From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

Bicycle-related traumatic injuries: a retrospective study during COVID-19 pandemic

BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention.METHODS:This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June 2021.Medical records were reviewed and consolidated.Descriptive analyses were used to summarize patient characteristics,and differences in characteristics subgrouped by triage acuity and discharge status were analyzed.RESULTS:The study included 272 patients with a mean age of 43 years and a male predominance(71.7%).Most presented without referrals(88.2%)and were not conveyed by ambulances(70.6%).Based on acuity category,there were 24(8.8%)Priority 1(P1)patients with 7 trauma activations,174(64.0%)and 74(27.2%)P2 and P3 patients respectively.The most common injuries were fractures(34.2%),followed by superficial abrasion/contusion(29.4%)and laceration/wound(19.1%).Thirteen(4.8%)patients experienced head injury and 85 patients(31.3%)were documented to be wearing a helmet.The majority occurred on the roads as traffic accidents(32.7%).Forty-two patients(15.4%)were admitted with a mean length of stay of 4.1 d and 17(6.3%)undergone surgical procedures.Out of 214(78.7%)discharged patients,no re-attendances or mortality were observed.In the subgroup analysis,higher acuity patients were generally older,with higher proportions of head injuries leading to admission.CONCLUSION:Our study highlights significant morbidities in bicycle-related injuries.There is also a high proportion of fractures in the young healthy male population.Injury prevention is paramount and we propose emphasizing helmet use and road user safety.

Incorporating empirical knowledge into data-driven variable selection for quantitative analysis of coal ash content by laser-induced breakdown spectroscopy

Laser-induced breakdown spectroscopy(LIBS)has become a widely used atomic spectroscopic technique for rapid coal analysis.However,the vast amount of spectral information in LIBS contains signal uncertainty,which can affect its quantification performance.In this work,we propose a hybrid variable selection method to improve the performance of LIBS quantification.Important variables are first identified using Pearson's correlation coefficient,mutual information,least absolute shrinkage and selection operator(LASSO)and random forest,and then filtered and combined with empirical variables related to fingerprint elements of coal ash content.Subsequently,these variables are fed into a partial least squares regression(PLSR).Additionally,in some models,certain variables unrelated to ash content are removed manually to study the impact of variable deselection on model performance.The proposed hybrid strategy was tested on three LIBS datasets for quantitative analysis of coal ash content and compared with the corresponding data-driven baseline method.It is significantly better than the variable selection only method based on empirical knowledge and in most cases outperforms the baseline method.The results showed that on all three datasets the hybrid strategy for variable selection combining empirical knowledge and data-driven algorithms achieved the lowest root mean square error of prediction(RMSEP)values of 1.605,3.478 and 1.647,respectively,which were significantly lower than those obtained from multiple linear regression using only 12 empirical variables,which are 1.959,3.718 and 2.181,respectively.The LASSO-PLSR model with empirical support and 20 selected variables exhibited a significantly improved performance after variable deselection,with RMSEP values dropping from 1.635,3.962 and 1.647 to 1.483,3.086 and 1.567,respectively.Such results demonstrate that using empirical knowledge as a support for datadriven variable selection can be a viable approach to improve the accuracy and reliability of LIBS quantification.

Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries

Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage.In this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro ptosis.We also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury.In conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

Ultrafast dynamics of femtosecond laser-induced high spatial frequency periodic structures on silicon surfaces

Femtosecond laser-induced periodic surface structures(LIPSS)have been extensively studied over the past few decades.In particular,the period and groove width of high-spatial-frequency LIPSS(HSFL)is much smaller than the diffraction limit,making it a useful method for efficient nanomanufacturing.However,compared with the low-spatial-frequency LIPSS(LSFL),the structure size of the HSFL is smaller,and it is more easily submerged.Therefore,the formation mechanism of HSFL is complex and has always been a research hotspot in this field.In this study,regular LSFL with a period of 760 nm was fabricated in advance on a silicon surface with two-beam interference using an 800 nm,50 fs femtosecond laser.The ultrafast dynamics of HSFL formation on the silicon surface of prefabricated LSFL under single femtosecond laser pulse irradiation were observed and analyzed for the first time using collinear pump-probe imaging method.In general,the evolution of the surface structure undergoes five sequential stages:the LSFL begins to split,becomes uniform HSFL,degenerates into an irregular LSFL,undergoes secondary splitting into a weakly uniform HSFL,and evolves into an irregular LSFL or is submerged.The results indicate that the local enhancement of the submerged nanocavity,or the nanoplasma,in the prefabricated LSFL ridge led to the splitting of the LSFL,and the thermodynamic effect drove the homogenization of the splitting LSFL,which evolved into HSFL.

