Πέμπτη 14 Σεπτεμβρίου 2017

Asymmetry between ON and OFF alpha ganglion cells of mouse retina: integration of signal and noise from synaptic inputs

Abstract

ON and OFF pathways in the retina include functional pairs of neurons that, at first glance, appear to have symmetrically similar responses to brightening and darkening, respectively. Upon careful examination, however, functional pairs exhibit asymmetries in receptive field size and response kinetics. Until now, descriptions of how light-adapted retinal circuitry maintains a preponderance of signal over the noise have not distinguished between ON and OFF pathways. Here I present evidence of marked asymmetries between members of a functional pair of sustained alpha ganglion cells in the mouse retina. The ON cell exhibited a proportionately greater loss of SNR (signal-to-noise power ratio) from its presynaptic arrays to its postsynaptic currents. Thus the ON cell combines signal and noise from its presynaptic arrays of bipolar and amacrine cells less efficiently than the OFF cell does. Yet the inefficiency of the ON cell is compensated by its presynaptic arrays providing a higher SNR than the arrays presynaptic to the OFF cell, apparently to improve visual processing of positive contrasts. Dynamic clamp experiments were performed that introduced synaptic conductances into ON and OFF cells. When the amacrine-modulated conductance was removed, the ON cell's spike train exhibited an increase in SNR. The OFF cell, however, showed the opposite effect of removing amacrine input, which was a decrease in SNR. Thus ON and OFF cells have different modes of synaptic integration with direct effects on the SNR of the spike output.

This article is protected by copyright. All rights reserved



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WIDEROE Dash 8 = "The local bus"

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How can a nation W.O. a funktional lokal transport system provide seriouse health care ..? Seriously ..? If you`r comunety is so dissfunctiounat that it is unable to get you to your Doc. Why pay tax ..? Are you living in the "Stone Age" ..? Just asking... From Norway :-) ExEMTNor

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Is Dexmedetomidine a Miracle Drug for Sedation in Patients With Neuroacanthocytosis With Involuntary Movements?.

No abstract available

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Distribution Patterns of the Vulnerable Vessels Around Cervical Nerve Roots: A Computed Tomography-Based Study.

Objective: The aim of the study was to evaluate the prevalence of vulnerable vessels around the target of cervical transforaminal epidural steroid injection at the C3-C7 cervical nerve root levels in a clinical setting. Design: Retrospective, cross-sectional study was conducted. Participants: Patients complaining of neck or arm pain with no previous surgical history and who had undergone both precontrast and contrast-enhanced neck computed tomography were included retrospectively. Results: In 26 (21.0%) of 124 patients, none of the vulnerable vessels around the target of cervical transforaminal epidural steroid injection around both sides of the C3-C7 nerve roots were observed. Of 248 cervical root levels, the C3 level had 103 vessels (41.5%), the C4 level had 110 vessels (44.4%), the C5 level had 98 vessels (39.5%), the C6 level had 59 vessels (23.8%), and the C7 level had 34 vessels (13.7%) close to each target nerve root. In addition, variations of the vertebral artery at the C4-C7 level were observed in 11 (8.9%) of 124 patients. Conclusions: To prevent unexpected critical complications involving injury to vulnerable vessels during cervical transforaminal epidural steroid injection, it is recommended to routinely evaluate the vulnerable vessels around the cervical nerve root with computed tomography or Doppler ultrasound before cervical transforaminal epidural steroid injection, especially for the upper cervical nerve root level. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Effect of Full-Length Carbon Fiber Insoles on Lower Limb Kinetics in Patients With Midfoot Osteoarthritis: A Pilot Study.

Objectives: We investigated the effects of full-length carbon fiber (FCF) insoles on gait, muscle activity, kinetics, and pain in patients with midfoot osteoarthritis (OA). Design: We enrolled 13 patients with unilateral midfoot OA (mild: Visual Analog Scale [VAS] range, 1-3; moderate, VAS range, 4-7) and healthy controls. All participants were asked to walk under two conditions: with and without FCF insole. The outcome measures were ground reaction force, quantitative gait parameters, electromyography activities and pain severity (VAS). Results: In the patients with moderate midfoot OA, significantly longer gait cycle and higher muscle activity of lower limb during loading-response phase were observed while walking without FCF insoles. In the mild midfoot OA group, there was no significant difference in VAS score (without, 2.0 +/- 1.0 vs. with, 2.0 +/- 0.5) with FCF insole use. However, significantly reduced VAS score (without, 5.5 +/- 1.4 vs. with, 2.0 +/- 0.5) and muscle activity of the tibialis anterior and increased muscle activity of gastrocnemius were observed in the moderate midfoot OA group by using an FCF insole (P

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The Minimal Clinically Important Difference for the Rasch Neuropsychiatric Inventory Irritability and Aggression Scale for Traumatic Brain Injury

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Publication date: Available online 14 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): James F. Malec, Flora M. Hammond
ObjectiveTo determine the Minimal Clinically Important Difference (MCID) for a Rasch measure derived from the Irritability/Lability and Agitation/Aggression subscales of the Neuropsychiatric Inventory (NPI-TBI-IA).DesignDistribution-based statistical methods were applied to retrospective data to determine candidates for the MCID. These candidates were evaluated by anchoring the NPI-TBI-IA to Global Impression of Change (GIC) ratings by participants, significant others, and a supervising physician.Main Outcome MeasureNPI-TBI-IA.SettingPostacute rehabilitation outpatient clinic.Participants274 cases with observer ratings; 232 cases with self-ratings by participants with moderate-severe TBI at least 6 months post-injury.ResultsFor observer ratings on the NPI-TBI-IA, anchored comparisons found an improvement of ½ SD was associated with at least minimal general improvement on GIC by a significant majority (69-80%); ½ SD improvement on participant NPI-TBI-IA self-ratings was also associated with at least minimal improvement on the GIC by a substantial majority (77-83%). The percent indicating significant global improvement did not increase markedly on most ratings at higher levels of improvement on the NPI-TBI-IA.ConclusionsA ½ SD improvement on the NPI-TBI-IA indicates the MCID for both observer and participant ratings on this measure.



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Benefits of the Restorative Exercise and Strength Training for Operational Resilience and Excellence Yoga Program for Chronic Lower Back Pain in Service Members: A Pilot Randomized Control Trial

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Publication date: Available online 14 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Krista Beth Highland, Audrey Schoomaker, Winifred Rojas, Josh Suen, Ambareen Ahmed, Zhiwei Zhang, Sarah Fink Carlin, Christian Calilung, Michael Kent, Chester Buckenmaier
ObjectiveTo examine the feasibility and preliminary effectiveness of an individualized yoga program.DesignPilot randomized control trial.SettingMilitary medical center.ParticipantsPatients (N=68) with chronic LBP.InterventionsRestorative Exercise and Strength Training for Operational Resilience and Excellence (RESTORE) program (9-12 individual yoga sessions) or treatment-as-usual (control) for 8-week period.Main Outcome MeasuresThe primary outcome was past 24-hour pain scores (Defense and Veterans Pain Rating Scale). Secondary outcomes included disability (Roland-Morris Disability Questionnaire), physical functioning, and symptom burden (Patient Reported Outcomes Measurement Information System-29 subscales). Assessment occurred at baseline, Week 4, Week 8, 3-month follow-up, and 6-month follow-up. Exploratory outcomes included the proportion of participants in each group reporting clinically meaningful changes at 3-month and 6-month follow-ups.ResultsGeneralized linear mixed models with sequential Bonferroni-corrected pairwise significance tests and chi-square analyses examined longitudinal outcomes. Secondary outcome significance tests were Bonferroni-adjusted for multiple outcome tests. The RESTORE group reported improved pain, compared to the control group. Secondary outcomes did not retain significance after Bonferroni-adjustments for multiple outcomes. Though, a greater proportion RESTORE participants reported clinically-meaningfully changes in all outcome at 3-month follow-up and symptom burden at 6-month follow-up.ConclusionRESTORE may be a viable non-pharmacologic approach to LBP with minimal side effects and research efforts are needed to compare effectiveness of RESTORE delivery formats (e.g., group versus individual) or to other treatment modalities.



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Rasch Analysis, Dimensionality, and Scoring of the Neuropsychiatric Inventory (NPI) Irritability and Aggression Subscales in Individuals with Traumatic Brain Injury

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Publication date: Available online 14 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): James F. Malec, Timothy E. Stump, Patrick O. Monahan, Jacob Kean, Dawn Neumann, Flora M. Hammond
ObjectiveTo develop, for versions completed by individuals with traumatic brain injury (TBI) and an observer, a more precise metric for the Neuropsychiatric Inventory (NPI) Irritability and Aggression scales using all behavioral item ratings for use with individuals with TBI and address the dimensionality of the represented behavioral domains.DesignRasch and confirmatory factor analyses of retrospective baseline NPI data from three treatment studies.SettingPostacute rehabilitation clinic.Participants287 cases with observer ratings; 238 cases with self-ratings by participants with complicated mild, moderate or severe TBI at least 6 months post-injury.Main Outcome MeasureFrequency and severity ratings from NPI Irritability/Lability and Agitation/Aggression subscales.ResultsConfirmatory factor analyses of both observer and participant ratings showed good fit for either a one-factor or two-factor solution. Consistent with this, the Rasch model also fit the data well with aggression items indicating the more severe end of the construct and irritability items populating the milder end.ConclusionsIrritability and aggression appear to represent different levels of severity of a single construct. The derived Rasch metric offers a measure of this construct based on responses to all specific items that is appropriate for parametric statistical analysis and may be useful in research and clinical assessments of individuals with TBI.



