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Modern changes in warfare have shown an increased incidence of lumbar spine injuries caused by underbody blast events. The susceptibility of the lumbar spine during these scenarios could be exacerbated by coupled moments that act with the rapid compressive force depending on the occupant’s seated posture. In this study, a combined loading lumbar spine vertebral body fracture injury criteria (Lic) across a range of postures was established from 75 tests performed on instrumented cadaveric lumbar spine specimens. The spines were predominantly exposed to axial compressive forces from an upward vertical thrust with 64 of the tests resulting in at least one vertebral body fracture and 11 in no vertebral body injury. The proposed Lic utilizes a recommended metric (κ), based on prismatic beam failure theory, resulting from the combination of the T12-L1 resultant sagittal force and the decorrelated bending moment with optimized critical values of Fr,crit = 5824 N and My,crit = 1155 Nm. The 50% risk of lumbar spine injury corresponded to a combined metric of 1, with the risk decreasing with the combined metric value. At 50% injury risk the Normalized Confidence Interval Size improved from 0.24 of a force-based injury reference curve to 0.17 for the combined loading metric.

OBJECTIVE In recent years, based on injuries predicted using machine learning, there have been efforts to reduce imaging performed on trauma patients. While useful, such efforts do not incorporate results from studies investigating the pathophysiology of traumatic events. The objective of this study was to identify potentially symptomatic vertebral foramen narrowing in the presence of minor to moderate (AIS ≤ 2 levels of severity) thoracolumbar fractures sustained in motor vehicle crashes (MVCs). METHODS Hospital records and images of patients admitted to a Level One trauma center between the years 2014 and 2018 with the diagnosis of thoracolumbar fracture were reviewed. Spinal injuries were scored using the AIS v2015. In addition, the geometry of the neural foramina, particularly the height of the foramina and intervertebral disk at the posterior region, were measured using reconstructed sagittal computed tomography (CT) images. The criteria for foraminal narrowing were associated with

OBJECTIVE The objective is to report sex-related variation in 3-point belt-related abdominal injuries in Crash Injury Research Engineering Network (CIREN) cases. METHODS A query of CIREN cases was made for those with the highest ranked Collision Deformation Classification (CDC) to the front plane, a principal direction of force (PDOF) ±20° from 0°, and Abbreviated Injury Scale (AIS) 2+ abdomen injuries attributed to the seat belt. Patterns of injury were categorized as above the crest of the ilium, injuries below the crest of the ilium, and injuries above and below the ilium. This was done in the context of autonomous vehicle occupant kinematics testing results. Twelve 5th and 95th percentile 3-point belt-restrained postmortem human subjects were subjects; test speeds and recline angles varied. Abdomen injuries were anticipated; none were observed. RESULTS Thirty-five occupants with belt-related abdominal injuries were identified. Seventeen case occupants sustained an injury only within the pelvic contents: 5 women and 12 men. Nine of the 17 were at or above the 81st percentile for height, 13 were between the 62nd and 80th percentile for height, and 4 were less than the 50th percentile for height. CONCLUSIONS The stature component of the body mass index (BMI) appears to be a plausible candidate for an independent variable that is a contributing factor explaining the incidence of pelvic contents injuries when a 3-point belt-restrained occupant is involved in a frontal impact.

Modern environmental scenarios such as autonomous vehicles, aircrafts, and military vehicles position the human body in a nonstandard posture and induce multiplanar loads; however, current spine alignment methods and loading are based on sagittal and planar loads. The objective of this study is to develop a posture control device and demonstrate its ability to induce multiplanar loads to the human cadaver spinal columns. The inferior end of the device was designed to allow a full six degree-of-freedom control for positioning the specimen via a coupled x-y cross table, vertical lift platform, and triaxial rotation mechanism. The superior end of the device was designed such that the cranial fixation of the specimen could be attached to the piston of the electrohydraulic testing apparatus directly or via a rotary disc through a slider-crank mechanism. The former attachment induces complex forces and moments, while the latter induces controlled moments with minimal forces. The usability of the posture control device was demonstrated by conducting experiments with a thoracolumbar spinal column for combined forces and moments, and with a head-neck column for complex moments, and in both cases, the uniaxial travel of the piston was at a dynamic rate. The posture control device can be used to study the biomechanics of the spine under complex loads and with different postures and develop injury criteria for different field environments.

The goal of the present study was to examine the effect of vertebral body fracture on the InterVertebral Foraminal IVF parameters with an input acceleration to the seat bottom in the inferior-to-superior direction.A series of 43 isolated lumbar spines underwent vertical dynamic loading using the vertical accelerative device to determine the influence of inferior to superior loading through the lumbar spine on the intervertebral foramen (IVF) geometries. Existence of foraminal stenosis was quantified using pre- and post-test computed tomography (CT) images. Foraminal height (IVF_Ht) and posterior disk height (PD_Ht) were the key IVF parameters.There was a significant (p 0.05) decrease in the post-test IVF measurements compared to the pretest measurements. Furthermore, 30% of the total 49 AIS 2 cases and 70% of the total 21 AIS 3 cases had IVF values below the literature reported thresholds for IVF_Ht of15 mm and PD_Ht of4 mm, indicating likely occurrence of foraminal stenosis.These results underscore the need to assess foraminal geometry in compression fractures of the lumbar spine from vertical dynamic loading.

To describe the demographics and clinical findings in patients with otorrhoea in Angola.A total of 411 patients with otorrhoea presenting in the ear, nose and throat clinic in Luanda and healthcare centres in other Angolan provinces underwent interview and clinical examination. We describe the demographics and clinical characteristics of the patients.The majority (64%) of patients were children15 years (age ranged from 1 month to 77 years; median age 10.9 years) while 31% were children5 years. In 83% of the patients, otorrhoea had lasted14 days at the time of the examination indicating chronic suppurative otitis media (CSOM), which was confirmed with otoscopy in 72% of patients. Acute otitis media occurred in 16% of patients and was more common in children than in adults (22% vs. 10%; P = 0.007). Median duration of otorrhoea was12 months. Earache (67%), fever (20%), dizziness (17%), nausea and/or vomiting (6%) were the main symptoms. Adult patients reported noticing hearing impairment (HI) more often than the parents of child patients (72% vs. 50%; P 0.0001). Reported HI correlated with otorrhoea duration (P 0.0001), presence of earache, dizziness, and measles or meningitis in history. The level of education in the family did not correlate with symptom duration.Otorrhoea is mainly due to CSOM and affects patients long-term in Angola. Otorrhoea duration is the strongest predictor of HI. Education on OM and its treatment is needed to prevent HI.Décrire les données démographiques et les résultats cliniques chez les patients atteints d'otorrhée en Angola. MÉTHODES: Au total, 411 patients atteints d'otorrhée visitant la clinique ORL à Luanda et dans les centres de soins de santé d'autres provinces angolaises ont subi un entretien et un examen clinique. Nous décrivons les caractéristiques démographiques et cliniques des patients. RÉSULTATS: La majorité (64%) des patients étaient des enfants15 ans (tranche d'âge de 1 mois à 77 ans; âge médian de 10,9 ans) tandis que 31% étaient des enfants5 ans. Chez 83% des patients, l'otorrhée avait duré14 jours au moment de l'examen indiquant une otite moyenne suppurée chronique (OMSC), qui a été confirmée par otoscopie chez 72% des patients. Une otite moyenne aiguë est survenue chez 16% des patients et était plus fréquente chez les enfants que chez les adultes (22% vs 10%; P = 0,007). La durée médiane de l'otorrhée était12 mois. Les maux d'oreille (67%), la fièvre (20%), les étourdissements (17%), les nausées et/ou les vomissements (6%) étaient les principaux symptômes. Les patients adultes ont rapporté avoir remarqué une déficience auditive (DA) plus souvent que les parents d'enfants patients (72% vs 50%; P0,0001). La DA rapportée était en corrélation avec la durée de l'otorrhée (P0,0001), la présence de maux d'oreille, d'étourdissements et de rougeole ou de méningite dans les antécédents. Le niveau d'éducation dans la famille n'était pas corrélé à la durée des symptômes.L'otorrhée est principalement due à l’OMSC et affecte les patients à long terme en Angola. La durée de l'otorrhée est le meilleur prédicteur de la DA. L'éducation sur l'OM et son traitement est nécessaire pour prévenir la DA.

Injury criteria are used in military, automotive, and aviation environments to advance human safety. While injury risk curves (IRCs) for the human pelvis are published under vertical loading, there is a paucity of analysis that describe IRCs under lateral impact. The objective of the present study is to derive IRCs under this mode. Published data were used from 60 whole-body postmortem human surrogate (PMHS) tests that used repeated testing protocols. In the first analysis, from single impact tests, all injury data points were considered as left censored and noninjury points were considered as right censored, while repeated testing results were treated as interval censored data. In the second analysis, injury data were treated uncensored. Peak force was used as the response variable. Age, total body mass, gender, and body mass index (BMI) were used as covariates in different combinations. Bayesian survival analysis model was used to derive the IRCs. Plus-minus 95% credible intervals (CI) and their normalized CI sizes (NCIS) were obtained. This is the first study to develop IRCs in whole body PMHS tests to describe the human pelvic tolerance under lateral impact using Bayesian models.

