A wealth of evidence supports the developmental period as being an important determinant for future health status, as well as life expectancy.
This article is protected by copyright. All rights reserved
Understanding soccer players' match-related fatigue and recovery profiles likely helps with developing conditioning programs that increase team performance and reduce injuries and illnesses. In order to improve match recovery (the return-to-play process and ergogenic interventions) it is also pivotal to determine if match simulation protocols and actual match-play lead to similar responses.
(1) To thoroughly describe the development of fatigue during actual soccer match play and its recovery time course in terms of physiological, neuromuscular, technical, biochemical and perceptual responses, and (2) to determine similarities of recovery responses between actual competition (11 vs. 11) and match simulations.
A first screening phase consisted of a systematic search on PubMed (MEDLINE) and SportDiscus databases until March 2016. Inclusion criteria were: longitudinal study with soccer players; match or validated protocol; duration > 45 min; and published in English.
A total of 77 eligible studies (n = 1105) were used to compute 1196 effect sizes (ES). Half-time assessments revealed small to large alterations in immunological parameters (e.g. leukocytes, ES = 1.9), a moderate decrement in insulin concentration (ES = − 0.9) and a small to moderate impairment in lower-limb muscle function (ES = − 0.5 to − 0.7) and physical performance measures (e.g. linear sprint, ES = − 0.3 to − 1.0). All the systematically analyzed fatigue-related markers were substantially altered at post-match. Hamstrings force production capacity (ES = − 0.7), physical performance (2–4%, ES = 0.3−0.5), creatine kinase (CK, ES = 0.4), well-being (ES = 0.2−0.4) and delayed onset muscle soreness (DOMS, ES = 0.6–1.3) remained substantially impaired at G + 72 h. Compared to simulation protocols, 11 vs. 11 match format (CK, ES = 1.8) induced a greater magnitude of change in muscle damage (i.e. CK, ES = 1.8 vs. 0.7), inflammatory (IL-6, ES = 2.6 vs. 1.1) and immunological markers and DOMS (ES = 1.5 vs. 0.7) than simulation protocols at post-assessments. Neuromuscular performances at post-match did not differ between protocols.
While some parameters are fully recovered (e.g. hormonal and technical), our systematic review shows that a period of 72 h post-match play is not long enough to completely restore homeostatic balance (e.g. muscle damage, physical and well-being status). The extent of the recovery period post-soccer game cannot consist of a 'one size fits all approach'. Additionally, the 'real match' (11 vs. 11 format) likely induces greater magnitudes of perceptual (DOMS) and biochemical alterations (e.g. muscle damage), while neuromuscular alterations were essentially similar. Overall, coaches must adjust the structure and content of the training sessions during the 72-h post-match intervention to effectively manage the training load within this time-frame.
Athletes may complete consecutive exercise sessions with limited recovery time between bouts (e.g. ≤ 4 h). Nutritional strategies that optimise post-exercise recovery in these situations are therefore important.
This two-part review investigated the effect of consuming carbohydrate (CHO) and protein with water (W) following exercise on subsequent athletic (endurance/anaerobic exercise) performance.
Studies were identified by searching the online databases SPORTDiscus, PubMed, Web of Science and Scopus.
Investigations that measured endurance performance (≥ 5 min duration) ≤ 4 h after a standardised exercise bout (any type) under the following control vs. intervention conditions were included: Part 1: W vs. CHO ingested with an equal volume of W (CHO + W); and, Part 2: CHO + W vs. protein (PRO) ingested with CHO and an equal volume of W (PRO + CHO + W), where CHO or energy intake was matched.
Publications were examined for bias using the Rosendal scale. Random-effects meta-analyses and meta-regression analyses were conducted to evaluate intervention efficacy.
The quality assessment yielded a Rosendal score of 63 ± 9% (mean ± standard deviation). Part 1: 45 trials (n = 486) were reviewed. Ingesting CHO + W (102 ± 50 g CHO; 0.8 ± 0.6 g CHO kg−1 h−1) improved exercise performance compared with W (1.6 ± 0.7 L); %Δ mean power output = 4.0, 95% confidence interval 3.2–4.7 (I 2 = 43.9). Improvement was attenuated when participants were 'Fed' (a meal 2–4 h prior to the initial bout) as opposed to 'Fasted' (p = 0.012). Part 2: 13 trials (n = 125) were reviewed. Ingesting PRO + CHO + W (35 ± 26 g PRO; 0.5 ± 0.4 g PRO kg−1) did not affect exercise performance compared with CHO + W (115 ± 61 g CHO; 0.6 ± 0.3 g CHO·kg body mass−1 h−1; 1.2 ± 0.6 L); %Δ mean power output = 0.5, 95% confidence interval − 0.5 to 1.6 (I 2 = 72.9).
Athletes with limited time for recovery between consecutive exercise sessions should prioritise CHO and fluid ingestion to enhance subsequent athletic performance.
CRD42016046807.
Locomotor gaits depend on the interplay between distributed spinal neural networks termed central pattern generators generating rhythmic and coordinated movements, primary afferents and descending supraspinal inputs. Recent studies demonstrated that the mouse display a rich repertoire of locomotor gaits. Changes in locomotor gaits occur in mutant mice lacking particular neurons or molecular signaling pathways implicated in the normal establishment of these neural networks Given the role of the Down Syndrome Cell Adherence Molecule (DSCAM) to the formation and maintenance of spinal interneuronal circuits and sensorimotor integration, we have investigated its functional contribution to locomotor gaits over a wide range of locomotor speeds using freely walking mice. We show here that the DSCAM2J mutation, while not precluding any gait, impairs the age- and speed-dependent modulation of locomotor gaits. It impairs the ability of mice to maintain their locomotion at high treadmill speeds. DSCAM2J mutation induces the dominance of lateral walk over trot and the emergence of aberrant gaits for mice, such as pace and diagonal walk. Locomotor gaits were also more labile in DSCAM2J mutant mice, i.e. less stable, less attractive and less predictable than their wild-type littermates. Our results suggest that the DSCAM mutation affects the behavioral repertoire of gaits in an age- and speed-dependent manner.
Individuals vary significantly with respect to rate and degree of improvement with motor practice. While the regions that underlie motor learning have been well described, neurophysiological factors underlying differences in response to motor practice are less well understood. The present study examined both resting state and event-related EEG coherence measures of connectivity as predictors of response to motor practice on a motor sequencing task using the dominant hand. Thirty-two healthy, young, right-handed participants underwent resting EEG prior to motor practice. Response to practice was evaluated both across the single session of motor practice, and 24-hours later at a retention test of short-term motor learning. Behaviorally, the group demonstrated statistically significant gains both in single-session motor improvement and across-session motor learning. A resting-state measure of whole brain coherence with primary motor cortex (M1) at baseline robustly predicted subsequent motor improvement (validated R2=0.55) and motor learning (validated R2=0.68) in separate partial least squares regression models. Specifically, greater M1 coherence with left frontal-premotor cortex (PMC) at baseline was characteristic of individuals likely to demonstrate greater gains in both motor improvement and motor learning. Analysis of event-related coherence with respect to movement found the largest changes occurring in areas implicated in planning and preparation of movement, including PMC and frontal cortices. While event-related coherence provided a stronger prediction of practice-induced motor improvement (validated R2=0.73) it did not predict the degree of motor learning (validated R2=0.16). These results indicate that connectivity in the resting-state is a better predictor of consolidated learning of motor skills.
