The intersectionality of gender and poverty on symptom suffering among adolescents with cancer.

BACKGROUND: To determine if the intersectionality of gender and poverty is associated with health disparities among adolescents with cancer. We hypothesized unobserved latent classes of patients exist with respect to cancer-related symptoms; and class classification varies by gender-poverty combinations. PROCEDURE: Cross-sectional data were collected among adolescents with cancer and families (N = 126 dyads) at four tertiary pediatric hospitals. Adolescents were aged 14-21 years, English speaking, cancer diagnosis, not developmentally delayed, psychotic, homicidal, suicidal, or severely depressed. Latent class analysis and multinomial logit models were used for analysis. Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric symptom measures, Short forms, evaluated anxiety, depressive symptoms, pain interference, and fatigue. Family-reported household income used 2016 Federal Poverty Level (FPL) guidelines. RESULTS: Three distinct groups of patients were identified using PROMIS symptom patterns: High Distress-25%; High Physical/Low Psychological Distress-14%; and Low Distress-62%. Female adolescents living in households with incomes at or below the 2016 FPL had 30 times the odds of being classified in the High Distress class (higher probabilities of experiencing anxiety, depressive symptoms, pain interference, and fatigue) compared to those in the High Physical/Low Psychological Distress class (female and poverty: AOR = 30.27, 95% CI 1.23, 735.10), and this was statistically significant (ß = 3.41, 95% CI 0.21, 6.60; p = .04) but not compared to those in Low Distress. CONCLUSION: Adolescent females with cancer with households in poverty had significantly greater odds of experiencing high symptom distress, compared to those with high physical but low psychological distress. More comprehensive screening and intervention, as needed, may decrease disparities.

Pediatric Advance Care Planning and Families' Positive Caregiving Appraisals: An RCT.

BACKGROUND AND OBJECTIVES: Little is known about how families respond to pediatric advance care planning. Physicians are concerned that initiating pediatric advance care planning conversations with families is too distressing for families. We examined the effect of family centered pediatric advance care planning intervention for teens with cancer (FACE-TC) advance care planning on families' appraisals of their caregiving, distress, and strain. METHODS: In a randomized clinical trial with adolescents with cancer and their families conducted from July 2016 to April 2019 in 4 tertiary pediatric hospitals, adolescents and family dyads were randomly assigned at a 2:1 intervention/control ratio to either the 3 weekly sessions of FACE-TC (Advance Care Planning Survey; Next Steps: Respecting Choices; Five Wishes) or treatment-as-usual. Only the family member was included in this study. Generalized estimating equations assessed the intervention effect measured by Family Appraisal of Caregiving Questionnaire. RESULTS: Families' (n = 126) mean age was 46 years; 83% were female, and 82% were white. FACE-TC families significantly increased positive caregiving appraisals at 3-months postintervention, compared with those in the control group (ß = .35; 95% confidence interval [CI] 0.19 to 0.36; P = .03). No significant differences were found between groups for strain (ß = -.14; 95% CI = -0.42 to 0.15; P = .35) or distress (ß = -.01; CI = -0.35 to 0.32; P = .93). CONCLUSIONS: Families benefited from participation in FACE-TC, which resulted in positive appraisals of their caregiving for their child with cancer, while not significantly burdening them with distress or strain. Clinicians can be assured of the tolerability of this family-supported model.

Shared spiritual beliefs between adolescents with cancer and their families.

