Contextual Facilitators and Barriers of Community Reintegration among Injured Female Military Veterans: A Qualitative Study

Publication date: Available online 1 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Brent L. Hawkins, Brandi M. Crowe
ObjectiveTo understand the facilitators and barriers to community reintegration (CR) among injured female veterans.DesignPhenomenological qualitative designSettingCommunityParticipantsCommunity-dwelling female veterans with physical and/or psychological injury (N=13).InterventionsNoneMain Outcome MeasuresNoneResultsConventional content analysis revealed three types of facilitators, including: (a) strong social supports; (b) impactful programs; and (c) protective personal beliefs. Six types of barriers included: (a) inadequate services; (b) lack of access to services; (c) poor social support; (d) difficulty trusting others; (e) non-supportive personal beliefs; and (f) injury factors.DiscussionMultiple environmental and personal factors acted as facilitators and barriers to CR. Findings are relatively consistent with previous veteran and civilian community reintegration research that indicates the importance of health-related services, attitudes of others, and social support. However, females in this study reported being impacted by many of these facilitators and barriers because of their gender.ConclusionsThis study supports the need to foster social support among injured female veterans throughout the rehabilitation process to promote CR. Long-term social support can be gained by incorporating services such as adjunctive therapies, recreation, and other social programming into the rehabilitation repertoire to help with CR for all veterans, particularly females.



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What is the longitudinal profile of impairments and can we predict difficulty caring for the profoundly-affected arm in the first year post-stroke?

Publication date: Available online 1 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Rhoda Allison, Cherry Kilbride, Jade Chynoweth, Siobhan Creanor, Ian Frampton, Jonathon Marsden
ObjectiveTo establish the longitudinal profile of impairments of body functions and activity limitations of the arm, and evaluate potential predictors of difficulty caring for the profoundly-affected arm post-stroke.DesignProspective cohort study.SettingThree UK stroke services.ParticipantsPeople unlikely to regain functional use of the arm (N=155) were recruited at 2-4 weeks post-stroke, and followed up at 3, 6 and 12 months. Potential predictors at baseline were hypertonicity, pain, motor control, mood, sensation/perception, age and stroke severity.InterventionsNAMain Outcome MeasuresDifficulty caring for the arm (LASIS), pain, hypertonicity, range of movement, arm function and skin integrity. Multi-variable linear regression identified the best fitting model for predicting LASIS at 12 months.ResultsOne hundred and ten participants (71%) were reviewed at one year. There was a large variation in the profile of arm functions and activity limitations. Inability or severe difficulty caring for the arm affected 29% of participants. Hypertonicity developed in 77%, with severe hypertonicity present in 25%. Pain was reported by 65%, 94% developed shoulder contracture and 6% had macerated skin. Difficulty caring for the arm increased with age, greater level of hypertonicity and stroke classification; collectively these factors accounted for 33% of the variance in LASIS.ConclusionsAt one year post-stroke, there was a high incidence of impairments of body functions and activity limitations in people with a profoundly-affected arm. Individual profiles were very variable and although some pre-disposing factors have been identified, it remains difficult to predict who is at greatest risk.



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Development of a Computerized Adaptive Test of Children’s Gross Motor Skills

Publication date: Available online 1 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Chien-Yu Huang, Li-Chen Tung, Yeh-Tai Chou, Hing-Man Wu, Kuan-Lin Chen, Ching-Lin Hsieh
ObjectiveThis study aimed to develop a computerized adaptive test (CAT) for gross motor skills (GM-CAT) as a diagnostic test and an outcome measure, using the gross motor subtest of the Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT-GM) as the candidate item bank. Moreover, we examined the psychometric properties and the efficiency of the GM-CAT.SettingA developmental center of a medical centerDesignRetrospective study.ParticipantsChildren with and without developmental delay (N=1,738)InterventionsNot Applicable.Main Outcome MeasuresThe CDIIT-GM contains 56 universal items on gross motor skills assessing children's antigravity control, locomotion, and body movement coordination.ResultsThe item bank of the GM-CAT had 44 items that met the dichotomous Rasch model's assumptions. High Rasch person reliabilities were found for each estimated gross motor skill for the GM-CAT (Rasch person reliabilities = 0.940 ∼ 0.995, standard error = 0.68∼2.43). For children of 6 ∼ 71 months, the GM-CAT had good concurrent validity (rs = 0.97 ∼ 0.98), adequate to excellent diagnostic accuracy (area under receiver operating characteristics curve = 0.80 ∼ 0.98), and moderate to large responsiveness (effect size =0.65 ∼ 5.82). The averages of items administered for the GM-CAT were 7 to 11, depending on the age group.ConclusionsThe results of this study support the use of the GM-CAT as a diagnostic and outcome measure to estimate children's gross motor skills in both research and clinical settings.



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Long-Term Functional Outcomes in Military Service Members and Veterans after Traumatic Brain Injury/Polytrauma Inpatient Rehabilitation

Publication date: Available online 1 September 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Max Gray, Joyce Chung, Fatima Aguila, T. Gavin Williams, Jeffrey K. Teraoka, Odette A. Harris
ObjectiveTo determine the impact of the established Polytrauma/TBI infrastructure on immediate post-treatment functional gains, the long-term sustainability of any gains and participation-related community reintegration outcomes in a baseline cohort of patients eight years post-admission.DesignRetrospective review and prospective repeated measures of an inception cohort.SettingVeterans Affairs Palo Alto, Polytrauma Rehabilitation Center (PRC)Participants44 patients consecutively admitted to the PRC inpatient rehabilitation unit during its first full Fiscal Year, 2006.InterventionsThe PRC infrastructure and the formalized rehabilitation for Polytrauma/TBI.Main Outcome MeasuresFunctional Independence Measure scores at admission, discharge, 3 months and 8 years post discharge; participation-related socioeconomic factors reflecting community reintegration eight years after admission.ResultsFunctional gains were statistically significantly increased from admission to discharge. Improvements were maintained at both 3 months post-discharge and 8 years post-discharge. The socio-economic data collected at 8 year follow-up showed greater than 50% either competitively employed or continuing their education and 100% living in a non-institutionalized setting.ConclusionsThis study addresses a concern regarding the long-term functional outcomes of rehabilitation patients treated by the established infrastructure of the Polytrauma System of Care inpatient rehabilitation centers. The results suggest that Polytrauma/TBI rehabilitation care utilizing a comprehensive, integrated approach is effective and durable in achieving functional gains and successful community reintegration within our initial PRC cohort. Follow-up of subsequent FY cohorts would add to the validity of these outcome findings.



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Depression in the School-Aged Child With Type 1 Diabetes: Implications for Pediatric Primary Care Providers

Depression is a common comorbid condition experienced by children with type 1 diabetes that, if undiagnosed, can lead to deterioration in glycemic control and other serious health complications. Although it is documented that children with type 1 diabetes experience high rates of depression, a comprehensive clinical guide does not exist to help direct the pediatric provider on how to best care for these children. The purpose of this article is to synthesize current evidence to aid the pediatric primary care provider in the detection and management of depression in the school-aged child with type 1 diabetes.

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Health-Related Quality of Life Outcomes of a Telehealth Care Coordination Intervention for Children With Medical Complexity: A Randomized Controlled Trial

The purpose of this study was to explore health-related quality of life (HRQL) and family impact in the context of an advanced practice registered nurse–delivered telehealth care coordination intervention for children with medical complexity (CMC). This was a secondary outcomes analysis of a randomized controlled trial with 163 families of CMC in an existing medical home. HRQL and family impact were measured using the PedsQL measurement model. Bivariate and analysis of covariance analyses were conducted to explore associations at baseline and the intervention effect over 2 years.

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Incontinentia Pigmenti: A Summary Review of This Rare Ectodermal Dysplasia With Neurologic Manifestations, Including Treatment Protocols

Incontinentia pigmenti is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene (formerly known as NEMO). There are 27.6 new cases per year worldwide; 65% to 75% are sporadic mutations, and 25% to 35% are familial. It is usually lethal in males, but females survive because of X-inactivation mosaicism. The disorder is typically identified by unique skin findings, a series of four stages that emerge throughout the first year of life. The central nervous system manifestations in the eye and in the brain cause the most disability.

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Development and validation of a new scoring system to determine the necessity of small-bowel endoscopy in obscure gastrointestinal bleeding

Small bowel capsule endoscopy (SBCE) is the recommended first-line procedure for obscure gastrointestinal bleeding (OGIB). However, a method for predicting the necessity of subsequent double-balloon endoscopy (DBE) has not been established.