Musculoskeletal injuries to the lower leg and foot-ankle joint are associated with external mechanical loads resulting from motor vehicle crashes, under body blasts, falls from height, or sports. As an intrinsic material property, the bone mineral density (BMD) is related to bone strength. The clinically recognized biological sites for BMD evaluation are the hip and spine. The focus of this study was to define the correlation between BMD from standard clinical sites (hip and lumbar spine) compared to BMD from non-standard sites (foot-ankle-distal tibia bones). Twenty-one post-mortem human subjects (PMHS) with mean age, height, and mass of 63 ± 11 years, 179 ± 7 cm, and 86 ± 13 kg, respectively were used for analysis. Clinical BMD software (Mindways Software, Inc.) was used for trabecular BMD quantification using quantitative computed tomography (QCT). In quantification of BMD of the foot-ankle-distal tibia (hind foot), the trabecular BMD of the talus (316 ± 86mg/cc) was highest followed by the distal tibia (238 ± 72 mg/cc) and then calcaneus (147 ± 51 mg/cc). To correlate BMD values from foot bone regions with the central skeleton BMD values within the same PMHS, there were 18 lumbar spine and 12 hip BMDs available. The BMD of the distal tibia correlated best with the hip intertrochanter BMD (R2 of 0.72). Calcaneus BMD best correlated with the hip femoral neck BMD (R2 = 0.64). In summary, the hind foot bone BMD values correlated better with the hip as compared to the lumbar spine BMD from the same PMHS. These findings indicate that, in the absence of a direct measure of foot-bone BMD, hip BMD might be a better predictor of injury risk to hind foot rather than lumbar spine BMD, or alternatively, calcaneal trabecular BMD can be used to predict the risk of injury to hip. Further, these relationships between central and peripheral regions can also be implemented in finite element models for improved failure predictions.

Analyses of recent automotive accident data indicate an increased risk of injury for small female occupants compared to males in similar accidents. Females have been shown to be more susceptible to spinal injuries than males. To protect this more vulnerable population, advanced anthropomorphic test devices (ATDs) and computer human body models are being developed and require biofidelity curves for validation. The aim of this study is to generate female-specific 3D kinematic corridors in near- and far-side oblique frontal impacts for the head, spine, and pelvis.Eight specimens were procured and prescreened for mass, stature, and quantitative computed tomography bone mineral density and preexisting injuries to minimize biologic variability. Sets of 4 noncolinear retroreflective targets were placed on the back of the head; dorsal spine at T1, T8, and L2; and posterior sacrum. Instrumented computed tomography scans were obtained to measure the orientation and position of the markers relative to anatomic fiducials. The specimens were placed on a buck representative of a generic automotive driver's seat environment designed to minimize lower-extremity and pelvic motion. The buck was oriented such that the buck centerline was seated 30° from the impact vector in either a near- or far-side oblique frontal configuration. Preposition of the occupant was specified to the 50th percentile male H-point location, thigh and tibial angles, and torso angle. Impact was delivered via a servo-acceleration sled to the base of the buck with a 30 km/h 9 g trapezoidal pulse. Occupants were restrained by a standard 3-point belt that had a custom load-limiter device set to 2 kN at the D-ring side of the shoulder belt. Target motion was recorded at 1 kHz using a 3D optical motion capture system. Anatomic motion of the head, spine, and pelvis was calculated relative to the seat, and the average response was determined from 4 near-side and 4 far-side tests. The borders of the corridor were determined by calculating a standard deviational ellipse in the x, y, and z planes at each time step.Plots of the biofidelity corridors for near- and far-side tests are shown in planes parallel to the seat from the lateral, rear, and overhead directions. Averaged peak excursions in the fore/aft and lateral directions are compared for the near- and far-side corridors. Near-side female and male tests are similarly compared.In general, average peak excursions were greater in the far-side configuration than in the near-side configuration. Peak excursion results compared well with similar tests conducted on male postmortem human subjects (PMHS). The kinematic corridors developed in the current study serve as a set of biofidelity corridors for the development of current and future physical and computational surrogates.

The human cervical spine sustains compressive loading in automotive events and military operational activities, and the contact and noncontact loading are the two primary impact modes. Biomechanical and anatomical studies have shown differences between male and female cervical spines. Studies have been conducted to determine the human tolerance in terms of forces from postmortem human subject (PMHS) specimens from male and female spines; however, parametric risk curves specific to female spines are not available from contact loading to the head-neck complex under the axial mode. This study was conducted to develop female-spine based risk curves from PMHS tests. Data from experiments conducted by the authors using PMHS upright head-spines were combined with data from published studies using inverted head-spines. The ensemble consisted of 20 samples with ages ranging from 29 to 95 years. Except one, all specimens sustained neck injuries, consisting of fractures to cervical vertebrae, and disruptions to the intervertebral disc and facet joints, and ligaments. Parametric survival analysis was used to derive injury probability curves using the compressive force, uncensored for injury and right censored for noninjury data points. The specimen age was used as the covariate. Injury probability curves were derived using the best fit distribution, and the ± 95% confidence interval limits were obtained. Results indicated that age is a significant covariate for injury for the entire ensemble. Peak forces were extracted for 35, 45, and 63 (mean) years of age, the former two representing the young (military) and the latter, the automobile occupant populations. The forces of 1.2 kN and 2.9 kN were associated with 5% and 50% probability of injury at 35 years. These values at 45 years were 1.0 kN and 2.4 kN, and at 63 years, they were 0.7 kN and 1.7 kN. The normalized widths of the confidence intervals at these probability levels for the mean age were 0.74 and 0.48. The preliminary injury risk curves presented should be used with appropriate caution. This is the first study to develop risk curves for females of different ages using parametric survival analysis, and can be used to advance human safety, and design and develop manikins for military and other environments.

Biomechanical/anatomic limitations may limit the successful implantation, maintenance, and risk acceptance of posterior cervical plate/rod fixation for one stage decompression-fusion. A method of posterior fixation (crisscross) that resolves biomechanical deficiencies of previous facet wiring techniques and not reliant upon screw implantation has been devised. The biomechanical performance of the new method of facet fixation was compared to the traditional lateral mass plate/screw fixation method.Thirteen human cadaver spine segments (C2-T1) were tested under flexion-compression loading and four were evaluated additionally under pure-moment load. Preparations were evaluated in a sequence of surgical alterations with intact, laminectomy, lateral mass plate/screw fixation, and crisscross facet fixation using forces, displacements and kinematics.Combined loading demonstrated significantly lower bending stiffness (p 0.05) between laminectomy compared to crisscross and lateral mass plate/screw preparations. Crisscross fixation showed a comparative tendency for increased stiffness. The increased overall motion induced by laminectomy was resolved by both fixation techniques, with crisscross fixation demonstrating a comparatively more uniform change in segmental motions.The crisscross technique of facet fixation offers immediate mechanical stability with resolution of increased flexural rotations induced by multi-level laminectomy. Many of the anatomic limitations and potentially deleterious variables that may be associated with multi-level screw fixation are not associated with facet wire passage, and the subsequent fixation using a pattern of wire connection crossing each facet joint exhibits a comparatively more uniform load distribution. Crisscross wire fixation is a valuable addition to the surgical armamentarium for extensive posterior cervical single-stage decompression-fixation.

Introduction: Literature reveals several peritoneal dialysis laparoscopic catheter insertion techniques developed to improve long- term results for treatment chronic kidney failure with the technic of peritoneal dialysis. The purpose of the study is evaluation of developed and recommended minimally invasive laparoscopic technic for chronic peritoneal dialysis catheter placement using specially constructed trocar. Materials and Methods: Retrospective study included 804 patients in 10 departments of surgery. Surgical and non surgical complications related to PD catheter placement were analysed: bleeding, dialysate leak, early SSI, peritonitis, catheter tip migration, catheter obstruction, omental wrapping and visceral perforations. Available software (Microsoft® Excel for Windows 10, MedCalc, Mariakerke, Belgium) was used for statistical analysis (presented as percentages, mean ± SD or median). Conclusions: The presented technique with specially constructed trocar is a simple and effective procedure with fewer complications comparing to literature. The advantages of this method include long rectus sheath tunnel with the deep cuff placed pre- peritoneally, the small size of the entrance into the peritoneum and accurate position and control of catheter tip in the pelvis.