BACKGROUND: FAmily CEntered (FACE) Advance Care Planning helps family decision makers to understand and honor patients' preferences for future health care, if patients cannot communicate. Spiritual well-being is a key domain of pediatric oncology care and an integral dimension of pediatric advance care planning. PROCEDURE: As part of four-site randomized controlled trial of FACE for teens with cancer, the functional assessment of chronic illness therapy-spiritual well-being- version 4 (FACIT-Sp-EX-4) was completed independently by 126 adolescents with cancer/family dyads. The prevalence-adjusted and bias-adjusted kappa (PABAK) measured congruence on FACIT-Sp-EX-4. RESULTS: Adolescents (126) had mean age of 16.9 years, were 57% female and 79% White. Religious/spiritual classifications were: Catholic (n = 18), Protestant (n = 76), Mormon (n = 3), none/atheist (n = 22), other (n = 5), and unknown (n = 2). Agreement at item level between spiritual well-being of adolescents and families was assessed. Three items had ≥90% agreement and Excellent PABAK: "I have a reason for living," "I feel loved," "I feel compassion for others in the difficulties they are facing." Three items had <61% agreement and Poor PABAK: "I feel a sense of harmony within myself," "My illness has strengthened my faith or spiritual beliefs," "I feel connected to a higher power (or God)." Dyadic congruence was compared by social-demographics using median one-way analysis. Male family members (median = 72%) were less likely to share spiritual beliefs with their adolescent than female family members (median = 83%), P = .0194. CONCLUSIONS: Family members may not share spiritual beliefs with adolescents and may be unaware of the importance of spiritual well-being for adolescents.

Association of Religious and Spiritual Factors With Patient-Reported Outcomes of Anxiety, Depressive Symptoms, Fatigue, and Pain Interference Among Adolescents and Young Adults With Cancer.

Importance: The associations of spiritual and religious factors with patient-reported outcomes among adolescents with cancer are unknown. Objective: To model the association of spiritual and religious constructs with patient-reported outcomes of anxiety, depressive symptoms, fatigue, and pain interference. Design, Setting, and Participants: This cross-sectional study used baseline data, collected from 2016 to 2019, from an ongoing 5-year randomized clinical trial being conducted at 4 tertiary-referral pediatric medical centers in the US. A total of 366 adolescents were eligible for the clinical trial, and 126 were randomized; participants had to be aged 14 to 21 years at enrollment and be diagnosed with any form of cancer. Exclusion criteria included developmental delay, scoring greater than 26 on the Beck Depression Inventory II, non-English speaking, or unaware of cancer diagnosis. Exposures: Spiritual experiences, values, and beliefs; religious practices; and overall self-ranking of spirituality's importance. Main Outcomes and Measures: Variables were taken from the Brief Multidimensional Measurement of Religiousness/Spirituality (ie, feeling God's presence, daily prayer, religious service attendance, being very religious, and being very spiritual) and the spiritual well-being subscales of the Functional Assessment of Chronic Illness Therapy (meaning/peace and faith). Predefined outcome variables were anxiety, depressive symptoms, fatigue, and pain interference from Patient-Reported Outcomes Measurement Information System pediatric measures. Results: A total of 126 individuals participated (72 [57.1%] female participants; 100 [79.4%] white participants; mean [SD] age, 16.9 [1.9] years). Structural equation modeling showed that meaning and peace were inversely associated with anxiety (ß = -7.94; 95% CI, -12.88 to -4.12), depressive symptoms (ß = -10.49; 95% CI, -15.92 to -6.50), and fatigue (ß = -8.90; 95% CI, -15.34 to -3.61). Feeling God's presence daily was indirectly associated with anxiety (ß = -3.37; 95% CI, -6.82 to -0.95), depressive symptoms (ß = -4.50; 95% CI, -8.51 to -1.40), and fatigue (ß = -3.73; 95% CI, -8.03 to -0.90) through meaning and peace. Considering oneself very religious was indirectly associated with anxiety (ß = -2.81; 95% CI, -6.06 to -0.45), depressive symptoms (ß = -3.787; 95% CI, -7.68 to -0.61), and fatigue (ß = -3.11, 95% CI, -7.31 to -0.40) through meaning and peace. Considering oneself very spiritual was indirectly associated with anxiety (ß = 2.11; 95% CI, 0.05 to 4.95) and depression (ß = 2.8, 95% CI, 0.07 to 6.29) through meaning and peace. No associations were found between spiritual scales and pain interference. Conclusions and Relevance: In this study, multiple facets of spirituality and religiousness were associated with anxiety, depression, and fatigue, all of which were indirectly associated with the participant's sense of meaning and peace, which is a modifiable process. Although these results do not establish a causal direction, they do suggest palliative interventions addressing meaning-making, possibly including a spiritual or religious dimension, as a novel focus for intervention development.

Congruence Gaps Between Adolescents With Cancer and Their Families Regarding Values, Goals, and Beliefs About End-of-Life Care.

