Background: This review aims to explore the regulatory mechanism of microglial exosomes, particularly focusing on the role of miR-124-3p, in modulating neuroinflammation and promoting neuronal repair following traumatic brain injury (TBI). Methods: Multiple studies investigating the impact of microglial exosomal miRNAs, specifically miR-124-3p, on injured neurons and brain microvascular endothelial cells (BMVECs) in the context of TBI were reviewed. Results: Animal models of TBI, in vitro cell culture experiments, RNA sequencing analysis, and functional assays were employed to elucidate the mechanisms underlying the effects of miR-124-3p-loaded exosomes on neuroinflammation and neuronal repair. The increased expression of miR-124-3p in microglial exosomes after TBI inhibited neuronal inflammation and promoted neurite outgrowth. This effect was achieved by promoting the anti-inflammatory M2 polarization of microglia, suppressing mTOR signaling through downregulation of PDE4B, and inducing autophagy in BMVECs. These actions collectively contributed to neuroprotection, reduced blood-brain barrier leakage, and improved neurologic outcomes in animal models of TBI. Conclusion: Microglial exosomes, particularly those carrying miR-124-3p, have emerged as promising candidates for therapeutic interventions in TBI. These exosomes exhibit neuroprotective effects, attenuate neuroinflammation, and promote neuronal repair and plasticity. Targeting miR-124-3p and utilizing microglial exosomes as therapeutic agents hold great potential for future clinical translation in TBI management. However, further research is required to fully elucidate the underlying mechanisms and optimize their delivery strategies for effective treatment in human TBI cases.

Body weight support (BWS) and incline running (IR) are commonly used either during rehabilitation or during training separately, with many positive effects on athletes’ performance and rehabilitation. The aim of this study is to investigate the effect of BWS and IR. In eighteen healthy men (age: 20.3 ± 1.2 yr, body weight: 70.2 ± 4.8 kg, body height: 179.6 ± 5.4 cm), the changes in electromyographic activity (EMGA) during a 10-min run with BWS (15% or 30% of body weight; in different occasions) and IR at 7%, as well as jumping performance and gait spatiotemporal parameters were evaluated. Lower Rating of Perceived Exertion and a significant decrease in VL (33,4%), SOL (17%), and GL EMGA (28.5%, p < 0.05) but not in GM (10.5%, p > 0.05), were observed during BWS30% at 7% slope compared to flat running. Also, low-frequency fatigue of the quadriceps was induced only after running without BWS at 7% slope (P = 0.011). No changes were found in jumping performance (p = 0.246) and gait spatiotemporal parameters (p > 0.05) except for flight time (p < 0.006). In conclusion, compared to normal flat running, BWS reduces electromyographic activity and fatigue during slope running.

The alterations of coagulation status in patients with Severe Burn Injury are associated with serious complications, increased morbidity and mortality. This study aims to compare Rotational Thromboelastometry(ROTEM)–a Viscoelastic Coagulation Assays(VCAs) with Conventional Coagulation Assays(CCAs) including Prothrombin time(PT), Activated Partial Thromboplastin time(aPTT), International normalized ratio(INR), Complete Blood Count(CBC) and Coagulation Factors during the early five post- burn days in Survivors and Non- Survivors with Severe Burn Injury in order to correlate these results with Burn Coagulopathy and Prognosis. Seventeen Sur-vivors and ten Non- Survivors, with a mean Total Burn Surface Area(TBSA) of 33,78% were in-cluded in our study. Even though CCAs measurements were abnormal, they were unable to detect overall burn patients’ coagulopathy. On the contrary, VCAs from day 2 to day 5 took pathological values, especially for Non- survivors. Those changes were underlined through pathological values of Coagulation Factors. As a result, CCAs were considered poor indicators of coagulation status in burn injury, whereas VCAs were more accurate in demonstrating coagulation alterations from the early post- burn period and detecting patients in greater risk of mortality. These advantages of VCAs could be used for timely intervention in high risk patients and for the guidance of blood product transfusions.

Background and Objectives: Angioembolization has emerged as an effective therapeutic approach for pelvic hemorrhages; however, its exact effect size remains uncertain. Therefore, we conducted this systematic review and meta-analysis to investigate the effect size of embolization-related pelvic complications after nonselective angioembolization compared to that after selective angioembolization in patients with pelvic injury accompanying hemorrhage. Materials and Methods Relevant articles were collected by searching the PubMed, EMBASE, and Cochrane databases until June 24, 2023. Meta-analyses were conducted using odds ratios (ORs) for binary outcomes. Quality assessment was conducted using the risk of bias tool in non-randomized studies of interventions. Results: Five studies examining 357 patients were included in the meta-analysis. Embolization-related pelvic complications did not significantly differ between patients with nonselective and selective angioembolization (OR 1.581, 95% confidence interval [CI] 0.592 to 4.225, I2 = 0%). However, in-hospital mortality was more likely to be higher in the nonselective group (OR 2.232, 95% CI 1.014 to 4.913, I2 = 0%) than in the selective group. In the quality assessment, two studies were found to have a moderate risk of bias, whereas two studies exhibited a serious risk of bias. Conclusions: Despite the favorable outcomes observed with nonselective angioembolization concerning embolization-related pelvic complications, determining the exact effect sizes was limited owing to the significant risk of bias and heterogeneity. Nonetheless, the low incidence of ischemic pelvic complications appears to be a promising result.

There is a growing interest in glial cells in the central nervous system due to their important role in maintaining brain homeostasis both under physiological conditions and after injury. A significant amount of evidence has been accumulated regarding their capacity to exert either pro-inflammatory or anti-inflammatory effects under different pathological conditions. In combination with their known proliferative potential, they contribute not only to the limitation of brain damage and tissue remodeling but also to neuronal repair and synaptic recovery. Moreover, reactive glial cells can modulate the processes of neurogenesis, proliferation, and migration of neurons in the existing neural circuits in the adult brain. By discovering precise signals within specific niches, the regulation of sequential processes in adult neurogenesis holds the potential to unlock strategies that can stimulate the generation of functional neurons, whether in response to injury or as a means of addressing degenerative neurological conditions. Cerebral ischemic stroke, a condition falling within the realm of acute vascular disorders affecting the circulation of the brain, stands as a prominent global cause of disability and mortality. Extensive investigations into glial plasticity and their intricate interactions with other cells in the central nervous system have predominantly relied on studies conducted on experimental animals, including rodents and primates. However, valuable insights have also been gleaned from in vivo studies involving post-stroke patients, utilizing highly specialized imaging techniques. Following the attempts to map brain cells, the role of various transcription factors in modulating gene expression in response to cerebral ischemia is gaining increasing popularity. Although the results obtained thus far remain incomplete and occasionally ambiguous, they serve as a solid foundation for the development of strategies aimed at influencing the recovery process after ischemic brain injury.

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany and the retraction of phenformin (N-Phenethylbiguanide) because of the letal complication of acidosiss,metformin (1-1-dimethylbiguanide) was first released in France in 1959 and then in the USA in 1995 for oral treatment of diabetes type 2. Acute gastrointestinal side effects often lead to dose reduction and strongly limit adherence to therapy.Main long-term consequences are deficency of vitamin B12 and of iron and sometimes also acidosis development. Intravenously injected F18-labelled glucose in metformin-treated type 2 diabetics accumulates in the the small and even more in the large intestine.The densitometry picture observed in metformin-treated diabetics is similar to that observed in patients after bowel-cleansing or chronically taking different types of laxatives where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to „attraction“ of glucose from the hepatocyte to the intestine,possibly through its secretion into the bile.Metformin is not different from the other biguanides ,synthalin B and phenformin.The mechanism of action,and the side effects are comparable to those of laxatives.

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p < 0.001). Its concentration >2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values >5.1 nmol/l and urine TIMP2*IGBP7 levels > 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

The knowledge on anatomy, function, biomechanics, and role on surgical procedures of the anterolateral ligament (ALL) of the knee is still controversial. Only a few papers have examined the ALL in children. The aim of this review is to analyse all the available literature about ALL in pediatric population. Following the PRISMA criteria, the literature was systematically reviewed, examining all the articles about ALL in pediatric patients. Eight articles were involved in the study. Five cadaveric studies, 2 diagnostic studies and 1 Cross-sectional study were found. The identification of the ALL is not always possible in diagnostic studies using the Magnetic Resonance (MRI) or in dissecting specimens. A high variability in the presence of the ligament, in its origin and insertion were found among the studies. In younger patients is more difficult to identify the ligament than in older children, suggesting that its presence may develop at some point during the growth. Further studies are needed for a detailed knowledge of the ALL.

COVID-19 is a highly infectious respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major cause of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6, TNF-α, and TGF-β1) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

GI endoscopy forms an important part in a daily practice of a gastroenterologist. Musculoskeletal injuries related to GI endoscopy are on the rise. Observational studies and surveys depict the importance of proper ergonomical environment when performing GI endoscopy. Our aim is to outline preventive measures in gastrointestinal (GI) endoscopy in reducing possibility for occupational injury. We review most relevant studies that outline the gravity of the problem. A detailed analysis of proposed ergonomical recommendations is performed, outlining crucial steps in injury prevention. Proper ergonomical education is a key-step in preventing occupational injury. Robotics and other mechanical solutions offer a variety of approaches tackling the ergonomical challenge. Implementing proper ergonomical education and mechanical solutions lowers the possibility if occupational injury. Strategies and appliances presented are beneficial to all GI endoscopy practitioners.

Streptococcus pneumoniae is one of the associated bacteria that can cause the rare but high mortality hematological disease known as purpura fulminans (PF) in both adults and children. Patients with PF can progress quickly to sepsis and multiorgan failure, especially in immunocompromised individuals and young children. Due to the thrombotic blockage of blood arteries in PF, there is diffuse intravascular thrombosis and hemorrhagic infarction of the skin, which evolves from ecchymosis to skin necrosis, risk of limb sequelae, sepsis and fatality. We present a case of a previously healthy 1-year and 9-month female who was admitted to the Intensive Care Unit of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș"- Bucharest, Romania. The patient presented with erythematous patches on left upper limb and trunk, tachycardia, tachypnea, hypotension, anuria and altered sensorium with an indication of intubation for 8 Glasgow Coma Scale (GCS). Cerebrospinal culture grew Streptococcus pneumoniae serotype 1. She required peritoneal dialysis due to acute kidney injury (AKI) and surgeries for affected areas. After multiple organ system failures, our patient evolved rapidly to irreversible tissue necrosis and death. We aim to report a rare case of PF associated with pneumococcal meningoencephalitis in immunocompetent children to better appreciate the risk of fatal evolution when managing this disease in children. To date, few studies report favourable evolution. We discuss the etiology, rapid diagnosis and treatment of immunocompetent children with PF and the importance of interprofessional teams to increase the outcomes in patients with infectious diseases.

Background: This study investigated the incidence, characteristics and functional outcomes associated with unplanned Acute Care Unit Readmissions (ACUR) during inpatient traumatic brain injury (TBI) rehabilitation in an Asian cohort. Methods: Retrospective review of electronic medical records from single rehabilitation unit was conducted from 1 Jan 2012 to 31 Dec 2014. Inclusion criteria were first TBI, aged &gt;18 years, admitted &lt; 6 months of TBI. ACUR were characterized into either of neurological, medical or neurosurgical subtypes. The main outcome measure was discharge Functional Independence Measure (FIM). Secondary outcomes included rehabilitation length of stay (RLOS). Results: Of 121 eligible TBI records, the incidence of ACUR was 14% (n=17), comprising neurologic (76.5%) and medical (23.5%) subtypes, occurring at median of 13 days (IQR 6, 28.5) after rehabilitation admission. Patients without ACUR had significantly higher admission mean (SD) FIM score compared to those with ACUR (FIM ACUR-negative 63.4 (21.1) vs FIM ACUR-positive 50.53(25.4), P =0.026). Significantly lower discharge FIM was noted in those with ACUR compared to those without. (FIM ACUR-positive 65.8(31.4) vs FIM ACUR-negative 85.4 (21.1), P = 0.023) Furthermore, a significant near-doubling of RLOS was noted in ACUR patients compared to non-ACUR counterparts [ACUR-positive median 55 days (IQR 34.50, 87.50) vs ACUR-negative median 28 days (IQR 16.25, 40.00), P = 0.002]. Conclusion: This study highlights the significant negative functional impact and lengthening of rehabilitation duration of ACUR on inpatient rehabilitation outcome for TBI.

Burn injuries have profound implications for aesthetics, functionality, and patient survival. Umbilical cord lining mesenchymal stem cells (SCL-MSCs) have emerged as a potential therapeutic approach for burn wounds due to their easy isolation, favorable differentiation capabilities, and low immunogenicity. This study aimed to evaluate the growth characteristics of SCL-MSCs and their effectiveness in treating burn wounds. Mechanical isolation was employed to extract mesenchymal stem cells from the umbilical cord lining membrane. The isolated cells underwent characterization, including analysis of HLA-E, G, and DR expression, and assessment of immunogenicity against rabbit antigens using ELISA. A rabbit model was utilized to administer burn treatment. SCL-MSCs exhibited typical morphology of mesenchymal stem cells and demonstrated robust proliferation. These cells expressed CD90, HLA-E, and HLA-G markers while lacking HLA-DR expression. Intact cells and supercrushed cell fluid displayed minimal and unstable immunogenicity. SCL-MSCs exhibited remarkable differentiation potential toward fibroblast lineages, with differentiated fibroblasts showing elevated collagen production and efficient sheet formation. In the experimental rabbit model, burn wounds covered with SCL-MSC tegaderm material plates exhibited superior healing compared to controls. The stem cell material plate area demonstrated reduced inflammatory cell counts (P &lt; 0.01) and increased fibroblast count, neovascularization, and mitotic index (P &lt; 0.01). These findings highlight the potential of SCL-MSCs as a valuable resource for burn wound research and treatment.