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Issue Information



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WIDEROE Dash 8 = "The local bus"

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How can a nation W.O. a funktional lokal transport system provide seriouse health care ..? Seriously ..? If you`r comunety is so dissfunctiounat that it is unable to get you to your Doc. Why pay tax ..? Are you living in the "Stone Age" ..? Just asking... From Norway :-) ExEMTNor

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WIDEROE Dash 8 = "The local bus"

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How can a nation W.O. a funktional lokal transport system provide seriouse health care ..? Seriously ..? If you`r comunety is so dissfunctiounat that it is unable to get you to your Doc. Why pay tax ..? Are you living in the "Stone Age" ..? Just asking... From Norway :-) ExEMTNor

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WIDEROE Dash 8 = "The local bus"

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How can a nation W.O. a funktional lokal transport system provide seriouse health care ..? Seriously ..? If you`r comunety is so dissfunctiounat that it is unable to get you to your Doc. Why pay tax ..? Are you living in the "Stone Age" ..? Just asking... From Norway :-) ExEMTNor

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Influence of Past Injurious Exercise on Fiber Type Specific Acute Anabolic Response to Resistance Exercise in Skeletal Muscle

We investigated influence of past injurious exercise on anabolic response of skeletal muscle fibers to resistance exercise (RE). Wistar rats were divided into exercise (E) and exercise after injury (I-E) groups. At age 10 wk, the right gastrocnemius muscle in each rat in the I-E group was subjected to strenuous eccentric contractions. Subsequently, RE was imposed on the same muscle of each rat at 14 wk of age in both groups. Peak joint torque and total force generation per body mass during RE were similar between the groups. Muscle protein synthe-sis (MPS) in the I-E group was higher than that in the E group 6 h after RE. Furthermore, lev-els of phospho-p70S6K (Thr389) and phospho-ribosomal protein S6 (phospho-rpS6) (Ser240/244), a downstream target of p70S6K, were higher in the I-E group than in the E group. For the anabolic response in each fiber type, the I-E group showed a higher MPS response in IIb, IIa, and I and a higher phospho-rpS6 response in IIx, IIa, and I than the E group. In the I-E group, the relative content of myosin heavy chain (MHC) IIa was higher and that of MHC IIb was lower than those in the E group. In addition, type IIa fibers showed a lower MPS response to RE than type IIb fibers in the I-E group. In conclusion, the past injurious exercise enhanced the MPS and phospho-rpS6 responses in type IIb, IIa, and I fibers and type IIx, IIa, and I fibers, respectively.



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Impact of sleep restriction on local immune response and skin barrier restoration with and without 'multi-nutrient' nutrition intervention

Systemic immune function is impaired by sleep restriction. However, the impact of sleep restriction on local immune responses, and to what extent any impairment can be mitigated by nutritional supplementation is unknown. We assessed the effect of 72-h sleep restriction (2-h nightly sleep) on local immune function and skin barrier restoration of an experimental wound, and determined the influence of habitual protein intake (1.5 g·kg-1·d-1) supplemented with arginine, glutamine, zinc sulfate, vitamin C, vitamin D3 and omega-3 fatty acids compared to lower protein intake (0.8 g·kg-1·d-1) without supplemental nutrients on these outcomes. Wounds were created in healthy adults by removing the top layer of ≤ 8 forearm blisters induced via suction, after adequate sleep (AS) or 48-h of a 72-h sleep restriction period (SR; 2-h nightly sleep). A subset of participants undergoing sleep restriction received supplemental nutrients during and after sleep restriction (SR+). Wound fluid was serially sampled 48-hpost-blistering to assess local cytokine responses. The IL-8 response of wound fluid was higher for AS compared to SR (area-under-the-curve (log10), 5.1±0.2 and 4.9±0.2 pg·mL-1, respectively (P=0.03); and, both IL-6 and IL-8 concentrations were higher for SR+ compared to SR (p<0.0001), suggestive of a potentially enhanced early wound healing response. Skin barrier recovery was shorter for AS (4.2 ± 0.9 days) compared to SR (5.0 ± 0.9 days) (P=0.02), but did not differ between SR and SR+ (P=0.18). Relatively modest sleep disruption delays wound healing. Supplemental nutrition may mitigate some decrements in local immune responses, without detectable effects on wound healing rate.



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Left Ventricular Strain Rate is Reduced during Voluntary Apnea in Healthy Humans

During an apneic event, sympathetic nerve activity increases resulting in subsequent increases in left ventricular afterload and myocardial work. It is unknown how cardiac mechanics are acutely impacted by the increased myocardial work during an apneic event. 10 healthy individuals (23 ± 3 yrs) performed multiple voluntary end-expiratory apnea (VEEA) maneuvers exposed to room air, while a subset (n=7) completed multiple VEEA exposed to hyperoxic air (100% FiO2). Beat-by-beat blood pressure, heart rate and stroke volume were measured continuously. Effective arterial elastance (EA) was calculated as an index of cardiac afterload and myocardial work calculated as the rate pressure product (RPP). Tissue Doppler echocardiography was used to measure left ventricular (LV) tissue velocities, and deformation via strain, and strain rate (SR). Systolic blood pressure (18 ± 13 mmHg, p<0.01), EA (0.13 ± 0.10 mmHg/mL, p<0.01), and RPP (9 ±10 mmHg x bpm 10-2, p<0.01) significantly increased with room air VEEA. This occurred in parallel with decreases in peak longitudinal systolic (-0.62 ± 0.41cm s-1, p<0.01) and early LV filling (-2.81 ± 1.99 cm s-1, p<0.01) myocardial velocities. Longitudinal SR (-0.30 ± 0.321/s, p=0.01) was significantly decreased during room air VEEA. VEEA with hyperoxia did not alter (p>0.18) EA or RPP and attenuated the systolic blood pressure response compared to room air. Myocardial velocities and LV strain rate response to VEEA were unchanged (p=0.30) with hyperoxia. Consistent with our hypotheses, VEEA-induced increases in EA and myocardial work impact left ventricular mechanics, which may depend, in part, on stimulation of peripheral chemoreceptors.



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Sympathetic function during whole-body cooling is altered in hypertensive adults

During moderate cold exposure, cardiovascular-related morbidity and mortality increase disproportionately in hypertensive adults (HTN); however, the mechanisms underlying this association are not well defined. We hypothesized that whole-body cold stress would evoke exaggerated increases in blood pressure (BP) and muscle sympathetic nerve activity (MSNA) in HTN compared to normotensive adults (NTN) and that sympathetic baroreflex function would be altered during cooling in HTN. MSNA (peroneal microneurography) and beat-to-beat BP (Finometer) were measured continuously in 10 NTN (6M/4W; age 53±3 yrs; resting BP 125±3/79±1 mmHg) and 13 HTN (7M/6W; age 58±2 yrs; resting BP 146±5/88±2 mmHg) during whole-body cooling-induced reductions in mean skin temperature (Tsk; water-perfused suit) from 34.0 to 30.5°C. During cooling, the increase in mean arterial pressure was greater in HTN (NTN: 6±2 vs. HTN: 11±1 mmHg; P=0.02) and accompanied by exaggerated increases in MSNA (NTN: 8±3 vs. HTN: 20±3 bursts•(100 heartbeats)-1; P<0.01). The slope of the relation between MSNA and diastolic BP did not change during cooling in NTN (Tsk 34.0°C: -4.4±0.8 vs. Tsk 30.5°C: -5.0±0.3 bursts•(100 heartbeats)-1•mmHg-1; P=0.47) but increased in HTN (Tsk 34.0°C: -3.6±0.4 vs. Tsk 30.5°C: -5.4±0.4 bursts•(100 heartbeats)-1•mmHg-1; P=0.02). These findings demonstrate that the cooling-induced increases in BP and MSNA are exaggerated in HTN. Further, during cooling, sympathetic baroreflex sensitivity increases in HTN, but not NTN, presumably to allow for baroreflex-mediated buffering of excessive cooling-induced increases in BP. Collectively, these findings suggest that sympathetic function is altered during whole-body cooling in hypertension.



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Meaningful Methods for Increasing Human Papillomavirus Vaccination Rates: An Integrative Literature Review

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States and is a well-known cause of oropharyngeal, cervical, vaginal, vulvar, penile, and anal cancers. Despite the proven efficacy of the HPV vaccine, vaccination rates remain persistently low. Much literature has focused on attitudes toward the HPV vaccine; however, researchers have also investigated strategies clinicians can use to improve vaccination attitudes and acceptance. Such strategies include provider education, vaccine reminder/recall, and chart audit and feedback.

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Minimally invasive endoscopic thyroid surgery using a collar access: experience in 246 cases with the CEViTS technique

Abstract

Background

The arguments for applying minimally invasive techniques are, besides cosmetic results, reduced access trauma and less postoperative pain. In thyroid surgery, cosmetic aspects are gaining importance. Whether minimally invasive endoscopic thyroid surgery is less painful has not been shown yet.

Method

In this study, we analyse the outcome of 246 patients who underwent cervical endoscopic video-assisted thyroid surgery (CEViTS) regarding the surgery itself, their postoperative pain and satisfaction with the procedure.

Results

CEViTS is routinely performed in our hospital. In this study, no postoperative bleedings that would have made a reoperation necessary occurred. All lobectomies could be completed endoscopically. In two cases, conversions (enlargement of the 5-mm incision to 25 mm) were necessary. Transient nerve palsy was registered in three patients (1.22%). One patient (0.41%) had a permanent palsy of the recurrent laryngeal nerve. In comparison to open surgery (n = 173 patients), the 246 CEViTS patients had a significantly lower pain level (p = 0.047).

Conclusions

Cervical endoscopic video-assisted thyroid surgery (CEViTS) can be considered a safe, less traumatizing and useful minimally invasive procedure in endoscopic thyroid surgery.



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Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model

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Publication date: Available online 14 September 2017
Source:International Journal of Psychophysiology
Author(s): Sara F. Milrad, Daniel L. Hall, Devika R. Jutagir, Emily G. Lattie, Sara J. Czaja, Dolores M. Perdomo, Mary Ann Fletcher, Nancy Klimas, Michael H. Antoni
IntroductionChronic Fatigue Syndrome (CFS) is a poorly understood illness that is characterized by diverse somatic symptoms, hypothalamic pituitary adrenal (HPA) axis dysfunction and heightened inflammatory indicators. These symptoms are often exacerbated and accompanied by psychological distress states and depression. Since depression is known to be associated with HPA axis dysfunction and greater inflammation, a psychoneuroendocrinological (PNE) model of inflammation was examined in persons diagnosed with CFS in order to uncover underlying biopsychosocial mechanisms in this poorly understood chronic illness.MethodsBaseline data were drawn from two randomized controlled trials testing the efficacy of different forms of psychosocial intervention, and included psychological questionnaires, di-urnal salivary cortisol, and blood samples. Data were analyzed with structural equation modeling (SEM).ResultsThe sample (N=242) was mostly middle-aged (Mage=49.36±10.9, range=20–73years), Caucasian (70.1%), female (84.6%), highly educated (88.6% completed some college, college, or graduate program), and depressed (CES-D M=23.87±12.02, range 2–57). The SEM supporting a psychoneuroendocrinological model of immune dysregulation in CFS fit the data χ2 (12)=17.725, p=0.1243, RMSEA=0.043, CFI=0.935, SRMR=0.036. Depression was directly related to evening salivary cortisol and inflammation, such that higher evening cortisol predicted greater depressive symptoms (β=0.215, p<0.01) and higher pro-inflammatory cytokines (interleukin-2 [IL-2], IL-6, and tumor necrosis factor-alpha [TNF-α] levels (β=0.185, p<0.05), when controlling for covariates.DiscussionResults highlight the role of depression, cortisol and inflammation in possible biological mechanisms involved in the pathophysiology of CFS. Time-lagged, longitudinal analyses are needed to fully explore these relationships.