Importance: Lack of pediatric advance care planning has been associated with poor communication, increased hospitalization, poor quality of life, and legal actions. Clinicians presume that families understand adolescents' treatment preferences for end-of-life care. Objective: To examine patient-reported end-of-life values and needs of adolescents with cancer and congruence with their families' understanding of these needs. Design, Setting, and Participants: This cross-sectional survey was conducted among adolescent-family dyads from July 16, 2016, to April 30, 2019, at 4 tertiary care pediatric US hospitals. Participants included 80 adolescent-family dyads (160 participants) within a larger study facilitating pediatric advance care planning. Adolescent eligibility criteria included being aged 14 to 21 years, English speaking, being diagnosed with cancer at any stage, and knowing their diagnosis. Family included legal guardians for minors or chosen surrogate decision-makers for those aged 18 years or older. Data analysis was performed from April 2019 to November 2019. Exposure: Session 1 of the 3-session Family Centered Pediatric Advance Care Planning for Teens With Cancer intervention. Main Outcomes and Measures: The main outcome was congruence between adolescents with cancer and their families regarding adolescents' values, goals, and beliefs about end-of-life care. Prevalence-adjusted and bias-adjusted κ (PABAK) values were used to measure congruence on the Lyon Advance Care Planning Survey-Revised (Patient and Surrogate versions). Results: A total of 80 adolescent-family dyads (160 participants) were randomized to the intervention group in the original trial. Among the adolescents, 44 (55.0%) were female and 60 (75.0%) were white, with a mean (SD) age of 16.9 (1.8) years. Among family members, 66 (82.5%) were female and 65 (81.3%) were white, with a mean (SD) age of 45.3 (8.3) years. Family members' understanding of their adolescent's beliefs about the best time bring up end-of-life decisions was poor: 86% of adolescents wanted early timing (before getting sick, while healthy, when first diagnosed, when first sick from a life-threatening illness, or all of the above), but only 39% of families knew this (PABAK, 0.18). Families' understanding of what was important to their adolescents when dealing with their own dying was excellent for wanting honest answers from their physician (PABAK, 0.95) and understanding treatment choices (PABAK, 0.95) but poor for dying a natural death (PABAK, 0.18) and being off machines that extend life, if dying (PABAK, 0). Conclusions and Relevance: Many families had a poor understanding of their adolescent's values regarding their own end-of-life care, such as when to initiate end-of-life conversations and preference for being off machines that extend life. Pediatric advance care planning could minimize these misunderstandings with the potential for a substantial impact on quality of care.

PROMIS pediatric measures validated in a longitudinal study design in pediatric oncology.

PURPOSE: This study assessed the responsiveness to change over time and theorized associations of Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric measures in children and adolescents in treatment for cancer to determine measure readiness for use in cancer clinical trials. METHODS: We administered eight PROMIS (three symptom, two psychological, and three performance) pediatric short-form measures and the Symptom Distress Scale (SDS) to 96 pediatric oncology patients at three time points during a course of chemotherapy. We assessed responsiveness using paired t tests and generalized estimating equation (GEE) models, calculated standardized response mean (SRM) values for PROMIS measures, and examined scores over three data points (T1-T3). Guided by the theory of unpleasant symptoms (TOUS), we examined associations among the PROMIS measures, the SDS, and other variables using GEE. RESULTS: The paired t tests showed statistically significant changes in two psychological measures and one performance measure from T1 to T2; three symptom, two psychological and two performance measures from T2 to T3; and three symptom and two psychological measures from T1 to T3. Findings from GEE models indicate PROMIS pediatric measures had statistically significant short-term and long-term changes, controlling for demographic and clinical variables. One performance measure did not achieve significant change at any time point. We found positive support for theorized relationships in the TOUS. CONCLUSIONS: Most of the PROMIS pediatric measures demonstrated changes over time and had significant relationships as theorized, thus supporting concurrent and construct validity of these measures when administered to pediatric oncology patients during a course of chemotherapy. This evidence supports the measures' readiness for use in clinical trials.

Executive Function and Psychosocial Quality of Life in School Age Children with Congenital Heart Disease.

