ABSTRACTPurposeProtracted quadriceps muscle atrophy is observed after anterior cruciate ligament reconstruction (ACL-R). The aim of this study was to assess if quadriceps strength training with eccentric overload (CON/ECC+) is more efficient to induce muscle regeneration after ACL-R than conventional concentric/eccentric (CON/ECC) strength training.MethodsBiopsies from the vastus lateralis muscle were obtained from 37 recreational athletes after 12 weeks of regular rehabilitation following ACL-R and again after 12 weeks with twice a week either conventional CON/ECC (n = 16) or CON/ECC+ (n = 21) one-legged supervised leg-press training. Immunohistochemical analyses were used to determine satellite cell number (SC, Pax7+), activated SCs (Pax7+/MyoD+), fibers expressing myosin heavy chain (MHC) I, II and neonatal, fiber cross sectional area (FCSA). Magnetic resonance imaging was performed to measure quadriceps cross sectional area (MCSA) and isokinetic testing for the measurement of quadriceps strength.ResultsCON/ECC+ induced a significantly (p = 0.002) greater increase in MCSA than CON/ECC. There also was a significant increase in the FCSAs of all fiber types and in quadriceps strength, however, without significant difference between training groups. Only CON/ECC+ training lead to a significant (p
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Τετάρτη 31 Ιανουαρίου 2018
Effects of Acute Salbutamol Intake on Peripheral and Central Fatigue in Trained Men
ABSTRACTPurposeErgogenic effect in physically active subjects has been reported following acute salbutamol (SAL) intake. β2-agonists have potential stimulant effects within the central nervous system that could be involved in this ergogenic effect. We hypothesized that acute SAL intake would induce changes in cerebral responses during exercise, with significant improvement in cerebral oxygenation and voluntary activation (VA) contributing to an increase in muscle performance.MethodsFourteen trained male subjects (25 ± 5 years) performed repeated isometric knee extensions until task failure (TF) following 4 mg (oral) SAL, 800 μg (inhaled) SAL, or placebo intake. VA, corticospinal excitability and inhibition assessed by transcranial magnetic stimulation (TMS) and changes in hemoglobin concentrations assessed by near infrared spectroscopy were measured before and during the fatiguing task.ResultsSAL had no significant effect both at rest and during exercise on prefrontal cortex oxygenation (e.g. changes in oxyhemoglobin concentration at TF: 4 mg SAL 11.4 ± 11.1 versus 800 μg SAL 10.4 ± 10.6 versus placebo 10.8 ± 8.1 μmol; P = 0.314) and neuromuscular function (e.g. VATMS at TF: 90.2 ± 6.6 versus 92.6 ± 5.0 versus 90.1 ± 7.0%; P = 0.760). SAL had no effect on the number of contractions until TF (95 ± 51 versus 100 ± 52 versus 93 ± 47; P = 0.629).ConclusionThese results indicate that acute SAL intake had no effect on central and peripheral mechanisms of neuromuscular fatigue and did not improve quadriceps endurance. Purpose Ergogenic effect in physically active subjects has been reported following acute salbutamol (SAL) intake. β2-agonists have potential stimulant effects within the central nervous system that could be involved in this ergogenic effect. We hypothesized that acute SAL intake would induce changes in cerebral responses during exercise, with significant improvement in cerebral oxygenation and voluntary activation (VA) contributing to an increase in muscle performance. Methods Fourteen trained male subjects (25 ± 5 years) performed repeated isometric knee extensions until task failure (TF) following 4 mg (oral) SAL, 800 μg (inhaled) SAL, or placebo intake. VA, corticospinal excitability and inhibition assessed by transcranial magnetic stimulation (TMS) and changes in hemoglobin concentrations assessed by near infrared spectroscopy were measured before and during the fatiguing task. Results SAL had no significant effect both at rest and during exercise on prefrontal cortex oxygenation (e.g. changes in oxyhemoglobin concentration at TF: 4 mg SAL 11.4 ± 11.1 versus 800 μg SAL 10.4 ± 10.6 versus placebo 10.8 ± 8.1 μmol; P = 0.314) and neuromuscular function (e.g. VATMS at TF: 90.2 ± 6.6 versus 92.6 ± 5.0 versus 90.1 ± 7.0%; P = 0.760). SAL had no effect on the number of contractions until TF (95 ± 51 versus 100 ± 52 versus 93 ± 47; P = 0.629). Conclusion These results indicate that acute SAL intake had no effect on central and peripheral mechanisms of neuromuscular fatigue and did not improve quadriceps endurance. Accepted for Publication: 19 January 2018 Corresponding author: Dr. Samuel Verges, Laboratoire HP2 (U1042 INSERM), Univ. Grenoble Alpes, UM Sports Pathologies, Hôpital Sud, Avenue Kimberley, 38 434 Echirolles - France. E-mail: sverges@chu-grenoble.fr This work has been funded by the French Anti-Doping Agency. The authors declare that they have no conflict of interest. The authors declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the American College of Sports Medicine. © 2018 American College of Sports Medicine
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Ablation of the carotid bodies in disease: meeting its adverse effects
Abstract
Its now 26 years since the publication of a seminal study that showed that carotid body (CB) chemoreceptors are involved in the progression of chronic intermittent hypoxia-induced hypertension.
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Phrenic motor neuron adenosine 2A receptors elicit phrenic motor facilitation
Abstract
Cervical spinal adenosine 2A (A2A) receptor activation elicits a prolonged increase in phrenic nerve activity, an effect known as phrenic motor facilitation (pMF). The specific cervical spinal cells expressing the relevant A2A receptors for pMF are unknown. This is an important question since the physiological outcome of A2A receptor activation is highly cell-type specific. Thus, we tested the hypothesis that the relevant A2A receptors for pMF are expressed in phrenic motor neurons per se versus non-phrenic neurons of the cervical spinal cord. A2A receptor immunostaining significantly colocalizes with NeuN-positive neurons (89 ± 2%). Intrapleural siRNA injections were used to selectively knock down A2A receptors in cholera toxin B-subunit-labelled phrenic motor neurons. A2A receptor knock down was verified by a ∼45% decrease in A2A receptor immunoreactivity within phrenic motor neurons versus non-targeting siRNAs (siNT; P < 0.05). There was no evidence for knock-down in cervical non-phrenic motor neurons. In anaesthetized, paralyzed and ventilated rats, pMF induced by cervical (C3-4) intrathecal injections of the A2A receptor agonist CGS21680 was greatly attenuated in siA2A (21%) versus siNT treated rats (147%; P < 0.01). There were no significant effects of siA2A on phrenic burst frequency. Collectively, our results support the hypothesis that phrenic motor neurons express the A2A receptors relevant to A2A receptor-induced pMF.
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Immediate and delayed loading of fixed dental prostheses supported by single or two splinted implants. A histomorphometric study in dogs
Abstract
Objective
To evaluate presumptive differences in osseointegration at implants supporting crowns that are physiologically loaded either immediately or 3 months after installation.
Material and methods
All premolars and first molars were extracted bilaterally in six dogs. After 3 months of healing, three implants were installed in the premolar region and two in the molar region in one side of the mandible. Likewise, after another 3 months, five implants were installed in the contralateral side, and impressions were taken bilaterally. Within 48 hours, two single crowns were screwed bilaterally onto two implants in the premolar region, and two splinted crowns reproducing the shape of the first molar were screwed bilaterally onto the implants in the molar region. The mesial implants were used as no-loaded controls. Sacrifices were performed after 3 months and histological analyses were performed.
Results
At the premolar sites, mineralized bone-to-implant contact (MBIC%) was 78.0±4.0% and 70.9±7.9% at the delayed and immediately loaded sites, respectively. This difference was statistically significant. At the control implants, MBIC% was 61.4±14.7% and 63.1±13.1% at the delayed and the immediately loaded sites, respectively. At the molar sites, MBIC% was 79.2 ±10.9% and 61.1±10.3% at the delayed and immediately loaded sites, respectively.
Conclusions
Applying a delayed loading to fixed dental prostheses supported by single- or two-splinted implants yielded higher proportions of bone-to-implant contact (osseointegration) compared to immediately loaded implants. Moreover, both types of loading protocols yielded a higher rate of osseointegration compared to unloaded implant sites after 3 months following implant installation.
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Breastfeeding, Parenting, and Infant Attachment Behaviors
Abstract
Objectives Infants and toddlers need secure attachments in order to develop the social competence required to successfully navigate later peer and adult relationships. Breastfeeding is a parenting factor that has been associated with child emotional development—specifically the attachment between children and their mothers. Yet, this link may simply be the result of other parenting behaviors that are associated with breastfeeding. Thus, our objective is to examine whether the link between infant attachment behaviors and breastfeeding endures when accounting for a broad array of in-depth measures of parenting. Methods We use the Early Childhood Longitudinal Study of children from 9 months to 2 years of age collected by the National Center for Education Statistics. Using Ordinary Least Squares regression, data analyses examine the association between the Toddler Attachment Sort-45 (TAS-45) measures of toddler-parent attachment (infant attachment security and temperamental dependency) and breastfeeding practices. We also examine individual items of the TAS-45 to isolate specific attachment behaviors that have the strongest associations with breastfeeding. Results We find an enduring link between children who are predominantly breastfed for six or more months and infant attachment security. However, we find no evidence that breastfeeding is linked to a child's temperamental dependency. Of the nine items used to examine infant attachment behaviors, we find that breastfed children are rated as having slightly higher scores on two measures ("warm and cuddly," "cooperative") and lower scores on one measure ("demanding/angry"). Conclusions for Practice Breastfeeding has an important link to the child's use of their caregiver as a secure base for exploration and a place of comfort when distressed (infant attachment security). Yet, breastfeeding does not appear to reduce a child's temperamental dependency or level of clinginess as measured by how demanding, fussy or distressed the child becomes when separated.
