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Mild traumatic brain injury (mTBI) is a common consequence of head injury but there are no recognized interventions to promote recovery of the brain. We previously showed that photobiomodulation (PBM) significantly reduced the number of apoptotic cells in adult rat hippocampal organotypic slice cultures. In this study, we first optimized PBM delivery parameters for use in mTBI, conducting cadaveric studies to calibrate 660 and 810 nm lasers for transcutaneous delivery of PBM to the cortical surface. We then used an in vivo weight drop mTBI model in adult rats and delivered daily optimized doses of 660, 810 nm, or combined 660/810 nm PBM. Functional recovery was assessed using novel object recognition (NOR) and beam balance tests, whilst histology and immunohistochemistry were used to assess the mTBI neuropathology. We found that PBM at 810, 660 nm, or 810/660 nm all significantly improved both NOR and beam balance performance, with 810 nm PBM having the greatest effects. Histology demonstrated no overt structural damage in the brain after mTBI, however, immunohistochemistry using brain sections showed significantly reduced activation of both CD11b+ microglia and glial fibrillary acidic protein (GFAP)+ astrocytes at 3 days post‐injury. Significantly reduced cortical localization of the apoptosis marker, cleaved caspase‐3, and modest reductions in extracellular matrix deposition after PBM treatment, limited to choroid plexus and periventricular areas were also observed. Our results demonstrate that 810 nm PBM optimally improved functional outcomes after mTBI, reduced markers associated with apoptosis and astrocyte/microglial activation, and thus may be useful as a potential regenerative therapy. [ABSTRACT FROM AUTHOR]

Background: A dietary supplementation with conjugated linoleic acid (CLA) was shown to attenuate inflammation and increase the proportions of circulating regulatory T cells (Tregs) and M2-type macrophages in disease models such as autoimmune encephalitis and arteriosclerosis. Since Tregs and anti-inflammatory (M2-type) macrophages were found to enhance stroke recovery, we hypothesized that CLA-supplementation might improve stroke recovery via immune modulatory effects. Methods: Functional assessment was performed over 90 days after induction of experimental photothrombotic stroke in wild type mice (n = 37, sham n = 10). Subsequently, immunological characterization of different immunological compartments (n = 16), ex vivo magnetic resonance (MR, n = 12) imaging and immunohistochemical staining (n = 8) was performed. Additionally, we tested the effect of CLA in vitro on peripheral blood mononuclear cells from human stroke patients and healthy controls (n = 12). Results: MR diffusion tensor imaging (DTI) demonstrated enhanced microstructural reorganization of interhemispheric white matter tracts, dependent on lesion size. Functional recovery over 90 days remained unaffected. Detailed immunological analyses across various compartments revealed no significant long-term immunological alterations due to CLA. However, analyses of human blood samples post-stroke showed reduced levels of pro-inflammatory interferon-γ (IFN-γ) and tumor necrosis factor alpha (TNF-α) release by T-lymphocytes following in vitro treatment with CLA. Conclusion: We aimed to explore the efficacy of a dietary intervention with minimal known side effects that could be accessible to human stroke patients, regardless of the degree of disability, and without the risks associated with aggressive immunomodulatory therapies. Our main findings include improved microstructural reorganization in small infarcts and a reduced inflammatory response of human T cells in vitro. [ABSTRACT FROM AUTHOR]

Aims: Young people with first-episode psychosis (FEP) or at ultra-high risk (UHR) of psychosis often have lower vocational engagement than their peers. This study examines the effect of treatment in early intervention for psychosis services in Australia on engagement in education and employment. Methods: This is a naturalistic sample of young people aged 12–25 with FEP (n = 1574) and UHR (n = 1515), accessing treatment in the headspace Early Psychosis (hEP) programme. Engagement in education and employment was assessed at baseline and every 90 days in treatment. Mixed effects logistic regression were used to analyse changes over time. Results: On entering the hEP programme, approximately 49% of the young people with FEP and 28% of the young people at UHR status identified as Not in Education, Employment or Training (NEET). The odds of being NEET were reduced by 27% (95% confidence interval = [14, 39]) for every 6 months treatment for the FEP group, but no change in NEET status was observed in the UHR group. In both groups, absence from daily activities was significantly reduced during time in treatment. Conclusion: While there are methodological challenges analysing real-world non-control group cohort data, the findings indicate positive effects of the hEP programme on vocational and daily activity engagement for young people with FEP and at UHR status. A large proportion of the young people still identified as NEET after receiving treatment services, suggesting further refinement to ensure targeted and consistent vocational support throughout care. [ABSTRACT FROM AUTHOR]

Background: Despite progress in stroke therapy (e.g., revascularisation interventions by thrombolysis and/or thrombectomy, organised stroke care), many stroke survivors will have impairment of neurological function. We aimed to compare the cost-effectiveness of an oral natural formulation, MLC601, versus placebo in functional recovery among subjects receiving standard of care after an ischemic stroke of intermediate severity assessed with NIH Stroke Scale at baseline (b-NIHSS 8–14). Methods: A Markov cohort model with a 2-year time horizon was developed to simulate patients from a published randomised placebo-controlled clinical trial of MLC601 in their post-stroke functional recovery assessed by modified Rankin Score (mRS), from a health system perspective. Transition probabilities were derived from a multi-centre clinical trial in South East Asia. As cost and utility data were not collected in the trial, therefore we extracted them from the published literature. The main outcomes were incremental cost, incremental quality-adjusted life-year (QALY) gained, and incremental cost-effectiveness ratio (ICER). Besides base-case and sensitivity analyses, we performed subgroup analyses to explore the heterogeneity of patients with poor-prognosis factors (b-NIHSS 10–14, stroke onset to treatment time > 48 h, rehabilitation during first 3 month). All costs are expressed in 2022 Euro and USD, with an annual discount rate of 3% applied to costs and QALYs. Results: Base-case analysis showed that MLC601 was cost-effective compared with placebo, with €5,080 saved and 0.45 QALY gained, resulting in an ICER of -€11,352.50 per QALY gained. Similarly, results from subgroup analyses indicated that the use of MLC601 was a dominant strategy in all subgroups with poor-prognosis factors. Sensitivity analyses revealed the results were robust. Conclusion: Compared with placebo on top of standard stroke care, MLC601 was cost-effective in post-stroke functional recovery over two years. Due to the lack of cost and utility data from the study population, the results might not be generalizable to other settings. Further studies with country-specific data are needed to confirm the results of this study. Trial registration: URL http://www.clinicaltrials.gov. Unique identifier NCT00554723 November 7, 2007. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI. Methods: We generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology. Results: PNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis. Conclusion: Our findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery. [ABSTRACT FROM AUTHOR]