The Locus Coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We have previously reported that LC microstimulation caused a transient desynchronization of the population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here, we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum with the strongest modulation in gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, α2-adrenoreceotor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the prefrontal cortex and is essential for mediating sensory information along ascending noxious pathway.
Many studies highlight the remarkable plasticity demonstrated by spinal circuits following an incomplete spinal cord injury (SCI). Such plasticity can contribute to improvements in volitional motor recovery, such as walking function, although similar mechanisms underlying this recovery may also contribute to the manifestation of exaggerated responses to afferent input, or spastic behaviors. Rehabilitation interventions directed towards augmenting spinal excitability have shown some initial success in improving locomotor function. However, the potential effects of these strategies on involuntary motor behaviors may be of concern. Here, we provide a brief review of the mechanisms underlying recovery of volitional function and exaggerated reflexes, and the potential overlap between these changes. We then highlight findings from studies that explore changes in spinal excitability during volitional movement in controlled conditions, as well as altered kinematic and behavioral performance during functional tasks. The initial focus will be directed towards recovery of reflex and volitional behaviors following incomplete SCI, followed by recent work elucidating neurophysiological mechanisms underlying patterns of static and dynamic muscle activation following chronic incomplete SCI during primarily single-joint movements. We will then transition to studies of locomotor function and the role of altered spinal integration following incomplete SCI, including enhanced excitability of specific spinal circuits with physical and pharmacological interventions can modulate locomotor output. The effects of previous and newly developed strategies will need to focus on changes in both volitional function and involuntary spastic reflexes for the successful translation of effective therapies to the clinical setting. -
Neurons in the rostral nucleus of the solitary tract (rNST) convey taste information to both local circuits and pathways destined for forebrain structures. This nucleus is more than a simple relay, however, since rNST neurons differ in response rates and tuning curves relative to primary afferent fibers. To systematically study the impact of convergence and inhibition on firing frequency and breadth of tuning (BOT) in rNST, we constructed a mathematical model of its two major cell types: projection neurons and inhibitory neurons. First, we fit a conductance-based neuronal model to data derived from whole-cell patch clamp recordings of inhibitory and and non-inhibitory neurons in a mouse expressing VENUS under the control of the VGAT promoter. Then we used in vivo chorda tympani (CT) taste responses as afferent input to modeled neurons and assessed how the degree and type of convergence influenced model cell output frequency and BOT for comparison to in vivo gustatory responses from the rNST. Finally, we assessed how presynaptic and postsynaptic inhibition impacted model cell output. The results of our simulations demonstrated (1) increasing numbers of convergent afferents (2-10) results in a proportional increase in best-stimulus firing frequency but only a modest increase in BOT, (2) convergence of afferent input selected from the same best-stimulus class of CT afferents produced a better fit to real data from the rNST compared to convergence of randomly selected afferent input, (3) inhibition narrowed the BOT to more realistically model the in vivo rNST data.
Publication date: Available online 31 October 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Shawn Farrokhi, Brittney Mazzone, Susan Eskridge, Kaeley Shannon, Owen T. Hill
ObjectiveTo describe the incidence of overuse musculoskeletal injuries in service members with combat-related lower limb amputation.DesignRetrospective cohort study.SettingMilitary treatment facilities.ParticipantsA total of 791 service members with deployment-related lower limb injury: 496 with a major lower limb amputation and 295 with a mild lower limb injury.InterventionsNot applicable.Main Outcome MeasuresThe outcomes of interest were clinical diagnosis codes (International Classification of Diseases, Ninth Revision [ICD-9]) associated with musculoskeletal overuse injuries of the lumbar spine, upper limb, and lower limb regions one year before and one year after injury.ResultsThe overall incidence of developing at least one musculoskeletal overuse injury within the first year after lower limb amputation was between 59-68%. Service members with unilateral lower limb amputation were almost twice as likely to develop an overuse lower or upper limb injury as compared to those with mild combat-related injury. Additionally, service members with bilateral lower limb amputation were more than twice as likely to develop a lumbar spine injury and four times more likely to develop an upper limb overuse injury within the first year after amputation as compared to those with mild combat-related injury.ConclusionsIncidence of secondary overuse musculoskeletal injury is elevated in service members with lower limb amputation and warrants focused research efforts towards developing preventive interventions.
from Rehabilitation via xlomafota13 on Inoreader http://ift.tt/2ymuBSD
via IFTTT
Previous studies reported that laparoscopic surgery (LPS) improved postoperative outcomes in patients undergoing colorectal surgery within an enhanced recovery program (ERP). However, the effect of minimally invasive surgery on each ERP item has not been clarified, yet. The aim of this study is to assess the impact of LPS on adherence to ERP items and recovery as measured by time to readiness for discharge (TRD).
Prospectively collected data entered in an electronic Italian registry specifically designed for ERP were reviewed. Patients undergoing elective colorectal surgery were divided into three groups: successful laparoscopy, conversion to open surgery, primary open surgery. Adherence to 19 ERP elements and postoperative outcomes were compared among groups. Multivariate regression analysis was used to identify whether LPS had an independent role to improve ERP adherence and postoperative outcomes.
714 patients (successful LPS 531, converted 42, open 141) underwent elective colorectal surgery within an ERP. Epidural analgesia was used in the 75.1% of open group patients versus 49.9% of LPS group patients (p = 0.012). After surgery, oral feeding recovery, i.v. fluids suspension, removal of both urinary and epidural catheters occurred earlier in the LPS group both in the overall series and in uneventful patients only. Mean TRD and length of hospital stay were significantly shorter in the LPS group (p < 0.001 for both). Overall morbidity rate was 18.7% in the LPS group versus 32.6% in the open group (p = 0.001). At multivariate analysis, LPS was significantly associated to an increased adherence to postoperative ERP items, a shorter TRD, and a reduced overall morbidity, whereas rectal surgery and new stoma formation impaired postoperative recovery.
The present study showed that a successful laparoscopic procedure had an independent role to increase the adherence to postoperative ERP and to improve short-term postoperative outcome.
Incisional hernia repair is one of the most common general surgery operations being performed today. With the advancement of laparoscopy since the 1990s, we have seen vast improvements in faster return to normal activity, shorter hospital stays and less post-operative narcotic use, to name a few.
The key aims of this review were to measure the impact of minimally invasive surgery versus open surgery on health care utilization, cost, and work place absenteeism in the patients undergoing inpatient incisional/ventral hernia (IVH) repair.