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Comparison of s2-alar and traditional iliac screw pelvic fixation for pediatric neuromuscular deformity

Background ContextMany pelvic fixation options exist for posterior spinal fusion of pediatric neuromuscular scoliosis, including standard iliac screws (SIS) or a more recently introduced S2-Alar (S2A) technique. However, little data exists comparing the clinical and radiographic outcomes of these techniques.PurposeIdentify differences in clinical and radiographic outcomes for pediatric neuromuscular scoliosis patients treated with standard iliac screw (SIS) or S2-Alar (S2-A) pelvic fixation.Study Design/SettingRetrospective cohort study at a pediatric orthopaedic clinic.

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Long-term clinical results following Charite III lumbar total disc replacement

The lumbar total disc replacement (TDR) operation represents an alternative to lumbar fusion for the treatment of symptomatic lumbar intervertebral disc degeneration, and has gained increasing attention in recent years.

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An increase in the degree of olisthesis during axial loading reduces the dural sac size and worsens clinical symptoms in patients with degenerative spondylolisthesis

Previous studies have shown that axial loading during MRI significantly reduces the size of the dural sac compared with conventional MRI in patients with degenerative lumbar disease. In our previous study, axial-loaded MRI showed a significantly larger degree of olisthesis than conventional MRI in patients with degenerative spondylolisthesis (DS). Furthermore, the degree of olisthesis on axial-loaded MRI correlated more strongly with that observed on X-ray in the upright position. However, no study has investigated whether or not the increase in the degree of olisthesis during axial loading correlates with the reduction in the dural sac size and affects the severity of clinical symptoms in patients with DS.

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Surgical outcomes in the elderly with degenerative spondylolisthesis, comparative study between patients over 80 years of age and under 80 years- a gender, diagnosis, and surgical method matched two cohort analyses

In my country, the current life expectancy of an 80-year-old man is 88.4 years and that of an 80-year-old is woman is 89.8 years. Surgical candidates older than 80 years usually ask surgeons whether it would be safe for them to undergo surgery.

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The patient's experience with non-surgical treatment for lumbar spinal stenosis: a qualitative study

Lumbar spinal stenosis (LSS) is a highly prevalent disease in older adults that causes significant limitations in walking and other daily activities. There is a lack of research into optimal nonsurgical treatment approaches for LSS.

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Post-tetanic transcranial motor evoked potentials augments the amplitude of compound muscle action potentials recorded from innervated and non-innervated muscles

Transcranial electrical stimulation used to produce motor evoked potentials (TES-MEP) and subsequent compound muscle action potential (CMAP) recording is widely used to monitor motor function during surgery when there is risk of damaging the spinal cord. Nonetheless, some muscles do not produce CMAP amplitudes sufficient for intraoperative monitoring.

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Development and validation of a new scoring system to determine the necessity of small-bowel endoscopy in obscure gastrointestinal bleeding

Small bowel capsule endoscopy (SBCE) is the recommended first-line procedure for obscure gastrointestinal bleeding (OGIB). However, a method for predicting the necessity of subsequent double-balloon endoscopy (DBE) has not been established.

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A gene-based test of association through an orthogonal decomposition of genotype scores

Abstract

The burden test and the sequence kernel association test (SKAT) are two popular methods for detecting association with rare variants. Treated as two different sources of association information, they are adaptively combined to form an optimal SKAT (SKAT-O) method for optimal power. We show that the burden test is part of rather than independent of the SKAT. We introduce a new test statistic that is the sum of the burden statistic and a statistic asymptotically independent of the burden statistic. The performance of this new test statistic is demonstrated through extensive simulation studies and applications to a Genetic Analysis Workshop 17 data set and the Ocular Hypertension Treatment Study data.

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Testing a linear time invariant model for skin conductance responses by intraneural recording and stimulation

Abstract

Skin conductance responses (SCR) are increasingly analyzed with model-based approaches that assume a linear and time-invariant (LTI) mapping from sudomotor nerve (SN) activity to observed SCR. These LTI assumptions have previously been validated indirectly, by quantifying how much variance in SCR elicited by sensory stimulation is explained under an LTI model. This approach, however, collapses sources of variability in the nervous and effector organ systems. Here, we directly focus on the SN/SCR mapping by harnessing two invasive methods. In an intraneural recording experiment, we simultaneously track SN activity and SCR. This allows assessing the SN/SCR relationship but possibly suffers from interfering activity of non-SN sympathetic fibers. In an intraneural stimulation experiment under regional anesthesia, such influences are removed. In this stimulation experiment, about 95% of SCR variance is explained under LTI assumptions when stimulation frequency is below 0.6 Hz. At higher frequencies, nonlinearities occur. In the intraneural recording experiment, explained SCR variance is lower, possibly indicating interference from non-SN fibers, but higher than in our previous indirect tests. We conclude that LTI systems may not only be a useful approximation but in fact a rather accurate description of biophysical reality in the SN/SCR system, under conditions of low baseline activity and sporadic external stimuli. Intraneural stimulation under regional anesthesia is the most sensitive method to address this question.

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Saline-immersion therapeutic endoscopy (SITE): An evolution of underwater endoscopic lesion resection

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Italian consensus on diagnosis and management of Barrett’s Esophagus

Barrett's esophagus (BE) is recognized as a risk factor for esophageal adenocarcinoma. An expert panel was organized in Italy with the aim of drafting a series of statements on BE to guide diagnosis and management of patients with BE.

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Saline-immersion therapeutic endoscopy (SITE): An evolution of underwater endoscopic lesion resection

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Italian consensus on diagnosis and management of Barrett’s Esophagus

Barrett's esophagus (BE) is recognized as a risk factor for esophageal adenocarcinoma. An expert panel was organized in Italy with the aim of drafting a series of statements on BE to guide diagnosis and management of patients with BE.

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ZOLL announces call for presentations for Summit 2018

CHELMSFORD, Mass.— ZOLL® Medical Corporation, an Asahi Kasei Group Company that manufactures medical devices and related software solutions, today announced the call for presentations for SUMMIT 2018, which will take place in Denver, Colorado, May 8-10, 2018. Fire and EMS professionals who are interested in speaking should visit the Summit Presenter Page to review the guidelines and submit ...

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Bleeding control

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Bleeding control

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Staff Nurse – Vitalink - New Hanover Regional Medical Center

Staff Nurse – Vitalink Full-Time, Rotating Schedule New Hanover Regional Medical Center Wilmington, NC New Hanover Regional Medical Center's Emergency Transport Services (ETS) is a recognized leader at both state and national levels. Recent awards include: the 2016 American Heart Association Mission Lifeline Gold Award Recognition for EMS, AirLink, and VitaLink, the 2016 EMS National Association ...

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Critical Care Transport Paramedic – Vitalink - New Hanover Regional Medical Center

Critical Care Transport Paramedic – Vitalink Full-Time, Rotating Schedule New Hanover Regional Medical Center Wilmington, NC New Hanover Regional Medical Center's Emergency Transport Services (ETS) is a recognized leader at both state and national levels. Recent awards include: the 2016 American Heart Association Mission Lifeline Gold Award Recognition for EMS, AirLink, and VitaLink, the ...

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A volumetric technique for fossil body mass estimation applied to Australopithecus afarensis

Publication date: Available online 31 August 2017
Source:Journal of Human Evolution
Author(s): Charlotte A. Brassey, Thomas G. O'Mahoney, Andrew T. Chamberlain, William I. Sellers
Fossil body mass estimation is a well established practice within the field of physical anthropology. Previous studies have relied upon traditional allometric approaches, in which the relationship between one/several skeletal dimensions and body mass in a range of modern taxa is used in a predictive capacity. The lack of relatively complete skeletons has thus far limited the potential application of alternative mass estimation techniques, such as volumetric reconstruction, to fossil hominins. Yet across vertebrate paleontology more broadly, novel volumetric approaches are resulting in predicted values for fossil body mass very different to those estimated by traditional allometry. Here we present a new digital reconstruction of Australopithecus afarensis (A.L. 288-1; 'Lucy') and a convex hull-based volumetric estimate of body mass. The technique relies upon identifying a predictable relationship between the 'shrink-wrapped' volume of the skeleton and known body mass in a range of modern taxa, and subsequent application to an articulated model of the fossil taxa of interest. Our calibration dataset comprises whole body computed tomography (CT) scans of 15 species of modern primate. The resulting predictive model is characterized by a high correlation coefficient (r² = 0.988) and a percentage standard error of 20%, and performs well when applied to modern individuals of known body mass. Application of the convex hull technique to A. afarensis results in a relatively low body mass estimate of 20.4 kg (95% prediction interval 13.5–30.9 kg). A sensitivity analysis on the articulation of the chest region highlights the sensitivity of our approach to the reconstruction of the trunk, and the incomplete nature of the preserved ribcage may explain the low values for predicted body mass here. We suggest that the heaviest of previous estimates would require the thorax to be expanded to an unlikely extent, yet this can only be properly tested when more complete fossils are available.



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Pharmacogenomic Variability of Oral Baclofen Clearance and Clinical Response in Children with Cerebral Palsy

Pharmacogenomic variability can contribute to differences in pharmacokinetics and clinical responses. Pediatric patients with cerebral palsy (CP) with genetic variations have not been studied for these potential differences.