OBJECTIVE: To test a model to predict psychosocial quality of life (QOL) in children with congenital heart disease (CHD) via executive dysfunction. STUDY DESIGN: Parents of 91 children with CHD requiring surgery in the first year of life completed questionnaires by mail or as part of their cardiology clinic visit. Latent class analysis identified 2 groups of patients with different likelihoods of executive dysfunction. Select medical and demographic characteristics and executive dysfunction group membership were evaluated as predictors of QOL using structural equation modeling. RESULTS: In children with CHD, aortic obstruction, male sex, and premature birth predicted worse executive function, explaining 59% of the variance. Structural equation modeling results indicated that executive dysfunction plays an important mediating role, through which CHD with aortic obstruction, male sex, and premature birth indirectly affect psychosocial QOL. Neurologic abnormalities and single-ventricle CHD did not significantly predict executive dysfunction or QOL. CONCLUSIONS: Executive dysfunction is a strong predictor of psychosocial QOL at school age. Select medical and demographic risk factors did not directly predict QOL at school age in CHD; however, aortic obstruction, premature birth, and male sex impacted QOL indirectly by contributing to executive dysfunction. These findings suggest important risk factors for executive dysfunction that can be monitored, allowing for provision of early supports for executive skills development in an effort to improve long term psychosocial QOL in at-risk children with CHD.

[Epidemioclinical and Therapeutic Study of Condylomas (Genital Warts) in Dermato-Venereology Department (CHU Treichville, Abidjan, Côte d'Ivoire, 2013-2016)]. / Étude épidémioclinique et thérapeutique des condylomes vénériens dans un service de dermatovénéréologie (CHU Treichville, Abidjan, Côte d'Ivoire, 2013-2016).

We have conducted a retrospective study in the dermatology department of the CHU Treichville in Abidjan during 4 years. Three hundred and fifty cases of venereal warts were recorded with a hospital frequency of 1.5%, an average age of 29.37, a female predominance (51.3%), and a sex ratio (M/F) of 0.94. We have observed a giant condyloma in 0.9%, a main localization to the vulva (47.7%) and male genitalia (34.6%); HIV testing carried out in 60.8% of patients was positive in 80.7% of cases, all HIV1. Electrocoagulation was the mean treatment (93.1%), followed by cryotherapy (15 cases), chemotherapy (6 cases), and surgery (3 cases). Recurrences were reported in 9 cases (2.6%) of which more than half has occurred within a month.

Nous avons réalisé une étude rétrospective au sein du service de dermatologie du CHU de Treichville d'Abidjan pendant quatre ans. Trois cent cinquante cas de condylomes vénériens ont été recensés (1,5 % des hospitalisations en dermatologie) ; une moyenne d'âge de 29,37 ans ; une prédominance féminine (51,3 %) et un sexe-ratio (H/F) de 0,94. Nous avons observé un condylome géant dans 0,9 %, une localisation à la vulve (47,7 %) et aux organes génitaux externes masculins (34,6 %). Le dépistage du VIH-1, réalisé dans 60,8 % des cas, s'est avéré positif dans 80,7 % des cas, toujours avec VIH-1. L'électrocoagulation a été le traitement de choix (93,1 %), suivie de la cryothérapie (15 cas), la chimiothérapie (6 cas) et la chirurgie (3 cas). Des récidives ont été relevées dans neuf cas (2,6 %), dont plus de la moitié avant un mois.

Level of Concordance of Pre-, Intra-, and Postoperative Staging in Cervical Cancers (TREYA Study).

Concomitant radiochemotherapy is the therapeutic standard for locally advanced (Ib2 to IVa stage FIGO) cervical cancer. In the absence of a radiotherapy in many of our Sub-Saharan African countries, surgical resection is the only therapeutic method available in hopes of achieving a definite cure. However, criteria for curative surgery are not always met due to preoperative understaging of most of our patients. In addition to socioeconomic factors, the causes for understaging are numerous. These include the lack of personnel or underqualified personnel and the absence of complete workup to assess the resectability of the tumor, but above all the lack of decision-making through multidisciplinary consultation meetings. This study makes a plea in order to provide our hospitals with qualified personnel and adequate technical platform to allow efficient management of our patients with cervical cancer.

Social Impact of Facial Infantile Hemangiomas in Preteen Children.

