Traumatic brain injury (TBI) is among the leading causes of mortality and long-term impairment globally. TBI has a dynamic pathology encompassing a variety of metabolic and molecular events that occur in two phases, primary and secondary. An external forceful blow to the brain initiates the primary phase, which is followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, rise in oxidative stress, activation of glial cells, and damage to the blood-brain barrier (BBB), resulting in paracellular leakage. There is currently no FDA-approved drug for TBI, but existing approaches rely on delivering small and macromolecular treatments, which are severely constrained by the BBB, poor retention, off-target toxicity, and complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for diagnosis and treatment of TBI. Tissue engineering and use of biomaterials is one such alternative approach. With this approach, neuronal stem cell therapy is combined with synthetically generated tissue materials such as hydrogels, self-assembling peptides, and electrospun nanofibers, which may induce neurite outgrowth, differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines tissue engineering and the use of biomaterials as potential treatments for TBI, including their synthesis, mechanisms of action, and limitations. The review also discusses challenges facing tissue engineering and biomaterial technology including survival rate of transplanted stem cells and the development of biodegradable, biocompatible, and mechanically flexible biomaterials. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help guide the design of future TBI therapies.

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by TUNEL staining and PARP and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, inverted screen test, and climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI.

Head injury is among the most devastating types of injury, specifically called Traumatic Brain Injury (TBI). There is need to diminish the morbidity related with TBI and to improve the outcome of patients suffering TBI. Among the improvements on the treatment of TBI, neuroprotection is one of the upcoming improvements. Citicoline has been used in the management of brain ischemia related disorders, such as TBI. Citicoline has biochemical, pharmacological, and pharmacokinetic characteristics that make it a potentially useful neuroprotective drug for the management of TBI. A short review of these characteristics is included in this paper. Also, a narrative review of almost all the published or communicated studies performed with this drug in the management of patients with head injury is included. Based on the results obtained in these clinical studies, it is possible to conclude that citicoline was able to accelerate recovery of consciousness and to improve the outcome of this kind of patients, with an excellent safety profile. Thus, citicoline could have a potential role in the management of TBI.

Traumatic brain injury (TBI) is a major source of worldwide morbidity and mortality. Patients suffering from TBI exhibit a higher susceptibility to bone loss and an increased rate of bone fractures; however, the underlying mechanisms remain poorly defined. Herein, we observed significantly lower bone quality and elevated levels of inflammation in bone and bone marrow niche after controlled cortical impact-induced TBI in in-vivo CD-1 mice. Further, we identified dysregulated NFB signaling, an established mediator of osteoclast differentiation and bone loss, within the bone marrow niche of TBI mice. Ex vivo studies revealed increased osteoclast differentiation in bone marrow-derived cells from TBI mice, as compared to sham injured mice. Finally, we found bone marrow derived extracellular vesicles (EVs) from TBI mice enhanced the colony forming ability and osteoclast differentiation efficacy of bone marrow cells and activated NFB signaling genes in bone marrow-derived cells. Taken together, we provide evidence that TBI-induced inflammatory stress on bone and the bone marrow niche may activate NFB leading to accelerated bone loss. Targeted inhibition of these signaling pathways may reverse TBI-induced bone loss and reduce fracture rates.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride and calcium levels. This study aims to provide insights into these disturbances within the first 24 hours post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. Results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI 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: 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<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 traumatic brain injury mTBI is a common occurrence around the world, associated with a variety of blunt force and torsion injuries affecting all age groups. Most never reach medical attention, and identification of acute injury and later clearance to return to usual activities is relegated to clinical evaluation particularly in sports injuries. Advanced structural imaging is rarely performed due to the usual absence of associated acute anatomic/hemorrhagic changes. This review targets physiologic imaging techniques available to identify subtle blood brain barrier dysfunction and white matter tract shear injury, and their association with chronic traumatic encephalopathy. These techniques provide needed objective measures to assure recovery from injury in those patients with persistent cognitive/emotional symptoms and in the face of repetitive mTBI.

Background: Alongside their long-term effects - post-concussion syndrome (PCS) - mild traumatic brain injuries (mTBI) are significant public health concerns. Currently, there is a lack of reliable biomarkers for diagnosing and monitoring mTBI and PCS. Exosomes are small extracellular vesicles secreted by cells that have recently emerged as a potential source of biomarkers for mTBI and PCS due to their ability to cross the blood-brain barrier and reflect the pathophysiology of brain injury. This study aimed to investigate the role of salivary exosomal biomarkers in mTBI and PCS. Methods: A systematic review using the PRISMA guidelines was conducted, and studies were selected based on their relevance to the topic. Results: Studies have shown that exosomal tau, phosphorylated tau (p-tau), amyloid beta (Aβ), and microRNAs (miRNAs) are potential biomarkers for mTBI and PCS. Specifically, elevated levels of exosomal tau and p-tau have been associated with mTBI and PCS, as well as with repetitive mTBI. Dysregulated exosomal miRNAs have also been observed in individuals with mTBI and PCS. Additionally, exosomal Prion cellular protein (PRPc), coagulation factor XIII (XIIIa), synaptogyrin-3, IL-6, and aquaporins have been identified as promising biomarkers for mTBI and PCS. Conclusion: Salivary exosomal biomarkers have the potential to serve as non-invasive and easily accessible diagnostic and prognostic tools for mTBI and PCS. Further studies are needed to validate these biomarkers and to develop standardized protocols for their use in clinical settings. Salivary exosomal biomarkers can improve the diagnosis, monitoring, and treatment of mTBI and PCS, leading to improved patient outcomes.

People experiencing homelessness are at risk from a number of co-morbidities including traumatic brain injury, mental health disorders and various infections. Little is known about the rehabilitation needs of this population. This study took advantage of unique access to a specialist ‘Access’ GP practice for people experiencing homelessness and a local inclusion health initiative to explore the five year period prevalence of these conditions in a population of people experiencing homelessness, through electronic case record searches; and identify barriers and facilitators to healthcare provision for this population in the context of an interdisciplinary and multi specialist inclusion health team, through semi structured interviews with 12 staff working in primary and secondary care who interact with this population. The five year period prevalence of TBI, infections and mental health disorders was 9.5%, 4% and 22.8% respectively. Of those who had suffered a brain injury only 3, had accessed rehabilitation services. Themes from thematic analysis of interviews included: lack of resource, stigmatisation, under recognised multi-morbidity (including from brain injury) as barriers, trauma-informed, person-centred, adaptable, & integrated and collaborative models of care as facilitators. The combination of quantitative and qualitative data suggests a potential role for rehabilitation medicine in inclusion health initiatives.

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.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (>1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

Traumatic Brain Injury represents a significant public health concern due to its role in traumatic death and disability, often caused by head impacts or rapid accelerations. Despite advancements in Finite Element Head Models, existing models primarily represent adult males, neglecting anatomical and physiological differences between genders and age groups. Additionally, the mechanistic roles of specific intracranial tissues, such as the dura mater, have conventionally been overlooked. To better understand the mechanical behavior of the brain and its injured regions in the context of TBI, including the dura mater, this study proposes the development of a Female Finite Element Head Model. This model, representative of a middle-aged female subject, was developed using medical image-derived geometry and finite element modeling techniques. The validation results demonstrate a similarity between the numerical displacement curves and those obtained experimentally. In the model with dura mater, the numerical results show analogous behavior to the experimental results, despite minimal variations in the amplitude of the curves. These advancements highlight the significance of including the dura mater in biomechanical brain modeling. Incorporating the dura mater in Finite Element Head Models produces more realistic results than models without it. This emphasizes the importance of enhancing biomechanical models to better represent anatomical complexity.

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.

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.

Emotion recognition and social inference impairments are well-documented post-traumatic brain injury (TBI) yet the mechanisms underpinning these are not fully understood. We examined dynamic emotion recognition, social inference abilities, and eye fixation patterns between adults with and without TBI. Eighteen individuals with TBI and 18 matched non-TBI participants were recruited and underwent all three components of The Assessment of Social Inference Test (TASIT). The TBI group were less accurate in identifying emotions compared to the non-TBI group. Individuals with TBI also scored lower when distinguishing sincere and sarcastic conversations but scored similarly to those without TBI during lie vignettes. Finally, those with TBI also had difficulty understanding the actor’s intentions, feelings, and beliefs compared to participants without TBI. No group differences were found for eye fixation patterns and there were no associations between fixations and behavioural accuracy scores. This conflicts with previous studies and might be related to an important distinction between static and dynamic stimuli. Visual strategies appeared goal- and stimulus-driven, with attention being distributed to the most diagnostic area of the face for each emotion. These findings suggest that low-level visual deficits may not be modulating emotion recognition and social inference disturbances post-TBI.

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.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

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.

Traumatic brain injury (TBI) affects millions of people each year. Previous studies using the central fluid percussion injury (CFPI) model in adult male rats indicated that elevated intracranial pressure (ICP) was associated with long-term effects, including neuronal cell loss and increased sensory sensitivity post-injury and secondary ICP elevation, that were not seen following injury alone. Investigations also indicated that Cathepsin B (Cath B), a lysosomal cysteine protease, may play a role in the pathological progression of neuronal membrane disruption; however, the specific impact of Cath B inhibition following CFPI remains unknown. Thus, the focus of this study was to evaluate the effects of Cath B inhibition via intracerebroventricular infusion of CA-074Me 2w following injury with or without secondary elevation of ICP. This was accomplished using adult male rats continuously infused with CA-074Me or 10% DMSO as a vehicle control for 2w following either sham injury, a CFPI only, or a CFPI with subsequent ICP elevation to 20mmHg. We assessed Cath B activity in the lateral neocortices and liver, evaluated protein levels of Cath B and Cath B binding partners AIF, Bcl-XL, and Bak. We also conducted histological analyses of total cell counts to assess for cell loss, membrane disruption, and Cath B localization. Finally, we investigated somatosensory changes with the whisker nuisance task. Overall, this study demonstrated that Cath B is not a direct driver of membrane disruption, however, administration of CA-074Me alters Cath B localization and reduced hypersensitivity, emphasizing Cath B being an important component in late secondary pathologies.