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Reliability and validity of subjective measures of aerobic intensity in adults with spinal cord injury: a systematic review

To systematically synthesize and appraise research regarding test-retest reliability or criterion validity of subjective measures for assessing aerobic exercise intensity in adults with spinal cord injury (SCI).

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Long Term Effects of Orthoses Use on the Changes of Foot and Ankle Joint Motions of Spastic CP Children

Orthoses are commonly prescribed to children with cerebral palsy (CP) in order to provide foot correction and to improve ambulatory function. Immediate effects of ankle foot orthosis (AFOs) have been investigated, but long term kinematic effects are lacking clinical evidence.

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Unilateral Lower Extremity Pain Due to Malignancy Managed with Cordotomy

Cancer pain management is comprehensive, and it generally begins with pharmacotherapy in a step-wise approach per analgesic guidelines established decades ago by the World Health Organization. This analgesic ladder involves the prescribing of co-analgesics, adjuvants, and opioids, with each step depending on pain severity. Although the majority of cancer pain responds to this strategy, there exist patients who do not respond adequately or experience significant side effects or intolerance to pain medications.

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Bleeding control

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Diagnostic exome sequencing in early-onset Parkinson's disease confirms VPS13C as a rare cause of autosomal-recessive Parkinson's disease

Parkinson's disease (PD) is a genetically heterogeneous disorder and new putative disease genes are discovered constantly. Therefore, whole exome sequencing could be an efficient approach to genetic testing in PD. To evaluate its performance in early-onset sporadic PD, we performed diagnostic exome sequencing in 80 individuals with manifestation of PD symptoms at age 40 or earlier and a negative family history of PD. Variants in validated and candidate disease genes and risk factors for PD and atypical Parkinson syndromes were annotated, followed by further analysis for selected variants. We detected pathogenic variants in Mendelian genes in 6.25% of cases and high-impact risk factor variants in GBA in 5% of cases, resulting in overall maximum diagnostic yield of 11.25%. One individual was compound heterozygous for variants affecting canonical splice sites in VPS13C, confirming the causal role of protein-truncating variants in this gene linked to autosomal-recessive early-onset PD. Despite the low diagnostic yield of exome sequencing in sporadic early-onset Parkinson's disease, the confirmation of the recently discovered VPS13C gene highlights its advantage over using predefined gene panels.

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Bleeding control

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Suspect arrested after stealing ambulance in Calif.

The suspect led officers on a chase along a Southern California freeway

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Skeletal muscle mitochondrial mass is linked to lipid and metabolic profile in individuals with spinal cord injury

Abstract

Purpose

Changes in metabolism and body composition after spinal cord injury (SCI) predispose individuals to obesity, type II diabetes, and cardiovascular disease. A link between lean mass and skeletal muscle mitochondrial mass has been reported but it is unknown how skeletal muscle mitochondrial mass and activity impact metabolic health. This study examined the relationship between skeletal muscle mitochondrial mass, activity and metabolic profile in individuals with chronic SCI.

Methods

Twenty-two men with motor complete SCI participated in the study. Citrate synthase (CS) and complex III (CIII) activity was measured in vastus lateralis biopsies. Metabolic profile was assessed by intravenous glucose tolerance test, basal metabolic rate (BMR), maximum oxygen uptake (VO₂ peak) and blood lipid profile.

Results

Skeletal muscle CS activity was negatively related to the cholesterol:high density lipoprotein cholesterol (HDL-C) ratio and triglycerides (r = −0.60, p = 0.009; r = −0.64, p = 0.004, respectively). CS activity was positively related to insulin sensitivity and BMR (r = 0.67, p = 0.006; r = 0.64, p = 0.005, respectively). Similar relationships were found for CIII and metabolic profile, but not CIII normalized to CS. Many of the relationships between CS and metabolism remained significant when age, level of injury, or time since injury were accounted for. They also remained significant when CS activity was normalized to total lean mass.

Conclusions

These results suggest that an increase in skeletal muscle mitochondrial mass is associated with improved metabolic health independent of age, level of injury, or time since injury in individuals with chronic SCI. This highlights the importance of maintaining and improving mitochondrial health in individuals with SCI.

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Effects of 10 days of separate heat and hypoxic exposure on heat acclimation and temperate exercise performance

Adaptations to heat and hypoxia are typically studied in isolation but are often encountered in combination. Whether the adaptive response to multiple stressors affords the same response as when examined in isolation is unclear. We examined 1) the influence of overnight moderate normobaric hypoxia on the time course and magnitude of adaptation to daily heat exposure and 2) whether heat acclimation (HA) was ergogenic and whether this was influenced by an additional hypoxic stimulus. Eight males [Vo_2max = 58.5 (8.3) ml·kg^–1·min^–1] undertook two 11-day HA programs (balanced-crossover design), once with overnight normobaric hypoxia (HA_Hyp): 8 (1) h per night for 10 nights [FIO2 = 0.156; S_pO₂ = 91 (2)%] and once without (HA_Con). Days 1, 6, and 11 were exercise-heat stress tests [HST (40°C, 50% relative humidity, RH)]; days 2–5 and 7–10 were isothermal strain [target rectal temperature (T_re) ~38.5°C], exercise-heat sessions. A graded exercise test and 30-min cycle trial were undertaken pre-, post-, and 14 days after HA in temperate normoxia (22°C, 55% RH; F_IO₂ = 0.209). HA was evident on day 6 (e.g., reduced T_re, mean skin temperature (T_sk), heart rate, and sweat [Na⁺], P < 0.05) with additional adaptations on day 11 (further reduced T_sk and heart rate). HA increased plasma volume [+5.9 (7.3)%] and erythropoietin concentration [+1.8 (2.4) mIU/ml]; total hemoglobin mass was unchanged. Peak power output [+12 (20) W], lactate threshold [+15 (18) W] and work done [+12 (20) kJ] increased following HA. The additional hypoxic stressor did not affect these adaptations. In conclusion, a separate moderate overnight normobaric hypoxic stimulus does not affect the time course or magnitude of HA. Performance may be improved in temperate normoxia following HA, but this is unaffected by an additional hypoxic stressor.

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High glucose increases action potential firing of catecholamine neurons in the nucleus of the solitary tract by increasing spontaneous glutamate inputs

Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brain stem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal, and stress. However, it is not known if they respond to changes in glucose. Here we determined whether NTS-CA neurons respond to changes in glucose concentration and the mechanism involved. We found that decreasing glucose concentrations from 5 mM to 2 mM to 1 mM, significantly decreased action potential firing in a cell-attached preparation, whereas increasing it back to 5 mM increased the firing rate. This effect was dependent on glutamate release from afferent terminals and required presynaptic 5-HT₃Rs. Decreasing the glucose concentration also decreased both basal and 5-HT₃R agonist-induced increase in the frequency of spontaneous glutamate inputs onto NTS-CA neurons. Low glucose also blunted 5-HT-induced inward currents in nodose ganglia neurons, which are the cell bodies of vagal afferents. The effect of low glucose in both nodose ganglia cells and in NTS slices was mimicked by the glucokinase inhibitor glucosamine. This study suggests that NTS-CA neurons are glucosensing through a presynaptic mechanism that is dependent on vagal glutamate release, 5-HT₃R activity, and glucokinase.

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Seasonal factors influence quantal transmitter release and calcium dependence at amphibian neuromuscular junctions

Amphibian neuromuscular junctions (NMJs) are composed of hundreds of neurotransmitter release sites that exhibit nonuniform transmitter release probabilities and demonstrated seasonal modulation. We examined whether recruitment of release sites is variable when the extracellular calcium concentration ([Ca²⁺]_o) is increased in the wet and dry seasons. The amount of transmitter released from the entire nerve terminal increases by approximately the fourth power as [Ca²⁺]_o is increased. Toad (Bufo marinus) NMJs were visualized using 3,3'-diethyloxardicarbocyanine iodide [DiOC₂(5)] fluorescence, and focal loose patch extracellular recordings were used to record the end-plate currents (EPCs) from small groups of release sites. Quantal content (_e), average probability of quantal release (p_e), and the number of active release sites (n_e) were determined for different [Ca²⁺]_o. Our results indicated that the recruitment of quantal release sites with increasing [Ca²⁺]_o differs spatially (between different groups of release sites) and also temporally (in different seasons). These differences were reflected by the nonuniform alterations in p_e and n_e. Most release site groups demonstrated an increase in both p_e and n_e when [Ca²⁺]_o increased. In ~30% of release site groups examined, p_e decreased while n_e increased only during the active period (wet season). Although the dry season induced parallel right shift in the quantal release versus extracellular calcium concentration when compared with the wet season, the dependence of quantal content on [Ca²⁺]_o was not changed. These results demonstrate the flexibility, reserve, and adaptive capacity of neuromuscular junctions in maintaining appropriate levels of neurotransmission.

