Acute intoxication with diisopropylfluorophosphate promotes cellular senescence in the adult male rat brain.

Acute intoxication with high levels of organophosphate (OP) cholinesterase inhibitors can cause cholinergic crisis, which is associated with acute, life-threatening parasympathomimetic symptoms, respiratory depression and seizures that can rapidly progress to status epilepticus (SE). Clinical and experimental data demonstrate that individuals who survive these acute neurotoxic effects often develop significant chronic morbidity, including behavioral deficits. The pathogenic mechanism(s) that link acute OP intoxication to chronic neurological deficits remain speculative. Cellular senescence has been linked to behavioral deficits associated with aging and neurodegenerative disease, but whether acute OP intoxication triggers cellular senescence in the brain has not been investigated. Here, we test this hypothesis in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague-Dawley rats were administered DFP (4 mg/kg, s.c.). Control animals were administered an equal volume (300 µL) of sterile phosphate-buffered saline (s.c.). Both groups were subsequently injected with atropine sulfate (2 mg/kg, i.m.) and 2-pralidoxime (25 mg/kg, i.m.). DFP triggered seizure activity within minutes that rapidly progressed to SE, as determined using behavioral seizure criteria. Brains were collected from animals at 1, 3, and 6 months post-exposure for immunohistochemical analyses of p16, a biomarker of cellular senescence. While there was no immunohistochemical evidence of cellular senescence at 1-month post-exposure, at 3- and 6-months post-exposure, p16 immunoreactivity was significantly increased in the CA3 and dentate gyrus of the hippocampus, amygdala, piriform cortex and thalamus, but not the CA1 region of the hippocampus or the somatosensory cortex. Co-localization of p16 immunoreactivity with cell-specific biomarkers, specifically, NeuN, GFAP, S100ß, IBA1 and CD31, revealed that p16 expression in the brain of DFP animals is neuron-specific. The spatial distribution of p16-immunopositive cells overlapped with expression of senescence associated ß-galactosidase and with degenerating neurons identified by FluoroJade-C (FJC) staining. The co-occurrence of p16 and FJC was positively correlated. This study implicates cellular senescence as a novel pathogenic mechanism underlying the chronic neurological deficits observed in individuals who survive OP-induced cholinergic crisis.

Enhancing Image-Guided Radiation Therapy for Pancreatic Cancer: Utilizing Aligned Peak Response Beamforming in Flexible Array Transducers.

To develop ultrasound-guided radiotherapy, we proposed an assistant structure with embedded markers along with a novel alternative method, the Aligned Peak Response (APR) method, to alter the conventional delay-and-sum (DAS) beamformer for reconstructing ultrasound images obtained from a flexible array. We simulated imaging targets in Field-II using point target phantoms with point targets at different locations. In the experimental phantom ultrasound images, image RF data were acquired with a flexible transducer with in-house assistant structures embedded with needle targets for testing the accuracy of the APR method. The lateral full width at half maximum (FWHM) values of the objective point target (OPT) in ground truth ultrasound images, APR-delayed ultrasound images with a flat shape, and images acquired with curved transducer radii of 500 mm and 700 mm were 3.96 mm, 4.95 mm, 4.96 mm, and 4.95 mm. The corresponding axial FWHM values were 1.52 mm, 4.08 mm, 5.84 mm, and 5.92 mm, respectively. These results demonstrate that the proposed assistant structure and the APR method have the potential to construct accurate delay curves without external shape sensing, thereby enabling a flexible ultrasound array for tracking pancreatic tumor targets in real time for radiotherapy.

Photoacoustic Imaging and Characterization of Bone in Medicine: Overview, Applications, and Outlook.