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Phase I/II Trial of Anticarcinoembryonic Antigen Radioimmunotherapy, Gemcitabine, and Hepatic Arterial Infusion of Fluorodeoxyuridine Postresection of Liver Metastasis for Colorectal Carcinoma

Cancer Biotherapy & Radiopharmaceuticals Sep 2017, Vol. 32, No. 7: 258-265.


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Dual Targeting of Epidermal Growth Factor Receptor and HER3 by MEHD7945A as Monotherapy or in Combination with Cisplatin Partially Overcomes Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma Cell Lines

Cancer Biotherapy & Radiopharmaceuticals Sep 2017, Vol. 32, No. 7: 229-238.


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Synthesis, Positron Emission Tomography Imaging, and Therapy of Diabody Targeted Drug Lipid Nanoparticles in a Prostate Cancer Murine Model

Cancer Biotherapy & Radiopharmaceuticals Sep 2017, Vol. 32, No. 7: 247-257.


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Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects

Cancer Biotherapy & Radiopharmaceuticals Sep 2017, Vol. 32, No. 7: 266-273.


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A new primate assemblage from La Verrerie de Roches (Middle Eocene, Switzerland)

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Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): Raef Minwer-Barakat, Judit Marigó, Damien Becker, Loïc Costeur
Primates reached a great abundance and diversity during the Eocene, favored by warm temperatures and by the development of dense forests throughout the Northern Hemisphere. Here we describe new primate material from La Verrerie de Roches, a Middle Eocene karstic infill situated in the Jura Region (Switzerland), consisting of more than 80 dental remains. The primate assemblage from La Verrerie de Roches includes five different taxa. The best represented primate is Necrolemur aff. anadoni, similar in size and overall morphology to Necrolemur anadoni but resembling in some features the younger species Necrolemur antiquus. Microchoerines are also represented by two species of Pseudoloris, P. pyrenaicus and Pseudoloris parvulus, constituting the unique joint record of these two species known up to now. Remains of Adapiformes are limited to one isolated tooth of a large anchomomyin and another tooth belonging to the small adapine Microadapis cf. sciureus. The studied primate association allows assigning La Verrerie de Roches to the Robiacian Land Mammal Age. More specifically, this site can be confidently situated between the MP15 and MP16 reference levels, although the primate assemblage probably indicates some degree of temporal mixing. This is the first record of P. pyrenaicus and a form closely related to N. anadoni out of the Iberian Peninsula. The identification of these microchoerines in Switzerland gives further support to the connection of NE Spain and Central Europe during the Middle Eocene.



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Hominin track assemblages from Okote Member deposits near Ileret, Kenya, and their implications for understanding fossil hominin paleobiology at 1.5 Ma

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Publication date: Available online 13 September 2017
Source:Journal of Human Evolution
Author(s): Kevin G. Hatala, Neil T. Roach, Kelly R. Ostrofsky, Roshna E. Wunderlich, Heather L. Dingwall, Brian A. Villmoare, David J. Green, David R. Braun, John W.K. Harris, Anna K. Behrensmeyer, Brian G. Richmond
Tracks can provide unique, direct records of behaviors of fossil organisms moving across their landscapes millions of years ago. While track discoveries have been rare in the human fossil record, over the last decade our team has uncovered multiple sediment surfaces within the Okote Member of the Koobi Fora Formation near Ileret, Kenya that contain large assemblages of ∼1.5 Ma fossil hominin tracks. Here, we provide detailed information on the context and nature of each of these discoveries, and we outline the specific data that are preserved on the Ileret hominin track surfaces. We analyze previously unpublished data to refine and expand upon earlier hypotheses regarding implications for hominin anatomy and social behavior. While each of the track surfaces discovered at Ileret preserves a different amount of data that must be handled in particular ways, general patterns are evident. Overall, the analyses presented here support earlier interpretations of the ∼1.5 Ma Ileret track assemblages, providing further evidence of large, human-like body sizes and possibly evidence of a group composition that could support the emergence of certain human-like patterns of social behavior. These data, used in concert with other forms of paleontological and archaeological evidence that are deposited on different temporal scales, offer unique windows through which we can broaden our understanding of the paleobiology of hominins living in East Africa at ∼1.5 Ma.



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Paleoecological insights from fossil freshwater mollusks of the Kanapoi Formation (Omo-Turkana Basin, Kenya)

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Publication date: Available online 13 September 2017
Source:Journal of Human Evolution
Author(s): Bert Van Bocxlaer
The Early Pliocene Kanapoi Formation of the Omo-Turkana Basin consists of two fluvial/deltaic sedimentary sequences with an intermediate lacustrine sequence that was deposited in Paleolake Lonyumun, the earliest large lake in the basin. Overall, the geology and vertebrate paleontology of the Kanapoi Formation are well studied, but its freshwater mollusks, despite being a major component of the benthic ecosystem, have not been subjected to in-depth study. Here I present the first treatment of these mollusks, which have been retrieved mainly from the lacustrine but also from the upper fluvial sediments, with a focus on paleoecological implications. Overall, the freshwater mollusk fauna is reasonably diverse and contains the gastropods Bellamya (Viviparidae), Melanoides (Thiaridae), Cleopatra (Paludomidae) and Gabbiella (Bithyniidae), as well as the unionoid bivalves Coelatura, Pseudobovaria (Unionidae), Aspatharia, Iridina (Iridinidae) and Etheria (Etheriidae). Material is typically recrystallized and lithified and its taphonomy suggests deposition in a system with intermediate energy, such as a beach, with post-depositional deformation and abrasion. The mollusk assemblage is indicative of perennial, fresh and well-oxygenated waters in the Kanapoi region. It suggests that Paleolake Lonyumun had largely open shores with limited vegetation and that swampy or ephemeral backwaters were rare. Overall, these findings support earlier paleoecological interpretations based on the fish assemblage of Paleolake Lonyumun at Kanapoi. Moreover, mollusk assemblages from this lake are very similar across the Omo-Turkana Basin (Nachukui, Usno, Mursi and Koobi Fora Formations) suggesting that the lacustrine paleoecological conditions found in the Kanapoi Formation existed throughout the basin.



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Phase I/II Trial of Anticarcinoembryonic Antigen Radioimmunotherapy, Gemcitabine, and Hepatic Arterial Infusion of Fluorodeoxyuridine Postresection of Liver Metastasis for Colorectal Carcinoma

Cancer Biotherapy & Radiopharmaceuticals Sep 2017, Vol. 32, No. 7: 258-265.


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Fla. theme park offers free admission to first responders

By Dewayne Bevil Orlando Sentinel ORLANDO, Fla. — WonderWorks, a science-driven attraction on Orlando's International Drive, is offering discounts to Florida residents and free admission to first responders for a limited time. International Drive attraction WonderWorks will give free admission to first responders through October. There's a shorter-term deal for Florida residents in the ...

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Synthesis, Positron Emission Tomography Imaging, and Therapy of Diabody Targeted Drug Lipid Nanoparticles in a Prostate Cancer Murine Model

Cancer Biotherapy & Radiopharmaceuticals Sep 2017, Vol. 32, No. 7: 247-257.


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Dual Targeting of Epidermal Growth Factor Receptor and HER3 by MEHD7945A as Monotherapy or in Combination with Cisplatin Partially Overcomes Cetuximab Resistance in Head and Neck Squamous Cell Carcinoma Cell Lines

Cancer Biotherapy & Radiopharmaceuticals Sep 2017, Vol. 32, No. 7: 229-238.


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Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects

Cancer Biotherapy & Radiopharmaceuticals Sep 2017, Vol. 32, No. 7: 266-273.


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Off-duty firefighter-EMT saves fellow firefighter at hockey game

Michael Dimond had just finished a game when his friend collapsed on the ice

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ADAR RNA editing in human disease; more to it than meets the I

Abstract

We review the structures and functions of ADARs and their involvements in human diseases. ADAR1 is widely expressed, particularly in the myeloid component of the blood system, and plays a prominent role in promiscuous editing of long dsRNA. Missense mutations that change ADAR1 residues and reduce RNA editing activity cause Aicardi–Goutières Syndrome, a childhood encephalitis and interferonopathy that mimics viral infection and resembles an extreme form of Systemic Lupus Erythmatosus (SLE). In Adar1 mouse mutant models aberrant interferon expression is prevented by eliminating interferon activation signaling from cytoplasmic dsRNA sensors, indicating that unedited cytoplasmic dsRNA drives the immune induction. On the other hand, upregulation of ADAR1 with widespread promiscuous RNA editing is a prominent feature of many cancers and particular site-specific RNA editing events are also affected. ADAR2 is most highly expressed in brain and is primarily required for site-specific editing of CNS transcripts; recent findings indicate that ADAR2 editing is regulated by neuronal excitation for synaptic scaling of glutamate receptors. ADAR2 is also linked to the circadian clock and to sleep. Mutations in ADAR2 could contribute to excitability syndromes such as epilepsy, to seizures, to diseases involving neuronal plasticity defects, such as autism and Fragile-X Syndrome, to neurodegenerations such as ALS, or to astrocytomas or glioblastomas in which reduced ADAR2 activity is required for oncogenic cell behavior. The range of human disease associated with ADAR1 mutations may extend further to include other inflammatory conditions while ADAR2 mutations may affect psychiatric conditions.



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Duke Life Flight: Procession home for the fallen

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This is the procession bringing the fallen Duke Life Flight crew home from the Medical Examiner's Office. In this video, the crew members are being brought by their home base at the Johnston County Airport (JNX).

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Duke Life Flight: Procession home for the fallen

maxresdefault.jpg

This is the procession bringing the fallen Duke Life Flight crew home from the Medical Examiner's Office. In this video, the crew members are being brought by their home base at the Johnston County Airport (JNX).

