Pericardial involvement of sarcoidosis is a rare cause for acute heart failure, and usually occurs as a result of the development of a pericardial effusion leading to cardiac tamponade. Even rarer ...still, is the manifestation of constrictive pericarditis. We report a case of sarcoidosis with lung, pleural, and pericardial involvement with effusive-constrictive pericarditis leading to cardiac tamponade.
A 34-year-old Caucasian man presented for evaluation of a history of worsening exertional dyspnea, edema, and weight loss. A high-resolution chest computed tomography showed diffuse pulmonary nodules with upper lobe predominance and in a perilymphatic distribution; large right pleural effusion; and large pericardial effusion with pericardial thickening. A transthoracic echocardiogram demonstrated early tamponade physiology for which a pericardial drain was placed. After removal of the drain he developed cardiogenic shock from cardiac tamponade attributed to the reaccumulation of a pericardial effusion and urgent pericardial window was performed. Serial echocardiography was concerning for organization and localization of the pericardial fluid. Cardiac magnetic resonance imaging demonstrated a significant reduction in pericardial slippage between the parietal and visceral layers around the heart collectively suggestive of constrictive pericarditis. Confirmation of effusive-constrictive pericarditis was noted on right heart catheterization. He then underwent pericardiectomy, which on histopathologic evaluation demonstrated non-necrotizing granulomas, thus confirming pericardial involvement of sarcoidosis.
We report a case demonstrating unique manifestations of sarcoidosis; effusive-constrictive pericarditis presenting with acute congestive heart failure.
•The most common manifestation of pericardial sarcoidosis is a pericardial effusion.•Constrictive pericarditis is a rare presentation of pericardial sarcoidosis and can lead to cardiac tamponade.•Clinicians should be aware of the life threatening manifestations of sarcoidosis.
Adopting a systems view and regenerative philosophy can indicate how to regenerate ecosystem function on commercial-scale agro-ecological landscapes. Adaptive multi-paddock grazing management is an ...example of an approach for grazinglands. Leading conservation farmers have achieved superior results in ecosystem improvement, productivity, soil carbon and fertility, water-holding capacity and profitability. Their method is to use multiple paddocks per herd with short grazing periods, long recovery periods, and adaptively changing recovery periods, residual biomass, animal numbers and other management elements as conditions change. In contrast, much research on grazing management has not followed adaptive research protocols to account for spatial effects, for sufficient time to produce resource improvement, sound animal production, and socio-economic goals under constantly varying conditions on rangelands. We briefly review what management has achieved best outcomes and show how previous reviews of grazing studies were limited in scope and applicability to larger, more complex landscapes. We argue that future research can provide better understanding of how multi-paddock grazing management can improve socio-ecological resilience in grazing ecosystems, while avoiding unintended consequences of possible management options, by involving realistic scale and context, partnering with innovative land managers on real operations, applying adaptive treatments, and combining field studies with modelling approaches.
Acute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care units. As there is rising evidence about immuno-modulatory effects of lipid emulsions required for ...parenteral nutrition of ARDS patients, we sought to investigate whether infusion of conventional soybean oil (SO)-based or fish oil (FO)-based lipid emulsions rich in either n-6 or n-3 fatty acids, respectively, may influence subsequent pulmonary inflammation.
In a randomized controlled, single-blinded pilot study, forty-two volunteers received SO, FO, or normal saline for two days. Thereafter, volunteers inhaled pre-defined doses of lipopolysaccharide (LPS) followed by bronchoalveolar lavage (BAL) 8 or 24 h later. In the murine model of LPS-induced lung injury a possible involvement of resolvin E1 (RvE1) receptor ChemR23 was investigated. Wild-type and ChemR23 knockout mice were infused with both lipid emulsions and challenged with LPS intratracheally.
In volunteers receiving lipid emulsions, the fatty acid profile in the plasma and in isolated neutrophils and monocytes was significantly changed. Adhesion of isolated monocytes to endothelial cells was enhanced after infusion of SO and reduced by FO, however, no difference of infusion on an array of surface adhesion molecules was detected. In neutrophils and monocytes, LPS-elicited generation of pro-inflammatory cytokines increased in the SO and decreased in the FO group. LPS inhalation in volunteers evoked an increase in neutrophils in BAL fluids, which decreased faster in the FO group. While TNF-α in the BAL was increased in the SO group, IL-8 decreased faster in the FO group. In the murine model of lung injury, effects of FO similar to the volunteer group observed in wild-type mice were abrogated in ChemR23 knockout mice.
