Long-term Injury Research Articles

Definition, Quantification, and Utility of Biomarkers of Repetitive Brain Injury in Predicting Concussion and Other Long-Term Injury Risks in Patients With Atrial Fibrillation (Concussion AF)

Definition, Quantification, and Utility of Biomarkers of Repetitive Brain Injury in Predicting Concussion and Other Long-Term Injury Risks in Patients With Atrial Fibrillation (Concussion AF)

Chemogenetic Silencing of the Locus Coeruleus–Basolateral Amygdala Pathway Abolishes Pain-Induced Anxiety and Enhanced Aversive Learning in Rats

BackgroundPain affects both sensory and emotional aversive responses, often provoking anxiety-related diseases when chronic. However, the neural mechanisms underlying the interactions between anxiety and chronic pain remain unclear. MethodsWe characterized the sensory, emotional, and cognitive consequences of neuropathic pain (chronic constriction injury) in a rat model. Moreover, we determined the role of the locus coeruleus (LC) neurons that project to the basolateral amygdala (BLA) using a DREADD (designer receptor exclusively activated by designer drugs). ResultsChronic constriction injury led to sensorial hypersensitivity in both the short term and long term. Otherwise, long-term pain led to an anxiety-like profile (in the elevated zero maze and open field tests), as well as increased responses to learn aversive situations (in the passive avoidance and fear conditioning tests) and an impairment of nonemotional cognitive tasks (in the novel object recognition and object pattern of separation tests). Chemogenetic blockade of the LC-BLA pathway and intra-BLA or systemic antagonism of beta-adrenergic receptors abolished both long-term pain-induced anxiety and enhanced fear learning. By contrast, chemogenetic activation of this pathway induced anxiety-like behaviors and enhanced the aversive learning and memory index in sham animals, although it had little effect on short- and long-term chronic constriction injury animals. Interestingly, modulation of LC-BLA activity did not modify sensorial perception or episodic memory. ConclusionsOur results indicate that dimensions associated with pain are processed by independent pathways and that there is an overactivation of the LC-BLA pathway when anxiety and chronic pain are comorbid, which involves the activity of beta-adrenergic receptors.

Occupational Safety and Health Practices among Farmers in Wadi Al Far'a Area, Palestine

Background: Agriculture is considered a vital sector and it is ranked as the fourth cause for occupational non- fatal injury in the Palestinian society. Methods: A quantitative study in Wadi Al Far’a area was implemented in 2017. Four hundred farmers were interviewed and completed a questionnaire. The researcher requested information about the farmers and their work, along with a description of the injury and its seriousness and whether they were injured during the past twelve months. Moreover, information regarding farmer awareness about the preventive measures was taken. A descriptive analysis, χ2 testing and binary logistic regression were conducted using SPSS (version 20). Results: The analysis showed that 71% of the interviewed farmers were injured, of which 51% of the injuries were concentrated in the hands of the farmers, while 36% of the farmers were injured by stab wounds from sharp objects, and 45% of the accidents were caused by hand equipments. The analysis also showed that 4.2% of the farmers reported that the injuries were serious and needed hospital treatment, while 47.6% needed a rest for a day or less and 2% were left with long-term injuries accompanied by medical certificates. Fewer injuries were found among farmers who attended an occupational safety course and who wore protective uniforms. The binary regression results revealed that farmers coming from big families, who own the farms and work as full time farmers in big fields, were at a higher risk to become injured. While elderly farmers were at a lower risk to be injured. Conclusion: Strengthening the National Committee for Occupational Safety combined with safety education; through the use of safety equipment and the improvement of preventive measures that are needed to improve occupational safety for farmers at the Palestinian level.

Neuro-Behavioral Status and the Hippocampal Expression of Metabolic Associated Genes in Wild-Type Rat Following a Ketogenic Diet.

