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Objectives: Although there are many benefits of short-stay hospital admissions for high volume, pediatric surgical procedures, this model of care places greater responsibility on parents for the management of children's pain. This study aimed to document the trajectory of child pain outcomes and a range of parent-reported functional outcomes following discharge from a short-stay surgical admission. Moreover, we aimed to document the trajectory of parental perceived personal coping resources. Second, we assessed whether parental dispositional factors, assessed before hospital discharge, predicted the child's pain intensity and parent-reported functional recovery., Methods: Participants included children (aged 4 to 14 y) admitted for a short-stay tonsillectomy or appendectomy, and their parents. Parents completed a questionnaire before discharge from hospital. Demographic and surgical information was recorded from medical records. Following discharge, daily assessments of pain and functioning were carried out over a 10-day period using iPods or mobile phones. Predischarge and postdischarge data were obtained for 55 child and parent dyads., Results: Pain intensity scores returned to low levels (2/10 or less) by day 5 for appendectomy and day 10 for tonsillectomy. Parents' perceived personal coping resources increased more slowly following tonsillectomy than appendectomy. Controlling for time since surgery and parental coping resources, parental pain-related catastrophizing was a significant predictor of child pain and functional recovery., Discussion: Short-stay surgery results in parents facing considerable burden in managing their child's pain and functional impairment over a 10-day period. The potential value of screening for parental pain-related catastrophizing before discharge from hospital warrants further consideration and may enable identification of children likely to experience poorer recovery., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Vaccine coverage data are typically collected through vaccine registers and retrospective surveys. Alternatively, cross-sectional serosurveys enable direct estimation of vaccine coverage from antibody prevalence by exploiting correlated seropositivity for multi-antigen vaccines. Here, we extend previous methods by accounting for temporal antibody decline in estimating vaccine coverage for measles-mumps-rubella vaccine using serial serosurvey data., Methods: We introduce a Markovian cohort model of antibody waning and boosting applied to dichotomous seropositivity data for measles, mumps, and rubella. Simulation studies are used to test model identifiability and to explore bias induced by previous methods that ignore waning. The cohort model is then fitted to three Australian serosurveys, entailing estimates of vaccine coverage from routine and catch-up vaccination as well as waning rates for each antigen., Results: The simulation results show that the cohort model is identifiable and qualitatively captures the decline in seropositivity observed in older children. When fitted to all three Australian surveys, the estimated seroconversion and waning parameters are similar to estimates based on recent meta-analyses, whereas the coverage estimates appear consistent with previous Australian survey-based estimates., Discussion: We show that previous methods of estimating coverage from serological data can be improved by fitting a cohort model with waning and boosting processes to serial serosurvey data, furthermore yielding estimates of more parameters of interest such as rates of waning. In settings where serial serosurvey data is available, our method could be duplicated or applied to related questions such as coverage in routine two-dose schedules or from other combination vaccines.

Microvascular inflammation occurs during resuscitation following hemorrhagic shock, causing multiple organ dysfunction and mortality. Preclinical evidence suggests that hypothermia may have some benefit in selected patients by decreasing this inflammation, but this effect has not been extensively studied. Intravital microscopy was used to visualize mesenteric venules of anesthetized rats in real time to evaluate leukocyte adherence and mast cell degranulation. Animals were randomly allocated to normotensive or hypotensive groups and further subdivided into hypothermic and normothermic resuscitation (n = 6 per group). Animals in the shock groups underwent mean arterial blood pressure reduction to 40 to 45 mmHg for 1 h via blood withdrawal. During the first 2 h following resuscitation by infusion of shed blood plus double that volume of normal saline, rectal temperature of the hypothermic groups was maintained at 32°C to 34°C, whereas the normothermic groups were maintained between 36°C to 38°C. The hypothermic group was then rewarmed for the final 2 h of resuscitation. Leukocyte adherence was significantly lower after 2 h of hypothermic resuscitation compared with normothermic resuscitation: (2.8 ± 0.8 vs. 8.3 ± 1.3 adherent leukocytes, P = 0.004). Following rewarming, leukocyte adherence remained significantly different between hypothermic and normothermic shock groups: (4.7 ± 1.2 vs. 9.5 ± 1.6 adherent leukocytes, P = 0.038). Mast cell degranulation index (MDI) was significantly decreased in the hypothermic (1.02 ± 0.04 MDI) versus normothermic (1.22 ± 0.07 MDI) shock groups (P = 0.038) after the experiment. Induced hypothermia during resuscitation following hemorrhagic shock attenuates microvascular inflammation in rat mesentery. Furthermore, this decrease in inflammation is carried over after rewarming takes place.