Spinal Cord Injury in children can be a devastating condition in children with profound implications for their overall health and quality of life. In this review we aim to provide a concise overview of the key aspects associated with SCI in pediatric population. Firstly, we discuss the etiology and epidemiology of SCI in children, highlighting the diverse range of causes. We explore the unique anatomical and physiological characteristics of the developing spinal cord that contribute to the specific challenges faced by pediatric patients. Next, we delve into the clinical presentation and diagnostic methods, emphasizing the importance of prompt and accurate diagnosis to facilitate appropriate interventions. Furthermore, we approach the multidisciplinary management of pediatric SCI, encompassing acute medical care, surgical interventions, and ongoing supportive therapies. Finally, we explore emerging research and innovative therapies in the field and we emphasize the need for continued advancements in understanding and treating SCI in children to improve their functional independence and overall quality of life.

Long coronavirus disease 2019 (COVID-19) may occur after experiencing acute COVID-19 infec-tion with many effects on patients´ kidneys. This study aimed to evaluate the clinical and labora-tory aspects of kidney function in individuals with long COVID in the Amazon region of Brazil. This cross-sectional study selected participants from a ‘long COVID’ clinical care program. Clini-cal data and baseline demographics were obtained, and blood samples were collected to quantify kidney-related markers. Patients were evaluated after COVID-19 infection at several time points as follows: 0–3 months, 3–6 months, 6–12 months, and 12 months. Altogether, 246 patients were selected for this study, and only 79 were hospitalised (9 in the intensive care unit because of COVID-19. Of the patients, 38 were diagnosed with hypertension after COVID-19, 52 cases had to have their medications adjusted, and 83 patients presented with kidney function decline. The older age group and individuals with glycaemic alterations presented with a higher risk of devel-oping kidney dysfunction. Therefore, health professionals should monitor long-term kidney mark-ers in long COVID.

Single and multi-vehicle crashes are a significant issue that causes economic and social costs and has therefore gained attention. This study explored the factors associated with injury severity for both single- and multi-vehicle crashes using over 550,000 crash data points in Japan between 2019 and 2021. We identified the determinants of road infrastructure and traffic control while controlling for driver, vehicle, environmental, and accident characteristics by applying ordered logit and bias-reduced binomial regression models. Our findings are as follows. 1) Traffic control variables did not affect single-vehicle crashes. 2) Guardrails had a higher severity in both single-vehicle crashes and multi-vehicle crashes at intersections. 3) The impact of the centerline differed between intersections and non-intersections for multi-vehicle crashes.  These results of this study provide transportation agencies with important guidance as to the road infrastructure and transport control.

Accidental soft tissue injuries are a frequent injury. We report a case involving a 37-year-old man with a soft tissue wound failing conservative treatment. The use of applied fibrin membranes and concentrated growth factors yielded a resolution of the injury in 16 months without need of skin grafting.

Background: Early diagnosis of acute brain injury (ABI) is critical for patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) to guide anticoagulation strategy; however, neurological assessment in ECMO is often limited by patient sedation. Methods: In this pilot study of adults from June 2018 to May 2019, plasma samples of glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and Tau were collected daily after VA-ECMO cannulation and measured using a multiplex platform. Primary outcomes were the occurrence of ABI, assessed clinically, and neurologic outcome, assessed by modified Rankin Scale (mRS). Results: Of 20 consented patients (median age=48.5 years; 55% female), 8 (40%) had ABI and 15 (75%) had unfavorable neurologic outcomes at discharge. 10 (50%) patients were centrally cannulated. The median duration on ECMO was 4.5 days (IQR: 2.5-9.5). Peak GFAP, NFL, and Tau levels were higher in patients with ABI vs. without (AUC = 0.77; 0.85; 0.57, respectively) and in patients with unfavorable vs. favorable neurologic outcomes (AUC = 0.64; 0.59; 0.73, respectively). GFAP elevated first, NFL elevated to the highest degree, and Tau showed limited change regardless of ABI. Conclusion: Plasma biomarkers may facilitate early detection of ABIs in VA-ECMO where neurological exam is limited and assist timely clinical decision-making.

The cough assessment is fundamental in the weaning process as it gives information on the possibility to expel food and secretion from the airways. The majority of persons suffering from severe acquired brain injury (ABI) are not able to cough voluntarily due to severe motor deficits. In the present study, we evaluated the cough reflex in ABI patients using a new method based on a capsaicin spray stimulation test. 100 Healthy controls demographically matched with 50 ABI patients were included in this study. Clinical observations demonstrated robust cough response in both healthy controls and ABI patients, as well as the safety and tolerability of capsaicin spray stimulation. ABI patients with dysphagia were characterized by slower and delayed cough responses. Further studies are needed to validate this feasible, less-invasive, and simple-to-comprehend technique in inducing cough reflex. According to this preliminary evidence, we believe that this test might be translated into a simple and effective treatment to improve cough strength training reflexive cough modulation in ABI patients.

Background: Craniofacial injuries are thought to be commonly associated with traumatic brain injury (TBI), but there is conflicting evidence in the literature. The objective of this retrospective cohort study is to evaluate the incidence of TBI in patients with craniofacial trauma. Methods: The study included 2982 consecutive patients with either solitary or concurrent diagnoses of TBI and facial fractures, seen and evaluated at a single level II trauma center between January 1, 2010 and December 31, 2020. Continuous variables were compared against whether the patient had one or both diagnoses.Results: Of the target population, 55.8% had a solitary diagnosis of TBI, 30.28% had a solitary diagnosis of facial fractures, and 13.92% had concurrent diagnoses of both TBI and facial fractures. Patients with concurrent diagnoses had a significantly longer mean length of stay (LOS) compared to those with solitary diagnoses (9.92 ± 16.33 days vs. 6.21 ± 10.96 days, p&lt;0.01), but age (p=0.68) and ICU LOS (p=0.09) did not differ significantly between the two groups. Conclusions: Trauma to the face should be given special attention due to the close relationship between facial bones and the brain. Patients with concurrent diagnoses of TBI and facial fractures had worse hospital outcomes than those with solitary diagnoses of either TBI or facial trauma.

Mild TBI (mTBI) accounts for most TBI cases, the leading cause of morbidity and mortality worldwide. Despite their high incidence, mTBI pathophysiology remains largely unknown. Recent studies have shown that the inflammatory response is activated early after mTBI and can persist for several weeks or months. However, limited evidence on the utility of inflammatory biomarkers as predictors of clinical outcomes in mTBI was previously provided. Thus, this study aims to provide an overview of the current knowledge on the role of inflammation in the pathogenesis of mTBI and the potential of some inflammatory biomolecules as biomarkers of mTBI. Thus, it was shown that the increase of IL-6, TNF-α, and IL-1β plasma levels could be implicated in the development of the early post-concussion symptoms. On the other hand, the persistence of the increased plasmatic concentrations of IL-10 and IL-8 for as long as six months following the brain injury event could suggest chronic inflammation leading to neuroinflammation and late or persistent symptoms. In this context, our findings showed that the inflammatory biomarkers could be relevant in diagnosing or predicting recovery or long-term outcomes of mTBI.

Background: The systemic inflammatory index (SII) is a new inflammatory marker that has been the subject of various studies in diseases with chronic inflammation. Diabetic nephropathy is also a disease that goes with chronic inflammation. We aimed to evaluate the relationship be-tween SII and diabetic nephropathy. Methods: Patients with diabetes who applied to our outpatient clinic are included in the study. Diabetic patients are divided into two groups: those with diabetic nephropathy and those with-out. In addition, healthy individuals who applied to our clinic for general check-ups during these dates are included as control group. The SII values and other characteristics of the three study groups are compared. Results: The median SII value for those with DKI was 584 (178-4819); for those without DKI, it was 282 (64-618); and for the control group, it was 236 (77.5-617) (p<0.001). SII was significantly and positively correlated with BMI, weight, blood glucose, HbA1c, CRP and creatinine, and neg-atively correlated with glomerular filtration rate (GFR) value. The SII value higher than 336 has 75% sensitivity and 70% specificity in detecting DKI. Conclusion: The SII value could predict diabetic kidney injury in diabetics and it could be used as an adjunctive diagnostic tool.

Purpose: To reassess the results of former meta-analyses focusing on the relationship between novel HES preparations (130/0.4 and 130/0.42) and acute kidney injury. Previous meta-analyses are based on studies referring to partially or fully unpublished data or data from abstracts only. Methods: The studies included in the former meta-analyses were scrutinized by the authors independently. We completed a critical analysis of the literature, including the strengths, weaknesses and modifiers of the studies when assessing products, formulations and outcomes. Results: Both the published large studies and meta-analyses show significant bias in the context of the deleterious effect of 6% 130/0.4-0.42 HES. Without (1) detailed hemodynamic data, (2) the exclusion of other nephrotoxic events and (3) a properly performed evaluation of the dose-effect relationship; the AKI-inducing property of 6% HES 130/0.4 or 0.42 could not be accounted as evidence. The administration of HES is safe and effective if the recommended dose is respected. Conclusion: Our review suggests that there is questionable evidence for the deteriorating renal effect of these products. Further well-designed, randomized and controlled trials are needed. Further conclusions formulated for resource-rich environments should not be extended to more resource-scarce environments without proper qualifiers provided.

Soccer is type of sport that carries a high risk of injury. Injury is not only cause in the unlucky soccer carrier and also team performance as well as financial effects can be worse since soccer is a team-based game. The duration of recovery from a soccer injury typically relies on its type and severity. Therefore, we conduct this research in order to predict the probability of players injury type using machine learning technologies in this paper. Furthermore, we compare different machine learning models to find the best fit model. Supervised classification machine learning models are applied in this paper. We gathered information about 54 professional soccer players who are playing in the top five European leagues based on their career history.

This study aimed to describe the injury profiles of young Korean baseball players according to position and age as the proportion and distribution of injuries based on playing position and age remains unclear. A total of 271 elite youth baseball players aged 8 to 16 years were divided into two groups: elementary school (ES) (n=135) and middle school (MS) (n=136). The participants' basic, baseball practice, and injury information were collected. Injuries in the MS group were not limited to the elbow and shoulder, and the injury prevalence varied by age group and baseball position. The most injured body region in the ES group was the elbow joint, regardless of the position. In contrast, the most injured body region in the MS group was the lower back, except for infielders whose elbows were the most injured. Additionally, the MS group was more likely to experience injuries of the lower back (OR=4.27, 95% CI=2.47–7.40), shoulder (OR=1.93, 95% CI=1.08–3.43; P=0.024), and knee (OR=2.15, 95% CI=1.17–3.94; P=0.012). Our findings indicate that excessive practice and lack of rest during MS (growth spurt period) can significantly increase the risk of lower back problems in young baseball players.

Prolonged exercise induces acute renal injury; however, the precise mechanism remains unclear. We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody, sedentary with antineutrophil antibody, exhaustive exercise with control antibody, and exhaustive exercise with antineutrophil antibody. Antineutrophil (1A8) or control antibody was administered intraperitoneally to the mice prior to their running on a treadmill. Renal histology was assessed 24 h after exhaustive exercise, and the concentration of kidney injury molecule (KIM)-1 was measured using enzyme-linked immunosorbent assay. The expression levels of inflammatory cytokines were measured using quantitative reverse transcriptase-polymerase chain reaction. Furthermore, nicotinamide adenine dinucleotide phosphate oxidase activity and hydrogen peroxide concentration in the kidneys were measured. The pathologic changes were manifested as congested and swollen glomeruli, tubular dilatation, and nuclear infiltration after exhaustive exercise. These changes were suppressed by the administration of the 1A8 antibodies. KIM-1 concentration increased after exhaustive exercise but were reduced by the 1A8 antibodies. Treatment with the 1A8 antibody also decreased exhaustive exercise-induced inflammation and reactive oxygen species levels in the kidney. These results suggest that neutrophils contribute to exercise-induced acute renal injury by regulating inflammation and reactive oxygen species levels.

The study aimed to identify football players at high risk (HR) for anterior cruciate ligament (ACL) injury via a four-test battery and assess possible factors affecting classification. Ninety-one professional and semi-professional athletes participated in a field-based preseason screening. Aknowledged inter-limb asymmetry limits for quadriceps and hamstrings isometric strength, and Single Leg Triple Hop for distance, in addition to the Landing Error Scoring System (LESS) comprised the test-battery. Additional assessment of hip adductors and core stability completed the global functional profile of the players. Sixty-one players were identified as HR and 30 as low-risk (LR) for ACL injury. Test-battery classified adequately 78,0% of them (Chi-square= 27,485 p=,000), identifying only 4 misclassified cases in the LR group, this low number being important for avoiding improper treatment of injury-prone athletes. All partcipants were considered healthy, and history of a previously rehabilitated injury did not interfere with the results. LESS seems to be the optimal criterion for classification and also the best predictor of both the initial grouping and the secondary one with the wrong vs correct classification cases. The proposed test-battery provides a promising option for field-based preseason ACL-risk assessment of football players and needs to be studied prospectively.

Despite the available literature on traumatic brain injury (TBI) biomarkers elsewhere, data are limited or non-existent in sub-Saharan Africa (SSA). The aim of the study was to analyse associations in acute TBI between admission serum biomarker concentrations and TBI severity, CT-scan findings and outcome as well as explore the influence of concurrent Toxoplasma gondii infection. Concentrations of serum biomarkers (GFAP, NFL Tau, UCH-L1, and S100B) were measured and Toxoplasma gondii detected in samples obtained <24 hours post-injury. The GOSE was used to evaluate 6 months outcome. All biomarkers levels increased with severity of TBI, but this increase was significant only for NFL (P=0.01). GFAP values significantly increased (P=0.026) in those with unfavorable outcome. Tau levels were higher in those who died (P=0.017). GFAP and NFL were sensitive to CT-scan pathology (p values respectively 0.004 and 0.002). S100B levels were higher (P<0.001) in TBI patients seropositive to Toxoplasma gondii. NFL was found to be sensitive to TBI severity while NFL and GFAP were predictive of CT intracranial abnormalities. Increased levels of GFAP and Tau were associated with poorer outcomes 6 months after TBI. S100B levels were significantly higher in T. gondii seropositive TBI patients.