We analyzed data from the Truven Health Analytics MarketScan® Commercial Claims and Encounters Database. Total of 2557 patients were included in the analysis.
Of the patient that underwent IVH surgery, 24.5% (n = 626) were done utilizing minimally invasive surgical (MIS) techniques and 75.5% (n = 1931) were done open. Ninety-day post-surgery outcomes were significantly lower in the MIS group compared to the open group for total payment ($19,288.97 vs. $21,708.12), inpatient length of stay (3.12 vs. 4.24 days), number of outpatient visit (5.48 vs. 7.35), and estimated days off (11.3 vs. 14.64), respectively. At 365 days post-surgery, the total payment ($27,497.96 vs. $30,157.29), inpatient length of stay (3.70 vs. 5.04 days), outpatient visits (19.75 vs. 23.42), and estimated days off (35.71 vs. 41.58) were significantly lower for MIS group versus the open group, respectively.
When surgical repair of IVH is performed, there is a clear advantage in the MIS approach versus the open approach in regard to cost, length of stay, number of outpatient visits, and estimated days off.
Minimal access adrenal surgery (MAAS) for adrenal pathologies is the standard for many pediatric surgical centers. However, the literature offers few reports and minimal evidence from small case series. The aim of this study was to evaluate the outcomes of pediatric MAAS through a multi-center data analysis.
Pediatric patients who underwent MAAS between January 2002 and December 2013 were retrospectively included. Data analysis was conducted using Spss software (Welch's t-test, X-square, Fisher tests, multiple regression model).
Six European centers participated, 68 patients were included with mean age of 5.2 years (2 months–16 years). Lesion volume was of 18.1 cc (0.78–145.6), with a mean diameter of 2.8 cm (1.1–6.5). Localization was 50% left-sided masses, 45.6% right-side masses, and 4.4% bilateral. Histological examination revealed 36 neuroblastomas, 15 adenomas, nine pheochromocytomas, three ganglioneuromas, two ganglioneuroblastomas, one bilateral hyperplasia, one adrenocortical carcinoma, an alveolar sarcoma, and a calcification. Surgical access was transperitoneal in 63 (92.6%) and retroperitoneal in 5 (7.4%). Mean operative time was 170 ± 87 min (285 ± 30 min for bilateral lesions). Mean hospital stay was 4.2 ± 2.5 days. Complications included blood loss requiring transfusion in five patients (7.4%) and a diaphragmatic tear. Infiltration of surrounding structures correlated with intraoperative complication rate (p = 0.027) and operative time (p < 0.01). No mass rupture, conversion, or post-operative complications were observed. Median follow-up was 52 months (1–161). Two recurrences occurred in patients with pheochromocytoma. Age, weight, symptoms, characteristics at imaging, chemistry, volume, or histology, did not influence operative time, hospital stays, or complication rate.
Pediatric MAAS was safe adopted for masses up to 145.6 cc, with a very low rate of complication. Conversion to open is not necessary even in the presence of infiltrations. MAAS should represent the first-line treatment for selected cases in centers experienced in laparoscopy.
We report the case of a 33-year-old Caucasian American man diagnosed with celiac disease in Japan. He presented to a community hospital because of chronic watery diarrhea and weight loss for 6 months. The laboratory data showed low serum albumin and serum cholesterol. A colonoscopy was normal. He was referred to our hospital for further work-up. Serum tissue transglutaminase immunoglobulin A (IgA) and endomysial antibody were positive. The HLA type was DQ2. Esophagogastroduodenoscopy (EGD) revealed nodular and mosaic-patterned mucosa from the bulb to the second part of the duodenum. The histopathological findings were consistent with Marsh type 3c of the modified Marsh classification for celiac disease. The patient was instructed to follow a gluten-free diet (GFD). Six months after the initiation of the GFD, his symptom and the levels of serum albumin and cholesterol were improved, and the serum tissue transglutaminase IgA and endomysial antibody became negative. However, EGD showed little improvement. Capsule endoscopy also revealed mosaic-patterned mucosa, nodular mucosa, and scalloping of the folds of the duodenum and proximal small intestine. There was no definite improvement in histopathological findings. Collectively, the GFD was effective in this patient with celiac disease, but it should be maintained to achieve endoscopic and histopathologic healing.
Nativity is not often considered in the study of health disparities. We conducted a cross-sectional, parent-reported survey of demographics, socioeconomic characteristics, healthcare access, and health conditions in New York City schoolchildren (n = 9029). US-born children with US-born parents (US/US) had higher socioeconomic status, better access to healthcare, and reported higher rates of disease diagnoses compared to US-born children with immigrant parents and to immigrant children. Dental cavities were the only condition in which US/US children reported lower prevalence. US/US children had the best healthcare access, most favorable parent-reported health status and highest rate of satisfaction with healthcare. The magnitude of racial/ethnic disparities varied based on nativity of the children being compared. Factors such as the healthy immigrant effect and differential diagnosis rates may explain the results. In conclusion, nativity influences disease burdens and should be considered in health disparities studies.
The Department of Homeland Security OEC released the data to guide the development of policies, programs and funding
from EMS via xlomafota13 on Inoreader http://ift.tt/2xKmVVz
via IFTTT
By EMS1 Staff CALGARY, Alberta — An injured paramedic is on a mission to paint 100 portraits of first responders in 100 days to raise awareness of job fatigue. Calgary Herald reported that paramedic Naomi Fox, who is currently recovering from hip surgery from a work-related injury, wants to raise awareness about the physical and mental fatigue paramedics face on the job. "In order to keep ...
from EMS via xlomafota13 on Inoreader http://ift.tt/2h4aYqL
via IFTTT
Microbial Drug Resistance , Vol. 0, No. 0.