Oxygen is essential for the maintenance of life, and when oxygen levels decline to critical levels, a program of complex mechanisms exists to i) sense hypoxia, ii) respond to minimize acute tissue injury, and iii) result in adaptations that offer protection against further hypoxia challenges. Alternative adaptation-related protection may also be inducible through the increased activity of hypoxia-inducible factors activated by hypoxia mimics such as iron chelation with deferoxamine (DFA). We have characterized a set of hypoxia-related responses at the microvasculature and postulated that microvascular injury in response to hypoxia could be reproduced by the reduction of bioavailable iron through chelation by DFA. We were able to induce a similar degree of leukocyte adherence and emigration and vascular leak with DFA infusion as compared with hypoxia exposure in an intact physiological rodent model. However, in contrast to hypoxia-exposed groups, we were unable to detect reactive oxygen species or alter the injury pattern with reactive oxygen species scavenger in the groups treated with DFA. Thus, we demonstrate that DFA mimics the pattern and intensity of hypoxia-related injury on the microvasculature; however, differences in the time course and mechanism of injury were identified. In addition, DFA saturated with iron did not completely reverse the effects of DFA, suggesting a mechanism(s) beyond a reduction in the bioavailability of iron. These findings may have importance in the targeting of iron for the development of hypoxia mimics that may offer protection against subsequent hypoxia exposure in clinical setting such as myocardial infarction and stroke.

In response to hypoxia, an inflammatory cascade is initiated and microvascular injury ensues. Specifically, within 10 min, leukocyte adherence to the endothelium begins, and leukocyte emigration and vascular leak soon follow. Activated protein C (APC) has been reported to have both anticoagulant and anti-inflammatory properties. Activated protein C is best described in its role as a treatment for sepsis. However, it has been used, with some success, in experimental models of hypoxic injury. We hypothesized that APC would be protective against microvascular injury during systemic hypoxia. Randomized prospective animal study. Adult male Sprague-Dawley rats. To characterize the microvascular response to APC exposure during hypoxia, four rat groups were used: saline control, APC infusion alone (100 mg/kg bolus), hypoxia alone (10% O2), and simultaneous hypoxia + APC infusion. Measurements of leukocyte adherence (no. per 100-microm venule), leukocyte emigration (no. per 4,000 microm(2)), and venular leak by fluorescein isothiacyanate-labeled albumin (Fo/Fi) were performed during intravital microscopy of the intact venular bed. Leukocyte adherence decreased from 14.5 (+/-1.2) cells/100-microm venule in hypoxic rats to 4.4 (+/-1.5) cells/100-microm venule in those treated with both hypoxic gas and APC infusion (P < 0.001). Similarly, leukocyte emigration in hypoxic rats reached 12.3 (+/- 2.2) cells/4,000-microm(2) venule, but was reduced to 3.5 (+/-0.3) cells/4,000-microm(2) venule (P <.001). Venular permeability to protein was also significantly decreased in the APC-treated group from 0.82 (+/-0.14) to 0.25 (+/-0.14) (P < 0.001). The infusion of APC attenuates the inflammatory response during systemic hypoxia at the microvascular level, as evidenced by measurements of leukocyte adherence, emigration, and venular permeability. Further investigation is needed to examine the potential role of APC in the treatment of hypoxic injury.

