Although several non-pharmacological interventions have been tested in the management of Fibromyalgia (FM), there is little consensus regarding the best options for the treatment of this health ...condition. The purpose of this network meta-analysis (NMA) is to investigate the comparative efficacy and acceptability of non-pharmacological interventions for FM, in order to assist clinical decision making through a ranking of interventions in relation to the most important clinical outcomes in these patients. We will perform a systematic search to identify randomised controlled trials of non-pharmacological interventions endorsed in guidelines and systematic reviews. Information sources searched will include major bibliographic databases without language or date restrictions (MEDLINE, Cochrane Library, EMBASE, AMED, PsycINFO and PEDro). Our primary outcomes will be pain intensity, patient-reported quality of life (QoL), and acceptability of treatment will be our secondary outcome. Risk of bias of the included trials will be assessed using the Cochrane risk of bias tool (RoB2). For each pairwise comparison between the different interventions, we will present mean differences (MDs) for pain intensity and QoL outcomes and Relative Risks (RRs) for acceptability, both with respective 95% confidence intervals (CIs). Initially, standard pairwise meta-analyses will be performed using a DerSimonian-Laird random effects model for all comparisons with at least two trials and then we will perform a frequentist NMA using the methodology of multivariate meta-analysis assuming a common heterogeneity parameter, using the mvmeta command and network suite in STATA. In the NMA, two different types of control group, such as placebo/sham and no intervention/waiting list will be combined as one node called "Control". The competing interventions will be ranked using the P-score, which is the frequentist analogue of surface under the cumulative ranking curve (SUCRA) for the outcomes of interest at immediate- (intervention duration of up to 2 weeks), short- (over 2 weeks up to 12 weeks) and long-terms (over 12 weeks). The confidence in the results from NMA will be assessed using the Confidence in Network Meta-analysis (CINeMA) framework.
Tensegrity Systems Oliveira, Mauricio C; Skelton, Robert E
Springer eBooks,
2009, 20090430
eBook
Odprti dostop
Tensegrity Systems discusses analytical tools to design energy efficient and lightweight structures employing the concept of 'tensegrity.' This word is Buckminister Fuller's contraction of the words ...'Tensile' and 'Integrity,' which suggests that integrity or, as we would say, stability of the structure comes from tension. In a tensegrity structure the rigid bodies (the bars), might not have any contact, thus providing extraordinary freedom to control shape, by controlling only tendons. Tensegrity Systems covers both static and dynamic analysis of special tensegrity structural concepts, which are motivated by biological material architecture. Drawing upon years of practical experience and using numerous examples and illustrative applications, Robert Skelton and Mauricio C. de Oliveira discuss: The design of tensegrity structures using analytical tools The integration of tensegrity systems into a combined framework including structural design and control design The rules for filling space (tesselation) with self-similar structures that guarantee a specific mechanical property are provided Tensegrity Systems will be of interest to all engineers who design or control light-weight structures, including deployable and robotic structures, and shape controllable structures. Also, Engineers interested in the study of advanced dynamics will find new and useful algorithms for multibody systems.
We report an alternative random laser (RL) architecture based on a flexible and ZnO-enriched cellulose acetate (CA) fiber matrix prepared by electrospinning. The electrospun fibers, mechanically ...reinforced by polyethylene oxide and impregnated with zinc oxide powder, were applied as an adsorbent surface to incorporate plasmonic centers (silver nanoprisms). The resulting structures - prepared in the absence (CA-ZnO) and in the presence of silver nanoparticles (CA-ZnO-Ag) - were developed to support light excitation, guiding and scattering prototypes of a RL. Both materials were excited by a pulsed (5 Hz, 5 ns) source at 355 nm and their fluorescence emission monitored at 387 nm. The results suggest that the addition of silver nanoprisms to the ZnO- enriched fiber matrix allows large improvement of the RL performance due to the plasmon resonance of the silver nanoprisms, with ~80% reduction in threshold energy. Besides the intensity and spectral analysis, the RL characterization included its spectral and intensity angular dependences. Bending the flexible RL did not affect the spectral characteristics of the device. No degradation was observed in the random laser emission for more than 10,000 shots of the pump laser.
Cytosolic DNA arising from intracellular bacterial or viral infections is a powerful pathogen-associated molecular pattern (PAMP) that leads to innate immune host defence by the production of type I ...interferon and inflammatory cytokines. Recognition of cytosolic DNA by the recently discovered cyclic-GMP-AMP (cGAMP) synthase (cGAS) induces the production of cGAMP to activate the stimulator of interferon genes (STING). Here we report the crystal structure of cGAS alone and in complex with DNA, ATP and GTP along with functional studies. Our results explain the broad DNA sensing specificity of cGAS, show how cGAS catalyses dinucleotide formation and indicate activation by a DNA-induced structural switch. cGAS possesses a remarkable structural similarity to the antiviral cytosolic double-stranded RNA sensor 2'-5'oligoadenylate synthase (OAS1), but contains a unique zinc thumb that recognizes B-form double-stranded DNA. Our results mechanistically unify dsRNA and dsDNA innate immune sensing by OAS1 and cGAS nucleotidyl transferases.
The fungal cell wall is located outside the plasma membrane and is the cell compartment that mediates all the relationships of the cell with the environment. It protects the contents of the cell, ...gives rigidity and defines the cellular structure. The cell wall is a skeleton with high plasticity that protects the cell from different stresses, among which osmotic changes stand out. The cell wall allows interaction with the external environment since some of its proteins are adhesins and receptors. Since, some components have a high immunogenic capacity, certain wall components can drive the host's immune response to promote fungus growth and dissemination. The cell wall is a characteristic structure of fungi and is composed mainly of glucans, chitin and glycoproteins. As the components of the fungal cell wall are not present in humans, this structure is an excellent target for antifungal therapy. In this article, we review recent data on the composition and synthesis, influence of the components of the cell wall in fungi-host interaction and the role as a target for the next generation of antifungal drugs in yeasts (
and
) and filamentous fungi (
).
