Patients with rheumatic diseases may face 'discounting' (denying and patronising) or 'lack of understanding' because of having symptoms without external clinical signs, but instruments to assess such ...invalidation experiences are lacking.
To develop and evaluate the Illness Invalidation Inventory (3*I), to compare invalidation experiences of two groups of patients who differ in visual signs and laboratory findings-rheumatoid arthritis (RA) and fibromyalgia-and to examine the association of invalidation with health status.
A questionnaire (eight items with respect to five sources: spouse, family, medical professionals, work environment and social services) was constructed. It was completed by 142 patients with RA and 167 patients with fibromyalgia.
Principal axis factoring with oblimin rotation yielded two factors with high internal consistency (α>0.70): 'discounting' (five items) and 'lack of understanding' (three items). Patients with fibromyalgia experienced significantly more discounting and lack of understanding from their family, medical professionals, colleagues and social services than did patients with RA. Both patient groups experienced more invalidation from social services, colleagues and family than from medical professionals and spouses. More discounting and lack of understanding correlated with poorer mental well-being and social functioning in both patient groups. Discounting correlated with more physical disability and pain in patients with RA.
The 3*I is a brief, reliable instrument for assessing patients' perceptions of invalidation from different sources, which differ between patient groups and are associated with health status. Future validation research should clarify the clinical impact of invalidation on treatment adherence and outcome.
Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are ...unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive 'threat' system and underactive 'soothing' system, might keep the 'salience network' (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.
Background
Current clinical guidelines identify several psychological treatments for irritable bowel syndrome (IBS). IBS patients, however, have elevated trauma, life stress, relationship conflicts, ...and emotional avoidance, which few therapies directly target. We tested the effects of emotional awareness and expression training (EAET) compared to an evidence‐based comparison condition—relaxation training—and a waitlist control condition.
Methods
Adults with IBS (N=106; 80% female, Mean age=36 years) were randomized to EAET, relaxation training, or waitlist control. Both EAET and relaxation training were administered in three, weekly, 50‐minute, individual sessions. All patients completed the IBS Symptom Severity Scale (primary outcome), IBS Quality of Life, and Brief Symptom Inventory (anxiety, depressive, and hostility symptoms) at pretreatment and at 2 weeks posttreatment and 10 weeks follow‐up (primary endpoint).
Key Results
Compared to waitlist controls, EAET, but not relaxation training, significantly reduced IBS symptom severity at 10‐week follow‐up. Both EAET and relaxation training improved quality of life at follow‐up. Finally, EAET did not reduce psychological symptoms, whereas relaxation training reduced depressive symptoms at follow‐up (and anxiety symptoms at posttreatment).
Conclusions & Inferences
Brief emotional awareness and expression training that targeted trauma and emotional conflicts reduced somatic symptoms and improved quality of life in patients with IBS. This emotion‐focused approach may be considered an additional treatment option for IBS, although research should compare EAET to a full cognitive‐behavioral protocol and determine which patients are best suited for each approach. Registered at clinicaltrials.gov (NCT01886027).
This randomized controlled trial compared the effects of emotional awareness and expression training with relaxation training, and a waitlist control condition. This study demonstrated that emotional awareness and expression training reduced IBS symptoms and improved quality of life, which points to the value of this novel approach for patients with IBS.
Research into the neurobiological and psychosocial mechanisms involved in fibromyalgia has progressed remarkably in recent years. Despite this, current accounts of fibromyalgia fail to capture the ...complex, dynamic, and mutual crosstalk between neurophysiological and psychosocial domains. We conducted a comprehensive review of the existing literature in order to: a) synthesize current knowledge on fibromyalgia; b) explore and highlight multi-level links and pathways between different systems; and c) build bridges connecting disparate perspectives. An extensive panel of international experts in neurophysiological and psychosocial aspects of fibromyalgia discussed the collected evidence and progressively refined and conceptualized its interpretation. This work constitutes an essential step towards the development of a model capable of integrating the main factors implicated in fibromyalgia into a single, unified construct which appears indispensable to foster the understanding, assessment, and intervention for fibromyalgia.
•Fibromyalgia is a common, complex and highly disabling condition.•Central sensitization is the currently prevailing paradigm of its pathophysiology.•This concept largely disregards the flagrant psychosocial carvings of fibromyalgia.•These two fields are, nonetheless, involved in a prolific multidirectional crosstalk.•This underscores the need for an integrative framework to advance the field.
External and internal rectal prolapse with their affiliated rectocele and enterocele, are associated with debilitating symptoms such as obstructed defecation, pelvic pain and faecal incontinence. ...Since perineal procedures are associated with a higher recurrence rate, an abdominal approach is commonly preferred. Despite the description of greater than three hundred different procedures, thus far no clear superiority of one surgical technique has been demonstrated. Ventral mesh rectopexy(VMR) is a relatively new and promising technique to correct rectal prolapse. In contrast to the abdominal procedures of past decades, VMR avoids posterolateral rectal mobilisation and thereby minimizes the risk of postoperative constipation. Because of a perceived acceptable recurrence rate, good functional results and low mesh-related morbidity in the short to medium term, VMR has been popularized in the past decade. Laparoscopic or robotic-assisted VMR is now being progressively performed internationally and several articles and guidelines propose the procedure as the treatment of choice for rectal prolapse. In this article, an outline of the current status of laparoscopic and robotic ventral mesh rectopexy for the treatment of internal and external rectal prolapse is presented.