from Mary Ann Liebert, Inc. publishers via xlomafota13 on Inoreader http://ift.tt/2io1qn0
via IFTTT
EMS providers need to be involved in educating communities in how to provide the initial response to critically injured patients
from EMS via xlomafota13 on Inoreader http://ift.tt/2gTImge
via IFTTT
No abstract available
No abstract available
No abstract available
BACKGROUND: Publication bias within systematic reviews may result in incorrect conclusions leading to inappropriate clinical decisions and a decreased quality of patient care. Searching clinical trial registries for unpublished studies is one possible solution to minimise publication bias. OBJECTIVES: To examine rates of clinical trial registry searches in systematic reviews published in respected anaesthesiology journals and whether these searches found trials (or data) eligible for inclusion; to compare rates of registry searches between published reviews and similar reviews within the Cochrane Anaesthesia, Critical and Emergency Care Group; to conduct trial registry searches for a subset of reviews, determining whether eligible studies were overlooked; to investigate whether reporting of results in completed anaesthesia trials on ClinicalTrials.gov followed guidelines. DESIGN: A cross-sectional study of systematic reviews published in 10 anaesthesiology journals and the Cochrane Library. SETTING AND PARTICIPANTS: PubMed and the Cochrane Library were searched for systematic reviews or meta-analyses. MAIN OUTCOME MEASURES: The primary outcome was the number of systematic reviews that searched clinical trial registries for unpublished trials. Secondary outcomes included the number of registered trials in the ClinicalTrial.gov registry and the number of trials reporting trial results which were available on the ClinicalTrials.gov database and which should have been considered in a systematic review. RESULTS: The PubMed search yielded 507 records, and 415 remained after exclusions. Of these, 49 (11.8%) included a search of clinical trial registries. In total, 12 systematic reviews reported finding unpublished data but only five incorporated the data into their analyses. Of the Cochrane reviews, 58.9% (43/73) reported registry searches. Among a sample of 30 systematic reviews that omitted registry searches, we found many studies within the registries that were probably eligible to be included in the systematic reviews. For completed trials within the ClinicalTrials.gov database, only 15.4% reported results. CONCLUSION: The majority of systematic reviews in anaesthesiology did not include data from clinical trial registries. Exclusion of statistically nonsignificant data may lead to a biased interpretation of the data and hence inappropriate clinical interventions. TRIAL REGISTRATION: Registered in University hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000021932).
No abstract available
BACKGROUND: The association between the quality of evidence in systematic reviews and authors' conclusions regarding the effectiveness of interventions relevant to anaesthesia has not been examined. OBJECTIVE: The objectives of this study were: to determine the proportion of systematic reviews in which the authors made a conclusive statement about the effect of an intervention; to describe the quality of evidence derived from outcomes in reviews that used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) working group system for grading the quality of evidence; and to identify review characteristics associated with conclusiveness. DESIGN: Cross-sectional analysis of Cochrane systematic reviews from the Anaesthesia, Critical Care and Emergency Review Group was undertaken. DATA SOURCES: The Cochrane webpage was used to identify reviews for inclusion (http://.ace.cochrane.org/ ). ELIGIBILITY CRITERIA: New and updated versions of systematic reviews published up to 17 September 2015 were eligible. Protocols for systematic reviews were excluded. RESULTS: A total of 159 reviews were included. GRADE was used in 103 reviews (65%). Of these, high-level evidence for the primary outcome was identified in 11 reviews (10%). The main reasons that quality of evidence for the primary outcome was downgraded were risk of bias (n = 44; 43%) and imprecision (n = 36; 35%). Authors of 47% (n = 75) of the total number of reviews made conclusive statements about the effects of interventions. Independent predictors of conclusiveness in the subgroup of reviews with GRADE assessments were quality of evidence for the primary outcome (odds ratio 2.03; 95% confidence interval: [1.18 to 3.52] and an increasing number of studies included in reviews (OR 1.05; 95% CI: [1.01 to 1.09]). CONCLUSION: It was common for conclusive statements to be made about the effects of interventions despite evidence for the primary outcome being rated less than high quality. Improving methodological quality of trials would have the greatest impact on improving the quality of evidence.
No abstract available
BACKGROUND: Publication performance in anaesthesiology hints at research activity and attractiveness for a particular centre or country for anaesthetists. OBJECTIVE: The aim of this retrospective bibliographic study is to compare the publication performance of anaesthesiology departments within the countries of the European Union (EU) and European Free Trade Association (EFTA) combined. Outcome measures were the number of publications, the number of original articles, the average impact factor and the number of publications and average impact factor per million inhabitants. METHODS: Articles from anaesthesiology departments within the EU and EFTA countries published between 1 January 2001 and 31 December 2015 were included. Articles were electronically imported from Medline into a database and linked to anaesthesiology departments according to the authors' affiliations. Publication performance was assessed for 2001 to 2005, 2006 to 2010, 2011 to 2015 and 2001 to 2015. RESULTS: From 2001 to 2015, the absolute number of articles increased from 10 513 to 19 037 (+81%), whereas the number of original research articles decreased from 3786 to 1563 (−58%). Germany had the most publications (8948) with 1967 of these being original articles. Denmark achieved not only the highest average impact factor per million inhabitants (319.9) but also the most articles per anaesthesiologist (1.46), and per million habitants (105.7). Countries which moved up the income scale to a higher income class also increased the number of publications. DISCUSSION: In the EU and EFTA countries, the total number of publications increased from 2001 to 2015, but the number of original research articles fell by more than 50%. CONCLUSION: Between 2001 and 2015, in the EU and EFTA countries, the number of publications increased, whereas the number of original articles decreased. Germany published most, but Denmark had most publications per anaesthesiologist and per capita, and also achieved the highest impact factor per article.
BACKGROUND: The annual congress of the European Society of Anaesthesiology (ESA) is one of the largest anaesthesia congresses in the world and exhibits more than 1200 abstracts annually. OBJECTIVES: The aims of this study were to quantify the frequency of inadequate evidence of ethical approval for abstracts submitted to the ESA congress and to examine whether abstracts without appropriate ethical approval were subsequently accepted. DESIGN AND SETTING: All abstracts submitted in 2015 were adjudicated according to European ethical criteria. MAIN OUTCOME MEASURE: The proportion of submitted abstracts that lacked evidence of appropriate ethics committee approval. Secondary outcomes included the proportion of accepted abstract that lacked evidence of appropriate ethical approval; the proportion of correctly identified case reports; the proportion of accepted abstracts that lacked evidence of appropriate ethics committee approvals corresponding to location (within/outside Europe); and the proportion of accepted abstracts that lacked evidence of appropriate ethics committee approvals corresponding to a specific area of research. RESULTS: In total, 1792 abstracts were reviewed and 1572 (87.7%) involved humans. In 527 (29.4%), the authors failed to demonstrate adequate ethical approval with higher rates in abstracts submitted from Europe (32.1%) than the rest of the world (23.5%), P 
