive cells within tumor microenvironments, providing suitable targets for cancer therapy. Various immune cells express NKG2D receptors, including natural killer (NK) cells and CD8+ T cells. Interactions between NKG2DL and NKG2D receptors are essential for NK cell elimination of osteosarcoma tumor initiating cells. In this report, we used NKG2D-NKG2DL interactions to optimize an immunotherapeutic strategy against osteosarcoma. We evaluated in vitro and in vivo the safety and cytotoxic capacity against osteosarcoma cells of CD45RA- memory T cells expressing an NKG2D-4-1BB-CD3z chimeric antigen receptor (CAR). Experimental Design: CD45RA- cells from healthy donors were transduced with NKG2D CARs containing 4-1BB and CD3z signaling domains. NKG2D CAR expression was analyzed by flow cytometry. In vitro cytotoxicity of NKG2D-CAR+ CD45RA- T cells against osteosarcoma was evaluated by performing conventional 4-hour europium-TDA release assays. For the in vivo orthotopic model, 531MII YFP-luc osteosarcoma cells were used as targets in NOD-scid IL2Rgnull mice. Results: Lentiviral transduction of NKG2D-4-1BB-CD3z markedly increased NKG2D surface expression in CD45RA- cells. Genetic stability was preserved in transduced cells. In vitro, NKG2D-CAR+ memory T cells showed significantly increased cytotoxicity than untransduced cells against osteosarcoma cell lines, while preserving the integrity of healthy cells. NKG2D-CAR+ memory T cells had considerable antitumor activity in a mouse model of osteosarcoma, whereas untransduced T cells were ineffective. Conclusions:Our results demonstrate NKG2D-4-1BB-CD3z CAR-redirected memory T cells target NKG2DL-expressing osteosarcoma cells in vivo and in vitro and could be a promising immunotherapeutic approach for patients with osteosarcoma.

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DNA-methyltransferase 1 Induces Dedifferentiation of Pancreatic Cancer Cells through Silencing of Krüppel-like factor 4 Expression

Purpose: The dismal prognosis of pancreatic cancer has been linked to poor tumor differentiation. However, molecular basis of pancreatic cancer differentiation and potential therapeutic value of the underlying molecules remain unknown. We investigated the mechanistic underexpression of Krüppel-like factor 4 (KLF4) in pancreatic cancer and defined a novel epigenetic pathway of its activation for pancreatic cancer differentiation and treatment. Experimental Design: Expressions of KLF4 and DNMT1 in pancreatic cancer tissues were determined by immunohistochemistry and the genetic and epigenetic alterations of KLF4 in and KLF4's impact on differentiation of pancreatic cancer were examined using molecular biology techniques. The function of dietary 3,3'-diindolylmethane (DIM) on miR-152/DNMT1/KLF4 signaling in pancreatic cancer was evaluated using both cell culture and animal model. Results: Overexpression of DNMT1 and promoter hypermethylation contributed to decreased KLF4 expression in and associated with poor differentiation of pancreatic cancer. Manipulation of KLF4 expression significantly affected differentiation marker expressions in pancreatic cancer cells. DIM treatment significantly induced miR-152 expression, which blocked DNMT1 protein expression and its binding to KLF4 promoter region, and consequently, reduced promoter DNA methylation and activated KLF4 expression in pancreatic cancer cells. Additionally, DIM treatment caused significant inhibition of cell growth in vitro and tumorigenesis in animal model of pancreatic cancer. Conclusions: This is the first demonstration that dysregulated KLF4 expression associates with poor differentiation of pancreatic cancer. Epigenetic activation of miR-152/DNMT1/KLF4 signaling pathway by dietary DIM causes differentiation and significant growth inhibition of pancreatic cancer cells, highlighting its translational implications for pancreatic and other cancers.

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Radiosensitization of adenoid cystic carcinoma with MDM2 inhibition

Purpose: Adenoid cystic carcinoma (ACC) is a rare cancer arising from the major or minor salivary gland tissues of the head and neck. There are currently no approved systemic agents or known radiosensitizers for ACC. Unlike the more common head and neck squamous cell carcinomas that frequently harbor TP53 mutations, ACC contain TP53 mutations at a rate of <5%, rendering them an attractive target for MDM2 inhibition. Experimental Design: We report the successful establishment and detailed characterization of a TP53-WT ACC patient derived xenograft (PDX) which retained the histologic features of the original patient tumor. We evaluated this model for response to the MDM2 inhibitor AMG 232 as monotherapy and in combination with radiation (RT). Results: AMG 232 monotherapy induced modest tumor growth inhibition and RT monotherapy induced a transient tumor growth delay in a dose dependent fashion. Strikingly, combination treatment of AMG 232 with RT (including low dose RT of 2 Gy/fraction) induced dramatic tumor response and high local tumor control rates three months following treatment. Post treatment analysis revealed that while both AMG 232 and RT alone induced TP53 tumor suppressive activities, combination therapy amplified this response with potent induction of apoptosis after combination treatment. Conclusions: These data identify that MDM2 inhibition can provide potent radiosensitization in TP53-WT ACC. In light of the absence of effective systemic agents for ACC, the powerful response profile observed here suggests that clinical trial evaluation of this drug/RT combination may be warranted to improve local control in this challenging malignancy.