The generation of oxygen radicals during leukocyte-endothelial cell interaction is considered to represent one of the fundamental steps of microvascular injury following ischemia and reperfusion. Indirect evidence also suggests that this relationship may be important following hemorrhagic shock. The purpose of this study was to characterize the temporal changes of reactive oxygen species (ROS) in the mesenteric microvascular endothelium, in vivo, as a consequence of hemorrhagic shock and reperfusion, and to correlate this ROS production to leukocyte adherence. Following a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mmHg for 1 h in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of small intestine were examined to quantitate changes in ROS generation and leukocyte adherence. Sprague-Dawley rats were injected with dihydrorhodamine 123, a hydroperoxide-sensitive fluorescent probe that is trapped within viable cells as a nonfluorescent form and then converted to the mitochondrion-selective form rhodamine 123 by hydroperoxides. The fluorescent light emission from rhodamine 123 was recorded with digital microscopy and downloaded to a computerized image analysis program. Our results demonstrated an 80% increase in ROS generation beginning within 5 min into resuscitation and a 10-fold increase in leukocyte adherence that occurred at 10 min after resuscitation. Both ROS generation and leukocyte adherence were attenuated with pre-shock administration of platelet activating factor (PAF) antagonist, WEB 2086, and the CD11/CD18a antibody, anti-LFA-1beta. Our findings suggest that ROS production in endothelial cells is increased during reperfusion following hemorrhagic shock and that the mechanism of expression is mediated in part by both PAF expression and subsequent leukocyte adherence.

The pathogenesis of generalized microvascular injury following hemorrhagic shock and total ischemia appears to be dependent on leukocytes interacting with the venular endothelium. The purpose of this study was to compare leukocyte adherence and sequestration following hemorrhagic shock with that of total ischemia in the small bowel mesentery of rats. Leukocyte adherence and sequestration was measured by direct visualization in vivo using intravital microscopy. In addition, sequestration was also quantitated by measuring tissue levels of myeloperoxidase, a marker of leukocyte infiltration. Mean arterial blood pressure was decreased to 40 mm Hg for 30 min (hemorrhagic shock group). In the total ischemia group, both the superior and inferior mesenteric arteries were clamped for 30 min followed by reperfusion. Hemorrhagic shock (9.4+/-1.5 cell/100 microm) and total ischemia (8.3+/-3 cell/100 microm) caused a statistically significant increases in leukocyte adherence 60 min postinsult as compared with controls (.9+/-1.5 cell/100 microm). However, the increase in leukocyte adherence appeared earlier and to a greater degree initially following total ischemia. Leukocyte sequestration as measured by intravital microscopy was significant only after total ischemia [(24.6+/-1.7 cell/(100 microm)2; p<.01] and not hemorrhagic shock [3.4+/-.6 cell/(100 microm)2] versus controls [2.2+/-.2 cell/(100 microm)2]. This difference in sequestration was also confirmed by tissue levels of myeloperoxidase. The results of this study suggest that the microvascular response following hemorrhagic shock is different than that of total ischemia, and caution is warranted when extrapolating the experimental results of one to the other.

Rationale and Objectives: Signal processing techniques have been used to generate parametric ultrasound images that describe properties of tissue microstructure., Methods: Images of the average scatterer size (D) and integrated backscatter coefficient (IBC) for normal dog kidneys were examined., Results: With parametric ultrasound the authors identified sources of cortical backscatter and observed microanatomical changes corresponding to ischemia. In particular, scatterer size images acquired in vitro and in vivo show it is possible to rapidly assess changes and differences in the average glomerular diameter and the average arteriolar cross-sectional diameter., Conclusions: A more direct interpretation of sonographic image data is possible with this new type of imaging. Parametric imaging may have a diagnostic role as a means to differentiate among conditions producing increased cortical echogenicity and to detect important structural indicators such as glomerular hypertrophy.

