The Relationship Between Respite Care and Child Abuse Potential in Parents of Children with Developmental Disabilities: A Preliminary Report

This study longitudinally examined the impact of respite care services on child abuse potential and family relations in a sample of parents (N = 14) whose children were admitted for respite care to a center for developmental disability. A sample of parents (N = 18) whose children were admitted for short-term hospitalization (STH) was used as a contrast group. In addition, we examined the interrelationships between child abuse potential, family relations, and parenting stress at 3 time points. Parents completed measures of child abuse potential, family relations, and parenting stress at time of admission, discharge, and at a 2-month follow-up. Results indicated that neither respite care nor STH resulted in significant effects on child abuse potential or family relations although trends were found in the expected direction. Strong interrelationships were found between child abuse potential, family relations, and parenting stress at each of the 3 time points. These preliminary results suggest that respite care may be insufficient to directly impact child abuse potential; however, interventions that target variables related to abuse (e.g., quality of family relations, parenting stress) might be beneficial.     

Allergen challenge alters lymphocyte phosphodiesterase activity in horses with heaves

Heaves is an allergic airway disease in horses characterised by reversible airway obstruction, bronchial hyperresponsiveness and airway inflammation associated with a Th(2) response. Cyclic nucleotide-dependent signalling pathways can regulate lymphocyte function. In this study, we examined lymphocyte PDE activity comparing horses with heaves to healthy control animals. Total PDE activity and the effects of isoenzyme selective inhibitors were measured before, 5 and 24 h after the start of a 7 h allergen challenge. Allergen challenge had no effect on either total cAMP PDE activity or its inhibition by the PDE4 selective inhibitor, rolipram, and the non-selective PDE inhibitor, theophylline. In contrast, the PDE3 selective inhibitor, quazinone, caused significantly greater inhibition of cAMP PDE activity before challenge in the heaves susceptible group. Additionally, total cGMP PDE activity was significantly lower 24 h after the start of challenge in the heaves affected group (11+/-2 and 21+/-3 pmol/min/mg for heaves and control animals, respectively) and the PDE5 selective inhibitor, zaprinast, caused significantly less inhibition in the heaves group at this time point. The functional significance of these findings was explored by examining the effect of PDE3, PDE4 and PDE5 selective inhibitors on mitogen-induced mononuclear cell proliferation before and 24 h after the start of allergen challenge. Proliferation decreased after challenge in the heaves group (stimulation index=328+/-110 and 200+/-72 before and after challenge, respectively) whilst remaining constant in the control group (stimulation index=161+/-13 and 183+/-45 before and after challenge, respectively). However, all three PDE inhibitors caused a similar amount of inhibition at each time point and the effect of a combination of a PDE3 and a PDE5 inhibitor was simply additive in both groups. These results suggest differences in the control of lymphocyte PDE activity in horses with heaves.     

Summary: peripheral pharmacology of cough

Hypersensitivity of the 'cough receptors' is one of the primary causes of uncontrollable and nonproductive cough. These receptors are therefore the logical targets in developing antitussive therapeutics. The articles in this section focus primarily on the types of lung afferents mediating the cough reflexes and the mechanisms involved in regulating the activity and sensitivity of these afferents. Several major issues have been discussed in these presentations, including the pharmacologic, physiologic and neurochemical characteristics of the cough receptors; the effect of phenotypic switch of the rapidly adapting receptors (RARs) during chronic airway infection; the interaction between RARs and C-fiber afferents both at the receptor level and in the centrally mediated reflex pathway; and the cellular mechanisms and ion channel species involved in the hypersensitivity of the cough receptors. A number of important questions have emerged from these investigations. Answers to these questions should further advance our understanding of the peripheral mechanisms of cough reflexes.     