The development of therapeutic strategies to reduce impairments following spinal cord injury (SCI) motivates an active area of research, because there are no effective therapies. One strategy is to address injury‐induced demyelination of spared axons by promoting endogenous or exogenous remyelination. However, previously, we showed that new myelin was not necessary to regain hindlimb stepping following moderate thoracic spinal cord contusion in 3‐month‐old mice. The present analysis investigated two potential mechanisms by which animals can re‐establish locomotion in the absence of remyelination: compensation through intact white matter and conduction through spared axons. We induced a severe contusion injury to reduce the spared white matter rim in the remyelination deficient model, with no differences in recovery between remyelination deficient animals and injured littermate controls. We investigated the nodal properties of the axons at the lesion and found that in the remyelination deficient model, axons express the Nav1.2 voltage‐gated sodium channel, a sub‐type not typically expressed at mature nodes of Ranvier. In a moderate contusion injury, conduction velocities through the lesions of remyelination deficient animals were similar to those in animals with the capacity to remyelinate after injury. Detailed gait analysis and kinematics reveal subtle differences between remyelination deficient animals and remyelination competent controls, but no worse deficits. It is possible that upregulation of Nav1.2 channels may contribute to establishing conduction through the lesion. This conduction could contribute to compensation and regained motor function in mouse models of SCI. Such compensatory mechanism may have implications for interpreting efficacy results for remyelinating interventions in mice and the development of therapies for improving recovery following SCI. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of whole-body cryotherapy (WBC) on acute recovery after a single high-intensity training day. Twelve elite professional male rowers from the national aquatic training base. They were randomly divided into a WBC group (n = 6) and a control group (CON group, n = 6). They performed a high-intensity training program, with a single session immediately followed by WBC (-110°C, 3 min) or recovered naturally for 3 min (CON group). Rowing performance, skin temperature, heart rate, blood pressure, and blood lactate concentrations were recorded before training, immediately, 5 min, and 15 min after the intervention. Blood samples were collected early in the morning of the day of intervention and that of the following day. The results indicated that 1) the blood lactate concentrations after WBC were significantly lower than pre-training (p < 0.05); 2) the maximum power significantly decreased immediately after WBC compared to pre-training (p < 0.05); 3) a significant main effect of time was observed for average speed, which significantly decreased after WBC (p < 0.05); 4) a significant main effect of time for blood parameters was observed. Specifically, hematocrit, cortisol, and hemoglobin were significantly lower after WBC than pre-intervention, whereas testosterone/cortisol was significantly higher than pre-intervention (p < 0.05). The results of this study showed that a single session of WBC had a positive effect on accelerating the elimination of blood lactate after HIT, but did not significantly change rowing performance and physiological parameters. A single session of WBC was not an effective strategy for elite rowers for acute recovery after HIT. [ABSTRACT FROM AUTHOR]

Objective: Spinal cord injury (SCI), one of the major disabilities concerning central nervous system injury, results in permanent tissue loss and neurological impairment. The existing therapeutic options for SCI are limited and predominantly consist of chemical compounds. In this study, we delved into the neuroprotective effects of myricetin, a natural flavonoid compound, and the underlying mechanisms, specifically in the context of SCI, utilizing an in vivo model. Previously, our investigations revealed an elevation in the phosphorylated form of Lin-11, Isl-1, and Mec-3 kinase1 (LIMK1) at chronic time points postinjury, coinciding with neuronal loss and scar formation. Our primary objective here was to assess the potential neuroprotective properties of myricetin in SCI and to ascertain if these effects were linked to LIMK inhibition, a hitherto unexamined pathway to date. Methods: Computational docking and molecular dynamics simulation studies were performed to assess myricetin's potential to bind with LIMK. Then, using a rat contusion model, SCI was induced and different molecular techniques (Western blot, Evans Blue assay, quantitative reverse transcription polymerase chain reaction and immunohistochemistry) were performed to determine the effects of myricetin. Results: Remarkably, computational docking models identified myricetin as having a better interaction profile with LIMK than standard. Subsequent to myricetin treatment, a significant downregulation in phosphorylated LIMK expression was observed at chronic time points. This reduction correlated with a notable decrease in glial and fibrotic scar formation, and enhanced neuroprotection indicating a positive outcome in vivo. Conclusion: In summary, our findings underscore myricetin's potential as a bioactive compound capable of attenuating SCI-induced injury cascades by targeting the LIMK pathway. [ABSTRACT FROM AUTHOR]

This study aimed to assess the effects of the timing of administering botulinum neurotoxin A (BoNT/A) on nerve regeneration in rats. Sixty 6-week-old rats with a sciatic nerve injury were randomly divided into four groups: the immediately treated (IT) group (BoNT/A injection administered immediately post-injury), the delay-treated (DT) group (BoNT/A injection administered one week post-injury), the control group (saline administered one week post-injury), and the sham group (only skin and muscle incisions made). Nerve regeneration was assessed 3, 6, and 9 weeks post-injury using various techniques. The levels of glial fibrillary acid protein (GFAP), astroglial calcium-binding protein S100β (S100β), growth-associated protein 43 (GAP43), neurofilament 200 (NF200), and brain-derived neurotrophic factor (BDNF) in the IT and DT groups were higher. ELISA revealed the highest levels of these proteins in the IT group, followed by the DT and control groups. Toluidine blue staining revealed that the average area and myelin thickness were higher in the IT group. Electrophysiological studies revealed that the CMAP in the IT group was significantly higher than that in the control group, with the DT group exhibiting significant differences starting from week 8. The findings of the sciatic functional index analysis mirrored these results. Thus, administering BoNT/A injections immediately after a nerve injury is most effective for neural recovery. However, injections administered one week post-injury also significantly enhanced recovery. BoNT/A should be administered promptly after nerve damage; however, its administration during the non-acute phase is also beneficial. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the effect of cigarette smoking on functional recovery during inpatient rehabilitation for spinal cord injury. Methods: A total of 78 persons with spinal cord injury admitted to a rehabilitation hospital were included in this prospective observational study. The participants were divided into two groups: smokers and nonsmokers. Functional independence measurement (FIM) scores at baseline and discharge were recorded. The Hospital Anxiety and Depression scale (HADS) was used to assess emotional status. Results: Thirty-four people (43%) participants were cigarette smokers. Mean ages were 41.29±14.03 and 41.39±16.79 years for the smokers and non-smokers, respectively. Mean disease durations were 5.82±4.13 and 5.20±4.42 months in the smokers and non-smokers, respectively. Baseline FIM scores were 29.97±14.49 and 36.00±15.48 in the smoker and non-smoker groups, respectively (p=0.84). A statistically significant improvement in FIM scores was observed in both groups at discharge (p=0.001). The increase in FIM scores were 10.94±9.58 and 17.52±11.05 in the smoker and nonsmoker groups, respectively (p=0.007). FIM gain was higher in the non-smoker group (p=0.007). The mean HADS anxiety scores were 5.91±4.03 and 7.41±4.3 in the smoker and non-smoker groups, respectively (p=0.12). The mean HADS depression scores were 5.59±3.9 and 6.20±3.70 in the smoker and non-smoker groups, respectively (p=0.47). Conclusion: A significant functional improvement was observed in both smokers and nonsmokers with spinal cord injury after inpatient rehabilitation. Functional recovery was higher in the non-smoker group. [ABSTRACT FROM AUTHOR]

Background: Distal end radius fractures are common injuries treated in orthopedic practice, with varying treatment modalities influencing outcomes. Aims and Objectives: The study was designed to compare the outcomes between open reduction and internal fixation (ORIF) with plating and K-wires plus casting in patients treated for distal end radius fractures. Materials and Methods: One hundred patients with distal end radius fractures were included and divided into two groups: Group A (ORIF with plating) and Group B (K-wires plus casting), with 50 patients in each group. Parameters included were healing time, complication rates, functional recovery, patient satisfaction scores, pain levels during recovery, and the time to return to daily activities. Results: Group A demonstrated a shorter average healing time (8 weeks) compared to Group B (9 weeks). Complication rates showed 5% malunion and 4% delayed union in Group A, against 12% and 6%, respectively, in Group B. Functional recovery was higher in Group A, with 93% grip strength and 88% range of motion recovery. Patient satisfaction was also higher in Group A (8.5 out of 10) compared to Group B (7.5 out of 10). Pain levels during recovery were lower in Group A, and the time to return to daily activities was shorter (8 weeks for Group A versus 10 weeks for Group B). Conclusion: The study suggests that ORIF with plating offers better outcomes in terms of healing time, complication rates, functional recovery, patient satisfaction, pain management, and quicker return to daily activities than K-wires plus casting for distal end radius fractures. [ABSTRACT FROM AUTHOR]