Spinal cord injury (SCI) is a condition that affects between 8.8 and 246 people in a million and, unlike many other neurological disorders, it affects mostly young people, causing deficits in sensory, motor, and autonomic functions. Promoting regrowth of axons is one of the most important goals for the neurological recovery of patients after SCI, but it is also one of the most challenging goals. A key event after SCI is the formation of a glial scar around the lesion core, which is mainly comprised of astrocytes, NG2+-glia, and microglia. Traditionally, the glial scar has been regarded as detrimental for recovery because it may act as a physical barrier for axon regrowth and release various inhibitory factors. However, more and more evidence now suggest that the glial scar is beneficial for the surrounding spared tissue after SCI. Here, we review experimental studies that used genetic and pharmacological approaches to ablate specific populations of glial cells in rodent models of SCI, in order to understand their functional role. The studies showed that ablation of either astrocytes, NG2+-glia or microglia may result in disorganization of glial scar, increased inflammation, extended tissue degeneration and impaired recovery after SCI. Hence, glial cells and glial scar appear as important beneficial players after SCI.

Extracorporeal membrane oxygenation (ECMO), in conjunction with its life-saving benefits, carries a significant risk of acute brain injury (ABI). Hypoxic-ischemic brain injury (HIBI) is one of the most common types of ABI in ECMO patients. Various risk factors such as history of hypertension, high day 1 lactate level, low pH, cannulation technique, large peri-cannulation PaCO2 drop (∆PaCO2), and early low pulse pressure, have been associated with the development of HIBI in ECMO patients. The pathogenic mechanisms of HIBI in ECMO are complex and multifactorial, attributing to the underlying pathology requiring initiation of ECMO and the risk of HIBI associated with ECMO itself. HIBI is likely to occur in the peri-cannulation or peri-decannulation time secondary to underlying refractory cardiopulmonary failure before or after ECMO. Current therapeutics target pathological mechanisms, cerebral hypoxia and is-chemia, by employing targeted temperature management in the case of extracorporeal cardiopulmonary resuscitation (eCPR), and optimizing cerebral O2 saturations and cerebral perfusion. This review describes the pathophysiology, neuromonitoring, and therapeutic techniques to improve neurological outcomes in ECMO patients so as to prevent and minimize the morbidity of HIBI. Further studies aimed at stand-ardizing the most relevant neuromonitoring techniques, optimizing cerebral perfusion, and minimizing the severity of HIBI once it occurs will improve long-term neurological outcomes in ECMO patients.

Traumatic brain injury (TBI) affects millions of people annually, however, our knowledge of the diffuse pathologies associated with TBI is limited. As diffuse pathologies, including axonal injury and neuroinflammatory changes, are difficult to visualize in the clinical population, animal models are used. In the current study we used the central fluid percussion injury (CFPI) model in a micro pig to study the potential scalability of these diffuse pathologies in a gyrencephalic brain of a species with inflammatory systems very similar to humans. We found that both axonal injury and microglia activation within the thalamus and corpus callosum are positively correlated to the weight-normalized pressure pulse, while subtle changes in blood gas and mean arterial blood pressure are not. We also found that the majority of tissue generated up to 10 years previously is viable for immunofluorescent labeling after long-term refrigeration storage. This study indicates that a micro pig CFPI model could allow for specific investigations of various degree of diffuse pathological burdens following TBI.

Background: Thoracic endovascular aortic repair (TEVAR) has become the standard treatment for blunt thoracic aortic injury (BTAI). Some small observational studies revealed aortic morphological changes after TEVAR in patients with BTAI. However, these studies were limited by the rarity of the condition and small sample sizes. To address this gap, the current study aims to conduct a systematic review and meta-analysis of existing literature to provide evidence on the degree of immediate and long-term aortic diameter change following TEVAR for BTAI. Methods: This systematic review and meta-analysis of studies published up to March 2023, was conducted in accordance with the PRISMA statement. Studies eligible for inclusion were studies evaluating aortic diameter change post-TEVAR in BTAI patients. Results: 14 articles, including 353 patients, were included after review. Treatment and measurement protocols varied among individual studies resulting in high heterogeneity of the results. Our meta-analysis demonstrated an immediate post-intervention dilation 2.41 mm and 2.63 mm of the proximal and distal aortic necks’, respectively, as well as continuous dilation of the respective regions at a rate of 0.35 mm/year and 0.49 mm/year. Conclusion: TEVAR in BTAI leads to immediate post-intervention and continuous aortic dilation and morphological changes with possible future important clinical consequences.

Background: Functional Movement Screening (FMS) allows for rapid assessment of an individual’s physical activity level and timely detection of sports injury risk. However, traditional functional movement screening often requires on-site assessment by experts, which is time-consuming and prone to subjective bias. Therefore, the study of automated functional movement screening has become increasingly important. Methods: In this study, we propose an automated assessment method for FMS based on the improved Gaussian Mixture Model (GMM). First, the oversampling of minority samples is conducted, the movement features are manually extracted from the FMS dataset collected with two Azure Kinect depth sensors, then we train the Gaussian mixture model with different scores (1 point, 2 points, 3 points) of feature data separately, finally, we conducted FMS assessment by the Maximum Likelihood estimation. Results: The improved GMM has a higher scoring accuracy (Improved GMM:0.8) compared to other models (Traditional GMM=0.38, Adaboost.M1=0.7, Naïve-Bayes=0.75), and the scoring results of improved GMM have a high level of agreement with the expert scoring (kappa=0.67). Conclusions: The results show that the proposed method based on the improved Gaussian mixture model can effectively perform the FMS assessment task and it is potentially feasible to use depth cameras for FMS assessment.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2’-fucosyllactose (2’-FL), a human milk oligosaccharide, has anti-inflammatory effects and plays a protective role in arterial thrombosis, but its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2’-FL and its potential mechanisms in a mouse model of ischemic stroke. The administration of 2’-FL led to a reduction in the size of cerebral infarct and reactive oxygen species (ROS)-related products in the brain of MCAO mice. Further, 2’-FL promotes the recovery of neurological deficits and motor function in neurological scores and behavior tests. Biochemical studies showed that 2’-FL reduced upregulated IL-10 and downregu-lated TNF-α. Additionally,2’-FL enhanced M2-type microglial polar2’-FL upregulated IL-10 and downregulated TNF-α ization at 7 days after MCAO, with an increase in IL-4 levels and STAT6 activation at 3 days after MCAO. Our data showed that 2’-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type mi-croglial polarization in MCAO mice. These results demonstrate that 2’-FL is a potentially effective therapeutic agent for ischemic stroke.

Background and Objectives: Acute lung injury (ALI) is an inflammatory response in the lung caused by bacteria, viruses, trauma and other factors that results in lack of alveolar surfactant and subsequently respiratory distress. Endothelial-to-mesenchymal transition (EndoMT) is closely related to ALI-induced pulmonary fibrosis development and progression. This study examined the effect of milk fat globulin factor 8 (MFGE8) knockdown and overexpression on lipopolysaccharide (LPS)-induced EndoMT. Methods: Total MFGE8 activity in patients with acute respiratory distress syndrome (ARDS) and healthy volunteers was assessed using a colorimetric kit. In vitro, cell morphology was observed by microscopy, and invasion and migration were tested by Transwell and scratch assays. Specific siRNAs were transfected into HLMECs to downregulate MFGE8, and CD31 and α-SMA protein expression was detected by fluorescence microscopy and FCM. MFGE8, BMP, Smad 1, Smad4, Smad5, Snail, CD31 and α-SMA protein and gene expression was assessed by western blotting (WB) and qRT‒PCR. In vivo, the changes in cell morphology and alveolar septum in the lung of mice (C57BL/6, aged 7-8 weeks, male) were observed by H&E staining. In addition, ECM deposition in lung tissue was detected by Masson staining. CD31 and α-SMA protein expression in lung tissue was measured by WB. Results: The serum level of MFGE8 was lower in the ARDS group than in the control group. MFGE8 was identified as a protective factor associated with hospital survival. In vitro, the treatment of human lung microvascular endothelial cells (HLMECs) with LPS for 96 h clearly changed the cells from the typical cobblestone shape of ECs to spindle-like fibroblasts. The scratch and Transwell assay results indicated that endothelial cell migration and invasion were enhanced in the LPS group compared with the control group. Fluorescence microscopy, FCM, WB and PCR showed that LPS greatly inhibited CD31 (endothelial marker) expression and increased α-SMA (mesenchymal marker) expression. These data showed that LPS could induce EndoMT in HLMECs. Notably, siRNA-treated HLMECs yielded the same results. The administration of rhMFGE8 to HLMECs in the LPS or LPS+siRNA group ameliorated the changes in cell morphology and decreased cell migration and invasion. rhMFGE8 attenuated the effect of LPS or LPS+siRNA on EndoMT induction by increasing CD31 and decreasing α-SMA protein and gene expression. Moreover, activation of BMP/Smad1/5-Smad4 signalling in response to LPS and Snail (related to EndoMT transcription factors) expression were increased by MFGE8 knockdown but inhibited by rhMFGE8. In vivo, H&E staining revealed a thickened alveolar septum in the LPS group, and the thickness increased over time; in contrast, rhMFGE8 reversed this effect. ECM deposition occurred early in ALI induced by LPS and increased over time, and the administration of rhMFGE8 reversed this effect. WB showed that LPS inhibited CD31 protein expression and increased α-SMA protein expression in lung tissue. Conclusions: rhMFGE8 exerts a protective effect early in LPS-induced EndoMT through BMP/Smad1/5/Smad4 signalling and could be a therapeutic target in ALI.

In this paper I tentatively answer 50 questions sampled from a pool of over 10,000 weekly questions formulated by students in a course entitled “The Self”. The questions pertain to various key topics about self-processes, such as self-awareness, self-knowledge, self-regulation, self-talk, self-esteem, and self-regulation. The students’ weekly questions and their answers highlight what is currently know about the self. Answers to the student questions also allow for the identification of some recurrent lessons about the self. Some of these lessons include: all self-processes are interconnected (e.g., prospection depends on autobiography), self-terms must be properly defined (e.g., self-rumination and worry are not the same), inner speech plays an important role in self-processes, controversies are numerous (are animals self-aware?), measurement issues abound (e.g., self-reflection as an operationalization of self-awareness), deficits in some self-processes can have devastating effects (e.g., self-regulatory deficits may lead to financial problems), and there are lots of unknowns about the self (e.g., gender differences in Theory-of-Mind).

Nutraceuticals are bioactive compounds present in foods, utilized to ameliorate health, prevent diseases, and support the proper functioning of the human body. They have gained attention due to their ability to hit multi-targets and act as antioxidants, anti-inflammatory agents, and modulators of immune response and cell death. Therefore, nutraceuticals are being studied to prevent and treat liver ischemia–reperfusion injury (IRI). This study evaluated the effect of a nutraceutical solution formed by resveratrol, quercetin, omega-3 fatty acid, selenium, ginger, avocado, leucine, and niacin on liver IRI. IRI was performed with 60 min of ischemia and 4 hours of reperfusion in male Wistar rats. Afterward, the animals were euthanized to study hepatocellular injury, cyto-kines, oxidative stress, gene expression of apoptosis-related genes, TNF-alpha and Caspase 3 proteins, and histology. Our results show that the nutraceutical solution was able to decrease apoptosis and histologic injury. The suggested mechanisms of action are a reduction in gene expression and the Caspase 3 protein and a reduction in the TNF-alpha protein in liver tissue. The nutraceutical solution was unable to decrease transaminases and cytokines. These findings suggest that the nutraceuticals used favored the protection of hepatocytes and their combination represent a promising therapeutic proposal against liver IRI.

Winter frost injury is a major limiting factor for olive cultivation in temperate regions. The response of olive shoots to freezing stress can be used for selecting resistant genotypes to freezing. The electrolyte leakage (EL) and tetrazolium tests (TZ) are commonly used to evaluate dead tissues in cold stress studies. The temperature-response curve of dead tissues to lethal temperature (LT) is measured with models to calculate LT50 and LT90. In this study, we evaluated the accuracy and efficiency of eighteen non-linear regression models (NLRs) in calculating LT50 and LT90 of freezing stress in different olive cultivars at various stages of dormancy. After evaluating the prediction performance of NLR models, it was found that only eight models were suitable for the purpose of this research out of the 18 models examined. The 2p-logistic and Gompertz models were selected for modeling EL and TZ, respectively. Our research findings indicate that the Roughani, Kawi, and Zard varieties of olive trees exhibit the best performance in cold weather conditions. Our findings provide valuable insights into selecting frost-resistant cultivars and designing effective strategies for cold acclimation in olive cultivation.

Tetranychid outbreaks have been detected since 2016 in southern highbush blueberries (SHB); however, it was not until 2019 when the southern red mite (SRM), Oligonychus ilicis (Acari: Tetranychidae) was confirmed as the pest causing severe bronzing and stunting, in multiple Florida and Georgia commercial blueberry plantings. There is little known about the management of SRM in SHB and only three miticides (fenazaquin, fenpyroximate, and acequinocyl), have recently been registered for use in SHB between 2019 and 2020. Similarly, there is no knowledge regarding the existence of natural enemies of SRM in SHB. This is the first report of naturally occurring predatory mites (Amblyseius sp. and Neoseiulus ilicis) associated with SRM in SHB. Predatory mites were recorded in treated bushes after evaluating the performance of seven miticides used to manage SRM populations including spiromesifen, acequinocyl, sulfur, sulfur + molasses, bifenazate, fenpyroximate, and fenazaquin. Miticide efficacy was rated based on the number of SRM recorded on collected leaves and plant damage ratings using an arbitrary index (from 0= no bronzing to 4= 100% bronzing). Additionally, the presence or absence of predatory mites per sample was recorded. Fenpyroximate used as the standard miticide, significantly reduced mite numbers seven days after application, as well as acequinocyl and fenazaquin. Only plants treated with fenpyroximate or fenazaquin showed significantly less bronzing compared with the control plants. Overall, fenpyroximate and fenazaquin demonstrated the best performance for managing O. ilicis on SHB and safe to naturally occurring predatory mites. Lastly, the level of growers’ awareness regarding SRM was assessed using surveys in 2020 to design adequate educational materials available to the grower community.

