Blast injuries are common among the military service members and veterans.One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss.Treating hearing loss using minocycline ...Blast injuries are common among the military service members and veterans.One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss.Treating hearing loss using minocycline is restricted by optimal drug concentration,route of administration,and its half-life.Therefore,therapeutic approach using novel therapeutic delivery method is in great need.Among the different delivery methods,nanotechnology-based drug delivery is desirable,which can achieve longer systemic circulation,pass through some biological barriers and specifically targets desired sites.The current study aimed to examine therapeutic effect of minocycline and its nanoparticle formulation in moderate blast induced hearing loss rat model through central auditory system.The I.v.administered nanoparticle at reduced dose and frequency than regularly administered toxic dose.After moderate blast exposure,rats had hearing impairment as determined by ABR at 7-and 30-days post exposure.In chronic condition,free minocycline also showed the significant reduction in ABR threshold.In central auditory system,it is found in this study that minocycline nanoparticles ameliorate excitation in inferior colliculus;and astrocytes and microglia activation after the blast exposure is reduced by minocycline nanoparticles administration.The study demonstrated that in moderate blast induced hearing loss,minocycline and its nanoparticle formulation exhibited the optimal therapeutic effect on the recovery of the ABR impairment and a protective effect through central auditory system.In conclusion,targeted and non-targeted nanoparticle formulation have therapeutic effect on blast induced hearing loss.展开更多
Zebrafish have the potential to regrow injured organs and tissues,but their use as a model for hearing regeneration following blast injury has never been reported.In this study,zebrafish were exposed to a blast wave p...Zebrafish have the potential to regrow injured organs and tissues,but their use as a model for hearing regeneration following blast injury has never been reported.In this study,zebrafish were exposed to a blast wave produced by an underwater blast wave generator.The first peak sound pressures produced by this generator were up to 224dB and 160kPa,measured at 25cm away from the machine.Zebrafish hearing sensitivity was examined by analyzing auditory evoked potentials from 1 to 35 days post blast wave exposure.Cell death and cell proliferation in inner ear organs,including the saccule,lagena,and utricle,were investigated using a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay,and cell proliferation assay using 5-ethynyl-20-deoxyuridine,respectively.Significant differences in auditory evoked potential thresholds were observed between exposed and control groups,demonstrating both blast wave-induced hearing loss and recovery of hearing sensitivity.An apoptosis assay revealed significantly increased numbers of terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labelingpositive cells in the inner ear sensory epithelia of exposed groups compared with the control group.However,numbers of 5-ethynyl-20-deoxyuridine-positive cells in the inner ear of exposed groups recovered to a normal level within 10 post blast wave exposure.Furthermore,blast wave exposure caused brain injury with increased cell apoptosis and decreased neurogenesis.Compared with drug or noise-induced zebrafish models,our blast wave-induced model elicited more serious hearing loss phenotypes,which required more time to return to a normal level.Overall,this zebrafish model can provide a reliable animal model for both hearing loss and regeneration research.The study was approved by the Shanghai 6th Hospital Animal Care and Use Committee,China(approval No.2017-0196)on February 28,2017.展开更多
Background: Acute acoustic trauma (AAT) is an acute hearing impairment caused by intense noiseimpact. The current management strategy for AAT with substantial hearing loss in the Dutch militaryis the combination thera...Background: Acute acoustic trauma (AAT) is an acute hearing impairment caused by intense noiseimpact. The current management strategy for AAT with substantial hearing loss in the Dutch militaryis the combination therapy with corticosteroids and hyperbaric oxygen therapy (HBOT). In a previousstudy, early initiation of the combination therapy was associated with better outcomes. Therefore, weperformed a new analysis to assess the difference in hearing outcome between patients in whomcombination therapy was started within two days, versus after more than two days.Methods: A retrospective analysis was performed on military patients diagnosed with AAT with substantial hearing loss who presented between February 2018 and March 2020. Absolute and relativehearing improvement between first and last audiograms were calculated for all affected frequencies(defined as loss of 20 dB on initial audiogram). We also determined the amount of patients whorecovered to the level of Dutch military requirement, and performed speech discrimination tests.Results: In this analysis, 30 male patients (49 ears) with AAT were included. The median age was 24.5years (IQR 23e29). The median time to initiation of therapy with corticosteroids and HBOT were one andtwo days, respectively. HBOT was started within two days in 31 ears, and after more than two days in 18ears. The mean absolute and relative hearing gains were 18.8 dB (SD 14.6) and 46.8% (SD 31.3) on allaffected frequencies. The 100% discrimination/speech perception level improved from 64.0 dB to 51.7 dB(gain 12.3 dB ± 14.1). There was significantly more improvement in absolute and relative hearingimprovement when HBOT was started in 2 days, compared to >2 days.Conclusion: Our analysis shows results in favor of early initiation ( 2 days) of the combination treatmentof HBOT and corticosteroids in patients with AAT.展开更多
