Robustness Enhancement of Sensory Transduction by Hair Bundles

How do biological systems ensure robustness of function despite developmental and environmental variation? Our sense of hearing boasts exquisite sensitivity, precise frequency discrimination, and a broad dynamic range. Experiments and modeling imply, however, that the auditory system achieves this performance for only a narrow range of parameter values. Although the operation of some systems appears to require precise control over parameter values, I describe how the function of the ear might instead be made robust to parameter perturbation. The sensory hair cells of the cochlea are physiologically vulnerable: small changes in parameter values could compromise hair cells\u27 ability to detect stimuli. Most ears, however, remain highly sensitive despite differences in their physical properties. I propose that, rather than exerting tight control over parameters, the auditory system employs a homeostatic mechanism that increases the robustness of its operation to variation in parameter values. To slowly adjust the response to sinusoidal stimulation, the homeostatic mechanism feeds back to its adaptation process a rectified version of the hair bundle\u27s displacement. When homeostasis is enforced, the range of parameter values for which the sensitivity, tuning sharpness, and dynamic range exceed specified thresholds can increase by more than an order of magnitude. Certain characteristics of the hair cell\u27s behavior might provide a means to determine through experiment whether such a mechanism operates in the auditory system. This homeostatic strategy constitutes a general principle by which many biological systems might ensure robustness of function

Predictors of airway hyperreactivity in house dust mite allergic patients

Introduction: Airway hyperresponsiveness (AHR) is a cardinal feature of asthma. Asthma is a heterogenous disorder which consists of different phenotypes and endotypes. Mechanisms leading to AHR may differ in different asthma subtypes. Allergy to perennial allergens, including house dust mites (HDM) is a major risk factor for asthma development. The aim of this study was to determine predictors of AHR in a well-characterized population of HDM-allergic patients.Material and methods: In a retrospective analysis 843 patients with HDM-allergic rhinitis with/without asthma were evaluated. The following parameters were included in the analysis: serum concentration of total (t)- and Dermatophagoides pteronyssinus (Dp)-specific IgE, fractional exhaled nitric oxide concentration (FeNO), lung function tests, bronchial challenge with histamine, age sex, and body mass index (BMI). Linear regression analysis was used to determine predictors of AHR.Results: In a simple linear regression analysis baseline lung function results expressed as either forced expiratory volume in 1 s (FEV1) or maximal expiratory flow at 50% of the forced vital capacity (MEF50), FeNO, tIgE, DpIgE, age and BMI affected AHR. A multiple regression analysis demonstrated that in the whole group of HDM-allergic patients the most important, independent predictors of AHR were MEF50, FeNO and DpIgE.Conclusion: Even in a well-characterized asthma phenotype several processes participate in development of AHR. Major, independent predictors of AHR: lung function parameters, FeNO and DpIgE indicate possible targets for therapeutic intervention in a population of HDM-allergic patients

Literature Review—Transthoracic Echocardiography, Computed Tomography Angiography, and Their Value in Clinical Decision Making and Outcome Predictions in Patients with COVID-19 Associated Cardiovascular Complications

The sudden outbreak of the COVID-19 pandemic posed a great threat to the world’s healthcare systems. It resulted in the development of new methods and algorithms for the diagnosis and treatment of both COVID-19 and its complications. Diagnostic imaging played a crucial role in both cases. Among the most widely used examinations are transthoracic echocardiography (TTE) and computed tomography angiography (CTA). Cardiovascular complications in COVID-19 are frequently associated with a severe inflammatory response, which results in acute respiratory failure, further leading to severe complications of the cardiovascular system. Our review aims to discuss the value of TTE and CTA in clinical decision making and outcome prediction in patients with COVID-19-associated cardiovascular complications. Our review revealed the high clinical value of various TTE findings and their association with mortality and the prediction of patients’ clinical outcomes, especially when used with other laboratory parameters. The strongest association between increased mortality and findings in TTE was observed for tachycardia and decreased left ventricular ejection fraction (odds ratio (OR) 24.06) and tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio (TAPSE/PASP ratio) \u3c 0.31 mm/mmHg (OR 17.80). CTA is a valuable tool in diagnosing COVID-19-associated pulmonary embolism, but its association with mortality and its predictive role should always be combined with laboratory findings and patients’ medical history. D-dimers \u3e 3000 ng/mL were found as the strongest predictors of pulmonary embolism (PE) (OR 7.494). Our review indicates the necessity for an active search for cardiovascular complications in patients with severe COVID-19, as they are linked with an increased probability of fatal outcomes

Matrix Metalloproteinase 9 (MMP-9) and Interleukin-8 (IL-8) in Gingival Crevicular Fluid after Regenerative Therapy in Periodontal Intrabony Defects with and without Systemic Antibiotics-Randomized Clinical Trial.