Photoacoustic techniques have shown promise in identifying molecular changes in bone tissue and visualizing tissue microstructure. This capability represents significant advantages over gold standards (i.e., dual-energy X-ray absorptiometry) for bone evaluation without requiring ionizing radiation. Instead, photoacoustic imaging uses light to penetrate through bone, followed by acoustic pressure generation, resulting in highly sensitive optical absorption contrast in deep biological tissues. This review covers multiple bone-related photoacoustic imaging contributions to clinical applications, spanning bone cancer, joint pathologies, spinal disorders, osteoporosis, bone-related surgical guidance, consolidation monitoring, and transsphenoidal and transcranial imaging. We also present a summary of photoacoustic-based techniques for characterizing biomechanical properties of bone, including temperature, guided waves, spectral parameters, and spectroscopy. We conclude with a future outlook based on the current state of technological developments, recent achievements, and possible new directions.

Theoretical Framework to Predict Generalized Contrast-to-Noise Ratios of Photoacoustic Images With Applications to Computer Vision.

The successful integration of computer vision, robotic actuation, and photoacoustic imaging to find and follow targets of interest during surgical and interventional procedures requires accurate photoacoustic target detectability. This detectability has traditionally been assessed with image quality metrics, such as contrast, contrast-to-noise ratio, and signal-to-noise ratio (SNR). However, predicting target tracking performance expectations when using these traditional metrics is difficult due to unbounded values and sensitivity to image manipulation techniques like thresholding. The generalized contrast-to-noise ratio (gCNR) is a recently introduced alternative target detectability metric, with previous work dedicated to empirical demonstrations of applicability to photoacoustic images. In this article, we present theoretical approaches to model and predict the gCNR of photoacoustic images with an associated theoretical framework to analyze relationships between imaging system parameters and computer vision task performance. Our theoretical gCNR predictions are validated with histogram-based gCNR measurements from simulated, experimental phantom, ex vivo, and in vivo datasets. The mean absolute errors between predicted and measured gCNR values ranged from 3.2 ×10-3 to 2.3 ×10-2 for each dataset, with channel SNRs ranging -40 to 40 dB and laser energies ranging 0.07 [Formula: see text] to 68 mJ. Relationships among gCNR, laser energy, target and background image parameters, target segmentation, and threshold levels were also investigated. Results provide a promising foundation to enable predictions of photoacoustic gCNR and visual servoing segmentation accuracy. The efficiency of precursory surgical and interventional tasks (e.g., energy selection for photoacoustic-guided surgeries) may also be improved with the proposed framework.

Shear Wave Speed estimator using Continuous Wavelet Transform for Crawling Wave Sonoelastography.

Crawling Wave Sonoelastography (CWS) is an elastography ultrasound-based imaging approach that provides tissue stiffness information through the calculation of Shear Wave Speed (SWS). Many SWS estimators have been developed; however, they report important limitations such as the presence of artifacts, border effects or high computational cost. In addition, these techniques require a moving interference pattern which could be challenging for in vivo applications. In this study, a new estimator based on the Continuous Wavelet Transform (CWT) is proposed. This allows the generation of a SWS image for every sonoelasticity video frame. Testing was made with data acquired from experiments conducted on a gelatin phantom with a circular inclusion. It was excited with two vibration sources placed at both sides with frequencies ranging from 200 Hz to 360 Hz in steps of 20 Hz. Results show small variation of the SWS image across time. Additionally, images were compared with the Phase Derivative method (PD) and the Regularized Wavelength Average Velocity Estimator (R-WAVE). Similar SWS values were obtained for the three estimators within a certain region of interest in the inclusion (At 360 Hz, CWT: 5.01±0.2m/s, PD: 5.11±0.28m/s, R-WAVE: 4.51±0.62m/s) and in the background (At 360 Hz, CWT: 3.67±0.15m/s, PD: 3.69±0.23m/s, R-WAVE: 3.58±0.24m/s). CWT also presented the lowest coefficient of variation and the highest contrast-to-noise ratio for most frequencies, which allows better discrimination between regions.Clinical relevance-This study presents a new Shear Wave Speed estimator for Crawling Wave Sonoelastography, which can be useful to characterize soft tissue and detect lesions.

Sex-specific acute and chronic neurotoxicity of acute diisopropylfluorophosphate (DFP)-intoxication in juvenile Sprague-Dawley rats.