While a ketogenic diet (KD) is a well-established therapy for medically intractable epilepsy, clinical evidence of relevant adverse events of a KD has also been reported. We asked whether this kind of diet would have deleterious effects on wild-type brain function by evaluating KD-induced biochemical changes in the hippocampus as well as neurobehavioral changes occurring in wild-type rats. Fifty-four Sprague-Dawley rats were randomly assigned to three groups on postnatal day 28 (P28): wild-type rats fed with a KD qd (daily for 4 weeks, KD) or qod (every other day for 4 weeks, KOD), and wild-type rats fed with standard normal laboratory diet (ND). Neurobehavioral changes were observed on P35, P42, and P49. The hippocampal mossy fiber sprouting, the expression levels of zinc transporters (ZnTs) and lipid metabolism related genes were detected by Timm staining, RT-qPCR and western blot analysis, respectively, on P58. The KD-treated KOD and KD groups showed a significant delay of negative geotaxis reflex on P35, but not on P42 or P49. In the open field test, daily KD treatment only led to a reduction in exploratory activity and increased grooming times but induced no significant changes in the scores of vertical activity or delay time. KD qod treated rats (KOD) displayed a slight delay in the place navigation test on P35 compared with the KD group. There were no significant differences in Timm staining among the three groups. In parallel with these changes, KD treatment (both KD and KOD) induced significantly downregulated mRNA levels of Apoa1, Pdk4, and upregulated expression of ApoE, ANXN7, and cPLA2 in the hippocampus when compared with the ND group (except in the case of ApoE in the KOD group). Notably, both the mRNA and protein levels of cPLA2 in the KOD rats were significantly downregulated compared with the KD group but still markedly higher than in the ND group. No significant difference was found in ZnTs among the three groups. Our data suggest that early-life KD can provoke minor neurobehavioral effects in particular a delay in negative geotaxis reflex and an increase in grooming activity. The hippocampal lipid metabolism signaling pathway, especially cPLA2, may be the target of the protective effect of KD on long-term brain injury after developmental seizures.

Matrilin-2 prevents the TNFα-induced apoptosis of WB-F344 cells via suppressing JNK pathway.

Oval cells, a kind of hepatic progenitor cell quiescent at normal condition, activates to proliferate and differentiate into hepatocytes under severe and long-term liver injury, which usually raises severe inflammation. However, how oval cell survives in the inflammatory milieu interne is still unclear. Tumor necrosis factor α (TNFα), mimicking inflammatory hepatic milieu interne, was used to treat oval cell line, WB-F344, to test the protective function of matrilin-2. In this study, our data suggested that matrilin-2 prevented TNFα-induced apoptosis in WB-F344 cells via inhibiting ASK1/MKK7/JNK pathway. In conclusion, we determined that matrilin-2 plays the key role in maintaining the survival of oval cell and guarantees its proliferation under various injury factors.

Challenges of talent development in alpine ski racing: a narrative review

ABSTRACTAlpine ski racing is one of the most popular sports in many countries; nevertheless, selection disadvantages and severe injuries result in high dropout rates. In this review we summarize existing knowledge about the specific challenges associated with selection bias and injuries, and their effects on talent development in ski racing.The relative age effect (RAE) appears in all age categories of national Austrian and international alpine ski racing. Relatively younger athletes seem to only have a chance for selection if they are early maturing. Talent selection processes should consider both the biological maturity status as well as the relative age; additionally, a competition system based on a rotating cut-off date might contribute to a reduction of RAE. Youth and adolescent ski racers report lower injury rates compared to World Cup athletes. The knee was the most affected body part in relation to traumatic injuries. The most frequently reported overuse injuries were knee pain (youth) and low back pain (adolescent level). Athlete-related modifiable risk factors were core strength, neuromuscular control, leg extension strength and limb asymmetries. Based on these findings, prevention measures should be expanded to contribute to long-term injury prevention. In future research more multi-disciplinary, longitudinal studies should be performed.

Associations between leisure time physical activity and cardiovascular risk factors among older adults with long-term spinal cord injury.

This is a cross-sectional study. To describe the association between cardiovascular risk factors (body mass index (BMI), waist circumference (WC), blood pressure, blood glucose and lipids) and leisure time physical activity (LTPA) in older adults with long-term spinal cord injury (SCI). Community settings, southern Sweden. Data from the baseline data collection of the Swedish Aging with Spinal Cord Injury Study (SASCIS) (n = 123, 71% men, injury levels C1-L5, American Spinal Injury Association Impairment Scale A-D, mean age 63 years, mean time since injury 24 years). Data were collected through home interviews, assessments and blood samples. The Physical Activity Recall Assessment for People with SCI was used to assess LTPA. Associations were investigated using multivariable linear regression analyses adjusted for age, gender, level and severity of injury, cause of injury, time since injury and tobacco use. More minutes per day of moderate-to-heavy LTPA were significantly associated with a lower BMI (Beta = -0.31; p = 0.001) and a lower WC (Beta = -0.24; p = 0.009). More minutes per day of total LTPA (mild intensity or greater) were associated with a higher systolic blood pressure (Beta = 0.27; p = 0.041) among participants with tetraplegia. No other significant associations between the cardiovascular risk factors and total LTPA were found. Participation in daily LTPA is associated with better cardiovascular health with regard to BMI and WC in older adults with long-term SCI. Further studies are needed to establish the specific amount of activity needed to obtain positive health effects in this group and the directional causality of the associations. Not applicable.

