Evaluation of DAMAGE Algorithm in Frontal Crashes.

With the current trend of including the evaluation of the risk of brain injuries in vehicle crashes due to rotational kinematics of the head, two injury criteria have been introduced since 2013 - BrIC and DAMAGE. BrIC was developed by NHTSA in 2013 and was suggested for inclusion in the US NCAP for frontal and side crashes. DAMAGE has been developed by UVa under the sponsorship of JAMA and JARI and has been accepted tentatively by the EuroNCAP. Although BrIC in US crash testing is known and reported, DAMAGE in tests of the US fleet is relatively unknown. The current paper will report on DAMAGE in NCAP-like tests and potential future frontal crash tests involving substantial rotation about the three axes of occupant heads. Distribution of DAMAGE of three-point belted occupants without airbags will also be discussed. Prediction of brain injury risks from the tests have been compared to the risks in the real world. Although DAMAGE correlates well with MPS in the human brain model across several test scenarios, the predicted risk of AIS2+ brain injuries are too high compared to real-world experience. The prediction of AIS4+ brain injury risk in lower velocity crashes is good, but too high in NCAP-like and high speed angular frontal crashes.

Evaluation of Brain Rotational Injury Criteria (BrIC) in vehicle frontal crashes.

OBJECTIVE: The objective of this study was to estimate strains in the human brain in regulatory, research, and due care frontal crashes by simulating those impacts. In addition, brain strain simulations were estimated for belted human volunteer tests and in impacts between two players in National Football League (NFL), some with no injury and some with mild Traumatic Brain Injuries (mTBI). METHODS: The brain strain responses were determined using version 5 of the Global Human Body Modeling Consortium (GHBMC) 50th percentile human brain model. One hundred and sixty simulations with the brain model were conducted using rotational velocities and accelerations of Anthropomorphic Test Devices (ATD's) or those of human volunteers in sled or crash tests, as inputs to the model and strain related responses like Maximum Principal Strains (MPS) and Cumulative Strain Damage Measure (CSDM) in various regions of the brain were monitored. The simulated vehicle tests ranged from sled tests at 24 and 32 kph delta-V with three-point belts without airbags to full scale crash and sled tests at 56 kph and a series of Research Mobile Deformable Barrier (RMDB) tests described in Prasad et al. RESULTS: The severity of rotational input into the model as represented by BrIC, averaged between 0.5 and 1.2 for the various test conditions, and as high as 1.5 for an individual case. The MPS responses for the various test conditions averaged between 0.28 and 0.86 and as high as 1.3 in one test condition. The MPS responses in the brain for volunteers, low velocity sled, and NCAP tests were similar to those in the no-mTBI group in the NFL cases and consistent with real world accident data. The MPS responses of the brain in angular crash and sled tests were similar to those in the mTBI group. CONCLUSIONS: The brain strain estimations do not indicate the likelihood of severe-to-fatal brain injuries in the crash environments studied in this paper. However, using the risk functions associated with BrIC, severe-to-fatal brain injuries (AIS4+) are predicted in several environments in which they are not observed or expected.

An estimation of physiochemical properties of bladder cancer drugs via degree-based chemical bonding topological descriptors.

The use of topological descriptors remains a significant approach due to numerous advances in the field of drug design. Descriptors provide numerical representations of a molecule's chemical characteristics when used with QSPR models. The QSPR analysis for bladder medications is the main focus of this study. Linear regression model is developed for the computed indices values, the physicochemical properties of the bladder medications are examined.Communicated by Ramaswamy H. Sarma.

A deep learning approach to detect blood vessels in basal cell carcinoma.