STAT3 pathway regulates lung-derived brain metastasis initiating cell capacity through miR-21 activation

Brain metastases (BM) represent the most common tumor to affect the adult central nervous system. Despite the increasing incidence of BM, likely due to consistently improving treatment of primary cancers, BM remain severely understudied. In this study, we utilized patient-derived stem cell lines from lung-to-brain metastases to examine the regulatory role of STAT3 in brain metastasis initiating cells (BMICs). Annotation of our previously described BMIC regulatory genes with protein-protein interaction network mapping identified STAT3 as a novel protein interactor. STAT3 knockdown showed a reduction in BMIC self-renewal and migration, and decreased tumor size in vivo. Screening of BMIC lines with a library of STAT3 inhibitors identified one inhibitor to significantly reduce tumor formation. Meta-analysis identified the oncomir microRNA-21 (miR-21) as a target of STAT3 activity. Inhibition of miR-21 displayed similar reductions in BMIC self-renewal and migration as STAT3 knockdown. Knockdown of STAT3 also reduced expression of known downstream targets of miR-21. Our studies have thus identified STAT3 and miR-21 as cooperative regulators of stemness, migration and tumor initiation in lung-derived BM. Therefore, STAT3 represents a potential therapeutic target in the treatment of lung-to-brain metastases.     

Positive end-expiratory pressure titration in acute respiratory distress syndrome patients: impact on right ventricular outflow impedance evaluated by pulmonary artery Doppler flow velocity measurements

OBJECTIVE: Positive end-expiratory pressure (PEEP) titration in acute respiratory distress syndrome patients remains debatable. We used two mechanical approaches, calculation of the compliance of the respiratory system and determination of the lower inflexion point of the pressure-volume curve of the respiratory system, to identify specific PEEPs (PEEPS and PEEPA) whose impact on right ventricular (RV) outflow was compared with Doppler analysis of pulmonary artery flow velocity. DESIGN: Prospective, open, clinical study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Sixteen consecutive ventilator-dependent acute respiratory distress syndrome patients. INTERVENTIONS: Two PEEPs were determined: PEEPS was the highest PEEP associated with the highest value of respiratory compliance, and PEEPA was the coordinate of the lower inflexion point of the inspiratory pressure-volume curve on the pressure axis plus 2 cm H2O. MEASUREMENTS AND MAIN RESULTS: We observed a large difference between the two PEEPs, with PEEPA (13 + 4 cm H2O) > PEEPS (6 + 3 cm H2O). Changes in RV outflow impedance produced by tidal ventilation with zero end-expiratory pressure (ZEEP) and after application of these two PEEPs were assessed by Doppler study of pulmonary artery flow velocity obtained by a transesophageal approach, with particular reference to the end-expiratory and end-inspiratory pulmonary artery velocity-time integral, as reflecting RV stroke output, and mean acceleration as reflecting RV outflow impedance during an unchanged flow period. A significant inspiratory reduction in pulmonary artery velocity-time integral (from 11.8 + 0.3 to 10.0 + 0.3 cm) and mean acceleration (from 11.9 + 0.9 to 8.0 + 0.9 m/sec2) was observed with ZEEP, showing a reduction in RV stroke index (from 29.0 + 0.9 to 26.0 + 0.6 cm3/m2) by a sudden increase in outflow impedance during tidal ventilation. Application of PEEPA, which improved Pao2 (102 + 40 vs. 65 + 18 torr with ZEEP), worsened the inspiratory drop in RV stroke index (21.6 + 0.8 cm3/m2), resulting in a significant reduction in cardiac index compared with ZEEP (from 3.0 + 1.0 to 2.7 + 1.1). Application of PEEPS, which also significantly improved Pao2 (81 + 21 torr), was associated with a lesser impact on RV outflow impedance (inspiratory mean acceleration: 9.5 + 1 m/sec2) and cardiac index (3.2 + 1.0) than PEEPA. CONCLUSION: RV outflow impedance evaluated by the Doppler technique appeared sensitive to PEEP titration. Application of PEEPA worsened RV systolic function impairment produced by tidal ventilation. Conversely, application of PEEPS reduced RV systolic function impairment, suggesting an association with a lower pulmonary vascular resistance.     

Platelet-activating factor: a possible mediator of the dual response to allergen?