Neurologic recovery after deep hypothermic circulatory arrest in rats: A description of a long-term survival model without blood priming.

Brain injury associated with deep hypothermic circulatory arrest (DHCA) has been recognized in patients with congenital heart diseases and those undergoing aortic arch surgeries. However, the preclinical investigation of long-term cerebral injury and recovery mechanisms related to DHCA has been restricted to a satisfactory recovery animal model with a determined recovery time. This study aimed to evaluate the feasibility of a long-term surviving DHCA model without blood priming in rats, in order to investigate the pathophysiology of long-term complications in further studies. Twelve Sprague-Dawley rats were divided into 2 groups: sham group (n=3) and DHCA group (n=9). The DHCA group was further assigned to the surviving time of postoperative day 2, 14, and 30 (n=3, respectively). The entire cardiopulmonary bypass (CPB) circuit consisted of a modified reservoir, a custom-designed small-volume membrane oxygenator, a roller pump and a heater/cooler. A 24-G catheter was cannulated in the branch of the left femoral artery for arterial blood pressure monitoring. Cardiopulmonary bypass was established via the right external jugular vein-right atrium and tail artery. Rats were cooled to a rectal temperature of 18°C, followed by 30minutes of DHCA with global ischemia. After re-warming for approximately 40minutes, the animals were weaned from the CPB at 35.5°C. Blood gas and hemodynamic parameters were recorded preoperatively and intraoperatively, and at 2, 14, and 30 days postoperatively. Thereafter, the brains were perfusion fixed and histologically analyzed. All DHCA processes were successfully achieved, and none of the rats died. Blood gas analysis and hemodynamic parameters at each time point were normal, and vital signs of all rats were stable. Histopathologic deficits in the hippocampus (pathological score, surviving hippocampal neurons, and Ki67-positive neurons) manifested after 30 minutes of DHCA, which persisted for at least 14 days and recovered after 30 days. A novel and simple long-term recovery model of DHCA in rats was established in the present study, and histopathologic deficits were observed after clinically relevant 30-minute DHCA durations, in order to determine the 30-day recovery time frame.

The Long-lasting Radioprotective Effect of Caffeic Acid in Mice Exposed to Total Body Irradiation by Modulating Reactive Oxygen Species Generation and Hematopoietic Stem Cell Senescence-Accompanied Long-term Residual Bone Marrow Injury.

Total body irradiation (TBI) serves as an effectively curative therapy for cancer patients and adversely causes long-term residual bone marrow (BM) injury with premature senescence of hematopoietic stem cells (HSCs), which is mediated by increased production of reactive oxygen species (ROS). In the present study, we investigated how the exposure time of TBI in a mouse model affects HSCs and whether the treatment of caffeic acid (CA), a known dietary phenolic antioxidant, has a radioprotective effect. Single (S)-TBI at a sublethal dose (5 Gy) caused relatively higher induction of mitochondrial ROS and senescence-related factors in HSCs than those in hematopoietic progenitor cells (HPCs) and Lineage-Sca-1+c-Kit+ (LSK) cells, as well as reduced clonogenic formation and donor cell-derived reconstituting capacity. Repetitive double (D)-TBI (two months after the S-TBI at a dose of 5Gy) further weakened HSPC function via mitochondrial ROS accumulation and senescence-associated β-galactosidase (SA-β-gal) activity. Oral administration of CA (20 mg/kg) five times before and once immediately after TBI ameliorated ROS generation and TBI-induced HSC senescence and its radioprotective effect was long lasting in S-TBI mice but not in D-TBI mice. Further, supplementation of CA also induced apoptotic cell death of colon cancer cells. Collectively, these findings indicate that CA has a dual effect, ameliorating HSC senescence-accompanied long-term BM injury in S-TBI mice and stimulating apoptotic cell death of colon cancer cells.

