Elevation of cyclic AMP causes an imbalance between NF-κB and p53 in NALM-6 cells treated by doxorubicin

We previously showed that cAMP can inhibit DNA damage-induced wild type p53 accumulation in human pre-B NALM-6 cells, leading to a profound reduction of their apoptotic response. Here, we provide evidence for the potentiation of DNA damage-induced NF-κB activation by cAMP. We found that inhibition of NF-κB activation prevents the inhibitory effect of cAMP on doxorubicin-induced apoptosis. Moreover, cAMP exerts its inhibitory effect on doxorubicin-induced apoptosis in a PKA-independent manner. The present study also shows that elevation of cAMP prolongs the phosphorylation of IκB and subsequent activation of NF-κB in doxorubicin treated NALM-6 cells in a proteasome-dependent manner. Taken together, our results demonstrate that cAMP abrogates the balance between apoptotic and antiapoptotic transcription factors that are hallmarks of DNA damage signaling. © 2010 Federation of European Biochemical Societies

An investigation of the nature of fear within ACL-injured subjects when exposed to provocative videos: a concurrent qualitative and quantitative study

Fear is a factor contributing to poor return to sport after an anterior cruciate (ACL) injury, however the identification and assessment of fear is challenging. To improve understanding of fear, this study qualitatively and quantitatively assessed responses to videos depicting threat to knee stability in people who had experienced an ACL injury. ACL-injured participants who had above average fear on the Tampa Scale of Kinesiophobia and were at least 1-year post-injury/surgery were eligible. Participants were shown four videos depicting sequentially increasing threat to their knee stability (running, cut-and-pivot, feigned knee injury during cut-and-pivot, series of traumatic knee injuries). Qualitative interviews explored participants feeling related to viewing the videos. Participants quantitatively self-rated fear and distress in response to each video. Seventeen participants were included in this study (71% female, with an average time since last ACL injury of 5 ½ years). Five themes were identified: (1) Evoked physiological responses, (2) Deeper contextualisation of the meaning of an ACL injury influencing bodily confidence, (3) Recall of psychological difficulties, (4) Negative implications of a re-injury, and (5) Change to athletic identity. Quantitatively, direct proportionality was noticed between threat level and reported fear and distress. Specifically, participants reported increasing levels of fear and distress as the videos progressed in threat level, with the largest increase seen between a cut-and-pivot movement to a feigned injury during a cut and pivot. The results support the notion that in addition to being a physical injury, an ACL injury has more complex neurophysiological, psychological, and social characteristics which should be considered in management. Using video exposure in the clinic may assist identification of underlying psychological barriers to recovery following an ACL injury, facilitating person-centred care

Pelvic trauma : WSES classification and guidelines

Complex pelvic injuries are among the most dangerous and deadly trauma related lesions. Different classification systems exist, some are based on the mechanism of injury, some on anatomic patterns and some are focusing on the resulting instability requiring operative fixation. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic impairment of pelvic ring function and the associated injuries. The management of pelvic trauma patients aims definitively to restore the homeostasis and the normal physiopathology associated to the mechanical stability of the pelvic ring. Thus the management of pelvic trauma must be multidisciplinary and should be ultimately based on the physiology of the patient and the anatomy of the injury. This paper presents the World Society of Emergency Surgery (WSES) classification of pelvic trauma and the management Guidelines.Peer reviewe

Absolute risk and predictors of the growth of acute spontaneous intracerebral haemorrhage: a systematic review and meta-analysis of individual patient data.

Background Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography. Methods In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known. Findings Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07). Interpretation In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials

Understanding Fear after an Anterior Cruciate Ligament Injury: A Qualitative Thematic Analysis Using the Common-Sense Model

Fear is a significant factor affecting successful return to sport following an anterior cruciate ligament (ACL) injury. However, there is a lack of understanding of the emotional drivers of fear and how fear beliefs are formed. This study qualitatively explored the contextual and emotional underpinnings of fear and how these beliefs were formed, with reference to the Common-Sense Model of Self-Regulation. Face-to-face online interviews were conducted with ACL-injured participants (n = 18, 72% female) with a mean age of 28 years (range 18–50 years). Participants were either 1 year post ACL reconstruction surgery (n = 16) or at least 1 year post injury without surgery (n = 2) and scored above average on a modified Tampa Scale of Kinesiophobia. Four participants were playing state-level sport or higher. Five themes emerged describing factors contributing to fear: ‘External messages’, ‘Difficulty of the ACL rehabilitation journey’, ‘Threat to identity and independence’, ‘Socioeconomic factors’, and ‘Ongoing psychological barriers’. A sixth theme, ‘Positive coping strategies’, provided insight into influences that could reduce fear and resolve negative behaviors. This study identified a broad range of contextual biopsychosocial factors which contribute to fear, supporting the notion that ACL injuries should not be treated through a purely physical lens. Furthermore, aligning the themes to the common-sense model provided a conceptual framework conveying the inter-related, emergent nature of the identified themes. The framework provides clinicians with a means to understanding fear after an ACL injury. This could guide assessment and patient education