Treating a patient with traumatic brain injury requires an interdisciplinary approach because of the pervasive, profound and protean manifestations of this condition. In this review, key aspects of the medical history and review of systems will be described in order to highlight how the role of any provider must evolve to become a better patient advocate. Although this review is written from the vantage point of a vision care provider, it is hoped that patients, caregivers and providers will recognize the need for the team approach; it truly takes a village.

Traumatic brain injury (TBI) is an important global clinical issue, requiring not only prevention but also effective treatment. Following TBI, diverse parallel and intertwined pathological mechanisms affecting biochemical, neurochemical, and inflammatory pathways can have severe impact on the patient’s quality of life. The current review summarizes evidence for utility of amantadine in TBI in connection to its mechanism of action. Amantadine combining multiple mechanisms of action may offer both neuroprotective and neuroactivating effects in TBI patients. Indeed, use of amantadine in TBI has been encouraged by several clinical practice guidelines/recommendations. Amantadine is also available as infusion which may be of particular benefit in unconscious patients with TBI, due to immediate delivery to the central nervous system and the possibility of precise dosing. In other situations, orally administered amantadine may be used. There are several questions that remain to be addressed: Can amantadine be effective in disorders of consciousness requiring long-term treatment and in combination with drugs approved for treatment of TBI? Do the observed beneficial effects of amantadine extend to disorders of consciousness due to factors other than TBI? Well controlled clinical studies are warranted to ultimately confirm its utility in the TBI and provide answers these questions.

Traumatic brain injury (TBI) is a global healthcare concern affecting millions, with wide-ranging symptoms including sensory and behavioral changes that can persist long-term. Due to similarities with human brain cytoarchitecture and inflammation, minipig models are advantageous for translational TBI research. However, gaps in knowledge exist regarding their behavioral and sensory sequelae following injury. Therefore, in this study, we assessed changes in approachability using a forced human approach task (FHAT) and mechanical nociception using the von Frey Test in adult male and female Yucatan minipigs for up to one week following a sham or central fluid percussion injury (cFPI). Specifically, the FHAT assessed each animal’s response to a forced interaction with either a known or unknown experimenter. To evaluate changes in nociceptive sensory sensitivity, von Frey monofilaments ranging from 0.008 to 300 grams of force were applied to the pinna of the ear or base of the tail. We found that forced approachability was affected by experimenter familiarity as well as cFPI in a sex-specific manner at subacute timepoints. We also found reductions in sensitivity following cFPI on the ear in male minipigs and on the tail in female minipigs. Overall, the current study demonstrates that cFPI produces both behavioral and sensory changes in minipigs up to one-week post-injury.

Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive. In this study, hindlimb postural asymmetry (HL-PA) development in rats subjected to focal TBI was investigated to explore the potential roles of laminin and collagen IV within the ECM of selected hindlimb muscles in the emergence of motor deficits following TBI. A focal TBI was induced by ablating the left sensorimotor cortex in rats and motor deficits were assessed by measuring HL-PA. The expression of laminin and collagen IV in eight selected muscles on each side of the hindlimbs from both TBI and sham-operated rats were studied using immunohistochemistry and semi-quantitatively analyzed. Results indicated that the TBI rats exhibited HL-PA, characterized by flexion of the contralateral (right) hindlimb. In the sham-operated rats the immunoreactive components of laminin and collagen IV were evenly and smoothly distributed along the border of the muscle fibers in all the investigated muscles. In contrast, in the TBI rats the pattern was broken into aggregated granule-like immunoreactive components. Such a labeling pattern was detected in all the investigated muscles both from the contra-and ipsilateral side of the TBI rats. However, in TBI rats most of the muscles from the contralateral hindlimb showed a significant increased expression of these two proteins in comparison with those from the ipsilateral hindlimb. In comparison to sham-operated rats, there was a significant increase in laminin and collagen IV expression in various contralateral hindlimb muscles in the TBI rats. These findings suggest potential implications of laminin and collagen IV in the development of motor deficits following a focal TBI.

Purpose: Dysarthria, a neurological injury of the motor component of the speech circuitry, is of common consequences of traumatic brain injury (TBI). Palilalia is a speech disorder characterized by involuntary repetition of words, phrases, or sentences. Based on the evidence supporting the effectiveness of transcranial direct current stimulation (tDCS) in some speech and language disorders, we hypothesized that using tDCS would enhances the effectiveness of speech therapy in a client with chronic dysarthria following TBI. Method: We applied the constructs of the “Be Clear” protocol, a relatively new approach in speech therapy in dysarthria, together with tDCS on a chronic subject who affected by dysarthria and palilalia after TBI. Since there was no research on the use of tDCS in such cases, regions of interest (ROIs) were identified based on deviant brain electrophysiological patterns in speech tasks and resting state compared with normal expected patterns using the Quantitative Electroencephalography (QEEG) analysis. Results: Measures of perceptual assessments of intelligibility, an important index in the assessment of dysarthria, ​​were superior to the primary protocol results immediately and 4 months after intervention. We did not find any factor other than the use of tDCS to justify this superiority. The percentage of repeated words, an index in palilalia assessment, had a remarkable improvement immediately after intervention but fell somewhat after 4 months. We justified this case with subcortical origins of palilalia. Conclusion: Our present case-based findings suggested that applying tDCS together with speech therapy may improve intelligibility in similar case profiles as compared to traditional speech therapy. To reconfirm the effectiveness of the above approach in cases with dysarthria following TBI, more investigation need to be pursued.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition caused by repeated traumatic brain injuries (TBIs) leading to cognitive, behavioral, and motor dysfunctions. This study examined the relationship between cognitive impairment and clinical syndromes among 145 CTE patients aged 18 to 75 years who underwent inpatient treatment at the Ternopil Regional Clinical Psychoneurological Hospital between 2021 and 2022. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), with results classified into four categories: normal, mild impairment, moderate impairment, and dementia. Statistical analysis revealed significant associations between cognitive impairment and specific neuroimaging changes, including ventricular dilatation. Clinical syndromes, such as cognitive disorder syndrome, also showed significant associations with cognitive impairment (p &lt; 0.001). Using logistic regression, we developed a predictive model to estimate the probability of cognitive impairment based on various clinical features, including memory loss, attention deficits, and sleep disturbances. The model demonstrated high accuracy, with a receiver operating characteristic (ROC) curve showing a sensitivity of 91.0% and a specificity of 92.5%, yielding an area under the curve (AUC) of 0.964 (95% CI: 0.934 - 0.994). These findings suggest that specific neuroimaging and clinical features can predict cognitive impairment in CTE patients.

Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood-brain barrier (BBB), which prevents passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of pro-inflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance in KAFAK-treated mice. This study demonstrates KAFAK's ability to cross the blood-brain barrier, to lower pro-inflammatory cytokine levels in vivo, and to restore function after a moderate TBI.

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely diagnose and assess complications long-term. Insufficient information is available regarding how to precisely diagnose and assess mTBI. This study identified and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated in this pilot study, including 11 mTBI cases (27.3% females; mean age of 28.7 years, SD=5.92) and 14 healthy controls (64.3% females; mean age of 22.0, SD=4.13). All the participants were assessed for cognitive (by NIH toolbox—executive function, memory, and processing speed), psychological (by PROMIS—depression, anxiety, and sleep disturbances), visual function (by King-Devick and binocular accommodative tests), postural balance performance (by a force plate), and blood 5-mC% (global methylation) levels. Students with mTBI reported significantly poorer episodic memory, severe anxiety, and more sleep disturbance problems. They also had higher blood 5-mC% level (all p’s<.05). No significant differences were found in visual function and postural balance. These findings validate changes in cognitive, psychosocial, and global DNA methylation long after mTBI.

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.

Survivors of severe brain injury may require care in a neurointensive care unit (neuro-ICU), where the brain is vulnerable to secondary brain injury. Thus, there is a need for noninvasive, bedside, continuous cerebral blood flow monitoring approaches in the neuro-ICU. Our goal is to address this need through combined measurements of EEG and functional optical spectroscopy (EEG-Optical) instrumentation and analysis to provide a complementary fusion of data about brain activity and function. The present case demonstrates in a patient with traumatic brain injury, noninvasive cerebral blood flow transients can be recorded that correlate with gold-standard invasive measurements and with the frequency content changes in the EEG data during clinical care.

Traumatic brain injury (TBI) causes multiple cerebrovascular disruptions and oxidative stress, resulting in pathophysiological mechanisms. These are often accompanied by serious impairment in cerebral blood flow autoregulation, as well as neuronal and glial degeneration. Most currently available early antioxidant therapies lack sufficient efficacy. However, the application of a newly developed class of biologically compatible carbon-based nanoclusters, namely poly-ethylene-glycol-functionalized hydrophilic carbon clusters (PEG-HCCs), mitigate secondary injury after a TBI in early studies. In the present pilot study, we explore the efficacy of PEG-HCCs in an open blast rat model of TBI. Here we report on the neuroprotective efficacy of PEG-HCCs.