Preclinical efforts to improve medical countermeasures against organophosphate (OP) chemical threat agents have largely focused on adult male models. However, age and sex have been shown to influence the neurotoxicity of repeated low-level OP exposure. Therefore, to determine the influence of sex and age on outcomes associated with acute OP intoxication, postnatal day 28 Sprague-Dawley male and female rats were exposed to the OP diisopropylfluorophosphate (DFP; 3.4 mg/kg, s.c.) or an equal volume of vehicle (∼80 µL saline, s.c.) followed by atropine sulfate (0.1 mg/kg, i.m.) and pralidoxime (2-PAM; 25 mg/kg, i.m.). Seizure activity was assessed during the first 4 h post-exposure using behavioral criteria and electroencephalographic (EEG) recordings. At 1 d post-exposure, acetylcholinesterase (AChE) activity was measured in cortical tissue, and at 1, 7, and 28 d post-exposure, brains were collected for neuropathologic analyses. At 1 month post-DFP, animals were analyzed for motor ability, learning and memory, and hippocampal neurogenesis. Acute DFP intoxication triggered more severe seizure behavior in males than females, which was supported by EEG recordings. DFP caused significant neurodegeneration and persistent microglial activation in numerous brain regions of both sexes, but astrogliosis occurred earlier and was more severe in males compared to females. DFP males and females exhibited pronounced memory deficits relative to sex-matched controls. In contrast, acute DFP intoxication altered hippocampal neurogenesis in males, but not females. These findings demonstrate that acute DFP intoxication triggers seizures in juvenile rats of both sexes, but the seizure severity varies by sex. Some, but not all, chronic neurotoxic outcomes also varied by sex. The spatiotemporal patterns of neurological damage suggest that microglial activation may be a more important factor than astrogliosis or altered neurogenesis in the pathogenesis of cognitive deficits in juvenile rats acutely intoxicated with OPs.

Strain differences in the extent of brain injury in mice after tetramethylenedisulfotetramine-induced status epilepticus.

Acute intoxication with tetramethylenedisulfotetramine (TETS) can trigger status epilepticus (SE) in humans. Survivors often exhibit long-term neurological effects, including electrographic abnormalities and cognitive deficits, but the pathogenic mechanisms linking the acute toxic effects of TETS to chronic outcomes are not known. Here, we use advanced in vivo imaging techniques to longitudinally monitor the neuropathological consequences of TETS-induced SE in two different mouse strains. Adult male NIH Swiss and C57BL/6J mice were injected with riluzole (10 mg/kg, i.p.), followed 10 min later by an acute dose of TETS (0.2 mg/kg in NIH Swiss; 0.3 mg/kg, i.p. in C57BL/6J) or an equal volume of vehicle (10% DMSO in 0.9% sterile saline). Different TETS doses were administered to trigger comparable seizure behavior between strains. Seizure behavior began within minutes of TETS exposure and rapidly progressed to SE that was terminated after 40 min by administration of midazolam (1.8 mg/kg, i.m.). The brains of vehicle and TETS-exposed mice were imaged using in vivo magnetic resonance (MR) and translocator protein (TSPO) positron emission tomography (PET) at 1, 3, 7, and 14 days post-exposure to monitor brain injury and neuroinflammation, respectively. When the brain scans of TETS mice were compared to those of vehicle controls, subtle and transient neuropathology was observed in both mouse strains, but more extensive and persistent TETS-induced neuropathology was observed in C57BL/6J mice. In addition, one NIH Swiss TETS mouse that did not respond to the midazolam therapy, but remained in SE for more than 2 h, displayed robust neuropathology as determined by in vivo imaging and confirmed by FluoroJade C staining and IBA-1 immunohistochemistry as readouts of neurodegeneration and neuroinflammation, respectively. These findings demonstrate that the extent of injury observed in the mouse brain after TETS-induced SE varied according to strain, dose of TETS and/or the duration of SE. These observations suggest that TETS-intoxicated humans who do not respond to antiseizure medication are at increased risk for brain injury.

Persistent neuropathology and behavioral deficits in a mouse model of status epilepticus induced by acute intoxication with diisopropylfluorophosphate.