Functional recovery is a new, nonstandardized building design objective, intended to improve a building's capacity to maintain or rapidly restore basic intended functions after a natural hazard event. Current building seismic design standards, which target life-safety performance objectives, provide limited requirements to ensure buildings maintain, or rapidly recover, function after earthquakes. Therefore, the expected functional recovery performance that is provided by current building codes is unclear. To provide clear and systematic insights to inform the development of prescriptive and performance-based design standards, this study documents the functional recovery performance for a set of 60 reinforced concrete archetype buildings. The results indicate that the estimated functional recovery time for reinforced concrete buildings designed to life-safety standards may approach 1 year, on average, for design-level earthquakes. Additionally, while increased strength and stiffness requirements significantly reduce the likelihood of a building being marked as unsafe due to structural damage, additional design provisions for nonstructural components are required to ensure a high confidence of rapid recovery. The findings from this study clarify the expected post-earthquake recovery of modern reinforced concrete buildings and identify key trends in underlying damage and response mechanisms required to improve future building performance. [ABSTRACT FROM AUTHOR]

Stroke is one of the most significant causes of death and long-term disability globally. Overproduction of reactive oxygen species by NADPH oxidase (NOX) plays an important role in exacerbating oxidative stress and causing neuronal damage after a stroke. There is growing evidence that NOX inhibition prevents ischemic injury and that the role of NOX in brain damage or recovery depends on specific post-stroke phases. In addition to studies on post-stroke neuroprotection by NOX inhibition, recent reports have also demonstrated the role of NOX in stroke recovery, a critical process for brain adaptation and functional reorganization after a stroke. Therefore, in this review, we investigated the role of NOX in stroke recovery with the aim of integrating preclinical findings into potential therapeutic strategies to improve stroke recovery. [ABSTRACT FROM AUTHOR]

The diaphragm, which is crucial for ventilation, is the primary muscle responsible for inspiration. Patients with severe burns who experience diaphragmatic dysfunction have an increased risk of mortality. Unfortunately, there are currently no effective medications available to prevent or treat this condition. The objective of our study is to utilize bioinformatics to identify potential genes and drugs associated with diaphragmatic dysfunction. In this study, text-mining techniques were utilized to identify genes associated with diaphragmatic dysfunction and recovery. Common genes were then analyzed using GO and KEGG pathway analysis, as well as protein–protein interaction network analysis. The obtained hub genes were processed using Cytoscape software, and their expression levels in diaphragmatic dysfunction were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in severe burn rats. Genes that were confirmed were then examined in drug–gene interaction databases to identify potential drugs associated with these genes. Our analysis revealed 96 genes that were common to both the "diaphragm dysfunction" and "functional recovery" text mining concepts. Gene enrichment analysis identified 19 genes representing 10 pathways. qRT-PCR showed a significant increase in expression levels of 13 genes, including CCL2, CCL3, CD4, EGF, HGF, IFNG, IGF1, IL17A, IL6, LEP, PTGS2, TGFB1, and TNF, in samples with diaphragmatic dysfunction. Additionally, we found that a total of 56 drugs targeted 5 potential genes. These findings provide new insights into the development of more effective drugs for treating diaphragmatic dysfunction and also present substantial opportunities for researching new target pharmacology and promoting drugs in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Background: Exploration of the benefits and timing of surgical decompression in spinal cord injury (SCI) has been a research hotspot. However, despite the higher volume and increasing emphasis on quality there remains no bibliometric view on SCI and surgical decompression. In this study, we aimed to perform bibliometric analysis to reveal the core countries, affiliations, journals, authors, and developmental trends in SCI and surgical decompression across the past 50years. Methods: Articles and reviews were retrieved from web of science core collection between 1975 and 2024. The bibliometrix package in R was used for data analysis and visualizing. Results: A total of 8,688 documents were investigated, indicating an ascending trend in annual publications. The USA and China played as the leaders in scientific productivity. The University of Toronto led in institutional productions. Core authors, such as Michael G. Fehlings, showed high productivity, and occasional authors showed widespread interests. Core journals like Spine and Spinal Cord served as beacons in this field. The interaction of core authors and international collaboration accentuated the cross-disciplinary feature of the field. Prominent documents emphasized the clinical significance of early decompression in 24h post SCI. Conclusion: Based on comprehensive bibliometric analysis and literature review, we identified the hotspots and future directions of this field: (1) further investigation into the molecular and cellular mechanisms to provide preclinical evidence for biological effects of early surgical decompression in SCI animal models; (2) further evaluation and validation of the optimal time window of surgical decompression based on large cohort, considering the inherent heterogeneity of subpopulations in complicated immune responses post SCI; (3) further exploration on the benefits of early decompression on the neurological, functional, and clinical outcomes in acute SCI; (4) evaluation of the optimal surgical methods and related outcomes; (5) applications of artificial intelligence-based technologies in spinal surgical decompression. [ABSTRACT FROM AUTHOR]

Regular exercise improves several functions, including cognition, in patients with stroke. However, the effect of regular exercise on neurogenesis related to cognition remains doubtful. We investigated the most effective exercise intensity for functional recovery after stroke using RNA sequencing following regular treadmill exercise. Photothrombotic cerebral infarction was conducted for 10-week-old male Sprague-Dawley rats (n = 36). A Morris water maze (MWM) test was performed before a regular treadmill exercise program (5 days/week, 4 weeks). Rats were randomly divided into four groups: group A (no exercise); group B (low intensity, maximal velocity 18 m/min); group C (moderate intensity, maximal velocity 24 m/min) and group D (high intensity, maximal velocity 30 m/min). After 4 weeks, another MWM test was performed, and all rats were sacrificed. RNA sequencing was performed with ipsilesional hippocampal tissue. On the day after cerebral infarction, no differences in escape latency and velocity were observed among the groups. At 4 weeks after cerebral infarction, the escape latencies in groups B, C, and D were shorter than in group A. The escape latencies in groups B and C were shorter than in group D. The velocity in groups A, B, and C was faster than in group D. Thirty gene symbols related to neurogenesis were detected (p < 0.05, fold change > 1.0, average normalized read count > four times). In the neurotrophin-signaling pathway, the CHK gene was upregulated, and the NF-κB gene was downregulated in the low-intensity group. The CHK and NF-κB genes were both downregulated in the moderate-intensity group. The Raf and IRAK genes were downregulated in the high-intensity group. Western blot analysis showed that NF-κB expression was lowest in the moderate-intensity group, whereas CHK and Raf were elevated, and IRAK was decreased in the high-intensity group. Moderate-intensity exercise may contribute to neuroplasticity. Variation in the expression of neurotrophins in neurogenesis according to exercise intensity may reveal the mechanism of neuroplasticity. Thus, NF-κB is the key neurotrophin for neurogenesis related to exercise intensity. [ABSTRACT FROM AUTHOR]