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How Can Supervisors Contribute to the Return to Work of Employees Who have Experienced Depression?

Abstract

Background In Western countries, work disability due to depression is a widespread problem that generates enormous costs. Objective The goal of this study was to determine the types and prevalence of supervisor contributions during the different phases of the return-to-work (RTW) process (before and during the sick-leave absence, and during the RTW preparations) of employees diagnosed with depression. Moreover, we sought to determine which contributions actually facilitate employees’ RTW, and to identify the work accommodations most frequently implemented by supervisors at the actual time of their employee’s RTW. Methods Telephone interviews were conducted in Québec (Canada) with 74 supervisors working with employees who were already back at work or still on sick leave due to depression. A sub-sample of 46 supervisors who had already taken measures to facilitate their employees’ RTW was questioned about the work accommodations implemented. Results Most of the supervisors got along well with their employees before their sick leave and 72% stayed in contact with them during their leave. Nearly 90% of the supervisors encouraged their employees to focus primarily on their recovery before their RTW, but 43% pressured their employees to RTW as soon as possible. Cox regression analyses performed for the entire sample revealed that “the supervisors’ intention to take measures to facilitate their employees’ RTW” was the only significant predictor of the RTW at the time of the interview. The Kaplan–Meier survival curve showed that 50% of the employees were expected to RTW within the first 8 months of absence. Four of the most frequently implemented work accommodations were actions directly involving the supervisor (i.e. providing assistance, feedback, recognition, and emotional support to the employee). Conclusions This study shed light on the less explored point of view of the supervisor involved in the RTW process of employees post-depression. It highlighted the most frequent and effective supervisor contributions to the process. These results can be used to develop concrete action plans for training supervisors to contribute to the sustainable RTW of employees on sick leave due to depression.

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Gastric lanthanosis (lanthanum deposition) in dialysis patients treated with lanthanum carbonate

Lanthanum carbonate (LaC) is used to prevent hyperphosphatemia in dialysis patients. It is commonly believed that there is little LaC absorption from the intestines. However, La deposition in the gastric mucosa, which we coined “gastric lanthanosis”, was recently reported. We describe here the clinicopathological features of and a possible mechanism for gastric lanthanosis. This study included 23 patients with definite gastric lanthanosis. We extracted characteristic clinicopathological features of gastric lanthanosis by computed tomography (CT) imaging and endoscopic, histologic, electron-microscopic, and element analysis examinations. The Helicobacter pylori infection rate in the lanthanosis group was much lower than that among the general population. The clinicopathological features characteristic of gastric lanthanosis were mucosal high-density linear appearance by CT, reflective bright-white spots (BWS) by gastroscopy, eosinophilic histiocytes occasionally phagocytizing foreign materials by histology, and numerous electron-dense particles in the histiocytes. The particles had burr-like skeletons resembling La crystals. Gastric lanthanosis is an under-reported, but not a rare lesion. It is characterized by endoscopic BWS and histologic eosinophilic histiocytes in dialysis patients treated with LaC. The proposed mechanism for gastric lanthanosis is that LaC is dissolved by gastric juice, crystallized within the mucosa and is phagocytized by histiocytes.

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A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival

Glioblastoma (GBM) has a dismal prognosis. Evidence from preclinical tumor models and human trials indicates the role of GBM initiating cells (GIC) in GBM drug resistance. Here, we propose a new treatment option with tumor enzyme-activatable, combined therapeutic and diagnostic (theranostic) nanoparticles, which caused specific toxicity against GBM tumor cells and GICs. The theranostic cross-linked iron oxide nanoparticles (CLIO) were conjugated to a highly potent vascular disrupting agent (ICT) and secured with a matrix-metalloproteinase (MMP-14) cleavable peptide. Treatment with CLIO-ICT disrupted tumor vasculature of MMP-14 expressing GBM, induced GIC apoptosis and significantly impaired tumor growth. In addition, the iron core of CLIO-ICT enabled in vivo drug tracking with MR imaging. Treatment with CLIO-ICT plus temozolomide achieved tumor remission and significantly increased survival of human GBM bearing mice by more than 2 fold compared to treatment with temozolomide alone. Thus, we present a novel therapeutic strategy with significant impact on survival and great potential for clinical translation.