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Academy News – January PM&R
As the primary medical society for the specialty of PM&R, your Academy is focused on moving the specialty and you forward. Academy membership supports initiatives to assist our members with:
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The Family Caregiving Dilemma
We often assume that, on discharge from inpatient rehabilitation, families will provide caregiving for their loved ones. The discharge process involves assessing the intensity and skill level of assistance needed by the patient, and decisions about placement recommendations often hinge on the intensity and availability of caregiving resources. This responsibility often falls on family members, and there are ethical issues involving allocation of resources, family duties, and potential harms, among others.
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Re: Is the Routine Use of a Functional Electrical Stimulation Cycle for Lower Limb Movement Standard of Care for Acute Spinal Cord Injury Rehabilitation?
I would like to thank Drs. Stampas and York for their very interesting Point/Counterpoint debate on the use of functional electrical stimulation (FES) cycles as part of the standard of care for patients with spinal cord injury (SCI) [1]. Although some of the authors' points may apply only to their hypothetical patient, other comments appear intended to be generalizable. One example of the latter is Dr. York's statement that "Although there is literature describing the use of FES cycling in chronic SCI to improve the bulk of stimulated muscles, leg bone density, cardiovascular health, and metabolic parameters, such as body fat reduction and glucose tolerance improvement, these effects last only as long as the FES cycling is continued." The same can be said of exercise and physical activity in able-bodied individuals.
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PM&R Manuscript Reviewers
We extend our sincere gratitude to the following individuals who reviewed manuscripts for PM&R between November 2016 and October 2017. Peer-reviewers are the life-blood of scientific journals and their sacrifice of time and effort has greatly and specifically contributed to PM&R's success.
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Emerging Technological Advances in Musculoskeletal Ultrasound
Musculoskeletal (MSK) ultrasound (US) use has increased greatly in the past few decades [1,2]. There was a 71.7% increase in outpatient diagnostic MSK US studies from 2000 to 2009, with most of the increase due to use by nonradiologist physicians and podiatrists [3]. In the field of PM&R, residents, fellows, and practitioners are increasingly seeking US education [4].
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Maintaining Opioid Prescription for Chronic Back Pain: Pro Versus Con
A 28-year-old single man presents to your clinic for a new patient evaluation. He has had low back pain for 5 years after a motor vehicle collision. The diagnosis was diskogenic low back pain that was identified by a combination of magnetic resonance imaging and provocation diskography. A microdiskectomy procedure performed 1 year after the collision was not effective in reducing his pain. He eventually was referred to a pain management provider, who supported the ongoing use of hydrocodone/acetaminophen 10 mg/325 mg, 4 per day.
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Randomized Trial on the Effects of Attentional Focus on Motor Training of the Upper Extremity Using Robotics with Individuals after Chronic Stroke
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Grace Kim, Jim Hinojosa, Ashwini Rao, Mitch Batavia, Michael O'Dell
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Diagnostic Accuracy of the Veteran Affairs’ Traumatic Brain Injury Screen
Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Theresa Louise-Bender Pape, Bridget Smith, Judith Babcock-Parziale, Charlesnika T. Evans, Amy A. Herrold, Kelly Phipps Maieritsch, Walter M. High
ObjectiveTo comprehensively estimate the diagnostic accuracy and reliability of the Department of Veterans Affairs (VA) TBI Clinical Reminder Screen (TCRS).DesignCross-sectional, prospective, observational study using the Standards for Reporting of Diagnostic Accuracy (STARD) criteria.SettingThree VA Polytrauma Network Sites.Participants433 Operation Iraqi Freedom, Operation Enduring Freedom (OEF/OIF) Veterans.Main Outcome MeasuresTCRS, Comprehensive TBI Evaluation (CTBIE), Structured TBI Diagnostic Interview (STDI), Symptom Attribution and Classification Algorithm (SACA), Clinician-Administered PTSD Scale (CAPS).Results45% of Veterans screened positive on the TCRS for TBI. For detecting occurrence of historical TBI, the TCRS had 0.56-0.74 sensitivity (Se), 0.63-0.93 specificity (Sp), 25-45% Positive Predictive Value (PPV), 91-94% Negative Predictive Value (NPV), and 4-13 diagnostic odds ratio (DOR). For accuracy of attributing active symptoms to the TBI, the TCRS had 0.64-0.87 Se, 0.59-0.89 Sp, 26-32% PPV, 92-95% NPV, and 6-9 DOR. The Se was higher for Veterans with PTSD (0.80-0.86) relative to Veterans without PTSD (0.56-0.82). The Sp, however, was higher among Veterans without PTSD (0.75-0.90) relative to Veterans with PTSD (0.36-0.73). All indices of diagnostic accuracy changed when participants with questionably valid (QV) test profiles were eliminated from analyses.ConclusionsThe utility of the TCRS to screen for mTBI depends on the stringency of the diagnostic reference standard to which it is being compared, the presence/absence of PTSD and QV test profiles. Further development, validation, and use of reproducible diagnostic algorithms for symptom attribution following possible mTBI would improve diagnostic accuracy.
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What are the determinants of dental care expenditures in institutions for adults with disabilities? Findings from a National Survey
Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Diane Naouri, Clémence Bussiere, Nathalie Pelletier-Fleury
ObjectiveTo analyze the determinants of dental care expenditures among adults with disabilities living in institutions.DesignThe French National Health and Disability Survey - Institution Section (cross sectional survey, 2009), and The French National Health Insurance database (SNIIRAM).SettingInstitutional setting.ParticipantsPeople living in institutions for adults with cognitive, sensory, and mobility disabilities for whom the dental care expenditures from the SNIIRAM were available (456 institutions and 2,222 individuals).InterventionNot applicable.Main Outcome MeasuresWe used a Heckman selection model to correct for potential sample selection bias due to the high percentage of non-dental-care users. The selection equation modeled whether the individual had consulted a dentist at least once whereas the outcome equation explained the dental care expenditures. Disability severity was assessed by scoring mobility and cognitive functional limitations. Regressions also included sociodemographics and others health-related variables.ResultsIndividuals with the highest cognitive limitation scores, without family visits, without supplementary health insurance and with a poor oral health status were less likely to consult a dentist. After controlling for potential selection bias, the only variable that remained statistically significant in the outcome equation was the oral health status: when individuals with a poor health status had consulted at least once, they had a greater level of dental care expenditure.ConclusionsFunctional limitations were barriers to accessing dental care even in institutions for adult with disabilities. These barriers should be overcome as they may worsen their oral health status and well-being. Given the lack of literature on this specific topic, our results are very important from a policy perspective. Health authorities should be alerted by these findings.
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Lower quadriceps rate of force development is associated with worsening physical function in adults with or at risk for knee osteoarthritis: 36-month follow-up data from the Osteoarthritis Initiative
Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Bo Hu, Søren Thorgaard Skou, Barton L. Wise, Glenn N. Williams, Michael C. Nevitt, Neil A. Segal
ObjectiveThe purpose of this study was to determine the association between quadriceps rate of force development (RFD) and decline in self-reported physical function and objective measures of physical performance.DesignLongitudinal cohort studySettingCommunity-based sample from 4 urban areasParticipantsOsteoarthritis Initiative participants with or at risk for knee OA, who had no history of knee/hip replacement, knee injury, or rheumatoid arthritis (N=2630).InterventionsNot applicable.Main Outcome Measure(s)Quadriceps RFD (N/sec) was measured during isometric strength testing using the Good Strength chair. Worsening physical function was defined as the Minimal Clinically Important Difference for worsening self-reported WOMAC physical function (WOMAC-PF) score, 20-meter walk time, and repeated chair stand time over 36 months.ResultsCompared to the slowest tertile of RFD, the fastest tertile had lower risk for worsening of WOMAC-PF at 36-month follow-up, with an odds ratio (OR, 95%CI) of 0.68 (0.51, 0.92) after adjustment for age, sex, BMI, depression, history of chronic diseases, and knee pain. In women, in comparison with the slowest tertile of RFD, the fastest tertile had a lower risk for worsening of WOMAC-PF at 36-month follow-up, with an adjusted OR of 0.57 (0.38, 0.86). This decreased risk did not reach statistical significance in men (OR 0.81 (0.52, 1.27)). No statistically significant associations were detected between baseline RFD and walk or chair stand times.ConclusionsOur results indicate that higher quadriceps rate of force development is associated with decreased risk for worsening self-reported physical function but not with decreased risk for worsening of physical performance.
