Mechanical strain to maxillary incisors during direct laryngoscopy.

BACKGROUND: While most Direct laryngoscopy leads to dental injury in 25-39% of cases. Dental injury occurs when the forces and impacts applied to the teeth exceed the ability of the structures to dissipate energy and stress. The purpose of this study was to measure strain, (which is the change produced in the length of the tooth by a force applied to the tooth) strain rate, and strain-time integral to the maxillary incisors and determine if they varied by experience, type of blade, or use of an alcohol protective pad (APP). METHODS: A mannequin head designed to teach and test intubation was instrumented with eight single axis strain gauges placed on the four maxillary incisors: four on the facial or front surface of the incisors and four on the lingual or back, near the insertion of the incisor in the gums to measure bending strain as well as compression. Anesthesiology faculty, residents, and certified registered nurse anesthetists intubated with Macintosh and Miller blades with and without APP. Using strain-time curves, the maximum strain, strain rate, and strain time integral were calculated. RESULTS: Across the 92 subjects, strain varied 8-12 fold between the 25th and 75th percentiles for all four techniques, but little by experience, while strain rate and strain integral varied 6-13 fold and 15-26 fold, respectively, for the same percentiles. Intubators who had high strain values with one blade tended to have high strains with the other blade with and without the APP (all pairwise correlation rho = 0.42-0.63). CONCLUSIONS: Strain varies widely by intubator and that the use of the APP reduces strain rate which may decrease the risk of or the severity of dental injury.

Predictive imaging of chemotherapeutic response in a transgenic mouse model of pancreatic cancer.

The underglycosylated mucin 1 tumor antigen (uMUC1) is a biomarker that forecasts the progression of adenocarcinomas. In this study, we evaluated the utility of a dual-modality molecular imaging approach based on targeting uMUC1 for monitoring chemotherapeutic response in a transgenic murine model of pancreatic cancer (KCM triple transgenic mice). An uMUC1-specific contrast agent (MN-EPPT) was synthesized for use with magnetic resonance imaging (MRI) and fluorescence optical imaging. It consisted of dextran-coated iron oxide nanoparticles conjugated to the near infrared fluorescent dye Cy5.5 and to a uMUC1-specific peptide (EPPT). KCM triple transgenic mice were given gemcitabine as chemotherapy while control animals received saline injections following the same schedule. Changes in uMUC1 levels following chemotherapy were monitored using T2-weighted MRI and optical imaging before and 24 hr after injection of the MN-EPPT. uMUC1 expression in tumors from both groups was evaluated by histology and qRT-PCR. We observed that the average delta-T2 in the gemcitabine-treated group was significantly reduced compared to the control group indicating lower accumulation of MN-EPPT, and correspondingly, a lower level of uMUC1 expression. In vivo optical imaging confirmed the MRI findings. Fluorescence microscopy of pancreatic tumor sections showed a lower level of uMUC1 expression in the gemcitabine-treated group compared to the control, which was confirmed by qRT-PCR. Our data proved that changes in uMUC1 expression after gemcitabine chemotherapy could be evaluated using MN-EPPT-enhanced in vivo MR and optical imaging. These results suggest that the uMUC1-targeted imaging approach could provide a useful tool for the predictive assessment of therapeutic response.

Factor VIII and Incident Hypertension in Black and White Adults: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort.

BACKGROUND: Nearly half of all Americans have hypertension, and Black adults experience a disproportionate burden. Hypercoagulability may relate to hypertension risk, and higher levels of factor VIII increase thrombosis risk. Black adults have higher factor VIII and more hypertension than other groups. Whether higher factor VIII associates with incident hypertension is unknown. METHODS: The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) study measured certain biomarkers in a sex-race stratified sample of 4,400 REGARDS participants who attended both visits. We included BioMedioR participants, excluding those with prevalent hypertension, missing factor VIII level, or covariates of interest. Modified Poisson regression estimated risk ratios (RR) for incident hypertension by higher log-transformed factor VIII level per SD (SD of log-transformed factor VIII, 0.33). Weighting was applied to take advantage of REGARDS sampling design. RESULTS: Among the 1,814 participants included (55% female, 24% Black race), the median follow-up was 9.5 years and 35% (2,146/6,138) developed hypertension. Black participants had a higher median (IQR) factor VIII level (105.6%; 87.1%-126.9%) than White participants (95.6%; 79.8%-115.9%; P < 0.001). The age- and sex-adjusted Black-White hypertension RR was 1.45 (95% CI 1.28, 1.63). Higher factor VIII was not associated with more hypertension (final model RR 1.01; 95% CI 0.94, 1.07). CONCLUSIONS: In a prospective study of Black and White adults without prevalent hypertension, factor VIII was not associated with greater hypertension risk.