Spinal cord injuries (SCIs) often result in secondary damage; therefore, interventions beyond current cell transplantation methods must be explored. The innate phagocytic propensity of macrophages are exploited for artificially aged erythrocytes and developed a delivery system fusing erythrocytes with reactive oxygen species (ROS)‐reactive nanoparticles prepared from a diselenide‐bond cross‐linked organic compound. The system targets peripheral blood macrophages, delivering anti‐glutamate drug‐loaded nanoparticles to the SCI site, releasing the drug upon ROS stimulation. This efficiently enables targeted drug delivery and reprograms peripheral macrophages through synergistic action with erythrocytes and encapsulated nucleic acids, effectively modulating the immune microenvironment in the SCI zone (significantly reduces neuronal apoptosis and alters the macrophage phenotype in the SCI region). The approach effectively addresses glutamate toxicity and immune inflammation by effectively regulating the lesion microenvironment, providing protection to neurons and creating favorable conditions for regeneration. Departing from the conventional “red blood cell backpack” model, the “chocolate chip cookie” concept is paradigm‐altering, enabling multifaceted erythrocyte functions. Collectively, the system comprehensively enhances the post‐SCI microenvironment. Its efficacy in SCI treatment and innovative drug delivery approach open new possibilities for neural function recovery. By laying the groundwork for future clinical applications, the research pioneers a transformative path toward advancing SCI therapeutics. [ABSTRACT FROM AUTHOR]

Background and objectives: Fatigue has been associated with adverse effects on recovery from ischemic stroke based on previous observational research. The purpose of our study was to explore the potential causal association of fatigue with poor functional outcome after ischemic stroke by employing Mendelian randomization (MR). Methods: A set of instrumental variables, comprising 36 single-nucleotide polymorphisms (SNPs) that are only related to fatigue, were derived from a genome-wide association study (GWAS) that included 449,019 general individuals. The functional outcomes after ischemic stroke were derived from a GWAS (Genetics of Ischemic Stroke Functional Outcome Network) involving 6,021 survivors. Two-sample MR methods were used to assess the causal effect, including inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode. In bidirectional MR analysis, the reverse causal association was analyzed using the Wald ratio method. The mediation effects of lipid metabolites were analyzed using two-step MR analysis. Results: Genetic liability to fatigue was causally associated with the poor functional outcome (modified Rankin Scale =3 at 3 months) after ischemic stroke (OR = 4.20, 95%CI [1.11-15.99], p < 0.05). However, genetic predicted poor functional outcome after ischemic stroke was not associated with fatigue (OR = 1.00, 95%CI [0.99-1.02], p > 0.05). The results of the two-step MR showed that cholesteryl esters to total lipids ratio in large very low-density lipoprotein (VLDL) (ME = -0.13, p < 0.05); concentration of very large VLDL particles (ME = -0.13, p < 0.05); free cholesterol in large VLDL (ME = -0.13, p < 0.05); free cholesterol to total lipids ratio in very large VLDL (ME = -0.22, p < 0.05); phospholipids in large VLDL (ME = -0.15, p < 0.05); phospholipids in very large VLDL (ME = -0.13, p < 0.05); phospholipids to total lipids ratio in large highdensity lipoprotein (HDL) (ME = -0.17, p < 0.05); total lipids in very large VLDL (ME = -0.14, p < 0.05); triglycerides in small VLDL (ME = -0.11, p < 0.05); and triglycerides to total lipids ratio in large HDL (ME = -0.10, p < 0.05) assumed a pivotal role in mediating the association between fatigue and poor functional outcome after ischemic stroke. Conclusion: Our study provides evidence supporting the causal association between fatigue and the poor functional outcome after ischemic stroke, which emphasizes the importance of implementing interventions aimed at addressing fatigue. This could offer a therapeutic target to improve recovery after ischemic stroke and warrant exploration in a clinical context. One potential mechanism by which fatigue affects functional outcomes after ischemic stroke is through the action of lipid metabolites. [ABSTRACT FROM AUTHOR]

Heart failure poses a significant challenge to healthcare systems and society at large, mainly due to its increasing prevalence among the aging population and its association with frequent hospitalizations with high mortality rates. At its core, heart failure management seeks to emphasize myocardial recovery across the spectrum of disease, from acute cardiogenic shock to ambulatory heart failure, with care ranging from consideration of mechanical circulatory support to medication optimization. In this review, we propose a definition of "recovery" that extends beyond the restoration of normal myocardial dynamics to the entire human organism, ultimately improving functional capacity and clinical outcomes. Prioritizing this more holistic definition of "recovery" allows a broader representation of the spectrum of disease and corresponding management that falls under the "heart failure" umbrella. In so doing, a more synchronized delivery of care across settings and disciplines may be feasible for the modern patient living with heart failure. [ABSTRACT FROM AUTHOR]

In recent years, there has been marked interest in looking at the psychological consequences of medical conditions, such as traumatic or acquired brain injuries. Coping strategies are essential for clinical recovery and for dealing with the stressful events that a clinical condition brings with it. The purpose of this review is to analyze studies that explore how coping strategies influence psychological changes in patients with acquired brain injury. Studies were identified from research in the PubMed, Scopus, and Embase databases. According to our findings, patients with ABI utilize different coping strategies based on the circumstances and factors such as the diagnosis severity, their age, time lived with the pathology, and personal characteristics, which have an influence on quality of life and rehabilitation. This review demonstrated that coping strategies have an impact on different aspects of the clinical and personal lives of patients with ABI. The rehabilitation process must consider the influence of these mechanisms on dealing with situations, as they can change cognitive and emotional perceptions of patients' experience with the disease, as well as laying the foundations for functional or dysfunction in terms of the propensity of a person for the path of psychological and physical recovery. [ABSTRACT FROM AUTHOR]

Objective: To rigorously evaluate the impact of the percentage of parenchymal volume preserved (PPVP) and how well the preserved parenchyma recovers from ischaemia (Recischaemia) on functional outcomes after partial nephrectomy (PN) using an accurate and objective software‐based methodology for estimating parenchymal volumes and split renal function (SRF). A secondary objective was to assess potential predictors of the PPVP. Patients and Methods: A total of 894 PN patients with available studies (2011–2014) were evaluated. The PPVP was measured from cross‐sectional imaging at ≤3 months before and 3–12 months after PN using semi‐automated software. Pearson correlation evaluated relationships between continuous variables. Multivariable linear regression evaluated predictors of ipsilateral glomerular filtration rate (GFR) preserved and the PPVP. Relative‐importance analysis was used to evaluate the impact of the PPVP on ipsilateral GFR preserved. Recischaemia was defined as the percentage of ipsilateral GFR preserved normalised by the PPVP. Results: The median tumour size and R.E.N.A.L. nephrometry score were 3.4 cm and 7, respectively. In all, 49 patients (5.5%) had a solitary kidney. In all, 538 (60%)/251 (28%)/104 (12%) patients were managed with warm/cold/zero ischaemia, respectively. The median pre/post ipsilateral GFRs were 40/31 mL/min/1.73 m2, and the median (interquartile range [IQR]) percentage of ipsilateral GFR preserved was 80% (71–88%). The median pre/post ipsilateral parenchymal volumes were 181/149 mL, and the median (IQR) PPVP was 84% (76–92%). In all, 330 patients (37%) had a PPVP of <80%, while only 34 (4%) had a Recischaemia of <80%. The percentage of ipsilateral GFR preserved correlated strongly with the PPVP (r = 0.83, P < 0.01) and loss of parenchymal volume accounted for 80% of the loss of ipsilateral GFR. Multivariable analysis confirmed that the PPVP was the strongest predictor of ipsilateral GFR preserved. Greater tumour size and endophytic and nearness properties of the R.E.N.A.L. nephrometry score were associated with a reduced PPVP (all P ≤ 0.01). Solitary kidney and cold ischaemia were associated with an increased PPVP (all P < 0.05). Conclusions: A reduced PPVP predominates regarding functional decline after PN, although a low Recischaemia can also contribute. Tumour‐related factors strongly influence the PPVP, while surgical efforts can improve the PPVP as observed for patients with solitary kidneys. [ABSTRACT FROM AUTHOR]