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Turning Data Into Information Opportunities To Advance Rehabilitation Quality, Research And Policy
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Janet Prvu Bettger, Vu Q.C. Nguyen, J. George Thomas, Tami Guerrier, Qing Yang, Mark A. Hirsch, Terrence Pugh, Gabrielle Harris, Mary Ann Eller, Carol Pereira, Deanna Hamm, Eric A. Rinehardt, Matthew Shall, Janet P. Niemeier
Attention to healthcare quality and safety has increased dramatically. The focus internally within an organization is not without influence from external policy and research findings. Compared with other specialties, efforts to align and advance rehabilitation research, practice and policy using electronic health record data are in the early stages. In this special communication we define quality, apply the dimensions of quality to rehabilitation, and illustrate the feasibility and utility of electronic health record data for research on rehabilitation care quality and outcomes. Using data generated at the point of care provides the greatest opportunity for improving the quality of health care, producing generalizable evidence to inform policy and practice, and ultimately benefiting the health of the populations we serve.
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Effectiveness of Neuromuscular Electrical Stimulation on Lower Limb Hemiplegic Patients following Chronic Stroke: A Systematic Review
Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Zhongqiu Hong, Minghong Sui, Zhiqiang Zhuang, Huihua Liu, Xiuyuan Zheng, Chuanping Cai, Dongmei Jin
ObjectiveTo investigate the effectiveness of neuromuscular electrical stimulation (NMES) with or without other interventions in improving lower limb activity after chronic stroke.Data SourceElectronic databases including PubMed, EMBase, Cochrane Library, PEDro (Physiotherapy Evidence Database) and PsycINFO were searched from the inception to January, 2017.Study SelectionWe selected the randomized controlled trials (RCTs) involving chronic stroke survivors with lower limb dysfunction and comparing NMES or combined with other interventions with control of no electrical-stimulated treatment.Data ExtractionThe primary outcome was defined as lower limb motor function, and the secondary outcomes included gait speed, Berg Balance scale, Timed Up and Go, Six-Minute Walk Test, Modified Ashworth Scale and Range of Motion .Data SynthesisTwenty-one RCTs involving 1,481 participants were identified from 5,759 retrieved articles. Pooled analysis showed that NMES had a moderate but statistically significant benefits on lower limb motor function (SMD 0.42, 95% CI 0.26 to 0.58), especially when NMES combined with other interventions or treatment time within either 6 or 12 weeks. NMES also had significant benefits on gait speed, balance, spasticity and range of motion but had no significant difference in walking endurance after NMES.ConclusionNMES combined with or without other interventions has beneficial effects in lower limb motor function in chronic stroke survivors. These data suggest that NMES should be a promising therapy to apply in chronic stroke rehabilitation to improve the capability of lower extremity in performing activities.
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Pre-operative Risk Factors for Postoperative Falls in Persons with Hip or Knee Arthroplasty: A Longitudinal Study of Data from the Osteoarthritis Initiative
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Daniel L. Riddle, Gregory J. Golladay
ObjectiveThe primary purpose was to identify preoperative risk factors associated with post-hospitalization falls over an approximate 2-year postoperative period in patients undergoing hip and knee arthroplasty.DesignThe study utilized a longitudinal cohort design.SettingParticipants were recruited from communities surrounding four urban university-based medical centers.ParticipantsAll participants underwent hip or knee arthroplasty over a 9-year study period and were followed yearly in the Osteoarthritis Initiative study.Main Outcome Measure.The primary outcome measure was a self-reported history of falls over the two-year postoperative period. A fall was recorded when the participant reported landing on the floor or ground. Preoperative predictors of falls derived from prior evidence included preoperative fall history, depressive symptom severity, narcotic use, age, activity level and comorbidity. Multinomial regression analysis was applied to determine factors that predicted either a single fall or multiple falls during a two-year postoperative period.ResultsPreoperative predictors of multiple postoperative falls were a preoperative history of falling, depressive symptoms and hip versus knee arthroplasty. Patients with hip arthroplasty were more than twice as likely (Odds Ratio = 2.26, 95% CI = 1.21, 4.20) as patients with knee arthroplasty to have multiple self-reported falls in the first two postoperative years. No predictors were found for persons who reported falling only once postoperatively. Findings were generally supported in a sensitivity analysis.ConclusionsClinicians involved with the pre-and postoperative care of persons undergoing hip or knee arthroplasty can use these findings to inform fall risk screening and intervention delivery to reduce fall risk in patients who are at risk for multiple falls following hip or knee arthroplasty.
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Effects of community-based exercise in adults with severe burns: a randomized controlled trial
Publication date: Available online 31 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Charles D. Voigt, Guillermo Foncerrada, Raquel Peña, Ashley N. Guillory, Clark R. Andersen, Craig G. Crandall, Steven E. Wolf, David N. Herndon, Oscar E. Suman
ObjectiveTo investigate the efficacy of community-based exercise programs (COMBEX) in the rehabilitation of adult burn patients as compared to standard of care (SOC).DesignRandomized controlled trial, with 2:1 randomization.SettingAssessments were performed in a hospital setting. The intervention was performed in a community setting.ParticipantsAdult patients with ≥ 30% total body surface area burns were randomized to participate in COMBEX (N = 31) or standard of care (SOC) (N = 14). Patient sampling was consecutive and referred.InterventionsThe COMBEX program consisted of 12 weeks of exercise with a community-based trainer after hospital discharge. The SOC group did not receive exercise training.Main Outcome MeasuresChange in lean body mass index, peak torque, and VO2 max from discharge to 12 weeks post discharge, presented as mean ± SE.ResultsThe COMBEX group showed a significant increase in VO2 max compared to SOC (COMBEX: Δ = 7.723 ± 1.522 mL/kg/min, p = 0.0006; SOC: Δ = 2.200 ± 1.150 mL/kg/min, p = 0.0765; COMBEX vs SOC, p = 0.0236). The COMBEX group exhibited a significant within group increase in lean body mass index (Δ = 1.107 ± 0.431 kg/m2, p = 0.0003; SOC: Δ = 1.323 ± 0.873 kg/m2, p = 0.2808). Both groups showed significant within group increases in peak torque (COMBEX: Δ = 35.645 ± 7.566 N m, p = 0.0003; SOC: Δ = 34.717 ± 11.029 N m, p = 0.0082). No significant differences were noted between the 2 groups for LBMI or peak torque.ConclusionsPatients who participate in a community-based exercise program show significant improvements in cardiopulmonary fitness compared to standard of care, supporting the use of COMBEX as an alternative therapy to SOC in adults with severe burns.