After infusion of conventional lipid emulsions, leukocytes exhibited increased adhesive and pro-inflammatory features. In contrast, FO-based lipid emulsions reduced monocyte adhesion, decreased pro-inflammatory cytokines, and neutrophil recruitment into the alveolar space possibly mediated by ChemR23-signaling. Lipid emulsions thus exert differential effects in human volunteers and mice in vivo.
DRKS00006131 at the German Clinical Trial Registry, 2014/05/14.
Background
The incidence of infection after posterior cervical spine surgery ranges from 0 to 18%. Higher rates have been reported after posterior procedures compared with anterior procedures, but ...these studies have been for small series. We report on our rate of surgical site infection (SSI) after posterior cervical spine surgery and the risk factors that influence these infections.
Methods
We retrospectively reviewed the records of 90 consecutive patients who underwent posterior cervical spine procedures at a major spinal referral center between 1998 and 2007. The main indications for surgery were trauma and degenerative conditions. Tumors and primary infections were excluded. Medical records of these patients were examined for evidence of SSI as diagnosed by Centers for Disease Control and Prevention criteria.
Results
Using stringent criteria for diagnosing SSI, we found 15 infected patients (16.67%). The postoperative use of a Philadelphia hard collar was found to be a significant risk factor for SSI with a relative risk of 15.30 (95% confidence interval 2.10 to 111.52). Almost half of infected patients (47%) required reoperation for wound debridement, with four requiring skin flap closure. All 15 patients had successful outcomes with complete resolution of their infection.
Conclusions
This study confirms a high incidence of SSI after posterior cervical surgery. The most significant risk factors for SSI were found to be a traumatic etiology and postoperative use of a collar. We believe it is important to develop strategies to minimize the risk of infection after posterior cervical surgery, which include questioning the postoperative use of collars.
Maintaining or enhancing the productive capacity and resilience of rangeland ecosystems is critical for the continued support of people who depend on them for their livelihoods, especially in the ...face of climatic change. This is also necessary for the continued delivery of ecosystem services derived from rangelands for the broader benefit of societies around the world. Multi-paddock grazing management has been recommended since the mid-20th century as an important tool to adaptively manage rangelands ecosystems to sustain productivity and improve animal management. Moreover, there is much anecdotal evidence from producers that, if applied appropriately, multi-paddock grazing can improve forage and livestock production. By contrast, recent reviews of published rangeland-based grazing systems studies have concluded that, in general, field trials show no superiority of vegetation or animal production in multi-paddock grazing relative to continuous yearlong stocking of single-paddock livestock production systems. Our goal is to provide a framework for rangeland management decisions that support the productivity and resiliency of rangelands and then to identify why different perceptions exist among rangeland managers who have effectively used multi-paddock grazing systems and research scientists who have studied them. First, we discuss the ecology of grazed ecosystems under free-ranging herbivores and under single-paddock fenced conditions. Second, we identify five principles underpinning the adaptive management actions used by successful grazing managers and the ecological, physiological, and behavioral framework they use to achieve desired conservation, production, and financial goals. Third, we examine adaptive management principles needed to successfully manage rangelands subjected to varying environmental conditions. Fourth, we describe the differences between the interpretation of results of grazing systems research reported in the scientific literature and the results reported by successful grazing managers; we highlight the shortcomings of most of the previously conducted grazing systems research for providing information relevant for rangeland managers who aim to achieve desired environmental and economic goals. Finally, we outline knowledge gaps and present testable hypotheses to broaden our understanding of how planned multi-paddock grazing management can be used at the ranching enterprise scale to facilitate the adaptive management of rangelands under dynamic environmental conditions.
•We analyze conservation-award winning grazing management and conventional research.•We analyze managing rangeland ecological processes to achieve environment goals.•We outline limitations of small-scale research and importance of adaptive management.•We identify knowledge gaps, testable hypotheses and future research needs.
The aim of this study was to determine whether compression garments improve intermittent-sprint performance and aid performance or self-reported recovery from high-intensity efforts on consecutive ...days.
Following familiarization, 14 male rugby players performed two randomized testing conditions (with or without garments) involving consecutive days of a simulated team sport exercise protocol, separated by 24 h of recovery within each condition and 2 weeks between conditions. Each day involved an 80-min high-intensity exercise circuit, with exercise performance determined by repeated 20-m sprints and peak power on a cart dynamometer (single-man scrum machine). Measures of nude mass, heart rate, skin and tympanic temperature, and blood lactate (La-) were recorded throughout each day; also, creatine kinase (CK) and muscle soreness were recorded each day and 48 h following exercise.