IMPORTANCE: Involuted infantile facial hemangiomas (IHs) may adversely affect the social skills of children. OBJECTIVE: To assess the social impact of involuted facial IHs, with or without prior treatment, in preteen children. DESIGN, SETTING, AND PARTICIPANTS: An observational, cross-sectional study of social anxiety and skills in preteen children with facial IHs diagnosed during infancy. The study took place in an academic institution and a community dermatology practice between January 1, 2013, and July 30, 2014. Records on 236 children with IHs located in a cosmetically sensitive area were identified; of those, 144 potential participants (parents) were reached by telephone and mailed study packets. Thirty completed questionnaires were returned. Data analysis was performed from August 1, 2014, to September 7, 2015. INTERVENTIONS: The questionnaires included the following psychiatric scales: (1) Social Anxiety Scale for Children-Revised (SASC-R), completed by parents and children, including the domains of Fear of Negative Evaluation and Social Avoidance/Distress in New Situations (SAD-New) (higher scores indicate greater social anxiety), and (2) Social Competency Inventory (SCI), completed by parents, including the domains of Prosocial Behavior and Social Initiative (lower scores indicate poorer social competency). MAIN OUTCOMES AND MEASURES: Demographics, clinical details, and survey responses were collected. Analysis was conducted using t tests to compare scores for each survey domain with established normative data and between sex as well as between treatment vs nontreatment groups. RESULTS: Of the 144 potential participants, 30 (21%) responded. The mean age of the preteen subjects was 10.0 years (range, 5.4-12.9 years) with a 2:1 female to male ratio. Twenty-five children (83%) had a single IH, and the remaining 5 participants (17%) had multiple IHs, with at least 1 IH in a cosmetically sensitive area. The periocular region was the most common site of the IH (10 [33%]), followed by the nose (6 [20%]), cheek (5 [17%]), forehead (4 [13%]), lip or perioral region (4 [13%]), and ear (1 [3%]). Eighteen children (60%) had received treatment for their IH. With results reported as mean (SD), the SASC-R test showed that social anxiety of the children was not increased over normative data; however, those who did not receive IH treatment had significantly greater anxiety for new situations compared with those who received treatment (SAD-New: 15.5 [5.1] vs 11.5 [3.8]; P = .02). Results of the SCI scale indicated that the Prosocial Orientation domain score for the children was similar to normative data (3.96 [0.48] vs 3.89 [0.55], P = .50). Social Initiative domain scores were significantly poorer in children who did not receive treatment vs those who received treatment (3.45 [0.43] vs 4.03 [0.55]; P = .006). CONCLUSIONS AND RELEVANCE: Preteen children with involuted, untreated facial IHs have higher Social Anxiety domain scores in new situations and decreased Social Initiative domain scores compared with children who receive treatment for facial IH. Although this study is limited by a small sample size, it raises important considerations for whether early treatment of facial IHs in cosmetically sensitive areas has a beneficial effect on social skills in preteens.

The use of near-infrared spectroscopy during an extubation readiness trial as a predictor of extubation outcome.

OBJECTIVES: To determine whether the measurement of cerebral and somatic regional oxygen saturation during an extubation readiness trial predicts extubation failure in postoperative cardiac patients. DESIGN: Prospective observational study. SETTING: Tertiary care center cardiac ICU. PATIENTS: Pediatric patients 1 day to 21 years old following cardiac surgery for congenital heart disease. Patients were included if they were intubated for greater than 12 hours and were undergoing an extubation readiness trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data collection included patient demographic, procedural, laboratory, and physiologic variables. Regional oxygen saturation values were recorded using near-infrared spectroscopy at baseline, during a 2-hour extubation readiness trial, and in the first 2 hours postextubation. Ninety-nine extubation readiness trials were conducted in 79 patients. Adjusting for baseline somatic regional oxygen saturation, logistic regression analysis demonstrated that patients with a decline in their minimum somatic regional oxygen saturation of at least 10% during an extubation readiness trial had a 6-time increased odds of extubation failure (p = 0.02; 95% CI, 1.26-29.8). Receiver-operating characteristic curve analysis demonstrated that a 12% decline in the minimum regional oxygen saturation best predicted extubation failure with 54% sensitivity and 82% specificity. CONCLUSIONS: A 12% decline in somatic regional oxygen saturation during an extubation readiness trial is associated with an increased risk of extubation failure following a successful extubation readiness trial. The addition of somatic regional oxygen saturation measurements to an extubation readiness trial may improve our ability to predict extubation outcome.

