This evidence-based clinical practice guideline is a revision of the 2004 acute otitis media (AOM) guideline from the American Academy of Pediatrics (AAP) and American Academy of Family Physicians. ...It provides recommendations to primary care clinicians for the management of children from 6 months through 12 years of age with uncomplicated AOM. In 2009, the AAP convened a committee composed of primary care physicians and experts in the fields of pediatrics, family practice, otolaryngology, epidemiology, infectious disease, emergency medicine, and guideline methodology. The subcommittee partnered with the Agency for Healthcare Research and Quality and the Southern California Evidence-Based Practice Center to develop a comprehensive review of the new literature related to AOM since the initial evidence report of 2000. The resulting evidence report and other sources of data were used to formulate the practice guideline recommendations. The focus of this practice guideline is the appropriate diagnosis and initial treatment of a child presenting with AOM. The guideline provides a specific, stringent definition of AOM. It addresses pain management, initial observation versus antibiotic treatment, appropriate choices of antibiotic agents, and preventive measures. It also addresses recurrent AOM, which was not included in the 2004 guideline. Decisions were made on the basis of a systematic grading of the quality of evidence and benefit-harm relationships. The practice guideline underwent comprehensive peer review before formal approval by the AAP. This clinical practice guideline is not intended as a sole source of guidance in the management of children with AOM. Rather, it is intended to assist primary care clinicians by providing a framework for clinical decision-making. It is not intended to replace clinical judgment or establish a protocol for all children with this condition. These recommendations may not provide the only appropriate approach to the management of this problem.
Membrane overexpression of the receptor tyrosine kinase ErbB-2 (MErbB-2) accounts for a clinically aggressive breast cancer (BC) subtype (ErbB-2-positive) with increased incidence of metastases. We ...and others demonstrated that nuclear ErbB-2 (NErbB-2) also plays a key role in BC and is a poor prognostic factor in ErbB-2-positive tumors. The signal transducer and activator of transcription 3 (Stat3), another player in BC, has been recognized as a downstream mediator of MErbB-2 action in BC metastasis. Here, we revealed an unanticipated novel direction of the ErbB-2 and Stat3 interaction underlying BC metastasis. We found that Stat3 binds to its response elements (GAS) at the ErbB-2 promoter to upregulate ErbB-2 transcription in metastatic, ErbB-2-positive BC. We validated these results in several BC subtypes displaying metastatic and non-metastatic ability, highlighting Stat3 general role as upstream regulator of ErbB-2 expression in BC. Moreover, we showed that Stat3 co-opts NErbB-2 function by recruiting ErbB-2 as its coactivator at the GAS sites in the promoter of microRNA-21 (miR-21), a metastasis-promoting microRNA (miRNA). Using an ErbB-2 nuclear localization domain mutant and a constitutively activated ErbB-2 variant, we found that NErbB-2 role as a Stat3 coactivator and also its direct role as transcription factor upregulate miR-21 in BC. This reveals a novel function of NErbB-2 as a regulator of miRNAs expression. Increased levels of miR-21, in turn, downregulate the expression of the metastasis-suppressor protein programmed cell death 4 (PDCD4), a validated miR-21 target. Using an in vivo model of metastatic ErbB-2-postive BC, in which we silenced Stat3 and reconstituted ErbB-2 or miR-21 expression, we showed that both are downstream mediators of Stat3-driven metastasis. Supporting the clinical relevance of our results, we found an inverse correlation between ErbB-2/Stat3 nuclear co-expression and PDCD4 expression in ErbB-2-positive primary invasive BCs. Our findings identify Stat3 and NErbB-2 as novel therapeutic targets to inhibit ErbB-2-positive BC metastasis.
Abstract Background Identification of biomarkers in lung cancer, a leading cause of cancer-related mortality, has a meaningful clinical relevance in the quest of novel prognostic factors and ...therapeutic targets. The glycan-binding protein galectin-1 (Gal-1) modulates tumor progression by mediating cell–cell and cell–extracellular matrix interactions, as well as angiogenesis and tumor immune-escape. Previous works reported the expression of Gal-1 in lung cancer, although its clinical significance remains uncertain. Objective To assess the clinicopathologic relevance and prognostic value of Gal-1 expression in a cohort of 103 Stage I–III non-small cell lung cancer (NSCLC) patients. Methods Gal-1 expression was determined by immunohistochemistry in tumor tissue samples. The percentage of immunoreactive tumor cells and stroma, as well as the presence of blood vessels with positively stained endothelium in the tumor and surrounding normal tissue, were recorded. Results were correlated with the clinicopathologic factors of the patients (Spearman's rank correlation coefficient, chi-square test) and overall survival by univariate (Kaplan Meier) and multivariate analyses (Cox regression hazard model). Results We did not observe significant associations between Gal-1 expression and relevant clinicopathologic features at diagnosis of NSCLC. However, Kaplan Meier analysis revealed a significant association between Gal-1 expression and overall survival, when Gal-1 expression was analyzed on tumor cells alone (“tumor cell percentage”) or when an integrated score accounting for tumor cell as well as stromal expression of Gal-1 (“total score”) was assessed. Patients showing high Gal-1 expression evidenced a poorer clinical outcome. Furthermore, “total score” remained significantly associated with survival by multivariate Cox regression analysis in the whole cohort of patients, even when controlling for the classical predictors and prognostic factors of NSCLC. Conclusion We conclude that Gal-1 expression may be a useful biomarker for better prediction of the clinical outcome and management of NSCLC patients.