IntroductionUnderbody blast loading can result in injuries to the pelvis and the lumbosacral spine. The purpose of this study was to determine human tolerance in this region based on survival analysis.MethodsTwenty-six unembalmed postmortem human surrogate lumbopelvic complexes were procured and pretest medical images were obtained. They were fixed in polymethylmethacrylate at the cranial end and a six-axis load cell was attached. The specimens were aligned in a seated soldier posture. Impacts were applied to the pelvis using a custom vertical accelerator. The experimental design consisted of non-injury and injury tests. Pretest and post-test X-rays and palpation were done following non-injury test, and after injury test medical imaging and gross dissections were done. Injuries were scored using the Abbreviated Injury Scale (AIS). Axial and resultant forces were used to develop human injury probability curves (HIPCs) at AIS 3+ and AIS 4 severities using survival analysis. Then ±95% CI was computed using the delta method, normalised CI size was obtained, and the quality of the injury risk curves was assigned adjectival ratings.ResultsAt the 50% probability level, the resultant and axial forces at the AIS 3+ level were 6.6 kN and 5.9 kN, and at the AIS 4 level these were 8.4 kN and 7.5 kN, respectively. Individual injury risk curves along with ±95% CIs are presented in the paper. Increased injury severity increased the HIPC metrics. Curve qualities were in the good and fair ranges for axial and shear forces at all probability levels and for both injury severities.ConclusionsThis is the first study to develop axial and resultant force-based HIPCs defining human tolerance to injuries to the pelvis from vertical impacts using parametric survival analysis. Data can be used to advance military safety under vertical loading to the seated pelvis.

We have previously shown that topical opioids including morphine and its congeners promote healing of full thickness ischemic wounds in rats. We examined the contribution of mu opioid receptor (MOPr)-mediated healing of full thickness ischemic wounds using MOPr and delta or kappa opioid receptor (DOPr or KOPr) knockout (KO) mice. Wound closure in the early (day 5) as well as later phases was delayed in topical morphine or PBS treated MOPr-KO mice compared to reciprocal treatments of wounds in wild-type (WT) mice. MOPr expression was significantly upregulated at 30 min in the wound margins and colocalized with wound margins and vasculature in the epidermal and dermal layers of the skin. We next examined whether neuropeptide expression was involved in the mechanism of MOPr-mediated wound closure. Substance P (SP) and calcitonin gene related peptide (CGRP) immunoreactivity (ir) was significantly increased in the skin of MOPr-KO mice as compared to WT mice. Neuropeptide-ir was increased significantly in PBS-treated wounds of MOPr and WT mice, but morphine treatment reduced neuropeptide immunoreactivity in both as compared to PBS. Wounding of keratinocytes led to the release of opioid peptide beta-endorphin (β-END) in conditioned medium, which stimulated the proliferation of endothelial cells. MOPr-selective (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, CTOP) and non-selective OPr antagonist naloxone inhibited endothelial proliferation induced by wounded keratinocyte conditioned medium. Additionally, accelerated wound area closure in vitro by morphine was suppressed by methylnaltrexone, a non-selective OPr antagonist with high affinity for MOPr. Morphine and its congeners stimulated the proliferation of endothelial cells from WT mice but not those from MOPr-KO mice. Furthermore, morphine-induced mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) phosphorylation in endothelial cells was significantly decreased in MOPr-KO mice as compared to WT mice. Collectively, these data suggest that MOPr plays a critical role in the proliferation phase with the formation of granulation tissue during wound healing.

The objectives of this study were to derive lower neck injury metrics/criteria and injury risk curves for the force, moment, and interaction criterion in rear impacts for females. Biomechanical data were obtained from previous intact and isolated post mortem human subjects and head–neck complexes subjected to posteroanterior accelerative loading. Censored data were used in the survival analysis model. The primary shear force, sagittal bending moment, and interaction (lower neck injury criterion, LNic) metrics were significant predictors of injury. The most optimal distribution was selected (Weibulll, log normal, or log logistic) using the Akaike information criterion according to the latest ISO recommendations for deriving risk curves. The Kolmogorov–Smirnov test was used to quantify robustness of the assumed parametric model. The intercepts for the interaction index were extracted from the primary risk curves. Normalized confidence interval sizes (NCIS) were reported at discrete probability levels, along with the risk curves and 95% confidence intervals. The mean force of 214 N, moment of 54 Nm, and 0.89 LNic were associated with a five percent probability of injury. The NCIS for these metrics were 0.90, 0.95, and 0.85. These preliminary results can be used as a first step in the definition of lower neck injury criteria for women under posteroanterior accelerative loading in crashworthiness evaluations.

Injury criteria are used in military, automotive, and aviation environments to advance human safety. While Injury Risk Curves (IRCs) for the human pelvis are published under vertical loading, there is a paucity of analysis that describe IRCs under lateral impact. The objective of the present study is to derive IRCs under this mode. Published data were used from 60 whole-body Post Mortem Human Surrogate (PMHS) tests that used repeated testing protocols. In the first analysis, from single impact tests, all injury data points were considered as left censored and noninjury points were considered as right censored, while repeated testing results were treated as interval censored data. In the second analysis, injury data were treated uncensored. Peak force was used as the response variable. Age, total body mass, gender, and Body Mass Index (BMI) were used as covariates in different combinations. Bayesian survival analysis model was used to derive the IRCs. Plus-minus 95% credible intervals (CI) and their Normalized CI Sizes (NCIS) were obtained. This is the first study to develop IRCs in whole body PMHS tests to describe the human pelvic tolerance under lateral impact using Bayesian models.

The objective of this study was to determine force-based lumbar spine injury criteria due to vertical impact using Post Mortem Human Surrogate (PMHS) experiments. Mounted personnel in military vehicles sustain loads from the pelvis in combat events such as underbody blast loadings. Forty-three post mortem human subject thoracolumbar spinal columns were obtained, screened for pre-existing trauma, bone mineral densities (BMDs) were determined, pre-test radiological images were taken, fixed at the ends in polymethylmethacrylate, load cells were attached to the ends of the fixation, positioned on custom vertical accelerator device based on a military-seating posture, and impacted at the base. Posttest images were obtained, and gross dissection was done to confirm injuries, classified into single and multilevel groups, groups A and B. Axial and resultant forces at the thoracolumbar (proximal) and lumbosacral (distal) joints were used as response variables to develop lumbar spine injury risk curves using parametric survival analysis. The Brier score metric was used to rank the variables. Age, BMD, column length, and vertebral body and intervertebral disc areas were used as covariates. The optimal metric describing the underlying response to injury was the distal resultant force for group A and proximal axial force for group B specimens. Force-BMD for group A and force-body area for group B were the best combinations. The IRCs with ±95% confidence intervals and quality of risk curves are given in the paper, and they serve as lumbar spine injury criteria. The present human cadaver Injury Risk Curves (IRCs) can be used to conduct matched pair tests to obtain dummy-based injury assessment risk curves/values to predict injury. The present IRCs can be used in human body finite element models. The relationship between covariates and primary forces presented in this study contribute to a better understanding of the role of demographic, geometric, and material factors to impact acceleration loading.

AIMS/HYPOTHESIS: Peptide hormones are first synthesised as larger, inactive precursors that are converted to their active forms by endopeptidase cleavage and post-translational modifications, such as amidation. Recent, large-scale genome-wide studies have suggested that two coding variants of the amidating enzyme, peptidylglycine α-amidating monooxygenase (PAM), are associated with impaired insulin secretion and increased type 2 diabetes risk. We aimed to elucidate the role of PAM in modulating beta cell peptide amidation, beta cell function and the development of diabetes. METHODS: PAM transcript and protein levels were analysed in mouse islets following induction of endoplasmic reticulum (ER) or cytokine stress, and PAM expression patterns were examined in human islets. To study whether haploinsufficiency of PAM accelerates the development of diabetes, Pam(+/−) and Pam(+/+) mice were fed a low-fat diet (LFD) or high-fat diet (HFD) and glucose homeostasis was assessed. Since aggregates of the PAM substrate human islet amyloid polypeptide (hIAPP) lead to islet inflammation and beta cell failure, we also investigated whether PAM haploinsufficiency accelerated hIAPP-induced diabetes and islet amyloid formation in Pam(+/−) and Pam(+/+) mice with beta cell expression of hIAPP. RESULTS: Immunostaining revealed high expression of PAM in alpha, beta and delta cells in human pancreatic islets. Pam mRNA and PAM protein expression were reduced in mouse islets following administration of an HFD, and in isolated islets following induction of ER stress with thapsigargin, or cytokine stress with IL-1β, IFN-γ and TFN-α. Despite Pam(+/−) only having 50% PAM expression and enzyme activity as compared with Pam(+/+) mice, glucose tolerance and body mass composition were comparable in the two models. After 24 weeks of HFD, both Pam(+/−) and Pam(+/+) mice had insulin resistance and impaired glucose tolerance, but no differences in glucose tolerance, insulin sensitivity or plasma insulin levels were observed in PAM haploinsufficient mice. Islet amyloid formation and beta cell function were also similar in Pam(+/−) and Pam(+/+) mice with beta cell expression of hIAPP. CONCLUSIONS/INTERPRETATION: Haploinsufficiency of PAM in mice does not accelerate the development of diet-induced obesity or hIAPP transgene-induced diabetes.