Ambulance Records as an Information Source to Document and Prevent Fall Injuries in Sweden

In Sweden, there has been only limited documentation for injuries requiring ambulance responses. The main objective of this study is, through the use of historic data, to assess the suitability of ambulance records to describe circumstances with fall injuries. Methods: The injury events data around patients were sourced from the ambulance data register. Descriptive statistics were used to describe injured patients based on age group, type of injury, place of injury, injury mechanism and consequence of an injury event. Two-group comparison was performed with Pearson’s chi-squared. Predictors of transport to hospital were identified using logistic regression analyses. Result: Ambulance provides unique data on all injury events, with direct implications for translational research, public policy and clinical practice (safety promotion). In 2002 ambulance attended 3964 injured people which represents 14% of ambulance attended workload in Värmland county, Sweden. The most common trauma location was the traffic area followed by residential area and nursing home. These three injury sites account for 2320 cases (61.6%). The most common cause of injury was falls (63.9%) followed by contact with another person (26.5%). Contact with another person is the most common site of injury in the traffic area (79.5%), and men aged 25-66 years are overrepresented. Conclusion: Logistic regression found that, age-group and place code were significant predictor for being attended by ambulance. Traffic, home and nursing homes were over-represented injury environments (61.6%) that require special attention. Most injury cases occur in the home and nursing homes among people over 67 years of age. Surprisingly, most of the injury events in the traffic environment are about hitting another person. Paramedics can provide rich and valuable data on injury events. Registration of such data is entirely possible and desirable, and can be used in preventive work.

Femtosecond laser-induced nanoparticle implantation into flexible substrate for sensitive and reusable microfluidics SERS detection

Surface-enhanced Raman spectroscopy(SERS)microfluidic system,which enables rapid detection of chemical and biological analytes,offers an effective platform to monitor various food contaminants and disease diagnoses.The efficacy of SERS microfluidic systems is greatly dependent on the sensitivity and reusability of SERS detection substrates to ensure repeated use for prolonged periods.This study proposed a novel process of femtosecond laser nanoparticle array(NPA)implantation to achieve homogeneous forward transfer of gold NPA on a flexible polymer film and accurately integrated it within microfluidic chips for SERS detection.The implanted Au-NPA strips show a remarkable electromagnetic field enhancement with the factor of 9×108 during SERS detection of malachite green(MG)solution,achieving a detection limit lower than 10 ppt,far better than most laser-prepared SERS substrates.Furthermore,Au-NPA strips show excellent reusability after several physical and chemical cleaning,because of the robust embedment of laser-implanted NPA in flexible substrates.To demonstrate the performance of Au-NPA,a SERS microfluidic system is built to monitor the online oxidation reaction between MG/NaClO reactants,which helps infer the reaction path.The proposed method of nanoparticle implantation is more effective than the direct laser structuring technique.It provides better performance for SERS detection,robustness of detection,and substrate flexibility and has a wider range of applications for microfluidic systems without any negative impact.

Research on a deconvolution algorithm for laser-induced fluorescence diagnosis based on the maximum entropy principle