BACKGROUND: Use of the internet as an information search tool has increased dramatically. Our study assessed preoperative use of the internet by patients to search for information regarding anaesthesia, surgery, pain or outcomes. OBJECTIVE(S): The aim of this study was to test whether patients used the internet prior to surgery and what kinds of information they looked for (anaesthetic technique, pain, adverse events, outcomes and surgery). Correlation between patient age and information sought about surgery from the internet was also explored. DESIGN: A prospective multicentre observational study. SETTING: In total, 14 French private and public institutions from May 2015 to January 2016. PATIENTS: In total, 3161 adult patients scheduled for elective surgery under regional or general anaesthesia. INTERVENTION(S): An anonymous questionnaire was presented to adult patients scheduled for elective surgery under regional or general anaesthesia for completion before the first meeting with the anaesthesiologist. The investigator at each centre completed specific items that the patient could not complete. MAIN OUTCOME MEASURES: We defined the primary endpoint as the number of patients who searched for information about their anaesthesia or surgery on the internet by the time of the their preanaesthetic consultation. RESULTS: Of the 3234 questionnaires distributed, responses were received from 3161 patients. Within this respondent sample, 1304 (45%) were professionally active and 1664 (59%) used the internet at least once per day. Among 3098 (98%) patients who answered the question concerning the primary endpoint, 1506 (48%) had searched the internet for information about their health. In total, 784 (25%) used the internet to find information about their surgery and 113 (3.5%) looked for specific information about anaesthesia. Of the 3161, 52% reported difficulty searching for appropriate information about anaesthesia on the internet. 'Daily use of the web' [odds ratio (OR) 2.0; (95% CI: 1.65 to 2.55) P 
No abstract available
BACKGROUND: Although both recorded lectures and serious games have been used to pretrain health professionals before simulation training on cardiopulmonary resuscitation, they have never been compared. OBJECTIVE: The aim of this study was to compare an online course and a serious game for pretraining medical students before simulation-based mastery learning on the management of sudden cardiac arrest. DESIGN: A randomised controlled trial. Participants were pretrained using the online course or the serious game on day 1 and day 7. On day 8, each participant was evaluated repeatedly on a scenario of cardiac arrest until reaching a minimum passing score. SETTING: Department of Simulation in Healthcare in a French medical faculty. PARTICIPANTS: Eighty-two volunteer second-year medical students participated between June and October 2016 and 79 were assessed for primary outcome. INTERVENTIONS: The serious game used was Staying Alive, which involved a 3D realistic environment, and the online course involved a PowerPoint lecture. MAIN OUTCOME MEASURES: The median total training time needed for students to reach the minimum passing score on day 8. This same outcome was also assessed 4 months later. RESULTS: The median training time (interquartile range) necessary for students to reach the minimum passing score was similar between the two groups: 20.5 (15.8 to 30.3) minutes in the serious game group versus 23 (15 to 32) minutes in the online course group, P = 0.51. Achieving an appropriate degree of chest compression was the most difficult requirement to fulfil for students in both groups. Four months later, the median training time decreased significantly in both groups, but no correlation was found at an individual level with the training times observed on day 8. CONCLUSION: The serious game used in this study was not superior to an online course to pretrain medical students in the management of a cardiac arrest. The absence of any correlation between the performances of students evaluated during two training sessions separated by 4 months suggests that some elements in the management of cardiac arrest such as compression depth can only be partially learned and retained after a simulation-based training. TRIAL REGISTRATION: ClinicalTrials.gov-NCT02758119.
No abstract availableThe three-layered visual cortex of turtle is characterized by extensive intracortical axonal projections and receives non-retinotopic axonal projections from lateral geniculate nucleus. What spatiotemporal transformation of visual stimuli into cortical activity arises from such tangle of malleable cortical inputs and intracortical connections? To address this question, we obtained band-pass filtered extracellular recordings of neural activity in turtle dorsal cortex during visual stimulation of the retina. We discovered important spatial and temporal features of stimulus-modulated cortical local field potential (LFP) recordings. Spatial receptive fields span large areas of the visual field, have an intricate internal structure, and lack directional tuning. The receptive field structure varies across recording sites in a distant-dependent manner. Such composite spatial organization of stimulus-modulated cortical activity is accompanied by an equally multifaceted temporal organization. Cortical visual responses are delayed, persistent, and oscillatory. Further, prior cortical activity contributes globally to adaptation in turtle visual cortex. In conclusion, these results demonstrate convoluted spatiotemporal transformations of visual stimuli into stimulus-modulated cortical activity that, at present, largely evade computational frameworks.
Human Waardenburg syndrome 2A (WS2A) is a dominant hearing loss (HL) syndrome caused by mutations in the microphthalmia-associated transcription factor (MITF) gene. In mouse models with MITF mutations, WS2A is transmitted in a recessive pattern, which limits the study of hearing loss (HL) pathology. In the current study, we performed ENU (ethylnitrosourea) mutagenesis that resulted in substituting a conserved lysine with a serine (p. L247S) in the DNA-binding domain of the MITF gene to generate a novel miniature pig model of WS2A. The heterozygous mutant pig (MITF +/L247S) exhibits a dominant form of profound HL and hypopigmentation in skin, hair, and iris, accompanied by degeneration of stria vascularis (SV), fused hair cells, and the absence of endocochlear potential, which indicate the pathology of human WS2A. Besides hypopigmentation and bilateral HL, the homozygous mutant pig (MITF L247S/L247S) and CRISPR/Cas9-mediated MITF bi-allelic knockout pigs both exhibited anophthalmia. Three WS2 patients carrying MITF mutations adjacent to the corresponding region were also identified. The pig models resemble the clinical symptom and molecular pathology of human WS2A patients perfectly, which will provide new clues for better understanding the etiology and development of novel treatment strategies for human HL.
The hepatic stellate cells (HSCs) localize at the space of Disse in the liver and have multiple functions. They are identified as the major contributor to hepatic fibrosis. Significant understanding of HSCs has been achieved using rodent models and isolated murine HSCs; as well as investigating human liver tissues and human HSCs. There is growing interest and need of translating rodent study findings to human HSCs and human liver diseases. However, species-related differences impose challenges on the translational research. In this review, we focus on the current information on human HSCs isolation methods, human HSCs markers, and established human HSC cell lines.
Golden cuttlefish (Sepia esculenta) is an important economic species in China. Because of the rapid decline of its natural resource, researchers are exploring breeding technique for this species. The major obstacle that hinders artificial breeding of S. esculenta is the low larvae survival rate. Mortality is especially high during the mouth-opening stage. Investigating the embryogenesis before the first feed could provide theoretical guidance for reproduction control and breeding of S. esculenta and other Sepia species. In this study, we analyzed the dynamics of the S. esculenta transcriptome along different stages of embryonic development by mRNA-sEq. Our bioinformatics protocol identified 1492 differentially expressed genes (DEGs) across the early developmental stages. Gene ontology enrichment analysis showed that the DEGs were significantly involved in developmental processes and molecular functions, including chitin metabolic process, peptidase activity, catalytic activity, and calcium ion binding. Our results indicated that genes related to cuttlebone development and gene regulation functions were active during the early life phase of S. esculenta. Hierarchical clustering of the DEGs reflected the successiveness of the developmental stages, revealing that gene expression patterns of neighboring stages were similar. The DEG analysis allowed us to identify specific genes and relevant biological pathways to better understand the molecular mechanisms during each developmental stage. This study provides novel insights into the processes underlying the early developmental stages of S. esculenta. The transcriptomic data and identified genes will serve as valuable references for the developmental biology of this species and will help promote its aquaculture research.
Gaucher disease (GD) is a recessively inherited autosomal lysosomal storage disease, the most severe of which is type 2, an acute neuronopathic form. We report an affected infant who inherited one mutant allele, Arg257Gln (c.887G>A; p.Arg296Gln) from his father, while the second, Gly202Arg (c.721G>A; p.Gly241Arg) arose by either maternal germline mosaicism or as a de novo mutation. This is the first time mutation Gly202Arg has been reported to be inherited non-traditionally. This report is part of a growing literature suggesting that GD can be inherited via germline or de novo mutations, and emphasizes that it is critical for clinicians to consider such inheritance when making diagnostic decisions or providing genetic counseling.