Stroke and traumatic brain injury leave many survivors with permanent neurological disabilities, and the development of therapeutics to enhance functional recovery is needed. Both residential and infiltrating immune cells participate in the acute inflammation after brain injury, exacerbating functional outcomes; however, some immune cells have been reported to alter their characteristic to a reparative phenotype. This review focused on the recent findings of the reparative immunity of myeloid cells. Functional recovery after injury is achieved through the combination of resolution of inflammation, reorganization of neuronal network, white matter repair, angiogenesis and extracellular matrix reorganization. In each process, myeloid cells play vital roles in leading to functional recovery. Further research on the diversity of immune cells implicated in neural repair will be promising to develop therapeutics enhancing functional recovery after brain tissue injuries. [ABSTRACT FROM AUTHOR]

Recent earthquakes have demonstrated that code-conforming modern (i.e. post-1970s) reinforced concrete (RC) buildings can satisfy life safety performance objectives. However, the accumulated earthquake damage in these modern buildings raised concerns about their performance in future events, contributing to widespread demolition and long-term closure of damaged buildings. The economic and environmental impacts associated with the demolition and long-term closure of modern buildings led to societal demands for improved design procedures to limit damage and shorten recovery time after earthquakes. To address societal demands, this study proposes a damage-control-oriented seismic design approach that targets functional recovery by ensuring structural component demands do not exceed the damage-control limit state (DLS) under design-level events. Herein, DLS is defined as the post-earthquake state beyond which the strength and deformation capacity of a structural component is compromised, and its performance in a future event cannot be relied upon without safety-critical repair. This study proposes a methodology to determine component deformation limits for the design of structures for damage control. Using the developed methodology, we propose component rotation limits for RC beams, columns, and walls. The seismic performance and capability of buildings designed using the proposed design approach to satisfy recovery-based performance objectives is demonstrated through nonlinear response history and recovery analyses (using the ATC-138 methodology) of four archetype frame buildings, designed per New Zealand standards to different beam deformation limits. The analyses show that building codes can achieve functional recovery using the proposed component deformation limits without the need for sophisticated recovery analyses. [ABSTRACT FROM AUTHOR]

Background: Temporomandibular disorders (TMDs) frequently cause orofacial pain and dysfunction, with treatment options spanning from conservative therapies to invasive surgical procedures. The aim of this systematic review was to analyze and compare the efficacy and safety profiles of conservative, minimally invasive interventions and surgical procedures in patients diagnosed with TMDs and disc displacement. Methods: Following PRISMA recommendations, PubMed, Scopus, and Web of Science databases were searched for randomized clinical trials (RCT). Data were synthesized in a table and evaluated through the Cochrane risk of bias 2 (RoB 2) tool. Results: Thirty-eight RCTs, most with moderate RoB, were selected. Conservative approaches, including physical therapy and occlusal devices, led to an improvement in symptoms and function. Pharmacological treatments demonstrated effectiveness in reducing pain and improving function; however, they can have undesirable side effects. Minimally invasive and invasive treatments also demonstrated efficacy, although most trials did not show their superiority to conservative treatments. Conclusion: The primary approach to TMDs should be a conservative, multimodal treatment plan tailored to patient complaints and characteristics. Treatment goals should focus on symptom control and functional recovery. Surgical treatment should be reserved for cases with a precise diagnosis and a clear etiology. [ABSTRACT FROM AUTHOR]

Abstract Background Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI. Methods We generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology. Results PNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis. Conclusion Our findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery.

Objective Spinal cord injury (SCI), one of the major disabilities concerning central nervous system injury, results in permanent tissue loss and neurological impairment. The existing therapeutic options for SCI are limited and predominantly consist of chemical compounds. In this study, we delved into the neuroprotective effects of myricetin, a natural flavonoid compound, and the underlying mechanisms, specifically in the context of SCI, utilizing an in vivo model. Previously, our investigations revealed an elevation in the phosphorylated form of Lin-11, Isl-1, and Mec-3 kinase1 (LIMK1) at chronic time points postinjury, coinciding with neuronal loss and scar formation. Our primary objective here was to assess the potential neuroprotective properties of myricetin in SCI and to ascertain if these effects were linked to LIMK inhibition, a hitherto unexamined pathway to date. Methods Computational docking and molecular dynamics simulation studies were performed to assess myricetin’s potential to bind with LIMK. Then, using a rat contusion model, SCI was induced and different molecular techniques (Western blot, Evans Blue assay, quantitative reverse transcription polymerase chain reaction and immunohistochemistry) were performed to determine the effects of myricetin. Results Remarkably, computational docking models identified myricetin as having a better interaction profile with LIMK than standard. Subsequent to myricetin treatment, a significant downregulation in phosphorylated LIMK expression was observed at chronic time points. This reduction correlated with a notable decrease in glial and fibrotic scar formation, and enhanced neuroprotection indicating a positive outcome in vivo. Conclusion In summary, our findings underscore myricetin’s potential as a bioactive compound capable of attenuating SCI-induced injury cascades by targeting the LIMK pathway.

Abstract Background Despite progress in stroke therapy (e.g., revascularisation interventions by thrombolysis and/or thrombectomy, organised stroke care), many stroke survivors will have impairment of neurological function. We aimed to compare the cost-effectiveness of an oral natural formulation, MLC601, versus placebo in functional recovery among subjects receiving standard of care after an ischemic stroke of intermediate severity assessed with NIH Stroke Scale at baseline (b-NIHSS 8–14). Methods A Markov cohort model with a 2-year time horizon was developed to simulate patients from a published randomised placebo-controlled clinical trial of MLC601 in their post-stroke functional recovery assessed by modified Rankin Score (mRS), from a health system perspective. Transition probabilities were derived from a multi-centre clinical trial in South East Asia. As cost and utility data were not collected in the trial, therefore we extracted them from the published literature. The main outcomes were incremental cost, incremental quality-adjusted life-year (QALY) gained, and incremental cost-effectiveness ratio (ICER). Besides base-case and sensitivity analyses, we performed subgroup analyses to explore the heterogeneity of patients with poor-prognosis factors (b-NIHSS 10–14, stroke onset to treatment time > 48 h, rehabilitation during first 3 month). All costs are expressed in 2022 Euro and USD, with an annual discount rate of 3% applied to costs and QALYs. Results Base-case analysis showed that MLC601 was cost-effective compared with placebo, with €5,080 saved and 0.45 QALY gained, resulting in an ICER of -€11,352.50 per QALY gained. Similarly, results from subgroup analyses indicated that the use of MLC601 was a dominant strategy in all subgroups with poor-prognosis factors. Sensitivity analyses revealed the results were robust. Conclusion Compared with placebo on top of standard stroke care, MLC601 was cost-effective in post-stroke functional recovery over two years. Due to the lack of cost and utility data from the study population, the results might not be generalizable to other settings. Further studies with country-specific data are needed to confirm the results of this study. Trial registration URL http://www.clinicaltrials.gov . Unique identifier NCT00554723 November 7, 2007.