A Study on the awareness of road safety for trucks transportation in Peninsular Malaysia

Safety is the first priority during the process of transportation as an accident occurs will cause a person’s life or long-term injury. This study identifies the awareness of road safety for trucks transportation in Peninsular Malaysia that highlight the factor of causing drivers not aware about the road safety for trucks transportation in Peninsular Malaysia which include driver behaviour, attitude and human error, surrounding environment, government legislative and distracted driving. Qualitative research approach is adopted in this study and in-depth interview was conducted to gather the data among the selected trucks operations company in Peninsular Malaysia. The finding show that speed performance results the safety procedure, the company greediness for small gains or profits results the awareness of safety their employees, the government’s legislation punishment is not very effective and also the employees lack of understanding on safety precaution results in their own risk. Therefore, Driver Behaviour, Attitude and Human Error, surrounding Environment, Government Legislative as well as Distracted Driving and Tracking are the important factor that cannot be neglected.

Long-term survival and acute kidney injury during hospitalization after major neurosurgical procedure

Long-term survival and acute kidney injury during hospitalization after major neurosurgical procedure

Attenuation of lipopolysaccharide-induced lung inflammation by ascorbic acid in rats: Histopathological and ultrastructural study.

Introduction:Lipopolysaccharide is a bacterial endotoxin that induces acute lung injury in experimental animals, which is similar to acute respiratory distress syndrome in humans. The induced tissue trauma ends in fibrosis. Understanding the pathogenesis is important in the prevention and treatment of the complications. This study was assigned to investigate the long-term lipopolysaccharide-induced lung injury and the postulated protective effect of ascorbic acid on these changes.Materials and methods:Twenty-four adult male albino rats were divided into three groups. Group I was the controls, group II received lipopolysaccharide and group III received lipopolysaccharide and ascorbic acid. After 30 days of starting treatment, lung tissue samples were obtained.Results:Group II lung tissues showed marked thickening of the alveolar septa with collapsed alveolar sacs, detached bronchial epithelium, inflammatory cell infiltration and excessive deposition of collagen. Group III showed mild thickening of the alveolar walls, scanty inflammatory cell infiltration, mild parabronchial fibrosis and less marked collagen deposition. α-Smooth muscle actin staining of group II showed marked expression of the actin-positive cells. Less potential expression of the dye was found in group III. Ultrastructural examination of group II showed evident structural changes in pneumocytes with capillary basement membrane irregularity and interruption compared to uniform basement membrane in group III with less prominent intracellular changes in pneumocytes.Conclusion:Ascorbic acid attenuated the inflammatory response and fibrosis in the lungs of rats treated with lipopolysaccharide as evidenced by the histological, immunohistochemical and ultrastructural studies.

Effect of small molecular weight soybean protein-derived peptide supplementation on attenuating burn injury-induced inflammation and accelerating wound healing in a rat model

The populations most afflicted by burn injuries have limited abilities to support the significant specialized requirements and costs for acute and long-term burn injury care. This article describes the results of optimizing the use of readily absorbed small molecular weight soybean protein enzymolysis-derived peptide to attenuate rat burn injury-induced inflammation and accelerate wound healing. A major full-thickness 30% total body surface area burn-injury rat model was utilized and the systemic white blood cell (WBC) counts, the relative level of stimulation index of respiratory burst, and the inflammatory markers procalcitonin (PCT), tumor necrosis factor-α (TNF-α), chemokine (C–C motif) ligand 3 (CCL-3), chemokine (C–C motif) ligand 11 (CCL-11) and interleukin-10 (IL-10) were assessed. The burn injury-induced neutrophil and macrophage immune cell infiltration of the cutaneous tissues was detected by immunohistochemical analysis of the protein markers myeloperoxidase (MPO) and cluster of differentiation 68 (CD-68). The local induction of the burn injury-induced toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B (TLR4/NF-κB) signaling pathway in the effected cutaneous tissues was determined by the quantification of the protein expression of TLR4 and phosphorylated NF-κB/p65 using Western blots. In addition, burn wound size and healing rate were assessed biweekly for 8 weeks by imaging and measuring the burn wound surface area, and the angiogenesis protein marker of cluster of differentiation 31 (CD-31) expression in cutaneous tissues was also detected by immunohistochemical analysis. The results showed that nutrient supplementation with optimized readily absorbed small molecular weight soybean protein-derived peptide resulted in a dramatic anti-inflammatory effect as evidenced by the significant increase in the burn injury-induced systemic white blood cell counts and their relative level of stimulation index of respiratory burst, reduction in the burn injury-induced activation of NF-κB transcriptional signaling pathways, significant reduction in the local burn injury-induced cutaneous infiltration of neutrophils and macrophages at all measured time points, reduction in wound size and improved rate of burn injury wound healing with increased CD-31 protein expression. These results indicated that dietary supplementation with small molecular weight soybean-derived peptides could be used as an adjunct therapy in burn injury management to reduce inflammation and improve overall patient outcomes.

