Using fibrincollagen composite hydrogel and silk for bio-inspired design of tympanic membrane grafts: a vibro-acoustic analysis

Tympanic membrane (TM) is vulnerable to a variety of middle ear diseases. In some cases, reconstruction or repair of the TM is essential for recovering the hearing. Although there are many kinds of materials and therapeutics for TM reconstruction, tissue engineering of the TM is still in its initial steps of advancement. Treatment of damaged TM is usually carried out by otology-related techniques such as myringoplasty and tympanoplasty. Most of the novel tympanoplasty methods employ artificial grafts made of biomaterials and polymers for scaffolds. One biomaterial candidate for design and fabrication of synthetic grafts is spider silk, which has excellent mechanical and acoustic characteristics. On the other hand, the structural function of the spider web is also one of the potential inspirations for designing tissue-engineered grafts on micro-scale explorations. In this study, a bio-inspired design and analysis of silky TM grafts are carried out employing finite element modeling and vibro-acoustic investigation. A comparative and statistical analysis is also performed with experimentally validated data to check the suitability of the materials and design. The numerical study shows that the proposed bio-inspired models are appropriate for TM graft design and fabrication. The effects of inspired architecture and materials on obtaining an optimum design for TM grafts are put into evidence via a parametric study, and pertinent conclusions are outlined

Monotone iterative procedure and systems of a finite number of nonlinear fractional differential equations

The aim of the paper is to present a nontrivial and natural extension of the comparison result and the monotone iterative procedure based on upper and lower solutions, which were recently established in (Wang et al. in Appl. Math. Lett. 25:1019-1024, 2012), to the case of any finite number of nonlinear fractional differential equations.The author is very grateful to the reviewers for the remarks, which improved the final version of the manuscript. This article was financially supported by University of Łódź as a part of donation for the research activities aimed at the development of young scientists, grant no. 545/1117

A Chaotic Quadratic Oscillator with Only Squared Terms: Multistability, Impulsive Control, and Circuit Design

Here, a chaotic quadratic oscillator with only squared terms is proposed, which shows various dynamics. The oscillator has eight equilibrium points, and none of them is stable. Various bifurcation diagrams of the oscillator are investigated, and its Lyapunov exponents (LEs) are discussed. The multistability of the oscillator is discussed by plotting bifurcation diagrams with various initiation methods. The basin of attraction of the oscillator is discussed in two planes. Impulsive control is applied to the oscillator to control its chaotic dynamics. Additionally, the circuit is implemented to reveal its feasibility

Whole-Blood Flow-Cytometric Analysis of Antigen-Specific CD4 T-Cell Cytokine Profiles Distinguishes Active Tuberculosis from Non-Active States

T-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB

Competency of Anopheles stephensi mysorensis strain for Plasmodium vivax and the role of inhibitory carbohydrates to block its sporogonic cycle

<p>Abstract</p> <p>Background</p> <p>Despite the abundance of studies conducted on the role of mosquitoes in malaria transmission, the biology and interaction of <it>Plasmodium </it>with its insect host still holds many mysteries. This paper provides the first study to follow the sporogonic cycle of <it>Plasmodium vivax </it>in a wild insecticide-resistant mysorensis strain of <it>Anopheles stephensi</it>, a major vector of vivax malaria in south-eastern Iran. The study subsequently demonstrates that host-parasite sugar binding interactions are critical to the development of this parasite in the salivary glands of its mosquito host. The identity of the receptors or sugars involved was revealed by a receptor "pre-saturation" strategy in which sugars fed to the mosquitoes inhibited normal host-parasite interactions.</p> <p>Methods</p> <p><it>Anopheles stephensi </it>mysorensis mosquitoes were artificially infected with <it>P. vivax </it>by feeding on the blood of gametocytaemic volunteers reporting to local malaria clinics in the Sistan-Baluchistan province of south-eastern Iran. In order to determine the inhibitory effect of carbohydrates on sporogonic development, vector mosquitoes were allowed to ingest blood meals containing both gametocytes and added carbohydrates. The carbohydrates tested were GlcNAc, GalNAc, arabinose, fucose, mannose, lactose, glucose and galactose. Sporogonic development was assessed by survival of the parasite at both the oocyst and sporozoite stages.</p> <p>Results</p> <p>Oocyst development was observed among nearly 6% of the fed control mosquitoes but the overall number of mosquitoes exhibiting sporozoite invasion of the salivary glands was 47.5% lower than the number supporting oocysts in their midgut. Of the tested carbohydrates, only arabinose and fucose slightly perturbed the development of <it>P. vivax </it>oocysts at the basal side of the mosquito midgut, and the remaining sugars caused no reductions in oocyst development. Strikingly however, sporozoites were completely absent from the salivary glands of mosquitoes treated with mannose, GalNAc, and lactose.</p> <p>Conclusion</p> <p>The study indicates that <it>An. stephensi </it>in southern Iran has the potential to survive long enough to be re-infected and transmit vivax malaria several times, based on the average adult female longevity (about 30 days) and its gonotrophic cycle (2–3 days) during the malaria transmission season. Certain sugar binding interactions are important for the development of <it>P. vivax </it>sporozoites, and this information may be instrumental for the development of transmission blocking strategies.</p