No differences (P=.20 to 0.40) were present between conditions on either day of the exercise protocol for repeated 20-m sprint efforts or peak power on a cart dynamometer. Heart rate, tympanic temperature, and body mass did not significantly differ between conditions; however, skin temperature was higher under the compression garments. Although no differences (P=.50) in La- or CK were present, participants felt reduced levels of perceived muscle soreness in the ensuing 48 h postexercise when wearing the garments (2.5+/-1.7 vs 3.5+/-2.1 for garment and control; P=.01).
The use of compression garments did not improve or hamper simulated team-sport activity on consecutive days. Despite benefits of reduced self-reported muscle soreness when wearing garments during and following exercise each day, no improvements in performance or recovery were apparent.
In the aftermath of the 2011 England riots, the then Prime Minister David Cameron referred to a ‘small number of families as the source of a large number of problems in society’ (Cameron, 2011). Soon ...after, the Troubled Families Programme was set up by the government to ‘turn around’ 120,000 troubled families. Despite government rhetoric focusing on ‘neighbours from hell’ (ibid.) the initial estimate of the number of troubled families did not include any indicators of problematic behaviours, such as crime or anti-social behaviour. Instead, a measure previously used by government to classify families with multiple social and economic disadvantages was used (Social Exclusion Task Force, 2007a). This article revisits the research behind the initial identification of the 120,000 troubled families and explores more widely the overlap between families with multiple social and economic disadvantage and their engagement in problematic behaviours. Our reanalysis of the original research data reveals that although families experiencing multiple social and economic disadvantage were at an increased risk of displaying problematic behaviour, only a small minority did so.
Free fatty acid receptor 2 (FFA2) is expressed on enteroendocrine L cells that release glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) when activated by short-chain fatty acids (SCFAs). ...Functionally GLP-1 and PYY inhibit gut transit, increase glucose tolerance, and suppress appetite; thus, FFA2 has therapeutic potential for type 2 diabetes and obesity. However, FFA2-selective agonists have not been characterized in vivo. Compound 1 (Cpd 1), a potent FFA2 agonist, was tested for its activity on the following: GLP-1 release, modulation of intestinal mucosal ion transport and transit in wild-type (WT) and FFA2(-/-) tissue, and food intake and glucose tolerance in lean and diet-induced obese (DIO) mice. Cpd 1 stimulated GLP-1 secretion in vivo, but this effect was only detected with dipeptidyl peptidase IV inhibition, while mucosal responses were PYY, not GLP-1, mediated. Gut transit was faster in FFA2(-/-) mice, while Cpd 1 slowed WT transit and reduced food intake and body weight in DIO mice. Cpd 1 decreased glucose tolerance and suppressed plasma insulin in lean and DIO mice, despite FFA2(-/-) mice displaying impaired glucose tolerance. These results suggest that FFA2 inhibits intestinal functions and suppresses food intake via PYY pathways, with limited GLP-1 contribution. Thus, FFA2 may be an effective therapeutic target for obesity but not for type 2 diabetes.
In a typical G protein coupled receptor drug discovery campaign, an in vitro primary functional screening assay is often established in a recombinant system overexpressing the target of interest, ...which offers advantages with respect to overall throughput and robustness of compound testing. Subsequently, compounds are then progressed into more physiologically relevant but lower throughput ex vivo primary cell assays and finally in vivo studies. Here we describe a dynamic mass redistribution (DMR) assay that has been developed in a format suitable to support medium throughput drug screening in primary human neutrophils. Neutrophils are known to express both CXC chemokine receptor (CXCR) 1 and CXCR2 that are thought to play significant roles in various inflammatory disorders and cancer. Using multiple relevant chemokine ligands and a range of selective and nonselective small and large molecule antagonists that block CXCR1 and CXCR2 responses, we demonstrate distinct pharmacological profiles in neutrophil DMR from those observed in recombinant assays but predictive of activity in neutrophil chemotaxis and CD11b upregulation, a validated target engagement marker previously used in clinical studies of CXCR2 antagonists. The primary human neutrophil DMR cell system is highly reproducible, robust, and less prone to donor variability observed in CD11b and chemotaxis assays and thus provides a unique, more physiologically relevant, and higher throughput assay to support drug discovery and translation to early clinical trials. SIGNIFICANCE STATEMENT: Neutrophil dynamic mass redistribution assays provide a higher throughput screening assay to profile compounds in primary cells earlier in the screening cascade enabling a higher level of confidence in progressing the development of compounds toward the clinic. This is particularly important for chemokine receptors where redundancy contributes to a lack of correlation between recombinant screening assays and primary cells, with the coexpression of related receptors confounding results.
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