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Highly Accurate Detection of Cancer In Situ with Intraoperative, Label-Free, Multimodal Optical Spectroscopy

Effectiveness of surgery as a cancer treatment is reduced when all cancer cells are not detected during surgery, leading to recurrences that negatively impact survival. To maximize cancer cell detection during cancer surgery, we designed an in situ intraoperative, label-free, optical cancer detection system that combines intrinsic fluorescence spectroscopy, diffuse reflectance spectroscopy, and Raman spectroscopy. Using this multimodal optical cancer detection system, we found that brain, lung, colon, and skin cancers could be detected in situ during surgery with an accuracy, sensitivity, and specificity of 97%, 100%, and 93%, respectively. This highly sensitive optical molecular imaging approach can profoundly impact a wide range of surgical and noninvasive interventional oncology procedures by improving cancer detection capabilities, thereby reducing cancer burden and improving survival and quality of life. Cancer Res; 77(14); 1–9. ©2017 AACR.

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Effect of humic acid on uranium(VI) retention and transport through quartz columns with varying pH and anion type

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): Liang Du, Shicheng Li, Xiaolong Li, Ping Wang, Zhaoya Huang, Zhaoyi Tan, Chunli Liu, Jiali Liao, Ning Liu
Humic acid (HA)¹ is ubiquitous in the environment and is an important factor in the migration behavior of U(VI) in the geological medium. The present work investigated the effect of HA on the migration behavior of U(VI) using quartz column experiments at different pH values and in the presence of various anions. The U(VI) adsorption characteristics and speciation were also studied to illuminate further the migration behavior of U(VI). Our results indicated that, at pH 6.0, HA slightly increased the migration velocity of U(VI) during the initial phase and reduced the quantity of eluted U(VI) because of the formation of HA-U(VI). The relative concentration (c/c0) of U(VI)was higher in the HA-U system at pH 8.0 than that at pH 5.0 because of the higher solubility of HA in basic solutions and the difference in charge of HA-U(VI). In the U-HA-anion system at pH 6.0, the breakthrough pore volumes (PVs²) of U(VI) in electrolytes containing Cl⁻ and SO4²⁻ anions (PV = 8) are much higher than for solutions containing phosphate (PV = 3), while the HA migration behavior was not significantly affected by the type of anion. Thus, the fast migration of U(VI) under HA and phosphate was attributed to phosphate rather than HA. This result suggests that phosphate should be given more attention in predictions of U(VI) migration, especially in regions with high groundwater phosphate content.

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Hepatocellular Malignant Neoplasm-NOS: A Clinicopathologic Study of 11 Cases from a Single Institution

Abstract

Aims

The primary aim of this study is to characterize hepatocellular malignant neoplasm, NOS (HEMNOS), a new provisional entity describing a subset of paediatric hepatocellular tumours, which have histological features of neither typical hepatoblastoma (HB) nor hepatocellular carcinoma (HCC).

Methods and results

The clinicopathological features of 11 patients with HEMNOS were analyzed retrospectively. The median age and serum alpha-fetoprotein level at diagnosis was 7 years and 182,000 ng/mL respectively. Ten patients presented with PRETEXT stage III/IV multifocal tumours, eight with major vascular involvement, three with lung metastases, and three with extrahepatic extension. The original pathology diagnoses were: HB in seven patients, HCC in two and HEMNOS in two. Our pathology review of pre-chemotherapy specimens showed that six tumours had equivocal/overlapping histological features of HB and HCC, four had predominant HB histology along with focal HCC-like histology, and one had HB histology. Seven of nine post-chemotherapy resection specimens showed predominant HCC-like histology. Beta-catenin, glypican 3 and spalt-like transcription factor 4 immunostaining showed that all the tumours had a mixed HB/HCC immunophenotype. Telomerase reverse-transcriptase immunostaining showed nuclear staining in nine of the eleven tumours. All patients received chemotherapy and achieved gross total primary tumor resection. Nine of the eleven patients were treated with established HB chemotherapy regimens. After a median follow-up of 6.1 years (range, 1.2 to 11.8 years), all patients were in remission.

Conclusions

HEMNOS is a subtype of HB with focal HCC-like histology, a high-risk clinical profile but favorable outcome following chemotherapy and complete tumor resection.

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Integration of visual and tactile information in reproduction of traveled distance

In the natural world, self-motion always stimulates several different sensory modalities. Here we investigated the interplay between a visual optic flow stimulus simulating self-motion and a tactile stimulus (air flow resulting from self-motion) while human observers were engaged in a distance reproduction task. We found that adding congruent tactile information (i.e. speed of the air flow and speed of visual motion are directly proportional) to the visual information significantly improves the precision of the actively reproduced distances. This improvement, however, was smaller than predicted for an optimal integration of visual and tactile information. In contrast, incongruent tactile information (i.e. speed of the air flow and speed of visual motion are inversely proportional) did not improve subjects' precision indicating that incongruent tactile information and visual information were not integrated. One possible interpretation of the results is a link to properties of neurons in the ventral intraparietal area (VIP) that have been shown to have spatially and action congruent receptive fields for visual and tactile stimuli.