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Analysis of common polymorphisms within NR1I2 and NR1I3 genes and tacrolimus dose-adjusted concentration in stable kidney transplant recipients

imageObjectives: Several genetic factors were identified to be responsible for interidividual variability in tacrolimus (TAC) pharmacokinetics, with the predominant role of CYP3A5 and CYP3A4 polymorphisms. In this study, genetic variants of NR1I2 and NR1I3 nuclear receptors (responsible for the regulation of drug-metabolizing enzymes and transporters at the transcriptional level) were evaluated for their potential association with altered TAC concentrations. Materials and methods: Two hundred and forty White kidney transplant patients were genotyped for five single-nucleotide polymorphisms (rs3814055, rs6785049, rs2276707, rs2307424, and rs2307418) in NR1I2 and NR1I3 genes. Genetic data were analyzed in relation to TAC dose-adjusted trough concentration measured 6 months after transplantation (unadjusted and adjusted for patient's CYP3A5 expresser status). Results: There were significant differences in TAC concentrations between patients with different NR1I2 rs3814055:C>T genotypes (mean values: 121.3 ng/ml mg/kg in major CC homozygotes, 169.6 ng/ml mg/kg in CT heterozygotes, and 186.0 ng/ml mg/kg in patients homozygous for the minor T allele) that remained significant after excluding CYP3A5 expressers from analysis. The TAC dose administered to minor T allele carriers (CT or TT genotype) was significantly lower (~22%) compared with CC homozygotes. For all the other loci analyzed, no significant associations were noted. Conclusion: Our results support the previous data on the functionality of NR1I2 rs3814055 single-nucleotide polymorphism that points to its association with interindividual differences in activity and inducibility of a broad range of drug-metabolizing enzymes and drug transporters.

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Replication confirms the association of loci in FOXE1, PDE8B, CAPZB and PDE10A with thyroid traits: a Genetics of Diabetes Audit and Research Tayside study (GoDARTS)

imageObjective: Replication of associations in genome-wide association studies is desirable to ensure that such signals are potentially clinically meaningful. This study aimed to replicate associations of selected single-nucleotide polymorphisms (SNPs) with hypothyroidism and serum thyroid-stimulating hormone (TSH) using electronic medical records (EMRs). Patients and methods: A cross-sectional study was carried out among patients of European Caucasian ethnicity from the Genetics of Diabetes Audit and Research Tayside recruited in Tayside (Scotland, UK). EMRs (biochemistry, prescribing, hospital admissions and demographics) were used to ascertain patients with hypothyroidism and their controls as well as average serum TSH concentration, and linked to genetic biobank data. Genetic tests of association were performed using logistic and linear regression models. Results: We analysed 1703 cases of hypothyroidism and 9457 controls. All four SNPs located on chromosome 9 at FOXE1 were associated with hypothyroidism with similar effect estimates (odds ratio=0.75–0.76, P

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Quality of anticoagulation control and hemorrhage risk among African American and European American warfarin users

imageObjective: We evaluated whether percent time in target range (PTTR), risk of over-anticoagulation [international normalized ratio (INR)>4], and risk of hemorrhage differ by race. As PTTR is a strong predictor of hemorrhage risk, we also determined the influence of PTTR on the risk of hemorrhage by race. Participants and methods: Among 1326 warfarin users, PTTR was calculated as the percentage of interpolated INR values within the target range of 2.0–3.0. PTTR was also categorized as poor (PTTR65 years) patients without venous thromboembolism indication and chronic kidney disease were more likely to attain PTTR of at least 60%. After accounting for clinical and genetic factors, and PTTR, African Americans had a higher risk of hemorrhage [hazard ratio (HR)=1.58; 95% confidence interval (CI): 1.04–2.41; P=0.034]. Patients with 60≤PTTR

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Effect of gene–gene and gene–environment interactions associated with antituberculosis drug-induced hepatotoxicity

imageObjectives: This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene–gene and gene–environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires. Patients and methods: We investigated 364 TB patients who received anti-TB drugs. Physicians collected demographic and clinical data to identify environmental risk factors for ATDH development. Polymorphisms were detected using gene sequencing, PCR, and PCR-restriction fragment length polymorphisms. A binary logistic regression analysis was carried out to compare the results of TB patients with and without the development of hepatotoxicity. The multifactor dimensionality reduction method was used to examine genetic and environmental interactions in association with ATDH. Results: This study suggests that the slow acetylator profile [odds ratio (OR): 3.02; 95% confidence interval (CI): 1.82–5.00; P

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Genome-wide association study of cardiotoxicity in the NCCTG N9831 (Alliance) adjuvant trastuzumab trial

imageObjectives: The major clinical side effect of the ERBB2-targeted breast cancer therapy, trastuzumab, is a decline in the left ventricular ejection fraction (LVEF). Improved markers are needed to better identify patients susceptible to cardiotoxicity. Methods: The NCCTG N9831 trial compared adjuvant doxorubicin and cyclophosphamide followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or concurrent paclitaxel and trastuzumab (arm C) in patients with HER2-positive breast cancer. A genome-wide association study was performed on all patients with available DNA (N=1446). We used linear regression to identify single nucleotide polymorphisms (SNPs) associated with decline in LVEF, adjusting for age, baseline LVEF, antihypertensive medications, and the first two principle components. Results: In total, 618 863 SNPs passed quality control and DNA from 1191 patients passed genotyping quality control and were identified as Whites of non-Hispanic origin. SNPs at six loci were associated with a decline in LVEF (P=7.73×10−6 to 8.93×10−8), LDB2, BRINP1, chr6 intergenic, RAB22A, TRPC6, and LINC01060, in patients who received chemotherapy plus trastuzumab (arms BC, N=800). None of these loci were significant in patients who received chemotherapy only (arm A, N=391) and did not increase in significance in the combined analysis of all patients. We did not observe association, P

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Duke Life Flight: Procession home for the fallen

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This is the procession bringing the fallen Duke Life Flight crew home from the Medical Examiner's Office. In this video, the crew members are being brought by their home base at the Johnston County Airport (JNX).

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Duke Life Flight: Procession home for the fallen

maxresdefault.jpg

This is the procession bringing the fallen Duke Life Flight crew home from the Medical Examiner's Office. In this video, the crew members are being brought by their home base at the Johnston County Airport (JNX).

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Climbing fibers predict movement kinematics and performance errors

Requisite for understanding cerebellar function is a complete characterization of the signals provided by complex spike (CS) discharge of Purkinje cells, the output neurons of the cerebellar cortex. Numerous studies have provided insights into CS function, with the most predominant view being that they are evoked by error events. However, several reports suggest that CSs encode other aspects of movements and do not always respond to errors or unexpected perturbations. Here, we evaluated CS firing during a pseudo-random manual tracking task in the monkey (Macaca mulatta). This task provides extensive coverage of the work space and relative independence of movement parameters, delivering a robust data set to assess the signals that activate climbing fibers. Using reverse correlation, we determined feedforward and feedback CSs firing probability maps with position, velocity, and acceleration, as well as position error, a measure of tracking performance. The direction and magnitude of the CS modulation were quantified using linear regression analysis. The major findings are that CSs significantly encode all three kinematic parameters and position error, with acceleration modulation particularly common. The modulation is not related to "events," either for position error or kinematics. Instead, CSs are spatially tuned and provide a linear representation of each parameter evaluated. The CS modulation is largely predictive. Similar analyses show that the simple spike firing is modulated by the same parameters as the CSs. Therefore, CSs carry a broader array of signals than previously described and argue for climbing fiber input having a prominent role in online motor control.

NEW & NOTEWORTHY This article demonstrates that complex spike (CS) discharge of cerebellar Purkinje cells encodes multiple parameters of movement, including motor errors and kinematics. The CS firing is not driven by error or kinematic events; instead it provides a linear representation of each parameter. In contrast with the view that CSs carry feedback signals, the CSs are predominantly predictive of upcoming position errors and kinematics. Therefore, climbing fibers carry multiple and predictive signals for online motor control.



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Emergent cortical circuit dynamics contain dense, interwoven ensembles of spike sequences

Temporal codes are theoretically powerful encoding schemes, but their precise form in the neocortex remains unknown in part because of the large number of possible codes and the difficulty in disambiguating informative spikes from statistical noise. A biologically plausible and computationally powerful temporal coding scheme is the Hebbian assembly phase sequence (APS), which predicts reliable propagation of spikes between functionally related assemblies of neurons. Here, we sought to measure the inherent capacity of neocortical networks to produce reliable sequences of spikes, as would be predicted by an APS code. To record microcircuit activity, the scale at which computation is implemented, we used two-photon calcium imaging to densely sample spontaneous activity in murine neocortical networks ex vivo. We show that the population spike histogram is sufficient to produce a spatiotemporal progression of activity across the population. To more comprehensively evaluate the capacity for sequential spiking that cannot be explained by the overall population spiking, we identify statistically significant spike sequences. We found a large repertoire of sequence spikes that collectively comprise the majority of spiking in the circuit. Sequences manifest probabilistically and share neuron membership, resulting in unique ensembles of interwoven sequences characterizing individual spatiotemporal progressions of activity. Distillation of population dynamics into its constituent sequences provides a way to capture trial-to-trial variability and may prove to be a powerful decoding substrate in vivo. Informed by these data, we suggest that the Hebbian APS be reformulated as interwoven sequences with flexible assembly membership due to shared overlapping neurons.

NEW & NOTEWORTHY Neocortical computation occurs largely within microcircuits comprised of individual neurons and their connections within small volumes (<500 μm3). We found evidence for a long-postulated temporal code, the Hebbian assembly phase sequence, by identifying repeated and co-occurring sequences of spikes. Variance in population activity across trials was explained in part by the ensemble of active sequences. The presence of interwoven sequences suggests that neuronal assembly structure can be variable and is determined by previous activity.



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Use of the Aplysia feeding network to study repetition priming of an episodic behavior

Many central pattern generator (CPG)-mediated behaviors are episodic, meaning that they are not continuously ongoing; instead, there are pauses between bouts of activity. This raises an interesting possibility, that the neural networks that mediate these behaviors are not operating under "steady-state" conditions; i.e., there could be dynamic changes in motor activity as it stops and starts. Research in the feeding system of the mollusk Aplysia californica has demonstrated that this can be the case. After a pause, initial food grasping responses are relatively weak. With repetition, however, responses strengthen. In this review we describe experiments that have characterized cellular/molecular mechanisms that produce these changes in motor activity. In particular, we focus on cumulative effects of modulatory neuropeptides. Furthermore, we relate Aplysia research to work in other systems and species, and develop a hypothesis that postulates that changes in response magnitude are a reflection of an efficient feeding strategy.