Background: Distal end radius fractures are common injuries treated in orthopedic practice, with varying treatment modalities influencing outcomes. Aims and Objectives: The study was designed to compare the outcomes between open reduction and internal fixation (ORIF) with plating and K-wires plus casting in patients treated for distal end radius fractures. Materials and Methods: One hundred patients with distal end radius fractures were included and divided into two groups: Group A (ORIF with plating) and Group B (K-wires plus casting), with 50 patients in each group. Parameters included were healing time, complication rates, functional recovery, patient satisfaction scores, pain levels during recovery, and the time to return to daily activities. Results: Group A demonstrated a shorter average healing time (8 weeks) compared to Group B (9 weeks). Complication rates showed 5% malunion and 4% delayed union in Group A, against 12% and 6%, respectively, in Group B. Functional recovery was higher in Group A, with 93% grip strength and 88% range of motion recovery. Patient satisfaction was also higher in Group A (8.5 out of 10) compared to Group B (7.5 out of 10). Pain levels during recovery were lower in Group A, and the time to return to daily activities was shorter (8 weeks for Group A versus 10 weeks for Group B). Conclusion: The study suggests that ORIF with plating offers better outcomes in terms of healing time, complication rates, functional recovery, patient satisfaction, pain management, and quicker return to daily activities than K-wires plus casting for distal end radius fractures.

Spinal cord injury (SCI) often results in irreversible loss of sensory and motor functions, and most SCIs are incurable with current medical practice. One of the hardest challenges in treating SCI is the development of a dysfunctional pathological microenvironment, which mainly comprises excessive inflammation, deposition of inhibitory molecules, neurotrophic factor deprivation, glial scar formation, and imbalance of vascular function. To overcome this challenge, implantation of functional biomaterials at the injury site has been regarded as a potential treatment for modulating the dysfunctional microenvironment to support axon regeneration, remyelination at injury site, and functional recovery after SCI. This review summarizes characteristics of dysfunctional pathological microenvironment and recent advances in biomaterials as well as the technologies used to modulate inflammatory microenvironment, regulate inhibitory microenvironment, and reshape revascularization microenvironment. Moreover, technological limitations, challenges, and future prospects of functional biomaterials to promote efficient repair of SCI are also discussed. This review will aid further understanding and development of functional biomaterials to regulate pathological SCI microenvironment.

Introduction: This study aimed to compare the effectiveness of endoscopic carpal tunnel release (ECTR) versus open carpal tunnel release (OCTR) in treating carpal tunnel syndrome (CTS), focusing on symptom relief, functional recovery and post-operative complications. Methods: A retrospective analysis was conducted on 44 patients diagnosed with CTS, randomly assigned to undergo either ECTR (n=23) or OCTR (n=21). Parameters evaluated included post-operative pain, grip strength, functional status using the Disability of the Arm, Shoulder and Hand (DASH) score and time to return to work. Results: Patients who underwent ECTR demonstrated superior functional recovery and quicker return to daily and work activities compared to those in the OCTR group. Grip strength improvement post-surgery showed no significant difference between the groups. However, ECTR patients reported significantly lower DASH scores and faster return to work, indicating better outcomes. There were fewer reports of post-operative complications and scar sensitivity in the ECTR group. Conclusion: ECTR provides an effective alternative to OCTR for CTS treatment, with advantages in functional recovery speed, reduced post-operative discomfort and faster return to work. These findings support the adoption of ECTR as a preferred surgical approach for CTS, highlighting its potential to improve patient outcomes with minimal complications.

Abstract Peripheral nerve injury (PNI) often leads to retrograde cell death in the spinal cord and dorsal root ganglia (DRG), hindering nerve regeneration and functional recovery. Repetitive magnetic stimulation (rMS) promotes nerve regeneration following PNI. Therefore, this study aimed to investigate the effects of rMS on post-injury neuronal death and nerve regeneration. Seventy-two rats underwent autologous sciatic nerve grafting and were divided into two groups: the rMS group, which received rMS and the control (CON) group, which received no treatment. Motor neuron, DRG neuron, and caspase-3 positive DRG neuron counts, as well as DRG mRNA expression analyses, were conducted at 1-, 4-, and 8-weeks post-injury. Functional and axon regeneration analyses were performed at 8-weeks post-injury. The CON group demonstrated a decreased DRG neuron count starting from 1 week post-injury, whereas the rMS group exhibited significantly higher DRG neuron counts at 1- and 4-weeks post-injury. At 8-weeks post-injury, the rMS group demonstrated a significantly greater myelinated nerve fiber density in autografted nerves. Furthermore, functional analysis showed significant improvements in latency and toe angle in the rMS group. Overall, these results suggest that rMS can prevent DRG neuron death and enhance nerve regeneration and motor function recovery after PNI.

Abstract Background With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs. Methods In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed. Discussion The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs. Trial Registration ClinicalTrials.gov Identifier: NCT06196008.

Nahida Nayaz Ahmed,1,&ast; Shuja Reagu,2,&ast; Samia Alkhoori,3 Amina Cherchali,4 Pradeep Purushottamahanti,5 Urooj Siddiqui4 1SEHA Mental Health & Wellbeing Services, College of Medicine and Health Sciences of the United Arab Emirates University, Abu Dhabi, United Arab Emirates; 2Weill Cornell Medicine, Doha, Qatar; Hamad Medical Corporation, Doha, Qatar; 3Rashid Hospital, Dubai Health, Dubai, United Arab Emirates; 4Viatris Middle East FZ-LLC, Dubai, United Arab Emirates; 5Global Medical Affairs, Viatris Inc., Bangalore, India&ast;These authors contributed equally to this workCorrespondence: Pradeep Purushottamahanti, Psychiatry Medical Lead, Global Medical Affairs, Viatris, 11th Floor, Prestige Tech Park Platina-3, Kadubeesanahalli, Bengaluru, 560103, India, Email pradeep.purushottamahanti@viatris.comAbstract: Up to 75% of individuals with major depressive disorder (MDD) may have residual symptoms such as amotivation or anhedonia, which prevent full functional recovery and are associated with relapse. Globally and in the Gulf region, primary care physicians (PCPs) have an important role in alleviating stigma and in identifying and monitoring the residual symptoms of depression, as PCPs are the preliminary interface between patients and specialists in the collaborative care model. Therefore, mental healthcare upskilling programmes for PCPs are needed, as are basic instruments to evaluate residual symptoms swiftly and accurately in primary care. Currently, few if any electronic enablers have been designed to specifically monitor residual symptoms in patients with MDD. The objectives of this review are to highlight how accurate evaluation of residual symptoms with an easy-to-use electronic enabler in primary care may improve functional recovery and overall mental health outcomes, and how such an enabler may guide pharmacotherapy selection and positively impact the patient journey. Here, we show the potential advantages of electronic enablers in primary care, which include the possibility for a deeper “dive” into the patient journey and facilitation of treatment optimisation. At the policy and practice levels, electronic enablers endorsed by government agencies and local psychiatric associations may receive greater PCP attention and backing, improve patient involvement in shared clinical decision-making, and help to reduce the general stigma around mental health disorders. In the Gulf region, an easy-to-use electronic enabler in primary care, incorporating aspects of the Hamilton Depression Rating Scale to monitor amotivation, and aspects of the Montgomery-Åsberg Depression Rating Scale to monitor anhedonia, could markedly improve the patient journey from residual symptoms through to full functional recovery in individuals with MDD.Keywords: electronic tools, functional recovery, knowledge gaps, major depression, primary care, residual outcomes