The objectives of this review were to 1)summarize the available evidence on the impact of hearing loss on quality of life(QOL)among U.S.active-duty service members,2)describe the QOL instruments that have been used to...The objectives of this review were to 1)summarize the available evidence on the impact of hearing loss on quality of life(QOL)among U.S.active-duty service members,2)describe the QOL instruments that have been used to quantify the impact of hearing loss on quality of life,3)examine national population-level secondary databases and report on their utility for studying the impact of hearing loss on QOL among active-duty service members,and 4)provide recommendations for future studies that seek to quantify the impact of hearing loss in this population.There is a lack of literature that addresses the intersection of hearing impairment,the military population,and quality of life measures.For audiological research,U.S.military personnel offer a unique research population,as they are exposed to noise levels and blast environments that are highly unusual in civilian work settings and can serve as a model population for studying the impact on QOL associated with these conditions.This review recommends conducting a study on the active-duty service member population using a measurement instrument suitable for determining decreases in QOL specifically due to hearing loss.展开更多
We consider the hearing loss injury among subjects in a crowd with a wide spectrum of individual intrinsic injury probabilities due to biovariability. For multiple acoustic impulses, the observed injury risk of a crow...We consider the hearing loss injury among subjects in a crowd with a wide spectrum of individual intrinsic injury probabilities due to biovariability. For multiple acoustic impulses, the observed injury risk of a crowd vs the effective combined dose follows the logistic dose-response relation. The injury risk of a crowd is the average fraction of injured. The injury risk was measured in experiments as follows: each subject is individually exposed to a sequence of acoustic impulses of a given intensity and the injury is recorded;results of multiple individual subjects were assembled into data sets to mimic the response of a crowd. The effective combined dose was adjusted by varying the number of impulses in the sequence. The most prominent feature observed in experiments is that the injury risk of the crowd caused by multiple impulses is significantly less than the value predicted based on assumption that all impulses act independently in causing injury and all subjects in the crowd are statistically identical. Previously, in the case where all subjects are statistically identical (i.e., no biovariability), we interpreted the observed injury risk caused by multiple impulses in terms of the immunity effects of preceding impulses on subsequent impulses. In this study, we focus on the case where all sound exposure events act independently in causing injury regardless of whether one is preceded by another (i.e., no immunity effect). Instead, we explore the possibility of interpreting the observed logistic dose-response relation in the framework of biovariability of the crowd. Here biovariability means that subjects in the crowd have their own individual injury probabilities. That is, some subjects are biologically less or more susceptible to hearing loss injury than others. We derive analytically the distribution of individual injury probability that produces the observed logistic dose-response relation. For several parameter values, we prove that the derived distribution is mathematically a proper density function. W展开更多
A flash bang is a non-lethal explosive device that delivers intensely loud bangs and bright lights to suppress potentially dangerous targets. It is usually used in crowd control, hostage rescue and numerous other miss...A flash bang is a non-lethal explosive device that delivers intensely loud bangs and bright lights to suppress potentially dangerous targets. It is usually used in crowd control, hostage rescue and numerous other missions. We construct a model for assessing quantitatively the risk of hearing loss injury caused by multiple flash bangs. The model provides a computational framework for incorporating the effects of the key factors defining the situation and for testing various sub-models for these factors. The proposed model includes 1) uncertainty in the burst point of flash bang mortar, 2) randomness in the dispersion of multiple submunitions after the flash bang mortar burst, 3) decay of acoustic impulse from a single submunition to an individual subject along the ground surface, 4) the effective combined sound exposure level on an individual subject caused by multiple submunitions at various distances from the subject, and 5) randomness in the spatial distribution of subjects in the crowd. With the mathematical model formulated, we seek to characterize the overall effect of flash bang mortar in the form of an effective injury area. We carry out simulations to study the effects of uncertainty and randomness on the risk of hearing loss injury of the crowd. The proposed framework serves as a starting point for a comprehensive assessment of hearing loss injury risk, taking into consideration all realistic and relevant features of flash bang mortar. It also provides a platform for testing and updating component models.展开更多
基金funding provided by Faculty seed grant (FSG) from NJIT, Newark, USA " (NC and Venkatesan Perumal).