This purpose of this study was to replicate foot–ankle injuries seen in the military and derive human injury probability curves using the human cadaver model. Lower legs were isolated below knee from seventeen unembalmed human cadavers and they were aligned in a 90–90 posture (plantar surface orthogonal to leg). The specimens were loaded along the tibia axis by applying short-time duration pulses, using a repeated testing protocol. Injuries were documented using pre- and post-test X-rays, computed tomography scans, and dissection. Peak force-based risk curves were derived using survival analysis and accounted for data censoring. Fractures were grouped into all foot–ankle (A), any calcaneus (B), and any tibia injuries (C), respectively. Calcaneus and/or distal tibia/pilon fractures occurred in fourteen tests. Axial forces were the greatest and least for groups C and B, respectively. Times attainments of forces for all groups were within ten milliseconds. The Weibull function was the optimal probability distribution for all groups. Age was significant (p

Purpose The purpose of this study was to determine injuries to osteo-ligamentous structures of cervical column, mechanisms, forces, severities and AIS scores from vertical accelerative loading. Methods Seven human cadaver head-neck complexes (56.9 ± 9.5 years) were aligned based on seated the posture of military soldiers. Army combat helmets were used. Specimens were attached to a vertical accelerator to apply caudo-cephalad g-forces. They were accelerated with increasing insults. Intermittent palpation and radiography were done. A roof structure mimicking military vehicle interior was introduced after a series of tests and experiments were conducted following similar protocols. Upon injury detection, CT and dissection were done. Temporal force responses were extracted, peak forces and times of occurrence were obtained, injury severities were graded, and spine stability was determined. Results Injuries occurred in tests only when the roof structure was included. Responses were tri-phasic: initial thrust, secondary tensile, tertiary roof contact phases. Peak forces: 1364-4382 N, initial thrust, 165-169 N, secondary tensile, 868-3368 N tertiary helmet-head roof contact phases. Times of attainments: 5.3-9.6, 31.7-42.6, 55.0-70.8 ms. Injuries included fractures and joint disruptions. Multiple injuries occurred in all but one specimen. A majority of injury severities were AIS = 2. Spines were considered unstable in a majority of cases. Conclusions Spine response was tri-phasic. Injuries occurred in roof contact tests with the helmeted head-neck specimen. Multiplicity and unstable nature of AIS = 2 level injuries, albeit at lower severities, might predispose the spine to long-term accelerated degenerative changes. Clinical protocols should include a careful evaluation of sub-catastrophic injuries in military patients.

IGFBP-3 has both stimulatory and inhibitory effects on cancer progression. The growth of EO771 mammary carcinoma cells as syngeneic tumors in C57BL/6 mice is reduced in Igfbp3-null (BP3KO) mice, suggesting that systemic IGFBP-3 enhances tumor progression. In this study we assessed the growth of EO771 cells expressing human IGFBP-3 in BP3KO mice. Cells expressing hIGFBP-3 showed decreased proliferation in vitro and increased levels of IGF-1 receptor (IGF1R) protein but not mRNA, consistent with sequestration of endogenous IGF by IGFBP-3. The growth rate of these cells was restored by exposure to IGF-1 or analogues with reduced affinity for IGFBP-3 (long Arg3-IGF-1) or IGF1R (Leu24-IGF-1). In EO771 cells implanted orthotopically into mice, hIGFBP-3 expression by the cells inhibited tumor establishment in BP3KO but not wild-type mice. For tumors that successfully established, final weight was not affected significantly by hIGFBP-3 expression. However, final tumor weight was inversely related to intratumoral T cell counts, and sera from BP3KO mice with tumors showed low-titer immunoreactivity against IGFBP-3. The contrasting effects on tumor establishment and progression of IGFBP-3 expressed by mammary carcinoma cells, compared to systemic stromal and circulating IGFBP-3, highlights the complexity of growth regulation by IGFBP-3 in mammary tumors.

Urinary schistosomiasis causes damage to the urological system. Ultrasound is a method that detects the burden of secondary disease, individually and in epidemiological studies. In this study, the Schistosoma haematobium-associated urinary tract pathology is analyzed before and after treatment in a short period of time. Seventy children who had previously participated in an epidemiological study on schistosomiasis in the city of Cubal, Angola, and had also performed urinary ultrasound between August 2013 and February 2014 were cited 6-8 months later to assess the possible reinfection and repeat new urinary ultrasound, analyzing changes at the level of urinary pathology. The presence of hematuria and proteinuria was also analyzed. Of the 70 children analyzed, 29 (41.4%) were girls, with an average age of 10.4 years (standard deviation 2.3). Fifty-three (75.7%) had an improvement in their bladder and/or kidney scores, whereas 12 (17.1%) had no change and five (7.1%) had progression of the disease. None of the parameters analyzed completely disappeared. After one single course of treatment with praziquantel, all the analyzed parameters showed regression. Improvement was greater in the urinary bladder than in the upper urinary tract, though these lesions also reversed; the reversion of all parameters was greater among children older than 10 years old than the younger ones. Proteinuria was the parameter with a smaller reduction. Ultrasound should be a usual tool for diagnosis and follow-up in urinary schistosomiasis, particularly in children; more accurate recommendations about follow-up in the case of children whose lesions do not reverse should be established.

To determine role of lordosis in cervical spine injuries using a novel competing risk analysis model.The first subgroup of published experiments (n = 20) subjected upright human cadaver head-neck specimens to impact loading. The natural lordosis was removed. The second (n = 21) and third (n = 10) subgroups of published tests subjected inverted specimens to head impact loading. Lordosis was preserved in these 2 subgroups. Using axial force and age as variables, competing risks analysis techniques were used to determine the role of lordosis in the risk of bone-only, ligament-only, and bone and ligament injuries.Bony injuries were focused more at 1 level to a straightened spine, and ligament injuries were spread around multiple levels. Age was not a significant (P0.05) covariate. A straightened spine had 3.23 times higher risk of bony injuries than a lordotic spine. The spine with maintained lordosis had 1.14 times higher risk of ligament injuries, and 2.67 times higher risk of bone and ligament injuries than a spine without lordosis (i.e., preflexed column).Increased risk of bony injuries in a preflexed spine and ligament injuries in a lordotic spine may have implications for military personnel, as continuous use of helmets in the line of duty affects the natural curvature; astronauts, as curvatures are less lordotic after missions; and civilian patients with spondylotic myelopathy who use head protective devices, as curvatures may change over time in addition to the natural aging process.

Under body blast (UBB) loading to military transport vehicles is known to cause foot-ankle fractures to occupants due to energy transfer from the vehicle floor to the feet of the soldier. The soldier posture, the proximity of the event with respect to the soldier, the personal protective equipment (PPE) and age/sex of the soldier are some variables that can influence injury severity and injury patterns. Recently conducted experiments to simulate the loading environment to the human foot/ankle in UBB events (~5ms rise time) with variables such as posture, age and PPE were used for the current study. The objective of this study was to determine statistically if these variables affected the primary injury predictors, and develop injury risk curves. Fifty belowknee post mortem human surrogate (PMHS) legs were used for statistical analysis. Injuries to specimens involved isolated and multiple fractures of varying severity. The Sanders classification was used to grade calcaneus severity and the AO/OTA classification for distal tibia fracture. Injury risk curves were developed using survival regression analysis and covariates were included whenever statistically significant (p

Lumbar endplate fractures were investigated in different experimental scenarios, however the biomechanical effect of segmental alignment was not outlined. The objectives of this study were to quantify effects of spinal orientation on lumbar spine injuries during single-cycle compressive loads and understand lumbar spine endplate injury tolerance. Twenty lumbar motion segments were compressed to failure. Two methods were used in the preparation of the lumbar motion segments. Group 1 (n = 7) preparation maintained pre-test sagittal lordosis, whereas Group 2 (n = 13) specimens had a free-rotational end condition for the cranial vertebra, allowing sagittal rotation of the cranial vertebra to create parallel endplates. Five Group 1 specimens experienced posterior vertebral body fracture prior to endplate fracture, whereas two sustained endplate fracture only. Group 2 specimens sustained isolated endplate fractures. Group 2 fractures occurred at approximately 41% of the axial force required for Group 1 fracture (p < 0.05). Imaging and specimen dissection indicate endplate injury consistently took place within the confines of the endplate boundaries, away from the vertebral periphery. These findings indicate that spinal alignment during compressive loading influences the resulting injury pattern. This investigation identified the specific mechanical conditions under which an endplate breach will take place. Development of endplate injuries has significant clinical implication as previous research identified internal disc disruption (IDD) and degenerative disc disease (DDD) as long-term consequences of the axial load-shift that occurs following a breach of the endplate. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1084-1091, 2016.