The Sars-Cov-2 pandemic led to several needed containing measures that conditioned the onset of depressive, anxiety and post-traumatic stress symptoms in population. These symptoms, espe-cially if not diagnosed and treated, can also occur in patients undergoing surgery with high im-pact on people’s lives, like hysterectomy. To evaluate the post-surgical distress and anx-ious-depressive symptoms following hysterectomy for benign disease focusing on the impact of COVID-19 pandemic. The prospective observational cohort study included patients undergoing hysterectomy for benign disease. Psychologic evaluation through social-demographic question-naires was obtained before surgery (T1), postoperatively (T2), and 3 months after surgery (T3). The HADS (Hospital Anxiety and Depression Scale) was used to evaluate anxious-depressive symptoms and the PCL-5 (Post-traumatic Stress Disorder Checklist for DSM-5) compared the on-set of post-surgical distress and anxiety and depressive symptoms. The pre-COVID-19 pan-demic period was compared to the post-COVID-19 pandemic phase. Patients treated after COVID-19 pandemic showed higher depressive symptoms rate compared to those treated before (p-value=0.02); conversely, pre-COVID-19 patients were more prone to develop a PTSD (p-value=0.04). A significative association between the occurrence PTSD and anxiety-depressive symptoms registered at T2 a (p-value=0.007) and T3 (p-value

Assessment of health-related quality of life (HRQoL) after pediatric traumatic brain injury (TBI) has been limited in children and adolescents due to a lack of disease-specific instruments. To fill this gap, the Quality of Life after Traumatic Brain Injury for Children and Adolescents (QOLIBRI-KID/ADO) was developed for the German-speaking population. Reference values from a comparable general population are essential for comprehending the impact of TBI on health and well-being. This study examines the validity of the German QOLIBRI-KID/ADO in a general pediatric population in Germany and provides reference values for use in clinical practice. Overall, 1997 children and adolescents aged 8-17 years from the general population and 300 from the TBI population participated in the study. The questionnaire was tested for reliability and validity. A measurement invariance (MI) approach was used to assess the comparability of the HRQoL construct between both samples. Reference values were determined by percentile-based stratification according to factors that significantly influenced HRQoL in regression analyses. The QOLIBRI-KID/ADO demonstrated strong psychometric properties. The HRQoL construct was measured largely equivalently in both samples, and reference values could be provided. The QOLIBRI-KID/ADO was considered reliable and valid for assessing HRQoL in a general German-speaking pediatric population, allowing for clinically meaningful comparisons between general and TBI populations.

Objective: To investigate whether the relationships between acute care occupational therapy (OT) and physical therapy (PT) utilization and community discharge are moderated by functional or physical performance at discharge among individuals hospitalized with traumatic brain injury (TBI). Setting: 14 acute care hospitals in the state of Colorado. Participants: We studied 5,599 adults hospitalized with TBI between June 2018 and April 2021. Design: In a secondary analysis of de-identified electronic health record (EHR) data, multivariable moderation logistic regression models were performed to calculate odds ratios (ORs) for the likelihood of community discharge among patients who utilized OT/PT services. Main Measures: Functional (activities of daily living [ADL]) and physical (mobility) performance at discharge, OT and PT utilization, and community discharge status. Results: Overall, 67% of patients discharged to the community. The mean age of the sample was 55 years (SD = 20 years). Most participants were male (64%) and non-Hispanic white (72%). Mean hospital length of stay was 6 days (SD = 6 days). Both OT and PT utilization (OT: OR= 1.21, 95% CI [1.11, 1.33]; PT: OR= 1.22, 95% CI [1.14, 1.30]) and discharge ADL and mobility scores (ADL: OR= 1.34, 95% CI [1.30, 1.39]; mobility: OR= 1.38, 95% CI [1.33, 1.42]) were significantly and positively associated with community discharge. The OT and PT utilization-by-discharge ADL and mobility interaction terms yielded slightly negative, but statistically significant moderation effects in both models (ORs= 0.99, 95% CIs [0.98, 1.00]); indicating the magnitude of the OT and PT utilization effect diminished as ADL and mobility scores increased. Several sociodemographic characteristics and clinical factors were also independently associated with community discharge in both models (p-values

Previous studies suggested that trauma-focused cognitive behavior therapy (TF-CBT) is effective in reducing symptoms of post-traumatic stress disorder (PTSD) and depression in children and adolescents. However, the effects of app-assisted TF-CBT-based interventions in psychiatric clinics compared to treatment-as-usual (TAU) are under-explored. The purpose of this study was to reveal the added value of the app-assisted TF-CBT-based intervention as an add-on to TAU. The digitalized measures of the Child and Adolescent Trauma Screen (CATS), The Adolescent Dissociative Experience Scale (A-DES), Short Moods and Feelings Questionnaire (SMFQ), PTSD Checklist (PCL-5), and Children's Post-Traumatic Cognitions Inventory (CPTCI) were applied at baseline and post-treatment. The app-assisted TF-CBT-based group participants started with higher levels of negative alterations in cognition and mood compared to TAU participants but at post-treatment, no significant differences were observed between the app-assisted TF-CBT and TAU groups. Within the app-assisted TF-CBT group, post-treatment scores were significantly lower in post-traumatic stress symptoms, intrusion symptoms, alterations in arousal and reactivity, overall post-traumatic cognitions, and belief in being "a fragile person in a scary world”. Within the TAU group, post-treatment scores were notably lower just in dissociation and intrusion symptoms. The study suggests that app-assisted TF-CBT-based intervention can be effective in addressing specific trauma-related symptoms. The findings imply the necessity for screening for traumatic experiences, incorporating trauma-informed care, implementation of TF-CBT into treatment protocols, utilization of app-assisted interventions, tailoring interventions to individual needs, and comprehensive assessment and monitoring of treatment progress.

Chronic traumatic encephalopathy (CTE) is a unique neurodegenerative disease that is associated with repetitive head impacts (RHI) in both civilian and military settings. In 2014, the research criteria for the clinical manifestation of CTE, traumatic encephalopathy syndrome (TES) were proposed to improve the clinical identification and understanding of the complex neuropathological phenomena underlying CTE. This review provides a comprehensive overview of the current understanding of the neuropathological and clinical features of CTE, proposed biomarkers of traumatic brain injury (TBI) in both research and clinical settings, and a range of treatments based on previous preclinical and clinical research studies. Due to the heterogeneity of TBI, there is no universally agreed-upon serum, CSF, or neuroimaging marker for its diagnosis. However, as our understanding of this complex disease continues to evolve, it is likely that there will be more robust, early diagnostic methods and effective clinical treatments. This is especially important given the increasing evidence of a correlation between TBI and neurodegenerative conditions, such as Alzheimer's disease and CTE¹. As public awareness of these conditions grows, it is imperative to prioritize both basic and clinical research, as well as the implementation of necessary safe and preventative measures.

Abstract Objectives To assess the causes and risk factors of posttraumatic stress disorder (PTSD) in adult asylum seekers and refugees. To explore whether the causes and risk factors of PTSD, between male and female adult refugees/ asylum seekers is different. Study design Systematic review of current literature. Data Sources PubMed, Web of Science, Scopus and Google Scholar up until February 2019 Method A structured systematic search was conducted in the relevant databases. Papers were excluded, if they failed to meet the inclusion and exclusion criteria. Afterwards, a qualitative assessment was performed on the selected papers. Results 12 Studies were included for the final analysis. All papers were either case studies/report or cross sectional studies. The number of traumatic events experienced by refugees/asylum seekers, is the most frequently reported pre-migration causes for PTSD development. Whilst acculturative stress, is the most common post migration stressor. There were mixed reports, regarding the causes of PTSD between both genders of refugees/asylum seekers. Conclusion This reviews’ findings, have potential clinical application into helping clinicians, to risk stratify refugees/asylum seekers for PTSD development and thus aid in embarking on earlier intervention measures. However, more rigorous research similar to this one, is needed for it to be implemented into clinical practice.

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.

The present review aimed to identify through what means neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system (CNS) that, when damaged, lead to distinct PTSD symptoms–namely dissociative reactions or flashbacks. Our review narrowed its focus to three common neurologic injuries including traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the role of noradrenergic neuromodulatory signaling on the HPA axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. This paper also described how damage to the CNS can alter the function of the limbic system and result in characteristic symptoms of PTSD like intrusive memories and acute psychological distress. Further, our review intended to draw attention to a lack of PTSD prognosis in TBI, SAH, and stroke patients who could benefit from early treatment. PTSD symptoms often compound with pre-existing issues further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD such that earlier diagnoses and appropriate treatment are observed in clinic.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality among all ages; despite the advances, understanding pathophysiological responses after TBI is still complex, involving multiple mechanisms. Previous reviews have focused on potential targets; however, the research on potential targets has continuously grown in the last five years, bringing even more alternatives and elucidating previous mechanisms. Knowing the key and updated pathophysiology concepts is vital for adequate management and better outcomes. This article reviews the underlying molecular mechanisms, the latest updates, and future directions for pathophysiology-based TBI management.

Background Posttraumatic stress disorder (PTSD) is a complex condition that represents a significant burden in terms of individual disability and societal costs. Despite decades of research investigating treatment options, PTSD remains a major cause of quality-of-life impairment. We hypothesized that patients with PTSD might benefit from peripheral somatosensory stimulation (PSS) therapy. Methods Six adult patients with clinically diagnosed PTSD were enrolled to undergo daily PSS therapy over a 4-week period. Patients completed two surveys evaluating satisfaction with treatment and overall well-being (Survey 1) and severity of PTSD symptoms (Survey 2). Survey 1 was completed weekly during the course of the study. Survey 2 was based on the 9-question National Stressful Events Survey PTSD Short Scale (NSESSS) and was completed as a baseline prior to initiation of therapy and then at the conclusion of the trial. All data were analyzed by an independent statistician. Results Six male patients were enrolled in the study; all completed the trial. All patients demonstrated a decrease in symptoms within one week of initiation of therapy. This benefit was sustained and appeared to further improve over the course of the trial. For Survey 1, the overall median scores demonstrated a significant time-dependent improvement across measurement times (p < 0.001). For Survey 2, patients had statistically significant improvements from baseline regarding feelings of being emotionally upset and being overly alert. Results from a cumulative link mixed model demonstrated that treatment yielded a 38.2-fold higher likelihood of transitioning from a higher PTSD score at baseline to a lower (improved) score at week 4. No adverse events were described by the patients. Conclusions PSS stimulation appeared to improve symptoms in all six patients with PTSD symptoms in this trial. Patients had unanimous and clinically meaningful improvement in overall PTSD symptoms with treatment. By week 4, all patients responded that they enjoyed the treatment and would like to keep their device. We suggest that further investigation into the potential usefulness of PSS therapy in patients with PTSD is warranted.