Aims: Anxiety, major depressive disorder and accelerated cognitive decline frequently complicate traumatic brain injury. Obesity and type 2 diabetes mellitus drive peripheral inflammation which can accelerate traumatic brain injury-associated neurodegeneration. The Zucker rat harbors G-protein coupled receptor agonist IgG autoantibodies and in vitro neurotoxicity caused by these autoantibodies was prevented by a novel synthetic fragment of the serotonin 2A receptor. The aim of the present study was to test whether genetic obesity manifested in Zucker diabetic fatty rat is associated with anxiety, depression and spatial memory impairment induced by mild traumatic brain injury. Furthermore, we investigated whether these neurobehavioral or neurodegenerative complications can be lessened by administration of a novel putative neuroprotective peptide. Methods: Age-matched lean and fatty diabetic Zucker rats were tested in the sucrose preference test (anhedonia), open field test in bright light (anxiety measure) and the Morris water maze (spatial memory) prior to receiving a sham-injury or lateral fluid percussion (LFP) mild traumatic brain injury. Behavioral testing was repeated at 1-week, 1-month, and 3-month intervals following injury. A synthetic peptide consisting of a portion of the 5- hydroxytryptamine (serotonin) 2A receptor (2 mg/kg) (or vehicle) was administered via intraperitoneal route every other day for 7 days after sham or LFP injury to lean rats or 7 days before and after sham or LFP injury to fatty rats. Results: Sucrose preference decreased transiently (one week after mild traumatic brain injury) in Zucker lean rats indicative of anhedonia. Baseline anxiety-like behavior (bright light, open field test) was lower in fatty vs. lean Zucker rats, and anxiety behavior increased significantly in fatty rats but not lean rats following mild traumatic brain injury. Mild traumatic brain injury impaired recall of spatial memory in fatty and lean rats, and the effect was longer-lasting in fatty rats. A synthetic peptide fragment of the 5-hydroxytryptamine 2A receptor enhanced recall of spatial learning one-week after sham injury in Zucker rats and it may have prevented ‘anhedonia’ one-week after TBI (LFP) in a subset of Zucker fatty and lean rats expressing near-normal baseline sucrose preference. Mean plasma 5-hydroxytryptamine 2A receptor autoantibody level (determined 2 weeks after injury) was 2.5-fold higher than background, but did not differ significantly in (sham- vs TBI) Zucker lean rats. Conclusions: These are the first data to suggest reduced baseline anxiety-like behavior in Zucker fatty (vs. lean) rats. The pronounced increases in anxiety , and spatial memory impairment experienced by Zucker fatty (vs lean) rats following mild traumatic brain injury may have accounted in part for absence of a 5-hydroxytryptamine 2A receptor peptide neuroprotective effect in brain- injured Zucker fatty rats.

Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that can lead to severe and irreversible consequences, including the complete loss of renal function. While standardized strategies for preventing IRI during "back-table" and cold preservation are available, various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and reperfusion of the kidney. These methods include pharmacological agents, mechanical interventions, and surgical techniques such as renal capsulotomy, ischemic preconditioning, venous blood reperfusion, renal perfusion, and the use of tissue engineering techniques like mesenchymal stromal/stem cells and/or decellularization. In this comprehensive analysis, we provide a detailed overview of pharmacological agents and intraoperative methods and approaches for the prevention and treatment of renal IRI. We begin by discussing the mechanisms of IRI and the challenges of preventing it during surgery. Then using a bibliometric analysis and molecular docking of brand-new legends we showed eplerenone have the most binding affinity to Aldehyde dehydrogenase (AD), Estrogen receptor (ER), Klotho protein, Mineralocorticoid receptor (MR), and Toll-like receptor 4 (TLR4) for preventing IRI comparing with other available therapeutics, Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. Next, we provide a comprehensive analysis of the potential benefits and limitations of various prevention strategies, including an in-depth discussion of the mechanisms of action of pharmacological agents, mechanical interventions, and surgical techniques. Furthermore, we introduce a novel scoring system for the prevention methods of kidney IRI, which takes into account the effectiveness, feasibility, and safety of each method. We then analyze the current state of clinical research in this area and discuss the implications of these methods for future clinical practice. Overall, this article provides a valuable resource for clinicians and researchers seeking to prevent and treat renal IRI in surgical settings, and introduces a new scoring system that can be used to guide the selection of the most effective and safe prevention methods.

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

Biomarkers have become an important tool in the diagnosis and management of cardio renal syndromes (CRS), a complex condition characterized by dysfunction in both the cardiovascular and renal systems. These biomarkers can help identify the presence and severity of CRS, predict its progression and outcomes, and facilitate personalized treatment options. Several biomarkers, including natriuretic peptides, troponins, and inflammatory markers, have been extensively studied in CRS and have shown promising results in improving diagnosis and prognosis. In addition, emerging biomarkers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin offer potential for early detection and intervention of CRS. However, the use of biomarkers in CRS is still in its infancy, and further research is needed to establish their utility in routine clinical practice. This review highlights the role of biomarkers in the diagnosis, prognosis, and management of CRS and discusses their potential as valuable clinical tools for personalized medicine in the future.

Piriform fossa and/or esophageal injuries caused by calibration tubes are relatively rare and re-main unelucidated. Herein, we report the case of a 36-year-old woman with morbid obesity, sleep apnea, and menstrual abnormalities who was scheduled to undergo laparoscopic sleeve gastrectomy (LSG). We inserted a 36-Fr Nelaton catheter made of natural rubber as a calibration tube during the surgery. However, excessive resistance was observed. We confirmed a submuco-sal layer detachment of approximately 5 cm from the left piriform fossa to the esophagus using intraoperative endoscopy. Additionally, LSG was performed using an endoscope as the guiding calibration tube. We inserted a nasogastric tube under endoscopy with a guidewire before com-pleting the surgery, hoping for a guiding effect on saliva flow. After 17 months, the patient suc-cessfully lost weight postoperatively without complaints of neck pain or discomfort during swallowing. Therefore, if the damage is limited to the submucosal layer, as in this case, conserva-tive therapy should be considered, which is similar to the concept of not requiring suture closure in endoscopic submucosal dissection. This case highlights the risk of iatrogenic injuries to the pi-riform fossa and/or esophagus during LSG and the importance of careful calibration tube inser-tion to prevent them.

Background: Corrosive injuries (CI) became medical problems related complications include esophageal, pyloric stricture, squamous cell carcinoma [1], physical and quality of life [2]. Endoscopic dilatation (ED) is primary therapy [3]. The ultrathin endoscope assisted method is potentially safe and useful in avoiding technical failure [4]. Methods: Retrospective study of esophageal and/or pyloric stricture after CI who underwent di-latation at Soetomo General Hospital (July 2018 – July 2022). One-biweekly ED using Ultrathin Endoscope Assisted Method then continued by Through The Scope (TTS) balloon or Bougie dila-tor. Target diameter is 14mm. Clinical outcome included successful, refractory, recurrent rate and complications related procedures Results: Fifteen patients with stricture related CI. Eleven patients underwent ED with total 73 procedures. Mean age 31,45 years, Male 6(54,6%), suicide attempt 7(63,6%), acid agent 9(81,8%) located at esophagus 3(27,3%), pylorus 3(27,3 %), or both 5(45,4%). Number of esophageal dilata-tion to achieve target 14mm was 1-2 and 2-15 procedures for simple and complex stricture with overall successful, recurrent and refractory rate were 75%, 12.5% and 12.5% respectively. Pyloric dilatation outcome were 62.5%, 25% and 12.5% for successful, recurrent and refractory rate re-spectively. Conclusions: Stricture-related corrosive injury has predominantly complex anatomical structure, more sessions are required and lower clinical outcome

Background: Irish dance is growing in popularity, evolving to a more athletic and demanding dance style. Aims: To conduct a systematic review, previously registered with PROSPERO, to identify prevalence, incidence, and injury pattern among Irish dancers and analyse associated risk factors. Methods: Six online databases, plus two dance-specific science publications were searched systematically. Studies were included if the pattern of injuries among Irish dancers were evaluated or the factors associated with injury were analysed, published in English or Portuguese, in peer-reviewed scientific journals. Four reviewers assessed the quality and level of evidence using the Downs and Black criteria and a modified Oxford Centre of Evidence-Based Medicine 2009 model, respectively. Results: Eleven articles were included, 8 level 3c (cross-sectional) and 3 level 3b (prospective). Mean DB percentage score was 63% ± 7,2%. Prevalence ranged from 72,2% to 92,6%, affecting mostly the foot/ankle complex. Only 2 articles reported incidence, which ranged from 3,4–10,6 injuries/1000 hours danced depending on injury definition. Psychological factors, elite level, and insufficient/poor sleep were associated with musculoskeletal injury. Conclusions: Injury prevalence and incidence is high in Irish dancers, with the foot and ankle more affected. Due to heterogeneity in injury definitions, methods, and populations, along with the need for improvement in studies quality, recommendations were made for future research.

Mild impacts to the head, particularly when repetitive in nature, are increasingly recognized to have a range of significant negative implications for brain health. Much of the ongoing research in the field is focused on the neurological consequences of these injuries, and the relationship between head impacts and long-term neurodegenerative conditions such as chronic traumatic encephalopathy and Alzheimer’s disease. However, our understanding of the complex relationship between applied mechanical force at impact, brain pathophysiology, and neurological function, remains incomplete. Past research has shown that mild head impacts, even below the threshold that results in cranial fracture, induce changes in cranial bone structure and morphology. These structural and physiological changes likely have implications for the transmission of mechanical force into the underlying brain parenchyma. Here, we review this evidence in the context of the current understanding of bone mechanosensitivity and the consequences of traumatic brain injuries or concussions. We postulate that heterogeneity of the calvarium including differing bone thickness due to prior impacts, age, or individual variability, may be a modulator of outcomes following subsequent head impacts. We advocate for greater consideration of cranial responses to head injury in both experimental and computer modeling of impact biomechanics, and raise the hypothesis that calvarial bone thickness represents a novel biomarker of brain injury vulnerability after head trauma.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

Preclinical studies have identified glial cells as pivotal players in the genesis and maintenance of neuropathic pain after nerve injury associated with diabetes, chemotherapy, major surgeries, and virus infections. Satellite glial cells (SGCs) in the dorsal root and trigeminal ganglia of the peripheral nervous system (PNS) and astrocytes in the central nervous system (CNS) express similar molecular markers and are protective under physiological conditions. They also serve similar functions in the genesis and maintenance of neuropathic pain, downregulating some of their homeostatic functions and driving pro-inflammatory neuro-glial interactions in the PNS and CNS, i.e. “gliopathy”. However, the role of SGCs in neuropathic pain is not simply as “peripheral astrocytes”. We delineate how these peripheral and central glia participate in neuropathic pain by producing different mediators, engaging different parts of neurons, and becoming active at different stages following nerve injury. Finally, we highlight the recent findings that SGCs are enriched with proteins related to fatty acid metabolism and signaling such as Apo-E, FABP7, and LPAR1. Targeting SGCs and astrocytes may lead to novel therapeutics for the treatment of neuropathic pain.

Introduction: CT perfusion (CTP) is an alternative tool to assess cerebral hemodynamics in brain trauma. As traumatic acute subdural hematomas (ASH) are severe lesions commonly associated with poor outcome, we aimed to evaluate the brain hemodynamics in this population. Methods: Five patients admitted at the emergency department sustaining traumatic acute subdural hematoma were evaluated. Preoperative CTP was performed immediately after nonenhanced head CT scan. Postoperative CTP was performed in four patients. The outcome was assessed 6 months after surgery using the extended Glasgow Outcome Scale. Results: 4 male and 1 female were evaluated. Mean age was 46y (SD: 8.1). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). The main mechanism of trauma was falling (four patients). There was a general improvement in cerebral blood flow (CBF) after surgery from 23.9 (SD: 6.1) to 30.7 ml/100g/min, (SD: 5.1) and in mean transit time (MTT) from 7.3 (SD: 1.3) to 5.8s (SD:1.0), although it is not statistically significant (p=0.06 and p=0.06, respectively). There was still a reduction in the cerebral blood volume (CBV) media when compared to the value after surgery, from 2.63 (SD: 1.10) to 2.34 ml/100g (SD: 0.67), which is not statistically significant (p=0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome was 0.94 (p=0.054). Only one patient died (three days after surgery). This patient was victim of car crash and had the highest preoperative MTT (9.97 seconds) and CBV (4.51 ml/100 g). Conclusion: Post-operative improvement of hemodynamic CTP parameters may be correlated with outcomes after ASH. Further studies with larger samples are required to confirm this hypothesis.

Background: The hypothesis is that a hypoxic-hyperoxic preconditioning (HHP) is associated with a protective effect on myocardial function by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients (n=120) were randomly assigned to an HHP and a control group. A safe inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 minutes) was determined by measuring the anaerobic threshold. At hyperoxic phase, 75-80% oxygen fraction was used during 30 minutes. Results: The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs 23 (41.1%), p=0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low more than 24 h in control group. The endothelial damage markers appeared to be predictors of postoperative complications. Conclusion: The HHP with individual parameters based on the anaerobic threshold is a safe procedure, it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

Right ventricular remodeling and its function are closely related to the symptom severity and survival of hypoxia pulmonary hypertension, but molecular mechanisms of cardiomyocyte hypertrophy and myocardial injury remain unclear. It evaluated the cardiac function (by right cardiac catheterization to measure right ventricular systolic pressure and mean pulmonary artery pressure), myocardial tissue morphology（Haematoxylin and Eosin）, myocardial hypertrophy (Wheat Germ Agglutinin Staining), then RNA sequencing was applied to explore the mechanism, which results were verified by western blot in final. Hypoxia developed pulmonary hypertension, right ventricular diastolic and systolic functions were enhanced in rats, such as the mean pulmonary artery pressure, systolic pressure of pulmonary artery, the max pressure of right ventricular, the mean right ventricular pressure, and the heart rate was significantly higher than that in control. We found that Hif-1 signaling pathway and p38-MAPK signaling pathway have been activated by hypoxia, and cardiomyocyte apoptosis also aggravated in the right ventricular, which might be one cause of cardiomyocyte hypertrophy and myocardial injury, and targeted intervention might be one potential prevention for cardiomyocyte hypertrophy and myocardial injury induced by hypoxia.