Laser-induced fluorescence(LIF)spectroscopy is employed for plasma diagnosis,necessitating the utilization of deconvolution algorithms to isolate the Doppler effect from the raw spectral signal.However,direct deconvolution becomes invalid in the presence of noise as it leads to infinite amplification of high-frequency noise components.To address this issue,we propose a deconvolution algorithm based on the maximum entropy principle.We validate the effectiveness of the proposed algorithm by utilizing simulated LIF spectra at various noise levels(signal-to-noise ratio,SNR=20–80 d B)and measured LIF spectra with Xe as the working fluid.In the typical measured spectrum(SNR=26.23 d B)experiment,compared with the Gaussian filter and the Richardson–Lucy(R-L)algorithm,the proposed algorithm demonstrates an increase in SNR of 1.39 d B and 4.66 d B,respectively,along with a reduction in the root-meansquare error(RMSE)of 35%and 64%,respectively.Additionally,there is a decrease in the spectral angle(SA)of 0.05 and 0.11,respectively.In the high-quality spectrum(SNR=43.96 d B)experiment,the results show that the running time of the proposed algorithm is reduced by about98%compared with the R-L iterative algorithm.Moreover,the maximum entropy algorithm avoids parameter optimization settings and is more suitable for automatic implementation.In conclusion,the proposed algorithm can accurately resolve Doppler spectrum details while effectively suppressing noise,thus highlighting its advantage in LIF spectral deconvolution applications.

Estimating the yield stress of soft materials via laser-induced breakdown spectroscopy

Taking three typical soft samples prepared respectively by loose packings of 77-,95-,and 109-μm copper grains as examples,we perform an experiment to investigate the energy-dependent laser-induced breakdown spectroscopy(LIBS)of soft materials.We discovered a reversal phenomenon in the trend of energy dependence of plasma emission intensity:increasing initially and then decreasing separated by a well-defined critical energy.The trend reversal is attributed to the laser-induced recoil pressure at the critical energy just matching the sample's yield strength.As a result,a one-to-one correspondence can be well established between the samples'yield stress and the critical energy that is easily obtainable from LIBS measurements.This allows us to propose an innovative method for estimating the yield stress of soft materials via LIBS with attractive advantages including in-situ remote detection,real-time data collection,and minimal destructive to sample.

Theoretical simulation study of laser-induced plasma bombardment on bacteria

With the rapid advancement of laser decontamination technology and growing awareness of microbial hazards,it becomes crucial to employ theoretical model to simulate and evaluate decontamination processes by laser-induced plasma.This study employs a two-dimensional axisymmetric fluid dynamics model to simulate the power density of plasma bombardment on bacteria and access its decontamination effects.The model considers the transport processes of vapor plasma and background gas molecules.Based on the destructive impact of high-speed moving particles in the plasma on bacteria,we investigate the bombardment power density under various conditions,including different laser spot sizes,wavelengths,plate's tilt angles,and plate-target spacing.The results reveal that the bombardment power density increases with a decrease in laser spot size and wavelength.For instance,when the plate is parallel to the target surface with a 1 mm spacing,the bombardment power density triples as the laser spot size decreases from 0.8 mm to 0.5 mm and quadruples as the wavelength decreases from 1064 nm to 266 nm.Notably,when the plate is parallel to the target with a relatively close spacing of 0.5 mm,the bombardment power density at 0°inclination increases sevenfold compared to 45°.This simulation study is essential for optimizing optical parameters and designing component layouts in decontamination devices using laser-induced plasma.The reduction of laser spot size,wavelength,plate-target spacing and aligning the plate parallel to the target,collectively contribute to achieving precise and effective decontamination.

Effect of matrix thermal properties on laser-induced plasma

The matrix thermal properties have an important impact on laser-induced plasma,as the thermal effect dominates the interaction between ns-pulsed laser and matter,especially in metals.We used a series of pure metals and aluminum alloys to measure plasma temperature and electron density through laser-induced breakdown spectroscopy,in order to investigate the effect of matrix thermal properties on laser-induced plasma.In pure metals,a significant negative linear correlation was observed between the matrix thermal storage coefficient and plasma temperature,while a weak correlation was observed with electron density.The results indicate that metals with low thermal conductivity or specific heat capacity require less laser energy for thermal diffusion or melting and evaporation,resulting in higher ablation rates and higher plasma temperatures.However,considering ionization energy,thermal effects may be a secondary factor affecting electron density.The experiment of aluminum alloy further confirms the influence of thermal conductivity on plasma temperature and its mechanism explanation.