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Probiotics for Preterm Infants: a strain specific systematic review and network meta-analysis
ABSTRACTObjectives:Several randomised controlled trials (RCTs) on the use of probiotics to reduce morbidity and mortality in preterm infants have provided inconsistent results. Whilst meta-analyses that group all of the used strains together, suggest efficacy, it is not possible to determine the most effective strain which is more relevant to the clinician. We therefore used a network meta-analysis (NMA) approach in order to identify strains with greatest efficacy.Methods:A PubMed search identified placebo-controlled or head-to-head RCTs investigating probiotics in preterm infants. From trials that recorded mortality, necrotising enterocolitis (NEC), late-onset sepsis (LOS), or time until full enteral feeding (TUFEF) as outcomes, data were extracted and Bayesian hierarchical random effects models were run to construct a NMA.Results:Fifty-one RCTs involving 11,231 preterm infants were included. Most strains or combinations of strains were only studied in one or a few RCTs. Only 3 out of 25 studied probiotic treatment combinations showed significant reduction in mortality rates. Seven treatments reduced NEC incidence, 2 reduced LOS, and 3 reduced TUFEF. There was no clear overlap of strains which were effective on multiple outcome domains.Conclusions:This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations. This may be due to an inadequate number, or size, of RCTs, or due to a true lack of effect for certain species. Further large and adequately powered RCTs using strains with the greatest apparent efficacy will be needed in order to more precisely define optimal treatment strategies. Objectives: Several randomised controlled trials (RCTs) on the use of probiotics to reduce morbidity and mortality in preterm infants have provided inconsistent results. Whilst meta-analyses that group all of the used strains together, suggest efficacy, it is not possible to determine the most effective strain which is more relevant to the clinician. We therefore used a network meta-analysis (NMA) approach in order to identify strains with greatest efficacy. Methods: A PubMed search identified placebo-controlled or head-to-head RCTs investigating probiotics in preterm infants. From trials that recorded mortality, necrotising enterocolitis (NEC), late-onset sepsis (LOS), or time until full enteral feeding (TUFEF) as outcomes, data were extracted and Bayesian hierarchical random effects models were run to construct a NMA. Results: Fifty-one RCTs involving 11,231 preterm infants were included. Most strains or combinations of strains were only studied in one or a few RCTs. Only 3 out of 25 studied probiotic treatment combinations showed significant reduction in mortality rates. Seven treatments reduced NEC incidence, 2 reduced LOS, and 3 reduced TUFEF. There was no clear overlap of strains which were effective on multiple outcome domains. Conclusions: This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations. This may be due to an inadequate number, or size, of RCTs, or due to a true lack of effect for certain species. Further large and adequately powered RCTs using strains with the greatest apparent efficacy will be needed in order to more precisely define optimal treatment strategies. Address correspondence and reprint requests to Johannes B. van Goudoever, Department of Paediatrics, Emma Children's Hospital-AMC & VU University Medical Center, Amsterdam, The Netherlands, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands (e-mail: h.vangoudoever@amc.nl; h.vangoudoever@vumc.nl). Received 23 October, 2017 Accepted 14 January, 2018 Trial identification number and URL: PROSPERO CRD42017064847; http://ift.tt/2BIKEXE Hopefully, collaborators can be categorized as an author and indexed in PubMed, and appear after clicking the collaborators link in PubMed. Then, even if you search in PubMed on one of the collaborator authors, PubMed recognizes it as an author. See for example: http://ift.tt/2np5wPk Sources of support: Preparation of the manuscript was made possible by an unrestricted ESPGHAN grant Disclosure of funding: No funding from the NIH, Welcome Trust, or HHMI. Preparation of the manuscript was made possible by an unrestricted ESPGHAN grant. Conflicts of interest and sources of funding: Besides general disclosures, authors were specifically asked whether they have had any financial relationship (including grant support) in the previous two years with any company that sells probiotic strain(s) or products containing such strain(s). C.H.P. van den Akker has nothing to declare on this specific topic, but his institution has received financial support for travel reimbursements, honorarium for lectures, and consultancy fees from Nutricia, Baxter, Nestl, Nutrition Institute, and Nestl,. J.B. van Goudoever has nothing to declare on this specific topic, but his institution has received financial support for grants, travel reimbursements, honorarium for lectures, and consultancy fees from Abbott, Baxter, Danone, Hipp, Mead Johnson Nutrition, Nestl, Nutrition Institute, Nutricia, Prolacta, and United Pharmaceuticals. He is founder and director of the Dutch Donor Human Milk Bank, member of the National Human Milk council and National Health Council. H. Szajewska has participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Arla, BioGaia, Biocodex, Danone, Dicofarm, Hipp, Nestl,, Nestl, Nutrition Institute, Nutricia, Mead Johnson, Merck, and Sequoia. N.D. Embleton has nothing to declare on this specific topic, but he has received lecture honoraria, and his institution has received research support from Nutricia, Prolacta Biosciences and Nestl, Nutrition Institute. He has provided un-paid scientific advice to Neobiomics, a non-profit organisation. I. Hojsak has participated as a clinical investigator for BioGaia and Chr Hansen. D. Reid has nothing to disclose. R. Shamir has participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Abbott, Danone Institute International, Enzymotec, Nestl, Nutrition Institute, and Nutricia. Collaborators: R. Berni Canani participated as a clinical investigator, and/or speaker for Alk Bello, DMG, Dicofarm, Humana, Kraft-Heinz, Mead Johnson Nutrition, Menarini, Nestl,, Nutricia, United Pharmaceuticals, and Wyeth. M. Domell"f has nothing to declare on this specific topic, but he has participated as a speaker, advisory board member, and/or clinical researcher for Baxter, Danone/Nutricia, Nestl,, Semper/Hero, and Wyeth. A. Guarino has participated in basic research supported by Biocodex, Mead Johnson and Dicofarm and in clinical trials and/or advisory boards and/or conference grant by Menarini and Biocodex. F. Indrio has participated as a clinical investigator and /or consultant and/or speaker for Arla Food, BioGaia, Noos, Nestl,, Nestl, Nutrition Institute, and Wyeth. S. Kolacek has participated as a clinical investigator, and/or speaker for Abbott, Arla, BioGaia, Chr. Hansen, Danone, Dukat, Nestl,, Nutricia, and MSD. W.A. Mihatsch declares that he studied the effects of BB12 in preterm infants and that he or his institution received financial support for grants, travel reimbursements, honorarium for lectures, and consultancy fees from Abbott, Baxter, Danone, Hipp, Humana, Mead Johnson, Nestl,, and Prolacta. He is member of the nutrition committee of the German Paediatric Society R. Orel has participated as a clinical investigator or speaker for Medis, Nutricia, Ewopharma, BioGaia, United Pharmaceuticals, Danone, Abbvie, and MSD. Y. Vandenplas has participated as a clinical investigator, and/or advisory board member, and/or consultant, and/or speaker for Abbott Nutrition, Aspen, BioGaia, Biocodex, Danone, Hero, Kabrita, Nestl, Nutrition Institute, Nutricia, Mead Johnson Nutrition, Merck, Olygose, Orafti, Phacobel, Rontis, Sari Husada, United Pharmaceuticals, Wyeth, and Yakult. Z. Weizman has participated as a clinical investigator, and/or consultant and/or speaker for BioCodex, BioGaia, Hipp, Materna, Mead Johnson, Nestl,, and Sensus. Author contributions: C.H.P. van den Akker, J.B. van Goudoever, and H. Szajewska proposed the idea of a network meta-analysis, were involved in the study design, selected appropriate studies, collected data, performed analyses, and wrote the manuscript. N.D. Embleton, I. Hojsak, and R. Shamir were involved in the study design and interpretation of results, and critically reviewed and approved the latest version of the manuscript. D. Reid developed software for this network meta-analysis and helped improving network models. R. Berni Canani, M. Domell"f, A. Guarino, F. Indrio, S. Kolacek, W.A. Mihatsch, R. Orel, Y. Vandenplas, and Z. Weizman critically reviewed and approved the latest version of the manuscript. Collaborators: [INCREMENT][INCREMENT]Roberto Berni Canani,[INCREMENT][INCREMENT]Alfredo Guarino,[INCREMENT][INCREMENT] Department of Translational Medical Sciences and European Laboratory for the Investigation of Food Induced Diseases and CEINGE Advanced Biotechnologies and Task Force on Investigations on Microbiome, University Federico II, Naples Italy; ++Magnus Domell"f, ++ Department of Clinical Sciences, Paediatrics, Ume+ University, Ume+, Sweden; **Flavia Indrio, ** Department of Paediatric Gastroenterology division, Ospedale Pediatrico Giovanni XXIII University of Bari Italy; oSanja Kolacek, ○ Children's Hospital Zagreb, University of Zagreb School of Medicine, Croatia; §§Walter A. Mihatsch, §§ Department of Paediatrics, Ulm University and Helios Hospital Pforzheim, Germany; ooRok Orel, ○ University Medical Centre Ljubljana, University Children's Hospital Ljubljana, Department of Gastroenterology, Hepatology and Nutrition; ##Yvan Vandenplas, ## Kidz Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium; [Combining Tilde][Combining Tilde]Zvi Weizman, [Combining Tilde][Combining Tilde]Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,
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Reliability and robustness of feedback-evoked brain-heart coupling after placebo, dopamine, and noradrenaline challenge
Source:International Journal of Psychophysiology
Author(s): Maximilian Lueckel, Christian Panitz, Urs M. Nater, Erik M. Mueller
External and internal performance feedback triggers not only neural but also cardiac modulations, suggesting communication between brain and heart during feedback processing. Using Cardio-Electroencephalographic Covariance Tracing (CECT), it has accordingly been shown that feedback-evoked centromedial single-trial EEG at the P300 latency intraindividually predicts subsequent changes in heart period – the so called N300H phenomenon. While previous findings suggest that the N300H depends on serotonin, its relationship to central dopamine and noradrenaline is currently unknown. Here, we tested (1) the psychometric properties of this CECT-based component and (2) its putative catecholaminergic mechanisms. N = 54 healthy male participants received either a α2-adrenoceptor antagonist (yohimbine, 10 mg; n = 18), D2-dopamine-receptor antagonist (sulpiride, 200 mg; n = 18), or a placebo (n = 18). Afterwards, they performed a gambling task with feedback after each trial, while EEG and ECG were recorded. Feedback successfully evoked a significant N300H both across all 54 participants and within each substance group. Importantly, we show that N300H can be reliably measured in a priori defined time windows with as few as 240 feedback trials and is relatively unaffected when removing extreme single-trial values. However, we could not find any significant substance effects on N300H magnitude as well as on univariate feedback-related measures (FRN, P300, heart period). Altogether, the N300H component proves as a robust and reliable marker of cortico-cardiac coupling evoked by feedback. Furthermore, these findings suggest a subordinate role of catecholamines (i.e., noradrenaline and dopamine) and sympathetic pathways in feedback-evoked brain-heart communication as measured with N300H.