The objective of the study was to develop a simple device, Vertical accelerator (Vertac), to apply vertical impact loads to Post Mortem Human Subject (PMHS) or dummy surrogates because injuries sustained in military conflicts are associated with this vector; example, under-body blasts from explosive devices/events. The two-part mechanically controlled device consisted of load-application and load-receiving sections connected by a lever arm. The former section incorporated a falling weight to impact one end of the lever arm inducing a reaction at the other/load-receiving end. The "launch-plate" on this end of the arm applied the vertical impact load/acceleration pulse under different initial conditions to biological/physical surrogates, attached to second section. It is possible to induce different acceleration pulses by using varying energy absorbing materials and controlling drop height and weight. The second section of Vertac had the flexibility to accommodate different body regions for vertical loading experiments. The device is simple and inexpensive. It has the ability to control pulses and flexibility to accommodate different sub-systems/components of human surrogates. It has the capability to incorporate preloads and military personal protective equipment (e.g., combat helmet). It can simulate vehicle roofs. The device allows for intermittent specimen evaluations (x-ray and palpation, without changing specimen alignment). The two free but interconnected sections can be used to advance safety to military personnel. Examples demonstrating feasibilities of the Vertac device to apply vertical impact accelerations using PMHS head-neck preparations with helmet and booted Hybrid III dummy lower leg preparations under in-contact and launch-type impact experiments are presented.

Background The prevalence of concurrent disease in hyperthyroid cats is unknown. Objectives To identify the prevalence of concurrent intra-abdominal disease using abdominal ultrasound examination (AUS) in hyperthyroid cats referred for radioactive iodine treatment (RIT) and to determine whether the requirement for pretreatment AUS is justified. Animals Five hundred and thirty-four client-owned cats diagnosed with hyperthyroidism and referred for RIT. Methods Retrospective study. Age, breed, sex, body weight, clinical signs, total serum T4 concentration, blood urea nitrogen (BUN) concentration, serum creatinine concentration, urine specific gravity (USG), AUS results, and biopsy or cytology results, or both (if obtained) were collected from the medical records. Results The prevalence of concurrent disease identified using AUS in hyperthyroid cats referred for RIT was 36.1%; 22.8% of the cats in the study had renal disease and 2.4% had confirmed neoplasia. Significant differences in median USG (P value 0.032) and median BUN (P value 0.028) were found between cats that had abnormal kidneys on AUS compared to those with normal-appearing kidneys. Only 2.2% of the cats were not treated with RIT as a result of changes identified on AUS and subsequently obtained cytology or biopsy results. Conclusions and Clinical Importance The results indicate that pretreatment AUS in hyperthyroid cats referred for RIT is unnecessary in most patients.

Background context Clinical studies have indicated that thoracolumbar trauma occurs in the civilian population at its junction. In contrast, injury patterns in military populations indicate a shift to the inferior vertebral levels of the lumbar spine. Controlled studies offering an explanation for such migrations and the associated clinical biomechanics are sparse in literature. Purpose The goals of this study were to investigate the potential roles of acceleration loading on the production of injuries and their stability characteristics using a human cadaver model for applications to high-speed aircraft ejection and helicopter crashes. Study design Biomechanical laboratory study using unembalmed human cadaver lumbar spinal columns. Methods Thoracolumbar columns from post-mortem human surrogates were procured, x-rays taken, intervertebral joints and bony components evaluated for degeneration, and fixed using polymethylmethacrylate. The inferior end was attached to a platform via a load cell and uniaxial accelerometer. The superior end was attached to the upper metal platform via a semi-circular cylinder. The pre-flexed specimen was preloaded to simulate torso mass. The ends of the platform were connected to the vertical post of a custom-designed drop tower. The specimen was dropped inducing acceleration loading to the column. Axial force and acceleration data were gathered at high sampling rates, filtered, and peak accelerations and inertia-compensated axial forces were obtained during the loading phase. Computed tomography images were used to identify and classify injuries using the three-column concept (stable vs. unstable trauma). Results The mean age, total body mass, and stature of the five healthy degeneration-free specimens were 42 years, 73 kg, and 167 cm. The first two specimens subjected to peak accelerations of approximately 200 m/sec 2 were classified as belonging to high-speed aircraft ejection-type and the other three specimens subjected to greater amplitudes (347–549 m/sec 2 ) were classified as belonging to helicopter crash-type loadings. Peak axial forces for all specimens ranged from 4.8 to 7.2 kN. Ejection-type loaded specimens sustained single-level injuries to the L1 vertebra; one injury was stable and the other was unstable. Helicopter crash-type loaded specimens sustained injuries at inferior levels, including bilateral facet dislocation at L4–L5 and L2–L4 compression fractures, and all specimens were considered unstable at least at one spinal level. Conclusions These findings suggest that the severity of spinal injuries increase with increasing acceleration levels and, more importantly, injuries shift inferiorly from the thoracolumbar junction to lower lumbar levels. Acknowledging that the geometry and load carrying capacity of vertebral bodies increase in the lower lumbar spine, involvement of inferior levels in trauma sparing the superior segments at greater acceleration inputs agree with military literature of caudal shift in injured levels. The present study offers an experimental explanation for the clinically observed caudal migration of spinal trauma in military populations as applied to high-speed aircraft ejection catapult and helicopter crashes.

OBJECTIVE To evaluate the usefulness of the WHO classification of ultrasound pathological changes and to establish risk factors for morbidity in a highly endemic setting. METHODS One hundred and fifty-seven ultrasounds were performed on school-aged children previously diagnosed with urinary schistosomiasis in Cubal, Angola. The findings were analysed according to the WHO guidelines. Factors for morbidity were studied. RESULTS Mean age of the children was 8.7 (SD 3.2) years. Pathological changes were found in 85.3% (84.7% in the bladder, 34.4% the ureter and 6.3% kidney lesions). The global score according to the WHO classification was 5.74. Male gender [OR 2.61 (1.04-6.58); P 0.043] and older age [OR 2.96 (1.17-7.46); P 0.023] were associated with a higher risk of developing any kind of urinary abnormality. Proteinuria was present in 61.7% of the children. Macroscopic haematuria [OR 2.48 (1.11-5.58); P = 0.02)] and a high level of proteinuria > 300 mg/dl [OR 5.70 (2.17-14.94); P 300 mg/dl)] were associated with abnormalities of the upper urinary tract and showed good positive and negative predictive values for the detection of pathology in the upper urinary tract (65.5% and 71.1%, respectively). CONCLUSIONS Severe urinary tract pathology was found in a high percentage of the children in our setting. Microhaematuria and proteinuria were good markers of morbidity, proteinuria being more precise for severe alterations of the upper urinary tract. We suggest initial and evolutive ultrasound in children diagnosed with schistosomiasis, and close monitoring including periodic controls. As schistosomiasis control efforts are currently focused on reducing morbidity, tests that detect the presence or degree of morbidity are essential for targeting treatment and tracking the progress of control campaigns.

Epidemiological studies show an association between obesity and poor breast cancer prognosis. We previously demonstrated that global IGFBP-3 deficiency, in IGFBP-3-null mice, resulted in a 50% reduction in mammary tumour growth over 3 weeks relative to tumours in wild-type (WT) C57BL/6 mice. This growth reduction was ameliorated by high fat feeding-induced obesity. This study aimed to examine how IGFBP-3 promotes tumour growth by influencing the immune tumour microenvironment in healthy and obese mice. Syngeneic EO771 cells, which lack detectable IGFBP-3 expression, were grown as orthotopic tumours in WT and IGFBP-3-null C57BL/6 mice placed on either a control chow or a high-fat diet (HFD), and examined by quantitative PCR and immunohistochemistry. In WT mice, increased stromal expression of IGFBP-3 was positively associated with tumour growth, supporting the hypothesis that IGFBP-3 in the microenvironment promotes tumour progression. Examining markers of immune cell subsets, gene expression of Ifng, Cd8a, Cd8b1 and Tnf and CD8 measured by immunohistochemistry were elevated in tumours of IGFBP-3-null mice compared to WT, indicating an accumulation of CD8+ T cells, but this increase was absent if the IGFBP-3-null mice had been exposed to HFD. Expression of these genes was negatively associated with tumour growth. Although similar among groups overall, Nkg2d and Tnfsf10 tumoural expression was associated with decreased tumour growth. Overall, the results of this study provide an immune-based mechanism by which host IGFBP-3 may promote breast tumour growth in the EO771 murine breast cancer model, and suggest that targeting IGFBP-3 might make a novel contribution to immune therapy for breast cancer.

The occupant retention and injuries under far-side impact are invariably dependent upon the effectiveness of the seatbelt restraint system, which is largely driven by parameters such as seatbelt pre-tensioner limiting load, D-ring position above and behind the shoulder, and friction coefficient between the torso and the seatbelt. The cumulative effect of systematic variation of these parameters on occupant kinematics under far-side is rarely studied in the literature. In this study, a systematic and detailed analysis was performed to understand the effect of these parameters on occupant retention. A rigid buck assembly with Global Human Body Model Consortium Human Body Model, validated with post mortem human surrogate experiments was used under two different impact scenarios—lateral and oblique. A simulation matrix of 16 cases was designed by varying the magnitude of the parameters for each impact scenario. Each case was graded as good, moderate, or poor retention based on the position of the shoulder seatbelt at the time of rebound. Head accelerations and excursions, chest compression, rib fractures, and neck moments of the HBM were analyzed to understand the effect of improved retention on occupant kinematics. Results showed that higher pre-tensioner limiting load, higher seatbelt friction, and backward position of D-ring improved retention in both lateral and oblique scenarios. Head acceleration, and excursions and chest compression decreased from poor retention cases to good retention cases for both impact scenarios. Rib fractures were higher in cases with poor retention as compared to those with good retention. The peak lateral neck moments changed marginally from poor to good retention; however, the rate of loading of the neck was significantly higher in good retention. Thus, the current study suggested that the backward D-ring position coupled with higher pretensioner limiting load and friction is likely to improve retention in far-side impacts and prevent injuries from the occupant slipping out of the restraint system. Better retention reduced occupant acceleration, excursion, chest compression and number of rib fractures, on the contrary it might instill higher injury vulnerability to neck and brain.