Behavioral, cognitive and histological changes following neonatal anoxia: Male and female rats’ differences at adolescent age

Neonatal anoxia induces long-term brain injury that may underlie neurobehavioral deficits at adolescence. Neonatal anoxia, induced by exposure of 30-hour old pups to 100% nitrogen, represents a non-invasive and global stimulus, which simulates clinical conditions of human pre-term babies (around 6 gestational months). Previous studies showed that neonatal anoxia induced impairments of spatial memory and altered anxiety-like behaviors in male rats tested at adult age. This study evaluated if neonatal anoxia induces similar behavioral effects in female rats, as compared to males, by testing the animals at adolescence, and also searched for possible cell losses in hippocampal subfields. Results in the Elevated Plus Maze test showed that anoxic females spent proportionally more time within the open arms as compared to anoxic males, suggesting a less anxious-like behavior. In the Morris Water Maze Test, latencies and path lengths of the anoxic subjects were longer as compared to control subjects, thus indicating that anoxia disrupted the cognitive functions required for spatial mapping. In addition, results showed that anoxia-induced disruption was greater in male rats as compared to female rats. Stereological analysis revealed that anoxic male rats exhibited significant cell losses in the dorsal hippocampus dentate gyrus and CA1 subfields, but not in CA3-2 subfield. Similar results were observed in the ventral hippocampus, but now with cell loss in the male CA3-2 subfield. There were also significant cell loss differences of anoxic male rats as compared to anoxic female rats. In conclusion, neonatal anoxia induces deleterious and long lasting behavioral and cognitive disruptions, and these effects were stronger in male rats as compared to female rats. These changes are congruent with the pattern of cell losses observed in hippocampal subfields. Together, these results emphasize the relevance of scientific research, aiming at clinical strategies and treatments, consider the sex differential patterns of response to neonatal injury.

Effects of High- and Low-LET Radiation on Human Hematopoietic System Reconstituted in Immunodeficient Mice

Over the last 50 years, a number of important physiological changes in humans who have traveled on spaceflights have been catalogued. Of major concern are the short- and long-term radiation-induced injuries to the hematopoietic system that may be induced by high-energy galactic cosmic rays encountered on interplanetary space missions. To collect data on the effects of space radiation on the human hematopoietic system in vivo, we used a humanized mouse model. In this study, we irradiated humanized mice with 0.4 Gy of 350 MeV/n 28Si ions, a dose that has been shown to induce tumors in tumor-prone mice and a reference dose that has a relative biological effectiveness of 1 (1 Gy of 250-kVp X rays). Cell counts, cell subset frequency and cytogenetic data were collected from bone marrow spleen and blood of irradiated and control mice at short-term (7, 30 and 60 days) and long-term ( 6 - 7 months) time points postirradiation. The data show a significant short-term effect on the human hematopoietic stem cell counts imparted by both high- and low-LET radiation exposure. The radiation effects on bone marrow, spleen and blood human cell counts and human cell subset frequency were complex but did not alter the functions of the hematopoietic system. The long-term data acquired from high-LET irradiated mice showed complete recovery of the human hematopoietic system in all hematopoietic compartments. The combined results demonstrate that, in spite of early perturbation, the longer term effects of high-LET radiation are not detrimental to human hematopoiesis in our system of study.

Knowledge and Attitude of Hungarian Athletes towards Long-term Sports Injuries

Abstract The purpose of this study was to investigate long-term sports injuries, their prevalence, general identification of and consultation about injuries, and the knowledge among Hungarian athletes related to injury prevention. A questionnaire was designed to survey athletes regarding these topics. Olympic medal winners, nationally selected athletes, and amateur athletes were surveyed, and altogether 502 completed questionnaires were obtained. The data was analyzed with the Chi-square test for dichotomous variables and the Kruskal-Wallis H-test for questions with the Likert scale to try the statistical power of the hypotheses. The results of our analysis show that athletes suffer injuries regardless of their level of play, and that athletes regard their sports to be moderately dangerous. Most athletes would compete despite the risk of permanent injury; they compete with injuries mostly of their own volition; and they will risk potential injuries or long-term health damage to gain exceptional outcomes. Success is the first and foremost desire of athletes, and the risk of injuries or even long-term health damage does not play an important role in the value system of Hungarian athletes. Sport managers and officers of sport federations must be made aware that the first line of prevention of sport injuries is comprehensive medical consultation with proper medical coverage.