Background: Traumatic brain injury (TBI) remains a significant risk factor for post-traumatic epilepsy (PTE). The pathophysiological mechanisms underlying the injury-induced epileptogenesis are under under investigation. The dentate gyrus, a structure highly susceptible to injury, and has been implicated in the evolution of seizure development. Methods: Utilizing the murine unilateral focal control cortical impact (CCI) injury, we evaluated seizure onset using 24/7 EEG video analysis at 2-4 months post-injury. Cellular changes in the dentate gyrus and hilus of the hippocampus were quantified by non-biased stereology and Imaris image analysis to evaluate Prox1-positive cell migration, astrocyte branching and morphology, as well as neuronal loss at four months post-injury. Isolation of region-specific astrocytes and RNA-seq was performed to determine differential gene expression in PTE+ vs. PTE- that may comport with the epileptogenic process. Results: CCI injury resulted in 37% PTE+-incidence, which increased with injury severity and hippocampal damage. Histological assessments uncovered a significant loss of hilar interneurons that coincided with aberrant migration of Prox1-positive granule cells and reduced astroglial branching in PTE+ compared to PTE- mice. We uniquely identified Cst3 as a PTE+-specific gene signature in astrocytes across all brain regions. Conclusions: These findings suggest that epileptogenesis may emerge following TBI due to distinct aberrant cellular remodeling events and key molecular changes in the dentate gyrus of the hippocampus.

Artificial regeneration is successful when high performing seedlings are transported with care to the planting site, stored for a short period in an environment without desiccation or fungal growth, and are planted in a deep hole so roots are in contact with moist soil. One of the requirements for success is the ability to avoid common planting mistakes. Due, in part, to use of container stock plus an increase in rainfall, average 1st year survival of pine seedlings (89%) in the southern United States is about 15% greater now than 45 years ago. However, when survival is less than 50% six months after planting, some landowners seek reimbursement for their loss. Some assume poor seedling quality was the cause without realizing that anaerobic soils or sudden freeze events or shallow planting holes or pruning roots, a lack of rain, or underground insects can kill pines. With a focus on pines planted in the southern United States, we list non-nursery factors that have killed seedlings in North America, Africa and Europe.

Altered expression of microRNAs (miRNAs) after spinal cord injury (SCI) has been described as being responsible for the main secondary responses, such as apoptosis. X-linked inhibitor apoptosis protein (XIAP) is a key apoptotic component involved in the progression of apoptotic programmed cell death. Several regulators have been described to modulate the XIAP's function, including the post-transcriptional regulator's miRNAs. The main aim of the present work is to identify miRNAs with altered expression after SCI which can regulate XIAP expression. Our bioinformatic analyses identified several candidate miRNAs that may regulate XIAP, among which miR-199a-5p may be involved in the downregulation of XIAP after SCI. Gene reporter assays and in vitro analyses in the neural C6 cell line confirmed the targeting of miR-199a-5p on the 3-UTR of the rat XIAP and its post-transcriptional regulation of XIAP protein level, but not at mRNA level. Analyses in a rat model of SCI revealed a trend towards increased expression of miR-199a-5p and a decrease in XIAP protein level at 3 days after injury. Finally, using a specific fluorescent in situ hybridization (FISH) probe for miR-199a-5p, we characterized the expression pattern of miR-199a-5p in cells of uninjured and rat-contused spinal cords. These findings provide new insights into apoptotic miRNA-mediated mechanisms after SCI, which will help us develop therapeutic strategies based on miRNAs for treating SCI.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study we investigate the clinical use in these directions of a “damage” type biomarker - Neutrophil Gelatinase-Associated Lipocalin (NGAL). Among patients with a high-risk profile undergoing scheduled coronary angiography and/or angioplasty, plasmsa NGAL was determined at baseline, at 4 and 24 hours after contrast administration. In the CI-AKI group, NGAL increased significantly at the 4th hour (132.33±72.83 ng/ml versus 111.48±65.06 ng/ml, p=0.006) and at the 24th hour (212 .93±276.61 ng/ml, p=0.008). In patients with subclinical CI-AKI, NGAL also increased significantly at the 4th hour (128.18±99 ng/ml, p=0.002) and reached levels close to those in patients with CI-AKI. Unlike new biomarker, however, serum creatinine did not change significantly in this group. The diagnostic power of NGAL is extremely good - AUC 0.847 (95% CI: 0.677-1.000; p=0.001) in CI-AKI and AUC 0.731 (95% CI: 0.539 – 0.924; p=0.024) in subclinical CI-AKI. NGAL may be a reliable biomarker for early diagnosis of clinical and subclinical forms of renal injury after contrast angiographic studies.

A Traumatic brain injury (TBI) is among the main causes of sudden death after head trauma. These injuries can result in severe degeneration and neuronal cell death in the CNS, including the retina which is a crucial part of the brain responsible for perceiving and transmitting visual information. The long-term effects of mild-repetitive TBI (rmTBI) are far less studied thus far, even though damages induced by repetitive injuries occurring in the brain are more common, especially amongst athletes. rmTBI can also have a detrimental effect on the retina and the pathophysiology of these injuries are likely to differ from the severe TBI (sTBI) retinal injury.Here we showed how rmTBI and sTBI can dissimilarly affect the retina. Our results indicate an increase in the number of activated microglial cells and Caspase3-positive cells in the retina in both traumatic models, suggesting a rise in the level of inflammation and cell death after TBI. The pattern of microglial activation appears evenly distributed and widespread but differs amongst the various retinal layers. sTBI induced microgial activation in both the superficial and deep retinal layers. In contrast to sTBI, no significant change occurred following the repetitive mild injury in the superficial layer, only the deep layer (spanning from the inner nuclear layer to the outer plexiform layer) shows microglial activation. This difference suggests that alternate response mechanisms play a role in the case of the different TBI incidents. The Caspase3 activation pattern showed a uniform increase in both the superficial and deep layers of the retina. This suggests a different action in the course of the disease in sTBI and rmTBI models and points to the need for new diagnostic procedures.Our present results suggest that the retina might serve as such a model of head injuries since the retinal tissue reacts to both forms of TBI and is the most accessible part of the human brain.

This paper, which is one of the few in the world dealing with this topic, presented the psychologist's work based on the concepts of mentalization and internal working models (IWMs) of attachment, with an adolescent girl who was prone to nonsuicidal self-injury. Gaga, a student in the first grade of high school, had visible scars from cutting her hands on the inner sides of both forearms. Gaga told the psychologist that her mother believes that this is an attempt to draw attention to her problems, and even a suicide attempt. Together with Gaga, the psychologist made a formulation of her mental difficulties. The main aim of the psychologist's work with Gaga was to control unpleasant impulses and emotions, so as to eliminate self-injury. This aim has been achieved through three global tasks: 1) that Gaga, in the relationship with the psychologist, builds her IWMs as positive, so that she can see herself as a person who is worthy of the love and support of close people; 2) to develop a stable capacity for mentalization; 3) to apply this acquired skills in the interpretation of her affective experiences. The mentalizing approach in working with Gaga was based on an attitude of emotional warmth, acceptance and authentic interest in her inner world. The psychologist's work with Gaga led to her better self-control, which resulted in the cessation of her self-injury. In her work with a psychologist, Gaga acquired positive IWMs, which she transferred into other significant interpersonal relationships.

Kidney diseases are a global health problem, and their frequency is continuously increasing. Available treatments provide limited kidney protection. The protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG) in several diseases have been extensively investigated. Experimental and clinical studies have shown that the antioxidant, anti-inflammatory, and anti-apoptotic properties of EGCG are promising for the treatment and/or prevention of kidney diseases. This review analyzes the available evidence on the effects, and the likely protective mechanisms of action, of EGCG in a broad spectrum of kidney diseases, including acute kidney injury, drug-induced nephrotoxicity, kidney stone disease, diabetic nephropathy, chronic kidney disease, and kidney fibrosis.

TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a four-items measure of the time to 10% alteration in any of patient self-reported measure, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat without exclusion. Results found comparable survivals, but H-IGRT significantly reduced the toxicity measured by lung diffusion capacity and alveolar volume as compared with CRT, G1 in 53% (31/59) versus 72% (44/61) patients, P=0.006; G2, 29% versus 48%, P=0.020. H-IGRT significantly reduced the risk of composite cardio-pulmonary alteration at 5 years, 10.2% versus 26.7%, P=0.024. In conclusion, TomoBreast is a proof-of-concept that image-guided radiation-therapy can improve the overall balance of lung-heart outcomes in breast cancer adjuvant therapy. Furthermore, the significance of the findings supports the efficacy of a small trial size design, which can be critical when clinical research resources are limited.

Sports traumatic brain injury (TBI) accounts for up to 20% of all sports injuries, and the number of cases is growing year by year due to an increase in the number of people involved in sports, the growing popularity of extreme and contact sports, as well as a high level of motivation to achieve record results. Mild TBI dominates, which can provoke the development of a very wide range of complications and negative consequences. In the programs for the prevention of complications and the rehabilitation of athletes after TBI, TBI features are not sufficiently considered, which significantly differ from household, road or criminal injuries. There are no instrumental methods for diagnosing the severity of the injury. Sports TBI is characterized by repeated frequent TBI, elevated body and brain temperature, peripheral redistribution of blood flow and hypocapnia, which significantly affect cerebral blood flow. Brain injury is an independent cause of the development of cerebral hyperthermia, which significantly worsens the consequences of TBI. To diagnose sports TBI, the method of microwave radiometry of the brain (MWR) can be used. For the prevention of complications, the technology of craniocerebral hypothermia (CCH), which allows for to reduce of physical general and cerebral hyperthermia, and increases the resistance of cerebral cortex neurons to hypoxia and trauma could be used However, these approaches in sports medicine are used sporadically, which, is due to the lack of awareness of coaches and doctors of sports teams. The purpose of the review is to present MWR and CCH in sports TBI.

The combined muscle-skeletal traumas (MST) are very frequent over the last few years. The emergency care try to save the life of the patient and to receive resuscitation treatment. The role of Trauma surgeon is to choose the right moment for surgery. Aim: To present the management of patient with combined height injury, fracture stabilization, partial foot amputation, local flaps, skin grafting and HIFU – thermotherapy as scar treatment. Materials and methods: 40 years old mail patient, injured after a fall from 8 meters in an elevator shaft. After resuscitation treatment to control the shock the Imaging results are: burst fracture of L3 with spinal canal stenosis, fracture of the sacral bone Denis I, fracture of the right humerus in the proximal third, Monteggia fracture of the left arm, fracture of the proximal third of the right tibia as well as comminuted fractures of both calves and of both heel bones. Results: After a few operations his final result was well healed bone fractures and a good quality soft tissue coverage allowing the patient a satisfactory quality of life. Conclusions: Combined traumas of the muscle- skeletal system are severe, serious and difficult to manage. The good outcome in their treatment requires a team approach between the different medical specialists.

Trauma to the spinal cord causes extensive neuronal death contributing to the loss of sensory-motor and autonomic functions below the injury level. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibitor of apoptosis protein (XIAP) after SCI may contribute to this rise of caspase activity. Accordingly, we have shown that the elevation of XIAP resulted in increased neuronal survival after SCI and improved functional recovery. Therefore, we hypothesize that neuronal overexpression of XIAP can be neuroprotective after SCI with improved functional recovery. In line with this, studies of a transgenic mouse with overexpression of XIAP in neurons revealed that higher levels of XIAP after spinal cord trauma favours neuronal survival, tissue preservation, and motor recovery after the spinal cord trauma. Using the human SH-SY5Y cells overexpressing XIAP we show further that XIAP reduced caspase activity and apoptotic cell death after pro-apoptotic stimuli. In conclusion, this study shows that the levels of XIAP expression are an important factor for the outcome after spinal cord trauma and identifies XIAP as an important therapeutic target for alleviating the deleterious effects of SCI.

Objectives The aim of this study was to measure the magnitude of forces in the joints of the lower limb whilst running barefoot and compare them to the forces generated whilst wearing running shoes with a thick midsole.MethodsTwenty-three volunteers who utilised running as their main sport or a training aid ran as training aid were included in this study. Each volunteer would run down a fourteen-meter-long corridor both barefoot and with running shoes. Forces for joints of the lower limb were collected using a Vicon motion analysis system and force plates. The joint forces for the ankles, knees and hips were taken as the largest joint force experienced during the stance phase and then averaged over five running trials.ResultsThere was significant reduction in the joint forces for the ankles, knees, and hips when barefoot running compared to the shod condition.ConclusionBarefoot running could be utilised to prevent both acute and degenerative injuries of the lower limb.

Among the possible improvements of Autonomous Emergency Braking (AEB) systems, reducing the intensity of the automatic braking process by studying the kinematics and general behavior of the pedestrian while crossing is crucial to determine the progressiveness of the braking, or replacing part of the braking process by an evasive maneuver when a collision is imminent. This paper proposes the integration of an autonomous avoidance system (Automatic Emergency Steering, AES) that acts directly on the steering system to generate an evasive maneuver and avoid a possible pedestrian collision (OPREVU-AES system), as well as the assessment of its effectiveness compared to a commercial AEB system. OPREVU and VULNEUREA are research projects in which INSIA and CEDINT have cooperated to improve driving assistance systems and the safety of pedestrians and cyclists through Virtual Reality (VR) techniques. The analysis of the kinematic and dynamic response of the OPREVU-AES system is conducted in CarSim© software. The effectiveness evaluation procedure is based on the reconstruction of a sample of road vehicle-to-pedestrian crashes (INSIA-UPM database), using the PCCrash® software, and taking as an indicator the probability of head injury severity (ISP). The results show that the AEB system would have prevented part of the collisions, especially after the incorporation of the OPREVU-AES system. In most of the cases where avoidance is not possible, a significant reduction of the ISP is achieved.

