Epinephrine Dosing Use During Extracorporeal Cardiopulmonary Resuscitation: Single-Center Retrospective Cohort.

OBJECTIVES: During pediatric cardiac arrest, contemporary guidelines recommend dosing epinephrine at regular intervals, including in patients requiring extracorporeal membrane oxygenation (ECMO). The impact of epinephrine-induced vasoconstriction on systemic afterload and venoarterial ECMO support is not well-defined. DESIGN: Nested retrospective observational study within a single center. The primary exposure was time from last dose of epinephrine to initiation of ECMO flow; secondary exposures included cumulative epinephrine dose and arrest time. Systemic afterload was assessed by mean arterial pressure and use of systemic vasodilator therapy; ECMO pump flow and Vasoactive-Inotrope Score (VIS) were used as measures of ECMO support. Clearance of lactate was followed post-cannulation as a marker of systemic perfusion. SETTING: PICU and cardiac ICU in a quaternary-care center. PATIENTS: Patients 0-18 years old who required ECMO cannulation during resuscitation over the 6 years, 2014-2020. Patients were excluded if ECMO was initiated before cardiac arrest or if the resuscitation record was incomplete. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 92 events in 87 patients, with 69 events having complete data for analysis. The median (interquartile range) of total epinephrine dosing was 65 mcg/kg (37-101 mcg/kg), with the last dose given 6 minutes (2-16 min) before the initiation of ECMO flows. Shorter interval between last epinephrine dose and ECMO initiation was associated with increased use of vasodilators within 6 hours of ECMO ( p = 0.05), but not with mean arterial pressure after 1 hour of support (estimate, -0.34; p = 0.06). No other associations were identified between epinephrine delivery and mean arterial blood pressure, vasodilator use, pump speed, VIS, or lactate clearance. CONCLUSIONS: There is limited evidence to support the idea that regular dosing of epinephrine during cardiac arrest is associated with increased in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

High-Frequency Oscillatory Ventilation in Pediatric Acute Lung Injury: A Multicenter International Experience.

OBJECTIVE: We aim to describe current clinical practice, the past decade of experience and factors related to improved outcomes for pediatric patients receiving high-frequency oscillatory ventilation. We have also modeled predictive factors that could help stratify mortality risk and guide future high-frequency oscillatory ventilation practice. DESIGN: Multicenter retrospective, observational questionnaire study. SETTING: Seven PICUs. PATIENTS: Demographic, disease factor, and ventilatory and outcome data were collected, and 328 patients from 2009 to 2010 were included in this analysis. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Patients were classified into six cohorts based on underlying diagnosis. We used univariate analysis to identify factors associated with mortality risk and multivariate logistic regression to identify independent predictors of mortality risk. An oxygenation index greater than 35 and immunocompromise exhibited the greatest predictive power (p < 0.0001) for increased mortality risk, and respiratory syncytial virus was associated with lowest mortality risk (p = 0.003). Differences in mortality risk as a function of oxygenation index were highly dependent on primary underlying condition. A trend toward an increase in oscillator amplitude and frequency was observed when compared with historical data. CONCLUSIONS: Given the number of centers and subjects included in the database, these findings provide a robust description of current practice regarding the use of high-frequency oscillatory ventilation for pediatric hypoxic respiratory failure. Patients with severe hypoxic respiratory failure and immunocompromise had the highest mortality risk, and those with respiratory syncytial virus had the lowest. A means of identifying the risk of 30-day mortality for subjects can be obtained by identifying the underlying disease and oxygenation index on conventional ventilation preceding the initiation of high-frequency oscillatory ventilation.

Airway opening pressure maneuver to detect airway closure in mechanically ventilated pediatric patients.