Laser-induced breakdown spectroscopy as a method for millimeter-scale inspection of surface flatness

A non-contact method for millimeter-scale inspection of material surface flatness via Laser-Induced Breakdown Spectroscopy(LIBS)is investigated experimentally.The experiment is performed using a planished surface of an alloy steel sample to simulate its various flatness,ranging from 0 to 4.4 mm,by adjusting the laser focal plane to the surface distance with a step length of 0.2 mm.It is found that LIBS measurements are successful in inspecting the flatness differences among these simulated cases,implying that the method investigated here is feasible.It is also found that,for achieving the inspection of surface flatness within such a wide range,when univariate analysis is applied,a piecewise calibration model must be constructed.This is due to the complex dependence of plasma formation conditions on the surface flatness,which inevitably complicates the inspection procedure.To solve the problem,a multivariate analysis with the help of Back-Propagation Neural Network(BPNN)algorithms is applied to further construct the calibration model.By detailed analysis of the model performance,we demonstrate that a unified calibration model can be well established based on BPNN algorithms for unambiguous millimeter-scale range inspection of surface flatness with a resolution of about 0.2 mm.

Use of induced pluripotent stem cell-derived brain cells,organoids,assembloids,and blood-brain barrier models in understanding alcohol and anesthetic-induced brain injuries:an emerging perspective

Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.

Estimating the grain size of microgranular material using laser-induced breakdown spectroscopy combined with machine learning algorithms

Recent work has validated a new method for estimating the grain size of microgranular materials in the range of tens to hundreds of micrometers using laser-induced breakdown spectroscopy(LIBS).In this situation,a piecewise univariate model must be constructed to estimate grain size due to the complex dependence of the plasma formation environment on grain size.In the present work,we tentatively construct a unified calibration model suitable for LIBS-based estimation of those grain sizes.Specifically,two unified multivariate calibration models are constructed based on back-propagation neural network(BPNN)algorithms using feature selection strategies with and without considering prior information.By detailed analysis of the performances of the two multivariate models,it was found that a unified calibration model can be successfully constructed based on BPNN algorithms for estimating the grain size in the range of tens to hundreds of micrometers.It was also found that the model constructed with a priorguided feature selection strategy had better prediction performance.This study has practical significance in developing the technology for material analysis using LIBS,especially when the LIBS signal exhibits a complex dependence on the material parameter to be estimated.

The Role of Age as a Risk Factor for Pickleball-Related Injuries

Pickleball is a popular sport that includes players from many different demographics. The popularity has resulted in not only increases in participation but also in activity related injuries. The purpose of this study was to identify risk factors along with potential mechanisms for injuries related to pickleball and identify effective countermeasures. Methods included the identification of pickleball related injuries from a US National Emergency Room database (NEISS). A narrative section of the database was used to identify and categorize potential mechanisms of injury. Results indicated that the types and mechanisms of injury relate to three specific age groups: younger, middle age, and older players. Injuries to younger players under the age of 26 are likely the result of misuse of sport equipment. Middle aged players from 26 to 50 sustained injuries more related activity overuse. However, there were more concerns with players over 50 years of age with a great percentage resulting in cardia arrest or symptoms leading to more severe cardiovascular conditions. While pickleball activity should be encouraged as it is a beneficial form of physical activity, there should be specific age-group interventions to reduce injury. It should be highly recommended that doctors approve the activity for individual at risk for heart conditions and supervision for adults in that age group.

Epidemiology of work-related hand and wrist injuries in a referral center: A descriptive study