New Findings
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What is the central question of this study?
We explored whether experimental cancer‐induced cachexia may alter mitochondrial respiratory chain (MRC) complexes and oxygen uptake in ...respiratory and peripheral muscles, and whether signalling pathways, proteasome and oxidative stress influence that process.
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What is the main finding and what is its importance?
In cancer cachectic mice, MRC complexes and oxygen consumption were decreased in the diaphragm and gastrocnemius. Blockade of nuclear factor‐κB and mitogen‐activated protein kinase actions partly restored the muscle mass and force and corrected the MRC dysfunction, while concomitantly reducing tumour burden. Antioxidants improved mitochondrial oxygen consumption without eliciting effects on the loss of muscle mass and force or the tumour size, whereas bortezomib reduced tumour burden without influencing muscle mass and strength or MRC function.
Abnormalities in mitochondrial content, morphology and function have been reported in several muscle‐wasting conditions. We specifically explored whether experimental cancer‐induced cachexia may alter mitochondrial respiratory chain (MRC) complexes and oxygen uptake in respiratory and peripheral muscles, and whether signalling pathways, proteasomes and oxidative stress may influence that process. We evaluated complex I, II and IV enzyme activities (specific activity assays) and MRC oxygen consumption (polarographic measurements) in diaphragm and gastrocnemius of cachectic mice bearing the LP07 lung tumour, with and without treatment with N‐acetylcysteine, bortezomib and nuclear factor‐κB (sulfasalazine) and mitogen‐activated protein kinases (MAPK, U0126) inhibitors (n= 10 per group for all groups). Whole‐body and muscle weights and limb muscle force were also assessed in all rodents at baseline and after 1 month. Compared with control animals, cancer cachectic mice showed a significant reduction in body weight gain, smaller sizes of the diaphragm and gastrocnemius, lower muscle strength, decreased activity of complexes I, II and IV and decreased oxygen consumption in both muscles. Blockade of nuclear factor‐κB and MAPK actions restored muscle mass and force and corrected the MRC dysfunction in both muscles, while partly reducing tumour burden. Antioxidants improved mitochondrial oxygen uptake without eliciting significant effects on the loss of muscle mass and force or tumour size, whereas the proteasome inhibitor reduced tumour burden without significantly influencing muscle mass and strength or mitochondrial function. In conclusion, nuclear factor‐κB and MAPK signalling pathways modulate muscle mass and performance and MRC function of respiratory and limb muscles in this model of experimental cancer cachexia, thus offering targets for therapeutic intervention.
Dehydration from viral gastroenteritis is a significant pediatric health problem. Oral rehydration therapy (ORT) is recommended as first-line therapy for both mildly and moderately dehydrated ...children; however, three quarters of pediatric emergency medicine physicians who are very familiar with the American Academy of Pediatrics recommendations for ORT still use intravenous fluid therapy (IVF) for moderately dehydrated children.
To test the hypothesis that the failure rate of ORT would not be >5% greater than the failure rate of IVF. Secondary hypotheses were that patients in the ORT group will (1) require less time initiating therapy, (2) show more improvement after 2 hours of therapy, (3) have fewer hospitalizations, and (4) prefer ORT for future episodes of dehydration.
A randomized, controlled clinical trial (noninferiority study design) was performed in the emergency department of an urban children's hospital from December 2001 to April 2003. Children 8 weeks to 3 years old were eligible if they were moderately dehydrated, based on a validated 10-point score, from viral gastroenteritis. Patients were randomized to receive either ORT or IVF during the 4-hour study. Treating physicians were masked and assessed all patients before randomization at 2 and 4 hours of therapy. Successful rehydration at 4 hours was defined as resolution of moderate dehydration, production of urine, weight gain, and the absence severe emesis (> or =5 mL/kg).