Nonpharmacologic control of postoperative supraventricular arrhythmias using AV nodal fat pad stimulation in a young animal open heart surgical model.

BACKGROUND: Supraventricular arrhythmias (junctional ectopic tachycardia [JET] and atrial tachyarrhythmias) frequently complicate recovery from open heart surgery in children and can be difficult to manage. Medical treatment of JET can result in significant morbidity. Our goal was to develop a nonpharmacological approach using autonomic stimulation of selective fat pad (FP) regions of the heart in a young canine model of open heart surgery to control 2 common postoperative supraventricular arrhythmias. METHODS AND RESULTS: Eight mongrel dogs, varying in age from 5 to 8 months and weighting 22±4 kg, underwent open heart surgery replicating a nontransannular approach to tetralogy of Fallot repair. Neural stimulation of the right inferior FP was used to control the ventricular response to supraventricular arrhythmias. Right inferior FP stimulation decreased baseline AV nodal conduction without altering sinus cycle length. AV node Wenckebach cycle length prolonged from 270±33 to 352±89 ms, P=0.02. Atrial fibrillation occurred in 7 animals, simulating a rapid atrial tachyarrhythmias. FP stimulation slowed the ventricular response rate from 166±58 to 63±29 beats per minute, P<0.001. Postoperative JET occurred in 7 dogs. FP stimulation slowed the ventricular rate during postoperative JET from 148±31 to 106±32 beats per minute, P<0.001, and restored sinus rhythm in 7/7 dogs. CONCLUSIONS: Right inferior FP stimulation had a selective effect on the AV node, and slowed the ventricular rate during postoperative JET and atrial tachyarrhythmias in our young canine open heart surgery model. FP stimulation may be a useful new technique for managing children with JET and atrial tachyarrhythmias.

PROMIS pediatric measures in pediatric oncology: valid and clinically feasible indicators of patient-reported outcomes.

BACKGROUND: Establishing the ability of children and adolescents with cancer to complete the NIH-sponsored PROMIS pediatric measures electronically and the preliminary validity estimates of the measures (both full item banks and short forms) in pediatric oncology will contribute to our knowledge of the impact of cancer treatment on these young patients. PROCEDURES: A total of 203 8- to 17-year olds were administered eight PROMIS pediatric measures in a cross-sectional study design to establish known-group validity. Of the 200 who completed all or most of the items, a slight majority were male (55.5%) and white (54%). Patients were either undergoing treatment for cancer (n = 93) or in survivorship following treatment for cancer (n = 107). Measures were completed using computer interface during an in-person interaction with researchers. RESULTS: Only 3 of 203 participants did not complete the PROMIS pediatric measures. As hypothesized, participants in treatment were significantly different (worse) on parent-reported clinical indicators (blood counts, fatigue, and appetite) and on seven self-reported measures (depression, anxiety, peer relationships, pain interference, fatigue, upper extremity function, and mobility) from participants in survivorship. Females reported worse fatigue, anger, and pain interference than males. Worse patient-reported outcomes for patients in active treatment persisted after adjusting for potential confounding variables. CONCLUSIONS: Children and adolescents in treatment for cancer or in survivorship and ranging from 8 to 17 years of age can complete multiple PROMIS pediatric measures using a computer interface during an outpatient clinic visit or inpatient admission. Findings establish known-group validity for PROMIS pediatric measures in pediatric oncology.

High-dose dexmedetomidine increases the opioid-free interval and decreases opioid requirement after tonsillectomy in children.