Background: There is an increasing interest in the role of EEG in neurorehabilitation. We primarily aimed to identify the knowledge base through highly influential studies. Our secondary aims were to imprint the relevant thematic hotspots, research trends, and social networks within the scientific community. Methods: We performed an electronic search in Scopus looking for studies reporting on rehabilitation in patients with neurological disabilities. The most influential papers outlined the knowledge base, while a word co-occurrence analysis imprinted the research hotspots. Likewise, co-citation analyses highlighted collaboration networks between Universities, authors, and countries. The results were presented in summary tables, burst detection plots, and geospatial maps. Finally, a content review based on the top-20 most cited articles completed our study. Results: Our current bibliometric study was based on 874 records from 420 sources. There was a vivid research interest in EEG use for neurorehabilitation, with an annual growth rate as high as 14.3%. The most influential paper was the study titled "Brain-computer interfaces, a review" by Nicolas-Alfonso LF and Gomez-Gill J, with 997 citations, followed by "Brain-computer interfaces in neurological rehabilitation" by Daly J. and Wolpaw JR (708 citations). The USA, Italy, and Germany were among the most productive countries. The research hotspots shifted with time from the use of “functional magnetic imaging” to EEG-based “brain-machine interface”, “motor imagery”, and “deep learning”. Conclusions: EEG constitutes the most significant input in brain-computer interfaces (BCI) and can be successfully used in the neurorehabilitation of patients with stroke, amyotrophic lateral sclerosis, and traumatic brain and spinal injury. EEG-based BCI facilitates training, communication, and control of wheelchair and exoskeletons. However, research is limited to specific scientific groups from developed countries. Evidence is expected to change with the broader availability of BCI and improvement in EEG filtering algorithms.

Acute kidney injury (AKI) is a complication that can occur after cardiac surgery and requires ongoing research in light of the exponential expansion of technological advancements and knowledge in medicine. In this study, we aim to evaluate the outcomes of treated electives of emergency aortic disease with high serum creatinine levels (SCr). Methods: The cohort includes 183 patients, all of whom have an aortic disease and whose SCr levels were checked upon admission on the first day in the intensive care unit (ICU) and upon discharge from the hospital. We examined the correlation of SCr levels with in-hospital mortality and immediate mortality at least six months after discharge as well as with cross-clamp time and bypass time.Results: A high SCr level upon admission is a significant predictive factor of n-hospital mortality (p = 0.001) but not immediate mortality (p = 0.409). A statistically significant correlation was also observed between elevated SCr level on the first day of ICU and aortic disease (p = 0.041) but not immediate mortality (p = 0.119). We observed a significant correlation between aortic disease and in-hospital mortality (p < 0.001), but no correlation was found between high SCr level on the first day of ICU and immediate mortality (p = 0.119). The cross-clamp time is statistically significant correlated with elevated SCr level (p = 0.013) and in-hospital mortality (p = 0.001) but not immediate mortality (p = 0.847). Furthermore, the bypass time is negatively correlated with a high SCr level on the first day of ICU (p = 0.090), in-hospital mortality (p = 0.410), and immediate mortality (p = 0.625). We also found that aortic disease is not correlated with elevated creatinine levels at ICU discharge (p = 0.152) or long-term mortality (p = 0.106). Conclusions: Although this study only included a small portion of the elaborate aspects of surgical and medical management developed around cardiac patients who received invasive treatment, the conclusions reached are nevertheless clearly relevant, as evidenced by the significantly correlations uncovered. In order to manage AKI after AAS and improve the outcome, the SCr level could be used as a marker for renoprotective strategy. Moving forward, these results serve as a first step in motivating us to expand the range of our research, collect newly relevant data, and use it to benefit patients.

In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic device whose structures and functions adapt to changing circumstances. While such changes also occur under physiological conditions, the most dramatic alterations take place during or after various pathological events. It is astonishing what mechanisms the musculo-skeletal system has evolved to come to grips with the damages. Many of these changes are maladaptive, but some appear to help adapt to the new conditions. Although myriads of studies, using manifold methods, have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases are still little understood, due to a number of reasons. We will here try to summarize some results and remaining problems in a selection of diseases, in particular spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and predominantly spinal cord injury (SCI) with occasional relations to stroke. Especially the changes in SCI (and stroke) depend on the cause, site and extent of the afflicted damage and are therefore multifarious. At the end, we will briefly summarize results indicating that operant, classical and instrumental conditioning can be used to produce plastic changes in healthy people, with potentials for applications to patients with spinal cord injury. In order not to overload the article, we will not delve deeply into sub-cellular processes.

Following spinal cord injury (SCI), pathological reflexes develop that result in altered bladder function and sphincter dis-coordination, with accompanying changes in the detrusor. Bladder chemodenervation is known to ablate the pathological reflexes, but the resultant effects on the bladder tissue are poorly defined. In a rodent model of contusion SCI, we examined the effect of early bladder chemodenervation with botulinum toxin A (BoNT-A) on bladder histopathology and collagen deposition. Adult female Long Evans rats were given a severe contusion SCI at spi-nal level T9. The SCI rats immediately underwent open laparotomy and received detrusor injec-tions of either BoNT-A (10 U/animal) or saline. At 8 weeks post injury, the bladders were col-lected, weighed, and examined histologically. BoNT-A injected bladders of SCI rats (SCI-BoNT-A) weighed significantly less than saline injected bladders of SCI rats (SCI-saline) (241 ± 25 mg vs. 183 ± 42 mg; p<0.05). Histological analyses showed that SCI resulted in significantly thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from uninjured animals (339 ± 89.0 m vs. 193 ± 47.9 m; p<0.0001). SCI-BoNT-A animals had significantly thinner bladder walls compared to SCI-saline animals (202 ± 55.4 m vs. 339 ± 89.0 m; p<0.0001). SCI-BoNT-A animals had collagen organization in the bladder walls similar to that of uninjured animals. Detrusor chemodenervation soon after SCI appears to preserve bladder tissue integrity, by reducing the development of detrusor fibrosis and hypertrophy associated with SCI.

Injury to the central nervous system (CNS), in most vertebrate animals, results in permanent damage and lack of function, due to their limited regenerative capacities. In contrast, echinoderms can fully regenerate their radial nerve cord (RNC) following transection, with little or no scarring. Investigators have associated the regenerative capacity of some organisms with the stress response and inflammation produced by the injury. Here we explore the gene activation profile of the stressed holothurian CNS. To do this, we performed RNA sequencing on isolated RNC explants submitted to the stress of transection and enzyme dissection and compared them to explants kept in culture for 3 days following dissection. We describe stress-associated genes, including members of heat-shock families, ubiquitin-related pathways, transposons, and apoptosis that were differentially expressed. Surprisingly, the stress response does not induce apoptosis in this system. Other genes associated with stress in other animal models, such as hero proteins and those associated with the integrated stress response, were not found to be differentially expressed either. Our results provide a new viewpoint on the stress response in the nervous system of an organism with an amazing regenerative capacity. This is the first step to deciphering the molecular processes that allow echinoderms to undergo fully functional CNS regeneration while also providing a comparative view for students of the stress response in other organisms.

Background: Cognitive-behavioral alterations can occur after an acquired brain injury. It is a stressful situa-tion for patient and relatives. Objectives: To develop and evaluate a synchronous online training program on emotional intelligence (EI) for caregivers of adult patients with cognitive-behavioral impairment due to acquired brain injury. Methods: A quasi-experimental study was designed, a target population of ten caregivers attended to a one-month virtual synchronous course about EI. The emotional status of caregivers was registered one-month-previous and one-month-post program using comparative measures: The Trait Meta-Mood Scale (TMMS-24) and the Positive and Negative Affect Schedule (PANAS). Results: Median age of the ten caregivers was 48 years, 80% of women with a median care-time of 6 years. 50% of them were spouses of the patients. 60% of the patients were affected by stroke (hemorrhagic or ischemic cause). The main cognitive impairment of the patients reported by relatives was memory deficit. After re-ceiving training, favorable changes were found regarding emotional affect measured with the PANAS, both positive (increase) and negative (decrease), as well as with the TMMS-24-mood-repair area (p < 0.05). Conclusions: Training in EI helps caregivers to make their mood more positive and improve aspects of their emotional intelligence such as emotional regulation.

This study aims to examine the cytotoxicity mechanisms of synthetic cathinone (bath salts) on rat primary cultured neurons and primary astroglial cells, and to assess their neurobehavioral effects on mice. We administered methylenedioxypyrovalerone (MDPV) to both rat primary cultured neurons and primary astroglial cells to assess cell injury. We also analyzed the effects of MDPV on these cell cultures using immunocytochemistry. We utilized western blotting to assess the breakdown of αII-spectrin and glial fibrillary acidic protein (GFAP) induced by MDPV. The western blotting experiment also included calpain and caspase inhibitors (SNJ1945 and Z-D-DCB, respectively) and pro-apoptotic and pro-necrotic agents (Staurosporine and calcium ionophore A23187, respectively). Lastly, we assessed MDPV’s effects on behavioral effects using rotarod, locomotor activity, elevated plus maze, Morris water maze, forced swimming, and open field tests. MDPV caused a dose-dependent release of LDH in both cerebrocortical neuron-astroglia mixed cultures and primary astroglial cultures. MDPV also caused neurite breakages and astroglial process retraction on immunocytochemistry. Lastly, MDPV induced αII-spectrin breakdown in western blotting experiments. Co-administration of calpain and caspase inhibitors reduced the degradation of αII-spectrin and GFAP. MDPV administration also increased anxiety-like behavior and locomotor activity in the mice. Synthetic cathinones, which share structural similarities with methamphetamine, also induce significant neurotoxic effects and neurobehavioral effects on rodent models. These neurotoxic effects are likely mediated by calpain and caspase-induced apoptosis and necrosis, while astroglial death is likely only due to calpain activation. Therefore, further research may focus on pharmacological interventions targeting these pathways to mitigate the cytotoxic impact of cathinones in humans.

Background. Traumatic brain injury (TBI) is the main cause of disabilities over the industrialized countries. Cognitive decline appears in the chronic phase of the pathology consecutively to cellular and molecular processes. Here we described the use of KCC2, a neuronal-specific potassium-chloride transporters as potent biomarker to predict cognitive dysfunctions after TBI. Methods. Using neuronal and total exosomes collection from blood serum in control and TBI subjects we were able to anticipate the decline of cognitive performance. Results. After TBI, we observed a significative and persistant loss of KCC2 expression in the blood exosomes that is correlated to changes in network activity and cellular processes such as secondary neurogenesis. Also we correlated this KCC2 loss in expression to the appearance of the cognitive decline observed in mice and more particularly we correlate the KCC2 loss of expression to the appearance of the depressive-like behavior. Conclusion. According to our protocol, we were able to confirm our previous findings in agreement with the potential therapeutic effect of bumetanide in the prevention of the post traumatic depression after TBI, by restoring the KCC2 expression thus preventing the massive neuronal death of interneurons and the secondary neurogenesis effect observed in such model.

Background: The incidence of traumatic acute subdural hematomas (ASDH) in elderly is increasing. Despite surgical evacuation, these patients have poor survival and low rate of functional outcome, and surgical timing plays a no clear role as predictor. We investigated if the timing of surgery has a major role in influencing outcome in these patients.Methods: We retrospectively retrieved clinical and radiological data of all patients ≥70 years operated on for post-traumatic ASDH in a 3 years period in 5 Italian Hospitals. Patients were divided in 3 surgical timing groups from hospital arrival: ultra-early (within 6h); early (6-24h); delayed (after 24h). Outcome was measured at discharge using two endpoints: survival (alive/dead) and functional outcome at Glasgow Outcome Scale (GOS). Univariate and multivariate predictor models were constructed.Results: We included 136 patients. About 33% died for consequences of ASDH and among the survivors only 24% were in good functional outcome at discharge. Surgical timing groups appeared different according to presenting GCS, which was on average lower in ultra-early surgery group, and radiological findings, which appeared worse in the same group. Delayed surgery was more frequent in patients with subacute clinical deterioration. Surgical timing appeared associated neither with survival nor with functional outcome also after stratification for preoperative GCS. Preoperative midline shift was the strongest outcome predictor. Conclusions: An earlier surgery was offered to patients with worse clinical-radiological findings. Also after stratification for GCS it was not associated with better outcome. Among the radiological markers, preoperative midline shift was the strongest outcome predictor.

Ischemia/reperfusion (I/R) injury results in cell death by inducing apoptosis. During I/R, early generation of mitochondrial reactive oxygen species (mtROS) can induce neighboring mitochondria to release additional ROS, a toxic cycle resulting in significant mitochondrial and cellular injury. Oxidative damage in the mitochondria contributes to various pathologies, including I/R injury. Accordingly, preventing mitochondrial oxidative damage should be therapeutically relevant for many disorders, including cardiovascular diseases. We recently discovered an Indole-Peptide-Tempo Conjugate (IPTC) that served as a novel bifunctional agent with both antioxidant and autophagy-modulating capacity. Here, we demonstrate that IPTC can protect H9C2 cardiomyocytes from hypoxia/reoxygenation (H/R) injury that results from mtROS overproduction due to impaired mitophagy and resultant mitochondrial dysfunction. We hypothesize that the mechanism of action of IPTC involves the capacity to decrease mtROS combined with induction of mitophagy.

Traumatic brain injury (TBI) is a major leading cause of death and disability. While previous studies regarding focal pathologies following TBI have been done, there is a lack of information concerning the role of analgesics and their influences on injury pathology. Buprenorphine (Bup), an opioid analgesic, is a commonly used analgesic in experimental TBI models. Our previous studies investigated the acute effects of Buprenorphine-sustained release-Lab (Bup-SR-Lab) on diffuse neuronal/glial pathology, neuroinflammation, cell damage, and systemic physiology. The current study investigated the longer-term chronic outcomes of Bup-SR-Lab treatment at 4 weeks following TBI utilizing a central fluid percussion injury (cFPI) model in adult male rats. Histological assessments of physiological changes, neuronal damage, cortical and thalamic cytokine expression, microglial and astrocyte morphological changes, and myelin alterations were done, as we had done in our acute study. In the current study the Whisker Nuisance Task (WNT) was also performed pre- and 4w post-injury to assess changes in somatosensory sensitivity following saline or Bup-SR-Lab treatment. Bup-SR-Lab treatment had no impact on overall physiology or neuronal damage at 4w post-injury regardless of region or injury, nor did it have any significant effects on somatosensory sensitivity. However, greater IL-4 cytokine expression with Bup-SR-Lab treatment was observed compared to saline treated animals. Microglia and astrocytes also demonstrated region-specific morphological alterations associated with Bup-SR-Lab treatment, in which cortical microglia and thalamic astrocytes were particularly vulnerable to Bup-mediated changes. There were discernable injury-specific and region-specific differences regarding myelin integrity and changes in specific myelin basic protein (MBP) isoform expression following Bup-SR-Lab treatment. This study indicates that use of Bup-SR-Lab could impact TBI-induced glial alterations in a region-specific manor 4w following diffuse brain injury.