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Spatially tuned normalization explains attention modulation variance within neurons

Spatial attention improves perception of attended parts of a scene, a behavioral enhancement accompanied by modulations of neuronal firing rates. These modulations vary in size across neurons in the same brain area. Models of normalization explain much of this variance in attention modulation with differences in tuned normalization across neurons (Lee J, Maunsell JHR. PLoS One 4: e4651, 2009; Ni AM, Ray S, Maunsell JHR. Neuron 73: 803–813, 2012). However, recent studies suggest that normalization tuning varies with spatial location both across and within neurons (Ruff DA, Alberts JJ, Cohen MR. J Neurophysiol 116: 1375–1386, 2016; Verhoef BE, Maunsell JHR. eLife 5: e17256, 2016). Here we show directly that attention modulation and normalization tuning do in fact covary within individual neurons, in addition to across neurons as previously demonstrated. We recorded the activity of isolated neurons in the middle temporal area of two rhesus monkeys as they performed a change-detection task that controlled the focus of spatial attention. Using the same two drifting Gabor stimuli and the same two receptive field locations for each neuron, we found that switching which stimulus was presented at which location affected both attention modulation and normalization in a correlated way within neurons. We present an equal-maximum-suppression spatially tuned normalization model that explains this covariance both across and within neurons: each stimulus generates equally strong suppression of its own excitatory drive, but its suppression of distant stimuli is typically less. This new model specifies how the tuned normalization associated with each stimulus location varies across space both within and across neurons, changing our understanding of the normalization mechanism and how attention modulations depend on this mechanism.

NEW & NOTEWORTHY Tuned normalization studies have demonstrated that the variance in attention modulation size seen across neurons from the same cortical area can be largely explained by between-neuron differences in normalization strength. Here we demonstrate that attention modulation size varies within neurons as well and that this variance is largely explained by within-neuron differences in normalization strength. We provide a new spatially tuned normalization model that explains this broad range of observed normalization and attention effects.



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Envelope contributions to the representation of interaural time difference in the forebrain of barn owls

Birds and mammals use the interaural time difference (ITD) for azimuthal sound localization. While barn owls can use the ITD of the stimulus carrier frequency over nearly their entire hearing range, mammals have to utilize the ITD of the stimulus envelope to extend the upper frequency limit of ITD-based sound localization. ITD is computed and processed in a dedicated neural circuit that consists of two pathways. In the barn owl, ITD representation is more complex in the forebrain than in the midbrain pathway because of the combination of two inputs that represent different ITDs. We speculated that one of the two inputs includes an envelope contribution. To estimate the envelope contribution, we recorded ITD response functions for correlated and anticorrelated noise stimuli in the barn owl's auditory arcopallium. Our findings indicate that barn owls, like mammals, represent both carrier and envelope ITDs of overlapping frequency ranges, supporting the hypothesis that carrier and envelope ITD-based localization are complementary beyond a mere extension of the upper frequency limit.

NEW & NOTEWORTHY The results presented in this study show for the first time that the barn owl is able to extract and represent the interaural time difference (ITD) information conveyed by the envelope of a broadband acoustic signal. Like mammals, the barn owl extracts the ITD of the envelope and the carrier of a signal from the same frequency range. These results are of general interest, since they reinforce a trend found in neural signal processing across different species.



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Motor learning in a complex balance task and associated neuroplasticity: a comparison between endurance athletes and nonathletes

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 nonathletes (NA). For this purpose, participants had to perform a multimodal balance task (MBT) training on 2 sessions, which were separated by 1 wk. 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 would showed superior initial SBT performance and stronger MBT-induced improvements in SBT learning rates compared with NA. On a cortical level, we hypothesized that MBT training would lead to differential learning-dependent functional changes in motor-related brain regions [such as primary motor cortex (M1)] during SBT performance. In fact, EA showed superior initial SBT performance, whereas 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 in EA. Even more interesting, learning rates were correlated with fNIRS changes in right M1/IPL. On the basis of 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.

NEW & NOTEWORTHY Motor expertise is associated with functional/structural brain plasticity. How such neuroplastic reorganization translates into altered motor learning processes remains elusive. We investigated endurance athletes (EA) and nonathletes (NA) in a multimodal balance task (MBT). EA showed superior static balance performance (SBT), whereas MBT-induced SBT improvements did not differ between groups. Functional near-infrared spectroscopy recordings revealed a differential MBT training-induced decrease of deoxygenated hemoglobin in left primary motor cortex and inferior parietal lobe between groups.



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Perspectives on classical controversies about the motor cortex

Primary motor cortex has been studied for more than a century, yet a consensus on its functional contribution to movement control is still out of reach. In particular, there remains controversy as to the level of control produced by motor cortex ("low-level" movement dynamics vs. "high-level" movement kinematics) and the role of sensory feedback. In this review, we present different perspectives on the two following questions: What does activity in motor cortex reflect? and How do planned motor commands interact with incoming sensory feedback during movement? The four authors each present their independent views on how they think the primary motor cortex (M1) controls movement. At the end, we present a dialogue in which the authors synthesize their views and suggest possibilities for moving the field forward. While there is not yet a consensus on the role of M1 or sensory feedback in the control of upper limb movements, such dialogues are essential to take us closer to one.



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The neural mechanisms able to predict future emotion regulation decisions

Emotion regulation is crucial in maintaining healthy psychological well-being, and its dysregulation is often linked to a range of neuropsychiatric disorders including depression. The neurobiological underpinnings of cognitive reappraisal, an emotion regulation strategy, have been shown to include the amygdala and regions of the prefrontal cortex. A novel study by Doré, Weber, and Ochsner (J Neurosci 37: 2580–2588, 2017) has demonstrated that neural activity in these regions during uninstructed visualization of affective stimuli can successfully predict which individuals are more likely to subsequently employ emotion regulation, and under what circumstances.



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The interaction of iron and the genome: for better and for worse

Publication date: Available online 14 September 2017
Source:Mutation Research/Reviews in Mutation Research
Author(s): Marie-Bérengère Troadec, Olivier Loréal, Pierre Brissot
Iron, as an essential nutrient, and the DNA, as the carrier of genetic information which is physically compacted into chromosomes, are both needed for normal life and well-being. Therefore, it is not surprising that close interactions exist between iron and the genome. On the one hand, iron, especially when present in excess, may alter genome stability through oxidative stress, and may favor cell cycle abnormalities and the development of malignant diseases. The genome also receives a feedback signal from the systemic iron status, leading to promotion of expression of genes that regulate iron metabolism. Conversely, on the other hand, DNA mutations may cause genetic iron-related diseases such as hemochromatosis, archetype of iron-overload diseases, or refractory iron deficiency anemia (IRIDA).



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A case of a mucin-producing bile duct tumor diagnosed over the course of 6 years

Abstract

We report a case of a mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB) diagnosed over a period of 6 years. A 64-year-old man underwent follow-up evaluations for an abdominal aortic aneurysm at our hospital. In 2009, a computed tomography (CT) scan revealed a simple hepatic cyst in segment 3 of the liver. Annual CT scans initially showed almost no change in the size or shape of the cyst. The cystic lesion, which measured 5 cm in 2014, had increased to 11 cm by 2015, and a solid component was detected within the cyst. A biliary cystic tumor was suspected and we performed a left lateral hepatectomy. Pathological examination showed that the papillary lesion in the cyst included adenocarcinoma and adenoma components. We diagnosed M-IPNB in 2015. Identification of the solid component of the cyst, as well as an increase in cyst diameter in the image analyses, was critical for diagnosis of M-IPNB.



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Comparison of the paediatric blade of the Pentax-AWS and Ovassapian airway in fibreoptic tracheal intubation in patients with limited mouth opening and cervical spine immobilization by a semi-rigid neck collar: a randomized controlled trial

Abstract
Background. We compared the performances of the paediatric blade of a Pentax Airway Scope and an Ovassapian airway in fibreoptic tracheal intubation in patients whose necks were stabilized by semi-rigid neck collars.Methods. Ninety patients were enrolled in this prospective, open-label, randomized controlled trial. Patients were randomly allocated to one of two groups (Group OVA-FOB and Group AWS-FOB). The time to tracheal intubation, success rate of tracheal intubation, number of optimization manoeuvres (jaw thrust), and difficulty of manipulation of the fibreoptic bronchoscope were compared between the groups.Results. The time to tracheal intubation was significantly shorter (32 vs 50 s; median difference 19 s; 95% confidence interval 14–25 s; P<0.001) and manipulation of the fibreoptic bronchoscope was significantly easier for Group AWS-FOB. Optimization manoeuvres were rarely required to facilitate fibreoptic tracheal intubation in Group AWS-FOB [jaw thrust, 0 (0%); jaw thrust with anterior neck collar removal, 1 (2%)] compared with that required in Group OVA-FOB [jaw thrust, 39 (87%); jaw thrust with anterior neck collar removal, 2 (4%)]. There was no significant difference in the success rate of tracheal intubation on the first attempt between groups [Group AWS-FOB, 45 (100%); Group OVA-FOB, 44 (98%)].Conclusions. Combined use of the paediatric blade of a Pentax Airway Scope and a fibreoptic bronchoscope enabled rapid tracheal intubation, minimizing the use of external manoeuvres of the airway, in patients with limited mouth opening and cervical spine immobilization by semi-rigid neck collars, compared with use of the Ovassapian airway and the fibreoptic bronchoscope.Clinical trial registration. NCT02827110.