The design, development, implementation and evaluation of IRISweb; A rugby-specific web-based injury surveillance system

ObjectivesTo describe the development, implementation and evaluation of a comprehensive injury surveillance system. DesignThe four phases;i) A survey of 58 medical professionals working in amateur rugby.ii) The design of a web-based injury surveillance system (IRISweb).iii) Recruitment of 21 of the top 58 amateur clubs to use IRISweb.iv) An evaluation survey of the 21 participating clubs. SettingIrish amateur rugby clubs. ParticipantsMedical professionals working in amateur rugby. Main outcome measuresPhase one investigated the injury monitoring practices in operation prior to the IRIS project. Phase four investigated the effectiveness and usefulness of IRISweb. ResultsTwenty-one clubs were recruited, however 2 clubs failed to provide a full season of data (10% dropout rate). Eighty-two percent of the remaining 19 clubs rated IRISweb as ‘good’ or ‘very good’. Facilitators of injury surveillance were; increased player adherence (65%) and notifications to update the system (59%), however, poor player adherence (71%) and medical staff availability (24%) were the main barriers. ConclusionsThe IRIS project is the first prospective long-term injury surveillance system in Irish amateur rugby, effectively tracking injuries to guide future evidence-based injury prevention strategies. This study highlights facilitators and barriers to injury surveillance within amateur sport.

Myokines in Home-Based Functional Electrical Stimulation-Induced Recovery of Skeletal Muscle in Elderly and Permanent Denervation.

Neuromuscular disorders, disuse, inadequate nutrition, metabolic diseases, cancer and aging produce muscle atrophy and this implies that there are different types of molecular triggers and signaling pathways for muscle wasting. Exercise and muscle contractions may counteract muscle atrophy by releasing a group of peptides, termed myokines, to protect the functionality and to enhance the exercise capacity of skeletal muscle. In this review, we are looking at the role of myokines in the recovery of permanent denervated and elderly skeletal muscle tissue. Since sub-clinical denervation events contribute to both atrophy and the decreased contractile speed of aged muscle, we saw a parallel to spinal cord injury and decided to look at both groups together. The muscle from lifelong active seniors has more muscle bulk and more slow fiber-type groupings than those of sedentary seniors, demonstrating that physical activity maintains slow motoneurons that reinnervate the transiently denervated muscle fibers. Furthermore, we summarized the evidence that muscle degeneration occur with irreversible Conus and Cauda Equina syndrome, a spinal cord injury in which the human leg muscles may be permanently disconnected from the peripheral nervous system. In these patients, suffering with an estreme case of muscle disuse, a complete loss of muscle fibers occurs within five to ten years after injury. Their recovered tetanic contractility, induced by home-based Functional Electrical Stimulation, can restore the muscle size and function in compliant Spinal Cord Injury patients, allowing them to perform electrical stimulation-supported stand-up training. Myokines are produced and released by muscle fibers under contraction and exert both local and systemic effects. Changes in patterns of myokine secretion, particularly of IGF-1 isoforms, occur in long-term Spinal Cord Injury persons and also in very aged people. Their modulation in Spinal Cord Injury and late aging are also key factors of home-based Functional Electrical Stimulation - mediated muscle recovery. Thus, Functional Electrical Stimulation should be prescribed in critical care units and nursing facilities, if persons are unable or reluctant to exercise. This will result in less frequent hospitalizations and a reduced burden on patients’ families and public health services.

Very Delayed Remote Ischemic Post-conditioning Induces Sustained Neurological Recovery by Mechanisms Involving Enhanced Angioneurogenesis and Peripheral Immunosuppression Reversal.