Background: Airway closure, which refers to the complete collapse of the airway, has been described under mechanical ventilation during anesthesia and more recently in adult patients with acute respiratory distress syndrome (ARDS). A ventilator maneuver can be used to identify airway closure and measure the pressure required for the airway to reopen, known as the airway opening pressure (AOP). Without that maneuver, AOP is unknown to clinicians. Objective: This study aims to demonstrate the technical adaptation of the adult maneuver for children and illustrate its application in two cases of pediatric ARDS (p-ARDS). Methods: A bench study was performed to adapt the maneuver for 3-50 kg patients. Four maneuvers were performed for each simulated patient, with 1, 2, 3, and 4 s of insufflation time to deliver a tidal volume (Vt) of 6 ml/kg by a continuous flow. Results: Airway closure was simulated, and AOP was visible at 15 cmH2O with a clear inflection point, except for the 3 kg simulated patient. Regarding insufflation time, a 4 s maneuver exhibited a better performance in 30 and 50 kg simulated patients since shorter insufflation times had excessive flowrates (>10 L/min). Below 20 kg, the difference in resistive pressure between a 3 s and a 4 sec maneuver was negligible; therefore, prolonging the maneuver beyond 3 s was not useful. Airway closure was identified in two p-ARDS patients, with the pediatric maneuver being employed in the 28 kg patient. Conclusions: We propose a pediatric AOP maneuver delivering 6 ml/kg of Vt at a continuous low-flow inflation for 3 s for patients weighing up to 20 kg and for 4 s for patients weighing beyond 20 kg.

Early diagnosis of COPD: myth or a true perspective.

The early stages of COPD have recently become a hot topic as many new risk factors have been proposed, but substantial knowledge gaps remain in explaining the natural history of the disease. If we are to modify the outcomes of COPD, early detection needs to play a critical role. However, we need to sort out the barriers to early detection and have a better understanding of the definition of COPD and its diagnosis and therapeutic strategies to identify and treat patients with COPD before structural changes progress. In this review, we aim to clarify the differences between early COPD, mild COPD and early detection of COPD, with an emphasis on the clinical burden and how different outcomes (quality of life, exacerbation, cost and mortality) are modified depending on which definition is used. We will summarise the evidence for the new multidimensional diagnostic approaches to detecting early pathophysiologic changes that potentially allow for future studies on COPD management strategies to halt or prevent disease development.

Investigation into using resonant frequency measurements to predict the mechanical properties of Ti-6Al-4V manufactured by selective laser melting.

There is a need to qualify additively manufactured parts that are used in highly regulated industries such as aerospace and nuclear power. This paper investigates the use of resonant ultrasound measurements to predict the mechanical properties of Ti-6Al-4V manufactured by selective laser melting using a Renishaw AM 250. It is first demonstrated why R2 should not be used to assess the predictive capability of a model, before introducing a method for calculating predicted R2, which is then used to assess the models. It is found that a linear model with the resonant frequency peaks as predictors cannot be used to predict elongation at failure or reduction in area. However, linear models did demonstrate better predictive capabilities for Young's modulus, yield strength, and especially ultimate tensile strength.

Short-term leptin treatment increases fatty acids uptake and oxidation in muscle of high fat-fed rats.