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.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved Pharmacotherapy and Psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we reviewed clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA) assisted Psychotherapy in PTSD patients, its pharmacokinetics and current treatment guidelines for PTSD. Based on the results of the efficacy of MDMA assisted Psychotherapy from six phases II Randomized controlled trials. MDMA-assisted Psychotherapy for PTSD has received the “Breakthrough Therapy” designation from the FDA. MDMA can potentially reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e. dopamine, serotonin, norepinephrine and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.

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.

Background: The practice of heading in soccer is widely recognized as an important aspect of the game both offensively and defensively, frequently implemented by players. However, concerns persist about the negative impact of this technique on players' cognitive function and symptoms, both in the short and long-term. This meta-review aims to systematically map the existing literature on soccer heading and its implications on the long-term effects; Methods: We conducted a meta-review of systematic reviews following PRISMA-ScR guidelines in PubMed, Embase and Web of Science databases. Searches were conducted between 21 February and 20 March 2024, in English, with a limitation to articles published between January 2000 and March 2024.; Results: Three systematic reviews were eligible for having addressed the subject of head-ball impacts in soccer and their physiological, neurological and cognitive impact. While most studies did not report any significant long-term changes, short-term impairments in memory and reaction time were observed in some instances, normalizing within 24 hours. Neurochemical markers showed mixed results, with increased NF-L levels persisting up to a month in certain cases. Visual reflexes and corticomotor inhibition also exhibited temporary dysfunctions post-heading; Conclusions: This meta-review highlighted the limited number of systematic reviews on the effects of heading in soccer in young and adult players. The current evidence suggests that while heading may lead to short-term cognitive and physiological changes, the long-term effects remain uncertain and probably under-studied. Further research, particularly with professional players and standardized methodologies on long-term follow-up, is needed to clarify these potential risks and inform safety measures in soccer.

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.

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.

We aimed to evaluate the feasibility and preliminary efficacy of trauma-focused group psychotherapy in adolescents who experienced traumatic events in Korea. Participants were assigned and recruited from two sites in Korea. Children in Disaster: Evaluation and Recovery (CIDER) V1.0 is a trauma-focused group psychotherapy approach consisting of psychoeducation, normalization, stabilization, and techniques of managing the traumatic memory. The CIDER intervention consists of eight 50-minute-long sessions. The effectiveness of the intervention was evaluated using the Korean version of the Children’s Response to Traumatic Events Scale-Revised (K-CRTES-R), the Beck Depression Inventory (BDI), the State Anxiety Inventory for Children (SAIC), and the Pediatric Quality of Life Inventory (PedQL). Data were analyzed by Wilcoxon signed-rank test. We recruited 22 traumatized adolescents (mean age 16 years; SD 1.43; range 13–18 years old; 71.4% boys) in this pilot study. The K-CRTES-R scores were significantly improved (Z = −2.85, p < 0.01). The BDI demonstrated the effectiveness of the therapy (Z = −2.35, p < 0.05). The assessment of the PedQL supported the effect of CIDER (Z = −3.08, p < 0.01). However, there was no statistically significant differences in the SAIC scores (Z = −1.90, p > 0.05). The results show that there is preliminary evidence that CIDER intervention reduces post-traumatic stress and depressive symptoms and improves quality of life. Our findings indicate that CIDER is feasible for treating adolescents exposed to traumatic events. Larger controlled trials are needed to establish the efficacy of this trauma-focused group psychotherapy and examine its impact on post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD), a mental disorder caused by exposure to traumatic stress, affects 5-10% of the world’s population. PTSD is associated with several medical and neurological comorbidities. It has been suggested that these are due to accelerated aging, and that changes in telomere length (TL) and telomerase enzyme activity may serve as biomarkers of this process. Early research in this field suggested that TL was significantly reduced in PTSD. The current review was conducted to provide a critical analysis of recent clinical and translational research on telomere length and telomerase in PTSD. The results of 26 clinical studies suggest that TL in PTSD is highly variable, and may be influenced by methodological, demographic, trauma-related and psychosocial factors. There is no evidence for altered telomerase activity in PTSD, though this was hypothesized by earlier workers in the field. Translational research suggests that exposure to traumatic stress does lead to TL shortening. Overall, it is likely that TL in PTSD depends on several variables that are specific to individuals and groups. Other markers of cellular aging, such as epigenetic changes, may be more specific indices of accelerated aging in patients with PTSD.

Adverse childhood experiences (ACEs) refer to traumatic life events in childhood that comprise abuse (e.g., psychological, physical, sexual), neglect (psychological and physical), indirect violence or household dysfunctions. Studies have found ACEs to be related to severe short-, medium- and long-term consequences in victims’ health. The current work consists of a real-world, multicentric, prevalence study of health outcomes in children <16 years suspected of ACEs by physicians. It relies on electronic health records and healthcare registries from a Portuguese local healthcare unit between January 2001 and December 2021 (N=40 536). Three health outcome groups were analyzed: (1) traumatic injuries and intoxications (2) mental health disorders, and (3) physical disorders. Keywords and ICD-9, ICD-10, and ICPC-2 codes from were employed. Children suspected of ACEs represent 2% (n=918). Social problems, injuries and intoxications, mental health disorders, and physical disorders arise in higher percentages in suspected victims than in non-suspected individuals. Findings uncover that child victims of ACEs may be underdiagnosed. Given the severe consequences for their current and future health, this should be taken as a critical warning for healthcare professionals. Detection and reports in health units are fundamental for early treatment, aiming to avoid an escalation of damage and prevent re-victimization.

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.

Traumatic myiasis is a parasitic infestation resulting from feeding fly larvae in traumatic lesions in the cutaneous tissues of vertebrate hosts. Species that cause traumatic myiasis are found in the families Calliphoridae and Sarcophagidae. This study evaluated the traumatic myiasis cases detected during examining animals brought to Dicle University Wildlife Rescue, Rehabilitation, Training, Practice, and Research Center with wound complaints between 2020-2022. Species determinations of the larvae collected from traumatic myiasis cases were detected in five different animals were made as morphological and molecular, and four species were detected, including Lucilia sericata, Wohlfahrtia magnifica, Calliphora vicina, and Calliphora vomitria. We report a case of traumatic myiasis in the Euphrates softshell turtle and Wild goat for the first time. In order to reduce the exposure of wild animals to traumatic myiasis, new strategies for fly control need to be developed.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

Previously we demonstrated, in rats, that the treatment with growth hormone (GH) and rehabilitation, carried out immediately after a motor cortical ablation, significantly improved the motor affectation produced by the lesion and induced the re-expression of nestin in the contralateral motor cortex. Here we analyze cortical proliferation after ablation of the frontal motor cortex and investigate the re-expression of nestin in the contralateral motor cortex and the role of the striatum and thalamus in motor recovery. The rats were subjected to ablation of the frontal motor cortex in the dominant hemisphere or sham-operated and immediately treated with GH or vehicle (V), for five days. At 1 dpi (days after injury), 5 rats received daily injections (4 days) of bromodeoxyuridine and were sacrificed. The other 15 rats (n = 5 / group) underwent treatment and rehabilitation and were sacrificed at 25 dpi. GH induced the greatest number of proliferating cells in the perilesional cortex. GH and rehabilitation produced the functional recovery of the motor lesion and increased the expression of nestin in the striatum. In the thalamic ventral nucleus ipsilateral to the lesion, cells positive for nestin and actin were detected, but this was independent of GH. Our data suggest that GH-induced striatal nestin is involved in motor recovery.

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.

The management of shoulder instability in children and adolescents is a challenging field of orthopaedics. There are several complicating factors which originate from the variable underlying cause that is often a unique combination of traumatic factors, ligamentous laxity, and the pattern of muscle contractility. As the cause is often multifactorial, this makes interpretation of the literature difficult as nomenclature is variable. The purpose of this review is to shed light on the nuances of paediatric and adolescent shoulder instability.

Memory and emotion are highly vulnerable to psychiatric disorders like post-traumatic stress disorder (PTSD), which has been linked to serotonin (5-HT) metabolism disruptions. In fact, over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) meta-bolic pathway, producing a variety of bioactive molecules. The aadat (kat2) gene encodes mito-chondrial kynurenine aminotransferase (KAT) isotype 2, responsible for kynurenic acid (KYNA) production. Little is known about its role in behavior. In CRISPR/Cas9-induced aadat knockout (kat2−/−) mice, we examined the effects on emotion, memory, motor function, Trp and its metabolite levels, enzyme activities in the plasma and the urine of 8-week-old males compared to wild-type mice. Transgenic mice showed more depressive-like behaviors in the forced swim test, but not in the tail suspension, anxiety, or memory tests. They also had fewer center field and corner entries, shorter walking distances, and fewer jumping counts in the open field test. Plasma metabolite levels are generally consistent with those of urine: KYN, antioxidant KYNs, 5-hydroxyindolacetic acid, and indole-3-acetic acid levels are lower; enzyme activities in KATs, kynureninase, and monoamine oxidase/aldehyde dehydrogenase are lower, but kynurenine 3-monooxygenase is higher; and ox-idative stress and excitotoxicity indices are higher. Transgenic mice show depression-like behavior in a learned helplessness model, emotional indifference, and motor deficits, coupled with a decrease in KYNA, a shift of Trp metabolism toward the KYN-3-HK pathway, and a partial decrease in the gut microbial Trp-indole pathway metabolite. This is the first evidence that deleting the aadat gene causes depression-like behaviors that are unique to despair experience, which appears to be linked to excitatory neurotoxic and oxidative stresses. This may lead to the development of a double-hit preclinical model in experience-based depression, better understanding of these complex condi-tions, and more effective therapeutic strategies by elucidating the relationship between Trp me-tabolism and PTSD pathogenesis.