Seventy-three patients were enrolled in the study: 36 were randomized to ORT and 37 were randomized to IVF. Baseline dehydration scores and the number of prior episodes of emesis and diarrhea were similar in the 2 groups. ORT demonstrated noninferiority for the main outcome measure and was found to be favorable with secondary outcomes. Half of both the ORT and IVF groups were rehydrated successfully at 4 hours (difference: -1.2%; 95% confidence interval CI: -24.0% to 21.6%). The time required to initiate therapy was less in the ORT group at 19.9 minutes from randomization, compared with 41.2 minutes for the IVF group (difference: -21.2 minutes; 95% CI: -10.3 to -32.1 minutes). There was no difference in the improvement of the dehydration score at 2 hours between the 2 groups (78.8% ORT vs 80% IVF; difference: -1.2%; 95% CI: -20.5% to 18%). Less than one third of the ORT group required hospitalization, whereas almost half of the IVF group was hospitalized (30.6% vs 48.7%, respectively; difference: -18.1%; 95% CI: -40.1% to 4.0%). Patients who received ORT were as likely as those who received IVF to prefer the same therapy for the next episode of gastroenteritis (61.3% vs 51.4%, respectively; difference: 9.9%; 95% CI: -14% to 33.7%).
This trial demonstrated that ORT is as effective as IVF for rehydration of moderately dehydrated children due to gastroenteritis in the emergency department. ORT demonstrated noninferiority for successful rehydration at 4 hours and hospitalization rate. Additionally, therapy was initiated more quickly for ORT patients. ORT seems to be a preferred treatment option for patients with moderate dehydration from gastroenteritis.
ObjectivePsychology is a high burnout profession; however, little empirical research has examined the emotional labour (i.e., surface acting, deep acting, expression of naturally felt emotions) of ...psychologists who provide psychological therapy. The present study examined whether a relationship exists between emotional labour and wellbeing (operationalised as burnout and affective symptoms) in this sample, and whether individual or work-related factors moderate this relationship.Method113 Australian psychologists who provide regular psychological therapy responded to an anonymous, online, cross-sectional survey. This survey collected information on demographic and workplace variables; it also contained measures of emotional labour and wellbeing.ResultsThe results indicated that, at a bivariate level, surface acting was a significant predictor of adverse wellbeing; deep acting had no predictive qualities; and the expression of naturally felt emotions was a significant predictor of improved wellbeing. Surface acting appeared to be the most salient predictor, and its relationship to burnout was moderated by compensation type.ConclusionsReported rates of burnout were high within our sample, and our findings suggest that the masking of emotions by psychologists (i.e., surface acting) may be a contributing factor to adverse wellbeing. These findings carry implications for psychological training and practice.
Doxorubicin is an anti-tumor antibiotic widely used in the management of cancer patients. Its main mechanism of action involves the generation of DNA damage and the inhibition of topoisomerase II, ...promoting apoptosis. AD 198 is a novel doxorubicin analog devoid of DNA binding and topoisomerase II inhibitory capacities. It has been proposed that AD 198 induces apoptosis by activating protein kinase C delta (PKCδ); a PKC isoform described as growth inhibitory in a large number of cell types. We have previously demonstrated that PKCδ overexpression in NMuMG cells induced the opposite effect, promoting proliferation and cell survival. In this study, we found that PKCδ overexpression confers an enhanced cell death resistance against AD 198 cytotoxic effect and against AD 288, another doxorubicin analog that preserves its mechanism of action. These resistances involve PKCδ-mediated activation of two well-known survival pathways: Akt and NF-κB. While the resistance against AD 198 could be abrogated upon the inhibition of either Akt or NF-κB pathways, only NF-κB inhibition could revert the resistance to AD 288. Altogether, our results indicate that PKCδ increases cell death resistance against different apoptosis inductors, independently of their mechanism of action, through a differential modulation of Akt and NF-κB pathways. Our study contributes to a better understanding of the mechanisms involved in PKCδ-induced resistance and may greatly impact in the rationale design of isozyme-specific PKC modulators as therapeutic agents.
Cue utilisation and situational awareness share similar properties since both constructs are dependent upon the application of feature-event associations in memory. The aim of this study was to ...investigate the extent to which cue utilisation and situational awareness contribute to learning a simplified, simulated rail control task incorporating an implicit pattern of train movements. Fifty-five undergraduate students completed an assessment of cue utilisation prior to completing the rail control task during periods of lower and higher task demands. Situational awareness was assessed using Situation Awareness Global Assessment Technique (SAGAT) queries. The results indicated that, while both cue utilisation and situational awareness were related to the detection of the implicit pattern of train movements, they contributed separately to performance on the simulated rail control task. The outcomes suggest that cue utilisation and situational awareness may be separate constructs, where cue utilisation constitutes a capacity variable that is associated with changes in response to task demand and situational awareness constitutes an outcome variable that emerges through task exposure.
•Cue utilisation and situational awareness engage similar cognitive structures.•Cue utilisation and situational awareness are associated with implicit learning.•No relationship is evident between cue utilisation and situational awareness.•Situational awareness predicts performance in high demand conditions.•Cue utilisation predicts performance in both low and high demand conditions.
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