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The role of robotic gait training coupled with virtual reality in boosting the rehabilitative outcomes in patients with multiple sclerosis
Motor impairment is the most common symptom in multiple sclerosis (MS). Thus, a variety of new rehabilitative strategies, including robotic gait training, have been implemented, showing their effectiveness. The aim of our study was to investigate whether an intensive robotic gait training, preceding a traditional rehabilitative treatment, could be useful in improving and potentiating motor performance in MS patients. Forty-five patients, who fulfilled the inclusion criteria, were enrolled in this study and randomized into either the control group (CG) or the experimental group (EG). A complete clinical evaluation, including the Expanded Disability Severity Scale, the Functional Independence Measure, the Hamilton Rating Scale for Depression, the time up and go test (TUG), and the Tinetti balance scale, was performed at baseline (T0), after 6 week (T1), at the end of rehabilitative training (T2), and 1 month later (T3). A significant improvement was observed in the EG for all the outcome measures, whereas the CG showed an improvement only in TUG. In contrast, from T1 to T2, only CG significantly improved in all outcomes, whereas the EG had an improvement only regarding TUG. From T2 to T3, no significant differences in Functional Independence Measure scores emerged for both the groups, but a significant worsening in Tinetti balance scale and TUG was observed for the CG and in TUG for the EG. Our study provides evidence that robotic rehabilitationn coupled with two-dimensional virtual reality may be a valuable tool in promoting functional recovery in patients with MS. * Margherita Russo and Vincenzo Dattola contributed equally to the writing of this article. Correspondence to Rocco S. Calabrò, MD, PhD, IRCCS Centro Neurolesi 'Bonino-Pulejo', S.S. 113, Contrada Casazza, 98124 Messina, Italy Tel: +39 090 6012 8954; fax: +39 090 6012 8950; e-mail: salbro77@tiscali.it Received October 14, 2017 Accepted December 13, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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If or when? Uncertainty's role in anxious anticipation
Abstract
Uncertainty is often associated with subjective distress and a potentiated anxiety response. Occurrence uncertainty, or the inability to predict if a threat will occur, has rarely been compared experimentally with temporal uncertainty, or the inability to predict when a threat will occur. The current study aimed to (a) directly compare the anxiogenic effects of anticipating these two types of uncertain threat, as indexed by the eyeblink startle response, and (b) assess the relationship between startle response to occurrence and temporal uncertainty and individual differences in self-reported intolerance of uncertainty and anxiety. The findings indicated that anticipation during occurrence uncertainty elicited a larger startle response than anticipating a certain threat, but anticipation during temporal uncertainty was superior at potentiating startle blink overall. Additional analyses of the effects of order and habituation further highlighted temporal uncertainty's superiority in eliciting greater startle responding. This suggests that, while uncertainty is physiologically anxiety provoking, some level of certainty that the threat will occur enhances the robustness of the physiological anxiety response. However, self-reported anxiety was equivalent for temporal and occurrence uncertainty, suggesting that, while defensive responding may be more affected by temporal uncertainty, people perceive both types of uncertainty as anxiogenic. Individual differences in the intolerance of uncertainty and other anxiety measures were not related to anticipatory startle responsivity during any of the conditions.
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ERP components and behavior in the auditory equiprobable go/no-go task: Inhibition in young adults
Abstract
Previous research suggests that young adults do not need active and effortful inhibition to successfully complete the auditory equiprobable go/no-go task, a view that was incorporated into Barry and De Blasio's sequential processing schema for this task. However, recent evidence in children suggests that view could be incorrect. The present research aims to clarify the functionality of the N2 and P3 subcomponents within the proposed schema, assessing the role of inhibition in this task. To optimize the quantification of the N2 and P3 subcomponents, separate temporal PCAs were applied to the go/no-go ERP data from 40 young adults. Correlations were then used to link subcomponent amplitudes with performance outcomes, informing a functional interpretation of each subcomponent. Larger N2b and P3a amplitudes were each linked to fewer commission errors. N2c amplitude also increased with intraindividual reaction time variability, but no performance outcomes were associated with P3b. These findings link the young adult N2b and P3a with inhibition in the auditory equiprobable task, confirming the importance of control for successful nontarget processing in that paradigm. The functionality of N2c and P3b remain unclear from our results. However, these outcomes improve our understanding of cognitive processing in equiprobable tasks, and contribute to an improved conceptualization of the sequential processing schema.
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A new mutation in the C-terminal end of TTC37 leading to a mild form of syndromic diarrhea/tricho-hepato-enteric syndrome in seven patients from two families
Syndromic diarrhea/tricho-hepato-enteric syndrome (SD/THE) is a rare congenital enteropathy with seven main clinical features: intractable diarrhea of infancy, hair abnormalities, intrauterine growth restriction (IUGR), facial dysmorphism, immune dysfunction, and liver and skin abnormalities. SD/THE is caused by mutations in TTC37 or SKIV2L, two genes encoding components of the human SKI complex. To date, approximately 50 SD/THE patients have been described with a wide spectrum of mutations, and only one recurrent mutation has been identified in independent families. We present a detailed description of seven patients of Turkish origin with the same new mutation in TTC37: c.4572 G>A p.(Trp1524X). All seven patients were homozygous for this mutation and presented the typical clinical features of SD/THE, but with a milder presentation than usual. All seven patients were alive at the last follow-up. Four out of seven patients had no IUGR, and four patients never required parenteral nutrition. All patients presented a better growth rate than previously described in patients with SD/THE, with 4/7 above the 3rd percentile. The mutation is localized only forty amino acids from the end of TTC37, and as TTC37 is longer than the yeast SKI3, it is possible that a truncated protein is expressed and plays a reduced role in the SKI complex.
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Nonsense mutations in FZD2 cause autosomal-dominant omodysplasia: Robinow syndrome-like phenotypes
Omodysplasia-2 (OMOD2; OMIM%16475) is a rare autosomal dominant (AD) skeletal dysplasia characterized by shortened humeri, short first metacarpal, craniofacial dysmorphism (frontal bossing, depressed nasal bridge, bifid nasal tip, and long philtrum), and variable degrees of genitourinary anomalies. This clinical phenotype overlaps with that of AD type Robinow syndrome. Recently, a mutation in FZD2 encoding a Frizzled Class Receptor 2 has been identified in a family with AD omodysplasia (an affected girl and her affected mother). Here, we present the second report on a heterozygous novel nonsense FZD2 mutation in OMOD2 or Robinow syndrome-like phenotype. The proband was a 16-year-old boy, who has been followed from infancy to adolescence. He presented with rhizomelic short stature with elbow restriction, mild facial dysmorphism (depressed broad bridge, short nose, anteverted nostrils, long philtrum, and low-set ears), and genital hypoplasia. Radiological examination in infancy showed short, broad humeri with relatively narrow distal ends, mildly broad femora, thick proximal ulnae with hypoplastic, dislocated proximal radii, and short first metacarpals. The abnormal skeletal pattern was persistent in adolescence; however, the humeri and femora became less undermodeled, while the humeri and radii became mildly bowed. Molecular analysis identified a de novo, heterozygous, nonsense mutation (c.1640C>A, p.S547*) in FZD2. The affected codon was next to the previously reported mutation (p.Trp548*). The results indicate that OMOD2 or Robinow syndome-like phenotype can be caused by a heterozygous nonsense FZD2 mutation impairing Wnt signaling. Further molecular studies will permit better clarification of the phenotypic spectrum in patients with OMOD2.
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Extending the phenotype associated with the CSNK2A1-related Okur–Chung syndrome—A clinical study of 11 individuals
Variants in the Protein Kinase CK2 alpha subunit, encoding the CSNK2A1 gene, have previously been reported in children with an intellectual disability and dysmorphic facial features syndrome: now termed the Okur–Chung neurodevelopmental syndrome. More recently, through trio-based exome sequencing undertaken by the Deciphering Developmental Disorders Study (DDD study), a further 11 children with de novo CSNK2A1 variants have been identified. We have undertaken detailed phenotyping of these patients. Consistent with previously reported patients, patients in this series had apparent intellectual disability, swallowing difficulties, and hypotonia. While there are some shared facial characteristics, the gestalt is neither consistent nor readily recognized. Congenital heart abnormalities were identified in nearly 30% of the patients, representing a newly recognized CSNK2A1 clinical association. Based upon the clinical findings from this study and the previously reported patients, we suggest an initial approach to the management of patients with this recently described intellectual disability syndrome.
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Growth pattern of Rahman syndrome
Recently, in a cohort study with "overgrowth syndrome with intellectual disability," five subjects were reported to have de novo heterozygous truncating variants in HIST1H1E, which encodes linker histone H 1.4. However, their growth pattern appeared complex that four out of five patients had a decreasing height percentile over time, and three of these patients began with above-average heights but exhibited reductions to average heights or below when they were older. Herein, we report a female patient with intellectual disability and distinctive facial features including a wide nasal bridge and prominent cheek bones. She did not exhibit skeletal overgrowth, but she had a short stature at 21 years of age. An exome analysis identified a de novo heterozygous 1-bp duplication in HIST1H1E, that is, c.433dup p.(Ala145Glyfs*51). The physical features of the proposita were essentially the same as those observed in patients with the aforementioned HIST1H1E-related overgrowth syndrome. Our review of the growth trajectories in seven patients showed that five of seven patients did not exhibit skeletal overgrowth. This "lack of overgrowth in overgrowth syndrome" is reminiscent of a subset of patients with a short stature who have Sotos syndrome, a prototypic overgrowth syndrome. Considering this complexity in growth, this newly identified condition should be referred to as Rahman syndrome.
