Do people with chronic pain judge their sleep differently? A qualitative study

People with chronic pain often report sleep of “poor quality”. However, it is unclear what defines sleep quality and whether their sleep quality judgment is influenced by factors other than sleep. We purposively interviewed 17 participants with and without chronic pain and thematically analyzed their interview transcripts. Four salient criteria for judging sleep quality were: (i) Memories of night-time sleep disruptions, (ii) Feelings on waking and cognitive functioning during the day, (iii) Ability to engage in daytime physical and social activity, and (iv) Changes in physical symptoms (and pain intensity among participants with chronic pain). Sleep quality judgment is complex and involves retrospective decision-making influenced by not only memories of the night but also how we feel and what we do during the day

Effects of sleep changes on pain-related health outcomes in the general population : a systematic review of longitudinal studies with exploratory meta-analysis

Emerging longitudinal research has highlighted poor sleep as a risk factor of a range of adverse health outcomes, including disabling pain conditions. In establishing the causal role of sleep in pain, it remains to be clarified whether sleep deterioration over time is a driver of pain and whether sleep improvement can mitigate pain-related outcomes. A systematic literature search was performed using PubMed MEDLINE, Ovid EMBASE, and Proquest PsycINFO, to identify 16 longitudinal studies involving 61,000 participants. The studies evaluated the effect of sleep changes (simulating sleep deterioration, sleep stability, and sleep improvement) on subsequent pain-related outcomes in the general population. A decline in sleep quality and sleep quantity was associated with a two- to three-fold increase in risk of developing a pain condition, small elevations in levels of inflammatory markers, and a decline in self-reported physical health status. An exploratory meta-analysis further revealed that deterioration in sleep was associated with worse self-reported physical functioning (medium effect size), whilst improvement in sleep was associated with better physical functioning (small effect size). The review consolidates evidence that changes in sleep are prospectively associated with pain-related outcomes and highlights the need for further longitudinal investigations on the long-term impact of sleep improvements

Changes in sleep duration, quality, and medication use are prospectively associated with health and well-being : analysis of the UK Household Longitudinal Study

Introduction: Sleep is a plausible target for public health promotion. We examined the association of changes in sleep with subsequent health and well-being in the general population. Aims and Methods: We analyzed data from the UK Household Longitudinal Survey, involving 30594 people (aged > 16) who provided data on sleep and health and well-being at both Wave 1 (2009–2011) and Wave 4 (2012–2014) assessments. Predicting variables were changes in sleep quantity, sleep quality, and sleep medication use over the 4-year period. Outcome variables were the General Health Questionnaire (GHQ-12) and the 12-Item Short-Form Health Survey (SF-12) mental (MCS) and physical (PCS) component scores at Wave 4. Linear regression on each outcome was fully adjusted for potential confounders and baseline values of the relevant predicting and outcome variables. Results: Better outcomes were associated with an increase in sleep duration (GHQ: β = 1.031 [95% confidence interval {CI}: −1.328, −0.734]; MCS: 1.531 [1.006, 2.055]; PCS: −0.071 [−0.419, 0.56]), sleep quality (GHQ: β = −2.031 [95% CI: −2.218, −1.844]; MCS: 3.027 [2.692, 3.361]; PCS: 0.924 [0.604, 1.245]), and a reduction in sleep medication use (GHQ: β = −1.929 [95% CI: −2.400, −1.459]; MCS: 3.106 [2.279, 3.933]; PCS: 2.633 [1.860, 3.406]). Poorer outcomes were on the other hand associated with a reduction in sleep duration, a decrease in sleep quality, and an increase in sleep medication use. Changes in sleep quality yielded the largest effects on the health and well-being outcomes. Conclusions: Changes in sleep were temporally associated with subsequent health and well-being. Initiatives that aim to protect a critical amount of sleep, promote sleep quality, and reduce sleep medication use may have public health values

Transferrin-Liposome-Mediated Systemic p53 Gene Therapy in Combination with Radiation Results in Regression of Human Head and Neck Cancer Xenografts

