The ability to accurately determine respiratory muscle strength is vitally important in patients with neuromuscular disorders (NMD). Sniff nasal inspiratory pressure (SNIP), a test of inspiratory ...muscle strength, is easier to perform for many NMD patients than the more commonly used determination of maximum inspiratory pressure measured at the mouth (MIP). However, due to an inconsistent approach in the literature, the optimal technique to perform the SNIP maneuver is unclear. Therefore, we systematically evaluated the impact of performing the maneuver with nostril contralateral to the pressure-sensing probe open (SNIPOP) versus closed (SNIPCL), on determination of inspiratory muscle strength in NMD patients as well as control subjects with normal respiratory muscle function.
NMD patients (n = 52) and control subjects without respiratory dysfunction (n = 52) were studied. SNIPOP, SNIPCL, and MIP were measured during the same session and compared using ANOVA. Agreement and bias were assessed with intraclass correlation coefficients (ICC) and Bland-Altman plots.
Mean MIP values were 58.2 and 94.0 cmH2O in NMD and control subjects, respectively (p<0.001). SNIPCL was greater than SNIPOP in NMD (51.9 ±31.0 vs. 36.9 ±25.4 cmH2O; p<0.001) as well as in controls (89.2 ±28.1 vs. 69.2 ±29.2 cmH2O; p<0.001). In both populations, the ICC between MIP and SNIPCL (NMD = 0.78, controls = 0.35) was higher than for MIP and SNIPOP (NMD = 0.53, controls = 0.06). In addition, SNIPCL was more often able to exclude inspiratory muscle weakness than SNIPOP.
SNIPCL values are systematically higher than SNIPOP in both normal subjects and NMD patients. Therefore, SNIPCL is a useful complementary test for ruling out inspiratory muscle weakness in individuals with low MIP values.
The aims of this study were to determine whether it is possible to use peptide microarrays obtained using the SPOT technique (immobilized on cellulose) and specific polyclonal antibodies to select ...fragments that reconstruct the outer sphere of proteins and to ascertain whether the selected peptide fragments can be useful in the study of their protein-protein and/or peptide-protein interactions. Using this approach, epidermal growth factor (EGF) fragments responsible for the interaction with the EGF receptor were searched. A library of EGF fragments immobilized on cellulose was obtained using triazine condensing reagents. Experiments on the interactions with EGFR confirmed the high affinity of the selected peptide fragments. Biological tests on cells showed the lack of cytotoxicity of the EGF fragments. Selected EGF fragments can be used in various areas of medicine.
Citrullination, a posttranslational modification, is catalyzed by peptidylarginine deiminases (PADs), a unique family of enzymes that converts peptidyl-arginine to peptidyl-citrulline. Overexpression ...and/or increased PAD activity is observed in rheumatoid arthritis (RA), Alzheimer's disease, multiple sclerosis, and cancer. Moreover, bacterial PADs, such as
PAD (PPAD), may have a role in the pathogenesis of RA, indicating PADs as promising therapeutic targets. Herein, six novel compounds were examined as potential inhibitors of human PAD4 and PPAD, and compared to an irreversible PAD inhibitor, Cl-amidine. Four of the tested compounds (compounds
,
,
, and
) exhibited a micromolar-range inhibition potency against PAD4 and no effect against PPAD in the in vitro assays. Compound
was able to inhibit the PAD4-induced citrullination of H3 histone with higher efficiency than Cl-amidine. In conclusion, compound
was highly effective and presents a promising direction in the search for novel RA treatment strategies.
We study the existence of densities for distributions of piecewise deterministic Markov processes. We also obtain relationships between invariant densities of the continuous time process and that of ...the process observed at jump times. In our approach we use functional-analytic methods and the theory of linear operator semigroups. By imposing general conditions on the characteristics of a given Markov process, we show the existence of a substochastic semigroup describing the evolution of densities for the process and we identify its generator. Our main tool is a new perturbation theorem for substochastic semigroups, where we perturb both the action of the generator and of its domain, allowing to treat general transport-type equations with non-local boundary conditions. A couple of particular examples illustrate our general results.
Acute short-term noninvasive ventilation (NIV) for hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD) has well-established benefits; however, the role of long-term home ...NIV remains controversial. In the past decade, studies utilizing aggressive NIV settings to maximally reduce carbon dioxide levels (PaCO2) have resulted in several positive clinical trials and led to updated guidelines on home NIV for stable hypercapnic COPD patients. This clinical respiratory review discusses the high-intensity NIV approach, summarizes recent key trials and guidelines pertaining to home NIV in COPD, and considers key clinical questions for future research and application in the Canadian context. With recent evidence and Canadian Thoracic Society (CTS) guidelines supporting the use of NIV in carefully selected COPD patients with persistent daytime hypercapnia, we believe it is time to reconsider our approach.
The problem of existence and uniqueness of absolutely continuous invariant measures for a class of piecewise deterministic Markov processes is investigated using the theory of substochastic ...semigroups obtained through the Kato–Voigt perturbation theorem on the L1-space. We provide a new criterion for the existence of a strictly positive and unique invariant density for such processes. The long time qualitative behavior of the corresponding semigroups is also considered. To illustrate our general results we give a detailed study of a two dimensional model of gene expression with bursting.
Monocyte chemoattractant protein-induced protein-1 (MCPIP-1) is a potent inhibitor of inflammatory response to pathogens. Acting as endonuclease against transcripts of inflammatory cytokines or ...transcription factors MCPIP-1 can significantly reduce the cytokine storm, thus limiting the tissue damage. As the adequate resolution of inflammation depends also on the efficient clearance of accumulated neutrophils, we focused on the role of MCPIP-1 in apoptosis and retention of neutrophils. We used peritoneal neutrophils from cell-specific MCPIP-1 knockout mice and showed prolonged survival of these cells. Moreover, we confirmed that MCPIP-1-dependent degradation of transcripts of antiapoptotic genes, including
, and for the first time
, serves as an early event in spontaneous apoptosis of primary neutrophils. Additionally, we identified previously unknown miRNAs as potential binding partners to the
transcript and their regulation suggest a role in MCPIP-1 half-life and translation. These phenomena may play a role as a molecular switch that balances the MCPIP-1-dependent apoptosis. Besides that, we determined these particular miRNAs as integral components of the GM-CSF-MCPIP-1 axis. Taken together, we identified the novel anti-inflammatory role of MCPIP-1 as a regulator of accumulation and survival of neutrophils that simultaneously promotes an adequate resolution of inflammation.
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