The objective of this study was to determine the influence of age and injury mechanism on cervical spine tolerance to injury from head contact loading using survival analysis.This study analyzed data from previously conducted experiments using post mortem human subjects (PMHS). Group A tests used the upright intact head-cervical column experimental model. The inferior end of the specimen was fixed, the head was balanced by a mechanical system, and natural lordosis was removed. Specimens were placed on a testing device via a load cell. The piston applied loading at the vertex region. Spinal injuries were identified using medical images. Group B tests used the inverted head-cervical column experimental model. In one study, head-T1 specimens were fixed distally, and C7-T1 joints were oriented anteriorly, preserving lordosis. Torso mass of 16 kg was added to the specimen. In another inverted head-cervical column study, occiput-T2 columns were obtained, an artificial head was attached, T1-T2 was fixed, C4-C5 disc was maintained horizontal in the lordosis posture, and C7-T1 was unconstrained. The specimens were attached to the drop test carriage carrying a torso mass of 15 kg. A load cell at the inferior end measured neck loads in both studies. Axial neck force and age were used as the primary response variable and covariate to derive injury probability curves using survival analysis.Group A tests showed that age is a significant (P.05) and negative covariate; that is, increasing age resulted in decreasing force for the same risk. Injuries were mainly vertebral body fractures and concentrated at one level, mid-to-lower cervical spine, and were attributed to compression-related mechanisms. However, age was not a significant covariate for the combined data from group B tests. Both group B tests produced many soft tissue injuries, at all levels, from C1 to T1. The injury mechanism was attributed to mainly extension. Multiple and noncontiguous injuries occurred. Injury probability curves, ±95% confidence intervals, and normalized confidence interval sizes representing the quality of the mean curve are given for different data sets.For compression-related injuries, specimen age should be used as a covariate or individual specimen data may be prescaled to derive risk curves. For distraction- or extension-related injuries, however, specimen age need not be used as a covariate in the statistical analysis. The findings from these tests and survival analysis indicate that the age factor modulates human cervical spine tolerance to impact injury.

Objective Few donors are available for restoration of sensibility in patients with complete brachial plexus injuries. The objective of our study was to evaluate the anatomical feasibility of using the intercostobrachial nerve (ICBN) as an axon donor to the lateral cord contribution to the median nerve (LCMN). Methods Thirty cadavers were dissected. Data of the ICBN and the LCMN were collected, including diameters, branches and distances. Results The diameters of the ICBN and the LCMN at their point of coaptation were 2.7mm and 3.7mm, respectively. The ICBN originated as a single trunk in 93.3% of the specimens and bifurcated in 73.3%. The distance between the ICBN origin and its point of coaptation to the LCMN was 54mm. All ICBNs had enough extension to reach the LCMN. Conclusion Transfer of the ICBN to the LCMN is anatomically feasible and may be useful for restoring sensation in patients with complete brachial plexus injuries. RESUMO Objetivo Poucos doadores estão disponíveis para a restauração da sensibilidade em pacientes com lesões completas do plexo braquial (LCPB). O objetivo deste estudo foi avaliar a viabilidade anatômica do uso do nervo intercostobraquial (NICB) como doador de axônios para a contribuição do cordão lateral para o nervo mediano (CLNM). Métodos Trinta cadáveres foram dissecados. Os dados do NICB e do CLNM foram coletados: diâmetros, ramos e distâncias. Resultados Os diâmetros do NICB e da CLNM no ponto de coaptação foram 2,7mm e 3,7mm, respectivamente. O NICB originou-se como um único tronco em 93,3% dos espécimes e bifurcou-se em 73,3%. A distância entre a origem do NICB e seu ponto de coaptação com a CLNM foi de 54mm. Todos os NICBs tiveram extensão suficiente para alcançar a CLNM. Conclusão A transferência do NICB para a CLNM é anatomicamente viável e pode ser útil para restaurar a sensibilidade em pacientes com LCPB.

A majority of traumatic brain injuries (TBI) in motor vehicle crashes and sporting environments are mild and caused by high-rate acceleration of the head. For injuries caused by rotational acceleration, both magnitude and duration of the acceleration pulse were shown to influence injury outcomes. This study incorporated a unique rodent model of rotational acceleration-induced mild TBI (mTBI) to quantify independent effects of magnitude and duration on behavioral and neuroimaging outcomes. Ninety-two Sprague-Dawley rats were exposed to head rotational acceleration at peak magnitudes of 214 or 350 krad/s(2) and acceleration pulse durations of 1.6 or 3.4 ms in a full factorial design. Rats underwent a series of behavioral tests including the Composite Neuroscore (CN), Elevated Plus Maze (EPM), and Morris Water Maze (MWM). Ex vivo diffusion tensor imaging (DTI) of the fixed brains was conducted to assess the effects of rotational injury on brain microstructure as revealed by the parameter fractional anisotropy (FA). While the injury did not cause significant locomotor or cognitive deficits measured with the CN and MWM, respectively, a main effect of duration was consistently observed for the EPM. Increased duration caused significantly greater activity and exploratory behaviors measured as open arm time and number of arm changes. DTI demonstrated significant effects of both magnitude and duration, with the FA of the amygdala related to both the magnitude and duration. Increased duration also caused FA changes at the interface of gray and white matter. Collectively, the findings demonstrate that the consequences of rotational acceleration mTBI were more closely associated with duration of the rotational acceleration impulse, which is often neglected as an independent factor, and highlight the need for animal models of TBI with strong biomechanical foundations to associate behavioral outcomes with brain microstructure.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of motor neurons. Familial ALS is strongly associated to dominant mutations in the gene for Cu/Zn superoxide dismutase (SOD1). Recent evidences point to skeletal muscle as a primary target in the ALS mouse model. Wnt/PI3 K signaling pathways and epithelial-mesenchymal transition (EMT) have important roles in maintenance and repair of skeletal muscle. Wnt/PI3 K pathways and EMT gene expression profile were investigated in gastrocnemius muscle from SOD1(G93A) mouse model and age-paired wild-type control in the presymptomatic ages of 40 and 80 days aiming the early neuromuscular abnormalities that precede motor neuron death in ALS. A customized cDNA microarray platform containing 326 genes of Wnt/PI3 K and EMT was used and results revealed eight up-regulated (Loxl2, Pik4ca, Fzd9, Cul1, Ctnnd1, Snf1lk, Prkx, Dner) and nine down-regulated (Pik3c2a, Ripk4, Id2, C1qdc1, Eif2ak2, Rac3, Cds1, Inppl1, Tbl1x) genes at 40 days, and also one up-regulated (Pik3ca) and five down-regulated (Cd44, Eef2 k, Fzd2, Crebbp, Piki3r1) genes at 80 days. Also, protein-protein interaction networks grown from the differentially expressed genes of 40 and 80 days old mice have identified Grb2 and Src genes in both presymptomatic ages, thus playing a potential central role in the disease mechanisms. mRNA and protein levels for Grb2 and Src were found to be increased in 80 days old ALS mice. Gene expression changes in the skeletal muscle of transgenic ALS mice at presymptomatic periods of disease gave further evidence of early neuromuscular abnormalities that precede motor neuron death. The results were discussed in terms of initial triggering for neuronal degeneration and muscle adaptation to keep function before the onset of symptoms.

Pigment epithelium derived factor (PEDF) exerts trophic actions to motoneurons and modulates nonneuronal restorative events, but its effects on neuroplasticity responses after spinal cord (SC) injury are unknown. Rats received a low thoracic SC photothrombotic ischemia and local injection of PEDF and were evaluated behaviorally six weeks later. PEDF actions were detailed in SC ventral horn (motor) in the levels of the lumbar central pattern generator (CPG), far from the injury site. Molecules related to neuroplasticity (MAP-2), those that are able to modulate such event, for instance, neurotrophic factors (NT-3, GDNF, BDNF, and FGF-2), chondroitin sulfate proteoglycans (CSPG), and those associated with angiogenesis and antiapoptosis (laminin and Bcl-2) and Eph (receptor)/ephrin system were evaluated at cellular or molecular levels. PEDF injection improved motor behavioral performance and increased MAP-2 levels and dendritic processes in the region of lumbar CPG. Treatment also elevated GDNF and decreased NT-3, laminin, and CSPG. Injury elevated EphA4 and ephrin-B1 levels, and PEDF treatment increased ephrin A2 and ephrins B1, B2, and B3. Eph receptors and ephrins were found in specific populations of neurons and astrocytes. PEDF treatment to SC injury triggered neuroplasticity in lumbar CPG and regulation of neurotrophic factors, extracellular matrix molecules, and ephrins.