Inflammatory reaction after ischemia-reperfusion contributes significantly to prognosis, and microglia activation is the main resource of inflammation in nervous system. STAT5 is proving to be a highly effective anti-inflammatory therapy with great potential, and inhibition of STAT5 has demonstrated significant anti-inflammation and therapeutic effects, but rarely focus on mechanism of neuroinflammation and brain injury from ischemia-reperfusion. It is the first time to found that the anti-inflammation of dauricine is mainly through STAT5-NF-κB pathway, might act as a STAT5 inhibitor. Dauricine suppressed the inflammation cytokines Eotaxin, KC, TNF-α, IL-1α, IL-1β, IL-6, IL-12β, IL-17α, and also inhibited the microglia activation. STAT5b mutant at Tyr-699 reversed the protective effect of dauricine on oxygen-glucose deprivation-reperfusion injury of neurons, and reactivated the suppression of dauricine on P-NF-κB of microglia. These results suggest that dauricine might suppress the neuroinflammation and protect the neuron from the injury of post-ischemia-reperfusion via mediating the microglia activation through STAT5-NF-κB pathway, and ss a potential therapeutic target for neuroinflammation, STAT5 needs to be raised concern in ischemic stroke.

Use of rhizosphere microorganisms provides an alternative or supplement to conventional plant breeding to improve water deficit tolerance of tomato plants. Experiment was carried out to explore the effect of two microbial species, AMF (Rhizophagus irregularis) and Bacillus subtilis, in single and co-application, on growth, colonization, and molecular aspects of tomato plants under drought stress. Co-inoculated plants showed less reduction in growth traits, photosynthetic pigments, colonization rate, and increased compatible solutes like proline which help in sustaining relative water content than non-inoculated plants. Inoculation considerably enhanced proline dehydrogenase activity, and significantly reduced both Δ1-pyrroline-5-carboxylate reductase Δ1-pyrroline-5-carboxylate synthetase activity causing lower proline accumulation in inoculated plants under drought stress. Co-inoculated plants showed obvious upregulation of antioxidant system, thus facilitating amelioration of oxidative stress through exclusion of reactive oxygen species. No inoculation under drought stress upregulated abscisic acid related genes expression but have no effect in plants inoculated either sole or mixed inoculation. Expression of aquaporin genes was upregulated in plants co-inoculated and with AMF alone under normal condition. However the expression of aquaporin genes were decreased or unaffected in plants inoculated with Bacillus subtilis but increased in non-inoculated plants. Co-applied AMF and bacillus subtilis substantially increase drought tolerance by upregulating proline metabolism, antioxidant enzymes and aquaporin genes. Therefore our results suggest that co-inoculation mediated drought tolerance is linked with increased proline accumulation, enhanced antioxidant enzyme activities and differential regulation of ABA biosynthetic and aquaporin genes, which is vital for osmotic adjustment of host plant.

Neurotrauma continues to contribute to significant mortality and disability. The need for better protective equipment is apparent. This review focuses on improved helmet design and the necessi-ty for continued research. We start by highlighting current innovations in helmet design for sport and subsequent utilization in the lay community for construction. The current standards by sport and organization are summarized. We then address current standards within the military envi-ronment. The pathophysiology is discussed with emphasis on how helmets provide protection. As innovative designs emerge, protection against secondary injury becomes apparent. Much research is needed, but this focused paper is intended to serve as a catalyst for improvement in helmet de-sign and implementation to provide more efficient and reliable neuroprotection across broad arenas.

Reparative osteogenesis in the damaged vertebrae is a complex cascade of morphological and biochemical processes that result in the consolidation of the vertebral body. This research was aimed at studying the features of reparative osteogenesis in damaged thoracic and lumbar vertebral bodies at different time points after injury. We analyzed the morphological findings of the vertebral tissues harvested during surgical interventions in 43 patients with recent, subacute and long-standing injuries to thoracic and lumbar spine, and found that cell differentiation in osteogenesis is closely related to angiogenesis and the metabolic cascade. In areas with sufficient oxygenation, good partial pressure of oxygen, and active growth of microvasculature the normal cycle of development and differentiation of osteoblasts and osteocytes occurs, and hypoxia and acidosis lead to pathological osteogenesis. The reclination maneuver with dorsal tools on Day 10-12 of the injury may be ineffective due to the formation of adhesions between fragments, and reclination of the body of the damaged vertebra two weeks or more after the injury is apparently doomed to failure. Timely ventral fusion performed for objective indications is the key to successful rehabilitation of patients, on the one hand, and reduction of the surgical trauma volume in the future, on the other.

Mild traumatic brain injury (mTBI) or concussion accounts for the bulk of all head injuries and represents a major health concern. Although an mTBI event may not manifest in neurobehavioral impairment, repeated injuries, known as repeated mTBI (rmTBI), can result in a cumulative effect that may progress to long-term cognitive and functional deficits. To date, there is no FDA-approved drug for TBI in general and rmTBI in particular. In previous studies, we have demonstrated the neuroprotective role of mitoquinone (MitoQ), a mitochondrial antioxidant, in an open head injury model and a model of repeated mild TBI (rmTBI) at a chronic time point (30 days). In this work, we set out to assess the neuroprotective potential of MitoQ at acute (3 days) and subacute time points (7 days) post-injury in a controlled cortical impact model of rmTBI. C57BL/6 male mice were injected intraperitoneally with MitoQ (5 mg/kg) one hour after the first mTBI, and three days after the first injury in both the 3-day and 7-day MitoQ + rmTBI subgroups, with an additional injection four days after the second injection in the 7-day group. Cognitive function was evaluated using the Morris water maze (MWM) while gross and fine motor functions were evaluated by the pole climbing, grip strength, and ladder rung tests. Dihydroethidium (DHE) staining was performed to evaluate oxidative stress while qRT-PCR was used to measure the gene expression of different antioxidant enzymes. Also, immunofluorescence staining was performed on brain tissue to assess the degree of microgliosis and astrocytosis. Our results showed that MitoQ conferred significant protection on days 3 and 7 post-injury against fine motor function impairment induced by rmTBI. Moreover, MitoQ enhanced cognitive function and reduced astrogliosis, microgliosis, and levels of oxidative stress on day 7 post-injury. However, antioxidant gene expression generally remained unaffected. In light of our results, MitoQ administration may be considered a preventive approach that helps to alleviate the neurological manifestations associated with rmTBI early before symptoms progress to long-term deficits.

As the problem of traction injuries to brachial plexus is a common one and of high socio-economic significance, the analysis of the surgical outcomes in patients with this pathology is significant for neurosurgery, neurology, traumatology-orthopedics, and rehabilitation. The aim of the research is to compare the short-term outcomes of using various surgical methods for managing patients with closed traction injuries of brachial plexus. Material and methods. The research involved 61 patients with closed traction injury of brachial plexus divided into two groups homogeneous in sex, age and severity of their neurological deficit: Group I – 33 patients who underwent microsurgical neurolysis, Group II – 28 patients who underwent microsurgical neurolysis combined with one-level electrostimulation. The dynamic assessment of clinical and functional status of upper limbs was performed using scale methods and electrophysiological monitoring. Results. The research revealed a more evident recovery of the upper limb function in Group II patients suggesting the method of microsurgical neurolysis combined with electrostimulation to be preferable in case of closed traction injuries to brachial plexus. Conclusion. The combination of microsurgical neurolysis with one-level electrostimulation improves the short-term outcomes of surgical treatment in patients with closed traction injuries of brachial plexus due to a sooner decrease in pain in postoperative period, and positive dynamics of clinical and electrophysiological parameters.

Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites between A-56 and A-75, and (ii) major C-terminal cleavage sites between T-383 and Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78, R-79, D-266 and A-267, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.

Background: Only few pediatric reports exist regarding the prevalence, cause and evolution of liver and renal injury in patients with anorexia nervosa (AN). The aim of this study is to describe the prevalence and the risk factors of hepatic and renal failure at admission and during hospitalization, especially during refeeding in a cohort of hospitalized adolescents with AN.Methods: In a retrospective cohort study of adolescents with AN in a single hospital of Marseille from 2013 to 2019, we compared four groups on admission: elevated aminotransferases (AT)/normal AT and renal injury/no renal injury to analyze the differences between them (demographic factors, anthropometric factors, disease duration, initial prescribed calories, speed of refeeding, aminotransferase level, glomerular filtration rate). We observed the evolution of AT and renal injury for these four groups during refeeding (by the increase of kilocalories). Results: A total of 29 subjects with AN met eligibility criteria (age: 14.2 years, female (86.2%), BMI at admission (Z-score= -2.8 standard deviation (SD)) with elevated AT (20.7 %) and renal injury (13.8 %) on admission. Lower Z-score BMI (-4.05 vs -2 SD, p = 0.013), lower expected weight for height (69% vs 76%, p = 0.034) and longer disease duration (2.1 vs 0.9 years, p =0,032) were significantly associated with elevated liver enzymes at admission. Lower Z-score BMI (-3.35 vs -2.5 SD, p = 0.002), lower expected weight for height at admission (69% vs 74,5%, p = 0.002) and loss of weight before admission (0.66 vs à 0.20 kg per day, p = 0.002) were associated with renal injury at admission. Time nadir BMI (13.5 vs 6.5 days, p = 0.034) and duration of hospitalization (55 vs 41 days, p = 0.036) were longer in elevated enzymes on admission group. During refeeding, liver enzymes (95% confidence interval (CI), odds ratio (OR) aspartate aminotransferase: -0.07 [-0.11; -0.03] and OR alanine aminotransferase: -0.16 [-0.27; -0.06]) and renal injury (95% CI, OR creatinine: -0.013 [-0.017; -0.008]) have normalized with the increase of calories, with significant association.Conclusions: The results of this study suggest that degree of malnutrition is associated with liver and renal injury on admission. Theses failures disappeared with refeeding. In the future, prospective multicentric studies could examine evolution of renal and hepatic failure undergoing refeeding in large pediatric cohort of AN.

Coronavirus disease 2019 restrictions impacted Canadians' daily living, especially those at higher risk of compromised health conditions. This study aimed to describe the physical, psychological, and social well-being of adults with disabilities, and older adults from May to June 2020. An online survey was used to administer standardized measures of mobility, anxiety and depression, boredom, resilience, technology readiness, social support, social networks, and participation. Seventy-two participants were recruited, with a mean age (SD) of 61.2 (13.8). 69.4% of participants had a disability, and 51.4% were older adults. 27.8% and 16.7% of participants exceeded the anxiety and depression cut-off scores, respectively. Boredom and restriction in participation were experienced by 76.4% and 80.1% of participants, respectively. Participants' mean (SD) resilience and life space scores were 72.4 (14.0) and 51.9 (24.0), respectively. Individuals with disabilities have comparatively higher mean anxiety (5.5 to 3.3), depression (4.8 to 2.9), and boredom (92.2 to 72.3) scores than those without. Individuals with a disability had lower resilience (69.9 to 78.0) and felt more life space restrictions (45.4 to 67.6). Our findings revealed issues with anxiety, boredom, participation, and life space activity. This information may provide supporting evidence when creating policies to mitigate existent health and social inequities.

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon^® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity. Genetic and pharmacological manipulation of TGF-β signaling pathway in animal models of CNS injury and disease alters pathological and functional outcomes. This review aims to provide recent understanding regarding astrocyte reactivity and TGF-β signaling in brain injury, aging, and neurodegeneration. Further, it explores how TGF-β signaling modulates astrocyte reactivity and function.

Acute kidney injury (AKI), especially if recurring represents a risk factor for future chronic kidney disease. In intensive care units, increased intraabdominal pressure is well-recognized as a significant contributor of AKI. However, the importance of transiently increased intra-abdominal pressures procedures is less commonly appreciated during laparoscopic surgery, the use of which has rapidly increased over the last few decades. Unlike the well-known autoregulation of the renal cortical circulation, medulla perfusion is modulated via partially independent regulatory mechanisms and strongly impacted by changes in venous and lymphatic pressures. In our review paper, we will provide a comprehensive overview of this evolving topic, covering a broad range from basic pathophysiology up to and including current clinical relevance. Key regulators of oxidative stress such as ischemia-reperfusion injury, the activation of inflammatory response and humoral changes interacting with procedural pneumoperitoneum formation and AKI risk will be recounted. Moreover, we present an in-depth review of the interaction of pneumoperitoneum formation with general anesthetic agents and animal models of congestive heart failure. A better understanding of the relationship between pneumoperitoneum formation and renal perfusion will support basic and clinical research, leading to improved clinical care and collaboration among specialists.

Cognitive rehabilitation is useful for many after traumatic brain injury (TBI), but we lack critical knowledge about which patients benefit the most from different approaches. Advanced neuroimaging techniques have provided important insight into brain pathology and systems plasticity after TBI and have potential to inform new practices in cognitive rehabilitation. In this study, we aimed to identify candidate structural brain measures with relevance for rehabilitation of cognitive control (executive) function after TBI. Twenty-eight patients (9 female, mean age 40.5 (SD = 13.04) years) with moderate/severe TBI (>21 months since injury) that participated in a randomized controlled cognitive rehabilitation trial (NCT02692352) were included in the analyses. Regional brain volume was extracted from T1-weighted MRI scans before treatment using tensor-based morphometry. Both positive and negative associations between treatment outcome (everyday cognitive control function) and regional brain volume were observed. The most robust structural brain measures with relevance for improvement in function were observed in midline fronto-parietal regions, including the anterior and posterior cingulate cortices. The study pro-vides proof of concept and valuable insight for planning future studies focusing on neuroimaging in cognitive rehabilitation after TBI.