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Further delineation of Temtamy syndrome of corpus callosum and ocular abnormalities
Temtamy syndrome is a syndromic form of intellectual disability characterized by ocular involvement, epilepsy and dysgenesis of the corpus callosum. After we initially mapped the disease to C12orf57, we noted a high carrier frequency of an ancient startloss founder mutation [c.1A>G; p.M1?] in our population, and variable phenotypic expressivity in newly identified cases. This study aims to combine 33 previously published patients with 23 who are described here for the first time to further delineate the phenotype of this syndrome. In addition to the known p.M1? founder, we describe four novel homozygous variants, thus increasing the number of Temtamy syndrome-related C12orf57 variants to seven, all but one predicted to be loss of function. While all patients presented with intellectual disability/developmental delay, the frequency of other phenotypic features was variable: 73.2% (41/56) had epilepsy, 63% (34/54) had corpus callosal abnormalities, 14.5% (8/55) had coloboma, and 16.4% (9/55) had microphthalmia. Our analysis also revealed a high frequency of less recognized features such as congenital heart disease (51.4%), and brain white matter abnormalities (38%, 19/50). We conclude that C12orf57 variants should be considered in the etiology of developmental delay/intellectual disability, even when typical syndromic features are lacking, especially in those who trace their ancestry to Saudi Arabia where a founder C12orf57 mutation is among the most common recessive causes of intellectual disability.
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Perthes disease: A new finding in Floating-Harbor syndrome
Floating-Harbor Syndrome (FHS; OMIM #136140) is an ultra-rare autosomal dominant genetic condition characterized by expressive language delay, short stature with delayed bone mineralization, a triangular face with a prominent nose, and deep-set eyes, and hand anomalies. First reported in 1973, FHS is associated with mutations in the SRCAP gene, which encodes SNF2-related CREBBP activator protein. Mutations in the CREBBP gene cause Rubinstein-Taybi Syndrome (RSTS; OMIM #180849, #613684), another rare disease characterized by broad thumbs and halluces, facial dysmorphisms, short stature, and intellectual disability, which has a phenotypic overlap with FHS. We describe a case of FHS associated with a novel SRCAP mutation and characterized by Perthes disease, a skeletal anomaly described in approximately 3% of patients with RSTS. Thus Perthes disease can be added to the list of clinical features that overlap between FHS and RSTS.
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Disclosure of Cardiac Variants of Uncertain Significance Results in an Exome Cohort
ABSTRACT
This study examined the impact of disclosing sub-classifications of genetic variants of uncertain significance (VUS) on behavioral intentions. We studied return of VUS results to 79 individuals with a cardiomyopathy-associated VUS, sub-classified into VUS-high or VUS-low. Primary outcomes were perceived risk (absolute and comparative), perceived severity, perceived value of information, self-efficacy, decision regret, and behavioral intentions to share results and change behaviors. There was no significant difference between the two sub-classes in overall behavioral intentions (t=0.023, p=0.982) and each of the individual items on the behavioral intentions scale; absolute (t=-1.138, p=0.259) or comparative (t=-0.463, p=0.645) risk perceptions; perceived value of information (t=0.582, p=0.563) and self-efficacy (t=-0.733, p=0.466). Decision regret was significantly different (t=2.148, p=0.035), with VUS-low (mean= 17.24, SD= 16.08) reporting greater regret. Combining the sub-classes, perceived value of information was the strongest predictor of behavioral intentions (β = 0.524, p <0.001). Participants generally understood the meaning of a genetic VUS result classification and reported satisfaction with result disclosure. No differences in behavioral intentions were found, but differences in decision regret suggest participants distinguish sub-classes of VUS results. The perceived value of VUS may motivate recipients to pursue health-related behaviors.
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Participation in Home Visitation is Associated with Higher Utilization of Early Intervention
Abstract
Objectives To determine whether participation in a home visiting program increases and expedites utilization of early intervention services for suspected developmental delays. Methods Children participating in Every Child Succeeds (ECS), a large home visiting (HV) program serving greater Cincinnati, between 2006 and 2012, were propensity score matched to a sample of children identified from birth records who did not receive services from ECS. Data were linked to early intervention (EI) data acquired from the Ohio Department of Health. Descriptive statistics were employed to evaluate success of the matching. Chi square and log-rank tests evaluated whether the proportion of children accessing EI and the time to EI services differed for families participating in HV compared to eligible children not participating. Logistic regression and Cox proportional hazards regression modeled the associations. Results Among 3574 HV and 3574 comparison participants, there was no difference in the time to EI service utilization; however a higher percentage of HV participants accessed services. Overall, 6% of the HV group and 4.3% of the comparison group accessed services (p = 0.001). Modeling revealed an odd ratio = 1.43 [95% confidence interval (CI) 1.16–1.78, p value = 0.001] and hazard ratio = 1.42 [95% CI 1.15–1.75, p value = 0.001]. Differences in utilization were greatest directly after birth and between approximately 2 and 3 years. Conclusions for Practise Participation in home visiting was associated with greater utilization of EI services during two important developmental time points, demonstrating that home visiting may serve as an important resource for facilitating access to early intervention services.
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Applicability of Kd for modelling dissolved 137Cs concentrations in Fukushima river water: Case study of the upstream Ota River
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): Kazuyuki Sakuma, Hideki Tsuji, Seiji Hayashi, Hironori Funaki, Alex Malins, Kazuya Yoshimura, Hiroshi Kurikami, Akihiro Kitamura, Kazuki Iijima, Masaaki Hosomi
A study is presented on the applicability of the distribution coefficient (Kd) absorption/desorption model to simulate dissolved 137Cs concentrations in Fukushima river water. The upstream Ota River basin was simulated using GEneral-purpose Terrestrial Fluid-flow Simulator (GETFLOWS) for the period 1 January 2014 to 31 December 2015. Good agreement was obtained between the simulations and observations on water and suspended sediment fluxes, and on particulate bound 137Cs concentrations under both base and high flow conditions. By contrast the measured concentrations of dissolved 137Cs in the river water were much harder to reproduce with the simulations. By tuning the Kd values for large particles, it was possible to reproduce the mean dissolved 137Cs concentrations during base flow periods (observation: 0.32 Bq/L, simulation: 0.36 Bq/L). However neither the seasonal variability in the base flow dissolved 137Cs concentrations (0.14–0.53 Bq/L), nor the peaks in concentration that occurred during storms (0.18–0.88 Bq/L, mean: 0.55 Bq/L), could be reproduced with realistic simulation parameters. These discrepancies may be explained by microbial action and leaching from organic matter in forest litter providing an additional input of dissolved 137Cs to rivers, particularly over summer, and limitations of the Kd absorption/desorption model. It is recommended that future studies investigate these issues in order to improve simulations of dissolved 137Cs concentrations in Fukushima rivers.
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Monitoring of soil radon by SSNTD in Eastern India in search of possible earthquake precursor
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): Argha Deb, Mahasin Gazi, Jayita Ghosh, Saheli Chowdhury, Chiranjib Barman
The present paper deals with monitoring soil radon-222 concentration at two different locations, designated Site A and Site B, 200 m apart at Jadavpur University campus, Kolkata, India, with a view to find possible precursors for the earthquakes that occurred within a few hundred kilometers from the monitoring site. The solid state nuclear track detector CR-39 has been used for detection of radon gas coming out from soil. Radon-222 time series at both locations during the period August 2012–December 2013 have been analysed. Distinct anomalies in the soil radon time series have been observed for seven earthquakes of magnitude greater than 4.0 M that occurred during this time. Of these, radon anomalies for two earthquakes have been observed at both locations A and B. Absence of anomalies for some other earthquakes has been discussed, and the observations have been compared with some earthquake precursor models.
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Increasing cardiac pyruvate dehydrogenase flux during chronic hypoxia improves acute hypoxic tolerance
Abstract
The pattern of metabolic reprogramming in chronic hypoxia shares similarities with that following myocardial infarction or hypertrophy, however the response of the chronically hypoxic heart to subsequent acute injury, and the role of metabolism is not well understood. Here, we determined the myocardial tolerance of the chronically hypoxic heart to subsequent acute injury, and hypothesised that activation of a key regulator of myocardial metabolism, the pyruvate dehydrogenase complex (PDC), could improve hypoxic tolerance. Mouse hearts, perfused in Langendorff mode, were exposed to 30 min of hypoxia, and lost 80% of pre-hypoxic function (P = 0.001), with only 51% recovery of pre-hypoxic function with 30 min of re-oxygenation (P = 0.046). Activation of the PDC with infusion of 1 mm dicholorocacetate (DCA) during hypoxia and re-oxygenation did not alter function. Acute hypoxic tolerance was assessed in hearts of mice housed in hypoxia for 3 wks. Chronic hypoxia reduced cardiac tolerance to subsequent acute hypoxia, with recovery of function 22% of pre-acute hypoxic levels, vs. 39% in normoxic control hearts (P = 0.012). DCA feeding in chronic hypoxia (per os, 70 mg kg day−1) doubled cardiac acetylcarnitine content, and this fell following acute hypoxia. This acetylcarnitine use maintained cardiac ATP and glycogen content during acute hypoxia, with hypoxic tolerance normalised. In summary, chronic hypoxia renders the heart more susceptible to acute hypoxic injury, which can be improved by activation of the PDC and pooling of acetylcarnitine. This is the first study showing functional improvement of the chronically hypoxic heart with activation of the PDC, and offers therapeutic potential in cardiac disease with a hypoxic component.