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Effect of Whisker Geometry on Contact Force Produced by Vibrissae Moving at Different Velocities

Rats and mice are able to perform a variety of subtle tactile discriminations using their mystacial vibrissae. Increasingly, the design and interpretation of neurophysiological and behavioral studies are inspired by and linked to a more precise understanding of the detailed physical properties of the whiskers and their associated hair follicles. Here we used a piezoelectric sensor (bimorph) to examine how contact forces are influenced by the geometry of individual whisker hairs. For a given point along a whisker, bimorph signals are linearly related to whisker movement velocity. The slope of this linear function, called velocity sensitivity (VS), diminishes non-linearly as whisker diameter decreases. Whiskers differ in overall length, thickness and proximal-distal taper. Thus velocity sensitivity varies along an individual whisker and among different whiskers on the mystacial pad. Thinner, shorter whiskers, such as those located rostrally in rats and those in mice, have lower overall velocity sensitivities, rendering them potentially less effective for mediating discriminations that rely on subtle velocity cues. The non-linear effect of diameter combined with the linear effect of arc length produces radial distance tuning curves wherein small differences in the proximal-distal location of impacts yields larger differences in signal magnitude. Such position-dependent cues could contribute to the localization of objects near the face. Proximal-to-distal changes in contact location during whisking sweeps could also provide signals that aid texture discrimination.

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Motor learning in a complex balance task and associated neuroplasticity: A comparison between endurance athletes and non-athletes

Studies suggested that motor expertise is associated with functional and structural brain alterations, which positively affect sensorimotor performance and learning capabilities. The purpose of the present study was to unravel differences in motor skill learning and associated functional neuroplasticity between endurance athletes (EA) and non-athletes (NA). For this purpose, participants had to perform a multimodal balance task (MBT) training on two sessions which were separated by one week. Before and after MBT-training, a static balance task (SBT) had to be performed. MBT-induced functional neuroplasticity and neuromuscular alterations were assessed by means of functional near infrared spectroscopy (fNIRS) and electromyography (EMG) during SBT performance. We hypothesized that EA will show superior initial SBT performance and stronger MBT-induced improvements in SBT learning rates as compared to NA. On a cortical level, we hypothesized that MBT training will lead to differential learning-dependent functional changes in motor-related brain regions (such as primary motor cortex (M1)) during SBT performance. In fact, EA show superior initial SBT performance while learning rates did not differ between groups. On a cortical level, fNIRS recordings (TIME x GROUP interaction) revealed a stronger MBT-induced decrease in left M1 and inferior parietal lobe (IPL) for deoxygenated hemoglobin (deoxyHb) in EA. Even more interesting, learning rates were correlated with fNIRS changes (oxyHb) in right M1/IPL. Based on these findings, we provide novel evidence for superior MBT training-induced functional neuroplasticity in highly trained athletes. Future studies should investigate these effects in different sports disciplines to strengthen previous work on experience-dependent neuroplasticity.

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Impact of Glutamatergic and Serotonergic Neurotransmission on Diaphragm Muscle Activity after Cervical Spinal Hemisection

Incomplete cervical spinal cord hemisection at C2 (SH) disrupts descending excitatory drive to phrenic motoneurons, paralyzing the ipsilateral diaphragm muscle. Spontaneous recovery over time is associated with increased phrenic motoneuron expression of glutamatergic N-methyl-D-aspartate (NMDA) and serotonergic 5-HT2A receptors. We hypothesized that NMDA and 5-HT2A receptor-mediated neurotransmission play a role in ipsilateral diaphragm muscle activity post-SH. Adult male Sprague-Dawley rats were implanted with bilateral diaphragm EMG electrodes for chronic EMG recordings up to 28 days post-SH (SH 28D). The extent of recovery was calculated by peak root-mean-square (RMS) EMG amplitude. In all animals, absence of ipsilateral activity was verified at 3 days post-SH. Diaphragm EMG activity was also recorded during exposure to hypoxia-hypercapnia (10% O₂-5% CO₂). In SH animals displaying recovery of ipsilateral diaphragm EMG activity at SH 28D, cervical spinal cord segments containing the phrenic motor nucleus (C3-C5) were surgically exposed and either the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-AP5, 100 mM, 30 μl) or 5-HT2A receptor antagonist ketanserin (40 mM, 30 μl) was instilled intrathecally. Following D-AP5, diaphragm EMG amplitude was reduced ipsilaterally, during both eupnea (42% of pre-D-AP5 value; p = 0.007) and hypoxia-hypercapnia (31% of pre-D-AP5 value; p = 0.015), with no effect on contralateral EMG activity or in uninjured controls. Treatment with ketanserin did not change ipsilateral or contralateral RMS EMG amplitude in SH animals displaying recovery at SH 28D. Our results suggest that spinal glutamatergic NMDA receptor-mediated neurotransmission plays an important role in ipsilateral diaphragm muscle activity after cervical spinal cord injury.