Advances in the understanding of leishmaniasis progression indicate that cellular interactions more complex than the Th1/Th2 paradigm define the course of infection. Th17 cells are a crucial ...modulator of adaptive immunity against
parasites acting mainly on neutrophil recruitment and playing a dual role at the site of infection. This review describes the roles of both these cell types in linking innate defense responses to the establishment of specific immunity. We focus on the Th17-neutrophil interaction as a crucial component of anti-
immunity, and the clinical evolution of cutaneous or visceral leishmaniasis. To date, information obtained through experimental models and patient evaluations suggests that the influence of the presence of interleukin (IL)-17 (the main cytokine produced by Th17 cells) and neutrophils during
infections is strictly dependent on the tissue (skin or liver/spleen) and parasite species. Also, the time at which neutrophils are recruited, and the persistence of IL-17 in the infection microenvironment, may also be significant. A clearer understanding of these interactions will enable better measurement of the influence of IL-17 and its regulators, and contribute to the identification of disease/resistance biomarkers.
Grade C periodontitis in young individuals is characterized by severe/rapid periodontal destruction, usually early onset, in systemically healthy individuals. An individual’s host response, triggered ...by a dysbiotic subgingival biofilm, has been reported as a contributor to the tissue destruction, although mechanisms of this response and contributions to such disease remain poorly understood. Nonsurgical treatment has resulted in positive clinical responses for both localized (now molar-incisor pattern) and generalized forms of grade C periodontitis, especially when adjunctive systemic antibiotics are used. Nonsurgical treatment may also affect host responses, although mechanisms leading to significant changes in this response remain unclear. Significant effects on inflammatory response to antigens/bacteria have been described posttreatment, but evidence for long-term effects remains limited. Nonsurgical treatment in these individuals may also modulate a variety of host markers in serum/plasma and gingival crevicular fluid along with clinical parameter improvements. The impact of other adjuncts to nonsurgical treatment focusing on controlling exacerbated immunoinflammatory responses needs to be further explored in grade C periodontitis in young individuals. Recent evidence suggests that nonsurgical treatment with adjunctive laser therapy may modulate host and microbial responses in those subjects, at least in the short term. Available evidence, while very heterogeneous (including variations in disease definition and study designs), does not provide clear conclusions on this topic yet provides important insights for future studies. In this review, studies within the past decade evaluating the impact of nonsurgical treatment on systemic/local host responses in young individuals with grade C periodontitis, as well as long-term clinical responses posttreatment, will be critically appraised and discussed.
Background: Clinical hypomagnesemia and experimental restriction of dietary magnesium increase cardiac arrhythmias. However, whether or not circulating or dietary magnesium at usual concentrations or ...intakes influences the risk of cardiovascular disease (CVD), including fatal ischemic heart disease (IHD), is unclear.Objective: We performed a systematic review and meta-analysis to investigate prospective associations of circulating and dietary magnesium with incidence of CVD, IHD, and fatal IHD.Design: Multiple literature databases were systematically searched without language restriction through May 2012. Inclusion decisions and data extraction were performed in duplicate. Linear dose-response associations were assessed by using random-effects meta-regression. Potential nonlinear associations were evaluated by using restricted cubic splines.Results: Of 2303 articles, 16 studies met the eligibility criteria; these studies comprised 313,041 individuals and 11,995 CVD, 7534 IHD, and 2686 fatal IHD events. Circulating magnesium (per 0.2 mmol/L increment) was associated with a 30% lower risk of CVD (RR: 0.70; 95% CI: 0.56, 0.88 per 0.2 mmol/L) and trends toward lower risks of IHD (RR: 0.83; 95% CI: 0.75, 1.05) and fatal IHD (RR: 0.61; 95% CI: 0.37, 1.00). Dietary magnesium (per 200-mg/d increment) was not significantly associated with CVD (RR: 0.89; 95% CI: 0.75, 1.05) but was associated with a 22% lower risk of IHD (RR: 0.78; 95% CI: 0.67, 0.92). The association of dietary magnesium with fatal IHD was nonlinear (P < 0.001), with an inverse association observed up to a threshold of ∼250 mg/d (RR: 0.73; 95% CI: 0.62, 0.86), compared with lower intakes.Conclusion: Circulating and dietary magnesium are inversely associated with CVD risk, which supports the need for clinical trials to evaluate the potential role of magnesium in the prevention of CVD and IHD.
Cyclic dinucleotides (CDNs) have central roles in bacterial homeostasis and virulence by acting as nucleotide second messengers. Bacterial CDNs also elicit immune responses during infection when they ...are detected by pattern-recognition receptors in animal cells. Here we perform a systematic biochemical screen for bacterial signalling nucleotides and discover a large family of cGAS/DncV-like nucleotidyltransferases (CD-NTases) that use both purine and pyrimidine nucleotides to synthesize a diverse range of CDNs. A series of crystal structures establish CD-NTases as a structurally conserved family and reveal key contacts in the enzyme active-site lid that direct purine or pyrimidine selection. CD-NTase products are not restricted to CDNs and also include an unexpected class of cyclic trinucleotide compounds. Biochemical and cellular analyses of CD-NTase signalling nucleotides demonstrate that these cyclic di- and trinucleotides activate distinct host receptors and thus may modulate the interaction of both pathogens and commensal microbiota with their animal and plant hosts.
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