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Localized and systemic variations in central motor drive at different local skin and muscle temperatures

This study investigated the ability to sustain quadriceps central motor drive while subjected to localized heat and metaboreceptive feedback from the contralateral leg. Eight active males each completed two counter-balanced trials, in which muscle temperature (T_m) of a single-leg (TEMP-LEG) was altered to 29.4°C (COOL) or 37.6°C (WARM), while the contralateral leg (CL-LEG) remained thermoneutral: 35.3°C and 35.2°C T_m in COOL and WARM, respectively. To activate metaboreceptive feedback, participants first performed one 120-s isometric maximal voluntary contraction (MVC) of the knee extensors in the TEMP-LEG, immediately followed by postexercise muscle ischemia (PEMI) via femoral blood flow occlusion. To assess central motor drive of a remote muscle group immediately following PEMI, another 120-s MVC was subsequently performed in the CL-LEG. Voluntary muscle activation (VA) was assessed using the twitch interpolation method. Perceived mental effort and limb discomfort were also recorded. In a cooled muscle, a significant increase in mean force output and mean VA (force, P < 0.001; VA, P < 0.05), as well as a significant decrease in limb discomfort (P < 0.05) occurred during the sustained MVC in the TEMP-LEG. However, no differences between T_m were observed in mean force output, mean VA, or limb discomfort during the sustained MVC in the CL-LEG (force, P = 0.33; VA, P > 0.68; and limb discomfort, P = 0.73). The present findings suggest that elevated local skin temperature and T_m can increase limb discomfort and decrease central motor drive, but this does not limit systemic motor activation of a thermoneutral muscle group.

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Renal vascular and glomerular pathologies associated with spontaneous hypertension in the nonhuman primate Chlorocebus aethiops sabaeus

Hypertension is a complex, multifactorial disease affecting an estimated 78 million adults in the United States. Despite scientific gains, the etiology of human essential hypertension is unknown and current experimental models do not recapitulate all the behavioral and physiological characteristics of the pathology. Researchers should assess the translational capacity of these models and look to other animal models for the discovery of new therapies. Chlorocebus aethiops sabaeus, the African Green Monkey (AGM), is a nonhuman primate that develops spontaneous hypertension and may provide a novel translational model for the study of hypertension and associated diseases. In a randomly selected group of 424 adult AGMs, 37% (157/424) exhibited systolic blood pressures (SBP) >140 mmHg (SBP: 172.0 ± 2.2 mmHg) and were characterized as hypertensive (HT). 44% (187/424) were characterized as normotensive with SBP <120 mmHg (NT, SBP: 99.6 ± 1.0 mmHg) and the remaining 18% (80/424) as borderline hypertensive (BHT, SBP: 130.6 ± 0.6 mmHg). When compared with NT animals, HT AGMs are older (8.7 ± 0.6 vs. 12.4 ± 0.7 yr, P < 0.05) with elevated heart rates (125.7 ± 2.0 vs. 137.7 ± 2.2 beats/min, P < 0.05). BHT animals had average heart rates of 138.2 ± 3.1 beats/min (P < 0.05 compared with NT) and were 11.00 ± 0.9 yr old. NT and HT animals had similar levels of angiotensinogen gene expression, plasma renin activity, and renal cortical renin content (P > 0.05). HT monkeys exhibit renal vascular remodeling (wall-to-lumen ratio NT 0.11 ± 0.01 vs. HT 0.15 ± 0.02, P < 0.05) and altered glomerular morphology (Bowman's capsular space: NT 30.9 ± 1.9% vs. HT 44.4 ± 3.1%, P < 0.05). The hypertensive AGM provides a large animal model that is highly similar to humans and should be studied to identify novel, more effective targets for the treatment of hypertension.

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Decreased myoblast differentiation in chronic binge alcohol-administered simian immunodeficiency virus-infected male macaques: role of decreased miR-206

Skeletal muscle stem cells play a critical role in regeneration of myofibers. We previously demonstrated that chronic binge alcohol (CBA) markedly attenuates myoblast differentiation potential and myogenic gene expression. Muscle-specific microRNAs (miRs) are implicated in regulation of myogenic genes. The aim of this study was to determine whether myoblasts isolated from asymptomatic CBA-administered simian immunodeficiency virus (SIV)-infected macaques treated with antiretroviral therapy (ART) showed similar impairments and, if so, to elucidate potential underlying mechanisms. Myoblasts were isolated from muscle at 11 mo after SIV infection from CBA/SIV macaques and from time-matched sucrose (SUC)-treated SIV-infected (SUC/SIV) animals and age-matched controls. Myoblast differentiation and myogenic gene expression were significantly decreased in myoblasts from SUC/SIV and CBA/SIV animals compared with controls. SIV and CBA decreased muscle-specific miR-206 in plasma and muscle and SIV decreased miR-206 expression in myoblasts, with no statistically significant changes in other muscle-specific miRs. These findings were associated with a significant increase in histone deacetylase 4 (HDAC4) and decrease in myogenic enhancer factor 2C (MEF2C) expression in CBA/SIV muscle. Transfection with miR-206 inhibitor decreased myotube differentiation, increased expression of HDAC4, and decreased MEF2C, suggesting a critical role of miR-206 in myogenesis. Moreover, HDAC4 was confirmed to be a direct miR-206 target. These results support a mechanistic role for decreased miR-206 in suppression of myoblast differentiation resulting from chronic alcohol and SIV infection. The parallel changes in skeletal muscle and circulating levels of miR-206 warrant studies to establish the possible use of plasma miR-206 as an indicator of impaired muscle function.

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EMT - Trust Ambulance Inc.

Respond to and manage non-emergent and occasional emergent transports as a BLS team member on a BLS or ALS unit.

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Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control

Abstract

Background

Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment-resistant epilepsy.

Objective

To characterize heart rate (HR) responses (HRR) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart.

Methods

In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n = 8, "cardiac" configuration) or with electrode positions reversed (n = 8, "epilepsy" configuration). In awake state, HRR were determined for each combination of pulse frequency (2–20 Hz), intensity (0–3.5 mA) and pulse widths (130–750 μs) over 14 months.

Results

At low intensities and higher frequency VNS, HR increases during VNS active phase owing to afferent modulation of parasympathetic central drive. When functional effects of afferent and efferent fibre activation are balanced, a null HRR is evoked [defined as "neural fulcrum"] during which HRR ≅ 0. As intensity increases further, HR is reduced during the active phase of VNS. While qualitatively similar, VNS delivered in the epilepsy configuration resulted in more pronounced HR acceleration and reduced HR deceleration during VNS. At termination, under anaesthesia, transection of the vagi rostral to stimulation site eliminated the augmenting response to VNS and enhanced the parasympathetic efferent-mediated suppressing effect on electrical and mechanical function of the heart.

Conclusions

VNS activates central then peripheral aspects of the cardiac nervous system. VNS control over cardiac function is maintained during chronic therapy.

This article is protected by copyright. All rights reserved

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The cerebellum does more than sensory prediction error-based learning in sensorimotor adaptation tasks

Individuals with damage to the cerebellum perform poorly in sensorimotor adaptation paradigms. This deficit has been attributed to impairment in sensory prediction error-based updating of an internal forward model, a form of implicit learning. These individuals can, however, successfully counter a perturbation when instructed with an explicit aiming strategy. This successful use of an instructed aiming strategy presents a paradox: In adaptation tasks, why do individuals with cerebellar damage not come up with an aiming solution on their own to compensate for their implicit learning deficit? To explore this question, we employed a variant of a visuomotor rotation task in which, before executing a movement on each trial, the participants verbally reported their intended aiming location. Compared with healthy control participants, participants with spinocerebellar ataxia displayed impairments in both implicit learning and aiming. This was observed when the visuomotor rotation was introduced abruptly (experiment 1) or gradually (experiment 2). This dual deficit does not appear to be related to the increased movement variance associated with ataxia: Healthy undergraduates showed little change in implicit learning or aiming when their movement feedback was artificially manipulated to produce similar levels of variability (experiment 3). Taken together the results indicate that a consequence of cerebellar dysfunction is not only impaired sensory prediction error-based learning but also a difficulty in developing and/or maintaining an aiming solution in response to a visuomotor perturbation. We suggest that this dual deficit can be explained by the cerebellum forming part of a network that learns and maintains action-outcome associations across trials.

NEW & NOTEWORTHY Individuals with cerebellar pathology are impaired in sensorimotor adaptation. This deficit has been attributed to an impairment in error-based learning, specifically, from a deficit in using sensory prediction errors to update an internal model. Here we show that these individuals also have difficulty in discovering an aiming solution to overcome their adaptation deficit, suggesting a new role for the cerebellum in sensorimotor adaptation tasks.