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Dissecting the Satellite DNA Landscape in Three Cactophilic Drosophila Sequenced Genomes

Eukayote genomes are replete with repetitive DNAs. This class includes tandemly repeated satellite DNAs (satDNA) which are among the most abundant, fast evolving (yet poorly studied) genomic components. Here, we used high throughput sequencing data from three cactophilic Drosophila species, D. buzzatii, D. seriema and D. mojavensis, to access and study their whole satDNA landscape. In total, the RepeatExplorer software identified five satDNAs, three previously described (pBuM, DBC-150 and CDSTR198) and two novel ones (CDSTR138 and CDSTR130). Only pBuM is shared among all three species. The satDNA repeat length falls within only two classes, between 130-200bp or between 340-390bp. FISH on metaphase and polytene chromosomes revealed the presence of satDNA arrays in at least one of the following genomic compartments: centromeric, telomeric, subtelomeric or dispersed along euchromatin. The chromosomal distribution ranges from a single chromosome to almost all chromosomes of the complement. Fiber-FISH and sequence analysis of contigs revealed interspersion between pBuM and CDSTR130 in the microchromosomes of D. mojavensis. Phylogenetic analyses showed that the pBuM satDNA underwent concerted evolution at both interspecific and intraspecific levels. Based on RNAseq data, we found transcription activity for pBuM (in D. mojavensis) and CDSTR198 (in D. buzzatii) in all five analyzed developmental stages, most notably in pupae and adult males. Our data revealed that cactophilic Drosophila present the lowest amount of satDNAs (1.9% to 2.9%) within the Drosophila genus reported so far. We discuss how our findings on the satDNA location, abundance, organization and transcription activity may be related to functional aspects.

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Characterizing the Pyrenophora teres f. maculata - Barley Interaction Using Pathogen Genetics

Pyrenophora teres f. maculate is the cause of the foliar disease spot form net blotch (SFNB) on barley. To evaluate pathogen genetics underlying the P. teres f. maculate- barley interaction, we developed a 105-progeny population by crossing two globally diverse isolates, one from North Dakota, USA and the other from Western Australia. Progeny were phenotyped on a set of four barley genotypes showing a differential reaction to the parental isolates, then genotyped using a restriction-site associated - genotype by sequencing (RAD-GBS) approach. Genetic maps were developed for use in quantitative trait locus (QTL) analysis to identify virulence-associated QTL. Six QTL were identified on five different linkage groups and individually accounted for 20 to 37% of the disease variation with the number of significant QTL ranging from two to four for the barley genotypes evaluated. The data presented demonstrates the complexity of virluence involved in the P. teres f. maculate-barley interaction and begins to lay the foundation for understanding this important interaction.

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Impaired visuomotor generalization by inconsistent attentional contexts

In daily life, people are constantly presented with situations to learn and acquire new motor skills in complex environments, where attention is often distracted by other events. Being able to generalize and perform the acquired motor action in different environments is a crucial part of visuomotor learning. The current study examined whether attentional distraction impairs generalization of visuomotor adaptation or whether consistent distraction can operate as an internal cue to facilitate generalization. Using a dual-task paradigm combining visuomotor rotational adaptation and an attention-demanding secondary task, we showed that switching the attentional context from training (dual-task) to generalization (single-task) reduced the range of transfer of visuomotor adaptation to untrained directions. However, when consistent distraction was present throughout training and generalization, visuomotor generalization was equivalent to without distractions at all. Furthermore, this attentional-context dependent generalization was evident even when sensory modality of distractions differed between training and generalization. Therefore, the general nature of the dual tasks, rather than the specific stimuli, is associated with visuomotor memory and serves as a critical cue for generalization. Taken together, we demonstrated that attention plays a critical role during sensorimotor adaptation in selecting and associating multisensory signals with motor memory. This finding provides insight into developing learning programs that are generalizable in complex daily environments. -

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Response preparation and execution during intentional bimanual pattern switching

During continuous bimanual coordination, in-phase (IP; 0° relative phase) and anti-phase (AP; 180° relative phase) patterns can be stably performed without practice. Paradigms in which participants are required to intentionally switch between these coordination patterns have been used to investigate the interaction between the performer's intentions and intrinsic dynamics of the body's preferred patterns. The current study examined the processes associated with switching preparation and execution through the use of a startling acoustic stimulus (SAS) as the switch stimulus. A SAS is known to involuntarily trigger pre-programmed responses at a shortened latency and thus can be used to probe advance preparation. Participants performed cyclical IP and AP bimanual elbow extension-flexion movements in which they were required to switch patterns in response to an auditory switch cue, which was either non-startling (80 dB) or a SAS (120 dB). Results indicated that reaction time to the switch stimulus (i.e., switch onset) was significantly reduced on startle trials, indicative of advance preparation of the switch response. Similarly, switching time was reduced on startle trials, which was attributed to increased neural activation caused by the SAS. Switching time was also shorter for AP to IP trials, but only when the switching stimulus occurred at either the midpoint or reversal locations within the movement cycle, suggesting that the switch location may affect the intrinsic dynamics of the system.