Organophosphate (OP) nerve agents and pesticides are a class of neurotoxic compounds that can cause status epilepticus (SE), and death following acute high-dose exposures. While the standard of care for acute OP intoxication (atropine, oxime, and high-dose benzodiazepine) can prevent mortality, survivors of OP poisoning often experience long-term brain damage and cognitive deficits. Preclinical studies of acute OP intoxication have primarily used rat models to identify candidate medical countermeasures. However, the mouse offers the advantage of readily available knockout strains for mechanistic studies of acute and chronic consequences of OP-induced SE. Therefore, the main objective of this study was to determine whether a mouse model of acute diisopropylfluorophosphate (DFP) intoxication would produce acute and chronic neurotoxicity similar to that observed in rat models and humans following acute OP intoxication. Adult male C57BL/6J mice injected with DFP (9.5 mg/kg, s.c.) followed 1 min later with atropine sulfate (0.1 mg/kg, i.m.) and 2-pralidoxime (25 mg/kg, i.m.) developed behavioral and electrographic signs of SE within minutes that continued for at least 4 h. Acetylcholinesterase inhibition persisted for at least 3 d in the blood and 14 d in the brain of DFP mice relative to vehicle (VEH) controls. Immunohistochemical analyses revealed significant neurodegeneration and neuroinflammation in multiple brain regions at 1, 7, and 28 d post-exposure in the brains of DFP mice relative to VEH controls. Deficits in locomotor and home-cage behavior were observed in DFP mice at 28 d post-exposure. These findings demonstrate that this mouse model replicates many of the outcomes observed in rats and humans acutely intoxicated with OPs, suggesting the feasibility of using this model for mechanistic studies and therapeutic screening.

Combined Ultrasound and Photoacoustic Image Guidance of Spinal Pedicle Cannulation Demonstrated With Intact ex vivo Specimens.

OBJECTIVE: Spinal fusion surgeries require accurate placement of pedicle screws in anatomic corridors without breaching bone boundaries. We are developing a combined ultrasound and photoacoustic image guidance system to avoid pedicle screw misplacement and accidental bone breaches, which can lead to nerve damage. METHODS: Pedicle cannulation was performed on a human cadaver, with co-registered photoacoustic and ultrasound images acquired at various time points during the procedure. Bony landmarks obtained from coherence-based ultrasound images of lumbar vertebrae were registered to post-operative CT images. Registration methods were additionally tested on an ex vivo caprine vertebra. RESULTS: Locally weighted short-lag spatial coherence (LW-SLSC) ultrasound imaging enhanced the visualization of bony structures with generalized contrast-to-noise ratios (gCNRs) of 0.99 and 0.98-1.00 in the caprine and human vertebrae, respectively. Short-lag spatial coherence (SLSC) and amplitude-based delay-and-sum (DAS) ultrasound imaging generally produced lower gCNRs of 0.98 and 0.84, respectively, in the caprine vertebra and 0.84-0.93 and 0.34-0.99, respectively, in the human vertebrae. The mean ± standard deviation of the area of -6 dB contours created from DAS photoacoustic images acquired with an optical fiber inserted in prepared pedicle holes (i.e., fiber surrounded by cancellous bone) and holes created after intentional breaches (i.e., fiber exposed to cortical bone) was 10.06 ±5.22 mm 2 and 2.47 ±0.96 mm 2, respectively (p 0.01). CONCLUSIONS: Coherence-based LW-SLSC and SLSC beamforming improved visualization of bony anatomical landmarks for ultrasound-to-CT registration, while amplitude-based DAS beamforming successfully distinguished photoacoustic signals within the pedicle from less desirable signals characteristic of impending bone breaches. SIGNIFICANCE: These results are promising to improve visual registration of ultrasound and photoacoustic images with CT images, as well as to assist surgeons with identifying and avoiding impending bone breaches during pedicle cannulation in spinal fusion surgeries.

Acute administration of diazepam or midazolam minimally alters long-term neuropathological effects in the rat brain following acute intoxication with diisopropylfluorophosphate.