A female in her 70s underwent esophagogastroduodenoscopy (EGD) for screening, and a 0-IIa lesion measuring approximately 15 mm was detected in the descending portion of the duodenum. Due to the malignant potency of the lesion, endoscopic submucosal dissection (ESD) was performed. Microperforation occurred during ESD. The lesion was removed en bloc and the post-ESD ulcer bed was closed with clips. The next day, the patient had abdominal pain and computed tomography (CT) revealed a small amount of free air in the retroperitoneal space. Since there were no findings to suggest panperitonitis, conservative medical management including fasting and antibiotics was continued. Abdominal pain subsequently improved. However, EGD on the 8th day after ESD for follow-up showed shedding of the post-ESD ulcer that penetrated the retroperitoneal space. A surgical approach was not indicated because a few days may have already passed since postoperative perforation occurred and the spread of inflammation to the retroperitoneum was suspected. In an attempt to promote closure of the perforated cavity, we patched polyglycolic acid sheets and fibrin glue to the cavity wall on days 17, 18, and 20 after ESD. The formation of granulation tissue was detected in the cavity one week later. CT showed an abscess in the right retroperitoneum, for which CT-guided abscess puncture was performed. Thereafter, the cavity gradually decreased. After the initiation of oral intake on postoperative day (POD) 63, the general condition of the patient was stable and she was discharged on POD 87. Polyglycolic acid sheets with fibrin glue and CT-guided abscess puncture were useful for closing the large cavity that developed after duodenal postoperative perforation.
Introduction The home and school environments play important roles in influencing children's health behaviours. However, their simultaneous influence on childhood obesity has not yet been examined. We explore the relationship of the home and school environments with childhood obesity, to determine whether this relationship is mediated by children's fruit and vegetable intake and physical behaviours. Methods This study uses baseline data from 9 to 11 year old children, their parents and school principals (matched data n = 2466) from the Obesity Prevention and Lifestyle Project. Child-reported behaviours, parent-reported home environment and principal-reported school environment data were collected via questionnaires. Trained researchers measured children's height and weight, and Body Mass Index (BMI, kg/m2) was calculated. Structural equation modelling was used to assess the relationship of the home and school environments with children's fruit and vegetable intake, physical activity behaviours, and children's BMI. Result The home diet environment was positively associated with child diet (β = 0.18, p < 0.001). The home physical activity environment had the largest inverse association with BMI (β = − 0.11, p < 0.001), indirectly through child physical activity (β = 0.28 ,p < 0.001). Schools' healthy eating policy implementation was significantly associated with child diet (β = 0.52, p < 0.05), but physical activity policy was not associated with child activity (β = − 0.007, p > 0.05). The school environment was not associated with child BMI. Discussion The home environment had a stronger association with healthier child behaviours, compared to the school environment. These findings suggest that future childhood obesity interventions targeting healthier home environments and supporting parents can promote healthier child eating and physical activity behaviours.
Obesity-induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (ECs) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC-A1 activity also drives obesity-related VAT remodeling and inflammation. Our studies utilized wild-type and EC-A1 knockout (KO) mice made obese by high-fat/high-sucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular ECs and increased expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in both VAT and ECs. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor 2-(S)-amino-6-boronohexanoic acid (ABH). In mouse aortic ECs, exposure to high glucose (25 mM) and Na palmitate (200 μM) reduced nitric oxide production and increased A1, TNF-α, VCAM-1, ICAM-1, and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. HFHS diet-induced VAT inflammation is mediated by EC-A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation.
Apolipoprotein AIV (ApoAIV) and cholecystokinin (CCK) are well-known satiating signals that are stimulated by fat consumption. Peripheral ApoAIV and CCK interact to prolong satiating signals. In the present study, we hypothesized that ApoAIV and CCK control energy homeostasis in response to high-fat diet feeding. To test this hypothesis, energy homeostasis in ApoAIV and CCK double knockout (ApoAIV/CCK-KO), ApoAIV knockout (ApoAIV-KO), and CCK knockout (CCK-KO) mice were monitored. When animals were maintained on a low-fat diet, ApoAIV/CCK-KO, ApoAIV-KO, and CCK-KO mice had comparable energy intake and expenditure, body weight, fat mass, fat absorption, and plasma parameters relative to the controls. In contrast, these KO mice exhibited impaired lipid transport to epididymal fat pads in response to intraduodenal infusion of dietary lipids. Furthermore, ApoAIV-KO mice had upregulated levels of CCK receptor 2 (CCK2R) in the small intestine while ApoAIV/CCK-KO mice had upregulated levels of CCK2R in the brown adipose tissue. After 20 wk of a high-fat diet, ApoAIV-KO and CCK-KO mice had comparable body weight and fat mass, as well as lower energy expenditure at some time points. However, ApoAIV/CCK-KO mice exhibited reduced body weight and adiposity relative to wild-type mice, despite having normal food intake. Furthermore, ApoAIV/CCK-KO mice displayed normal fat absorption and locomotor activity, as well as enhanced energy expenditure. These observations suggest that mice lacking ApoAIV and CCK have reduced body weight and adiposity, possibly due to impaired lipid transport and elevated energy expenditure.
Remote ischemic preconditioning (RIPC) is characterized by the cyclical application of limb blood flow restriction and reperfusion and has been shown to protect vital organs during a subsequent ischemic insult. Blood flow restriction exercise (BFRE) similarly combines bouts of blood flow restriction with low-intensity exercise and thus could potentially emulate the protection demonstrated by RIPC. One concern with BFRE, however, is the potential for an augmented rise in sympathetic outflow due to greater activation of the exercise pressor reflex. Because of the use of lower workloads, however, we hypothesized that BFRE would elicit an attenuated increase in sympathetic outflow [assessed via plasma norepinephrine (NE) and mean arterial pressure (MAP)] and middle cerebral artery velocity (MCAv) when compared with conventional exercise (CE). Fifteen subjects underwent two leg press exercise interventions: 1) BFRE-220 mmHg bilateral thigh occlusion at 20% 1 rep-max (1RM), and 2) CE-65% 1RM without occlusion. Each condition consisted of 4 x 5-min cycles of exercise, with 3 x 10-reps in each cycle. Five minutes of rest and reperfusion (for BFRE) followed each cycle. MAP increased with exercise (P < 0.001) and was 4–5 mmHg higher with CE versus BFRE (P ≤ 0.09). Mean MCAv also increased with exercise (P < 0.001) and was higher with CE compared with BFRE during the first bout of exercise only (P = 0.07). Plasma NE concentration increased with CE only (P < 0.001) and was higher than BFRE throughout exercise (P ≤ 0.02). The attenuated sympathetic response, combined with similar cerebrovascular responses, suggest that cyclical BFRE could be explored as an alternative to CE in the clinical setting.