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Regulation of axonal regeneration following spinal cord injury in the lamprey

Following rostral spinal cord injury (SCI) in larval lampreys, injured descending brain neurons, particularly reticulospinal (RS) neurons, regenerate their axons, and locomotor behavior recovers in a few weeks. However, axonal regeneration of descending brain neurons is mostly limited to relatively short distances, but the mechanisms for incomplete axonal regeneration are unclear. First, lampreys with rostral SCI exhibited greater axonal regeneration of descending brain neurons, including RS neurons, as well as more rapid recovery of locomotor muscle activity right below the lesion site, compared with animals with caudal SCI. In addition, following rostral SCI, most injured RS neurons displayed the "injury phenotype," whereas following caudal SCI, most injured neurons displayed normal electrical properties. Second, following rostral SCI, at cold temperatures (~4–5°C), axonal transport was suppressed, axonal regeneration and behavioral recovery were blocked, and injured RS neurons displayed normal electrical properties. Cold temperatures appear to prevent injured RS neurons from detecting and/or responding to SCI. It is hypothesized that following rostral SCI, injured descending brain neurons are strongly stimulated to regenerate their axons, presumably because of elimination of spinal synapses and reduced neurotrophic support. However, when these neurons regenerate their axons and make synapses right below the lesion site, restoration of neurotrophic support very likely suppress further axonal regeneration. In contrast, caudal SCI is a weak stimulus for axonal regeneration, presumably because of spared synapses above the lesion site. These results may have implications for mammalian SCI, which can spare synapses above the lesion site for supraspinal descending neurons and propriospinal neurons.

NEW & NOTEWORTHY Lampreys with rostral spinal cord injury (SCI) exhibited greater axonal regeneration of descending brain neurons and more rapid recovery of locomotor muscle activity below the lesion site compared with animals with caudal SCI. In addition, following rostral SCI, most injured reticulospinal (RS) neurons displayed the "injury phenotype," whereas following caudal SCI, most injured neurons had normal electrical properties. We hypothesize that following caudal SCI, the spared synapses of injured RS neurons might limit axonal regeneration and behavioral recovery.

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Long-interval intracortical inhibition is asymmetric in young but not older adults

Aging is typically accompanied by a decline in manual dexterity and handedness; the dominant hand executes tasks of manual dexterity more quickly and accurately than the nondominant hand in younger adults, but this advantage typically declines with age. Age-related changes in intracortical inhibitory processes might play a role in the age-related decline in manual dexterity. Long-interval intracortical inhibition (LICI) is asymmetric in young adults, with more sensitive and more powerful LICI circuits in the dominant hemisphere than in the nondominant hemisphere. Here we investigated whether the hemispheric asymmetry in LICI in younger adults persists in healthy older adults. Paired-pulse transcranial magnetic stimulation was used to measure LICI in the dominant and nondominant hemispheres of younger and older adults; LICI stimulus-response curves were obtained by varying conditioning stimulus intensity at two different interstimulus intervals [100 ms (LICI₁₀₀) and 150 ms]. We have replicated the finding that LICI₁₀₀ circuits are more sensitive and more powerful in the dominant than the nondominant hemisphere of young adults and extend this finding to show that the hemispheric asymmetry in LICI₁₀₀ is lost with age. In the context of behavioral observations showing that dominant hand movements in younger adults are more fluent than nondominant hand movements in younger adults and dominant hand movements in older adults, we speculate a role of LICI₁₀₀ in the age-related decline in manual dexterity.

NEW & NOTEWORTHY In younger adults, more sensitive and more powerful long-interval intracortical inhibitory circuits are evident in the hemisphere controlling the more dexterous hand; this is not the case in older adults, for whom long-interval intracortical inhibitory circuits are symmetric and more variable than in younger adults. We speculate that the highly sensitive and powerful long-interval intracortical inhibition circuits in the dominant hemisphere play a role in manual dexterity.

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Activation of ganglion cells and axon bundles using epiretinal electrical stimulation

Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses.

NEW & NOTEWORTHY Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.

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Using theoretical models from adult stroke recovery to improve use of noninvasive brain stimulation for children with congenital hemiparesis

Noninvasive brain stimulation has been widely used for adults with stroke to improve upper limb motor function. A recent study by Kirton and colleagues (Kirton A, Ciechanski P, Zewdie E, Andersen J, Nettel-Aguirre A, Carlson H, Carsolio L, Herrero M, Quigley J, Mineyko A, Hodge J, Hill M. Neurology 88: 259–267, 2017) applied noninvasive brain stimulation to children with congenital hemiparesis but found no significant effect of noninvasive brain stimulation on motor function. Here, we explore theories about cortical reorganization in both adult and children with hemiparesis and discuss how to improve the approaches of noninvasive brain stimulation to generate optimal motor improvement and development for children with congenital hemiparesis.

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Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement

Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate.

NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also demonstrate, for the first time in humans, a mechanism through which the premotor and sensory cortices are functionally connected to the STN.

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The visual encoding of purely proprioceptive intermanual tasks is due to the need of transforming joint signals, not to their interhemispheric transfer

To perform goal-oriented hand movement, humans combine multiple sensory signals (e.g., vision and proprioception) that can be encoded in various reference frames (body centered and/or exo-centered). In a previous study (Tagliabue M, McIntyre J. PLoS One 8: e68438, 2013), we showed that, when aligning a hand to a remembered target orientation, the brain encodes both target and response in visual space when the target is sensed by one hand and the response is performed by the other, even though both are sensed only through proprioception. Here we ask whether such visual encoding is due 1) to the necessity of transferring sensory information across the brain hemispheres, or 2) to the necessity, due to the arms' anatomical mirror symmetry, of transforming the joint signals of one limb into the reference frame of the other. To answer this question, we asked subjects to perform purely proprioceptive tasks in different conditions: Intra, the same arm sensing the target and performing the movement; Inter/Parallel, one arm sensing the target and the other reproducing its orientation; and Inter/Mirror, one arm sensing the target and the other mirroring its orientation. Performance was very similar between Intra and Inter/Mirror (conditions not requiring joint-signal transformations), while both differed from Inter/Parallel. Manipulation of the visual scene in a virtual reality paradigm showed visual encoding of proprioceptive information only in the latter condition. These results suggest that the visual encoding of purely proprioceptive tasks is not due to interhemispheric transfer of the proprioceptive information per se, but to the necessity of transforming joint signals between mirror-symmetric limbs.

NEW & NOTEWORTHY Why does the brain encode goal-oriented, intermanual tasks in a visual space, even in the absence of visual feedback about the target and the hand? We show that the visual encoding is not due to the transfer of proprioceptive signals between brain hemispheres per se, but to the need, due to the mirror symmetry of the two limbs, of transforming joint angle signals of one arm in different joint signals of the other.

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Interhemispheric interactions between trunk muscle representations of the primary motor cortex

Unilateral arm movements require trunk stabilization through bilateral contraction of axial muscles. Interhemispheric interactions between primary motor cortices (M1) could enable such coordinated contractions, but these mechanisms are largely unknown. Using transcranial magnetic stimulation (TMS), we characterized interhemispheric interactions between M1 representations of the trunk-stabilizing muscles erector spinae at the first lumbar vertebra (ES L1) during a right isometric shoulder flexion. These interactions were compared with those of the anterior deltoid (AD), the main agonist in this task, and the first dorsal interosseous (FDI). TMS over the right M1 elicited ipsilateral silent periods (iSP) in all three muscles on the right side. In ES L1, but not in AD or FDI, ipsilateral motor evoked potential (iMEP) could precede the iSP or replace it. iMEP amplitude was not significantly different whether ES L1 was used to stabilize the trunk or was voluntarily contracted. TMS at the cervicomedullary junction showed that the size of cervicomedullary evoked potential was unchanged during the iSP but increased during iMEP, suggesting that the iSP, but not the iMEP, is due to intracortical mechanisms. Using a dual-coil paradigm with two coils over the left and right M1, interhemispheric inhibition could be evoked at interstimulus intervals of 6 ms in ES L1 and 8 ms in AD and FDI. Together, these results suggest that interhemispheric inhibition is dominant when axial muscles are involved in a stabilizing task. The ipsilateral facilitation could be evoked by ipsilateral or subcortical pathways and could be used depending on the role axial muscles play in the task.

NEW & NOTEWORTHY The mechanisms involved in the bilateral coordination of axial muscles during unilateral arm movement are poorly understood. We thus investigated the nature of interhemispheric interactions in axial muscles during arm motor tasks in healthy subjects. By combining different methodologies, we showed that trunk muscles receive both inhibitory and facilitatory cortical outputs during activation of arm muscles. We propose that inhibition may be conveyed mainly through interhemispheric mechanisms and facilitation by subcortical mechanisms or ipsilateral pathways.