Psychiatric symptoms in children with low-grade glioma and craniopharyngioma: A systematic review.

The presentation of psychiatric symptoms in pediatric low-grade brain tumors is challenging because this can delay proper diagnosis and treatment. We performed a systematic review of psychiatric presenting symptoms of low-grade brain tumors in pediatric patients. We searched the PubMed and Web of Science databases of studies published in English from 1977 until 2019 reporting patients aged ≤21 years at the time of tumor diagnosis who exhibited psychiatric/behavioral symptoms before diagnosis of low-grade glioma (LGG), pilocytic astrocytoma (PA), or craniopharyngioma (CP). Our systematic search strategy coupled each tumor type with patient age and presenting symptoms by using different variations of the search terms "childhood" and "psychiatric symptoms" or "behavioral symptoms." We identified six unique articles that met our inclusion criteria in the LGG search, 27 in the PA search, and 32 in the CP search. Six patients were included in the LGG articles (age range, 3-16 years), 75 in the PA articles (age range, 0.5-21 years), and 87 in the CP articles (age range, 0.67-21 years). The most common presenting symptoms included eating disorders (n = 64) and behavioral changes (n = 49). Our findings demonstrate the need to establish clear criteria for neuroimaging indications for pediatric patients exhibiting eating disorders.

Alternating and Concurrent True Hyperkalemia and Pseudohyperkalemia in Adult Sickle Cell Disease.

Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients, and renal manifestations of SCN include renal ischemia, microinfarcts, renal papillary necrosis, and renal tubular abnormalities with variable clinical presentations. Intravascular hemolysis and reduced glomerular filtration rate with renal tubular dysfunction predispose to true hyperkalemia. Hemolytic crisis can be complicated by sepsis, leading to significant degrees of thrombocytosis, and thrombocytosis is a well-defined cause of pseudohyperkalemia. We describe a 40-year-old African American male patient with sickle cell anemia who exhibited alternating episodes of true hyperkalemia and pseudohyperkalemia, during consecutive hospital admissions. Clearly, true hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate and intensive treatment of pseudohyperkalemia leading to severe hypokalemia is also potentially lethal. The need for this caution is most imperative with the recent introduction of the safer and more potent potassium binders, patiromer and sodium zirconium cyclosilicate.

Toward a More Comprehensive Assessment of School Age Children with Hemiplegic Cerebral Palsy.

BACKGROUND: Cerebral palsy (CP) is the leading cause of disability in children. While motor deficits define CP, many patients experience behavioral and cognitive deficits which limit participation. The purpose of this study was to contribute to our understanding of developmental delay and how to measure these deficits among children with CP. METHODS: Children 5 to 15 years with hemiplegic CP were recruited. Cognition and motor ability were assessed. The brain injury associated with observed motor deficits was identified. Accelerometers measured real-world bilateral upper extremity movement and caregivers completed behavioral assessments. RESULTS: Eleven children participated, 6 with presumed perinatal stroke. Four children scored below average intelligence quotient while other measures of cognition were within normal limits (except processing speed). Motor scores confirmed asymmetrical deficits. Approximately one third of scores indicated deficits in attention, behavior, or depression. CONCLUSIONS: Our findings corroborate that children with CP experience challenges that are broader than motor impairment alone. Despite the variation in brain injury, all participants completed study procedures. IMPLICATIONS: Our findings suggest that measuring behavior in children with CP may require a more comprehensive approach and that caregivers are amenable to using online collection tools which may assist in addressing the therapeutic needs of children with CP.