Remote ischemic preconditioning (RIPC) can attenuate tissue damage sustained by ischemia-reperfusion injury. Blood flow restriction exercise (BFRE) restricts blood flow to exercising muscles. We implemented a novel approach to BFRE with cyclical bouts of blood flow restriction-reperfusion, reflecting the RIPC model. A concern about BFRE, however, is potential amplification of the exercise pressor reflex, which could be unsafe in at-risk populations. We hypothesized that cyclical BFRE would elicit greater increases in sympathetic outflow and arterial pressure than conventional exercise (CE) when performed at the same relative intensity. We also assessed the cerebrovascular responses due to potential implementation of BFRE in stroke rehabilitation. Fourteen subjects performed treadmill exercise at 65–70% maximal heart rate with and without intermittent BFR (4 x 5-min intervals of bilateral thigh-cuff pressure followed by 5-min reperfusion periods). Mean arterial pressure (MAP), plasma norepinephrine (NE), and middle and posterior cerebral artery velocities (MCAv and PCAv) were compared between trials. As expected, BFRE elicited higher concentration NE compared with CE (1249 ± 170 vs. 962 ± 114 pg/ml; P = 0.06). Unexpectedly, however, there were no differences in MAP between conditions (overall P = 0.33), and MAP was 4–5 mmHg lower with BFRE versus CE during the reperfusion periods (P ≤ 0.05 for reperfusion periods 3 and 4). There were no differences in MCAv or PCAv between trials (P ≥ 0.22), suggesting equivalent cerebrometabolic demand. The exaggerated sympathoexcitatory response with BFRE was not accompanied by higher MAP, likely because of the cyclical reperfusions. This cyclical BFRE paradigm could be adapted to cardiac or stroke rehabilitation, where exercising patients could benefit from the cardio and cerebro protection associated with RIPC.
Endothelial function and arterial stiffness are known to be altered in preeclamptic pregnancies. Previous studies have shown conflicting results regarding the best technique for assessing vascular function in pregnancy. In this study, we made a comprehensive evaluation of in vivo vascular function [including flow-mediated dilatation (FMD), peripheral arterial tonometry (PAT), and arterial stiffness] in preeclamptic patients and compared them with normal pregnancies. In addition, we assessed the relation between vascular function and systemic inflammation. Fourteen patients with preeclampsia (PE) and 14 healthy pregnant controls were included. Endothelial function was determined by FMD and PAT and arterial stiffness by carotid-femoral pulse-wave velocity and augmentation index. Systemic inflammation was assessed using mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR). The reactive hyperemia index, assessed using PAT, is decreased at the third trimester compared with the first trimester in a normal, uncomplicated pregnancy (P = 0.001). Arterial stiffness is significantly higher in PE versus normal pregnancy (P < 0.001). Endothelial function, obtained by FMD, is deteriorated in PE versus normal pregnancy (P = 0.015), whereas endothelial function assessment by PAT is improved in PE versus normal pregnancy (P = 0.001). Systemic inflammation (MPV and NLR) increases during normal pregnancy. FMD and PAT are disturbed in PE. Endothelial function, assessed by FMD and PAT, shows distinct results. This may indicate that measurements with FMD and PAT reflect different aspects of endothelial function and that PAT should not be used as a substitute for FMD as a measure of endothelial function in pregnancy.
Rainbow trout (Oncorhynchus mykiss) confined in pairs form social hierarchies in which subordinate fish typically experience fasting and high circulating cortisol levels, resulting in low growth rates. The present study investigated the role of AMP-activated protein kinase (AMPK) in mediating metabolic adjustments associated with social status in rainbow trout. After 3 days of social interaction, liver AMPK activity was significantly higher in subordinate than dominant or sham (fish handled in the same fashion as paired fish but held individually) trout. Elevated liver AMPK activity in subordinate fish likely reflected a significantly higher ratio of phosphorylated AMPK (phospho-AMPK) to total AMPK protein, which was accompanied by significantly higher AMPKα1 relative mRNA abundance. Liver ATP and creatine phosphate concentrations in subordinate fish also were elevated, perhaps as a result of AMPK activity. Sham fish that were fasted for 3 days exhibited effects parallel to those of subordinate fish, suggesting that low food intake was an important trigger of elevated AMPK activity in subordinate fish. Effects on white muscle appeared to be influenced by the physical activity associated with social interaction. Overall, muscle AMPK activity was significantly higher in dominant and subordinate than sham fish. The ratio of phospho-AMPK to total AMPK protein in muscle was highest in subordinate fish, while muscle AMPKα1 relative mRNA abundance was elevated by social dominance. Muscle ATP and creatine phosphate concentrations were high in dominant and subordinate fish at 6 h of interaction and decreased significantly thereafter. Collectively, the findings of the present study support a role for AMPK in mediating liver and white muscle metabolic adjustments associated with social hierarchy formation in rainbow trout.
Modern dairy cows meet the energy demand of early lactation by calling on hormonally driven mechanisms to increase the use of lipid reserves. In this context, we recently reported that fibroblast growth factor-21 (FGF21), a hormone required for efficient use of lipid reserves in rodents, is upregulated in periparturient dairy cows. Increased plasma FGF21 in early lactation coincides with elevated circulating concentrations of glucagon (GCG) and nonesterified fatty acids (NEFA). To assess the relative contribution of these factors in regulating FGF21, two experiments were performed in energy-sufficient, nonpregnant, nonlactating dairy cows. In the first study, cows were injected with saline or GCG every 8 h over a 72-h period. GCG increased hepatic FGF21 mRNA by an average of fivefold over matched controls but had no effect on plasma FGF21. In the second study, cows were infused and injected with saline, infused with Intralipid and injected with saline, or infused with Intralipid and injected with GCG. Infusions and injections were administered intravenously over 16 h and subcutaneously every 8 h, respectively. Intralipid infusion increased plasma NEFA from 92 to 550 µM within 3 h and increased plasma FGF21 from 1.3 to >11 ng/ml 6 h later; FGF21 mRNA increased by 34-fold in liver but remained invariant in adipose tissue. GCG injections during the Intralipid infusion had no additional effects on plasma NEFA, liver FGF21 mRNA, or plasma FGF21. These data implicate plasma NEFA as a key factor triggering hepatic production and increased circulating concentrations of FGF21 in early lactation.