This is the published version, also available here: http://dx.doi.org/10.1089/10430349950016357.The use of cationic liposomes as nonviral vehicles for the delivery of therapeutic molecules is becoming increasingly prevalent in the field of gene therapy. We have previously demonstrated that the use of the transferrin ligand (Tf) to target a cationic liposome delivery system resulted in a significant increase in the transfection efficiency of the complex [Xu, L., Pirollo, K.F., and Chang, E.H. (1997). Hum. Gene Ther. 8, 467-475]. Delivery of wild-type (wt) p53 to a radiation-resistant squamous cell carcinoma of the head and neck (SCCHN) cell line via this ligand-targeted, liposome complex was also able to revert the radiation resistant phenotype of these cells in vitro. Here we optimized the Tf/liposome/DNA ratio of the complex (LipT) for maximum tumor cell targeting, even in the presence of serum. The efficient reestablishment of wtp53 function in these SCCHN tumor cells in vitro, via the LipT complex, restored the apoptotic pathway, resulting in a significant increase in radiation-induced apoptosis that was directly proportional to the level of exogenous wtp53 in the tumor cells. More significantly, intravenous administration of LipT-p53 markedly sensitized established SCCHN nude mouse xenograft tumors to radiotherapy. The combination of systemic LipT-p53 gene therapy and radiation resulted in complete tumor regression and inhibition of their recurrence even 6 months after the end of all treatment. These results indicate that this tumor-specific, ligand-liposome delivery system for p53 gene therapy, when used in concert with conventional radiotherapy, can provide a new and more effective means of cancer treatment

Development of the pain-related beliefs and attitudes about sleep (PBAS) scale for the assessment and treatment of insomnia comorbid with chronic pain

Study Objectives Dysfunctional beliefs and attitudes about sleep is a cognitive-behavioral factor central to the development and perpetuation of insomnia. Previous works to unravel the complex interrelationship between pain and insomnia have not explored the role of inflexible beliefs about the sleep-pain interaction, possibly due to a lack of a valid instrument for doing so. The current study evaluated the psychometric and functional properties of a 10-item Pain-Related Beliefs and Attitudes about Sleep (PBAS) scale. Methods The PBAS scale was administered to four clinical samples of chronic pain patients with comorbid insomnia: to examine the scale’s psychometric properties (n=137), test-retest reliability (n=26), sensitivity to treatment (n=20), and generalizability (n=62). All participants completed the PBAS together with validated measures of pain interference, insomnia severity, and cognitive-behavioral processes hypothesized to underpin insomnia. Results The PBAS scale was found to be reliable, with adequate internal consistency and temporal stability. Factor analysis suggested a 2-factor solution representing beliefs about “pain as the primary cause of insomnia” and the “inevitable consequences of insomnia on pain and coping”. The PBAS total score was positively correlated with scores from the Insomnia Severity Index (ISI) scale, Dysfunctional Beliefs and Attitudes about Sleep (DBAS) scale, and the Anxiety and Preoccupation about Sleep Questionnaire (APSQ). It was a significant predictor of insomnia severity and pain interference. A significant reduction in PBAS was also observed in patients after receiving a hybrid cognitive-behavioral intervention for both pain and insomnia. Conclusions Pain-related sleep beliefs appear to be an integral part of chronic pain patients’ insomnia experience. The PBAS is a valid and reliable instrument for evaluating the role of these beliefs in chronic pain patients

Estimating risk of C. difficile transmission from PCR positive but cytotoxin negative cases

Background: The use of molecular methods to diagnose Clostridium difficile infection (CDI) has improved diagnostic yield compared to conventional methods. However, PCR testing can detect colonization and has introduced several practical challenges pertaining to need for treatment and isolation of cases. Methods: For all new cases detected by real-time PCR, concurrent cytotoxin assay was performed and genetic characterization with MLVA (multi-locus variable number tandem repeat analysis) was done to determine relatedness. We used PCR cycle threshold (Ct) of detection as surrogate marker for bacterial burden in stool. Results: Overall, 54 cases of CDI were detected during the study period. 42 were concurrently tested by CYT and characterized by MLVA. MLVA analysis revealed marked genetic diversity with no ongoing outbreaks; four cases were due to NAP1 strain. CYT-/PCR + cases had a higher median Ct value of detection compared to CYT+/PCR + cases (28.2 vs 22.5; p = 0.01). Among 25 strains that were genetically related, 9/11 isolates in this dominant cluster were positive by CYT compared to 4/14 in non-dominant clusters (p = 0.02). Conclusion: CYT-/PCR+ cases contribute to hospital based transmission. However, the risk of transmission of C. difficile from CYT +/PCR+ cases may be higher than those that are CYT-/PCR+. © 2014 Kamboj et al