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Τρίτη 30 Ιανουαρίου 2018
Ca2+ signalling in mouse urethral smooth muscle in situ: role of Ca2+ stores and Ca2+ influx mechanisms
Abstract
Urethral smooth muscle cells (USMC) generate myogenic tone and contribute to urinary continence. Currently, little is known about Ca2+ signalling in USMC in situ, and therefore little is known about the source(s) of Ca2+ required for excitation-contraction coupling. We characterized Ca2+ signalling in USMC within intact urethral muscles using a genetically encoded Ca2+ sensor, GCaMP3, expressed selectively in USMC. USMC fired spontaneous intracellular Ca2+ waves that did not propagate cell-to-cell across muscle bundles. Ca2+ waves increased dramatically in response to the α1-adrenoceptor agonist, phenylephrine (PE, 10 μm) and to ATP (10 μm). Ca2+ waves were inhibited by DEA-NONOate (10 μm). Ca2+ influx and release from SR stores contributed to Ca2+ waves, as Ca2+ free bathing solution and blocking the sarcoplasmic Ca2+-ATPase abolished activity. Intracellular Ca2+ release involved cooperation between RyRs and IP3Rs, as tetracaine and ryanodine (100 μm) and xestospongin C (1 μm) reduced Ca2+ waves. Ca2+ waves were insensitive to L-type Ca2+ channel modulators nifedipine (1 μm), nicardipine (1 μm), isradipine (1 μm) and FPL (1 μm), and were unaffected by the T-type Ca2+ channel antagonists NNC 55–0396 (1 μm) and TTA-A2 (1 μm). Ca2+ waves were reduced by the store operated Ca2+ entry (SOCE) blocker SKF 96365 (10 μm) and by an Orai antagonist, GSK-7975A (1 μm). The latter also reduced urethral contractions induced by PE, suggesting that Orai can function effectively as a receptor-operated channel. In conclusion, Ca2+ waves in mouse USMC are a source of Ca2+ for excitation-contraction coupling in urethral muscles.
This article is protected by copyright. All rights reserved
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Impact of Multiple Single-Nucleotide Polymorphisms Within mprF on Daptomycin Resistance in Staphylococcus aureus
Microbial Drug Resistance , Vol. 0, No. 0.
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Kinase-independent function of E-type cyclins in liver cancer [Genetics]
E-type cyclins (cyclins E1 and E2) are components of the core cell cycle machinery and are overexpressed in many human tumor types. E cyclins are thought to drive tumor cell proliferation by activating the cyclin-dependent kinase 2 (CDK2). The cyclin E1 gene represents the site of recurrent integration of the...
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Enhancer adoption caused by genomic insertion elicits interdigital Shh expression and syndactyly in mouse [Genetics]
Acquisition of new cis-regulatory elements (CREs) can cause alteration of developmental gene regulation and may introduce morphological novelty in evolution. Although structural variation in the genome generated by chromosomal rearrangement is one possible source of new CREs, only a few examples are known, except for cases of retrotransposition. In this...
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MAFA missense mutation causes familial insulinomatosis and diabetes mellitus [Genetics]
The β-cell–enriched MAFA transcription factor plays a central role in regulating glucose-stimulated insulin secretion while also demonstrating oncogenic transformation potential in vitro. No disease-causing MAFA variants have been previously described. We investigated a large pedigree with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset condition of recurrent hyperinsulinemic...
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Large genomic insertion at the Shh locus results in hammer toes through enhancer adoption [Genetics]
Enhancers are cis-regulatory elements which control the expression of genes in a defined spatiotemporal pattern, enabling the normal morphogenesis of organs and structures during embryogenesis. Enhancers control their target genes independently of their orientation or distance through chromosomal looping and are thought to evolve through various mutational mechanisms (1). A...
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Patient-Centered Values and Experiences with Emergency Department and Mental Health Crisis Care
Abstract
Little is known about what patients value in psychiatric crisis services or how they compare community-based services with those received in the emergency department. Three focus groups (n = 27) were held of participants who had received psychiatric crisis services in emergency departments or a community mental health center. Participants described care experiences and preferences. Focus groups were audio recorded, transcribed, and coded using a value-based lens. Themes included appreciation for feeling respected, basic comforts, and shared decision-making as foundations of quality care. Participants preferred the community mental health center. Research should address long-term outcomes to motivate change in psychiatric crisis care.
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Genomic structure of the native inhabitants of Peninsular Malaysia and North Borneo suggests complex human population history in Southeast Asia
Abstract
Southeast Asia (SEA) is enriched with a complex history of peopling. Malaysia, which is located at the crossroads of SEA, has been recognized as one of the hubs for early human migration. To unravel the genomic complexity of the native inhabitants of Malaysia, we sequenced 12 samples from 3 indigenous populations from Peninsular Malaysia and 4 native populations from North Borneo to a high coverage of 28–37×. We showed that the Negritos from Peninsular Malaysia shared a common ancestor with the East Asians, but exhibited some level of gene flow from South Asia, while the North Borneo populations exhibited closer genetic affinity towards East Asians than the Malays. The analysis of time of divergence suggested that ancestors of Negrito were the earliest settlers in the Malay Peninsula, whom first separated from the Papuans ~ 50–33 thousand years ago (kya), followed by East Asian (~ 40–15 kya), while the divergence time frame between North Borneo and East Asia populations predates the Austronesian expansion period implies a possible pre-Neolithic colonization. Substantial Neanderthal ancestry was confirmed in our genomes, as was observed in other East Asians. However, no significant difference was observed, in terms of the proportion of Denisovan gene flow into these native inhabitants from Malaysia. Judging from the similar amount of introgression in the Southeast Asians and East Asians, our findings suggest that the Denisovan gene flow may have occurred before the divergence of these populations and that the shared similarities are likely an ancestral component.
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Vitamin D and the Athlete: Current Perspectives and New Challenges
Abstract
The last decade has seen a dramatic increase in general interest in and research into vitamin D, with many athletes now taking vitamin D supplements as part of their everyday dietary regimen. The most recognized role of vitamin D is its regulation of calcium homeostasis; there is a strong relationship between vitamin D and bone health in non-athletic individuals. In contrast, data have consistently failed to demonstrate any relationship between serum 25[OH]D and bone health, which may in part be due to the osteogenic stimulus of exercise. Vitamin D may interact with extra-skeletal tissues such as muscle and the immune system to modulate recovery from damaging exercise and infection risk. Given that many athletes now engage in supplementation, often consuming extreme doses of vitamin D, it is important to assess whether excessive vitamin D can be detrimental to health. It has been argued that toxic effects only occur when serum 25[OH]D concentrations are greater than 180 nmol·l−1, but data from our laboratory have suggested high-dose supplementation could be problematic. Finally, there is a paradoxical relationship between serum 25[OH]D concentration, ethnicity, and markers of bone health: Black athletes often present with low serum 25[OH]D without physiological consequences. One explanation for this could be genetic differences in vitamin D binding protein due to ethnicity, resulting in greater concentrations of bioavailable (or free) vitamin D in some ethnic groups. In the absence of any pathology, screening may be unnecessary and could result in incorrect supplementation. Data must now be re-examined, taking into consideration bioavailable or "free" vitamin D in ethnically diverse groups to enable new thresholds and target concentrations to be established; perhaps, for now, it is time to "set vitamin D free".
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Administration of Caffeine in Alternate Forms
Abstract
There has been recent interest in the ergogenic effects of caffeine delivered in low doses (~ 200 mg or ~ 3 mg/kg body mass) and administered in forms other than capsules, coffee and sports drinks, including chewing gum, bars, gels, mouth rinses, energy drinks and aerosols. Caffeinated chewing gum is absorbed quicker through the buccal mucosa compared with capsule delivery and absorption in the gut, although total caffeine absorption over time is not different. Rapid absorption may be important in many sporting situations. Caffeinated chewing gum improved endurance cycling performance, and there is limited evidence that repeated sprint cycling and power production may also be improved. Mouth rinsing with caffeine may stimulate nerves with direct links to the brain, in addition to caffeine absorption in the mouth. However, caffeine mouth rinsing has not been shown to have significant effects on cognitive performance. Delivering caffeine with mouth rinsing improved short-duration, high-intensity, repeated sprinting in normal and depleted glycogen states, while the majority of the literature indicates no ergogenic effect on aerobic exercise performance, and resistance exercise has not been adequately studied. Studies with caffeinated energy drinks have generally not examined the individual effects of caffeine on performance, making conclusions about this form of caffeine delivery impossible. Caffeinated aerosol mouth and nasal sprays may stimulate nerves with direct brain connections and enter the blood via mucosal and pulmonary absorption, although little support exists for caffeine delivered in this manner. Overall, more research is needed examining alternate forms of caffeine delivery including direct measures of brain activation and entry of caffeine into the blood, as well as more studies examining trained athletes and female subjects.