The purpose of this study was to measure the effects of short-term (10 days) leptin treatment on insulin sensitivity as it pertains to fatty acid (FA) uptake, oxidation, and muscle triglyceride (mTG) synthesis in animals that have been administered a high-fat (HF) diet for 3 months. Male Wistar rats were randomly assigned to 1 of 4 groups. One group was fed a control diet (CON) and 3 groups were fed a HF diet. The HF and HF-leptin (HF-LEP) groups were fed the HF diet ad libitum and the amount of food eaten by the HF-pair fed (HF-P) group was equal to that of the HF-LEP group. At the end of the dietary period, rats were injected daily either with saline (CON, HF, HF-P) or with leptin (HF-LEP; 10 mg.kg-1.d-1) for 10 days before hindlimb perfusion. The perfusate contained 600 micromol/L palmitate traced with [14C]palmitate, 9 mmol/L glucose, and 100 microU/mL insulin. As dictated by the protocol, energy expenditure was not significantly different (P>.05) between HF-LEP and HF-P. Palmitate uptake and oxidation as well as mTG synthesis were greater (P<.05) in HF (9.8+/-0.3, 2.0+/-0.1, and 1.9+/-0.2 nmol.min-1.g-1) than in CON (8.0+/-0.4, 1.4+/-0.1, and 1.1+/-0.1 nmol.min-1.g-1) and this was associated with higher levels of mTG in HF. Palmitate uptake and oxidation were higher (P<.05) in HF-LEP (10.3+/-0.6 and 2.0+/-0.1 nmol.min-1.g-1) than in HF-P (8.3+/-0.5 and 1.5+/-0.2 nmol.min-1.g-1, P<.05), but mTG synthesis and mTG levels were not changed significantly by leptin treatment (P>.05). High-fat feeding decreased glucose uptake by 41% when compared with CON (2.4+/-0.4 vs 4.1+/-0.4 micromol.h-1.g-1; P<.05) but pair feeding alone (4.7+/-0.4 micromol.h-1.g-1) or leptin treatment (3.8+/-0.3 micromol.h-1.g-1) similarly prevented the HF diet-induced decrease in glucose uptake. These data indicate that short-term leptin treatment in HF-fed rats alters muscle FA metabolism by increasing FA uptake and oxidation relative to pair feeding alone. This results in a decrease in the FA esterification-oxidation ratio.

A Multidisciplinary Biospecimen Bank of Renal Cell Carcinomas Compatible with Discovery Platforms at Mayo Clinic, Scottsdale, Arizona.

To address the need to study frozen clinical specimens using next-generation RNA, DNA, chromatin immunoprecipitation (ChIP) sequencing and protein analyses, we developed a biobank work flow to prospectively collect biospecimens from patients with renal cell carcinoma (RCC). We describe our standard operating procedures and work flow to annotate pathologic results and clinical outcomes. We report quality control outcomes and nucleic acid yields of our RCC submissions (N=16) to The Cancer Genome Atlas (TCGA) project, as well as newer discovery platforms, by describing mass spectrometry analysis of albumin oxidation in plasma and 6 ChIP sequencing libraries generated from nephrectomy specimens after histone H3 lysine 36 trimethylation (H3K36me3) immunoprecipitation. From June 1, 2010, through January 1, 2013, we enrolled 328 patients with RCC. Our mean (SD) TCGA RNA integrity numbers (RINs) were 8.1 (0.8) for papillary RCC, with a 12.5% overall rate of sample disqualification for RIN <7. Banked plasma had significantly less albumin oxidation (by mass spectrometry analysis) than plasma kept at 25 °C (P<.001). For ChIP sequencing, the FastQC score for average read quality was at least 30 for 91% to 95% of paired-end reads. In parallel, we analyzed frozen tissue by RNA sequencing; after genome alignment, only 0.2% to 0.4% of total reads failed the default quality check steps of Bowtie2, which was comparable to the disqualification ratio (0.1%) of the 786-O RCC cell line that was prepared under optimal RNA isolation conditions. The overall correlation coefficients for gene expression between Mayo Clinic vs TCGA tissues ranged from 0.75 to 0.82. These data support the generation of high-quality nucleic acids for genomic analyses from banked RCC. Importantly, the protocol does not interfere with routine clinical care. Collections over defined time points during disease treatment further enhance collaborative efforts to integrate genomic information with outcomes.

Spontaneous human speech mimicry by a cetacean.