Background While cervical spine injury biomechanics reviews in motor vehicle and sports environments are available, there is a paucity of studies in military loadings. This article presents an analysis on the biomechanics and applications of cervical spine injury research with an emphasis on human tolerance for underbody blast loadings in the military. Methods Following a brief review of published military studies on the occurrence and identification of field trauma, postmortem human subject investigations are described using whole body, intact head–neck complex, osteo-ligamentous cervical spine with head, subaxial cervical column, and isolated segments subjected to differing types of dynamic loadings (electrohydraulic and pendulum impact devices, free-fall drops). Findings Spine injuries have shown an increasing trend over the years, explosive devices are one of the primary causal agents and trauma is attributed to vertical loads. Injuries, mechanisms and tolerances are discussed under these loads. Probability-based injury risk curves are included based on loading rate, direction and age. Interpretation A unique advantage of human cadaver tests is the ability to obtain fundamental data to delineate injury biomechanics and establish human tolerance and injury criteria. Definitions of tolerances of the spine under vertical loads based on injuries have implications in clinical and biomechanical applications. Primary outputs such as forces and moments can be used to derive secondary variables such as the neck injury criterion. Implications are discussed for designing anthropomorphic test devices that may be used to predict injuries in underbody blast environments and improve the safety of military personnel.

O objetivo deste trabalho é descrever, em três propriedades rurais no Estado de Mato Grosso, a epidemiologia, o quadro clínico e o patológico da obstrução intestinal por fitobezoares em bovinos que pastoreavam em piquetes com predomínio de Stylosanthes sp. pelo menos 60 dias. A morbidade variou de 3,3% a 15% e a mortalidade foi de 100%. O quadro clínico foi de cólica abdominal caracterizado por apatia, anorexia, inquietação, desconforto, sudorese e vocalização, seguido por episódios de diarreia ou diminuição da produção fecal, desidratação, hipomotilidade gastrintestinal, aumento do volume abdominal, decúbito esternal ou lateral com a cabeça voltada para o flanco e morte. O curso clínico foi de 2-7 dias. A principal alteração notada durante a necropsia dos bovinos foi a obstrução intestinal por fitobezoar ovoide de 2-5 cm de diâmetro, frequentemente no duodeno, próximo ao piloro, ocasionalmente em sua porção média. Na área de obstrução notou-se a necrose da parede intestinal que estava enegrecida e intensamente demarcada em relação a segmento adjacente normal, além de intenso espessamento associado a edema, congestão e hemorragia. O abomaso e os segmentos intestinais anteriores a obstrução apresentavam-se repletos de conteúdo alimentar líquido e posteriormente estava com ausência de conteúdo. O rúmen frequentemente tinha grande quantidade de conteúdo liquido a pastoso. Em todos os bovinos necropsiados múltiplas estruturas sólidas, arredondadas ou ovoides, esverdeadas (fitobezoares) foram observadas no abomaso. Estes achados indicam que pastagens com predomínio de Stylosanthes sp. predispõem a formação de fitobezoares, os quais podem levar à obstrução intestinal e morte em bovinos. The clinical and pathological findings of intestinal obstruction caused by phytobezoars in cattle consuming Stylosanthes sp. on three farms in Mato Grosso, Brazil, are described. The morbidity varied from 3.3 to 15% and the mortality was 100%. The animals stayed on pastures with predominance of Stylosanthes sp. for at least 60 days. The overall clinical picture was apathy followed by episodes of diarrhea or reduced feces and separation from the herd. Individual clinical signs were abdominal colic characterized by anorexia, discomfort, gastrointestinal hypomotility, dehydration, increased abdominal size, sweating, vocalization, sternal or lateral recumbence with the head on the flank. The clinical course lasted from 2 to 7 days. At necropsy, duodenal or pyloric obstruction was caused by ovoid phytobezoars of 2-4cm diameter; in the area of obstruction friable intestinal tissue with intense swelling, congestion, edema, and reddish mucosa was found. The rumen, abomasum and duodenum proximal to the site of obstruction was filled with greenish liquid, and absence of food contents was observed distally to the phytobezoars. Histologically, at the site of obstruction, the duodenum exhibited diffuse necrosis of the mucosal surface, thickening of the wall by submucosal edema, neutrophilic infiltration, fibrin deposition, necrosis of smooth muscle fibers, and marked congestion or hemorrhage. Pasture with the predominance of Stylosanthes sp. is a serious problem due to the possibility of phytobezoar formation, thus leading to intestinal obstruction and high mortality rates in cattle.

Nucleus replacement technologies are a minimally invasive alternative to spinal fusion and total disc replacement that have the potential to reduce pain and restore motion for patients with degenerative disc disease. Finite element modeling can be used to determine the biomechanics associated with nucleus replacement technologies. The current study focuses on a new nucleus replacement device designed as a conforming silicone implant with an internal void. A validated finite element model of the human lumbar L3-L4 motion segment was developed and used to investigate the influence of the nucleus replacement device on spine biomechanics. In addition, the effect of device design changes on biomechanics was determined. A 3D, L3-L4 finite element model was constructed from medical imaging data. Models were created with the normal intact nucleus, the nucleus replacement device, and a solid silicone implant. Probabilistic analysis was performed on the normal model to provide quantitative validation metrics. Sensitivity analysis was performed on the silicone Shore A durometer of the device. Models were loaded under axial compression followed by flexion/extension, lateral bending, or axial rotation. Compressive displacement, endplate stresses, reaction moment, and annulus stresses were determined and compared between the different models. The novel nucleus replacement device resulted in similar compressive displacement, endplate stress, and annulus stress and slightly higher reaction moment compared with the normal nucleus. The solid implant resulted in decreased displacement, increased endplate stress, decreased annulus stress, and decreased reaction moment compared with the novel device. With increasing silicone durometer, compressive displacement decreased, endplate stress increased, reaction moment increased, and annulus stress decreased. Finite element analysis was used to show that the novel nucleus replacement device results in similar biomechanics compared with the normal intact nucleus.

The objective of the present exploratory study is to understand occupant responses in oblique and side-facing seats in the aviation environment, which are increasingly installed in modern aircrafts. Sled tests were conducted using intact Post Mortem Human Surrogates (PMHS) seated in custom seats approximating standard aircraft geometry. End conditions were selected to represent candidate aviation seat and restraint configurations. Three-dimensional head center-of-gravity linear accelerations, head angular velocities, and linear accelerations of the T1, T6, and T12 spinous processes, and sacrum were obtained. Three-dimensional kinematics relative to the seat were obtained from retroreflective targets attached to the head, T1, T6, T12, and sacrum. All specimens sustained spinal injuries, although variations existed by vertebral level. While the tension mechanism was associated with cervical spine injuries, complex distraction-coupled with bending and tension was attributed to thoracolumbar spine injuries. Skeletal fractures to the ribcage were attributed to compression induced by the restraint from the seatbelt, the presence of the armrest, and/or severe motions of the unconstrained torso. Pelvic injuries were also attributed to restraint offered by the lap belt on the accelerating torso-pelvis complex in the absence of the armrest. Lower extremity injuries occurred due to the unconstrained motion (flailing mechanism). These results serve as an initial dataset to understand the kinematics of different body regions, injuries and patterns, and potential injury mechanisms describing PMHS responses in the aviation environment.

A new anthropomorphic test device (ATD) is being developed by the US Army to be responsive to vertical loading during a vehicle underbody blast event. To obtain design parameters for the new ATD, a series of non-injurious tests were conducted to derive biofidelity response corridors for the foot-ankle complex under vertical loading. Isolated post mortem human surrogate (PMHS) lower leg specimens were tested with and without military boot and in different initial foot-ankle positions. Instrumentation included a six-axis load cell at the proximal end, three-axis accelerometers at proximal and distal tibia, and calcaneus, and strain gages. Average proximal tibia axial forces for a neutral-positioned foot were about 2 kN for a 4 m/s test, 4 kN for 6 m/s test and 6 kN for an 8 m/s test. The force time-to-peak values were from 3 to 5 msec and calcaneus acceleration rise times were 2 to 8 msec. Compared to the neutral posture, the "off-axis" measures (e.g. shear and bending moment) were much greater in magnitude in plantar- or dorsi-flexed posture. The results as a function of velocity demonstrated uniform increases with increasing test velocities. The response corridors supplied from the present investigation will serve as initial design parameters for the ATD lower leg, and can also be used for validation for a human computational model.