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Intermuscular Coherence Reflects Functional Coordination

Coherence analysis has the ability to identify the presence of common descending drive shared by motor unit pools, and reveals its spectral properties. However, the link between spectral properties of shared neural drive and functional interactions among muscles remains unclear. We assessed shared neural drive between muscles of the thumb and index finger while participants executed two mechanically distinct precision pinch tasks, each requiring distinct functional coordination among muscles. We found that shared neural drive was systematically reduced or enhanced at specific frequencies of interest (~10 and ~40 Hz). While amplitude correlations between surface EMG signals also exhibited changes across tasks, only their coherence has strong physiological underpinnings indicative of neural binding. Our results support the use of intermuscular coherence as a tool to detect when co-activated muscles are members of a functional group or synergy of neural origin. Further, our results demonstrate the advantages of considering neural binding at 10, ~20, and >30 Hz, as indicators of task dependent neural coordination strategies.

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Removal of endogenous neuromodulators in a small motor network enhances responsiveness to neuromodulation

We studied the changes in sensitivity to a peptide modulator, crustacean cardioactive peptide (CCAP), as a response to loss of endogenous modulation in the stomatogastric ganglion (STG) of the crab, Cancer borealis. Our data demonstrate that removal of endogenous modulation for 24 hours increases the response of the LP neuron of the STG to exogenously applied CCAP. Increased responsiveness is accompanied by increases in CCAP receptor (CCAPr) mRNA levels in LP neurons, requires de novo protein synthesis, and can be prevented by co-incubation for the 24 hour period with exogenous CCAP. These results suggest that there is a direct feedback from loss of CCAP signaling to the production of CCAPr that increases subsequent response to the ligand. However, we also demonstrate that the modulator-evoked membrane current (IMI) activated by CCAP is greater in magnitude following combined loss of endogenous modulation and activity, compared with removal of just hormonal modulation. These results suggest that both receptor expression and an increase in the target conductance of the CCAP G-protein coupled receptor are involved in the increased response to exogenous hormone exposure following experimental loss of modulation in the STG.

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Caffeine Accelerates Recovery from General Anesthesia via Multiple Pathways

Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 minutes. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A2a adenosine receptor antagonist preladenant or the [cAMP]_i-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A2A receptor blockade and [cAMP]_i elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP]_i and adenosine receptor blockade play a role in this response.

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Discrimination of curvature from motion during smooth pursuit and fixation

Smooth pursuit and motion perception have mainly been investigated with stimuli moving along linear trajectories. Here we studied the quality of pursuit movements to curved motion trajectories in human observers and examined whether the pursuit responses would be sensitive enough to discriminate various degrees of curvature. In a two interval forced choice task subjects pursued a Gaussian blob moving along a curved trajectory and then they indicated in which interval the curve was flatter. We also measured discrimination thresholds for the same curvatures during a fixation. Motion curvature had some specific effects on smooth pursuit properties: trajectories with larger amounts of curvature elicited lower open-loop acceleration, lower pursuit gain and larger catch-up saccades compared to less curved trajectories. Initially, target motion curvatures were underestimated, however, around 300 ms after pursuit onset, pursuit responses closely matched the actual curved trajectory. We calculated perceptual thresholds for curvature discrimination, which were on the order of 1.5 degrees of visual angle (deg) for a 7.9 deg curvature standard. Oculometric sensitivity to curvature discrimination based on the whole pursuit trajectory was quite similar to perceptual performance. Oculometric thresholds based on smaller time windows were higher. Thus, smooth pursuit can quite accurately follow moving targets with curved trajectories, but temporal integration over longer periods is necessary to reach perceptual thresholds for curvature discrimination.