Although dolphins (Tursiops truncatus) have been trained to match numbers and durations of human vocal bursts and reported to spontaneously match computer-generated whistles, spontaneous human voice mimicry has not previously been demonstrated. The first to study white whale (Delphinapterus leucas) sounds in the wild, Schevill and Lawrence wrote that "occasionally the calls would suggest a crowd of children shouting in the distance". Fish and Mowbary described sound types and reviewed past descriptions of sounds from this vociferous species. At Vancouver Aquarium, Canada, keepers suggested that a white whale about 15 years of age, uttered his name "Lagosi". Other utterances were not perceptible, being described as "garbled human voice, or Russian, or similar to Chinese" by R.L. Eaton in a self-published account in 1979. However, hitherto no acoustic recordings have shown how such sounds emulate speech and deviate from the usual calls of the species. We report here sound recordings and analysis which demonstrate spontaneous mimicry of the human voice, presumably a result of vocal learning, by a white whale.

Pneumonia hospitalization in Brazil from 2003 to 2007.

OBJECTIVES: In emerging countries, pneumonia is a leading cause of hospitalization and death, particularly among the youngest and oldest. This retrospective study aimed to quantify the incidence of hospitalization due to all-cause pneumonia (HDTP) and in-hospital case fatality rates (CFRs) in all age groups, in five administrative regions of Brazil. METHODS: The International Classification of Diseases Tenth Revision coding for pneumonia (J12-J18) and an interactive web-based database of individuals covered by the Unified Health System in Brazil who were hospitalized from 2003 to 2007, were used to identify cases. In-hospital CFRs were the percentage of hospitalized cases that died. RESULTS: The overall HDTP incidence per 100,000 people of all ages decreased from 451 in 2003 to 388 in 2007. When categorized by age group, the HDTP incidence was lowest for those aged 5-49 years, and highest in children aged ≤4 years and adults aged ≥50 years. The in-hospital CFR increased from 2.89% in 2003 to 4.02% in 2007. Regional differences in HDTP incidence rates and in-hospital CFR were observed from 2003 to 2007. CONCLUSIONS: As expected, the highest HDTP rates were observed in the very young and the elderly. Regional differences in hospitalization incidence rates and in-hospital CFRs were observed.

Dolphins maintain cognitive performance during 72 to 120 hours of continuous auditory vigilance.

The present study reports the first use of a choice visual-vocal response time cognitive task, during 72 or 120 h of continuous auditory vigilance. Two adult bottlenose dolphins (Tursiops truncatus), NAY (male) and SAY (female), maintained a very high detection rate (91.1-98.7%) of random 1.5 s goal tones infrequently substituted in a background of frequent 0.5 s equal-amplitude tones over continuous 72 or 120 h sessions. In addition, a choice visual-vocal response time task (CVVRT) tested cognitive performance during night time sessions, when the dolphins would have ordinarily been resting or asleep as we had observed in previous studies. NAY and SAY detected a single-bar, posterior, vertical, green (S1g) or 3-bar, anterior, horizontal, red (S2r) LED light stimulus presented randomly to each eye. They responded with a different vocalization (whistle or pulse burst) to each stimulus (S1g or S2r) presented randomly to left and right eyes. The animals maintained high levels of goal tone detection without signs of sleep deprivation as indicated by behavior, blood indices or marked sleep rebound during 24 h of continuous post-experiment observation. Acoustic goal tone response time (AGTRT) overall did not change during the 72 h (F=0.528, P=0.655) or 120 h (F=0.384, P=0.816) sessions. Nor did CVVRT slow or degrade over the 72 h (F=4.188, P=0.104) or 120 h (F=2.298, P=0.119) AGTRT sessions.

Microsatellites from Lysiphlebus hirticornis Mackauer (Hymenoptera: Braconidae), a specialist primary parasitoid attacking the specialist tansy aphid, Metopeurum fuscoviride Stroyan (Hemiptera: Aphididae).

Nine polymorphic microsatellite loci were isolated from the specialist aphid parasitoid, Lysiphlebus hirticornis. In addition, two published loci from closely related Lysiphlebus species were also used. Allelic diversity and heterozygosity were quantified in samples collected from eight tansy plants growing in an area of approximately 150 m(2) in Jena, Germany.