PURPOSE: Blood vessels called telangiectasia are visible in skin lesions with the aid of dermoscopy. Telangiectasia are a pivotal identifying feature of basal cell carcinoma. These vessels appear thready, serpiginous, and may also appear arborizing, that is, wide vessels branch into successively thinner vessels. Due to these intricacies, their detection is not an easy task, neither with manual annotation nor with computerized techniques. In this study, we automate the segmentation of telangiectasia in dermoscopic images with a deep learning U-Net approach. METHODS: We apply a combination of image processing techniques and a deep learning-based U-Net approach to detect telangiectasia in digital basal cell carcinoma skin cancer images. We compare loss functions and optimize the performance by using a combination loss function to manage class imbalance of skin versus vessel pixels. RESULTS: We establish a baseline method for pixel-based telangiectasia detection in skin cancer lesion images. An analysis and comparison for human observer variability in annotation is also presented. CONCLUSION: Our approach yields Jaccard score within the variation of human observers as it addresses a new aspect of the rapidly evolving field of deep learning: automatic identification of cancer-specific structures. Further application of DL techniques to detect dermoscopic structures and handle noisy labels is warranted.

Electrospinning of food-grade nanofibres from whey protein.

In this study, electrospinning has been employed to produce micro to nano scale fibres of whey protein in order to investigate their potential for use in the food industry. Initially, spinning of pure whey protein proved challenging; so in order to facilitate the spinning of freshly prepared aqueous solutions, small amounts of polyethylene oxide (as low as 1% w/w in solution) were incorporated in the spinning solutions. The electrospun composite polyethylene-oxide/whey fibres exhibited diameters in the region of 100 to 400 nm, showing the potential to build fibre bundles from this size up. Time-dependent examinations of pure whey protein aqueous solutions were conducted using rheometery and small angle neutron scattering techniques, with the results showing a substantial change in the solution properties with time and stirring; and allowing the production of fibres, albeit with large diameters, without the need for an additive. The spinability is related to the potential of the whey protein composites to form aggregate structures, either through hydration and interaction with neighbouring proteins, or through interaction with the polyethylene oxide.

Neuroinflammation Induces Neurodegeneration.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Multiple Sclerosis (MS) are characterized by neuronal degeneration and neuronal death in specific regions of the central nervous system (CNS). In AD, neurons of the hippocampus and entorhinal cortex are the first to degenerate, whereas in PD, dopaminergic neurons in the substantia nigra degenerate. MS patients show destruction of the myelin sheath. Once the CNS neurons are damaged, they are unable to regenerate unlike any other tissue in the body. Neurodegeneration is mediated by inflammatory and neurotoxic mediators such as interleukin-1beta (IL-1ß), IL-6, IL-8, IL-33, tumor necrosis factor-alpha (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), CCL5, matrix metalloproteinase (MMPs), granulocyte macrophage colony-stimulating factor (GM-CSF), glia maturation factor (GMF), substance P, reactive oxygen species (ROS), reactive nitrogen species (RNS), mast cells-mediated histamine and proteases, protease activated receptor-2 (PAR-2), CD40, CD40L, CD88, intracellular Ca+ elevation, and activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-B (NF-kB). Activated microglia, astrocytes, neurons, T-cells and mast cells release these inflammatory mediators and mediate neuroinflammation and neurodegeneration in a vicious manner. Further, immune and inflammatory cells and inflammatory mediators from the periphery cross the defective blood-brain-barrier (BBB) and augment neuroinflammation. Though inflammation is crucial in the onset and the progression of neurodegenerative diseases, anti-inflammatory drugs do not provide significant therapeutic effects in these patients till date, as the disease pathogenesis is not yet clearly understood. In this review, we discuss the possible factors involved in neuroinflammation-mediated neurodegeneration.

Effects of resistance exercise and the use of anabolic androgenic steroids on hemodynamic characteristics and muscle damage markers in bodybuilders.