Acute intoxication with organophosphorus cholinesterase inhibitors (OPs) can trigger seizures that rapidly progress to life-threatening status epilepticus. Diazepam, long considered the standard of care for treating OP-induced seizures, is being replaced by midazolam. Whether midazolam is more effective than diazepam in mitigating the persistent effects of acute OP intoxication has not been rigorously evaluated. We compared the efficacy of diazepam vs. midazolam in preventing persistent neuropathology in adult male Sprague-Dawley rats acutely intoxicated with the OP diisopropylfluorophosphate (DFP). Subjects were administered pyridostigmine bromide (0.1 mg/kg, i.p.) 30 min prior to injection with DFP (4 mg/kg, s.c.) or vehicle (saline) followed 1 min later by atropine sulfate (2 mg/kg, i.m.) and pralidoxime (25 mg/kg, i.m.), and 40 min later by diazepam (5 mg/kg, i.p.), midazolam (0.73 mg/kg, i.m.), or vehicle. At 3 and 6 months post-exposure, neurodegeneration, reactive astrogliosis, microglial activation, and oxidative stress were assessed in multiple brain regions using quantitative immunohistochemistry. Brain mineralization was evaluated by in vivo micro-computed tomography (micro-CT). Acute DFP intoxication caused persistent neurodegeneration, neuroinflammation, and brain mineralization. Midazolam transiently mitigated neurodegeneration, and both benzodiazepines partially protected against reactive astrogliosis in a brain region-specific manner. Neither benzodiazepine attenuated microglial activation or brain mineralization. These findings indicate that neither benzodiazepine effectively protects against persistent neuropathological changes, and suggest that midazolam is not significantly better than diazepam. Overall, this study highlights the need for improved neuroprotective strategies for treating humans in the event of a chemical emergency involving OPs.

GPU implementation of photoacoustic short-lag spatial coherence imaging for improved image-guided interventions.

SIGNIFICANCE: Photoacoustic-based visual servoing is a promising technique for surgical tool tip tracking and automated visualization of photoacoustic targets during interventional procedures. However, one outstanding challenge has been the reliability of obtaining segmentations using low-energy light sources that operate within existing laser safety limits. AIM: We developed the first known graphical processing unit (GPU)-based real-time implementation of short-lag spatial coherence (SLSC) beamforming for photoacoustic imaging and applied this real-time algorithm to improve signal segmentation during photoacoustic-based visual servoing with low-energy lasers. APPROACH: A 1-mm-core-diameter optical fiber was inserted into ex vivo bovine tissue. Photoacoustic-based visual servoing was implemented as the fiber was manually displaced by a translation stage, which provided ground truth measurements of the fiber displacement. GPU-SLSC results were compared with a central processing unit (CPU)-SLSC approach and an amplitude-based delay-and-sum (DAS) beamforming approach. Performance was additionally evaluated with in vivo cardiac data. RESULTS: The GPU-SLSC implementation achieved frame rates up to 41.2 Hz, representing a factor of 348 speedup when compared with offline CPU-SLSC. In addition, GPU-SLSC successfully recovered low-energy signals (i.e., ≤268 µJ) with mean ± standard deviation of signal-to-noise ratios of 11.2 ± 2.4 (compared with 3.5 ± 0.8 with conventional DAS beamforming). When energies were lower than the safety limit for skin (i.e., 394.6 µJ for 900-nm wavelength laser light), the median and interquartile range (IQR) of visual servoing tracking errors obtained with GPU-SLSC were 0.64 and 0.52 mm, respectively (which were lower than the median and IQR obtained with DAS by 1.39 and 8.45 mm, respectively). GPU-SLSC additionally reduced the percentage of failed segmentations when applied to in vivo cardiac data. CONCLUSIONS: Results are promising for the use of low-energy, miniaturized lasers to perform GPU-SLSC photoacoustic-based visual servoing in the operating room with laser pulse repetition frequencies as high as 41.2 Hz.

Effects of early life exposure to traffic-related air pollution on brain development in juvenile Sprague-Dawley rats.