The aim of our study was to assess changes in the levels of IL-8 and MMP-9 in gingival crevicular fluid (GCF) collected from the periodontal pocket before and after regenerative surgery with deproteinized bovine bone mineral (DBBM) and collagen membrane (GTR) either independently (DBBM/GTR) or with the postoperative administration of antibiotic (DBBM/GTR+AB). The study involved 41 patients, each with one intrabony defect. IL-8 and MMP-9 were determined before therapy and after 2 weeks, 4 weeks and 6 months following the surgical procedure by means of dedicated ELISA kits. No statistical differences were observed in the levels of IL-8 and MMP-9 after 2 weeks, 4 weeks and 6 months between the groups. The changes in the level of MMP-9 over time were not statistically significant in any group. The changes in the level of IL-8 were significant for the group given antibiotic but not in the nonantibiotic group in the follow-up period. IL-8 and MMP-9 were found to correlate positively but not after 4 weeks in the test group. Current assessment of IL-8 and MMP-9 obtained from GCF samples provides evidence that collagen matrix turnover occurs actively during the early healing phase in the periodontium after regenerative procedures. We observed positive correlations of MMP-9 and IL-8 throughout the study. However, we failed to reveal any differences regard parameters studied between the two groups

Oocyte zona pellucida and meiotic spindle birefringence as a biomarker of pregnancy rate outcome in IVF-ICSI treatment

Objectives: IVF-ICSI procedures are accompanied by a continuous search for predictors of ART outcome. The properties of zona pellucida (ZP) have been believed to reflect the history of oocyte cytoplasmic maturation. The meiotic spindle (MS) is crucial for chromosomal alignment and proper separation of the maternal chromosomes. There is data suggesting that birefringent ZP and MS can clinically predict the oocyte quality and developmental potential of an embryo. The aim of the study was to examine the possible effect of ZP birefringent properties and MS visualization and localization as valuable predictors of IVF-ICSI effectiveness. Material and methods: The prospective study was performed during a 16-month period. A total of 51 patients undergoing in vitro fertilization - embryo transfer (IVF-ET) treatment procedure with intracytoplasmic sperm injection (ICSI) were included. Controlled ovarian hyperstimulation (COH) was done using either a long n=32 (62.75%) or an antagonist protocol n=19. In the group of the 48 examined patients (aged 25-40), 46 ET were performed, resulting in 24 positive pregnancy tests and 19 (39.59%) clinical pregnancies. Oocytes were examined as follows: ZP birefringence autoscoring (OCTAX PolarAIDE), numeral autoscoring, thickness and clinical evaluation; MS visualization, if MS was visualized, localization of MS in relation to the polar body (PB). Results: On day 3, 64.3% of the embryos were of good and 40.3% were of top quality. Visible differences, not statistically significant, were observed in the numeral score of ZP between oocytes selected and non-selected for ET. In cases when embryos were not of good or top quality, ZP score was higher (p=0.005 p=0.001). ZP manual evaluation indicated significantly stronger birefringence when pregnancy was not achieved (p=0.022). The rate of MS positive oocytes was the highest in the group with pregnancy, but it did not reach statistical significance (p=0.471). The MS localization in relation to the PB was in most oocytes very close

Prognostic significance of DAPK and RASSF1A promoter hypermethylation in non-small cell lung cancer (NSCLC).

The epigenetic inactivation of tumor suppressor genes may play an important role in the development and progression of many cancer types, including lung cancer. Therefore, we investigated the association between the aberrant promoter methylation of 2 genes: the Death-Associated Protein Kinase (DAPK) and the Ras Association Domain Family 1A (RASSF1A) by using methylation-specific PCR, and the clinicopathological features and prognosis in 70 radically resected non-small cell lung cancers (NSCLCs). Hypermethylation of the DAPK and RASSF1A promoters was found in 24 (34%), and in 18 (26%) tumor DNA samples, respectively. Regarding different clinicopathological features of NSCLCs, the DAPK promoter methylation was more frequently observed in squamous cell carcinoma (46%) than in adenocarcinoma (25%) and large cell carcinoma (22%), but there were no significant statistical differences (p=0.3). On the other hand, a statistically significant trend was observed between the RASSF1A methylation and a histological type of tumor (p=0.06). 45% of adenocarcinoma tumors showed RASSF1A promoter methylation in comparison to 17% of squamous cell carcinomas and 22% of large cell carcinomas. When both markers were analyzed according to the tumor-node-metastasis (TNM) staging system, no statistically significant differences were observed between stage I, II and IIIa, and the DAPK (p=0.2) and RASSF1A methylation (p=0.1). In comparison, when stage I and II were grouped together and considered vs. stage IIIa, a significant association between RASSF1A methylation and the TNM was found (p=0.03). The group of patients with tumors showing DAPK promoter methylation had significantly poorer overall survival rates (p=0.02) than the patients with tumors that did not show DAPK promoter methylation. However, the association between the RASSF1A promoter methylation status and the overall survival rates was not statistically significant (p=0.48). In conclusion, this paper supports the importance of epigenetic gene regulation in lung cancer progression and prognosis

Improved radiant burner material. Final report

Under DOE/ERIP funds were made available to Superkinetic, Inc. for the development of an improved radiant burner material. Three single crystal ceramic fibers were produced and two fiber materials were made into felt for testing as radiant burner screens. The materials were alpha alumina and alpha silicon nitride. These fibers were bonded with a high temperature ceramic and made into a structurally sound trusswork like screen composed of million psi fiber members. These screens were about 5% solid for 95 porosity as needed to permit the flow of combustable natural gas and air mixture. Combustion test proved that they performed very satisfactory and better than the current state of art screen and showed no visable degrade after testing. It is recommended that more time and money be put into expanding this technology and test these new materials for their maximum temperature and durability for production applications that require better burner material