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Integration of visual and tactile information in reproduction of traveled distance

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Effect of Whisker Geometry on Contact Force Produced by Vibrissae Moving at Different Velocities

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Motor learning in a complex balance task and associated neuroplasticity: A comparison between endurance athletes and non-athletes

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Impact of Glutamatergic and Serotonergic Neurotransmission on Diaphragm Muscle Activity after Cervical Spinal Hemisection

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Impaired visuomotor generalization by inconsistent attentional contexts

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Response preparation and execution during intentional bimanual pattern switching

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Intermuscular Coherence Reflects Functional Coordination

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Removal of endogenous neuromodulators in a small motor network enhances responsiveness to neuromodulation

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Caffeine Accelerates Recovery from General Anesthesia via Multiple Pathways

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Discrimination of curvature from motion during smooth pursuit and fixation

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Task-specific, dimension-based attentional shaping of motion processing in monkey area MT

Non-spatial selective attention is based on the notion that specific features or objects in the visual environment are effectively prioritized in cortical visual processing. Feature-based attention (FBA) in particular, is a well- studied process that dynamically and selectively addresses neurons preferentially processing the attended feature attribute (e.g. leftward motion). In everyday life, however, behavior may require high sensitivity for an entire feature dimension (e.g. motion), but experimental evidence for a feature dimension-specific attentional modulation on a cellular level is lacking. Therefore, we investigated neuronal activity in macaque motion-selective medio-temporal area (MT) in an experimental setting requiring the monkeys to detect either a motion change or a color change. We hypothesized that neural activity in MT is enhanced when the task requires perceptual sensitivity to motion. In line with this, we found that mean firing rates were higher in the motion task, and response variability and latency were lower as compared to the color task, despite identical visual stimulation. This task-specific, dimension-based modulation of motion processing emerged already in the absence of visual input, was independent of the relation between the attended and stimulating motion direction, and was accompanied by a spatially global reduction of neuronal variability. The results provide single cell support for the hypothesis of a feature dimension-specific top-down signal emphasizing the processing of an entire feature class.

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Task-specific, dimension-based attentional shaping of motion processing in monkey area MT

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Effect of orthognathic surgery on profile esthetics in Class II:1 malocclusions

Abstract

Objectives

To measure the effect of orthognathic surgery on Class II:1 profile silhouette esthetics and to identify pretreatment parameters and thresholds for consistent esthetic improvement.

Methods

Pre- and posttreatment black profile silhouettes of 20 patients with Class II:1 malocclusion who had received combined orthodontic/orthognathic treatment were evaluated retrospectively by 20 European orthodontists and laypeople each using a visual analogue scale (VAS). A variety of pretreatment skeletal and facial angles were measured cephalometrically and on the silhouette profiles. Descriptive statistics and Pearson’s correlation coefficients were calculated.

Results

The population showed a mean VAS improvement of 12.6%. VAS changes were significantly and directly related to pretreatment ANB in all evaluator groups (r = 0.48–0.59), whereas the interrelation with the degree of pretreatment profile convexity angle was less clear and statistically significant for the orthodontic evaluators only (r = −0.34 to −0.51). The highest correlation coefficients in all evaluator groups were seen for the relationship with pretreatment VAS scores (r = −0.64 to −0.73).

Conclusion

The lower the pretreatment VAS score and the profile convexity angles or the larger the pretreatment ANB angles were, the more the VAS improved. Pretreatment thresholds for consistent improvements were as follows: VAS score < 20 mm, ANB > 8°, and profile angle ≤ 155°.

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Incidence and severity of gingival invaginations associated with early versus late initiation of orthodontic space closure after tooth extraction

Abstract

Objective

Gingival invaginations are a common side effect of orthodontic extraction–space closure. The timing of initiating the closure of an extraction space varies greatly in clinical practice. In this multicenter pilot and randomized controlled trial, we prospectively investigated whether initiating space closure in the early stage of wound healing would benefit the incidence and severity of invaginations developing in the extraction sites.

Methods

A total of 368 patients were screened for indications to extract at least one mandibular premolar. Those recruited were randomly assigned to one of two treatment arms: initiation of space closure either 2–4 weeks (arm A) or ≥12 weeks (arm B) after tooth extraction. Clinical data regarding treatment process and periodontal tissue response were recorded during and after space closure and analyzed by a specialized biometrics unit. The study was performed under continuous surveillance by an independent study control center.

Results

A total of 74 extraction sites were analyzed. Regarding the incidence of gingival invaginations, there were no significant intergroup differences [p = 0.13; group A comprising 37/44 (84.1%) and group B 29/30 (96.7%) invaginated sites]. The same was true based on either maxillary (p = 0.52) or mandibular (p = 0.21) sites only, and the severity of the invaginations did not differ between the treatment arms.

Conclusions

As to the incidence and severity of gingival invaginations, we did not notice any statistically significant differences between the two timeframes. Our data do, however, provide a basis to identify additional confounders and to improve the accuracy of case-load estimations for future trials.

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Effects of combined orthodontic-orthognathic treatment for class II and III correction on posterior airway space

Abstract

Objectives

Comparison of treatment effects on the posterior airway space (PAS) in patients treated with combined orthodontic–orthognathic surgical treatment.