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

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

NEW & NOTEWORTHY Cortical processing serving visual perception prioritizes information according to current task requirements. We provide evidence in favor of a dimension-based attentional mechanism addressing all neurons that process visual information in the task-relevant feature domain. Behavioral tasks required monkeys to attend either color or motion, causing modulations of response strength, variability, latency, and baseline activity of motion-selective monkey area MT neurons irrespective of the attended motion direction but specific to the attended feature dimension.

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Comparison of the VTA and LC response to methylphenidate: a concomitant behavioral and neuronal study of adolescent male rats

Methylphenidate (MPD), also known as Ritalin, is a psychostimulant used to treat attention deficit hyperactivity disorder. However, it is increasingly being misused by normal adolescents for recreation and academic advantage. Therefore, it is important to elucidate the behavioral and neurophysiological effects of MPD in normal subjects. MPD inhibits the reuptake of catecholamines, mainly found in the ventral tegmental area (VTA) and locus coeruleus (LC). The VTA and LC normally mediate attention, motivation, and drug reward behaviors. Selective neuronal connections between the VTA and LC have been identified implicating regular interaction between the structures. The objective of this study was to compare the neuronal responses of the VTA and LC to MPD in normal adolescent rats. Animals were implanted with permanent electrodes in the VTA and LC, and neuronal units were recorded following acute and repetitive (chronic) saline or 0.6, 2.5, or 10.0 mg/kg MPD exposure. Animals displayed either behavioral sensitization or tolerance to all three doses of MPD. Acute MPD exposure elicited excitation in the majority of all VTA and LC units. Chronic MPD exposure elicited a further increase in VTA and LC neuronal activity in animals exhibiting behavioral sensitization and an attenuation in VTA and LC neuronal activity in animals exhibiting behavioral tolerance, demonstrating neurophysiological sensitization and tolerance, respectively. The similar pattern in VTA and LC unit activity suggests that the two structures are linked in their response to MPD. These results may help determine the exact mechanism of action of MPD, resulting in optimized treatment of patients.

NEW & NOTEWORTHY The same dose of 0.6, 2.5, and 10 mg/kg methylphenidate (MPD) elicits either behavioral sensitization or tolerance in adolescent rats. There is a direct correlation between the ventral tegmental area (VTA) and locus coeruleus (LC) neuronal response to chronic MPD exposure. Both the VTA and LC are involved in the behavioral and neurophysiological effects of chronic MPD.

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Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion

Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments.

NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural basis of motion perception in the marmoset, a small primate species that is becoming increasingly popular as an experimental model.

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Dynamic mechanisms of visually guided 3D motion tracking

The continuous perception of motion-through-depth is critical for both navigation and interacting with objects in a dynamic three-dimensional (3D) world. Here we used 3D tracking to simultaneously assess the perception of motion in all directions, facilitating comparisons of responses to motion-through-depth to frontoparallel motion. Observers manually tracked a stereoscopic target as it moved in a 3D Brownian random walk. We found that continuous tracking of motion-through-depth was selectively impaired, showing different spatiotemporal properties compared with frontoparallel motion tracking. Two separate factors were found to contribute to this selective impairment. The first is the geometric constraint that motion-through-depth yields much smaller retinal projections than frontoparallel motion, given the same object speed in the 3D environment. The second factor is the sluggish nature of disparity processing, which is present even for frontoparallel motion tracking of a disparity-defined stimulus. Thus, despite the ecological importance of reacting to approaching objects, both the geometry of 3D vision and the nature of disparity processing result in considerable impairments for tracking motion-through-depth using binocular cues.

NEW & NOTEWORTHY We characterize motion perception continuously in all directions using an ecologically relevant, manual target tracking paradigm we recently developed. This approach reveals a selective impairment to the perception of motion-through-depth. Geometric considerations demonstrate that this impairment is not consistent with previously observed spatial deficits (e.g., stereomotion suppression). However, results from an examination of disparity processing are consistent with the longer latencies observed in discrete, trial-based measurements of the perception of motion-through-depth.

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Caffeine accelerates recovery from general anesthesia via multiple pathways

Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A_2a adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP]_i)-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A_2A receptor blockade and [cAMP]_i elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP]_i and adenosine receptor blockade play a role in this response.

NEW & NOTEWORTHY Currently, there is no method to accelerate emergence from anesthesia. Patients "wake" when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that caffeine is effective even at high levels of anesthetic. We also show that caffeine operates by both elevating intracellular cAMP levels and by blocking adenosine receptors. This complicated pharmacology makes caffeine especially effective in accelerating emergence from anesthesia.

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The proinflammatory cytokine tumor necrosis factor-{alpha} excites subfornical organ neurons

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine implicated in cardiovascular and autonomic regulation via actions in the central nervous system. TNF-α^–/– mice do not develop angiotensin II (ANG II)-induced hypertension, and administration of TNF-α into the bloodstream of rats increases blood pressure and sympathetic tone. Recent studies have shown that lesion of the subfornical organ (SFO) attenuates the hypertensive and autonomic effects of TNF-α, while direct administration of TNF-α into the SFO increases blood pressure, suggesting the SFO to be a key site for the actions of TNF-α. Therefore, we used patch-clamp techniques to examine both acute and long-term effects of TNF-α on the excitability of Sprague-Dawley rat SFO neurons. It was observed that acute bath application of TNF-α depolarized SFO neurons and subsequently increased action potential firing rate. Furthermore, the magnitude of depolarization and the proportion of depolarized SFO neurons were concentration dependent. Interestingly, following 24-h incubation with TNF-α, the basal firing rate of the SFO neurons was increased and the rheobase was decreased, suggesting that TNF-α elevates SFO neuron excitability. This effect was likely mediated by the transient sodium current, as TNF-α increased the magnitude of the current and lowered its threshold of activation. In contrast, TNF-α did not appear to modulate either the delayed rectifier potassium current or the transient potassium current. These data suggest that acute and long-term TNF-α exposure elevates SFO neuron activity, providing a basis for TNF-α hypertensive and sympathetic effects.

NEW & NOTEWORTHY Considerable recent evidence has suggested important links between inflammation and the pathological mechanisms underlying hypertension. The present study describes cellular mechanisms through which acute and long-term exposure of tumor necrosis factor-α (TNF-α) influences the activity of subfornical organ neurons by modulating the voltage-gated transient Na⁺ current. This provides critical new information regarding the specific pathological mechanisms through which inflammation and TNF-α in particular may result in the development of hypertension.

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Effect of eye position during human visual-vestibular integration of heading perception

Visual and inertial stimuli provide heading discrimination cues. Integration of these multisensory stimuli has been demonstrated to depend on their relative reliability. However, the reference frame of visual stimuli is eye centered while inertia is head centered, and it remains unclear how these are reconciled with combined stimuli. Seven human subjects completed a heading discrimination task consisting of a 2-s translation with a peak velocity of 16 cm/s. Eye position was varied between 0° and ±25° left/right. Experiments were done with inertial motion, visual motion, or a combined visual-inertial motion. Visual motion coherence varied between 35% and 100%. Subjects reported whether their perceived heading was left or right of the midline in a forced-choice task. With the inertial stimulus the eye position had an effect such that the point of subjective equality (PSE) shifted 4.6 ± 2.4° in the gaze direction. With the visual stimulus the PSE shift was 10.2 ± 2.2° opposite the gaze direction, consistent with retinotopic coordinates. Thus with eccentric eye positions the perceived inertial and visual headings were offset ~15°. During the visual-inertial conditions the PSE varied consistently with the relative reliability of these stimuli such that at low visual coherence the PSE was similar to that of the inertial stimulus and at high coherence it was closer to the visual stimulus. On average, the inertial stimulus was weighted near Bayesian ideal predictions, but there was significant deviation from ideal in individual subjects. These findings support visual and inertial cue integration occurring in independent coordinate systems.

NEW & NOTEWORTHY In multiple cortical areas visual heading is represented in retinotopic coordinates while inertial heading is in body coordinates. It remains unclear whether multisensory integration occurs in a common coordinate system. The experiments address this using a multisensory integration task with eccentric gaze positions making the effect of coordinate systems clear. The results indicate that the coordinate systems remain separate to the perceptual level and that during the multisensory task the perception depends on relative stimulus reliability.

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Timing during transitions in Bengalese finch song: implications for motor sequencing

To investigate mechanisms of action sequencing, we examined the relationship between timing and sequencing of syllables in Bengalese finch song. An individual's song comprises acoustically distinct syllables organized into probabilistic sequences: a given syllable potentially can transition to several different syllables (divergence points), and several different syllables can transition to a given syllable (convergence points). In agreement with previous studies, we found that more probable transitions at divergence points occur with shorter intersyllable gaps. One intuition for this relationship is that selection between syllables reflects a competitive branching process, in which stronger links to one syllable lead to both higher probabilities and shorter latencies for transitions to that syllable vs. competing alternatives. However, we found that simulations of competitive race models result in overlapping winning-time distributions for competing outcomes and fail to replicate the strong negative correlation between probability and gap duration found in song data. Further investigation of song structure revealed strong positive correlation between gap durations for transitions that share a common convergent point. Such transitions are not related by a common competitive process, but instead reflect a common terminal syllable. In contrast to gap durations, transition probabilities were not correlated at convergence points. Together, our data suggest that syllable selection happens early during the gap, with gap timing determined chiefly by the latency to syllable initiation. This may result from a process in which probabilistic sequencing is first stabilized, followed by a shortening of the latency to syllables that are sung more often.