To elucidate the role of leptin in acute systemic inflammation, we investigated how its infusion at low, physiologically relevant doses affects the responses to bacterial lipopolysaccharide (LPS) in rats subjected to 24 h of food deprivation. Leptin was infused subcutaneously (0–20 μg·kg–1·h–1) or intracerebroventricularly (0–1 μg·kg–1·h–1). Using hypothermia and hypotension as biomarkers of systemic inflammation, we identified the phase extending from 90 to 240 min post-LPS as the most susceptible to modulation by leptin. In this phase, leptin suppressed the rise in plasma TNF-α and accelerated the recoveries from hypothermia and hypotension. Suppression of TNF-α was not accompanied by changes in other cytokines or prostaglandins. Leptin suppressed TNF-α when infused peripherally but not when infused into the brain. Importantly, the leptin dose that suppressed TNF-α corresponded to the lowest dose that limited food consumption; this dose elevated plasma leptin within the physiological range (to 5.9 ng/ml). We then conducted in vitro experiments to investigate whether an action of leptin on macrophages could parallel our in vivo observations. The results revealed that, when sensitized by food deprivation, LPS-stimulated peritoneal macrophages can be inhibited by leptin at concentrations that are lower than those reported to promote cytokine release. It is concluded that physiological levels of leptin do not exert a proinflammatory effect but rather an anti-inflammatory effect involving selective suppression of TNF-α via an action outside the brain. The mechanism of this effect might involve a previously unrecognized, suppressive action of leptin on macrophage subpopulations sensitized by food deprivation, but future studies are warranted.
The measurement of lung function in mice and rats is crucial for understanding how well small animal models of pulmonary disease recapitulate human clinical pathology but brings with it the challenge of making accurate measurements in animals as small as a mouse. Overcoming these challenges can be achieved in a number of ways, each based on a model idealization of how the lung works as a mechanical system. Accordingly, it is important to understand the theoretical basis on which an assessment of lung function rests to interpret experimental measurements appropriately. It is also crucial to attend to a number of practical issues that determine the quality of the measurements. The most accurate measurements of lung function in small animals are provided by the forced oscillation technique that provides lung resistance and elastance and its multifrequency generalization known as impedance. Measurement quality is maximized when the greatest possible degree of control is exerted over the amplitude and frequency with which air is oscillated in and out of the lungs, the mean or end-expiratory transpulmonary pressure pertaining to when the oscillations are applied, and the immediate past volume history of the lungs. It is also crucial that no spontaneous breathing efforts occur during the measurement period. Finally, there is no substitute for the skill in animal handling and surgical preparation that comes with practice; such a skill should be in place before embarking on any important series of experiments.
The skin is an accessible model circulation for studying vascular function and dysfunction across the lifespan. Age-related changes, as well as those associated with disease progression, often appear first in the cutaneous circulation. Furthermore, impaired vascular signaling and attendant endothelial dysfunction, the earliest indicators of cardiovascular pathogenesis, occur in a similar fashion across multiple tissue beds throughout the body, including the skin. Because microvascular dysfunction is a better predictor of long-term outcomes and adverse cardiovascular events than is large vessel disease, an understanding of age-associated changes in the control of the human cutaneous microcirculation is important. This review focuses on 1) the merits of using skin-specific methods and techniques to study vascular function, 2) microvascular changes in aged skin (in particular, the role of the endothelial-derived dilator nitric oxide), and 3) the impact of aging on heat-induced changes in skin vasodilation. While skin blood flow is controlled by multiple, often redundant, mechanisms, our laboratory has used a variety of distinct thermal provocations of this model circulation to isolate specific age-associated changes in vascular function. Skin-specific approaches and techniques, such as intradermal microdialysis coupled with laser-Doppler flowmetry (in vivo) and biochemical analyses of skin biopsy samples (in vitro), have allowed for the targeted pharmacodissection of the mechanistic pathways controlling skin vasoreactivity and study of the impact of aging and disease states. Aged skin has an attenuated ability to vasodilate in response to warm stimuli and to vasoconstrict in response to cold stimuli.
Intermittent hypoxia (IH) has been implicated in the cardiovascular consequences of obstructive sleep apnea (OSA). However, the lack of suitable experimental systems has precluded assessment as to whether IH is detrimental, protective, or both for the endothelium. The aim of the work was to determine the effects of frequency and amplitude of IH oxygenation swings on aortic endothelial wound healing. Monolayers of human primary endothelial cells were wounded and subjected to constant oxygenation (1%, 4%, 13%, or 20% O2) or IH at different frequencies (0.6, 6, or 60 cycles/h) and magnitude ranges (13–4% O2 or 20–1% O2), using a novel well-controlled system, with wound healing being measured after 24 h. Cell monolayer repair was similar at 20% O2 and 13% O2, but was considerably increased (approximately twofold) in constant hypoxia at 4% O2. The magnitude and frequency of IH considerably modulated wound healing. Cycles ranging 13–4% O2 at the lowest frequency (0.6 cycles/h) accelerated endothelial wound healing by 102%. However, for IH exposures consisting of 20% to 1% O2 oscillations, wound closure was reduced compared with oscillation in the 13–4% range (by 74% and 44% at 6 cycles/h and 0.6 cycles/h, respectively). High-frequency IH patterns simulating severe OSA (60 cycles/h) did not significantly modify endothelial wound closure, regardless of the oxygenation cycle amplitude. In conclusion, the frequency and magnitude of hypoxia cycling in IH markedly alter wound healing responses and emerge as key factors determining how cells will respond in OSA.
NEW & NOTEWORTHY Intermittent hypoxia (IH) induces cardiovascular consequences in obstructive sleep apnea (OSA) patients. However, the vast array of frequencies and severities of IH previously employed in OSA-related experimental studies has led to controversial results on the effects of IH. By employing an optimized IH experimental system here, we provide evidence that the frequency and magnitude of IH markedly alter human aortic endothelial wound healing, emerging as key factors determining how cells respond in OSA.
Colon cancer (CRC) is the third most common cancer worldwide. CRC develops through combinations of genetic and epigenetic changes. However, there is marked heterogeneity in the "driver gene" mutational profiles within and among colon cancers from individual patients, and these are not sufficient to explain differences in colon cancer behavior and treatment response. Global modulation of the tumor landscape may play a role in cancer behavior. Interferon-related developmental regulator 1 (IFRD1) is a transcriptional co-regulator that modulates expression of large gene cassettes and plays a role in gut epithelial proliferation following massive intestinal resection.
We address the hypothesis that increased IFRD1 expression in colon cancers is associated with poorer patient survival.
Tumor and normal tissue from colon cancer patient cohorts from the USA, Spain, and China were used for this study. Cancers were scored for the intensity of IFRD1 immunostaining. The primary clinical outcome was overall survival defined as time from diagnosis to death due to cancer. Kaplan–Meier method and log-rank analysis were used to assess the association between IFRD1 expression and survival.
Almost all (98.7%) colon cancers showed readily detectable IFRD1 expression, with immunoreactivity primarily in the tumor cytoplasm. High IFRD1 colon cancer expression was significantly associated with decreased 5-year patient survival. Patients in the American cohort with high IFRD1 expression had a poorer prognosis.
We have demonstrated that high IFRD1 protein expression in colon cancer is associated with poorer patient prognosis, suggesting a potential role for IFRD1 in modulating tumor behavior.
Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain.
To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation.
This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007–2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use.
A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan–Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications.
Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.