BACKGROUND Occupational hand and wrist injuries(OHWIs)account for 25%of work-related accidents in low-and middle-income countries.In Colombia,more than 500000 occupational accidents occurred in 2021,and although the rate declined to less than 5%in 2020 and 2021,at least one in four accidents involved a hand or wrist injury.AIM To describe the OHWIs in workers seen at the emergency room at a second-level hospital in Colombia.METHODS An observational study was performed using data from workers who experienced OHWIs and attended a second-level hospital,between June,2020 and May,2021.The overall frequency of OHWIs,as well as their distribution by sociodemo-graphic,clinical,and occupational variables,are described.Furthermore,association patterns between sex,anatomical area(fingers,hand,wrist),and type of job were analyzed by correspondence analysis(CA).RESULTS There were 2.101 workers treated for occupational accidents,423(20.3%)were cases of OHWIs,which mainly affected men(93.9%)with a median age of 31 years and who worked mainly in mining(75.9%).OHWIs were more common in the right upper extremity(55.3%)and comprised different types of injuries,such as contusion(42.1%),laceration(27.9%),fracture(18.7%),and crush injury(15.6%).They primarily affected the phalanges(95.2%),especially those of the first finger(25.7%).The CAs showed associations between the injured anatomical area and the worker’s job that differed in men and women(explained variance>90%).CONCLUSION One out of five workers who suffered occupational accidents in Cundinamarca,Columbia had an OHWI,affecting mainly males employed in mining.This occupational profile is likely to lead to prolonged rehabilitation,and permanent functional limitations.Our results might be useful for adjusting preventive measures in cluster risk groups.

The sex-specific associations between suicidality and post-traumatic stress disorder in patients with physical injuries

To theeditor:Post-traumatic stress disorder(PTSD)arises after traumatic experiences,presenting with symptoms like reliving trauma,avoidance of reminders,mood changes and increased arousal,significantly affecting life quality and daily functioning.1 A severe complication of PTSD is suicidality,notably contributing to the higher mortality among PTSD sufferers.

Characteristics of laser-induced breakdown spectroscopy of liquid slag

Rapid online analysis of liquid slag is essential for optimizing the quality and energy efficiency of steel production. To investigate the key factors that affect the online measurement of refined slag using laser-induced breakdown spectroscopy(LIBS), this study examined the effects of slag composition and temperature on the intensity and stability of the LIBS spectra. The experimental temperature was controlled at three levels: 1350℃, 1400℃, and 1450℃. The results showed that slag composition and temperature significantly affected the intensity and stability of the LIBS spectra. Increasing the Fe content and temperature in the slag reduces its viscosity, resulting in an enhanced intensity and stability of the LIBS spectra. Additionally, 42 refined slag samples were quantitatively analyzed for Fe, Si, Ca, Mg, Al, and Mn at 1350℃, 1400℃, and 1450℃.The normalized full spectrum combined with partial least squares(PLS) quantification modeling was used, using the Ca Ⅱ 317.91 nm spectral line as an internal standard. The results show that using the internal standard normalization method can significantly reduce the influence of spectral fluctuations. Meanwhile, a temperature of 1450℃ has been found to yield superior results compared to both 1350℃ and 1400℃, and it is advantageous to conduct a quantitative analysis of the slag when it is in a “water-like” state with low viscosity.

Risk factors for running-related injuries:An umbrella systematic review

Purpose:This umbrella systematic review(SR) of SRs and meta-analysis seeks to comprehensively synthesize existing literature to identify and consolidate the diverse range of risk factors contributing to running-related injuries(RRIs).Methods:Systematic searches were conducted on June 28,2023,across Web of Science,SPORTDiscus,Scopus,PubMed,and Cochrane Library.We included SRs,whether accompanied by meta-analyses or not,that focused on investigating risk factors for RRIs within observational studies.The methodological quality of the SRs was evaluated using the Assessing the Methodological Quality of Systematic Reviews Ⅱ.To assess the extent of overlap across reviews,the corrected covered area metric was calculated.Results:From 1509 records retrieved,13 SRs were included.The degree of overlap between SRs was low(4%),and quality varied from critically low(n=8) to low(n=5).Two hundred seven outcomes assessed in 148 primary studies were identified as being associated with the occurrence of RRIs.The effect sizes of the associations for which risk measures were reported(n=131) were classified as large(n=30,23%),medium(n=38,29%),small(n=48,37%) or no effect(n=15,11%).Running/training characteristics,health and lifestyle factors,along with morphological and biomechanical aspects,exhibit large effect sizes in increasing the risk for RRIs.Conclusion:Drawing from the outcomes of the low-quality SRs and associations with large effect sizes,our findings indicate that running/training characteristics and health and lifestyle factors,as well as morphological and biomechanical aspects,are all implicated in elevating the risk of RRIs,emphasizing the multifactorial basis of injury incidence in running.Given the low quality and heterogeneity of SR,individual findings warrant cautious interpretation.