Thiazolidinediones enhance skeletal muscle triacylglycerol synthesis while protecting against fatty acid-induced inflammation and insulin resistance.

In the present investigation, we studied the effects of thiazolidinedione (TZD) treatment on insulin-stimulated fatty acid (FA) and glucose kinetics in perfused muscle from high-fat (HF)-fed rats. We tested the hypothesis that TZDs prevent FA-induced insulin resistance by attenuating proinflammatory signaling independently of myocellular lipid levels. Male Wistar rats were assigned to one of three 3-wk dietary groups: control chow fed (CON), 65% HF diet (HFD), or TZD- (troglitazone or rosiglitazone) enriched HF diet (TZD + HFD). TZD treatment led to a significant increase in plasma membrane content of CD36 protein in muscle (red: P = 0.01, and white: P = 0.001) that correlated with increased FA uptake (45%, P = 0.002) and triacylglycerol (TG) synthesis (46%, P = 0.03) during the perfusion. Importantly, whereas HF feeding caused increased basal TG (P = 0.047), diacylglycerol (P = 0.002), and ceramide (P = 0.01) levels, TZD treatment only prevented the increase in muscle ceramide. In contrast, all of the muscle inflammatory markers altered by HF feeding ( upward arrowNIK protein content, P = 0.009; upward arrowIKKbeta activity, P = 0.006; downward arrowIkappaB-alpha protein, P = 0.03; and upward arrowJNK phosphorylation, P = 0.003) were completely normalized by TZD treatment. Consistent with this, HFD-induced decrements in insulin action were also prevented by TZD treatment. Thus our findings support the notion that TZD treatment causes increased FA uptake and TG accumulation in skeletal muscle under insulin-stimulated conditions. Despite this, TZDs suppress the inflammatory response to dietary lipid overload, and it is this mechanism that correlates strongly with insulin sensitivity.

Can the MMPI-2 discriminate between mild-moderate TBI and other neurologic and psychiatric populations?

MMPI-2 maintains an extensive empirical base with psychiatric populations, although more recently, neurologically compromised patients have documented unique elevation patterns. This study examined mild-moderate TBI patients, Alzheimer's Dementia patients, and Psychiatric controls on MMPI-2 scales. Participants included 160 outpatients (TBI n = 26, AD n = 74, Psychiatric n = 60). Controlling for family-wise-error, five ANCOVAs were conducted on five MMPI-2 scales, correcting for age and education. TBI and Psychiatric group means were significantly higher than AD group means for scales Hypochondriasis, Depression, and Hysteria at an alpha of .01. Results support previous research with mild TBI patients, and further document a unique pattern of elevations in this population.

Dolphin continuous auditory vigilance for five days.

The present report describes the first study of continuous vigilance in dolphins. Two adult bottlenose dolphins (Tursiops truncatus), WEN (male) and SAY (female), maintained a very high detection rate of randomly presented, infrequent, 1.5-s target tones in a background of frequent 0.5-s equal-amplitude tones over five continuous 120-h sessions. The animals were able to maintain high levels (WEN 97, 87, 99%; SAY 93, 96%) of target detection without signs of sleep deprivation as indicated by behavior, blood indices or marked sleep rebound during 24 h of continuous post-experiment observation. Target response time overall (F = 0.384; P = 0.816) did not change between day 1 and day 5. However, response time was significantly slower (F = 21.566, P = 0.019) during the night (21.00-04.00 h) when the dolphins would have ordinarily been resting or asleep.

Differential performance of Alzheimer's and vascular dementia patients on a brief battery of neuropsychological tests.