N-methyl-D-aspartate receptors (NMDARs) are the main class of ionotropic receptor for the ex-citatory neurotransmitter glutamate. It plays a crucial role in the permeability of Ca2+ ions and excitatory neurotransmission in the brain. Being heteromeric receptors, they are composed of sev-eral subunits, including two obligatory GluN1 subunits (eight splice variants) and regulatory GluN2 (GluN2A~D) and/or GluN3 (GluN3A~B) subunits. Widely distributed in the brain, they regulate other neurotransmission systems and are therefore involved in essential functions such as synaptic transmission, learning and memory, plasticity, excitotoxicity. The present review will discuss the physiopathological impacts of NMDAR and particularly GluN2A and GluN2B subu-nits in cognitive processes and neurodegenerative diseases (Alzheimer's disease, Huntington's disease, Parkinson's disease). The pharmacology of different NMDAR antagonists and their po-tentialities will be presented. In particular, a focus will be given on fluoroethylnormemantine (FENM), an investigational drug with very promising developments as a tomography radiotracer for NMDARs, an anxiolytic in post-traumatic stress disorder and a neuroprotective agent in Alzheimer's disease.

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.

Introduction: Detection of diaphragmatic injury in blunt trauma can be challenging in the absence of surgical exploration. Here we explore the mechanisms of injury and detection modes for patients with blunt trauma who had a diaphragmatic injury. Methods: This is a single-center, retrospective review conducted in a level 1 trauma center, 2016 to 2023, inclusive. We included all patients who presented with a blunt traumatic diaphragm injury (TDI). We identified nine patients with TDI using AIS injury description and type of trauma. Patient demographics, mechanism of injury, injury severity score (ISS), mode of diagnosis, and clinical outcomes were reviewed. Results: Of the nine patients identified with blunt TDI, two were associated with motor vehicle collisions, four were pedestrians struck, 1 from stab wounds, and 2 fell from the stairs. The mean ISS for the nine patients is 39.7. Of the nine patients with blunt TDI, four died in the trauma bay – two from traumatic arrest, and two died spontaneously. One patient died two days after admission. Of the four patients who survived, one had a diaphragm injury identified during video-assisted thoracic surgery (VATS) for retained hemothorax, and one patient had a diaphragm injury repaired during emergent exploratory laparotomy for other injuries. One patient had a diaphragm injury identified and repaired during diagnostic laparoscopy that was converted to open surgery, and the remaining patient had no diaphragm injury on diagnostic laparoscopy evaluation. Conclusions: Blunt trauma to the torso is usually a consequence of high-energy impact but can also occur following low-energy incidents, such as falls in elderly individuals. Imaging can be useful in detecting such injuries but is not 100% sensitive. A high index of suspicion should be maintained for diaphragmatic injury in high-energy blunt trauma.

Background: Traumatic events adversely affect the clinical course of obsessive-compulsive disorder (OCD). Our investigation explores the correlation between prolonged interpersonal trauma and the severity of symptoms related to obsessive-compulsive and anxiety disorders. Methods: The study follows a cross-sectional and observational design, employing the International Trauma Questionnaire (ITQ) to examine areas linked to interpersonal trauma, the Hamilton Anxiety Rating Scale (HAM-A), and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to assess anxious and obsessive-compulsive symptoms, respectively. Descriptive analysis, analysis of variance (ANOVA), and logistic regression analyses were conducted. Results: We recruited 107 OCD-diagnosed patients, categorizing them into subgroups based on the presence or absence of complex post-traumatic stress disorder (cPTSD). The ANOVA revealed statistically significant differences between the two groups in the onset age of OCD (p=0.083), psychiatric familial history (p=0.023), HAM-A, and Y-BOCS (p=0.000). Logistic regression indicated a statistically significant association between the presence of cPTSD and Y-BOCS scores (p=0.000). Conclusion: The coexistence of cPTSD in OCD exacerbates obsessive-compulsive symptoms and increases the burden of anxiety. Further advancements in this field are crucial for mitigating the impact of early trauma on the trajectory of OCD and associated anxious symptoms.

This study investigated the anatomical characteristics and pulp quality of tapped Styrax sumatrana wood to facilitate its further utilization. The transverse surface of the tapped S. sumatrana was light or greyish brown in the sapwood and reddish brown in the heartwood. The resin canals of the tapped wood were formed along the growth rings at the boundaries between the heartwood and sapwood. Furthermore, microscopic analyses revealed an irregular outline and rounded epithelial cells at the edges of the intercellular traumatic resin canal (TC). Approximately 8–16 epithelial cells surrounded the resin canals. The fibers in the tapped S. sumatrana were generally thin-walled, whereas those near the TC were thick-walled. Moreover, S. sumatrana were diffuse-porous and exhibited intermediately distinct or indistinct growth ring boundaries. The vessels were mainly in radial multiples and clusters of 3–5. In addition, they showed a diagonal-to-radial pattern arrangement and a few tangential bands. Deposits were observed in some vessels in the tapped part but were absent in the untapped part. The fiber length of the tapped S. sumatrana wood was classified as moderate to extensive and categorized as 2nd grade pulp quality. Finally, the cell walls were classified as thin to moderate.

COVID-19 pandemic has the potential to adversely affect the mental health of healthcare workers (HCWs). The public healthcare system in Greece was already facing serious challenges at the outset of the outbreak following years of austerity and an escalating refugee crisis. The multi-center, cross-sectional study aims to assess the levels and associated risk factors of anxiety, depression, traumatic stress and burnout of frontline staff in Greece. A total of 464 HCWs in six reference hospitals completed a self-administered questionnaire comprising of sociodemographic and work-related information and psychometric scales. The proportion of HCWs with symptoms of moderate/severe depression, anxiety and traumatic stress were 30%, 25% and 33% respectively. Burnout levels were particularly high with 65% of respondents scoring moderate/severe in Emotional Exhaustion, 92% severe in Depersonalization and 51% low/moderate in Personal Accomplishment. Predictive factors of adverse psychological outcomes included fear, perceived stress, risk of infection, lack of protective equipment and low social support. The psychological burden associated with Covid-19 in healthcare professionals in Greece is considerable with more than half experiencing at least mild mental health difficulties. Findings signal the need for immediate organizational and individually tailored interventions to enhance resilience and support wellbeing under pandemic conditions.

On March 2020 strict measures took place in Finland to limit the COVID -19 pandemic. A majority of the Finnish COVID -19 –patients have been located in the southern Finland and consequently cared for in the HUS Helsinki University Hospital. During the ongoing pandemic, HUS personnel’s psychological symptoms are followed via an electronic survey, which also delivers information on psychosocial support services. The baseline survey in June 2020 was sent to 25494 HUS employees out of whom 4804 (19%) answered; altogether 62.4% of the respondents were nursing staff and 8.9% medical doctors. While the follow-up continues for a year and a half, this report shares the sociodemographic characteristics of the respondents and the first results of psychological symptoms from the baseline survey. Out of those who were directly involved in pandemic patients` care, 43.4% reported potentially traumatic COVID-19 pandemic-related experiences vs. 21.8% among the other (p &lt; 0.001). While over a half of the personnel was symptomless, a group of respondents reported pandemic work –related traumatic events and concurrent depressive, insomnia and anxiety symptoms. This highlights the need to ensure appropriate psychosocial support services to all traumatized personnel and PTEs were present especially among nursing staff.

Individuals have different rumination patterns after experiencing traumatic events in different cultural backgrounds and situations. This study was aimed to explore the experience of Chinese young and middle-aged patients with acute coronary syndrome (ACS) to understand the content and nature of their rumination. Fourteen participants were selected using the purposive sampling method in XXX hospital from May 2023 to December 2023. Data were collected using semi-structured interviews and analyzed using Colaizzi’ s 7-step phenomenological method. The content of rumination in young and middle-aged patients with ACS can be summarized into 2 categories: non-adaptive rumination and adaptive rumination. Non-adaptive rumination included 3 themes: worry or anxiety, scare, and depression. Adaptive rumination included 4 themes: tracing of disease processes, enhancement of disease cognition, improvement of health awareness, and adjustment of lifestyle cognition. In conclusion, although Chinese young and middle-aged patients with ACS experience negative emotions after a traumatic cardiac event, they gradually make positive changes, and optimism and information support play important roles in this transition, which provide a fundamental understanding of rumination experiences in Chinese young and middle-aged patients with ACS and provide new data for healthcare providers when designing intervention programs to enhance post-traumatic growth in these patients.

Introduction: Hospitalization in a COVID-19 unit represents a significant source of stress and psychological distress for patients. Our study aims to determine the factors of psychological distress in the therapeutic and psychosocial management of patients hospitalized with a COVID-19 infection. Methods: This cross-sectional study was carried out over 8 months at the COVID-19 zone of the CHU HASSAN II of FES. 99 patients were evaluated within days of diagnosis by psychometric scales of anxiety, depression, and post-traumatic stress. In the course of this follow-up, we found the presence of psychological impacts in these patients, and we tried to find correlating factors between the occurrence of psychiatric disorders and the set of factors related to sociodemographic data, hospitalization course and treatments taken, as well as family support. Results: 35% of patients had scores in favor of post-traumatic stress disorder, 37% of the patients had definite depression and 50% had anxiety. Post-traumatic stress, depression, and anxiety were correlated with sociodemographic factors, hospitalization, treatments received, and length of stay. Conclusion: The prevalence of anxiety-depressive disorders and post-traumatic stress disorder was high in patients with COVID-19, hence the interest in providing psychological and psychosocial care in the emergency department.

In oral pathology, the appearance of a large ulcerated lesion may suggest a malignant process that requires an early diagnosis given the uneasiness of the patient and his or her family. Finding lingual carcinoma in children is, however, extremely rare We present the case of a 13-year-old girl who came to the oral medicine clinic, referred by her orthodontist, with a large round lesion on the ventral side of the tongue (15 x 12 mm) that did not heal, after three weeks of evolution and after eliminating the existing traumatic factors (orthodontic appliance in the lower jaw) and treatment with topical gel based on PVP (polyvinyl pyrrolidone), glycyrrhetinic acid and hyaluronic acid (Aloclair PLUS®). The objective of this article is analyse the possible causes and provide a review of the literature of a large ulcerated lesions.

Traumatic cardiac arrest has a high mortality. We report the case of a 65 years old women who presented a cardiac arrest following traffic accident. Examinations concluded to a tension gastro thorax with a delayed diagnosis. Naso gastric tube insertion was for many authors a temporary care while waiting for surgery. We report on the diagnostic difficulties found in the literature and a recent review of published cases.