Systemic profiles of micrornas, redox balance, and inflammation in lung cancer patients : influence of copd

Altres ajuts: This study has been supported by Spanish Ministry of Science and Innovation, Sociedad Española de Neumología y Cirugía Torácica (SEPAR) 2018 & 2020.Lung cancer (LC) risk increases in patients with chronic respiratory diseases (COPD). MicroRNAs and redox imbalance are involved in lung tumorigenesis in COPD patients. Whether systemic alterations of those events may also take place in LC patients remains unknown. Our objectives were to assess the plasma levels of microRNAs, redox balance, and cytokines in LC patients with/without COPD. MicroRNAs (RT-PCR) involved in LC, oxidized DNA, MDA-protein adducts, GSH, TEAC, VEGF, and TGF-beta (ELISA) were quantified in plasma samples from non-LC controls (n = 45), LC-only patients (n = 32), and LC-COPD patients (n = 91). In LC-COPD patients compared to controls and LC-only, MDA-protein adduct levels increased, while those of GSH decreased, and two patterns of plasma microRNA were detected. In both LC patient groups, miR-451 expression was downregulated, while those of microRNA-let7c were upregulated, and levels of TEAC and TGF-beta increased compared to the controls. Correlations were found between clinical and biological variables. A differential expression profile of microRNAs was detected in patients with LC. Moreover, in LC patients with COPD, plasma oxidative stress levels increased, whereas those of GSH declined. Systemic oxidative and antioxidant markers are differentially expressed in LC patients with respiratory diseases, thus implying its contribution to the pathogenesis of tumorigenesis in these patients

Self-Assembly of a Virus-Mimicking Nanostructure System for Efficient Tumor-Targeted Gene Delivery

This is the published version, also available here: http://dx.doi.org/10.1089/10430340252792594.Molecular therapy, including gene therapy, is a promising strategy for the treatment of human disease. However, delivery of molecular therapeutics efficiently and specifically to the target tissue remains a significant challenge. A human transferrin (Tf)-targeted cationic liposome-DNA complex, Tf-lipoplex, has shown high gene transfer efficiency and efficacy with human head and neck cancer in vitro and in vivo (Xu, L., Pirollo, K.F., Tang, W.H., Rait, A., and Chang, E.H. Hum. Gene Ther. 1999;10:2941-2952). Here we explore the structure, size, formation process, and structure-function relationships of Tf-lipoplex. We have observed Tf-lipoplex to have a highly compact structure, with a relatively uniform size of 50-90 nm. This nanostructure is novel in that it resembles a virus particle with a dense core enveloped by a membrane coated with Tf molecules spiking the surface. More importantly, compared with unliganded lipoplex, Tf-lipoplex shows enhanced stability, improved in vivo gene transfer efficiency, and long-term efficacy for systemic p53 gene therapy of human prostate cancer when used in combination with conventional radiotherapy. On the basis of our observations, we propose a multistep self-assembly process and Tf-facilitated DNA cocondensation model that may provide an explanation for the resultant small size and effectiveness of our nanostructural Tf-lipoplex system

Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival

The Pit1-Oct1-Unc86 domain (POU domain) transcription factor Brn3a controls sensory neuron survival by regulating the expression of Trk receptors and members of the Bcl-2 family. Loss of Brn3a leads to a dramatic increase in apoptosis and severe loss of neurons in sensory ganglia. Although recent evidence suggests that Brn3a-mediated transcription can be modified by additional cofactors, the exact mechanisms are not known. Here, we report that homeodomain interacting protein kinase 2 (HIPK2) is a pro-apoptotic transcriptional cofactor that suppresses Brn3a-mediated gene expression. HIPK2 interacts with Brn3a, promotes Brn3a binding to DNA, but suppresses Brn3a-dependent transcription of brn3a, trkA, and bcl-xL. Overexpression of HIPK2 induces apoptosis in cultured sensory neurons. Conversely, targeted deletion of HIPK2 leads to increased expression of Brn3a, TrkA, and Bcl-xL, reduced apoptosis and increases in neuron numbers in the trigeminal ganglion. Together, these data indicate that HIPK2, through regulation of Brn3a-dependent gene expression, is a critical component in the transcriptional machinery that controls sensory neuron survival