Clinical classification of an injury has traditionally involved medical imaging, patient history, and physical examination. The pathogenesis or process of injury has been viewed as a crucial component to estimating fracture stability and direct treatment. However, injury classification systems generally exclude pathogenesis and injury mechanisms because these components are often difficult to elucidate. Furthermore, the development of bone damage relative to the mechanical response is difficult to quantify, which limits the ability to define injury and develop injury criteria. Past advents of new knowledge about the mechanisms and progression of fracture have refined safety standards and engineering design for limiting injury. Post-hoc methodologies for identifying and classifying injuries for post-mortem human surrogate (PMHS) research are well established. Though bone fractures can be classified post hoc, questions remain. Surface acoustic sensing (SAS) is an effective approach to augment PMHS experimentation. The objective was to develop and validate an acoustic-emission-based method to characterize bone fractures during injurious loading conditions using acoustic emissions (AEs) in two bone types: vertebral body (VB) and long bone (LB). The newly developed method incorporated the Stockwell transform to estimate the relative energy release rate (RERR) from bone fracture using acoustic signal processing. Fractures were characterized through AE burst durations and frequency content. Results indicated that VB fractures from compression are prolonged processes compared to LB fracture, which was staccato in nature. Significant (p

Ductal plate malformations (DPMs) represent developmental biliary disorders with a wide phenotypic spectrum. This study characterizes DPM in 30 Boxer dogs. Median age was 1.5 (range, 0.3–10.0) years, with 12 dogs 30 profiles per portal tract, reduced luminal apertures, and negative Ki-67 immunoreactivity. CK19-positive biliary epithelium intersected directly with zone 1 hepatocytes as a signature feature when considered with other DPM characteristics. Phenotypic variation included a multiple small bile duct phenotype (all dogs), predominantly thin-walled sacculated ducts (4), well-formed saccular ducts (4), and sacculated segmental, interlobular, and intralobular ducts (Caroli malformation, 2 dogs, one with bridging portal fibrosis). Histologic evidence of portal venous hypoperfusion accompanied increased biliary profiles in every case. We propose that this spectrum of disorders be referred to as DPM with appropriate modifiers to characterize the unique phenotypes.

The objective of this study was to examine the role of body mass and subcutaneous fat in injury severity and pattern sustained by overweight drivers. Finite element models were created to represent the geometry and properties of subcutaneous adipose tissue in the torso with data obtained from reconstructed magnetic resonance imaging data-sets. The torso adipose tissue models were then integrated into the standard multibody dummy models together with increased inertial parameters and sizes of the limbs to represent overweight occupants. Frontal crash simulations were carried out considering a variety of occupant restraint systems and regional body injuries were measured. The results revealed that differences in body mass and fat distribution have an impact on injury severity and pattern. Even though the torso adipose tissue of overweight subjects contributed to reduce abdominal injury, the momentum effect of a greater body mass of overweight subjects was more dominant over the cushion effect of the adipose tissue, increasing risk of other regional body injuries except abdomen. Through statistical analysis of the results, strong correlations (p 0.01) were found between body mass index and regional body injuries except neck injury. The analysis also revealed that a greater momentum of overweight males leads to greater forward torso and pelvic excursions that account for higher risks (p 0.001) of head, thorax and lower extremity injury than observed in non-overweight males. The findings have important implications for improving the vehicle and occupant safety systems designed for the increasing global obese population.

A primary goal of biomechanical safety research is the definition of localized injury thresholds in terms of quantities that are repeatable and easily measureable during experimentation. Recent biomechanical experimentation using human cadavers has highlighted the role of lower cervical facet joints in the injury mechanism resulting from low-speed automotive rear impacts. The present study was conducted to correlate lower neck forces and moments with facet joint motions during simulated rear impacts in an effort to define facet joint injury tolerance thresholds that can be used to assess automobile safety. Four male and four female intact head-neck complexes were obtained from cadaveric specimens and subjected to simulated automotive rear impacts using a pendulum-minisled device. Cervical spine segmental angulations and localized facet joint kinematics were correlated to shear and axial forces, and bending moments at the cervico-thoracic junction using linear regression. R(2) coefficients indicated that spinal kinematics correlated well with lower neck shear force and bending moment. Correlation slope was steeper in female specimens, indicating greater facet joint motions for a given loading magnitude. This study demonstrated that lower neck loads can be used to predict lower cervical facet joint kinematics during automotive rear impacts. Higher correlation slope in female specimens corresponds to higher injury susceptibility in that population. Although lower neck shear force and bending moment demonstrated adequate correlation with lower cervical facet joint motions, shear force is likely the better predictor due to similarity in the timing of peak magnitudes with regard to maximum facet joint motions.

To determine head-neck biomechanics with a focus on lower neck injury metrics in frontal impact. The mid- and large-size Hybrid III dummies and the mid-size Test device for Human Occupant Restraint (THOR) were positioned on a buck. Tests were conducted at low, medium, and high (3.3, 6.7, and 15.7 m/s) change in velocities using 3 restraint types: normal 3-point belt with no pretension (type A), 10-cm pretension (type B), and 200 N pretension (type C). Repeat tests were conducted. Measured vertical and shear forces and sagittal bending moments were evaluated at the upper and lower regions of the neck to different types of belt systems and at different change in velocities. Peak values normalized with respect to the belt type A were used in the comparative analysis. Metrics transformed to the occipital condyles and T1 were also evaluated.All dummies showed good repeatability. Peak measured and transformed upper and lower neck moments were greatest in the large-size dummy. The mid-size Hybrid III dummy responded with greater forces and moments than the THOR. Regardless of dummy type, anthropometry, and velocity, peak lower neck moments were more sensitive to belt types than peak lower neck forces. A similar pattern was apparent for upper neck data. Moments in the THOR were more sensitive than moments in the mid-size Hybrid III dummy.This study offers quantitative generic restraint-based data and addresses response differences between dummies and dummies of the same family. Because of increased sensitivity to belt types at the upper and lower necks for both forces and moments, the THOR appears to be an improvement to better assess injury potential to rear seat occupants wherein frontal impact air bags do not exist.

Traumatic injuries from blunt, penetrating, and blast events expose the human body to unintentional and intentional external mechanical loads. To mitigate trauma and develop safety-engineered devices for clinical and bioengineering applications, it is critical to delineate the structural load-bearing anatomy and biomechanics of the various components of the human body. This article presents advances made in the understanding of the injury responses and tolerances through experiments conducted using intact or segmented tissues from postmortem human subjects (PMHS), and a considerable majority of data for the presentation has been extracted from studies conducted at the Institutions of the authors. The role of the PMHS model for studying traumatic injuries to the head and face, vertebral column (cervical, thoracic and lumbar spines), thorax, abdomen, pelvis, and lower extremities is discussed. Different impact loading scenarios, likely responsible for the initial trauma causation, are considered in the analysis and determination of the human response to injury. Clinical advances made using the PMHS model are discussed. This includes vertebral stabilization system evaluations secondary to traumatic injuries to the spinal column. The critical importance of using data from the PMHS model in developing validated computational models for advancing crashworthiness research, occupant safety in motor vehicle crashes, medical devices, and safety-engineering applications is highlighted. Clin. Anat., 2011. © 2011 Wiley-Liss, Inc. Language: en

Opioid receptor like-1 receptor (ORL 1 ) is selective for orphaninFQ/nociceptin (OFQ/N), a peptide linked to stress. Since immunologic stimuli exert stressor-like effects, the neuroendocrine and behavioral effects of the T-cell superantigen staphylococcal enterotoxin A (SEA) were tested in ORL 1 −/− and ORL 1 +/+ wildtype 129S6 mice. Within 2 h of SEA challenge both genotypes showed elevated corticosterone, but only wildtypes were elevated after 4 h, and had altered hypothalamic CRH mRNA. Although amygdaloid CRH and TNFα mRNA was increased by SEA, this did not vary with genotype. Interestingly, gustatory neophobia due to SEA challenge was augmented in ORL 1 −/− mice, although object neophobia tested 4 days later was abrogated. These results suggest differential requirements for ORL 1 in the mediation of neuroimmune effects exerted at different times after an immune challenge.

Neuron-glia interaction is involved in physiological function of neurons, however recent evidences have suggested glial cells as participants in neurotoxic and neurotrophic mechanisms of neurodegenerative/neuroregenerative processes. Histological techniques employing immunolabeling, historadiography and in situ hybridization have been useful to localize at cell levels molecules in normal and pathological situations. The intercellular accomplishment leading to neuronal injury in central nervous system disorders implies the performance of quantitative assays to better interpret the role of related molecules or signal pathways, however one limitation employing the whole tissue is the loss of cellular resolution. The laser capture microdissection was developed recently and allows the selection of specific cell types from their original environment after freezing and sectioning the tissue sampling, leading to the quantification of gene expression in individual cells, thus providing a unique opportunity to get new informations on cell signaling related to neurodegeneration. Here we reviewed the role of glial cell signaling on neurodegenerative disorders like ischemia, Parkinson and Alzheimer diseases, and also amyotrophic lateral sclerosis and what has been published with regards to single cell laser capture microdissection technique in the molecular biology investigation on these issues.