Certain allergic asthmatic patients exhibit a dual response in the lung following bronchial challenge with the appropriate allergen. Often this is paralleled by a cutaneous dual response when the antigen is injected intradermally. The mechanisms underlying such phenomena are not established, but some evidence suggests that the late response is a consequence of the early response. Since platelet activation has been observed following antigen challenge in asthmatic subjects, we have studied the ability of platelet activating factor (PAF-acether, AGEPC) to induce cutaneous inflammatory responses in man. In a time course study over 24 hr, PAF-acether produced a biphasic response: an immediate weal and flare reaction, which resolved within 1-2 hr and was followed some 3-6 hr later by a delayed reaction in which erythema associated with hyperalgesia was evident. These observations suggest that PAF-acether should be considered in the context of allergic asthma as a possible mediator of the dual response to allergen.     

A comparison between the clinical significance and growth mixture modelling early change methods at predicting negative outcomes

Abstract

Objective: Routine outcome monitoring benefits treatment by identifying potential no change and deterioration. The present study compared two methods of identifying early change and their ability to predict negative outcomes on self-report symptom and wellbeing measures. Method: 1467 voluntary day patients participated in a 10-day group Cognitive Behaviour Therapy (CBT) program and completed the symptom and wellbeing measures daily. Early change, as defined by (a) the clinical significance method and (b) longitudinal modelling, was compared on each measure. Results: Early change, as defined by the simpler clinical significance method, was superior at predicting negative outcomes than longitudinal modelling. The longitudinal modelling method failed to detect a group of deteriorated patients, and agreement between the early change methods and the final unchanged outcome was higher for the clinical significance method. Conclusions: Therapists could use the clinical significance early change method during treatment to alert them of patients at risk for negative outcomes, which in turn could allow therapists to prevent those negative outcomes from occurring.     

A protocol for quantifying cardiogenic oscillations in dynamic 129Xe gas exchange spectroscopy: The effects of idiopathic pulmonary fibrosis

The spectral parameters of hyperpolarized ¹²⁹Xe exchanging between airspaces, interstitial barrier, and red blood cells (RBCs) are sensitive to pulmonary pathophysiology. This study sought to evaluate whether the dynamics of ¹²⁹Xe spectroscopy provide additional insight, with particular focus on quantifying cardiogenic oscillations in the RBC resonance. ¹²⁹Xe spectra were dynamically acquired in eight healthy volunteers and nine subjects with idiopathic pulmonary fibrosis (IPF). ¹²⁹Xe FIDs were collected every 20 ms (T_E = 0.932 ms, 512 points, dwell time = 32 μs, flip angle ≈ 20°) during a 16 s breathing maneuver. The FIDs were pre‐processed using the spectral improvement by Fourier thresholding technique (SIFT) and fit in the time domain to determine the airspace, interstitial barrier, and RBC spectral parameters. The RBC and gas resonances were fit to a Lorentzian lineshape, while the barrier was fit to a Voigt lineshape to account for its greater structural heterogeneity. For each complex resonance the amplitude, chemical shift, linewidth(s), and phase were calculated. The time‐averaged spectra confirmed that the RBC to barrier amplitude ratio (RBC:barrier ratio) and RBC chemical shift are both reduced in IPF subjects. Their temporal dynamics showed that all three ¹²⁹Xe resonances are affected by the breathing maneuver. Most notably, several RBC spectral parameters exhibited prominent oscillations at the cardiac frequency, and their peak‐to‐peak variation differed between IPF subjects and healthy volunteers. In the IPF cohort, oscillations were more prominent in the RBC amplitude (16.8 ± 5.2 versus 9.7 ± 2.9%; P = 0.008), chemical shift (0.43 ± 0.33 versus 0.083 ± 0.05 ppm; P < 0.001), and phase (7.7 ± 5.6 versus 1.4 ± 0.8°; P < 0.001). Dynamic ¹²⁹Xe spectroscopy is a simple and sensitive tool that probes the temporal variability of gas exchange and may prove useful in discerning the underlying causes of its impairment.