Purpose Violence against paramedics is a complex – but underreported – problem. Extant research suggests organizational culture may play a role in sustaining cultural norms that downplay the significance and limit reporting. Our objective was to qualitatively explore paramedics’ experience with violence, with particular emphasis on understanding how organizational culture contributes to under-reporting. Approach We surveyed paramedics from a single, large, urban service in Ontario, Canada, asking participants to describe their experiences with violence, including whether – and why or why not – the incidents were reported. Within a constructivist epistemology, we used inductive thematic analysis with successive rounds of coding to identify and then define features of organizational culture that limit reporting. Findings A total of 196 (33% of eligible) paramedics completed the survey. Fully 98% of participants disclosed having experienced some form of violence; however only a minority (40%) reported the incidents to management, or the police (21%). We defined a framework within which a lack of support from management, and consequences for offenders, implicitly positions the ability of paramedics to “brush off” violent encounters as an expected professional competency. Disclosing emotional or psychological distress in response to violent encounters invited questions as to whether the individual is personally suited to paramedic work. Originality While the extant research has indicated that underreporting is a problem, our findings shed light on why – a critical first step in addressing what has been described as a serious public health problem.

Metabolic and ionic changes during ischaemia predispose the heart to the damaging effects of reperfusion. Such changes and the resulting injury differ between immature and adult heart. Therefore, cardioprotective strategies for adults need to be tested in immature heart. We have recently shown that simultaneous activation of PKA and EPAC confers marked cardioprotection in adult hearts. The aim of this study is to investigate the efficacy of this intervention in immature hearts and determine whether the mitochondrial permeability transition pore (MPTP) is involved. Isolated perfused Langendorff hearts from both adult and immature rats were exposed to global ischaemia and reperfusion injury (I/R) following control perfusion or perfusion after an equilibra-tion period with activators of PKA and/or EPAC. Functional outcome and reperfusion injury were measured and in parallel, mitochondria were isolated following 5 min reperfusion to determine whether cardioprotective interventions involved changes in MPTP opening behaviour. Perfusion for 5 minutes preceding ischaemia of injury- matched adult and immature hearts with 5 µM 8-Br (8-Br-cAMP-AM), an activator of both PKA and EPAC, led to significant reduction in post-reperfusion CK release and infarct size. Perfusion with this agent also led to a reduction in MPTP opening propensity in both adult and immature hearts. These data show that immature hearts are innately more resistant to I/R injury than adults, and that this is due to a reduced ten-dency to MPTP opening following reperfusion. Further, simultaneous stimulation of PKA & EPAC causes cardioprotection which is additive to the innate resistance.

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions that can lead to the loss of structure and/or function impairment. These changes can cause a partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, what in turn can affect the quality of life. For those reasons, PNI is a major public health concern. This review aims to revisit the concepts associated with the PNI. First, the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to explain the urge for new approaches and to understand the methods to evaluate nerve regeneration in a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

Concussion, also known as mild traumatic brain injury (mTBI), commonly causes transient neurocognitive symptoms, but in some cases, it causes cognitive impairment, including working memory (WM) deficit, which can be long-lasting and impede a patient’s return to work. The predictors of long-term cognitive outcomes following mTBI remain unclear because abnormality is often absent in structural imaging findings. The purpose of the study was to determine whether machine learning-based models using functional magnetic resonance imaging (fMRI) biomarkers and demographic or neuropsychological measures at baseline could effectively predict 1-year cognitive outcomes of concussion. We conducted a prospective, observational study of patients with mTBI who were compared with demographically-matched healthy controls enrolled between September 2015 to August 2020. Baseline assessments were collected within the first week of injury, and follow-ups were conducted at 6 weeks, 3 months, 6 months, and 1 year. Potential demographic, neuropsychological, and fMRI features were selected according to the significance of correlation with the estimated changes in WM ability. The support vector machine classifier was trained using these potential features and estimated changes in WM between the predefined time periods. Patients demonstrated significant cognitive recovery at the third month, followed by worsened performance after 6 months, which persisted until 1 year after concussion. Approximately half of the patients experienced prolonged cognitive impairment at 1-year follow up. Satisfactory predictions were achieved for patients whose WM function did not recover at 3 months (accuracy=87.5%), 6 months (accuracy=83.3%), 1 year (accuracy=83.3%), and performed worse at 1-year follow-up compared to baseline assessment (accuracy=83.3%). This study demonstrated the feasibility of personalized prediction for long-term postconcussive WM outcomes based on baseline fMRI and demographic features, opening a new avenue for early rehabilitation intervention in selected individuals with possible poor long-term cognitive outcomes.

Injury to the optic nerve, termed, traumatic optic neuropathy (TON) is a known comorbidity of traumatic brain injury (TBI) and is now known to cause chronic and progressive retinal thinning up to 35 years after injury. Although animal models of TBI have described the presence of optic nerve degeneration and research exploring acute mechanisms is underway, few studies in humans or animals have examined chronic TON pathophysiology outside the retina. We used a closed-head weight-drop model of TBI/TON in 6-week-old male C57BL/6 mice. Mice were euthanized 7-, 14-, 30-, 90-, and 150-days post injury (DPI) to assess histological changes in the visual system of the brain spanning a total of 12 regions. We show chronic elevation of FluoroJade-C, indicative of neurodegeneration, throughout the time course. Intriguingly, FJ-C staining revealed a bimodal distribution of mice indicating the possibility of subpopulations that may be more or less sus-ceptible to injury outcomes. Additionally, we show that microglia and astrocytes react to optic nerve damage in both temporally and regionally different ways. Despite these differences, as-trogliosis and microglial changes were alleviated between 14-30 DPI in all regions examined, perhaps indicating a potential critical period for intervention/recovery that may determine chronic outcomes.

The upper extremities limitation represents one of the essential functional impairments in patients with cervical spinal cord injury. Electromechanics assisted devices and robots are increasingly used in neurorehabilitation to help functional improvement in patients with neurological diseases. This review aimed to systematically report the evidence-based, state-of-art on clinical applications and robotic-assisted arm training (RAT) in motor and functional recovery in subjects affected by cervical spinal cord injury. The present study has been carried out within the framework of the Italian Consensus Conference on "Rehabilitation assisted by robotic and electromechanical devices for persons with disability of neurological origin" (CICERONE). PubMed/MEDLINE, Cochrane Library, and Physiotherapy Evidence Database (PEDro) databases were systematically searched from inception to September 2021. The 10-item PEDro scale assessed the study quality for the RCT and the AMSTAR-2 for the systematic review. Two different authors rated the studies included in this review. If consensus was not achieved after discussion, a third reviewer was interrogated. The 5-item Oxford CEBM scale was used to rate the level of evidence. A total of 11 studies were included. The selected studies were: two systematic reviews, two RCTs, one parallel-group controlled trial, one longitudinal intervention study and five case series. One RCT was scored as a high-quality study, while the systematic review was of low quality. RAT was reported as feasible and safe. Initial positive effects of RAT were found for arm function and quality of movement in addition to conventional therapy. The high clinical heterogeneity of treatment programs and the variety of robot devices could severely affect the generalizability of the study results; therefore, future studies are warranted to standardize the type of intervention and evaluate the role of robotic-assisted training in subjects affected by cervical spinal cord injury.

We validated a new noninvasive tool (B4C) to assess intracranial pressure waveform (ICPW) morphology in a set of neurocritical patients, correlating the data with ICPW obtained from invasive catheter monitoring. Materials and Methods: Patients undergoing invasive intracranial pressure (ICP) monitoring were consecutively evaluated using the B4C sensor. Ultrasound-guided manual internal jugular vein (IJV) compression was performed to elevate ICP from the baseline. ICP values, amplitudes, and time intervals (P2/P1 ratio and time-to-peak [TTP]) between the ICP and B4C waveform peaks were analyzed. Results: Among 41 patients, the main causes for ICP monitoring included traumatic brain injury, subarachnoid hemorrhage, and stroke. Bland-Altman’s plot indicated agreement between the ICPW parameters obtained using both techniques. The strongest Pearson’s correlation for P2/P1 and TTP was observed among patients with no cranial damage (r = 0.72 and 0.85, respectively) in detriment of those who have undergone craniotomies or craniectomies. P2/P1 values of 1 were equivalent between the two techniques (area under the receiver operator curve [AUROC], 0.9) whereas B4C cut-off 1.2 was predictive of intracranial hypertension (AUROC 0.9, p < 000.1 for ICP > 20 mmHg). Conclusion: B4C provided biometric amplitude ratios correlated with ICPW variation morphology and is useful for noninvasive critical care monitoring.

The postnatal rodent spinal cord in-vitro is a useful model to investigate early pathophysiological changes after injury. While low dose nicotine (1µM) induces neuroprotection, how higher doses affect spinal networks is unknown. Using spinal preparations of postnatal wild-type Wistar rat and Wnt1Cre2:Rosa26Tom double-transgenic mouse, we studied the effect of nicotine (0.5-10µM) on locomotor networks in-vitro. Nicotine 10µM induced motoneuron depolarization, suppressed monosynaptic reflexes, and decreased fictive locomotion in rat spinal cord. Delayed fall in neuronal numbers (including motoneurons) of central and ventral regions emerged without loss of dorsal neurons. Conversely, nicotine (0.5-1µM) preserved neurons throughout the spinal cord and strongly activated the Wnt1 signaling pathway. High-dose nicotine enhanced expression of S100 and GFAP in astrocytes suggesting their response to stress. Excitotoxicity induced by kainate was contrasted by nicotine (10µM) in the dorsal area and persisted in central and ventral regions with no change basal Wnt signaling. When combining nicotine with kainate, the activation of Wnt1 was reduced compared to kainate/sham. The present results suggest that high dose nicotine was neurotoxic to central and ventral spinal neurons as the neuroprotective role of Wnt signaling became attenuated. This also corroborates the risk of cigarette smoking for the foetus/newborn since tobacco contains nicotine.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To contain the virus, numerous preventive measures have been taken including isolation of patients, careful infection control, social distancing, and taking vaccine. So far, new confirmed and death cases are still increasing. SARS-CoV-2 invades cells by using the angiotensin converting enzyme 2 (ACE2). ACE2 is an essential enzyme of the renin-angiotensin system (RAS) which converts angiotensin II (Ang II) to angiotensin (1-7). ACE2 is expressed in different organs, including lung, heart, and kidney. A high number of COVID-19 patients developed kidney injury has been reported. Renal impairment and acute injury are associated with mortality of COVID-19, which is 14-16 times higher than other general patients. Acute Kidney Injury has been occured in 2.9 up to 43% of intensive care unit patients. The increasing evidence show that the components of RAS can activate the complement cascade, and cytokines production. Kidney injury caused by SARS-CoV-2 is related mainly to systemic and local inflammation. Moreover, the uncontrolled immune responses mediated by SARS-CoV-2 including hypercytokinaemia, secondary hemophagocytic lymphohistiocytosis, antibody dependent enhancement, complement system, and phagocytic cells activation can contribute in the virus pathogenesis leading to associated renal dysfunction. However, the role and crosstalk between of RAS components and immune response in mediating kidney injury remain undefined. In this review, we focus on the recent studies to provide the pathogenesis of SARS-CoV-2 interacting with RAS and immune responses to mediate kidney injury.

Current interventions are not effectives in preventing sepsis-induced acute kidney injury and its long-term outcomes or even after second renal insult. Therapeutic strategies using lipid mediators, as aspirin-triggered resolvin D1 (ATRvD1), can contribute for resolution of acute and chronic inflammation. In this study, we examined the potential effect of ATRvD1 on long-term kidney dysfunction after severe sepsis. Fifteen days after cecal ligation and puncture (CLP), sepsis-surviving BALB/c mice were subjected to a tubulointerstitial injury through intraperitoneal injections of bovine serum albumin (BSA) for 7 days, called subclinical acute kidney injury (subAKI) animal model. ATRvD1 treatment was performed right before BSA injections. On day 22 after CLP, urinary protein/creatinine ratio (UPC), histologic parameters, fibrosis, cellular infiltration, apoptosis, inflammatory markers levels, and mRNA expression were determined. ATRvD1 treatment mitigated tubulointerstitial injury by reducing the proteinuria excretion, UPC ratio, glomerular cell number and extracellular matrix deposition. Pro-fibrotic markers, as transforming growth factor β (TGFb), type 3 collagen and metalloproteinase (MMP)-3 and -9 were reduced after ATRvD1 administration. Post-septic mice treated with ATRvD1 were protected from renal apoptosis and recruitment of F4/80+ cells. Interleukin-1b (IL-1b) levels were increased in subAKI animal model, being attenuated by ATRvD1. Tumor necrosis factor-a (TNF-a), IL-10 and IL-4 mRNA expression was increased in the kidney of BSA-challenged post-septic mice and it was also reduced after ATRvD1. These results suggest that ATRvD1 protects the kidney against a second insult as BSA-induced tubulointerstitial injury and fibrosis by suppressing inflammatory and pro-fibrotic mediators in renal dysfunction after sepsis.

Introduction:In this study we evaluated the connivance of oxidative and antioxidative parameters in the pathogenesis of spinal cord injury (SCI). Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress may play a significant role in the pathophysiology of SCI. Furthermore, there is little information available in scientific literature about oxidative and antioxidative parameters in SCI patients. Methods:Oxidative stress was determined by measuring the levels of Lipid Peroxides (LPO) and Protein carbonyl in plasma and antioxidative parameters like Glutathione Reductase (GR), catalase and Glutathione peroxidase (GPx) in lysate in 40 SCI patients and 40 healthy subjects without SCI. However, pain was measured by McGill pain questionnaire. Results: Concentrations of catalase (p<0.01), GR (p<0.01) and GPx (p<0.01) were significantly lower in patients with SCI than in controls, and levels of oxidative stress parameters, LPO (p<0.01), Protein carbonyl (p<0.01) were significantly higher in patients than in controls. A significant positive correlation was found between LPO and pain score among SCI patients group. Furthermore, a significant positive correlation was also found between Protein carbonyl and pain score among SCI patients group than in control group. Conclusion: The present results indicate that SCI patients are exposed to oxidative stress and this escalated oxidative stress may play a role in the etiopathogenesis of the disease. Moreover, our results also show that increased oxidative stress parameters are more strongly amalgamated with pain in SCI patients.