Epidemiological studies link traffic-related air pollution (TRAP) to increased risk for various neurodevelopmental disorders (NDDs); however, there are limited preclinical data demonstrating a causal relationship between TRAP and adverse neurodevelopmental outcomes. Moreover, much of the preclinical literature reports effects of concentrated ambient particles or diesel exhaust that do not recapitulate the complexity of real-world TRAP exposures. To assess the developmental neurotoxicity of more realistic TRAP exposures, we exposed male and female rats during gestation and early postnatal development to TRAP drawn directly from a traffic tunnel in Northern California and delivered to animals in real-time. We compared NDD-relevant neuropathological outcomes at postnatal days 51-55 in TRAP-exposed animals versus control subjects exposed to filtered air. As indicated by immunohistochemical analyses, TRAP significantly increased microglial infiltration in the CA1 hippocampus, but decreased astrogliosis in the dentate gyrus. TRAP exposure had no persistent effect on pro-inflammatory cytokine levels in the male or female brain, but did significantly elevate the anti-inflammatory cytokine IL-10 in females. In male rats, TRAP significantly increased hippocampal neurogenesis, while in females, TRAP increased granule cell layer width. TRAP had no effect on apoptosis in either sex. Magnetic resonance imaging revealed that TRAP-exposed females, but not males, also exhibited decreased lateral ventricular volume, which was correlated with increased granule cell layer width in the hippocampus in females. Collectively, these data indicate that exposure to real-world levels of TRAP during gestation and early postnatal development modulate neurodevelopment, corroborating epidemiological evidence of an association between TRAP exposure and increased risk of NDDs.

The chemical convulsant diisopropylfluorophosphate (DFP) causes persistent neuropathology in adult male rats independent of seizure activity.

Organophosphate (OP) threat agents can trigger seizures that progress to status epilepticus, resulting in persistent neuropathology and cognitive deficits in humans and preclinical models. However, it remains unclear whether patients who do not show overt seizure behavior develop neurological consequences. Therefore, this study compared two subpopulations of rats with a low versus high seizure response to diisopropylfluorophosphate (DFP) to evaluate whether acute OP intoxication causes persistent neuropathology in non-seizing individuals. Adult male Sprague Dawley rats administered DFP (4 mg/kg, sc), atropine sulfate (2 mg/kg, im), and pralidoxime (25 mg/kg, im) were monitored for seizure activity for 4 h post-exposure. Animals were separated into groups with low versus high seizure response based on behavioral criteria and electroencephalogram (EEG) recordings. Cholinesterase activity was evaluated by Ellman assay, and neuropathology was evaluated at 1, 2, 4, and 60 days post-exposure by Fluoro-Jade C (FJC) staining and micro-CT imaging. DFP significantly inhibited cholinesterase activity in the cortex, hippocampus, and amygdala to the same extent in low and high responders. FJC staining revealed significant neurodegeneration in DFP low responders albeit this response was delayed, less persistent, and decreased in magnitude compared to DFP high responders. Micro-CT scans at 60 days revealed extensive mineralization that was not significantly different between low versus high DFP responders. These findings highlight the importance of considering non-seizing patients for medical care in the event of acute OP intoxication. They also suggest that OP intoxication may induce neurological damage via seizure-independent mechanisms, which if identified, might provide insight into novel therapeutic targets.

Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain.

BACKGROUND: Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. METHODS: On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. RESULTS: Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. CONCLUSIONS: These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells.

Real-Time Crawling Wave Sonoelastography for Human Muscle Characterization: Initial Results.

Imaging of musculoskeletal tissue dynamics is currently an exploratory field with the goal of aiding rehabilitation and performance evaluation of pathological or asymptomatic patients. In this pilot study, initial elasticity assessments of the biceps brachii were conducted in a novel crawling wave sonoelastography (CWS) system implemented on a research ultrasound instrument with graphical processing unit capabilities, displaying quantitative elasticity values at 4 frames per second. The CWS system computes the tissue stiffness with the generation of an interference pattern from external vibrators, which can overcome depth limitations of imaging systems with internal excitation sources. Validation on gelatin-based phantoms reported low bias of elasticity values (4.7%) at low excitation frequencies. Preliminary results on in vivo muscle characterization are in accordance with average elasticity values for relaxed and contracted tissues found in the literature, as well as for a range of weight loads.