The purpose of this article was to examine the differences in neuropsychological test performance between groups with Alzheimer's and vascular dementia. Patients included in this study were those diagnosed with Alzheimer's Disease (AD) or Vascular Dementia (VAD) through a series of neuroradiological tests that included at a minimum a CT or MRI scan and a SPECT scan. Of the 113 AD patients, the average age was 80.08 (SD = 5.91) years and average education was 12.85 (SD = 2.88). Of the 109 VAD patients, average age was 78.67 (SD = 5.35) and average education was 13.10 (SD = 2.65). Tests included selected subtests of the WAIS-R, Word Fluency, Rey Figure, Boston Naming Test, Math, Reading, and subtests from the WMS-R. Five tests showed significant differences in favor of the VAD group: Information, Similarities, Picture Completion, WRAT Mathematics, and the Boston Naming Test. Both groups did well on Reading, while both did poorly on the Rey and Word Fluency. Although both groups did poorly on memory measures, the VAD patients showed better performance. Overall, the two groups did not differ significantly on the more complex tests, but did differ on more basic tests and all the memory tests. This pattern of similar score on complex tests and different scores on basic tests demonstrates the theory that both types of dementia affected higher, more complex skills. Differences between the groups were only apparent when basic skills were compared and were not reflected in more complex and neuropsychologically "sensitive" tests.

AMPK activation is not critical in the regulation of muscle FA uptake and oxidation during low-intensity muscle contraction.

To determine the role of AMP-activated protein kinase (AMPK) activation on the regulation of fatty acid (FA) uptake and oxidation, we perfused rat hindquarters with 6 mM glucose, 10 microU/ml insulin, 550 microM palmitate, and [14C]palmitate during rest (R) or electrical stimulation (ES), inducing low-intensity (0.1 Hz) muscle contraction either with or without 2 mM 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR). AICAR treatment significantly increased glucose and FA uptake during R (P < 0.05) but had no effect on either variable during ES (P > 0.05). AICAR treatment significantly increased total FA oxidation (P < 0.05) during both R (0.38 +/- 0.11 vs. 0.89 +/- 0.1 nmol x min(-1) x g(-1)) and ES (0.73 +/- 0.11 vs. 2.01 +/- 0.1 nmol x min(-1) x g(-1)), which was paralleled in both conditions by a significant increase and significant decrease in AMPK and acetyl-CoA carboxylase (ACC) activity, respectively (P < 0.05). Low-intensity muscle contraction increased glucose uptake, FA uptake, and total FA oxidation (P < 0.05) despite no change in AMPK (950.5 +/- 35.9 vs. 1,067.7 +/- 58.8 nmol x min(-1) x g(-1)) or ACC (51.2 +/- 6.7 vs. 55.7 +/- 2.0 nmol x min(-1) x g(-1)) activity from R to ES (P > 0.05). When contraction and AICAR treatment were combined, the AICAR-induced increase in AMPK activity (34%) did not account for the synergistic increase in FA oxidation (175%) observed under similar conditions. These results suggest that while AMPK-dependent mechanisms may regulate FA uptake and FA oxidation at rest, AMPK-independent mechanisms predominate during low-intensity muscle contraction.

Síndrome de apnea/hipopnea obstructiva del sueño / Obstructive apnea/hypopnea syndrome during sleep

El síndrome de apnea-hipopnea obstructiva del sueño es un problema serio y de creciente prevalencia. Este artículo hace énfasis en que en nuestra consulta se debe considerar este diagnóstico y que debemos preguntar si hay sueño durante el día. Si existe somnolencia, indagar más con respecto a en qué situaciones se duerme el paciente y preguntarle a la pareja de cama si el paciente ronca habitualmente y/o si existen apneas durante el sueño. Si las respuestas son sugestivas de SAHOS, se debe de considerar referir a tal paciente a un especialista en desórdenes del sueño y/o realizar una polisomnografría nocturna en un laboratorio acreditado. Todos nos sorprenderemos de la incidencia de este problema si lo consideramos y de los beneficios que nuestros pacientes obtendrán si se les diagnostica y trata adecuadamente