Background: Stroke is gaining worldwide importance as the focus now shifts to non-communicable diseases. According to the World Health Organization, over 15 million people, equating to one in every 400 people, suffer stroke worldwide per year. There are many factors which affect the outcome of stroke – artery involved, size of the infarct, associated co-morbidities, age of the patient, collateral blood supply, and many more. Among those one of the factors proposed is stress hyperglycemia (SH). Aims and Objectives: The aims and objectives of the study are to identify the occurrence of SH in patients admitted with ischemic stroke and to assess the relation of SH in clinical outcomes in patients with ischemic stroke. Materials and Methods: The prospective study was conducted on patients admitted to medical college hospitals affiliated with VIMS, Ballari. All patients age more than 18 years presenting with acute-onset ischemic stroke were taken into the study, and GRBS was done at presentation and at every 6th hourly for 48 h to identify hyperglycemia. Hemoglobin A1c was done to rule out overt diabetes and previously undiagnosed diabetes mellitus. Clinical outcome and functional recovery using the modified ranking scale (MRS) were done at the time of admission, at discharge, and at every month for 3 months. Results: Out of 150 patients, 63 (42%) of them had SH. The majority of patients belong to 60–69 years age group. The mean age of patients with SH was 60.2 years and that of patients without SH was 57.75 years. MRS score at the time of admission and during follow-up was higher in SH patients than no SH patients (P

Probabilistic seismic performance assessment method for buildings offers a valuable approach to simulate the broader regional impacts: economic losses, downtime, and casualties. A crucial aspect of this process entails accounting for the spatial correlation of building performances, aiming for an accurate estimation of the probability of extreme regional losses, such as the simultaneous collapse of buildings with similar structural characteristics. In this study, a correlation model based on a Gaussian random field is employed, and several key challenges associated with its application are addressed. In addition, efficiency of five different methods of selecting station records from the same earthquake scenario is compared. The minimum number of earthquake records necessary to achieve a stable correlation result is determined. Additionally, spatial correlations derived from different history earthquake events are compared. By addressing these critical issues, this research contributes to refining the reliability of probabilistic methods for regional resilience assessment.

Spinal cord injury (SCI) has limited treatment options for regaining function. Adipose-derived stem cells (ADSCs) show promise owing to their ability to differentiate into multiple cell types, promote nerve cell survival, and modulate inflammation. This review explores ADSC therapy for SCI, focusing on its potential for improving function, preclinical and early clinical trial progress, challenges, and future directions.Preclinical studies have demonstrated ADSC transplantation's effectiveness in promoting functional recovery, reducing cavity formation, and enhancing nerve regrowth and myelin repair. To improve ADSC efficacy, strategies including genetic modification and combination with rehabilitation are being explored. Early clinical trials have shown safety and feasibility, with some suggesting motor and sensory function improvements.Challenges remain for clinical translation, including optimizing cell survival and delivery, determining dosing, addressing tumor formation risks, and establishing standardized protocols. Future research should focus on overcoming these challenges and exploring the potential for combining ADSC therapy with other treatments, including rehabilitation and medication.

The multi-disciplinary data and information available at a community level comprise the foundation of natural hazard resilience modeling. These data enable and inform mitigation and recovery planning decisions prior to and following damaging events such as earthquakes. This paper presents a multi-disciplinary seismic resilience modeling methodology to assess the vulnerability of the built environment and economic systems. This methodology can assist decision-makers with developing effective mitigation policies to improve the seismic resilience of communities. Two complementary modeling strategies are designed to examine the impacts of scenario earthquakes from a combined engineering and economic perspective. The engineering model is developed using a probabilistic fragility-based modeling approach and is analyzed using Monte Carlo (MC) simulations subject to seismic multi-hazard, including simulated ground shaking and resulting liquefaction of the soil, to quantify the physical damage to buildings and electric power substations (EPS). The outcome of the analysis is subsequently used as input to repair and recovery models to quantify repair cost and recovery time metrics for buildings and as input to functionality models to estimate the functionality of individual buildings and substations by accounting for their interdependency. The economic model consists of a spatial computable general equilibrium (SCGE) model that aggregates commercial buildings into sectors for retail, manufacturing, services, etc., and aggregates residential buildings into a wide range of household groups. The SCGE model employs building functionality estimates to quantify the economic losses. The outcomes of this integrated modeling consist of engineering and economic impact metrics, which are used to investigate mitigation actions to help inform a community on approaches to achieve its resilience goals. An illustrative case study of Salt Lake County (SLC), Utah, developed through an extensive collaborative partnership and engagement with SLC officials, is presented. The results demonstrate the effectiveness of the proposed methodology in quantifying the loss and functional recovery of infrastructure systems, the impacts on capital stock, employment, and household income and the effect of various mitigation strategies in reducing the losses and functional recovery time subject to earthquakes with varying intensities.

Abstract Aims To determine the prevalence and impact of emotional blunting (EB) in patients with major depressive disorder (MDD) in Japan, and identify treatment needs for EB using patients' perceptions and attitudes. Methods Eligible patients in Japan (aged 18–59 years) who reported a diagnosis of MDD and antidepressant medication use for >3 months were eligible to complete an online survey. The primary outcome was the prevalence of EB, self‐reported using a validated screening question. Secondary outcomes included the correlation between EB symptoms (measured by the Oxford Depression Questionnaire [ODQ]) and scores on the Patient Health Questionnaire 9‐item (PHQ‐9), Generalized Anxiety Disorder 7‐item (GAD‐7), Work and Social Adjustment Scale (WSAS), and the EuroQol 5‐Dimension 5‐Levels questionnaire (EQ‐5D‐5L). Descriptive questions were used to explore patients' perceptions and attitudes toward EB. Results In total, 3376 patients were included in the analysis (56% male; 48% aged 50–59 years). Overall, 67.1% of patients self‐reported symptoms of EB, with 10% rating these as severe. The mean (SD) ODQ total score was 78.2 (21.5), which increased with worsening EB symptoms. There were correlations between ODQ total scores and the PHQ‐9, GAD‐7, WSAS, and EQ‐5D‐5L scores (correlation coefficients: 0.67, 0.55, 0.56, −0.51, respectively; all p

Stroke is a leading cause of mortality worldwide and a major cause of disability having a high burden on patients, society, and caregiving systems. This study was conducted to investigate the presence of clusters of in-hospital patients with acute stroke based on demographic and clinical data. Cluster analysis reveals patterns in patient characteristics without requiring knowledge of a predefined patient category or assumptions about likely groupings within the data.