BACKGROUND: Anabolic androgenic steroids (AAS), synthetic compounds of testosterone commonly used as sport performance enhancers, could cause cardiovascular dysfunction and cell damage. Even though the side effects of AAS intake have been widely studied, yet little is known about how resistance exercise can alter these side effects. This study aimed to determine the effects of one session resistance exercise and the use of AAS on hemodynamic characteristics and muscle damage markers in professional bodybuilders. METHODS: Sixteen bodybuilders were divided into two groups: bodybuilders using AAS for at least 5 years (users; N.=8) and AAS-free bodybuilders (non-users; N.=8). The exercise protocol was a circuit strength training session involved three sets of 8-9 repetitions at 80-85% of 1-RM. Heart rate (HR), blood pressure (BP) and concentrations of serum creatine kinase (CK) and lactate dehydrogenase (LDH) were measured at three different time points, immediately before and after the exercise session and 24 hours following the exercise session. RESULTS: The users group showed greater basal levels of hemodynamic characteristics (i.e. HR and BP) and cell damage markers (i.e. CK and LDH) compared to those in the non-users group (all P<0.05). Furthermore, the exercise session significantly increased the levels of HR (P=0.02) and CK (P=0.01) in the users group compared to those in the non-users group immediately after the exercise. No significant differences were observed in BP and LDH responses to exercise between the users and the non-users groups (P>0.05). CONCLUSIONS: These findings indicate that the use of AAS could be potentially harmful as it enhances the levels of the hemodynamic characteristics and the muscle enzymes. These harmful effects of AAS intake could be more evident in response to resistance exercise.

[Diagnosis and treatment of spastic angina revealed by cardiac arrest]. / Mort subite et angor spastique: quelle stratégie diagnostique et thérapeutique?

The prevalence of vasospastic angina is said to be low in Europe, but maybe because of a lack of diagnosis in the daily practice. However, coronary spasm is a common cause of cardiac arrest, especially among patients free of cardiac illness, and it should be systematically investigated after an unexplained cardiac arrest. Intracoronary spasm provocation test exposes patients to a lower risk compared to the risk of spontaneous spastic angina. Accurate modalities and diagnostic criteria have to be clarified for European population. Avoiding external causes of coronary spasm (such as cigarette smoking or more generally consuming coronary spasm inducing drugs) and prescribing antispastic medicine (first of all calcium channel blockers) are the basis of vasospastic angina treatment. However, recurrent coronary spasms have been reported despite an appropriate treatment and implantable automatic defibrillator has been implanted after case discussion when the onset of illness was cardiac arrest. We report the case of a patient recovering from cardiac arrest who had a positive spasm coronary provocation test, and was treated with calcium channel blockers and had been an automatic defibrillator implanted, with a coronary spasm provocation test performed afterward still contentious. While discussing this case, we are making a literature review of the diagnosis and treatment of spastic angina revealed by cardiac arrest.

Development and validation of age-dependent FE human models of a mid-sized male thorax.

The increasing number of people over 65 years old (YO) is an important research topic in the area of impact biomechanics, and finite element (FE) modeling can provide valuable support for related research. There were three objectives of this study: (1) Estimation of the representative age of the previously-documented Ford Human Body Model (FHBM) -- an FE model which approximates the geometry and mass of a mid-sized male, (2) Development of FE models representing two additional ages, and (3) Validation of the resulting three models to the extent possible with respect to available physical tests. Specifically, the geometry of the model was compared to published data relating rib angles to age, and the mechanical properties of different simulated tissues were compared to a number of published aging functions. The FHBM was determined to represent a 53-59 YO mid-sized male. The aforementioned aging functions were used to develop FE models representing two additional ages: 35 and 75 YO. The rib model was validated against human rib specimens and whole rib tests, under different loading conditions, with and without modeled fracture. In addition, the resulting three age-dependent models were validated by simulating cadaveric tests of blunt and sled impacts. The responses of the models, in general, were within the cadaveric response corridors. When compared to peak responses from individual cadavers similar in size and age to the age-dependent models, some responses were within one standard deviation of the test data. All the other responses, but one, were within two standard deviations.

A risk score to predict 30-day mortality in patients with intra-aortic balloon pump implantation.

BACKGROUND: Several risk factors for early mortality after intra-aortic balloon pump (IABP) implantation have been described. METHODS: We performed a retrospective analysis in 120 patients receiving peri- or postoperative IABP support. Univariate and multivariate analyses were carried out to assess variables potentially influencing 30-day mortality in order to develop a risk score for the prognosis of survival and for the decision on optimal patient-specific treatment. RESULTS: The 4 parameters (mean arterial pressure, adrenaline dose, central venous pressure, and blood lactate concentrations) at 6 hours of IABP use were independently related to 30-day mortality. They were used to develop a risk score (0 - 4 points). With this score, patients who scored 3 or 4 points had no probability of surviving, whereas patients with a score of zero had a probability of 84.4 %. A prospectively screened cohort of 145 patients confirmed the reliability of our risk score. CONCLUSIONS: Our data demonstrate that a score can predict 30-day mortality in patients with IABP implantation. Such a score can be useful to find out whether or not ECMO/VAD implantation is necessary.

