Recovery, empowerment and rehabilitation: Do inpatient psychiatric rehabilitation services empower the individual?

Perceptions of the course and outcome from serious mental illness have changed over the last century and, more recently, the concept of recovery has gained prominence in this field. This paper reviews recent literature on recovery from serious mental illness and discusses both the meaning of the concept and the key contributing factors. Research suggests that empowerment is one of the most salient factors contributing to recovery and the relationship between recovery and empowerment is examined. Most research in the area of empowerment has, to date, focused on community settings and this paper considers the relevance of these ideas in other mental health settings. The relationship between empowerment, recovery and mental health services is discussed. Finally, conclusions are drawn and recommendations for further research are outlined

Direct Stenting versus Conventional Stenting in Patients with ST-Segment Elevation Myocardial Infarction—A COMPARE CRUSH Sub-Study

Background: Direct stenting (DS) compared with conventional stenting (CS) after balloon predilatation may reduce distal embolization during percutaneous coronary intervention (PCI), thereby improving tissue reperfusion. In contrast, DS may increase the risk of stent underexpansion and target lesion failure. Methods:In this sub-study of the randomized COMPARE CRUSH trial (NCT03296540), we reviewed the efficacy of DS versus CS in a cohort of contemporary, pretreated ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. We compared DS versus CS, assessing (1) stent diameter in the culprit lesion, (2) thrombolysis in myocardial infarction (TIMI) flow in the infarct-related artery post-PCI and complete ST-segment resolution (STR) one-hour post-PCI, and (3) target lesion failure at one year. For proportional variables, propensity score weighting was applied to account for potential treatment selection bias. Results: This prespecified sub-study included 446 patients, of whom 189 (42%) were treated with DS. Stent diameters were comparable between groups (3.2 ± 0.5 vs. 3.2 ± 0.5 mm, p = 0.17). Post-PCI TIMI 3 flow and complete STR post-PCI rates were similar between groups (DS 93% vs. CS 90%, adjusted OR 1.16 [95% CI, 0.56–2.39], p = 0.69, and DS 72% vs. CS 58%, adjusted OR 1.29 [95% CI 0.77–2.16], p = 0.34, respectively). Moreover, target lesion failure rates at one year were comparable (DS 2% vs. 1%, adjusted OR 2.93 [95% CI 0.52–16.49], p = 0.22). Conclusion:In this contemporary pretreated STEMI cohort, we found no difference in early myocardial reperfusion outcomes between DS and CS. Moreover, DS seemed comparable to CS in terms of stent diameter and one-year vessel patency.</p

The effect of electrical neurostimulation on collateral perfusion during acute coronary occlusion

<p>Abstract</p> <p>Background</p> <p>Electrical neurostimulation can be used to treat patients with refractory angina, it reduces angina and ischemia. Previous data have suggested that electrical neurostimulation may alleviate myocardial ischaemia through increased collateral perfusion. We investigated the effect of electrical neurostimulation on functional collateral perfusion, assessed by distal coronary pressure measurement during acute coronary occlusion. We sought to study the effect of electrical neurostimulation on collateral perfusion.</p> <p>Methods</p> <p>Sixty patients with stable angina and significant coronary artery disease planned for elective percutaneous coronary intervention were split in two groups. In all patients two balloon inflations of 60 seconds were performed, the first for balloon dilatation of the lesion (first episode), the second for stent delivery (second episode). The Pw/Pa ratio (wedge pressure/aortic pressure) was measured during both ischaemic episodes. Group 1 received 5 minutes of active neurostimulation before plus 1 minute during the first episode, group 2 received 5 minutes of active neurostimulation before plus 1 minute during the second episode.</p> <p>Results</p> <p>In group 1 the Pw/Pa ratio decreased by 10 ± 22% from 0.20 ± 0.09 to 0.19 ± 0.09 (p = 0.004) when electrical neurostimulation was deactivated. In group 2 the Pw/Pa ratio increased by 9 ± 15% from 0.22 ± 0.09 to 0.24 ± 0.10 (p = 0.001) when electrical neurostimulation was activated.</p> <p>Conclusion</p> <p>Electrical neurostimulation induces a significant improvement in the Pw/Pa ratio during acute coronary occlusion.</p

Minimally invasive versus open distal pancreatectomy (LEOPARD): Study protocol for a randomized controlled trial

Background: Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. Methods: LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. Discussion: The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. Trial registration: Dutch Trial Register, NTR5188. Registered on 9 April 201

Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system

BACKGROUND: Transcriptional control of mitochondrial metabolism is essential for cellular function. A better understanding of this process will aid the elucidation of mitochondrial disorders, in particular of the many genetically unsolved cases of oxidative phosphorylation (OXPHOS) deficiency. Yet, to date only few studies have investigated nuclear gene regulation in the context of OXPHOS deficiency. In this study we performed RNA sequencing of two control and two complex I-deficient patient cell lines cultured in the presence of compounds that perturb mitochondrial metabolism: chloramphenicol, AICAR, or resveratrol. We combined this with a comprehensive analysis of mitochondrial and nuclear gene expression patterns, co-expression calculations and transcription factor binding sites. RESULTS: Our analyses show that subsets of mitochondrial OXPHOS genes respond opposingly to chloramphenicol and AICAR, whereas the response of nuclear OXPHOS genes is less consistent between cell lines and treatments. Across all samples nuclear OXPHOS genes have a significantly higher co-expression with each other than with other genes, including those encoding mitochondrial proteins. We found no evidence for complex-specific mRNA expression regulation: subunits of different OXPHOS complexes are similarly (co-)expressed and regulated by a common set of transcription factors. However, we did observe significant differences between the expression of nuclear genes for OXPHOS subunits versus assembly factors, suggesting divergent transcription programs. Furthermore, complex I co-expression calculations identified 684 genes with a likely role in OXPHOS biogenesis and function. Analysis of evolutionarily conserved transcription factor binding sites in the promoters of these genes revealed almost all known OXPHOS regulators (including GABP, NRF1/2, SP1, YY1, E-box factors) and a set of novel candidates (ELK1, KLF7, SP4, EHF, ZNF143, and TEL2). CONCLUSIONS: OXPHOS genes share an expression program distinct from other genes encoding mitochondrial proteins, indicative of targeted nuclear regulation of a mitochondrial sub-process. Within the subset of OXPHOS genes we established a difference in expression between mitochondrial and nuclear genes, and between nuclear genes encoding subunits and assembly factors. Most transcription regulators of genes that co-express with complex I are well-established factors for OXPHOS biogenesis. For the remaining six factors we here suggest for the first time a link with transcription regulation in OXPHOS deficiency. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1883-8) contains supplementary material, which is available to authorized users

Bromodomain inhibitors correct bioenergetic deficiency caused by mitochondrial disease complex I mutations

Mitochondrial diseases comprise a heterogeneous group of genetically inherited disorders that cause failures in energetic and metabolic function. Boosting residual oxidative phosphorylation (OXPHOS) activity can partially correct these failures. Herein, using a high-throughput chemical screen, we identified the bromodomain inhibitor I-BET 525762A as one of the top hits that increases COX5a protein levels in complex I (CI) mutant cybrid cells. In parallel, bromodomain-containing protein 4 (BRD4), a target of I-BET 525762A, was identified using a genome-wide CRISPR screen to search for genes whose loss of function rescues death of CI-impaired cybrids grown under conditions requiring OXPHOS activity for survival. We show that I-BET525762A or loss of BRD4 remodeled the mitochondrial proteome to increase the levels and activity of OXPHOS protein complexes, leading to rescue of the bioenergetic defects and cell death caused by mutations or chemical inhibition of CI. These studies show that BRD4 inhibition may have therapeutic implications for the treatment of mitochondrial diseases

Subunits of Mitochondrial Complex I Exist as Part of Matrix- and Membrane-associated Subcomplexes in Living Cells*S⃞

Mitochondrial complex I (CI) is a large assembly of 45 different subunits, and defects in its biogenesis are the most frequent cause of mitochondrial disorders. In vitro evidence suggests a stepwise assembly process involving pre-assembled modules. However, whether these modules also exist in vivo is as yet unresolved. To answer this question, we here applied submitochondrial fluorescence recovery after photobleaching to HEK293 cells expressing 6 GFP-tagged subunits selected on the basis of current CI assembly models. We established that each subunit was partially present in a virtually immobile fraction, possibly representing the holo-enzyme. Four subunits (NDUFV1, NDUFV2, NDUFA2, and NDUFA12) were also present as highly mobile matrix-soluble monomers, whereas, in sharp contrast, the other two subunits (NDUFB6 and NDUFS3) were additionally present in a slowly mobile fraction. In the case of the integral membrane protein NDUFB6, this fraction most likely represented one or more membrane-bound subassemblies, whereas biochemical evidence suggested that for the NDUFS3 protein this fraction most probably corresponded to a matrix-soluble subassembly. Our results provide first time evidence for the existence of CI subassemblies in mitochondria of living cells