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.

Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that occurs following exposure to traumatic events. The prevalence of PTSD is estimated to be 5-10% worldwide, and it is associated with significant distress and disability. Recent evidence suggests that PTSD may be a risk factor for the development of subsequent neurodegenerative disorders, including Alzheimer’s dementia and Parkinson’s disease. Identification of biomarkers known to be associated with neurodegeneration in patients with PTSD would shed light on the pathophysiological mechanisms linking these disorders, and would also help in the development of preventive approaches aimed at reducing the risk of neurodegenerative disorders in PTSD. In the current review, the PubMed and Scopus databases were searched for studies aimed at identifying genetic, biochemical, neuroimaging or behavioral markers associated with neurodegeneration in patients with PTSD. Out of a total of 342 citations retrieved, 29 relevant studies were identified for inclusion in the review. The results of these studies suggest that several potentially relevant biological markers, including cerebral cortical thinning, disrupted white matter integrity, specific genetic polymorphisms, immune-inflammatory alterations, vitamin D deficiency, metabolic syndrome and parasomnias, may be associated with an increased risk of neurodegeneration in patients with PTSD. Though many of these results need replication, they highlight a number of biological pathways that plausibly link PTSD with neurodegenerative disorders, and suggest potentially valuable avenues for prevention and early intervention in this patient population.

Anxiety disorders are among the most common mental disorders worldwide, and often respond incompletely to existing treatments. Selenium, a micronutrient that is a component of several biologically active selenoproteins, is also involved in several aspects of brain functioning, and may exert antidepressant and anxiolytic effects through multiple pathways. The current paper is a scoping review of translational, observational and interventional evidence on the potential role of selenium and its compounds in the management of anxiety and related disorders. Evidence from animal models suggests that this approach may be promising. Though evidence from observational studies in humans is inconsistent and affected by several confounding factors, the available evidence from randomized controlled trials suggests that selenium supplementation may be beneficial in the management of certain anxiety-related conditions, such as anxiety in medically ill patients, prevention of anxiety following exposure to traumatic stress, and obsessive-compulsive disorder. This paper provides a critical evaluation of the existing evidence base, including unanswered questions that could serve as the focus of further research, and outlines the potential benefits and risks associated with the use of selenium in anxiety disorders.

The Coronavirus Disease 2019 (COVID-19) pandemic has had a major impact on the mental and physical health of hospitalized patients. In our study we focused on the onset of symptoms correlated with Post-traumatic stress disorder (PTSD), depression and physical disabilities in patients admitted to the Intensive Care Unit (ICU) because of a severe respiratory distress related to COVID-19 (COVID Group) compared with patients admitted to the same ICU for trauma and other medical conditions than COVID-19 (No-COVID Group). The physical symptoms and the level of disability were evaluated with the Glasgow Outcome Scale-Extended (GOS-E), the Quality of Life after Brain Injury (QOLIBRI) and the 3 levels version of EQ-5D (EQ-5D-3L) questionnaire; psychiatric symptoms were investigated using the Impact of Event Scale-Revised 22-item (IES-R), the Patient Health Questionnaire, 9-Item Version (PHQ-9) and the Generalized Anxiety Disorder Assessment, 7-items version (GAD-7). These questionnaires were administered 6 months after discharge. Patients in the No-COVID Group showed statistically significant more severe scores in all the physical assessments while similar relevant PTSD and depressive symptoms were reported in both groups. The results of the present study underline the psychopathological impact of being hospitalized in ICU because of COVID-19 even after 6 months from discharge ,suggesting the importance of assessing the psychiatric effects of COVID-19 in the long term in order to create supportive measures.

Background: Hypopituitarism is a potentially serious but often underdiagnosed condition that can occur following non-traumatic subarachnoid hemorrhage (SAH). The condition is characterized by the partial or complete deficiency of one or more pituitary hormones, leading to a range of clinical manifestations that may complicate the recovery process. This narrative review aims to synthesize the current literature on the prevalence, pathophysiology, and clinical implications of hypopituitarism associated with non-traumatic SAH. Methods: A comprehensive review of the literature was conducting by authors using databases such as PubMed, MEDLINE, and Scopus, focusing on studies published in the last two decades. Studies were selected based on their relevance to the topic, with an emphasis on those that reported on the prevalence, diagnostic approaches, pathophysiological mechanisms, and clinical outcomes of hypopituitarism post-SAH. Results: The review revealed a wide variability in the reported prevalence of hypopituitarism following non-traumatic SAH, ranging from 14% to 92.3%, depending on the diagnostic criteria, timing of assessment, and hormonal axes evaluated. Commonly affected hormones include growth hormone, gonadotropins, and cortisol. The pathophysiology of hypopituitarism in this context is multifactorial, involving ischemic damage, inflammation, and direct mechanical injury to the hypothalamic-pituitary axis. While some studies suggest a link between hypopituitarism and adverse clinical outcomes, the evidence remain inconclusive, highlighting the need for standardized diagnostic protocols and longitudinal studies. Conclusion: Hypopituitarism is a prevalent but often overlooked complication of non-traumatic SAH, with significant potential implications for long-term health outcomes. Routine endocrine evaluation and management of pituitary deficiencies are recommended to improve patient care. Future research should focus on refining diagnostic criteria, elucidating the underlying mechanisms, and evaluating the long-term impact of hormone replacement therapy in this patient population.

Traumatic pneumothorax (PTX) occurs in up to 50% of patients with severe polytrauma and chest injuries. Patients with traumatic PTX with clinical signs of tension physiology and hemodynamic instability are typically treated with an urgent decompressive thoracostomy, tube thoracostomy, or needle decompression. There is recent evidence that non-breathless patients with hemodynamically stable traumatic PTX can be managed conservatively through observation or a percutaneous pigtail catheter. We present here a 52-year-old woman who presented to the emergency department with 55 mm traumatic PTX. Following aspiration of 1500 ml of air, clinical improvement was immediately observed, allowing the patient to be discharged shortly thereafter. In hemodynamically stable patients with posttraumatic PTX, without specific risk factors or oxygen desaturation, observation or simple needle aspiration can be a reasonable approach. We aimed in this article to review the available literature on needle aspiration and conservative treatment of traumatic pneumothorax. A total of 12 studies were selected out of 190 articles on traumatic PTX, where conservative treatment versus chest tube decompression was compared. Our case report demonstrated that even a large PTX in a hemodynamically stable patient without other risk conditions, can be successfully treated conservatively with simple needle aspiration to avoid tube thoracostomy complications.

Purpose: To explore the influence of education and other factors on an athlete’s decision to return to sport post-concussion injury, and whether general risk-taking tendencies are related to return to sport post-concussion decisions in these athletes. Participants and Methods: A self-administered electronic survey was designed to examine their decision-making process when faced with scenario-based questions regarding returning to sport post-concussion injury. Students from the Health Sciences and Medicine Faculty at Bond University were invited to participate. Participants were allocated to a concussion education or non-education group prior to commencement of questionnaire via the random generator on Qualtrics software function. The risk propensity scale was used to assess the risk aversion of each participant. Results: Sixteen respondents were randomized evenly to education and non-education groups. Seven (43.8%) had previously received concussion education training prior to completing the questionnaire, with one (14%) choosing to return to sport in the scenario-based questions. The education group reported two (25%) respondents return to sport, while three (75%) respondents out of four returned to sport with no education or previous concussion training. Influential factors that impacted the decision whether to return to sport or not included: game importance, concussion severity and symptoms, and various internal and external factors. Finally, there was a divergence in results from the risk propensity scale when deciding to return to sport and general risk-taking propensities. Conclusion: This study identified several influential factors including game importance, concussion severity and symptoms which play a significant role in the return to sport decisions post-concussion injury.

Since January, the disease caused by the Sars Cov-2 virus has spread and following pandemic. In a few months, the virus is seriously affecting the health systems of the various countries of the world and placing people in difficult psychological conditions. Few scientific resources on mental health have been published but still no one has proposed an action plan to cope the future psychological problems.This manuscript provides a plan to easily frame the priorities of mental health area related to COVID-19 to be taken into consideration which should be disseminated and that should be known by all health professionals and also by the major administrators of public health.

(1) Background: although current theories of Post-Traumatic Stress Disorder (PTSD) had focused on depressed mood and intrusion, the mechanism through which depression increases the risk of PTSD remains unclear. Research has concentrated on the hyper-active negative valence system (NVS) (e.g., increased fear and threat responses), but a significant role for hypo-active positive valence system (PVS) (e.g., less neural activation towards rewards) was conceivable. (2) Methods: To investigate the implicit processing in a refugee’s sample, ratings of arousal, dominance, and valence for 60 IAPS pictures (positive, neutral, and negative) were collected from 42 individuals with probable PTSD, and 26 trauma-exposed individuals (M age = 28.49 years, SD = ± 7.78). (3) Results: ANOVAs revealed a main group effect (η2p = 0.379) on arousal, dominance, and valence dimensions, and pictures’ categories (η2p = 0.620). Participants with PTSD responded to unpleasant images with enhanced arousal and lower valence ratings compared with individuals without PTSD. Moreover, arousal ratings were negatively correlated with valence (r = - 0.709, p &lt; 0.01). (4) Conclusions: Our findings supported evidence according to which PTSD origins a state of maladaptive hyperarousal and difficulties in regulating emotions. Positive stimuli are considered less pleasant providing evidence for a complementary involvement of NVS and PVS in PTSD development.

Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognized, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P and its NK1 receptor have been widely studied as a potential therapeutic target. There is evidence that NK1 receptor antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1 receptor has been shown to reduce blood-brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1 receptor has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonist may have some benefit in reducing infection-driven inflammation. However, the NK1 receptor may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. As such, the purpose of this review is to provide a summary of the involvement of substance P in acute inflammation, particularly in the context of traumatic brain injury and stroke.