Developmental exposure to silver nanoparticles at environmentally relevant concentrations alters swimming behavior in zebrafish (Danio rerio).

Silver nanoparticles (Ag-NPs) are ubiquitous in household and medical products because of their antimicrobial activity. A consequence of the high volume of Ag-NP production and usage is increased amounts of Ag-NPs released into the environment. Their small size (1-100 nm) results in unique physiochemical properties that may increase toxicity relative to their bulk counterpart. Therefore, the goal of the present study was to assess the potential toxicity of environmentally relevant concentrations of Ag-NPs in zebrafish (Danio rerio). Wild-type tropical 5D zebrafish embryos were exposed to Ag-NPs from 4 to 120 h postfertilization at 0.03, 0.1, 0.3, 1, and 3 ppm (mg/L). Inductively coupled plasma-mass spectrometry confirmed concentration-dependent uptake of Ag into zebrafish as well as bioaccumulation over time. A morphological assessment revealed no significant hatching impairment, morphological abnormalities, or mortality at any concentration or time point examined. However, assessment of photomotor behavior at 3 d postfertilization (dpf) revealed significant hyperactivity in the 0.3, 1, and 3 ppm Ag-NP treatment groups. At 4 dpf, significant hyperactivity was observed only in the 3 ppm treatment group, whereas 5 dpf larvae exposed to Ag-NPs displayed no significant abnormalities in photomotor behavior. These findings suggest that nonteratogenic concentrations of Ag-NPs are capable of causing transient behavioral changes during development. Environ Toxicol Chem 2018;37:3018-3024. © 2018 SETAC.

Perinatal triphenyl phosphate exposure accelerates type 2 diabetes onset and increases adipose accumulation in UCD-type 2 diabetes mellitus rats.

Triphenyl phosphate (TPhP) is a flame retardant additive frequently found in consumer products and household dust. We administered 170µg of TPhP in maternal food from gestational day 8.5 to weaning and evaluated metabolic phenotypes of 3.5 month old male and female rats, and weight-matched males up to 6 months, to assess the development of obesity and type 2 diabetes mellitus (T2DM), respectively. Perinatal TPhP exposure increased body and fat mass in 3.5 month old male and female rats, while leptin and cumulative energy intake were elevated in males and females, respectively. Independent of body mass, perinatal TPhP exposure accelerated T2DM onset in males and increased plasma non-esterified- fasting fatty acids. These observations suggest that perinatal exposure to TPhP exacerbates the development of obesity in male and female UCDavis-T2DM rats and accelerates T2DM onset in male UCD-T2DM rats.

Pancreatitis aguda: etiología de 110 pacientes / Acute pancreatitis: etiology of 110 patients

Se hace una revisión de los factores causales de pancreatitis aguda en 110 casos, en el Hospital Provincial Docente "Manuel Ascunce Domenech", de Camagüey, en el período comprendido entre 1975 a 1983, ambos años inclusive, y se establece que la causa más importante de la enfermedad correspondió a los procesos de vías biliares, seguido de los factores idiopáticos y del alcoholismo. Se revisa la literatura de nuestro medio y comparan nuestros resultados con los otros autores

Pancreatitis aguda: etiología de 110 pacientes / Acute pancreatitis: etiology of 110 patients

Se hace una revisión de los factores causales de pancreatitis aguda en 110 casos, en el Hospital Provincial Docente "Manuel Ascunce Domenech", de Camagüey, en el período comprendido entre 1975 a 1983, ambos años inclusive, y se establece que la causa más importante de la enfermedad correspondió a los procesos de vías biliares, seguido de los factores idiopáticos y del alcoholismo. Se revisa la literatura de nuestro medio y comparan nuestros resultados con los otros autores (AU)