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Systematic review to determine which validated measurement tools can be used to assess risk of problematic analgesic use in patients with chronic pain

Abstract
Misuse of prescription opioids, and other drugs prescribed for chronic pain, has increased, with major concerns about harm. This review was undertaken to identify validated measurement tools for risk assessment and monitoring of chronic non-cancer pain patients being considered for, or currently prescribed, analgesic drugs with abuse potential.Selected databases (Embase, Medline, Cochrane library/CENTRAL, PsycINFO, PubMed, CINAHL) were systematically searched for studies evaluating tools for risk of analgesic misuse, either before, or during, analgesic therapy for chronic pain, using predetermined inclusion/exclusion criteria. Two independent reviewers assessed abstracts, selected full texts, extracted data and assessed quality.30 studies from 1844 met inclusion criteria, including three systematic reviews, with an additional four studies from bibliography review. The studies covered 14 tools pertaining to opioid use, with none for non-opioid analgesics.Although there is no single, clear factor identifying opioid misuse, previous substance misuse appears important. Deception, including lying to clinicians, and using drugs belonging to others are common features. Smoking history may be relevant.For predicting prescription opioid misuse, the pain medication questionnaire (PMQ) and the screener and opioid assessment for patients with pain (SOAPP) had the best evidence; both developed and validated in five separate studies (four each of acceptable quality). The current opioid misuse measure (COMM) performed best screening for current misuse, developed and validated in three studies of acceptable quality. A small number of tools may accurately predict, or identify, opioid misuse. There are none for non-opioid analgesics, where there is a potential need.

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Exercise training improves cardiac autonomic control, cardiac function, and arrhythmogenesis in rats with preserved-ejection fraction heart failure

Chronic heart failure is characterized by autonomic imbalance, cardiac dysfunction, and arrhythmogenesis. It has been shown that exercise training (ExT) improves central nervous system oxidative stress, autonomic control, and cardiac function in heart failure with reduced ejection fraction; however, to date no comprehensive studies have addressed the effects of ExT, if any, on oxidative stress in brain stem cardiovascular areas, cardiac autonomic balance, arrhythmogenesis, and cardiac function in heart failure with preserved ejection fraction (HFpEF). We hypothesize that ExT reduces brain stem oxidative stress, improves cardiac autonomic control and cardiac function, and reduces arrhythmogenesis in HFpEF rats. Rats underwent sham treatment or volume overload to induce HFpEF. ExT (60 min/day, 25 m/min, 10% inclination) was performed for 6 wk starting at the second week after HFpEF induction. Rats were randomly allocated into Sham+sedentary (Sed) (n = 8), Sham+ExT (n = 6), HFpEF+Sed (n = 8), and HFpEF+ExT (n = 8) groups. Compared with the HFpEF+Sed condition, HFpEF+ExT rats displayed reduced NAD(P)H oxidase activity and oxidative stress in the rostral ventrolateral medulla (RVLM), improved cardiac autonomic balance, and reduced arrhythmogenesis. Furthermore, a threefold improvement in cardiac function was observed in HFpEF+ExT rats. These novel findings suggest that moderate-intensity ExT is an effective means to attenuate the progression of HFpEF through improvement in RVLM redox state, cardiac autonomic control, and cardiac function.

NEW & NOTEWORTHY In the present study, we found that exercise reduced oxidative stress in key brain stem areas related to autonomic control, improved sympathovagal control of the heart, reduced cardiac arrhythmias, and delayed deterioration of cardiac function in rats with heart failure with preserved ejection fraction (HFpEF). Our results provide strong evidence for the therapeutic efficacy of exercise training in HFpEF.



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Random squat/stand maneuvers: a novel approach for assessment of dynamic cerebral autoregulation?

Squat/stand maneuvers (SSM) have been used to assess dynamic cerebral autoregulation (dCA), but always at a fixed frequency (FF). This study aimed to assess the use of random-frequency (RF) SSMs as a stimulus for measuring dCA and determine the reproducibility of FF and RFSSMs. Twenty-nine healthy volunteers [19 male, mean age 23.0 (4.9) yr] completed the study; 11 returned for a repeat visit (median 45 days). Heart rate, beat-to-beat blood pressure, middle cerebral artery (MCA) blood flow velocity, end-tidal CO2, and angle of the squat movement were measured. Subjects underwent four recordings: 5 min sitting, 5 min standing, FFSSMs (0.05Hz), and RFSSMs. Subjects were asked to rate the degree of exertion experienced while performing these maneuvers. Twenty-nine subjects completed the protocol; nine data sets were deemed unsuitable for further analysis. Mean ARI of 6.21 (1.04) while standing was significantly greater than during the SSMs (P < 0.01), with mean (SD) ARI during the FF and RFSSMs being 5.16 (1.43) and 5.37 (1.21), respectively. However, no significant difference was found between the ARI estimates from the two SSMs (P = 0.856) or for each of the four recordings between the two visits (P = 0.645). RFSSMs were found to be significantly less tiring than FFSSMs (P < 0.01). In conclusion, RFSSMs are an effective and noninvasive method of assessing dCA. There is no difference in the ARI estimates in comparison with FFSSMs. Although FFSSMs have been well tolerated previously, RFSSMs are preferred by healthy subjects and thus may be better tolerated by a patient population in a clinical setting.

NEW & NOTEWORTHY RFSSMs provided comparable estimates of autoregulatory indices to FFSSMs. Instead of point estimates at the driven frequency, RFSSMs generate a broader power spectrum of changes in arterial blood pressure and cerebral blood flow velocity, allowing direct comparison with spontaneous fluctuations through transfer function analysis. Moreover, random-frequency SSMs are preferred by participants. They are a novel tool by which larger blood pressure oscillations can be elicited for the reliable measurement of dynamic cerebral autoregulation.



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Leg blood flow is impaired during small muscle mass exercise in patients with COPD

Skeletal muscle blood flow is regulated to match the oxygen demand and dysregulation could contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). We measured leg hemodynamics and metabolites from vasoactive compounds in muscle interstitial fluid and plasma at rest, during one-legged knee-extensor exercise, and during arterial infusions of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively. Ten patients with moderate to severe COPD and eight age- and sex-matched healthy controls were studied. During knee-extensor exercise (10 W), leg blood flow was lower in the patients compared with the controls (1.82 ± 0.11 vs. 2.36 ± 0.14 l/min, respectively; P < 0.05), which compromised leg oxygen delivery (372 ± 26 vs. 453 ± 32 ml O2/min, respectively; P < 0.05). At rest, plasma endothelin-1 (vasoconstrictor) was higher in the patients with COPD (P < 0.05) and also tended to be higher during exercise (P = 0.07), whereas the formation of interstitial prostacyclin (vasodilator) was only increased in the controls. There was no difference between groups in the nitrite/nitrate levels (vasodilator) in plasma or interstitial fluid during exercise. Moreover, patients and controls showed similar vasodilatory capacity in response to both endothelium-independent (SNP) and endothelium-dependent (ACh) stimulation. The results suggest that leg muscle blood flow is impaired during small muscle mass exercise in patients with COPD possibly due to impaired formation of prostacyclin and increased levels of endothelin-1.

NEW & NOTEWORTHY This study demonstrates that chronic obstructive pulmonary disease (COPD) is associated with a reduced blood flow to skeletal muscle during small muscle mass exercise. In contrast to healthy individuals, interstitial prostacyclin levels did not increase during exercise and plasma endothelin-1 levels were higher in the patients with COPD.



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Potential involvement of lactate and interleukin-6 in the appetite-regulatory hormonal response to an acute exercise bout

High-intensity exercise suppresses appetite partly through changes in peripheral appetite-regulating hormones. Lactate and IL-6 mediate the release of these hormones in animal/cell models and may provide a mechanistic link between exercise intensity and appetite regulation. The current study examined changes in appetite-regulating hormones, lactate, and IL-6 after different intensities of running. Eight males completed four experimental sessions: 1) moderate-intensity continuous training (MICT; 65% Vo2max); 2) vigorous-intensity continuous training (VICT; 85% Vo2max); 3) sprint interval training (SIT; repeated "all-out" sprints); and 4) Control (CTRL; no exercise). Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), total peptide YY (PYY), lactate, IL-6, and appetite perceptions were measured pre-, immediately postexercise, 30 min postexercise, and 90 min postexercise. Energy intake was recorded over 3 days. VICT and SIT suppressed ghrelin (P < 0.001), although SIT elicited a greater (P = 0.016 vs. MICT) and more prolonged (P < 0.001 vs. all sessions) response. GLP-1 increased immediately after MICT (P < 0.001) and 30 min after VICT (P < 0.001) and SIT (P < 0.002), while VICT elicited a greater postexercise increase in PYY vs. MICT (P = 0.027). Postexercise changes in blood lactate and IL-6 correlated with the area under the curve values for ghrelin (r = –0.60, P < 0.001) and GLP-1 (r = 0.42, P = 0.017), respectively. Appetite was suppressed after exercise (P < 0.001), although more so after VICT (P < 0.027) and SIT (P < 0.001) vs. MICT, and energy intake was reduced on the day after VICT (P < 0.017 vs. MICT and CTRL) and SIT (P = 0.049 vs. MICT). These findings support an intensity-dependent paradigm for appetite regulation following exercise and highlight the potential involvement of lactate and IL-6.

NEW & NOTEWORTHY This study examines the involvement of two potential mechanisms (lactate and IL-6) that may explain the intensity-dependent effects of acute exercise on appetite-related parameters. Our findings support a clear intensity-dependent paradigm for appetite regulation following exercise, as highlighted by the change in acylated ghrelin and the suppression of appetite and energy intake after vigorous exercise (continuous and intermittent). Further, our findings extend previous work in animal/cell models by providing evidence for the potential role of lactate and IL-6 in mediating changes in appetite-related parameters following exercise in humans.



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Dietary nitrate restores compensatory vasodilation and exercise capacity in response to a compromise in oxygen delivery in the noncompensator phenotype

Recently, dietary nitrate supplementation has been shown to improve exercise capacity in healthy individuals through a potential nitrate-nitrite-nitric oxide pathway. Nitric oxide has been shown to play an important role in compensatory vasodilation during exercise under hypoperfusion. Previously, we established that certain individuals lack a vasodilation response when perfusion pressure reductions compromise exercising muscle blood flow. Whether this lack of compensatory vasodilation in healthy, young individuals can be restored with dietary nitrate supplementation is unknown. Six healthy (21 ± 2 yr), recreationally active men completed a rhythmic forearm exercise. During steady-state exercise, the exercising arm was rapidly transitioned from an uncompromised (below heart) to a compromised (above heart) position, resulting in a reduction in local pressure of –31 ± 1 mmHg. Exercise was completed following 5 days of nitrate-rich (70 ml, 0.4 g nitrate) and nitrate-depleted (70 ml, ~0 g nitrate) beetroot juice consumption. Forearm blood flow (in milliliters per minute; brachial artery Doppler and echo ultrasound), mean arterial blood pressure (in millimeters of mercury; finger photoplethysmography), exercising forearm venous effluent (ante-cubital vein catheter), and plasma nitrite concentrations (chemiluminescence) revealed two distinct vasodilatory responses: nitrate supplementation increased (plasma nitrite) compared with placebo (245 ± 60 vs. 39 ± 9 nmol/l; P < 0.001), and compensatory vasodilation was present following nitrate supplementation (568 ± 117 vs. 714 ± 139 ml ⋅ min–1 ⋅ 100 mmHg–1; P = 0.005) but not in placebo (687 ± 166 vs. 697 ± 171 min–1 ⋅ 100 mmHg–1; P = 0.42). As such, peak exercise capacity was reduced to a lesser degree (–4 ± 39 vs. –39 ± 27 N; P = 0.01). In conclusion, dietary nitrate supplementation during a perfusion pressure challenge is an effective means of restoring exercise capacity and enabling compensatory vasodilation.