Non-pharmacologic options like the ketogenic diet (KD) and intermittent fasting (IF) are practical nutritional interventions with minor reported side effects like gastrointestinal symptoms, dyslipidemia, and hypomagnesemia for various medical ailments. In conjunction with IF, KD shows promise in weight loss, diabetes management, cardiovascular disorders, polycystic ovarian syndrome, cancer, and chronic neurological disorders. Based on prior research, we have examined the mechanism of action of KD and IF and their effect on neurological diseases, cancer, and obesity. We have also suggested evidence-based recommendations for the safer practice of KD and IF. Despite potential benefits, long-term adherence to KD poses challenges. Periodic KD implementation may thus benefit newly diagnosed overweight or obese patients with type 2 diabetes mellitus, aiding blood glucose and lipid management while promoting weight loss. KD is a high-fat and low-carbohydrate diet with a ratio of fat to carbohydrates and protein being 4:1 or 3:1, and thus, for peripheral tissues and the brain, fatty acids become the mandatory source of cellular energy. Ketone bodies have been used as the primary energy source during fasting. KD has been utilized as an effective treatment for refractory epilepsy since the 1920s. Evidence of the neuroprotective role of KD in diseases like epilepsy, stroke, traumatic brain injury, Alzheimer’s disease, and other neurological diseases has been noted. Since the 1960s, KD has become a popular method for obesity treatment. In addition, KD has been suggested as a potent anticancer therapy when used alone or as an adjuvant. KD may increase tumor cell sensitivity when combined with classic chemotherapy and radiotherapy. Thus, the probability that modifying the diet can help manage obesity, cancer, and chronic neurological disease without depending on pharmacological treatment and their serious side effects for a lifetime is promising and requires further investigation. KD holds promise as a potential adjunctive therapy in various neurological disorders, offering new avenues for treatment and neuroprotection. IF has shown potential in slowing the progression of neurodegenerative diseases such as Alzheimer's and Parkinson's by promoting antioxidant defense and suppressing inflammation. KD and IF show promise in cancer therapy by targeting altered cancer cell metabolism. Additionally, KD may enhance the effects of standard treatments like chemotherapy and radiotherapy. Some of the most robust reports of keto's possible benefits have come from glioblastoma, a very aggressive brain cancer. KD has also shown strong evidence for its effectiveness in weight loss, mainly attributed to its appetite-suppressing action in ketosis. However, long-term adherence to KD can be challenging, and periodic KDs may help manage blood glucose and lipid levels in overweight or obese patients with type 2 diabetes mellitus. Likewise, IF may be more effective than regular calorie restriction for achieving weight loss goals when combined with exercise programs. More prospective human studies are warranted to evaluate both KD and IF's potential therapeutic effectiveness and safety.

The advancement of the pediatric traumatic brain injury (TBI) knowledge base requires biospecimens and data from large samples. This study seeks to describe a novel clinical research modality to establish best practices for enrolling a diverse pediatric TBI population and quantifying key information on enrollment into biobanks. Screening form responses were standardized and cleaned through Google Sheets. Data was used to analyze total individuals at each enrollment stage. R was utilized for final analysis, including chi-square goodness of fit and proportion statistical tests, to determine further significance and relationships. Issues throughout data cleaning shed light on limitations of the consent modality. Results suggest that through a diverse research team, the recruited sample exceeds traditional measures of representation (e.g. sex, race, ethnicity). Sex demographics of the study are representative of the local population. Screening for candidates is critical to the success of the consent modality. The consent modality may be modified to increase diversity of study population and accept bilingual candidates. Researchers must implement best practices, including increasing inclusivity of bilingual populations, utilizing technology, and improving participant follow-up, to improve health disparities for understudied clinical populations.

Background/Objectives Recurrent shoulder instability following Bankart lesion repair often necessitates surgical revision. Identified risk factors include young age, glenoid bone loss, and off-track Hill-Sachs lesions. This systematic review aims to understand failure rates of arthroscopic revision Bankart repair and if these aforementioned factors influence its success. Methods Following PRISMA guidelines, this systematic review, registered on PROSPERO, included twenty-four articles. Two independent reviewers assessed eligibility across three databases, focusing on recurrent instability as the primary endpoint, while also noting functional measures, adverse events, revision operations, and return-to-sport rates when available. Results Key surgical techniques for recurrent instability post-Bankart repair were identified, with revision arthroscopic Bankart being the most common (685/1032). Despite generally endorsed effectiveness, recurrence rates have increased over the past four years. Comparative analysis revealed significantly lower recurrence for open Latarjet compared to revision arthroscopic Bankart (p

Sedation is a ubiquitous practice in ICUs and NCCUs. It has the benefit of reducing cerebral energy demands, but also precludes an accurate neurologic assessment. Because of this, sedation is intermittently stopped for the purposes of a neurologic assessment, which is termed a neurologic wake-up test (NWT). NWTs are considered to be the gold-standard in continued assessment of brain-injured patients under sedation. NWTs also produce an acute stress response that is accompanied by elevations in blood pressure, respiratory rate, heart rate, and ICP. Utilization of cerebral microdialysis and brain tissue oxygen monitoring indicates that this is not mirrored by alterations in overall cerebral metabolism, and seldom affects oxygenation. The hard contraindications for the NWT are preexisting intracranial hypertension, barbiturate treatment, status epilepticus, and hyperthermia. However, hemodynamic instability, sedative use for primary ICP control, and sedative use for severe agitation or respiratory distress are considered significant safety concerns. Despite ubiquitous recommendation, it is not clear if additional clinically relevant information is gleaned through its use, especially with the contemporaneous utilization of multimodality monitoring. Various monitoring modalities provide unique and pertinent information about neurologic function, however, their role in improving patient outcomes and guiding treatment plans has not been fully elucidated. There is a paucity of information pertaining to the optimal frequency of NWTs, and if it differs based on type of injury. Only one concrete recommendation was found in the literature, exemplifying the uncertainty surrounding its utility. The most common sedative used and recommended is propofol because of its rapid onset, short duration, and reduction of cerebral energy requirements. Dexmedetomidine may be employed to facilitate serial NWTs, and should always be used in the non-intubated patient or if propofol infusion syndrome (PRIS) develops. Midazolam is not recommended due to tissue accumulation and residual sedation confounding a reliable NWT. Thus, NWTs are well tolerated in most patients and remain recommended as the gold-standard for continued neuromonitoring. Predicated upon one expert panel, they should be performed at least one time per day. Propofol or dexmedetomidine are the main sedative choices, both enabling a rapid awakening and consistent NWT.

Background: The vegetative state (VS)/unresponsive wakefulness syndrome (UWS) denotes brain-injured, awake patients who are seemingly without awareness. Still, up to 15% of these patients show signs of covert consciousness when examined by functional magnetic resonance imaging (fMRI) or EEG, which is known as cognitive motor dissociation (CMD). Most experts prefer the term unresponsive wakefulness syndrome to avoid the negative connotations associated with vegetative state and to highlight the possibility for CMD. However, the perception of VS/UWS by the public has never been studied systematically. Methods: Using an online crowdsourcing platform, we recruited 1297 participants from 32 countries. We investigated if vegetative state and unresponsive wakefulness syndrome might have a different influence on attitudes towards VS/UWS and CMD. Results: Participants randomized to be inquired about the vegetative state believed that CMD was less common (mean estimated frequency in unresponsive patients 38.07% ± SD 25.15) than participants randomized to unresponsive wakefulness syndrome (42.29% ± SD 26.63; p=0.016). Attitudes towards treatment withdrawal were similar. Most participants preferred unresponsive wakefulness syndrome (60.05%), although a sizeable minority favored vegetative state (24.21%; difference 35.84%, 95% CI 29.36 to 41.87; p<0.0001). Searches on PubMed and Google Trends revealed that unresponsive wakefulness syndrome is increasingly used by academics but not lay people.Discussion: Simply replacing vegetative state with unresponsive wakefulness syndrome may not be fully appropriate given that 1 of 4 prefer the first term. We suggest that physicians take advantage of the controversy around the terminology to explain relatives the concept of CMD and its ethical implications.

Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

This study examines the psychological repercussions of the COVID-19 pandemic on a medical team in an Israeli general hospital. The research explores the professional quality of life, burnout symptoms, secondary traumatic stress, and mindfulness among team members across three distinct phases of the pandemic. Analysis was conducted for different subgroups based on job roles and seniority, allowing for an evaluation of the phase-specific effects on the ProQOL (Professional Quality of Life) and mindfulness. Results align with established crisis trajectories, encompassing honeymoon/heroic phases, inventory, disillusionment, and recovery. The findings demonstrate a negative correlation between compassion satisfaction and burnout, as well as between mindfulness and burnout/secondary traumatic stress. Remarkably, male doctors exhibit a more pronounced negative impact on mindfulness compared to their female counterparts, primarily comprising healthcare workers. Temporal analysis reveals significant differences in compassion satisfaction and mindfulness, with baseline measurements being notably higher. Furthermore, the study sheds light on the vulnerability of male doctors, emphasizing the crucial role of hospital management in conveying the message and implementing effective measures to support professional quality of life. These findings underscore the necessity of prioritizing the well-being of medical professionals, particularly male doctors who face unique challenges in seeking assistance.

Background/Objectives: Post traumatic growth (PTG) has the potential to draw positive consequences from trauma. Hence, the interest of finding ways to promote PTG. Research has identified an attentional bias towards positive resilience-related words (e.g., “persistence”, “purpose”) in university students who report high PTG after experiencing adversities. Although people can respond to these experiences by showing low PTG, this bias seems to help with their struggle by making purposeful contents more accessible. Therefore, boosting attentional bias towards positive resilience-related words could help people with low PTG. Methods: In this study, the participants were thirty-six university students who had experienced bullying before entering university. Using a Stroop emotional task, they identified the color of resilience and neutral words, either positive or negative, before and after being submitted to transcranial direct current stimulation. Stimulation was targeted at the right temporal area involved in intentionality processing. Results: In the anodal condition, the results support a stimulation effect on the resilience attentional bias that could benefit participants with low PTG. A significant moderation of approach motivation for this effect was also found. Specifically, only when participants had medium or high approach motivation, did stimulation boost the attentional bias in students with low PTG. Conclusions: These results support that tDCS stimulation in this brain area is effective in enhancing resilience attentional bias in low PTG students. However, for this effect to occur it is necessary to have approach motivation, which is motivation related to goals.