The Impact of HIV Infection and CD4 Cell Count on the Performance of an Interferon Gamma Release Assay in Patients with Pulmonary Tuberculosis

BACKGROUND:The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance. METHODOLOGY/PRINCIPAL FINDINGS:161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/microl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39). CONCLUSIONS/SIGNIFICANCE:Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent

Low-molecular-weight heparin reduces hyperoxia-augmented ventilator-induced lung injury via serine/threonine kinase-protein kinase B

<p>Abstract</p> <p>Background</p> <p>High-tidal-volume mechanical ventilation and hyperoxia used in patients with acute lung injury (ALI) can induce the release of cytokines, including high-mobility group box-1 (HMGB1), oxygen radicals, neutrophil infiltration, and the disruption of epithelial and endothelial barriers. Hyperoxia has been shown to increase ventilator-induced lung injury, but the mechanisms regulating interaction between high tidal volume and hyperoxia are unclear. We hypothesized that subcutaneous injections of enoxaparin would decrease the effects of hyperoxia on high-tidal-volume ventilation-induced HMGB1 production and neutrophil infiltration via the serine/threonine kinase/protein kinase B (Akt) pathway.</p> <p>Methods</p> <p>Male C57BL/6, either wild type or Akt^+/-, aged between 6 and 8 weeks, weighing between 20 and 25 g, were exposed to high-tidal-volume (30 ml/kg) mechanical ventilation with room air or hyperoxia for 2 to 8 hours with or without 4 mg/kg enoxaparin administration. Nonventilated mice served as a control group. Evan blue dye, lung wet-to-dry weight ratio, free radicals, myeloperoxidase, Western blot of Akt, and gene expression of HMGB1 were measured. The expression of HMGB1 was studied by immunohistochemistry.</p> <p>Results</p> <p>High-tidal-volume ventilation using hyperoxia induced microvascular permeability, Akt activation, HMGB1 mRNA expression, neutrophil infiltration, oxygen radicals, HMGB1 production, and positive staining of Akt in bronchial epithelium. Hyperoxia-induced augmentation of ventilator-induced lung injury was attenuated with Akt deficient mice and pharmacological inhibition of Akt activity by enoxaparin.</p> <p>Conclusion</p> <p>These data suggest that enoxaparin attenuates hyperoxia-augmented high-tidal-volume ventilation-induced neutrophil influx and HMGB1 production through inhibition of the Akt pathway. Understanding the protective mechanism of enoxaparin related with the reduction of HMGB1 may help further knowledge of the effects of mechanical forces in the lung and development of possible therapeutic strategies involved in acute lung injury.</p

Use of a T cell interferon gamma release assay in the investigation for suspected active tuberculosis in a low prevalence area

<p>Abstract</p> <p>Background</p> <p>In settings with low background prevalence of tuberculosis (TB) infection, interferon-γ release assays (IGRA) could be useful for diagnosing active TB. This study aims to evaluate the performance of QuantiFERON^®-TB Gold (QFT-G) in the investigation for suspected active TB, with particular attention to patients originating in high-incidence countries. Furthermore, factors associated with QFT-G results in patients with active TB were assessed.</p> <p>Methods</p> <p>From patients investigated for clinically suspected active TB, blood was obtained for QFT-G testing, in addition to routine investigations. Positive (PPV) and negative (NPV) predictive values for QFT-G were calculated, comparing patients with confirmed TB and those with other final diagnoses. QFT-G results in TB patients originating from countries with intermediate or high TB incidence were compared with QFT-G results from a control group of recently arrived asymptomatic immigrants from high-incidence countries. Factors associated with QFT-G outcome in patients with confirmed TB were assessed.</p> <p>Results</p> <p>Among 141 patients, 41/70 (58.6%) with confirmed TB had a positive QFT-G test, compared to 16/71 (22.6%) patients with other final diagnoses, resulting in overall PPV of 71.9% and NPV of 67.6%. For patients with pulmonary disease, PPV and NPV were 61.1% and 67.7%, respectively, and 90.5% and 66.7% for subjects with extrapulmonary manifestations. Comparing patients from high-incidence countries with controls yielded a PPV for active TB of 76.7%, and a NPV of 82.7%. Patients with confirmed TB and positive QFT-G results were characterized by a lower median peripheral white blood cell count (5.9 × 10⁹/L vs. 8.8 × 10⁹/L; <it>P </it>< 0.001) and a higher median body mass index (22.7 vs. 20.7; <it>P </it>= 0.043) as compared to QFT-G-negative TB patients.</p> <p>Conclusion</p> <p>The overall PPV and NPV of QFT-G for identifying active TB were unsatisfactory, especially for pulmonary disease. Thus, the usefulness of QFT-G for this purpose is questionable. However, a high PPV was observed for extrapulmonary TB and QFT-G might be considered in the diagnostic process in this situation. The PPV and NPV for identifying active TB among persons originating from regions with high-and intermediate TB incidence was similar to that observed in subjects originating in the low-incidence region.</p