Ischemic conditioning is defined as a transient and subcritical period of ischemia integrated in an experimental paradigm that involves a stimulus of injurious ischemia, activating endogenous tissue repair mechanisms that lead to cellular protection under pathological conditions like stroke. Whereas ischemic pre-conditioning is irrelevant for stroke treatment, ischemic post-conditioning, and especially non-invasive remote ischemic post-conditioning (rPostC) is an innovative and potential strategy for stroke treatment. Although rPostC has been shown to induce neuroprotection in stroke models before, resulting in some clinical trials on the way, fundamental questions with regard to its therapeutic time frame and its underlying mechanisms remain elusive. Hence, we herein used a model of non-invasive rPostC of hind limbs after cerebral ischemia in male C57BL6 mice, studying the optimal timing for the application of rPostC and its underlying mechanisms for up to 3 months. Mice undergoing rPostC underwent three different paradigms, starting with the first cycle of rPostC 12 h, 24 h, or 5 days after stroke induction, which is a very delayed time point of rPostC that has not been studied elsewhere. rPostC as applied within 24 h post-stroke induces reduction of infarct volume on day three. On the contrary, very delayed rPostC does not yield reduction of infarct volume on day seven when first applied on day five, albeit long-term brain injury is significantly reduced. Likewise, very delayed rPostC yields sustained neurological recovery, whereas early rPostC (i.e., <24 h) results in transient neuroprotection only. The latter is mediated via heat shock protein 70 that is a well-known signaling protein involved in the pathophysiological cellular cascade of cerebral ischemia, leading to decreased proteasomal activity and decreased post-stroke inflammation. Very delayed rPostC on day five, however, induces a pleiotropic effect, among which a stimulation of angioneurogenesis, a modulation of the ischemic extracellular milieu, and a reversal of the stroke-induced immunosuppression occur. As such, very delayed rPostC appears to be an attractive tool for future adjuvant stroke treatment that deserves further preclinical attention before large clinical trials are in order, which so far have predominantly focused on early rPostC only.

Barriers and facilitators to integration of care for children with complex care needs across 30 European countries: A MOCHA study

Introduction: Approaches to the management of care of children with complex care needs CCN is known to vary among countries. Conducted as part of Models of Child Health Appraised MOCHA, an ongoing EU Horizon 2020 funded project, the aim of this study was to provide a contemporary account of the approaches to the integration of care at the acute/community interface for children with CCN across 30 European countries. Methods: In this non-experimental descriptive study, utilising a mixed-methods design, 30 European countries were surveyed, using a local country agent who was an expert in child health. Each survey consisted of a vignette and open and closed-ended questions adapted from the Standards for Systems of Care for Children and Youth with Special Health Care Needs 1 and the Eurobarometer Survey 2. Vignettes were developed based on three clinical exemplars: Long-term Ventilation LTV, Intractable Epilepsy, and Traumatic Brain Injury TBI. Categorical data were analysed using descriptive statistics. Textual data were analysed using Attride-Stirling’s thematic network analysis 3. This abstract presents results pertaining to the qualitative analysis of the main barriers and facilitators to the integration of care for each exemplar. Results: Twenty-three countries 76.7% responded to the three surveys. Barriers to integration of care were similar across all exemplars and included; poor care coordination, lack of clinical expertise and training, insufficient funding, the absence of standards of care, lack of specialist clinical pathways, geographical variation in care, limited progress in the use electronic health, and inadequate access to psychological support. Training and retention of skilled healthcare staff were identified as a facilitator of integration of care across all exemplars. The need for a national database LTV & TBI, timely transfers to specialist services LTV & TBI and enhanced family and school support TBI & Intractable Epilepsy were identified for two of the three exemplar conditions. Discussions: Although commonalities exist across the results presented, there may be individual critical junctures in care delivery that will demand care provisions that are specific to particular cohorts of children with different complex conditions. Conclusions: The results suggest that there are a variety of processes and structures that act as barriers and facilitators to the integration of care for children with CNN across Europe. Lessons learned: This study was reliant on data from a large number of informants being collated by local country agents across the 30 MOCHA countries. The process was assisted by the development and utilisation of a glossary of terms in each survey, which ensured uniform comprehension of the included terms. Limitations: Previous research has posed concerns regarding the external validity of using clinical vignettes to elicit opinion 4,5. Nonetheless, the use of clinical vignettes in this study allowed for the creation of a variety of care delivery situations pertaining to complex care that could be utilised in a standardised manner in surveys developed for use across 30 European countries. Suggestions for future research: Future research should be considered to explore innovative ways of minimising the barriers to integration of care for children with CCN.