Background: The present work aimed to estimate the economic impact of PTSD following COVID-19 in a population of patients affected by systemic autoimmune disease (SAD) using a cost-of-illness approach and accounting for the perspective of society. Methods: Considering data collected from SAD patients enrolled in a specialized outpatient clinic in the Tuscany region, Italy, generalized-linear-models and LASSO logistic regression were used to evaluate the impact of PTSD on costs and its relevance as possible predictors of being a high-cost patient, respectively. Results: Considering 301 SAD patients, 161 (51.2%) of whom diagnosed with PTSD, the overall costs were 3,670 [890;40,529] Euro per patient/year among patients with PTSD and 2,736.7 [283;21,078] Euro per patient/year among those without PTSD (P-value<0.001), with differences mainly attributable to significantly greater direct non-healthcare and indirect costs. PTSD was estimated to increase overall costs (β=0.296 (0.140), P-value=0.035), direct non-healthcare (β =1.193 (0.392), P-value =0.002) and indirect costs (β =3.741 (1.136), P-value =0.001). PTSD diagnosis was also significantly associated with the likelihood of being a high-cost patient. Conclusions: Findings from the present study offer a novel perspective on the economic impact of COVID-19 and provide valuable data for policymakers to better understand demand for healthcare services and associated costs.

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.

Post-concussion syndrome, recently recognized as a complication of mild traumatic brain injury, is considered a consequence of the summative effect of multiple concussions received over lifetime. In elderlies, the main mild brain trauma mechanism is fall (low impact force). Many falls are often not reported or noticed but may generate serious medical and medico-legal consequences. Our research question was to find if a single, very mild brain trauma can induce neuro-behavioral consequences in elderlies. One database was queried (PubMed – MeSH terminology) looking for histopathological, neuro-cognitive and behavioral changes that can be generated by sub-concussional trauma in senescent rodents, in comparison with young animals. 41 published research articles were selected. 17 of them used very mild brain trauma in young and senescent animals, in the same experiment (6 rats and 11 mice). 24 articles evaluated the effect of sub-threshold brain trauma in adult animals (no control group). Five trauma models were used (blast models were excluded). Neuro-inflammatory changes were detected immediate after very mild primary impact. In young animals, observed pathology disappeared fast (after 3 to 7 days). Increased apoptosis, mild axonal injury in white matter tracts plus maladaptive astrogliosis and microglial activation was stronger in aged animals, persisted over time (8 months) and significantly altered animals’ cognition and behavior. Associated preexisting pathology (hypertension, tau protein deposits, microbleeds, reactive inflammation) was often responsible for amplification of the primary impact results. As translation of observation is the weak spot of pathology and behavior animal research, further investigation is needed before to conclude that even a single, very mild brain trauma may have medical consequences on human senescent brain.

Background: Neurofeedback (NFB) or EEG-Biofeedback is a non-invasive therapeutic method, based on the theory of operating conditioning, and designed to change the functioning of the brain by sending feedback that provides positive or negative reinforcement. The goal is to teach the patient how to perceive specific cortical activation states and how to achieve them on purpose. NFB has been used to treat various mental disorders, including Post-traumatic Stress Disorder (PTSD). Traditional treatments for PTSD have several limitations; very few individuals are willing to relive the traumatic experience. Placing itself as an effective alternative, Neurofeedback allows the unresponsive patient to recourse to an alternative intervention to relieve their symptoms without reliving the anguish of trauma, consequently presuming a lower percentage of drop-out. Considering the importance of integrated approaches to clinical practice, NFB was integrated with Trauma-Informed Motivational Interviewing (TIMI). The TIMI approach is a new therapeutic paradigm for clinical interviews that aims to help users work through their trauma and transform it from a point of weakness to a point of strength. Integrating TIMI with NFB can help overcome the current trend of passive implementation of intervention tools, leading to greater user responsiveness and fewer residual symptoms. To improve treatment adherence, moreover, it has been suggested to incorporate Virtual Reality (VR) into the NFB system. VR, through the "sense of presence," provides a more immersive experience than 2D visualization, potentially resulting in faster cortical training. Lastly, the research protocol aims to focus on a population at high risk of PTSD that is often overlooked in research, such as workers who are victims of occupational PTSD.Methods: The study design involves in-depth analysis of a specific clinical case. Baseline measurements were taken for enrollment and at the following time points: T1 (pre-treatment), T2 (post-treatment), and T3 (follow-up). These measurements included various psychometric assessments to evaluate PTSD symptoms, treatment acceptability, safety, and adherence, as well as biological measures related to the brain's electrophysiological activity.Results and Conclusion: Our research reveals that the synergy between virtual reality-mediated Neurofeedback and trauma-motivational interviewing produces significant results. TIMINB stands out as a low-cost, effective, and completely risk-free procedure. This approach could represent a groundbreaking innovation in the field of Cyberpsychology and psychological therapies.

This review explores the application of the conservative management model for pain to sports-related concussions (SRCs), framing concussions as a distinct form of pain syndrome with a pathophysiological foundation in central sensitization. Drawing parallels with proven pain management models, we underscore the significance of a proactive approach to concussion management. Recognizing concussions as a pain syndrome allows for the tailoring of interventions in alignment with conservative principles. This review first covers the epidemiology and controversies surrounding prolonged concussion recovery and persistent post-concussion symptoms (PPCS). Next, the pathophysiology of concussions is presented within the central sensitization framework, emphasizing the need for early intervention to mitigate the neuroplastic changes that lead to heightened pain sensitivity. Five components of the central sensitization process specific to concussion injuries are highlighted as targets for conservative interventions in the acute period: peripheral sensitization, cerebral metabolic dysfunction, neuroinflammation, glymphatic system dysfunction, and pain catastrophizing. These proactive interventions are emphasized as pivotal in accelerating concussion recovery and reducing the risk of prolonged symptoms and PPCS, in line with the philosophy of conservative management.

There is growing recognition in research and policy of a mental health crisis among Canada’s paramedics but despite this, epidemiological surveillance of the problem is in its infancy. Just weeks before the emergence of the COVID-19 pandemic, we surveyed paramedics from a single, large, urban paramedic service in Ontario, Canada to assess for symptom clusters consistent with Post-Traumatic Stress Disorder (PTSD), major depressive disorder, and generalized anxiety disorder and to identify potential risk factors for each. In total, we received 589 completed surveys (a 97% completion rate) and found that 11% screened positive for PTSD, 15% for depression, and 15% for anxiety, with 1 in 4 active-duty paramedics screening positive for any of the three as recently as February 2020. In adjusted analyses, the risk of a positive screen varied as a function of employment classification, gender, self-reported resilience, and previous experience as a member of the service’s peer support team. Our findings support the position that paramedics screen positive for mental disorders at high rates – a problem likely to have worsened since the onset of the COVID-19 pandemic. We echo the calls of researchers and policymakers for urgent action to support paramedic mental health in Canada.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases, and psychiatric disorders. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants, and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses, and chronic diseases. KYN, kynurenic acid, xanthurenic acid, and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2, 3-oxygenases, and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines, and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia, and autism spectrum disorder.

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.

Role identity theory describes the purpose and meaning in life that comes, in part, from occupying social roles. While robustly linked to health and well-being, this may become, however, when an individual is unable to fulfil the perceived requirements of an especially salient role in the way that they believe they should. Amid high rates of mental illness among public safety personnel, we interviewed a purposely selected sample of 21 paramedics from a single service in Ontario, Canada to explore incongruence between an espoused and able-to-enact paramedic role identity. Situated in an interpretivist epistemology, and using successive rounds of thematic analysis, we developed a framework for role identity dissonance wherein chronic, identity-relevant disruptive events cause emotional and psychological distress. While some participants were able to recalibrate their sense of self and understanding of the role, for others, this dissonance was irreconcilable, contributing to disability and lost time from work. In addition to contributing a novel perspective on paramedic mental health and well-being, our work also offers a modest contribution to the theory in using the paramedic context as an example to consider identity disruption through chronic workplace stress.

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).

The Impact of Event Scale-Revised (IES-R) is the most popular measure of post-traumatic stress disorder (PTSD), which has been recently validated in Arabic. This instrumental study aimed to determine optimal cutoff scores of the IES-R and its subscales in Arab samples of psychiatric patients (N = 168, 70.8% females) and healthy adults (N = 992, 62.7% females) from Saudi Arabia during the COVID-19 pandemic as an ongoing collective traumatic event. Based on a cutoff score of 14 of the Depression Anxiety Stress Scale 8-items (DASS-8), receiver operator curve (ROC) analysis revealed two optimal points of 39.5 and 30.5 for the IES-R in the samples (area under the curve (AUC) = 0.86 &amp; 0.91, p values = 0.001, 95% CI: 0.80-0.92 &amp; 0.87 to 0.94, sensitivity = 0.85 &amp; 0.87, specificity = 0.73 &amp; 0.83, Youden index = 0.58 &amp; 0.70, respectively). Different cutoffs were detected for the six subscales of the IES-R, with numbing and avoidance expressing the lowest predictivity for distress. Meanwhile, hyperarousal followed by the irritability expressed stronger predictive capacity for distress than all subscales in both samples. In path analysis, pandemic-related irritability resulted from direct and indirect effects of key PTSD symptoms (intrusion, hyperarousal, and numbing). Irritability contributed to traumatic symptoms of sleep disturbance in both samples while the opposite was not true. The findings suggest usefulness of the IES-R at a score of 30.5 for detecting adults prone to trauma related distress, with higher scores needed for screening in psychiatric patients. Various PTSD symptoms may induce dysphoric mood, which represents a considerable burden that may induce circadian misalignment and more noxious psychiatric problems/ co-morbidities (sleep disturbance) in both healthy and diseased groups.