Immunocytochemistry has been used to assess the distribution of the mitosis-associated protein kinase, cdc2, in mature neurons of rat brain. A robust signal is apparent in most, but not all neurons in cerebellum, cortex and hippocampus. The signal is concentrated in neuronal nuclei with lower levels of immunoreactivity in neuronal cytoplasm. High resolution analysis indicates that the amount of cdc2 is uneven, suggesting that regulated amounts of enzyme may reflect different functional status of the neurons. In many cases, the kinase is concentrated at the nuclear periphery, implying that it may be particularly involved in phosphorylating substrates in this subnuclear compartment. These results indicate additional roles for cdc2 in terminally differentiated neurons which have undergone final mitosis.

Immunohistochemistry was used to assess the distribution of protein tyrosine kinases in Alzheimer's disease (AD) pathology. One of these, fyn, exhibited an interesting pattern of immunoreactivity. Low levels of immunoreactivity were apparent in neurons from both normal and AD brain. However a subset of neurons in AD brain exhibited intense fyn immunoreactivity. Double label immunohistochemistry revealed that fyn-positive neurons were also positive for abnormally phosphorylated microtubule-associated protein, tau. Proline-directed kinases, whose activity is regulated by phosphorylation on tyrosine, may be responsible for abnormal tau phosphorylation. These results identify fyn as a candidate kinase for regulating putative proline-directed kinases involved in abnormal tau phosphorylation.

Plasma levels of neurotensin are increased by ingestion of fat, making this peptide a candidate for mediation of pancreatic adaptation to dietary fat. We examined the effects of doses of neurotensin on pancreatic secretion and growth to determine whether doses stimulating secretion also increased pancreatic growth and lipase content in rats. Because neurotensin inhibits gastric secretion in other species, we also measured its effects on gastric secretion and growth. In conscious rats, neurotensin (33, 100, and 300 micrograms kg-1 subcutaneously in gelatin) produced dose-related increases in pancreatic amylase output and decreases in basal gastric secretion. Duration of acid inhibition by neurotensin was longer than stimulation of amylase secretion. Chronic administration of the same doses of neurotensin to groups of rats every 8 h for 5 days produced small but statistically significant trophic effects on the pancreas. The highest dose of neurotensin significantly increased pancreatic weight (16%) and content of DNA (12%), protein (17%), and chymotrypsinogen (60%) but did not affect amylase or lipase content. There were no effects of neurotensin on any measurement of oxyntic or pyloric gland area growth. We conclude that although neurotensin stimulates both pancreatic secretion and growth, it is not the mediator of fat-induced pancreatic adaptation.

Glucagon is structurally related to secretin but inhibits the effects of secretin and cholecystokinin (CCK) on pancreatic secretion in vivo. Because secretin is a weak stimulant of pancreatic growth and potentiates the trophic effects of CCK, we hypothesized that glucagon might inhibit CCK-induced pancreatic growth. Four groups of 10 rats were injected with saline, glucagon (30 micrograms/kg, equimolar to a known trophic dose of secretin), cerulein (0.67 microgram/kg), or glucagon plus cerulein every 8 h for 5 days. The pancreas was excised, weighed, and assayed for total content of DNA, protein, amylase, chymotrypsinogen, and lipase. In control and glucagon-alone groups, the small intestine was also removed, weighed, and assayed for DNA, protein, and disaccharidase content. Glucagon alone decreased pancreatic DNA and increased lipase content. Compared with cerulein-treated animals, animals treated with glucagon and cerulein showed significant decreases in pancreatic weight and content of protein, amylase, and chymotrypsinogen. Although glucagon had significant effects on intestinal protein, maltase, and sucrase contents in certain segments, there was no clear pattern of response. The data suggest that glucagon may be an inhibitory regulator of pancreatic growth, acting to block the effects of CCK on pancreatic hypertrophy.