Helicobacter pylori antibody profile in household members of children with H. pylori infection.

Intrafamilial spread is implicated as a major route for acquisition of Helicoobacter pylori infection. Investigating H. pylori cytotoxin-associated protein (CagA) and vacuolating toxin (VacA) antibodies within family members enabled the authors to evaluate this possibility further. Serum samples were collected prospectively from household members after their index children were diagnosed with active H. pylori infection. Serum samples were evaluated for anti-H. pylori immunoglobulin G antibody using the enzyme immunoassay (IEA) method and for H. pylori CagA and VacA antibodies with the commercially available immunoprobing Western blot kit. Ten different families participated in the study, including 10 pediatric patients and 31 household members. All patients and 28 household members (90%) were seropositive for H. pylori antibody by IEA and Western blot tests. Overall, 17 subjects (41.4%) were CagA positive, 14 (34.1%) were VacA positive, 11 (26.8%) were positive for both antibodies, and 22 (53.6%) were negative for both antibodies. A significant association in bacterial antibody profile was found between the patient index members and all household members (Cohen's kappa and Mentel-Haenszel methods). In four families, more than 66% of the household members harbored the same antibody profile, and in two families a completely different profile was observed. Moreover, a similar H. pylori antibody profile between the index patient and the mother was found in six families, and between the index patient and the father in two families. The data strongly suggest an intrafamiliar transmission for H. pylori infection.

Development of a rat model of toluene-abuse embryopathy.

A rat model was developed to study toluene-abuse embryopathy, a clinical syndrome which occurs in offspring of women who abuse toluene during pregnancy. On d 6-19 of gestation, eight dams received a daily gavage dose of toluene, 650 mg/kg body weight, diluted in corn oil, whereas eight control dams and eight pair-fed dams received corn oil. The fetuses were delivered on d 19 of gestation. In the toluene-exposed group, the weights of the fetuses were reduced by 21.6% (p < 0.001), and a delay in skeletal ossification was demonstrated. Toluene exposure significantly reduced the weight of the fetal brain by 11.9% (p < 0.001), as well as the weights of the heart, liver, and kidney. Organ weight/body weight ratios did not differ significantly. Morphometric analysis of brain sections demonstrated that toluene exposure resulted in smaller brains together with an increase in the size of the ventricular system and a reduction in the size of the caudate nucleus. Although toluene exposure resulted in a 13.7% reduction in maternal food consumption, the observations made in the pair-fed group did not differ from those made in the control group. These findings suggest that prenatal exposure to toluene results in generalized fetal growth retardation, and that these effects are not due to the reduction in maternal food consumption.

The effects of high-dose toluene on embryonic development in the rat.

Developmental disability, intrauterine growth retardation, renal anomalies, and dysmorphic features have been described in offspring of women who abuse toluene during pregnancy. A Sprague-Dawley rat model was developed to study this clinical syndrome. During d 6-19 of gestation, 11 treated dams received daily gavage doses of toluene, 520 mg/kg body weight, diluted in corn oil, and 11 control dams received corn oil. This dose of toluene simulates the blood toluene levels obtained after an inhalation exposure to 3290 ppm toluene, an inhalation level in the lower end of the range experienced by toluene abusers. Maternal weight gain was 24% less in the toluene-exposed group (p < 0.002); however, there were no maternal deaths. The fetuses were delivered on d 19 of gestation, and 287 fetuses (148 toluene exposed, 139 control) were examined. Toluene treatment did not affect the number of implantations or stillbirths. There were no toluene-induced major congenital malformations or neuropathologic changes noted. In the toluene-treated group, the weights of the fetuses were reduced by 9.4% (p < 0.004) and placental weights were reduced by 10.3% (p < 0.01). Toluene exposure also reduced fetal organ weights as follows: brain 4.6%, heart 5.9%, liver 13.2% (p < 0.02), and kidney 13% (p < 0.05). Organ weight/body weight ratios did not differ significantly, suggesting that prenatal toluene exposure produced a generalized growth retardation.