Astrocytes are increasingly recognised as partaking in complex homeostatic mechanisms critical for regulating neuronal plasticity following central nervous system (CNS) insults. Ischaemic stroke and traumatic brain injury are associated with high rates of disability and mortality. Depending on the context and type of injury, reactive astrocytes respond with diverse morphological, proliferative and functional changes collectively known as astrogliosis, which results in both pathogenic and protective effects. There is a large body of research on the negative consequences of astrogliosis following brain injuries. There is also growing interest in how astrogliosis might in some contexts be protective and help to limit the spread of the injury. However, little is known about how astrocytes contribute to the chronic functional recovery phase following traumatic and ischaemic brain insults. In this review, we explore the protective functions of astrocytes in various aspects of secondary brain injury such as oedema, inflammation and blood–brain barrier dysfunction. We also discuss the current knowledge on astrocyte contribution to tissue regeneration, including angiogenesis, neurogenesis, synaptogenesis, dendrogenesis and axogenesis. Finally, we discuss diverse astrocyte‐related factors that, if selectively targeted, could form the basis of astrocyte‐targeted therapeutic strategies to better address currently untreatable CNS disorders. [ABSTRACT FROM AUTHOR]

Unsuccessful axonal regeneration in transected spinal cord injury (SCI) is mainly attributed to shortage of growth factors, inhibitory glial scar, and low intrinsic regenerating capacity of severely injured neurons. Previously, we constructed an axonal growth permissive pathway in a thoracic hemisected injury by transplantation of Schwann cells overexpressing glial-cell-derived neurotrophic factor (SCs-GDNF) into the lesion gap as well as the caudal cord and proved that this novel permissive bridge promoted the regeneration of descending propriospinal tract (dPST) axons across and beyond the lesion. In the current study, we subjected rats to complete thoracic (T11) spinal cord transections and examined whether these combinatorial treatments can support dPST axons' regeneration beyond the transected injury. The results indicated that GDNF significantly improved graft–host interface by promoting integration between SCs and astrocytes, especially the migration of reactive astrocyte into SCs-GDNF territory. The glial response in the caudal graft area has been significantly attenuated. The astrocytes inside the grafted area were morphologically characterized by elongated and slim process and bipolar orientation accompanied by dramatically reduced expression of glial fibrillary acidic protein. Tremendous dPST axons have been found to regenerate across the lesion and back to the caudal spinal cord which were otherwise difficult to see in control groups. The caudal synaptic connections were formed, and regenerated axons were remyelinated. The hindlimb locomotor function has been improved. [ABSTRACT FROM AUTHOR]

Purpose: Living independently, as opposed to in sheltered housing or with caregivers, is an important aim in the recovery of individuals with psychosis, but the transition to independence can be challenging. This study aims to investigate how individuals with psychosis move between living arrangements and to identify the barriers and facilitators of moving towards independence. Methods: The living arrangements of 1119 individuals with non-affective psychosis from the Genetic Risk and Outcome of Psychosis study were assessed at baseline, at three- and six-year follow-ups and further categorized as either supported (sheltered housing or with parents) or independent (single or with partner/family). We estimated the probabilities of transitioning between the living statuses and investigated the influence of demographic characteristics, symptomatology, cognition, social support, and premorbid social adjustment on transition using Markov chain modelling. Results: The majority of individuals living in supported housing remained there during the six-year follow-up period (~ 60%). The likelihood of moving from supported to independent living was twice as high for participants who were younger, five-to-six times higher for women, twice as high for individuals with better overall cognition, and five times higher for those with a course of low positive symptoms. Conclusion: This study highlights that a large group of individuals with psychosis in supported housing is unlikely to move to independent living. Older men with cognitive impairments and who show continuous severe positive symptoms are the least likely to move living independently. Tailored interventions for these at-risk individuals could increase their chances of moving to independent living. [ABSTRACT FROM AUTHOR]

Background: Stroke is gaining worldwide importance as the focus now shifts to noncommunicable diseases. According to the World Health Organization, over 15 million people, equating to one in every 400 people, suffer stroke worldwide per year. There are many factors which affect the outcome of stroke – artery involved, size of the infarct, associated co-morbidities, age of the patient, collateral blood supply, and many more. Among those one of the factors proposed is stress hyperglycemia (SH). Aims and Objectives: The aims and objectives of the study are to identify the occurrence of SH in patients admitted with ischemic stroke and to assess the relation of SH in clinical outcomes in patients with ischemic stroke. Materials and Methods: The prospective study was conducted on patients admitted to medical college hospitals affiliated with VIMS, Ballari. All patients age more than 18 years presenting with acute-onset ischemic stroke were taken into the study, and GRBS was done at presentation and at every 6th hourly for 48 h to identify hyperglycemia. Hemoglobin A1c was done to rule out overt diabetes and previously undiagnosed diabetes mellitus. Clinical outcome and functional recovery using the modified ranking scale (MRS) were done at the time of admission, at discharge, and at every month for 3 months. Results: Out of 150 patients, 63 (42%) of them had SH. The majority of patients belong to 60–69 years age group. The mean age of patients with SH was 60.2 years and that of patients without SH was 57.75 years. MRS score at the time of admission and during follow-up was higher in SH patients than no SH patients (P<0.001). Patients with SH were more prone to urinary tract infection (n=19 [SH]; n=8 [no SH] P<0.001), bed sores (n=10 [SH]; n=18 [no SH] P<0.008), lower respiratory tract infection (n=30 [SH]; n=34 [no SH], P=0.000), and duration of hospital stay (P=0.000). Delay in presentation to a health facility after the onset of stroke symptoms was found to be a significant contributing factor in SH patients (P<0.003). Conclusion: The prevalence of SH in ischemic stroke is high. Patients with SH had longer duration of hospital stay, high mortality rate, higher incidence of complications, and poor functional recovery. [ABSTRACT FROM AUTHOR]

The proportion of patients with American Spinal Injury Association Impairment Scale (AIS) grade D traumatic spinal cord injuries (tSCI) is increasing. Although initial motor deficits can be relatively mild, some individuals fail to recover functional independence. This study aims to identify factors associated with failure to reach complete functional independence after AIS grade D tSCI. An observational prospective cohort study was conducted at a level 1 trauma center specialized in SCI care. A prospective cohort of 121 individuals with an AIS-D tSCI was considered. The baseline characteristics, length of acute stay, need for inpatient rehabilitation, and 12-month functional status were assessed. Univariate and classification and regression tree (CART) analyses were performed to identify factors associated with reaching complete versus incomplete functional independence (defined as perfect total SCIM III score at 12-month follow-up). There were 69.3%, 83.3%, and 61.4% individuals reaching complete independence in self-care, respiration/sphincter management, and mobility, respectively. A total of 64 individuals (52%) reached complete functional independence in all three domains. In the CART analysis, we found that patients are more likely to achieve complete functional independence when they have a baseline motor score ≥83 (65% individuals) and if they present fewer medical comorbidities (70% individuals if Charlson Comorbidity Index [CCI] ≤4). About half of individuals with AIS grade D tSCI can expect complete long-term functional independence. It is important to recognize early during acute care individuals with baseline motor score <83 or a high burden of comorbidities (CCI ≥5) to optimize their rehabilitation plan. [ABSTRACT FROM AUTHOR]

• Electroacupuncture improves motor, urinary, and bowel impairments in patients with acute transverse myelitis. • Electroacupuncture for acute transverse myelitis is cost-effective, simple, and has no associated adverse effects. • Acupuncture in the lesioned segment (near the spinal cord) is highly effective. Electroacupuncture (EA) has a positive effect on neurological repair and functional recovery following spinal cord disease. However, evidence of its effectiveness in acute transverse myelitis (ATM) cases is limited. A 48-year-old woman experienced headache and fever for 5 days, followed by a sudden onset of back pain, lower limb paralysis, and urinary and bowel dysfunction. The patient received intravenous medications. However, she did not experience improvement in clinical symptoms. She subsequently underwent acupuncture treatment. She regained walking ability and experienced improved bladder function and bowel control after 36 sessions of EA treatment. CARE guidelines informed the case study report. The MRC and ICIQ-UI-SF scores were used to verify changes in lower-extremity muscle strength and urination after EA treatment. Qualitative information was collected using feedback tables. Pharmacological treatment for ATM lacks clear advantages because of its complex pathophysiological mechanisms. Hence, EA could be recommended as a promising treatment modality for ATM. [ABSTRACT FROM AUTHOR]