Peptide-based urinary monitoring of fibrotic nonalcoholic steatohepatitis by mass-barcoded activity-based sensors.

Noninvasive detection of nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease, promises to improve patient screening, accelerate drug trials, and reduce health care costs. On the basis of protease dysregulation of the biological pathways of fibrotic NASH, we developed the Glympse Bio Test System (GBTS) for multiplexed quantification of liver protease activity. GBTS-NASH comprises a mixture of 19 mass-barcoded PEGylated peptides that is administered intravenously and senses liver protease activity by releasing mass-barcoded reporters into urine for analysis by mass spectrometry. To identify a protease signature of NASH, transcriptomic analysis of 355 human liver biopsies identified a 13-protease panel that discriminated clinically relevant NASH ≥F2 fibrosis from F0-F1 with high classification accuracy across two independent patient datasets. We screened 159 candidate substrates to identify a panel of 19 peptides that exhibited high activity for our 13-protease panel. In the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) mouse model, binary classifiers trained on urine samples discriminated fibrotic NASH from simple steatosis and healthy controls across a range of nondisease conditions and indicated disease regression upon diet change [area under receiver operating characteristics (AUROCs) > 0.97]. Using a hepatoprotective triple combination treatment (FXR agonist, ACC and ASK1 inhibitors) in a rat model of NASH, urinary classification distinguished F0-F1 from ≥F2 animals and indicated therapeutic response as early as 1 week on treatment (AUROCs >0.91). Our results support GBTS-NASH to diagnose fibrotic NASH via an infusion of peptides, monitor changes in disease severity, and indicate early treatment response.

Abusive Pediatric Thoracolumbar Fracture Due to Forced Hyperextension: Case Report, Biomechanical Considerations, and Review of the Literature.

Pediatric thoracolumbar fractures are rare due to the physiological differences which afford greater resilience to the immature spine. Most pediatric thoracolumbar fractures occur as the result of high energy trauma, such as motor vehicle accidents, and modes of reasonable accidental injuries are limited by age and developmental capabilities of the child. These fractures can occur as the result of inflicted blunt force trauma and child abuse, and in most cases, the mechanism of injury to the spine is not known. We report the death of a 29-month-old man due to blunt force trauma to the back and forced hyperextension of the thoracolumbar spine causing fracture of the fourth lumbar (L4) vertebral body. A complete forensic examination revealed a previous healing fracture of the anterior aspect of the L4 vertebral body, with acute disruption of the anterior longitudinal ligament overlying the fracture site, complete fracture of the vertebral body, and fatal retroperitoneal hemorrhage. We present a review of the biomechanical considerations of the pediatric spine, a survey of pediatric spinal fractures, and a review of the literature on pediatric abusive thoracolumbar fractures. In this case, there was never a provided explanation for how the injury occurred; however, understanding the biomechanics of the pediatric spine allowed for the determination of the mechanism, force required to produce this specific pattern of abusive spinal injury, and the manner of death.

Using accelerometry for measurement of motor behavior in children: Relationship of real-world movement to standardized evaluation.

BACKGROUND: When detected, children with asymmetrical motor impairment are referred for therapeutic interventions to maximize the child's ability to reach their health and developmental potential. Referal is dependent on standardized evaluation, which rarely examines upper extremity (UE) function within the context of real-world activity. Accelerometry provides an efficient method to objectively measure movement in children. The purpose of this study was to compare accelerometry to clinical assessment, specifically the Melbourne Assessment of Unilateral Upper Limb Function-2 (MA-2). METHODS: A total of 52 children between 1-17 years of age with asymmetrical motor deficits and age matched controls participated in this study. Participants wore bilateral accelerometers for 4 x 25 h. The use ratio (UR) and mono-arm use index (MAUI) were calculated to quantify asymmetrical impairment. The Melbourne Assessment of Unilateral Upper Limb Function-2 (MA-2) was administered and compared to accelerometry variables. RESULTS: The UR and MAUI were significantly different in children with and without deficits. The MAUI was significantly correlated with all domains of the MA-2: accuracy (r = 0.44, p = 0.026); fluency (r = 0.52, p = 0.006); dexterity (r = 0.53, p = 0.005); and range of motion (r = 0.49, p = 0.011). CONCLUSIONS: Our findings suggest a relationship between real-world movement and clinical evaluation.