PURPOSE: Dexmedetomidine, a selective α(2) adrenoreceptor agonist, has analgesic and sedative properties, minimal impact on respiratory parameters, and reportedly decreases analgesic requirements after surgery. Given its pharmacodynamic profile, dexmedetomidine might have a role for postoperative pain control in children undergoing tonsillectomy. In this study, we hypothesized that dexmedetomidine would delay and decrease opioid requirements after tonsillectomy. METHODS: In a double-blind controlled trial, participants undergoing tonsillectomy were randomized to receive one intravenous dose of fentanyl (1 µg·kg(-1) or 2 µg·kg(-1)) or dexmedetomidine (2 µg·kg(-1) or 4 µg·kg(-1)) immediately after endotracheal intubation. Primary outcomes included requirement for rescue morphine in the initial postoperative period. RESULTS: One hundred and one children were enrolled. During the postoperative period, dexmedetomidine (2 and 4 µg·kg(-1) groups combined) significantly prolonged the opioid-free interval of children who underwent tonsillectomy compared with fentanyl (1 and 2 µg·kg(-1) groups combined) (P < 0.001). Children treated with dexmedetomidine 2 µg·kg(-1) vs dexmedetomidine 4 µg·kg(-1) had similar cumulative incidence curves for time to morphine rescue, whereas there was a small difference in time to first morphine rescue administration when comparing fentanyl 1 µg·kg(-1) vs fentanyl 2 µg·kg(-1). Furthermore, length of stay in the postanesthesia care unit was significantly longer for children treated with dexmedetomidine vs children treated with fentanyl (P = 0.0016). CONCLUSIONS: High-dose dexmedetomidine decreases opioid requirements, prolongs the opioid-free interval after tonsillectomy, and prolongs length of stay in the postanesthesia care unit. It is conceivable that these early opioid-sparing effects could benefit patients at risk for respiratory complications early in the postoperative course after tonsillectomy (e.g., patients with obstructive sleep apnea). (ClinicalTrials.gov number, NCT00654511).

Bis(2-chloroethoxy)methane degradation by TiO2 photocatalysis: parameter and reaction pathway investigations.

Haloethers are widely used in industry, and the release of these species into the environment is of great concern because of their toxicity and carcinogenicity. The present study deals with the photocatalytic degradation of the haloether, bis(2-chloroethoxy)methane (BCEXM), in the presence of TiO(2) particles and UV-A (lambda=365 nm) radiation. About 99.5% of BCEXM was degraded after UV irradiation for 16h. Factors such as solution pH, TiO(2) dosage, and the presence of anions were found to influence the degradation rate. To obtain a better understanding of the mechanistic details of this TiO(2)-assisted photodegradation of BCEXM with UV irradiation, the intermediates of the processes were separated, identified, and characterized by the solid-phase microextraction (SPME) and gas chromatography/mass spectrometry (GC/MS) technique. To the best of our knowledge, this is the first report on the degradation pathways of BCEXM. The first step in the destruction of BCEXM is thought to be abstraction of a hydrogen by ()OH to form a carbon-centered radical which then reacts with O(2) to form a peroxyl radical. Peroxyl radicals react with one another and produce an alkoxy radical. The beta-bond fragmentation of the alkoxy radical produces different intermediates.

PAPIN. A novel multiple PSD-95/Dlg-A/ZO-1 protein interacting with neural plakophilin-related armadillo repeat protein/delta-catenin and p0071.

A neural plakophilin-related armadillo repeat protein (NPRAP)/delta-catenin interacts with one of Alzheimer disease-related gene products, presenilin 1. We have previously reported the interaction of NPRAP/delta-catenin with synaptic scaffolding molecule, which is involved in the assembly of synaptic components. NPRAP/delta-catenin also interacts with E-cadherin and beta-catenin and is implicated in the organization of cell-cell junctions. p0071, a ubiquitous isoform of NPRAP/delta-catenin, is localized at desmosomes in HeLa and A431 cells and at adherens junctions in Madin-Darby bovine kidney cells. We have identified here a novel protein interacting with NPRAP/delta-catenin and p0071 and named this protein plakophilin-related armadillo repeat protein-interacting PSD-95/Dlg-A/ZO-1 (PDZ) protein (PAPIN). PAPIN has six PDZ domains and binds to NPRAP/delta-catenin and p0071 via the second PDZ domain. PAPIN and p0071 are ubiquitously expressed in various tissues and are localized at cell-cell junctions in normal rat kidney cells and bronchial epithelial cells. PAPIN may be a scaffolding protein connecting components of epithelial junctions with p0071.