Methods

Pre- and postsurgical lateral cephalograms of 53 (34 females, 19 males) Caucasian patients were analyzed using a customized set of measurements. According to malocclusion (Class II or III) and surgical approach (either monognathic or bignathic), patients were allocated into four groups. PAS was assessed from cranial to caudal at six levels (P1–P6). Paired t tests were used for intragroup and t tests for independent samples for intergroup comparisons. Results were considered statistically significant at p < 0.05.

Results

In patients treated for Class II malocclusion, PAS retropalatally (P1 level) almost remained unchanged, whereas measurements at levels P2–P6 showed a mean increase ranging from approximately 2–5.5 mm. Significant changes were most pronounced in monognathic Class II patients (group 1) at levels P2–P4 with mean values ranging from approximately 3.7–5.5 mm. In patients treated for Class III malocclusion (groups 3 and 4), measurements at the P1 level almost remained unchanged in patients who underwent mandibular setback surgery (group 3), whereas the same measurements exhibited significant increase (>6 mm) in patients treated with bignathic surgery (group 4).

Conclusions

Bignathic surgery led to smaller changes of pharyngeal depth in Class II and III patients than monognathic surgery. Alterations of the PAS due to orthognathic surgery should be considered during orthodontic and presurgical treatment planning.

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Loss of CD55 in Eculizumab-Responsive Protein-Losing Enteropathy

To the Editor: Protein-losing enteropathy usually manifests as peripheral and visceral edema due to hypoalbuminemia. We followed a large consanguineous Muslim–Arab family that included six patients who had protein-losing enteropathy associated with hypercoagulability (Fig. S1A in the Supplementary…

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CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis

Genetic inquiry has contributed to our understanding of gastrointestinal diseases, associating at least 64 genes with early-onset or very-early-onset inflammatory bowel disease. Deleterious gene variants affect the intestinal epithelial barrier, phagocytosis processes, immune regulation, and…

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CRISPR/Cas9 targeting of GPRC6A suppresses prostate cancer tumorigenesis in a human xenograft model

GPRC6A is implicated in the pathogenesis of prostate cancer, but its role remains uncertain because of a purported tolerant gene variant created by substitution of a K..Y polymorphism in the 3rd intracellular ...

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Antibody targeting of claudin-1 as a potential colorectal cancer therapy

Metastatic colorectal cancer (mCRC) is one of the major causes of cancer-related death. Despite the substantial progress in mCRC management, it remains important to identify new therapeutic options and biologi...

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RERG suppresses cell proliferation, migration and angiogenesis through ERK/NF-κB signaling pathway in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a malignancy of the head and neck that is prevalent in Southeast Asia and southern China. Recent studies in epigenetics suggest that DNA methylation plays a pivotal role in th...

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Accuracy and Reliability of Intraoral Scanners: Are They the Better Option?

Abstract

Purpose of Review

The aim was to compare the accuracy of digital intraoral impressions with conventional impressions on the fabrication of different types of restorations. This study also compared the accuracy, reliability, and ease of use of different types of intraoral scanners available and correlated the results with the different scanning technologies.

Recent Findings

Digital impressions offer the same level of accuracy as conventional impressions regarding fabrication of crowns, fixed dental prostheses (FDPs), implant-supported crowns, and short-span FDPs with marginal gap values within the clinically acceptable range (<120 μm). However, for full-arch restorations, conventional impressions result in better accuracy.

Summary

Further enhancements needs to be undertaken regarding intraoral scanners to improve its accuracy regarding fabrication of full-arch restorations. Further in vivo studies evaluating the accuracy of intraoral digital impressions on the fabrication of a wider range of restorations such as inlays, veneers, and full-arch restoration need to be conducted.

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Bilateral inner ear damage after electrical injury: A case report

Publication date: Available online 28 June 2017
Source:Auris Nasus Larynx
Author(s): George Psillas, Marios Stavrakas, Ioanna Petrou, Dimitrios Rachovitsas, Konstantinos Markou
Electrical injury occurs as a result of direct contact with an electrical source. We present the case of a 62-year-old male patient, an electrician by profession, who was hit by a high-voltage electrical current while working with cables in proximity to a wet floor. The patient suffered from immediate loss of consciousness and five days later he started complaining of slight hearing loss, persistent vertigo, instability and bilateral tinnitus. A thorough audiological and vestibular examination revealed an extensive bilateral vestibulocochlear dysfunction. The exact pathogenetic mechanisms of inner ear dysfunction after electrical injury have not been fully elucidated, although it is believed that there is significant improvement with time. Long-term follow-up, medical assistance and psychological support are crucial factors for the patient management.

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Effect of orthognathic surgery on profile esthetics in Class II:1 malocclusions

Abstract

Objectives

To measure the effect of orthognathic surgery on Class II:1 profile silhouette esthetics and to identify pretreatment parameters and thresholds for consistent esthetic improvement.

Methods

Results

Conclusion

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Πληροφορίες

Τετάρτη 28 Ιουνίου 2017

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