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Assessing the Role of Muscle Protein Breakdown in Response to Nutrition and Exercise in Humans
Abstract
Muscle protein breakdown (MPB) is an important metabolic component of muscle remodeling, adaptation to training, and increasing muscle mass. Degradation of muscle proteins occurs via the integration of three main systems—autophagy and the calpain and ubiquitin-proteasome systems. These systems do not operate independently, and the regulation is complex. Complete degradation of a protein requires some combination of the systems. Determination of MPB in humans is technically challenging, leading to a relative dearth of information. Available information on the dynamic response of MPB primarily comes from stable isotopic methods with expression and activity measures providing complementary information. It seems clear that resistance exercise increases MPB, but not as much as the increase in muscle protein synthesis. Both hyperaminoacidemia and hyperinsulinemia inhibit the post-exercise response of MPB. Available data do not allow a comprehensive examination of the mechanisms behind these responses. Practical nutrition recommendations for interventions to suppress MPB following exercise are often made. However, it is likely that some degree of increased MPB following exercise is an important component for optimal remodeling. At this time, it is not possible to determine the impact of nutrition on any individual muscle protein. Thus, until we can develop and employ better methods to elucidate the role of MPB following exercise and the response to nutrition, recommendations to optimize post exercise nutrition should focus on the response of muscle protein synthesis. The aim of this review is to provide a comprehensive examination of the state of knowledge, including methodological considerations, of the response of MPB to exercise and nutrition in humans.
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Protection Before Impact: the Potential Neuroprotective Role of Nutritional Supplementation in Sports-Related Head Trauma
Abstract
Even in the presence of underreporting, sports-related concussions/mild traumatic brain injuries (mTBI) are on the rise. In the absence of proper diagnosis, an athlete may return to play prior to full recovery, increasing the risk of second-impact syndrome or protracted symptoms. Recent evidence has demonstrated that sub-concussive impacts, those sustained routinely in practice and competition, result in a quantifiable pathophysiological response and the accumulation of both concussive and sub-concussive impacts sustained over a lifetime of sports participation may lead to long-term neurological impairments and an increased risk of developing neurodegenerative diseases. The pathophysiological, neurometabolic, and neurochemical cascade that initiates subsequent to the injury is complex and involves multiple mechanisms. While pharmaceutical treatments may target one mechanism, specific nutrients and nutraceuticals have been discovered to impact several pathways, presenting a broader approach. Several studies have demonstrated the neuroprotective effect of nutritional supplementation in the treatment of mTBI. However, given that many concussions go unreported and sub-concussive impacts result in a pathophysiological response that, too, may contribute to long-term brain health, protection prior to impact is warranted. This review discusses the current literature regarding the role of nutritional supplements that, when provided before mTBI and traumatic brain injury, may provide neurological protection.
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Imbalance of synaptic actin dynamics as a key to the Fragile X syndrome?
Abstract
Our experiences and memories define who we are and evidence accumulates that memory formation is dependent on functional and structural adaptations of synaptic structures in our brain. Especially dendritic spines, the postsynaptic compartments of synapses, show a strong structure-to-function relationship and a high degree of structural plasticity. Although the molecular mechanisms are not completely understood, it is known that these modifications are highly dependent on the actin-cytoskeleton, the major cytoskeletal component of the spine. Given the crucial involvement of actin in these mechanisms, dysregulations of spine actin dynamics (reflected by alterations in dendritic spine morphology) can be found in a variety of neurological disorders ranging from schizophrenia to several forms of autism spectrum disorders like the Fragile X Syndrome (FXS). FXS is caused by a single mutation leading to an inactivation of the X-linked fragile X mental retardation 1 gene and loss of its gene product, the RNA-binding protein Fragile X Mental Retardation Protein 1 (FMRP) which normally can be found both pre- and postsynaptically. FMRP is involved in mRNA transport as well as regulation of local translation at the synapse and although hundreds of FMRP-target mRNAs could be identified only very few interactions between FMRP and actin-regulating proteins were reported and validated. In this review we want to give an overview about recent work by our lab and others providing evidence that dysregulated actin dynamics might indeed be at the very base of a deeper understanding of neurological disorders ranging from cognitive impairment to the autism spectrum.
This article is protected by copyright. All rights reserved
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Fat feeding facilitates hot bodies, but is resistance futile?
Abstract
High-fat diets (HFD) result in metabolic dysregulation and cardiometabolic abnormalities which contribute to the development of obesity and cardiovascular disease.
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Anatomic Relationship between the Hook of the Hamate and the Distal Transverse Carpal Ligament: Implications for Ultrasound Guided Carpal Tunnel Release
ABSTRACTObjectiveDuring ultrasound guided carpal tunnel release (USCTR), osseous landmarks may supplement direct visualization of the distal transverse carpal ligament (dTCL) to ensure a complete release. The purpose of this study was to determine the relationship between the apex of the hook of the hamate (aHH) and the dTCL within the transverse safe zone (TSZ) of the carpal tunnel.DesignTwenty unembalmed cadaveric specimens were dissected to determine the aHH-dTCL distance and the aHH-SPA distance (the distance between the aHH and the superficial palmar arch) at the ulnar and radial limits of the TSZ (the distance between the hook of the hamate or ulnar artery to the median nerve).ResultsThe aHH-dTCL distance averaged 11-12 mm across the TSZ (maximum 18.2 mm), whereas the aHH-SPA distance was significantly greater on the radial side of the TSZ compared to the ulnar side (22.6 ± 3.6 mm versus 14.0 ± 4.0 mm).ConclusionsThe dTCL lies approximately 11-12 mm distal to the aHH across the TSZ, with an upper limit of 18.2 mm. Along with direct sonographic visualization of the dTCL, the aHH can be used with other osseous landmarks to estimate the position of the dTCL during USCTR. Objective During ultrasound guided carpal tunnel release (USCTR), osseous landmarks may supplement direct visualization of the distal transverse carpal ligament (dTCL) to ensure a complete release. The purpose of this study was to determine the relationship between the apex of the hook of the hamate (aHH) and the dTCL within the transverse safe zone (TSZ) of the carpal tunnel. Design Twenty unembalmed cadaveric specimens were dissected to determine the aHH-dTCL distance and the aHH-SPA distance (the distance between the aHH and the superficial palmar arch) at the ulnar and radial limits of the TSZ (the distance between the hook of the hamate or ulnar artery to the median nerve). Results The aHH-dTCL distance averaged 11-12 mm across the TSZ (maximum 18.2 mm), whereas the aHH-SPA distance was significantly greater on the radial side of the TSZ compared to the ulnar side (22.6 ± 3.6 mm versus 14.0 ± 4.0 mm). Conclusions The dTCL lies approximately 11-12 mm distal to the aHH across the TSZ, with an upper limit of 18.2 mm. Along with direct sonographic visualization of the dTCL, the aHH can be used with other osseous landmarks to estimate the position of the dTCL during USCTR. Please send correspondence to: Jay Smith, M.D. Department of PM&R, W14 Mayo Building, 200 1st ST, SW, Rochester, MN 55905, Email: smith.jay@mayo.edu Acknowledgement of Funding Sources Funding provided by Mayo Clinic Institutional Funds. This project was supported by Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Neither funding source had a role in the study design, the collection, analysis and interpretation of data, the writing of the report or the decision to submit for publication. Declaration of Conflicting Interests Dr. Smith is Co-Founder and Chief Medical Officer for Sonex Health, LLC. Dr. Kakar is on the Medical Advisory Board for Sonex Health, LLC and is a consultant for Arthrex, Inc. and Skeletal Dynamics, LLC. Previous Presentation Results were presented in abbreviated form as a poster at the American Academy of Physical Medicine and Rehabilitation in October 2016. They have not been published, nor are they under consideration for publication elsewhere. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Effects of Different Exercise Modes on Arterial Stiffness and Nitric Oxide Synthesis
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Exercise Effects on Adipose Tissue Postprandial Lipolysis and Blood Flow in Children
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Comparison of Two Generations of ActiGraph Accelerometers: The CARDIA Study
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Video-Recorded Validation of Wearable Step Counters under Free-living Conditions
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Cloud computing for genomic data analysis and collaboration
Cloud computing for genomic data analysis and collaboration
Cloud computing for genomic data analysis and collaboration, Published online: 30 January 2018; doi:10.1038/nrg.2017.113
Next-generation sequencing technologies have fuelled a rapid rise in data, which require vast computational resources to store and analyse. This Review discusses the role of cloud computing in genomics research to facilitate data sharing and new analyses of archived sequencing data, as well as large-scale international collaborations.from Genetics via xlomafota13 on Inoreader http://ift.tt/2nrhmrd
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Plant genetics: Parasites plant microRNAs in the host
Plant genetics: Parasites plant microRNAs in the host
Plant genetics: Parasites plant microRNAs in the host, Published online: 30 January 2018; doi:10.1038/nrg.2018.3
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