NEW & NOTEWORTHY Previously, we identified young, healthy persons who suffer compromised exercise tolerance when exercising muscle perfusion pressure is reduced as a result of a lack of compensatory vasodilation. The ability of nitrate supplementation to restore compensatory vasodilation in such noncompensators is unknown. We demonstrated that beetroot juice supplementation led to compensatory vasodilation and restored perfusion and exercise capacity. Elevated plasma nitrite is an effective intervention for correcting the absence of compensatory vasodilation in the noncompensator phenotype.



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Timing of postexercise carbohydrate-protein supplementation: roles of gastrointestinal blood flow and mucosal cell damage on gastric emptying in humans

It is well known that protein ingestion immediately after exercise greatly stimulates muscle protein synthesis during the postexercise recovery phase. However, immediately after strenuous exercise, the gastrointestinal (GI) mucosa is frequently injured by hypoperfusion in the organ/tissue, possibly resulting in impaired GI function (e.g., gastric emptying; GE). The aim of this study was to examine the effect of GI blood flow on the GE rate. Eight healthy young subjects performed an intermittent supramaximal cycling exercise for 30 min, which consisted of a 120% Vo2peak for 20 s, followed by 20 W for 40 s. The subjects ingested 300 ml of a nutrient drink containing carbohydrate-protein at either 5 min postexercise in one trial (PE-5) or 30 min postexercise in another trial (PE-30). In the control trial (Con), the subjects ingested the same drink without exercise. The celiac artery blood flow (CABF) and superior mesenteric artery blood flow (SMABF) and GE rate were assessed by ultrasonography. Before drink ingestion in PE-5, CABF significantly decreased from baseline, whereas in PE-30, it returned to baseline. Following drink ingestion in PE-5, CABF did not change from baseline, but it significantly increased in PE-30 and Con. SMABF increased significantly later in PE-5 than in PE-30 and Con. The GE rate was consistently slower in PE-5 than in PE-30 and Con. In conclusion, the CABF response after exercise seems to modulate the subsequent GE rate and SMABF response.

NEW & NOTEWORTHY A carbohydrate-protein drink was ingested at either 5 min (i.e., profoundly decreased celiac artery blood flow; CABF) or 30 min (i.e., already recovered CABF) postexercise. In the 5-min postexercise trial, the gastric emptying (GE) rate and superior mesenteric artery blood flow (SMABF) response were slower than those in the 30-min postexercise trial. The GE rate and SMABF response may be altered depending on the postexercise CABF response.



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Novel analysis of 4DCT imaging quantifies progressive increases in anatomic dead space during mechanical ventilation in mice

Increased dead space is an important prognostic marker in early acute respiratory distress syndrome (ARDS) that correlates with mortality. The cause of increased dead space in ARDS has largely been attributed to increased alveolar dead space due to ventilation/perfusion mismatching and shunt. We sought to determine whether anatomic dead space also increases in response to mechanical ventilation. Mice received intratracheal lipopolysaccharide (LPS) or saline and mechanical ventilation (MV). Four-dimensional computed tomography (4DCT) scans were performed at onset of MV and after 5 h of MV. Detailed measurements of airway volumes and lung tidal volumes were performed using image analysis software. The forced oscillation technique was used to obtain measures of airway resistance, tissue damping, and tissue elastance. The ratio of airway volumes to total tidal volume increased significantly in response to 5 h of mechanical ventilation, regardless of LPS exposure, and airways demonstrated significant variation in volumes over the respiratory cycle. These findings were associated with an increase in tissue elastance (decreased lung compliance) but without changes in tidal volumes. Airway volumes increased over time with exposure to mechanical ventilation without a concomitant increase in tidal volumes. These findings suggest that anatomic dead space fraction increases progressively with exposure to positive pressure ventilation and may represent a pathological process.

NEW & NOTEWORTHY We demonstrate that anatomic dead space ventilation increases significantly over time in mice in response to mechanical ventilation. The novel functional lung-imaging techniques applied here yield sensitive measures of airway volumes that may have wide applications.



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Dynamic hyperinflation and exercise limitations in obese asthmatic women

Obese individuals and patients with asthma can develop dynamic hyperinflation (DH) during exercise; however, no previous study has investigated DH as a factor associated with reduced exercise capacity in obese asthmatic women. The aim of the present study was to examine the occurrence of DH and exercise limitations in obese asthmatics. Obese grade II [obese group (Ob-G); BMI 35–39.9 kg/m2; n=36] and nonobese [nonobese group (NOb-G); BMI 18.5-29.9 kg/m2; n=18] asthmatic patients performed a cardiopulmonary test to quantify peak Vo2 and a submaximal exercise test to assess DH. Anthropometric measurements, quadriceps endurance, and lung function were also evaluated. A forward stepwise regression was used to evaluate the association between exercise tolerance (wattage) and limiting exercise factors. Fifty-four patients completed the protocol. The Ob-G (n = 36) presented higher peak Vo2 values but lower power-to-weight ratio values than the NOb-G (P <0 .05). DH was more common in the Ob-G (72.2%) than in the NOb-G (38.9%, P < 0.05). The Ob-G had a greater reduction in the inspiratory capacity (–18 vs. –4.6%, P < 0.05). Exercise tolerance was associated with quadriceps endurance (r = 0.65; p<0.001), oxygen pulse (r = 0.52; p=0.001), and DH (r = –0.46, P = 0.005). The multiple regression analysis showed that the exercise tolerance could be predicted from a linear association only for muscular endurance (r = 0.82 and r2 = 0.67). This study shows that dynamic hyperinflation is a common condition in obese asthmatics; they have reduced fitness for activities of daily living compared to nonobese asthmatics. However, peripheral limitation was the main factor associated with reduced capacity of exercise in these patients.

NEW & NOTEWORTHY This is the first study to investigate the occurrence of dynamic hyperinflation (DH) in obese asthmatics. Our results demonstrate that obese asthmatics present a higher frequency and intensity of DH than nonobese asthmatics. We also show that physical deconditioning in this population is linearly associated with cardiac (O2 pulse), respiratory (DH), and peripheral muscle (resistance) limitation. However, multiple linear regression demonstrated that peripheral muscle limitation may explain the exercise limitation in this population.



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Effects of short-term exposure to sevoflurane on the survival, proliferation, apoptosis, and differentiation of neural precursor cells derived from human embryonic stem cells

Abstract

Purpose

Data from animal experiments suggest that exposure to general anesthetics in early life inhibits neurogenesis and causes long-term memory deficit. Considering short operating times and the popularity of sevoflurane in pediatric anesthesia, it is important to verify the effects of short-period exposure to sevoflurane on the developing brain.

Methods

We measured the effects of short-term exposure (2 h) to 3%, 6%, or 8% sevoflurane, the most commonly used anesthetic, on neural precursor cells derived from human embryonic stem cells, SNUhES32. Cell survival, proliferation, apoptosis, and differentiation on days 1, 3, 5, and 7 post treatment were analyzed.

Results

Treatment with 6% sevoflurane increased cell viability (P = 0.046) and decreased apoptosis (P = 0.014) on day 5, but the effect did not persist on day 7. Survival and apoptosis were not affected by 3% and 8% sevoflurane; there was no effect of proliferation at any of the tested concentrations. The differentiation of cells exposed to 6% or 8% sevoflurane decreased on day 1 (P = 0.033 and P = 0.036 for 6% and 8% sevoflurane, respectively) but was again normalized on days 3–7.

Conclusion

Clinically relevant treatment with sevoflurane for 2 h induces no significant changes in the survival, proliferation, apoptosis, and differentiation of human neural precursor cells, although supraclinical doses of sevoflurane do alter human neurogenesis transiently.



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137Cs and plutonium isotopes accumulation/retention in bottom sediments and soil in Lithuania: A case study of the activity concentration of anthropogenic radionuclides and their provenance before the start of operation of the Belarusian Nuclear Power Plant (NPP)

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): D. Marčiulionienė, B. Lukšienė, D. Montvydienė, O. Jefanova, J. Mažeika, R. Taraškevičius, R. Stakėnienė, R. Petrošius, E. Maceika, N. Tarasiuk, Z. Žukauskaitė, L. Kazakevičiūtė, M. Volkova
Knowledge of the background activity concentrations of anthropogenic radionuclides before the start of operations of the new nuclear facilities in Belarus is of great value worldwide. Inland water bodies in Lithuania (specifically the Neris River, the Nemunas River and the Curonian Lagoon) are near the site of the Belarusian NPP under construction and, for this reason, sediments and flooded soils from these sensitive areas were analysed for radiocesium and plutonium isotopes (macrophytes were analysed only for 137Cs) in 2011–2012. The 137Cs and 239+240Pu activity concentrations in bottom sediments from the Nemunas River, sampled in 1995–1996 and re-calculated to the year 2016, were compared with those of 2011–2012. The obtained activity of 137Cs in bottom sediments of the Nemunas River and Curonian Lagoon varied from 1 Bq/kg to 47.0 Bq/kg. The activity of 137Cs in the tested soils ranged from 5.3 B g/kg to 32.9 Bq/kg. The 239+240Pu activity in bottom sediments of the studied sampling sites varied between 0.016 and 0.34 Bq/kg and in flooded soils from 0.064 to 0.55 Bq/kg. The 238Pu activity values were very low or lower than the detection limit. The activity of 137Cs in macrophytes varied from values lower than the detection limit to 6 Bq/kg. A strong positive linear correlation for bottom sediments was calculated between: 239+240Pu and total organic carbon (TOC), r = 0.86, p-value 0.01; 239+240Pu and silt, r = 0.80, p-value 0.029; 137Cs and silt, r = 0.78, p-value 0.04; and 137Cs and TOC, r = 0.85, p-value 0.015. The similar peculiarities of 137Cs and 239+240Pu accumulation in bottom sediments and flooded soil allow us to assume that 137Cs can be used as a tracer for 239+240Pu in the initial stage of searching for radionuclide accumulation zones. A remaining impact of the Chernobyl fallout in average comprised: in the Lower Nemunas River and Curonian Lagoon sediments – 51%, in the Middle Nemunas River −90% and in the floodplains of the Nemunas River – 59%, while the provenance of plutonium in studied bottom sediments and flooded soil was the global fallout.