NEW & NOTEWORTHY Bengalese finch songs consist of probabilistic sequences of syllables. Previous studies revealed a strong negative correlation between transition probability and the duration of intersyllable gaps. We show here that the negative correlation is inconsistent with previous suggestions that timing at syllable transitions is governed by a race between competing alternatives. Rather, the data suggest that syllable selection happens early during the gap, with gap timing determined chiefly by the latency to syllable initiation.

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Contrasting speed-accuracy tradeoffs for eye and hand movements reveal the optimal nature of saccade kinematics

In contrast to hand movements, the existence of a neural representation of saccade kinematics is unclear. Saccade kinematics is typically thought to be specified by motor error/desired displacement and generated by brain stem circuits that are not penetrable to voluntary control. We studied the influence of instructed hand movement velocity on the kinematics of saccades executed without explicit instructions. When the hand movement was slow the saccade velocity decreased, independent of saccade amplitude. We leveraged this modulation of saccade velocity to study the optimality of saccades (in terms of velocity and endpoint accuracy) in relation to the well-known speed-accuracy tradeoff that governs voluntary movements (Fitts' law). In contrast to hand movements that obeyed Fitts' law, normometric saccades exhibited the greatest endpoint accuracy and lower reaction times, relative to saccades accompanying slow and fast hand movements. In the slow condition, where saccade endpoint accuracy suffered, we observed that targets were more likely to be foveated by two saccades resulting in step-saccades. Interestingly, the endpoint accuracy was higher in two-saccade trials, compared with one-saccade trials in both the slow and fast conditions. This indicates that step-saccades are a part of the kinematic plan for optimal control of endpoint accuracy. Taken together, these findings suggest normometric saccades are already optimized to maximize endpoint accuracy and the modulation of saccade velocity by hand velocity is likely to reflect the sharing of kinematic plans between the two effectors.

NEW & NOTEWORTHY The optimality of saccade kinematics has been suggested by modeling studies but experimental evidence is lacking. However, we observed that, when subjects voluntarily modulated their hand velocity, the velocity of saccades accompanying these hand movements was also modulated, suggesting a shared kinematic plan for eye and hand movements. We leveraged this modulation to show that saccades had less endpoint accuracy when their velocity decreased, illustrating that normometric saccades have optimal speed and accuracy.

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Neuromuscular electrical stimulation improves skeletal muscle regeneration through satellite cell fusion with myofibers in healthy elderly subjects

The aim of this study was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 wk of NMES were allowed to proliferate to provide myogenic populations of adult stem cells [myogenic precursor cells (MPCs)]. These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca²⁺ concentrations, and their expression of myogenic regulatory factors (PAX3, PAX7, MYF5, MYOD, and MYOG) and micro-RNAs (miR-1, miR-133a/b, and miR-206). The oxidative status of these MPCs was evaluated through superoxide anion production and superoxide dismutase and glutathione peroxidase activities. On dissected single skeletal myofibers, the nuclei were counted to determine the myonuclear density, the fiber phenotype, cross-sectional area, and tension developed. The MPCs obtained after NMES showed increased proliferation rates along with increased cytoplasmic free Ca²⁺ concentrations and gene expression of MYOD and MYOG on MPCs. Muscle-specific miR-1, miR-133a/b, and miR-206 were upregulated. This NMES significantly reduced superoxide anion production, along with a trend to reduction of superoxide dismutase activity. The NMES-dependent stimulation of muscle regeneration enhanced satellite cell fusion with mature skeletal fibers. NMES improved the regenerative capacity of skeletal muscle in elderly subjects. Accordingly, the skeletal muscle strength and mobility of NMES-stimulated elderly subjects significantly improved. NMES may thus be further considered for clinical or ageing populations.

NEW & NOTEWORTHY The neuromuscular electrical stimulation (NMES) effect on skeletal muscle regeneration was assessed in healthy elderly subjects for the first time. NMES improved the regenerative capacity of skeletal muscle through increased myogenic precursor cell proliferation and fusion with mature myofibers. The increased cytoplasmic free Ca²⁺ concentration along with MYOD, MYOG, and micro-RNA upregulation could be related to reduced O₂^·– production, which, in turn, favors myogenic regeneration. Accordingly, the skeletal muscle strength of NMES-stimulated lower limbs of healthy elderly subjects improved along with their mobility.

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Ontogeny of myosin isoform expression and prehensile function in the tail of the gray short-tailed opossum (Monodelphis domestica)

Terrestrial opossums use their semiprehensile tail for grasping nesting materials as opposed to arboreal maneuvering. We relate the development of this adaptive behavior with ontogenetic changes in myosin heavy chain (MHC) isoform expression from 21 days to adulthood. Monodelphis domestica is expected to demonstrate a progressive ability to flex the distal tail up to age 7 mo, when it should exhibit routine nest construction. We hypothesize that juvenile stages (3–7 mo) will be characterized by retention of the neonatal isoform (MHC-Neo), along with predominant expression of fast MHC-2X and -2B, which will transition into greater MHC-1β and -2A isoform content as development progresses. This hypothesis was tested using Q-PCR to quantify and compare gene expression of each isoform with its protein content determined by gel electrophoresis and densitometry. These data were correlated with nesting activity in an age-matched sample of each age group studied. Shifts in regulation of MHC gene transcripts matched well with isoform expression. Notably, mRNA for MHC-Neo and -2B decrease, resulting in little-to-no isoform translation after age 7 mo, whereas mRNA for MHC-1β and -2A increase, and this corresponds with subtle increases in content for these isoforms into late adulthood. Despite the tail remaining intrinsically fast-contracting, a critical growth period for isoform transition is observed between 7 and 13 mo, correlating primarily with use of the tail during nesting activities. Functional transitions in MHC isoforms and fiber type properties may be associated with muscle "tuning" repetitive nest remodeling tasks requiring sustained contractions of the caudal flexors.

NEW & NOTEWORTHY Little is understood about skeletal muscle development as it pertains to tail prehensility in mammals. This study uses an integrative approach of relating both MHC gene and protein expression with behavioral and morphometric changes to reveal a predominant fast MHC expression with subtle isoform transitions in caudal muscle across ontogeny. The functional shifts observed are most notably correlated with increased tail grasping for nesting activities.

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Postnatal airway growth in cystic fibrosis piglets

Mutations in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) anion channel cause CF. The leading cause of death in the CF population is lung disease. Increasing evidence suggests that in utero airway development is CFTR-dependent and that developmental abnormalities may contribute to CF lung disease. However, relatively little is known about postnatal CF airway growth, largely because such studies are limited in humans. Therefore, we examined airway growth and lung volume in a porcine model of CF. We hypothesized that CF pigs would have abnormal postnatal airway growth. To test this hypothesis, we performed CT-based airway and lung volume measurements in 3-wk-old non-CF and CF pigs. We found that 3-wk-old CF pigs had tracheas of reduced caliber and irregular shape. Their bronchial lumens were reduced in size proximally but not distally, were irregularly shaped, and had reduced distensibility. Our data suggest that lack of CFTR results in aberrant postnatal airway growth and development, which could contribute to CF lung disease pathogenesis.

NEW & NOTEWORTHY This CT scan-based study of airway morphometry in the cystic fibrosis (CF) postnatal period is unique, as analogous studies in humans are greatly limited for ethical and technical reasons. Findings such as reduced airway lumen area and irregular caliber suggest that airway growth and development are CF transmembrane conductance regulator-dependent and that airway growth defects may contribute to CF lung disease pathogenesis.

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Is the multidisciplinary support effective in preventing alcohol relapse after liver transplantation?

Introduction: Alcoholic liver disease (ALD) is one of the main indications for liver transplantation (LT) reaching about 30% in Europe and the United States. One of the most important burden in patients transplanted for ALD is alcohol relapse. In fact, according to the literature, the 20–50% of patients experience alcohol relapse in the first 5 years after LT. With this in mind, a program of program of multidisciplinary support to alcohol misuse (MSAM) was started up at the Transplant Unit of University of Rome "Sapienza" in 2004 involving a team of alcohol disorder specialists to help patients undergoing LD for ALD to cope with their alcohol use disorder.