Brainstem bilirubin toxicity in the newborn primate may be promoted and reversed by modulating PCO2.

The auditory brainstem response (ABR) was monitored during infusion of bilirubin in six ventilated newborn rhesus monkeys (138-145 d gestation) while acute changes in pH were produced by varying inspired CO2. Prolonged respiratory acidosis without bilirubin infusion produced minimal changes in the ABR (one animal). CO2 exposure, usually initiated when the bilirubin level reached approximately 20 mg/dL, decreased arterial pH to values ranging from 6.85 to 7.10. ABR changes, including prolongation of the wave II-IV peak to peak intervals and decreased wave amplitudes, first developed 2-4 h after initial exposure to CO2. Total and unbound bilirubin levels at this time ranged from 376 to 564 mumol/L (22-33 mg/dL) and 38 to 65 nmol/L (2.5-3.8 micrograms/dL), respectively. Correction of respiratory acidosis produced partial to complete reversal of ABR changes within 3 to 20 min. Reexposure to CO2 immediately reproduced the ABR abnormality. Production and reversal of the abnormal ABR was obtained through two to three cycles in three animals. Thus, when the brainstem bilirubin level was near the threshold for toxicity, the effect of changes in PCO2 on the ABR were immediate, suggesting that auditory pathway toxicity is initially mediated by a reversible pH-dependent bilirubin-membrane complex. In contrast to humans, in monkeys auditory toxicity appeared to be a late manifestation of bilirubin toxicity, inasmuch as all monkeys were obtunded and apneic 30-70 min before ABR abnormalities appeared. Notwithstanding these limitations, the results support the hypothesis that bilirubin toxicity can be both promoted and reversed by modulating brain pH.

Brain injury and protective effects of hypothermia using triphenyltetrazolium chloride in neonatal rat.

Colorless 2,3,5-triphenyltetrazolium chloride (TTC) is reduced by enzymes in functioning mitochondria to a red-colored compound, and has been used to differentiate areas of viable tissue from areas of infarction in adult animals. TTC was used to study the central nervous system protective effects of hypothermia on the neonatal rat exposed to hypoxia and ischemia. The effect of hypothermia on survival and weight gain was also determined. Seven-day-old Wistar rats with right carotid artery ligation were exposed to 3 hours of 8% oxygen and maintained at either 37 degrees C (n = 22) or 30 degrees C (n = 18). The survivors were sacrificed 2 days later and brain slices exposed to TTC. These slices were photographed and the percentage of damage to the right brain was estimated gravimetrically from the stained and unstained areas of enlarged images. The mean weight gains were 4.2 +/- 1.2 gm in the 30 degrees C group and -1.0 +/- 2.8 gm in the 37 degrees C group (P < .001). The survival in the 37 degrees C group was 77% and in the 30 degrees C group 100% (P < .025). The mean percentage damage to the right side of the brain in the 37 degrees C group was 45.5% (range: 0-87.5%); there was no detectable damage in any of the 30 degrees C group pups (P < .0001). In our study, TTC proved to be a rapid and simple method for assessing central nervous system injury in the neonatal rat. This study also confirms that moderate hypothermia is protective against hypoxic-ischemic brain injury.

Indications for measurement of total carbon dioxide in arterial blood.

There is increasing evidence of variability in pK1', the practical dissociation coefficient used in the Henderson-Hasselbalch equation to calculate arterial bicarbonate from measurements of arterial pH and pco2. The case presented here illustrates not only potential technical artifacts in arterial blood sampling, which can confuse, but also irreconcilable differences in the values of calculated arterial bicarbonate vs measured arterial and venous total carbon dioxide (carbon dioxide content). Measurements of total carbon dioxide in arterial blood will resolve such conflicts, particularly for acutely ill patients, and will reflect the correct bicarbonate measurements for use in therapeutic decisions.