Providing experiential information on early medical abortion: a qualitative evaluation of an animated personal account, Lara's Story.

BACKGROUND: An animated film has been created to provide information to women requesting early medical abortion (EMA). The 9 min film, Lara's Story, was created using one woman's personal account of her experience. This study evaluated the views of women who had recently undergone EMA on the film and its potential usefulness in providing experiential information to women requesting EMA. METHOD: Women who had undergone EMA within the past month were recruited. They were shown the film and interviewed in a semi-structured style. Interviews were recorded and transcribed verbatim. They were analysed using cross-sectional indexing and thematic analysis with an inductive approach. RESULTS: 13 women were interviewed. All reported that the film gave a realistic account of EMA and most agreed that they would have wanted to watch it before EMA had it been available. Some said that it might help women who were struggling with decision-making with regard to EMA and all said that there should be unrestricted access to the film from the website of the abortion service. The women commented that the animated style of the film allowed all groups of women to relate to the story. Some commented that Lara's experience of pain, bleeding and side effects such as nausea differed from their own and therefore felt that it would be useful to make more than one woman's account available. CONCLUSION: The availability of animated audiovisual films recounting women's experiences of EMA might be a valuable adjunct to clinical information for women seeking EMA.

The Interaction of Intramuscular Ketorolac (Toradol) and Concussion in a Rat Model.

The purpose of this study was to examine the interaction of a single dose of Toradol and head impact in an in vivo rat model for sport-related concussion using a validated rat concussion model. Thirty-five Sprague-Dawley rats were placed into one of four groups: (1) Control, (2) Impact Only, (3) Toradol Only, (4) Impact and Toradol. Animals in the impact groups were subjected to a single head impact. Animals in the Toradol group received a single intramuscular injection of Toradol prior to impact. We examined magnetic resonance imaging, serum S100-B and cognitive function using a Morris Water Maze. In the control group, latency decreased significantly from day 0 (74.9 s) to 24 h (57.4 s) after anesthesia. There was no statistically significant difference between time zero and 24 h after impact in the Impact only or Impact and Toradol group. Our findings indicate that there were no differences between cognitive ability, MRI findings or S100B in rats that were administered a single dose of Toradol and subjected to a single impact and rats that were subjected to a single impact only. In both impact groups there were transient changes in cognitive ability as measured by the Morris Water Maze.

Validity and sensitivity of 6 pain scales in critically ill, intubated adults.

BACKGROUND: Self-report is the best indicator of pain; however, pain is more difficult to assess in noncommunicative patients who may be receiving mechanical ventilation or sedated and unable to report pain. OBJECTIVES: To evaluate the validity and sensitivity of 6 pain scales (Adult Nonverbal Pain Scale; Behavior Pain Scale [BPS]; Comfort Scale; FACES; Face, Legs, Activity, Cry, and Consolability scale; Pain Assessment Behavioral Scale with Numeric Rating Scale [NRP]) to identify the best measure of pain in noncommunicative patients. METHODS: Fifty communicative and 100 noncommunicative patients receiving mechanical ventilation were observed before and during routine physical examination and endotracheal tube suctioning. RESULTS: All pain scales had moderate to high correlations with the patient's self-report during suctioning. The FACES score reported by the patient had the highest correlation with the patient's NRP score (r = 0.76, P < .001) during suctioning; associations between the BPS and NRP scores during physical examination were the weakest (r = 0.21, P = .20). All scales were sensitive in capturing the patient's pain response in all phases (P < .001); sensitivity was higher during suctioning (P < .001). Both participants and investigators rated pain higher on the FACES scale. CONCLUSIONS: These pain scales commonly used in noncommunicative critically ill adult patients are valid and sensitive for capturing changes in pain response during suctioning in both communicative and noncommunicative patients. However, caution must be used when using the FACES scale because subjectivity may lead to overtreatment or undertreatment of pain.