Graphical abstract

image


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Risk Factor Analysis Between Newly Screened and Established Hepatitis C in GI and Hepatology Clinics

Abstract

Background

Several studies show inconsistencies in the rate of hepatitis C virus (HCV) detection among baby boomers (born 1945–1965). We conducted a cross-sectional HCV screening followed by a case-controlled comparison of the newly screened population with established HCV subjects.

Method

Enrollment was offered to subjects aged 40–75 at our gastroenterology and hepatology clinics. Demographic data and potential risk factors were obtained, and HCV antibody test was offered to those who had never been screened and compared with a group with established HCV. Logistic regression analysis and Fisher's exact test were performed.

Results

Six hundred and seventy-five patients were offered participation, of whom 128 declined while 50 consented to participate but did not perform the HCV antibody test. Of 497 enrolled subjects, 252 patients had HCV, while 245 subjects (188 patients among "baby boomer") underwent screening for HCV. There were more females (62.4 vs. 41.7%) and immigrants (34.7 vs. 22.2%) among the newly screened group. Among the screened population, five patients had HCV antibody (2.04%), and two of them had positive viral load (0.82%) of whom only one fell in the baby boomer category (0.53%). Compared to HCV group, screened group had significantly lower-risk factors, such as IV drug use (1.22 vs. 43.3%), intranasal cocaine use (14.3 vs. 49.6%), and blood transfusion (18.8 vs. 32.5%).

Conclusion

We found a slightly lower but similar prevalence of HCV antibody when screening based on birth cohort as compared to larger baby boomer studies. Future studies evaluating addition of other screening strategies or possibly universal screening may be needed.



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Predicting short-term and long-term mortality of hospitalized Portuguese patients with alcoholic hepatitis

European Journal of Gastroenterology & Hepatology

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Moisturizers labeled ‘hypoallergenic’ may still have toxic chemicals

Reuters Health News

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Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma

British Journal of Surgery

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Cybersecurity is not a cost, it's an investment, experts say

Healthcare Finance News

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Is Annual Volume Enough? The Role of Experience and Specialization on Inpatient Mortality After Hepatectomy

Annals of Surgery

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Low FODMAP: A preliminary strategy to reduce gastrointestinal distress in athletes

Medicine and Science in Sports and Exercise

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Clinical significance of area of psoas major muscle on computed tomography after gastrectomy in gastric cancer patients

Annals of Nutrition and Metabolism

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Acute histological inflammatory activity is associated with clinical relapse in patients with ulcerative colitis in clinical and endoscopic remission.

Digestive and Liver Diseases

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Surgical management of gallbladder cancer: simple versus extended cholecystectomy and the role of adjuvant therapy

Annals of Surgery

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Adverse effects of chronic hepatitis B virus (HBV) infection on human sperm quality

Fertility and Sterility

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Randomized clinical trial of laparoscopic versus open pancreatoduodenectomy for periampullary tumours

British Journal of Surgery

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Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy

World Journal of Gastroenterology

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A healthy heart can also help keep the mind sharp

Reuters Health News

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Bifidobacterium infantis NLS super strain reduces the expression of α-defensin-5, a marker of innate immunity, in the mucosa of active celiac disease patients

Journal of Clinical Gastroenterology

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Higher incidence of pancreatic fistula in laparoscopic gastrectomy. Real-world evidence from a nationwide prospective cohort study

Gastric Cancer

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Cohort contributions to race- and gender-specific trends in the incidence of hepatocellular carcinoma in the USA

World Journal of Surgery

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Synaptotagmin-7 is overexpressed in hepatocellular carcinoma and regulates hepatocellular carcinoma cell proliferation via Chk1–p53 signaling

OncoTargets and Therapy

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Detection of acute gastroenteritis etiology in hospitalized young children: Associated factors and outcomes

Hospital Pediatrics

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Association between germline mutations in BRF1, a subunit of the RNA polymerase III transcription complex, and hereditary colorectal cancer

Gastroenterology

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Increased enteric glial cells in proximal margin of resection is associated with postoperative recurrence of Crohn's disease

Journal of Gastroenterology and Hepatology

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De novo SETD5 loss-of-function variant as a cause for intellectual disability in a 10-year old boy with an aberrant blind ending bronchus

Although rare, 3p microdeletion cases have been well described in the clinical literature. The clinical phenotype includes; intellectual disability (ID), growth retardation, facial dysmorphism, and cardiac malformations. Advances in chromosome microarray (CMA) testing narrowed the 3p25 critical region to a 124 kb region, and recent Whole Exome Sequencing (WES) studies have suggested that the SETD5 gene contributes significantly to the 3p25 phenotype. Loss-of-Function (LoF) variants in SETD5 are now considered a likely cause of ID. We report here a patient with a frameshift LoF variant in exon 12 of SETD5. This patient has features overlapping with other patients described with LoF SETD5 variants to include; similar facial morphology, feeding difficulties, ID, behavioral abnormalities and leg length discrepancy. In addition, he presents with an aberrant blind ending bronchus. This report adds to publications describing intragenic mutations in SETD5 and supports the assertion that de novo LoF mutations in SETD5 present with an overlapping but distinct phenotype in comparison with 3p25 microdeletion syndromes.



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Heteromeric α/β glycine receptors regulate excitability in parvalbumin-expressing dorsal horn neurons through phasic and tonic glycinergic inhibition

Abstract

The dorsal horn (DH) of the spinal cord is an important site for modality specific processing of sensory information and is essential for contextually relevant sensory experience. Parvalbumin-expressing inhibitory interneurons (PV + INs) have functional properties and connectivity that enables them to segregate tactile and nociceptive information. Here we examine inhibitory drive to PV + INs using targeted patch-clamp recording in spinal cord slices from adult transgenic mice that express enhanced green fluorescent protein in PV + INs. Analysis of inhibitory synaptic currents showed glycinergic transmission is the dominant form of phasic inhibition to PV + INs. In addition, PV + INs expressed robust glycine-mediated tonic currents, however, we found no evidence for tonic GABAergic currents. Manipulation of extracellular glycine by blocking either, or both, the glial and neuronal glycine transporters markedly decreased PV + IN excitability, as assessed by action potential discharge. This decreased excitability was replicated when tonic glycinergic currents were increased by electrically activating glycinergic synapses. Finally, we show that both phasic and tonic forms of glycinergic inhibition are mediated by heteromeric α/β glycine receptors. This differs from GABAA receptors in the dorsal horn, where different receptor stoichiometries underlie phasic and tonic inhibition. Together these data suggest both phasic and tonic glycinergic inhibition regulate the output of PV + INs and contribute to the processing and segregation of tactile and nociceptive information. The shared stoichiometry for phasic and tonic glycine receptors suggests pharmacology is unlikely to be able to selectively target each form of inhibition in PV + INs.

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Leukoencephalopathy-causing CLCN2 mutations are associated with impaired Cl− channel function and trafficking

Abstract

Mutations in CLCN2 have been recently identified in patients suffering from a type of leukoencephalopathy involving intramyelinic oedema. Here, we characterised most of these mutations, which reduce the function of the chloride channel ClC-2 and impair its plasma membrane (PM) expression. Detailed biochemical and electrophysiological analyses of the Ala500Val mutation revealed that defective gating and increased cellular and PM turnover contributed to defective A500V-ClC-2 functional expression. Co-expression of the adhesion molecule GlialCAM, which forms a tertiary complex with ClC-2 and megalencephalic leukoencephalopathy with subcortical cyst 1 (MLC1), rescued the functional expression of the mutant by modifying its gating properties. GlialCAM also restored the PM levels of the channel by impeding its turnover at the PM. This rescue required ClC-2 localisation to cell-cell junctions, since a GlialCAM mutant with compromised junctional localisation failed to rescue the impaired stability of mutant ClC-2 at the PM. Wild-type, but not mutant ClC-2 was also stabilised by MLC1 overexpression. We suggest that leukodystrophy-causing CLCN2 mutations reduce the functional expression of ClC-2, which is partly counteracted by GlialCAM/MLC1-mediated increase in the gating and stability of the channel.

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Exercise-induced Bronchoconstriction with Firefighting Contained Breathing Apparatus.

Purpose: Protective self-contained breathing apparatus (SCBA) used for firefighting delivers decompressed (cold), dehumidified air that may enhance the severity of exercise-induced bronchoconstriction (EIB) in those susceptible. We investigated the effect of SCBA during exercise on airway caliber in people with asthma and healthy controls. Methods: Two exercise challenges (EC) designed to elicit EIB were performed on separate days within one week. The initial challenge was breathing room air (ECRA) with workload titrated to elicit >60% estimated maximum voluntary ventilation. The exercise intensity was repeated for the second challenge using SCBA (ECSCBA). Forced expiratory volume in one second (FEV1) was measured before and up to 20min after exercise. Bronchial hyperresponsivenss (BHR) to the hyperosmolar mannitol test was measured in the subjects with asthma. Results: Twenty subjects with current asthma (mean[SD] age 27[6] years) and 10 healthy controls (31[5] years, p=0.1) were studied. The % fall in FEV1 following ECSCBA was greater in the mannitol positive asthma subjects (14.4 [15.1]%) compared to mannitol negative asthmatic subjects (1.6 [1.7]%, p=0.02) and controls (2.3 [2.3]%, p=0.04). The FEV1 response was not different between ECRA and ECSCBA (0.49 [5.57] %, p=0.6). No BHR to mannitol (n=7) was highly sensitive for identifying a negative response to ECSCBA (negative predictive value 100%). Conclusions: SCBA does not increase the propensity or severity for EIB in subjects with BHR. Those subjects with asthma but no BHR to inhaled mannitol did not exhibit EIB. BHR to a hyperosmolar stimulus maybe considered a useful screening tool for potential recruits with a history of asthma. (C) 2017 American College of Sports Medicine

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