The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular ...epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. Real-time analysis of 36 genomes and subsequent confirmation using all 120 samples sequenced in the country of origin revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events and thus allaying concerns of an emergent strain or extensive human-to-human transmission.
Archaeological excavations at the site of Dmanisi in the Republic of Georgia have uncovered two partial early Pleistocene hominid crania. The new fossils consist of a relatively complete cranium and ...a second relatively complete calvaria from the same site and stratigraphic unit that yielded a hominid mandible in 1991. In contrast with the uncertain taxonomic affinity of the mandible, the new fossils are comparable in size and morphology with Homo ergaster from Koobi Fora, Kenya. Paleontological, archaeological, geochronological, and paleomagnetic data from Dmanisi all indicate an earliest Pleistocene age of about 1.7 million years ago, supporting correlation of the new specimens with the Koobi Fora fossils. The Dmanisi fossils, in contrast with Pleistocene hominids from Western Europe and Eastern Asia, show clear African affinity and may represent the species that first migrated out of Africa.
Objectives This study sought to identify the effect of coronary autoregulation on myocardial perfusion during intra-aortic balloon pump (IABP) therapy. Background IABP is the most commonly used ...circulatory support device, although its efficacy in certain scenarios has been questioned. The impact of alterations in microvascular function on IABP efficacy has not previously been evaluated in humans. Methods Thirteen patients with ischemic cardiomyopathy (left ventricular ejection fraction: 34 ± 8%) undergoing percutaneous coronary intervention were recruited. Simultaneous intracoronary pressure and Doppler-flow measurements were undertaken in the target vessel following percutaneous coronary intervention, during unassisted and IABP-assisted conditions. Coronary autoregulation was modulated by the use of intracoronary adenosine, inducing maximal hyperemia. Wave intensity analysis characterized the coronary wave energies associated with balloon counterpulsation. Results Two unique diastolic coronary waves were temporally associated with IABP device use; a forward compression wave and a forward expansion wave caused by inflation and deflation, respectively. During basal conditions, IABP therapy increased distal coronary pressure (82.4 ± 16.1 vs. 88.7 ± 17.8 mm Hg, p = 0.03), as well as microvascular resistance (2.32 ± 0.52 vs. 3.27 ± 0.41 mm Hg cm s–1 , p = 0.001), with no change in average peak velocity (30.6 ± 12.0 vs. 26.6 ± 11.3 cm s–1 , p = 0.59). When autoregulation was disabled, counterpulsation caused an increase in average peak velocity (39.4 ± 10.5 vs. 44.7 ± 17.5 cm s–1 , p = 0.002) that was linearly related with IABP–forward compression wave energy (R2 = 0.71, p = 0.001). Conclusions Autoregulation ameliorates the effect of IABP on coronary flow. However, during hyperemia, IABP augments myocardial perfusion, principally due to a diastolic forward compression wave caused by balloon inflation, suggesting IABP would be of greatest benefit when microcirculatory reserve is exhausted.
MUC13 is a transmembrane mucin glycoprotein that is over produced by many cancers, although its functions are not fully understood. Nuclear factor-κB (NF-κB) is a key transcription factor promoting ...cancer cell survival, but therapeutically targeting this pathway has proved difficult because NF-κB has pleiotropic functions. Here, we report that MUC13 prevents colorectal cancer cell death by promoting two distinct pathways of NF-kB activation, consequently upregulating BCL-X
. MUC13 promoted tumor necrosis factor (TNF)-induced NF-κB activation by interacting with TNFR1 and the E3 ligase, cIAP1, to increase ubiquitination of RIPK1. MUC13 also promoted genotoxin-induced NF-κB activation by increasing phosphorylation of ATM and SUMOylation of NF-κB essential modulator. Moreover, elevated expression of cytoplasmic MUC13 and NF-κB correlated with colorectal cancer progression and metastases. Our demonstration that MUC13 enhances NF-κB signaling in response to both TNF and DNA-damaging agents provides a new molecular target for specific inhibition of NF-κB activation. As proof of principle, silencing MUC13 sensitized colorectal cancer cells to killing by cytotoxic drugs and inflammatory signals and abolished chemotherapy-induced enrichment of CD133
CD44
cancer stem cells, slowed xenograft growth in mice, and synergized with 5-fluourouracil to induce tumor regression. Therefore, these data indicate that combining chemotherapy and MUC13 antagonism could improve the treatment of metastatic cancers.
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