文摘Blast injuries are common among the military service members and veterans.One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss.Treating hearing loss using minocycline is restricted by optimal drug concentration,route of administration,and its half-life.Therefore,therapeutic approach using novel therapeutic delivery method is in great need.Among the different delivery methods,nanotechnology-based drug delivery is desirable,which can achieve longer systemic circulation,pass through some biological barriers and specifically targets desired sites.The current study aimed to examine therapeutic effect of minocycline and its nanoparticle formulation in moderate blast induced hearing loss rat model through central auditory system.The I.v.administered nanoparticle at reduced dose and frequency than regularly administered toxic dose.After moderate blast exposure,rats had hearing impairment as determined by ABR at 7-and 30-days post exposure.In chronic condition,free minocycline also showed the significant reduction in ABR threshold.In central auditory system,it is found in this study that minocycline nanoparticles ameliorate excitation in inferior colliculus;and astrocytes and microglia activation after the blast exposure is reduced by minocycline nanoparticles administration.The study demonstrated that in moderate blast induced hearing loss,minocycline and its nanoparticle formulation exhibited the optimal therapeutic effect on the recovery of the ABR impairment and a protective effect through central auditory system.In conclusion,targeted and non-targeted nanoparticle formulation have therapeutic effect on blast induced hearing loss.
基金the State Key Program of National Natural Science Foundation of China(No.81530029 to SY)International Cooperation and Exchange of the National Natural Science Foundation of China(No.8171001156 to SY)+1 种基金National Natural Science Foundation of China(No.81771007 to JW)the Major Program of Shanghai Committee of Science and Technology of China(No.14DJ1400202 to SY).
文摘Zebrafish have the potential to regrow injured organs and tissues,but their use as a model for hearing regeneration following blast injury has never been reported.In this study,zebrafish were exposed to a blast wave produced by an underwater blast wave generator.The first peak sound pressures produced by this generator were up to 224dB and 160kPa,measured at 25cm away from the machine.Zebrafish hearing sensitivity was examined by analyzing auditory evoked potentials from 1 to 35 days post blast wave exposure.Cell death and cell proliferation in inner ear organs,including the saccule,lagena,and utricle,were investigated using a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay,and cell proliferation assay using 5-ethynyl-20-deoxyuridine,respectively.Significant differences in auditory evoked potential thresholds were observed between exposed and control groups,demonstrating both blast wave-induced hearing loss and recovery of hearing sensitivity.An apoptosis assay revealed significantly increased numbers of terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labelingpositive cells in the inner ear sensory epithelia of exposed groups compared with the control group.However,numbers of 5-ethynyl-20-deoxyuridine-positive cells in the inner ear of exposed groups recovered to a normal level within 10 post blast wave exposure.Furthermore,blast wave exposure caused brain injury with increased cell apoptosis and decreased neurogenesis.Compared with drug or noise-induced zebrafish models,our blast wave-induced model elicited more serious hearing loss phenotypes,which required more time to return to a normal level.Overall,this zebrafish model can provide a reliable animal model for both hearing loss and regeneration research.The study was approved by the Shanghai 6th Hospital Animal Care and Use Committee,China(approval No.2017-0196)on February 28,2017.
文摘Background: Acute acoustic trauma (AAT) is an acute hearing impairment caused by intense noiseimpact. The current management strategy for AAT with substantial hearing loss in the Dutch militaryis the combination therapy with corticosteroids and hyperbaric oxygen therapy (HBOT). In a previousstudy, early initiation of the combination therapy was associated with better outcomes. Therefore, weperformed a new analysis to assess the difference in hearing outcome between patients in whomcombination therapy was started within two days, versus after more than two days.Methods: A retrospective analysis was performed on military patients diagnosed with AAT with substantial hearing loss who presented between February 2018 and March 2020. Absolute and relativehearing improvement between first and last audiograms were calculated for all affected frequencies(defined as loss of 20 dB on initial audiogram). We also determined the amount of patients whorecovered to the level of Dutch military requirement, and performed speech discrimination tests.Results: In this analysis, 30 male patients (49 ears) with AAT were included. The median age was 24.5years (IQR 23e29). The median time to initiation of therapy with corticosteroids and HBOT were one andtwo days, respectively. HBOT was started within two days in 31 ears, and after more than two days in 18ears. The mean absolute and relative hearing gains were 18.8 dB (SD 14.6) and 46.8% (SD 31.3) on allaffected frequencies. The 100% discrimination/speech perception level improved from 64.0 dB to 51.7 dB(gain 12.3 dB ± 14.1). There was significantly more improvement in absolute and relative hearingimprovement when HBOT was started in 2 days, compared to >2 days.Conclusion: Our analysis shows results in favor of early initiation ( 2 days) of the combination treatmentof HBOT and corticosteroids in patients with AAT.