Association of membrane-associated guanylate kinase-interacting protein-1 with Raf-1.

Membrane-associated guanylate kinase-interacting protein (MAGUIN)-1 was identified as a protein interacting with synaptic scaffolding molecule (S-SCAM) and postsynaptic density (PSD)-95/synapse-associated protein (SAP)90. MAGUIN-1 has a chimerical molecular structure composed of one sterile alpha motif, one PSD-95/Dlg-A/ZO-1 (PDZ), and one pleckstrin homology (PH) domain, and interacts with the PDZ domains of S-SCAM and PSD-95/SAP90 via its carboxyl-terminal PDZ-binding motif. MAGUIN-1 is considered as a mammalian homologue of Drosophila CNK, which is a Raf-interacting protein implicated in the regulation of eye development. Here we have tested whether MAGUIN-1 interacts directly with Raf-1. MAGUIN-1 and Raf-1 were coimmunoprecipitated from rat brain. MAGUIN-1 binds to the kinase domain of Raf-1, and Raf-1 binds to the middle region of MAGUIN-1 containing the PH domain. However, in contrast to the dominant active mutant of Ki-Ras, which interacts with Raf-1, recruits it to the plasma membrane from the cytosol, and activates it, MAGUIN-1 neither activates Raf-1 nor recruits it to the plasma membrane. MAGUIN-1 may link Raf-1 to components of synapses assembled by PSD-95/SAP90 and S-SCAM.

Isolation and characterization of mammalian homologues of Caenorhabditis elegans lin-7: localization at cell-cell junctions.

In Caenorhabditis elegans, the vulval induction is mediated by the let-23 receptor tyrosine kinase (RTK)/ Ras signaling pathway. The precise localization of the let-23 RTK at the epithelial junctions is essential for the vulval induction, and requires three genes including lin-2, -7, and -10. The mammalian homologue of lin-2 has been identified as a protein interacting with a neuronal adhesion molecule, neurexin, and named CASK. CASK has recently been reported to interact with syndecans and an actin-binding protein, band 4.1, at epithelial and synaptic junctions, and to play central roles in the formation of cell-cell junctions. The product of C. elegans lin-7 directly interacts with let-23 RTK and localize it at epithelial junctions. Here, we report three rat homologues of lin-7 ubiquitously expressed in various tissues. These homologues are accumulated at the junctional complex region in cultured Madin-Darby canine kidney cells, and are also localized at the synaptic junctions in neurons. The mammalian homologues of lin-7 may be implicated in the formation of cell-cell junctions.

Localization of membrane-associated guanylate kinase (MAGI)-1/BAI-associated protein (BAP) 1 at tight junctions of epithelial cells.

Membrane-associated guanylate kinase (MAGI)-1/BAI-associated protein (BAP) 1 and Synapse-associated protein (SAP) 97/human Discs-large tumor suppressor gene (hDLG) are ubiquitous isoforms of synaptic scaffolding molecule (S-SCAM) and Postsynaptic density (PSD)-95/SAP90, both of which are implicated in the structures of synapses, respectively. SAP97/hDLG is localized at epithelial junctions and may function as a scaffolding protein, but the subcellular localization or the function of MAGI-1/BAP1 has not been clarified. In intestinal epithelial cells, MAGI-1/BAP1 was localized at tight junctions, whereas SAP97/hDLG was localized diffusely at cell - cell junctions. In Madine Darby canine kidney (MDCK) cells, MAGI-1/BAP1 was colocalized with ZO-1, whereas SAP97/hDLG was colocalized with E-cadherin. In MDCK cells, dominant active and negative mutants of Rac1 small G protein changed the amounts of SAP97/hDLG at cell - cell junctions, but not that of MAGI-1/BAP1. When MDCK cells were switched to a low Ca2+ medium, E-cadherin disappeared from the plasma membrane, and cells were dissociated. The phorbol 12-myristate 13-acetate-treatment after the low Ca2+ switch induced a tight junction-like structure. MAGI-1/BAP1 was recruited with ZO-1 to this structure, but SAP97/hDLG or E-cadherin was not. These findings suggest that MAGI-1/BAP1 is a component of tight junctions of epithelial cells, and that its role is different from that of SAP97/hDLG.