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Cardiovascular risk assessment in alcoholic liver disease: A pilot study

Chronic alcohol abuse is a leading cause of cirrhosis, but is also associated with increased cardiovascular mortality. However, scant information is available on the determinants of atherosclerotic and cardiac disease in individuals with alcohol abuse.

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Early liver transplantation for severe acute alcoholic hepatitis: Pilot program in a single transplant centre in Italy

Background: Acute alcoholic hepatitis (AAH) is a clinical syndrome characterized by high mortality rates. There is increasing evidence that early liver transplantation (LT), performed within strict and standardized protocols, can improve survival.

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Hospital admissions for alcoholic and not alcoholic liver cirrhosis in Sicily (2007/2016)

Introduction: The leading causes of cirrhosis in Italy are alcohol intake, B and C Hepatitis viruses and metabolic syndrome. According to the Italian Institute of Statistics (ISTAT) the mortality rate for liver cirrhosis has decreased from 34.5 (1980) to 10.8/100,000 (2012). This favourable trend is due to the improvement of treatments and to a decreasing role of HBV and HCV infections. Only selected hospital based-series have showed this reduction for HBV and HCV related cirrhosis. These studies may be biased by patient selection.

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Editorial Board

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Blood alcohol concentration changes in laboratory samples during refrigerated storage

Background: Stability of blood alcohol concentration (BAC) in laboratory samples is very important when it is necessary to perform repeated analyses.

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Alcohol consumption survey in an outpatient center of gastroenterology in southern Italy

Background: Italy ranks first among the European countries in terms of wine production and tenth for annual pro-capita alcohol consumption. However, there are noteworthy regional differences and in particular between northern and southern regions. Few studies have analysed the alcohol consumption in different social contexts in order to better understand the relationship between environmental, cultural, and personal variables.

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Hospital dismissal data sheets on alcoholic liver diseases into three first aid divisions: A southern Italy survey

In 2010, the Health World Organisation identified alcohol as one of the prevalent evitable risk's factors in the development of liver and systemic diseases. Epidemiological data represent essential instruments to plan and realize prevention's strategies and to reduce detrimental alcohol consumption.

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Deep transcranial magnetic stimulation of the dorsolateral prefrontal cortex in alcohol use disorder patients: Effects on dopamine transporter availability and alcohol intake

Repetitive Transcranial Magnetic Stimulation (rTMS) of the dorsolateral prefrontal cortex may affect neuro-adaptations associated with alcohol use disorder (AUD), potentially influencing craving and alcohol intake. We investigated alcohol intake and dopamine transporter (DAT) availability by Single Photon Emission Computed Tomography (SPECT) in the striatum of AUD patients before and after deep rTMS. Fourteen patients underwent baseline clinical and SPECT assessment. Eleven out of fourteen patients were randomized into two groups for the REAL (n.

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The impact of a multidisciplinary team on alcohol recidivism and survival after liver transplantation for alcoholic disease

Introduction: Liver transplant (OLT) for patients with alcoholic abuse (AA) remains controversial, due to the risk of alcohol recidivism after transplantation, which ranges from 10 to 95%. To achieve a long-term post-OLT alcohol abstinence in AA patients, a comprehensive evaluation of the OLT candidate by a multidisciplinary team (MT), to include also a psychologist, a pharmacologist and a psychiatrist, is recommended, coupled with a strict follow-up post-OLT involving the same clinical team. Therefore, starting from 2014 a MT has been created at our Transplant Center in Modena, and a full evaluation from MT has been introduced as a requirement in the OLT screening for individuals with AA.

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Liver transplantation in patients with alcoholic liver disease: A retrospective study

Introduction: Alcoholic liver disease is the most common liver disease in the Western World. Alcohol abstinence represents the gold standard for its treatment. When liver function fails to improve in spite of alcohol abstinence, liver transplantation is the treatment of for end-stage alcoholic liver disease; however, many transplant centers are still reluctant to transplant these group of patients because of the risk of alcohol relapse, recurrence of the primary liver disease and associated post transplant complications.

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Evolution of liver transplantation for alcoholic liver disease: A single center study

Introduction: Alcohol-related liver disease (ALD) is a major indication for Liver Transplantation (LT), both for decompensated disease and for hepatocellular carcinoma (HCC). Recently, LT has been considered a therapeutic option for steroid non-responder Acute Alcoholic Hepatitis (AAH).

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Nutritional assessment in alcohol related disorders: Results from a cross sectional study on hospitalized patients

Introduction: Malnutrition is recognized as a frequent complication in alcoholic liver disease. Recently, several malnutrition screening and assessment tools have been recognized in clinical practice [1].

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Maximal exercise increases mucosal associated invariant T cell frequency and number in healthy young men

Abstract

Purpose

Mucosal associated invariant T (MAIT) cells have properties of the innate and acquired immune systems. While the response to vigorous exercise has been established for most leukocytes, MAIT cells have not been investigated. Therefore, the purpose was to determine if MAIT cell lymphocytosis occurs with acute maximal aerobic exercise and if this response is influenced by exercise duration, cardiovascular fitness, or body composition.

Methods

Twenty healthy young males with moderate fitness levels performed an extended graded exercise test until volitional fatigue. Peripheral blood mononuclear cells were isolated from venous blood obtained prior and immediately after exercise and were labeled to identify specific T cell populations using flow cytometry.

Results

The percentage of MAIT cells relative to total T cells significantly increased from 3.0 to 3.8% and absolute MAIT cell counts increased by 2.2-fold following maximal exercise. MAIT cell subpopulation proportions were unchanged with exercise. Within cytotoxic T lymphocytes (CTL), MAIT cells consisted of 8% of these cells and this remained constant after exercise. MAIT cell counts and changes with exercise were not affected by body composition, VO_2peak, or exercise duration.

Conclusions

Maximal exercise doubled MAIT cell numbers and showed preferential mobilization within total T cells but the response was not influenced by fitness levels, exercise duration, or body composition. These results suggest that acute exercise could be used to offset MAIT cell deficiencies observed with certain pathologies. MAIT cells also make up a substantial proportion of CTLs, which may have implications for cytotoxicity assays using these cells.

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A genetic variant in the placenta-derived MHC class I chain-related gene A increases the risk of preterm birth in a Chinese population

Abstract

Preterm birth (PTB) is a predominant contributor to neonatal mortality and morbidity worldwide. However, the pathophysiology of PTB is not well-understood. We tested the hypothesis that single-nucleotide polymorphisms (SNPs) in the placenta-derived MHC class I chain-related gene A (MICA) could disrupt placental development and hence result in PTB. Nineteen selected SNPs in MICA were genotyped in a case–control study of 127 premature infants and 634 term controls in a Chinese Han population. We found that significantly increased PTB risk was associated with homozygosity for the A variant of rs2256318 (adjusted odds ratio = 6.97 and 95% confidence interval = 2.34–20.74 for A/A, compared with G/G genotype, P = 0.001). In addition, the A/A genotype of rs2256318 was associated with decreased placental weight of neonates (β = −25.331; P = 0.033). Furthermore, stratified analysis demonstrated that the A/A genotype of rs2256318 was associated with increased PTB risk in female group. In addition, we observed statistical interaction between the polymorphism rs2516448 and sex (P = 0.04). No significant differences in the distribution of haplotypes between cases and controls were detected. Our results indicate that the polymorphism of rs2256318 in MICA may contribute to the etiology of PTB through interfering with placental development. These findings need to be further validated in larger and multi-ethnic populations.

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An allosteric gating model recapitulates the biophysical properties of IK,L expressed in mouse vestibular Type I hair cells

Abstract

Type I and Type II hair cells are the sensory receptors of the mammalian vestibular epithelia. Type I hair cells are characterized by their basolateral membrane being enveloped in a single large afferent nerve terminal, named calyx, and by the expression of a low-voltage-activated outward rectifying K⁺ current, I_K,L. The biophysical properties and molecular profile of I_K,L are still largely unknown. By using the patch-clamp whole-cell technique, we examined the voltage- and time-dependent properties of I_K,L in Type I hair cells of the mouse semicircular canal. We found that the biophysical properties of I_K,L were affected by an unstable K⁺ equilibrium potential (V_eqK⁺). Both the outward and inward K⁺ currents shifted V_eqK⁺ consistent with K⁺ accumulation or depletion, respectively, in the extracellular space, which we attributed to a residual calyx attached to the basolateral membrane of the hair cells. We therefore optimized the hair cell dissociation protocol in order to isolate mature Type I hair cells without their calyx. In these cells, the uncontaminated I_K,L showed a half-activation at –79.6 mV and a steep voltage dependence (2.8 mV). I_K,L also showed complex activation and deactivation kinetics, which we faithfully reproduced by an allosteric channel gating scheme where the channel is able to open from all (five) closed states. The "early" open states substantially contribute to I_K,L activation at negative voltages. This study provides the first complete description of the "native" biophysical properties of I_K,L in adult mouse vestibular Type I hair cells.

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