基金supported by the Air Force Research Laboratory under Contract No.FA8650-12-C-6358
文摘The objectives of this review were to 1)summarize the available evidence on the impact of hearing loss on quality of life(QOL)among U.S.active-duty service members,2)describe the QOL instruments that have been used to quantify the impact of hearing loss on quality of life,3)examine national population-level secondary databases and report on their utility for studying the impact of hearing loss on QOL among active-duty service members,and 4)provide recommendations for future studies that seek to quantify the impact of hearing loss in this population.There is a lack of literature that addresses the intersection of hearing impairment,the military population,and quality of life measures.For audiological research,U.S.military personnel offer a unique research population,as they are exposed to noise levels and blast environments that are highly unusual in civilian work settings and can serve as a model population for studying the impact on QOL associated with these conditions.This review recommends conducting a study on the active-duty service member population using a measurement instrument suitable for determining decreases in QOL specifically due to hearing loss.
文摘We consider the hearing loss injury among subjects in a crowd with a wide spectrum of individual intrinsic injury probabilities due to biovariability. For multiple acoustic impulses, the observed injury risk of a crowd vs the effective combined dose follows the logistic dose-response relation. The injury risk of a crowd is the average fraction of injured. The injury risk was measured in experiments as follows: each subject is individually exposed to a sequence of acoustic impulses of a given intensity and the injury is recorded;results of multiple individual subjects were assembled into data sets to mimic the response of a crowd. The effective combined dose was adjusted by varying the number of impulses in the sequence. The most prominent feature observed in experiments is that the injury risk of the crowd caused by multiple impulses is significantly less than the value predicted based on assumption that all impulses act independently in causing injury and all subjects in the crowd are statistically identical. Previously, in the case where all subjects are statistically identical (i.e., no biovariability), we interpreted the observed injury risk caused by multiple impulses in terms of the immunity effects of preceding impulses on subsequent impulses. In this study, we focus on the case where all sound exposure events act independently in causing injury regardless of whether one is preceded by another (i.e., no immunity effect). Instead, we explore the possibility of interpreting the observed logistic dose-response relation in the framework of biovariability of the crowd. Here biovariability means that subjects in the crowd have their own individual injury probabilities. That is, some subjects are biologically less or more susceptible to hearing loss injury than others. We derive analytically the distribution of individual injury probability that produces the observed logistic dose-response relation. For several parameter values, we prove that the derived distribution is mathematically a proper density function. W
文摘A flash bang is a non-lethal explosive device that delivers intensely loud bangs and bright lights to suppress potentially dangerous targets. It is usually used in crowd control, hostage rescue and numerous other missions. We construct a model for assessing quantitatively the risk of hearing loss injury caused by multiple flash bangs. The model provides a computational framework for incorporating the effects of the key factors defining the situation and for testing various sub-models for these factors. The proposed model includes 1) uncertainty in the burst point of flash bang mortar, 2) randomness in the dispersion of multiple submunitions after the flash bang mortar burst, 3) decay of acoustic impulse from a single submunition to an individual subject along the ground surface, 4) the effective combined sound exposure level on an individual subject caused by multiple submunitions at various distances from the subject, and 5) randomness in the spatial distribution of subjects in the crowd. With the mathematical model formulated, we seek to characterize the overall effect of flash bang mortar in the form of an effective injury area. We carry out simulations to study the effects of uncertainty and randomness on the risk of hearing loss injury of the crowd. The proposed framework serves as a starting point for a comprehensive assessment of hearing loss injury risk, taking into consideration all realistic and relevant features of flash bang mortar. It also provides a platform for testing and updating component models.
