Synthesis and Biological Properties of Polyphenol-Containing Linear and Dendrimeric Cationic Peptides.

Natural polyphenols are promising compounds for the pharmacological control of oxidative stress in various diseases. However, low bioavailability and rapid metabolism of polyphenols in a form of glycosides or aglycones have stimulated the search for the vehicles that would provide their efficient delivery to the systemic circulation. Conjugation of polyphenols with cationic amphiphilic peptides yields compounds with a strong antioxidant activity and ability to pass through biological barriers. Due to a broad range of biological activities characteristic of polyphenols and peptides, their conjugates can be used in the antioxidant therapy, including the treatment of viral, oncological, and neurodegenerative diseases. In this work, we synthesized linear and dendrimeric cationic amphiphilic peptides that were then conjugated with gallic acid (GA). GA is a non-toxic natural phenolic acid and an important functional element of many flavonoids with a high antioxidant activity. The obtained GA-peptide conjugates showed the antioxidant (antiradical) activity that exceeded 2-3 times the antioxidant activity of ascorbic acid. GA attachment had no effect on the toxicity and hemolytic activity of the peptides. GA-modified peptides stimulated the transmembrane transfer of the pGL3 plasmid encoding luciferase reporter gene, although GA attachment at the N-terminus of peptides reduced their transfection activity. Several synthesized conjugates demonstrated the antibacterial activity in the model of Escherichia coli Dh5α growth inhibition.

Role and Molecular Mechanisms of Alternative Splicing of Th2-Cytokines IL-4 and IL-5 in Atopic Bronchial Asthma.

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the respiratory tract. Allergic (atopic) asthma is the most common (up to 80% of cases) phenotype developing through the Th2-dependent mechanisms involving cytokines: IL-4, IL-5, IL-9, and IL-13. The genes encoding Th2-cytokines have a mosaic structure (encode exons and introns). Therefore, several mature mRNA transcripts and protein isoforms can be derived from a single mRNA precursor through alternative splicing, and they may contribute to BA pathogenesis. Analysis of the published studies and databases revealed existence of the alternative mRNA transcripts for IL-4, IL-5, and IL-13. The alternative transcripts of IL-4 and IL-5 carry open reading frames and therefore can encode functional proteins. It was shown that not only alternative mRNA transcripts exist for IL-4, but alternative protein isoforms, as well. Natural protein isoform (IL-4δ2) lacking the part encoded by exon-2 was identified. Similarly, alternative mRNA transcript with deleted exon-2 (IL-5δ2) was also identified for IL-5. In this review, we summarize current knowledge about the identified alternative mRNA transcripts and protein isoforms of Th2-cytokinins, first of all IL-4 and IL-5. We have analyzed biological properties of the alternative variants of these cytokines, their possible role in the allergic asthma pathogenesis, and considered their diagnostic and therapeutic potential.

Cell-Penetrating Peptides as Vehicles for Delivery of Therapeutic Nucleic Acids. Mechanisms and Application in Medicine.

Currently, nucleic acid therapeutics are actively developed for the treatment and prophylactic of metabolic disorders and oncological, inflammatory, and infectious diseases. A growing number of approved nucleic acid-based drugs evidences a high potential of gene therapy in medicine. Therapeutic nucleic acids act in the cytoplasm, which makes the plasma membrane the main barrier for the penetration of nucleic acid-based drugs into the cell and requires development of special vehicles for their intracellular delivery. The optimal carrier should not only facilitate internalization of nucleic acids, but also exhibit no toxic effects, ensure stabilization of the cargo molecules, and be suitable for a large-scale and low-cost production. Cell-penetrating peptides (CPPs), which match all these requirements, were found to be efficient and low-toxic carriers of nucleic acids. CPPs are typically basic peptides with a positive charge at physiological pH that can form nanostructures with negatively charged nucleic acids. The prospects of CPPs as vehicles for the delivery of therapeutic nucleic acids have been demonstrated in numerous preclinical studies. Some CPP-based drugs had successfully passed clinical trials and were implemented into medical practice. In this review, we described different types of therapeutic nucleic acids and summarized the data on the use of CPPs for their intracellular delivery, as well as discussed, the mechanisms of CPP uptake by the cells, as understanding of these mechanisms can significantly accelerate the development of new gene therapy approaches.

The clinical implications of Porphyromonas gingivalis and its detection methods - a systematic review.

INTRODUCTION: Mounting evidence has shown the significant correlation between periodontitis and the development of other comorbidities, such as cardiovascular disease due to periodontopathogenic bacterial migration and colonisation. As the main etiologic agent of periodontitis, the role of Porphyromonas gingivalis (P. gingivalis) has been widely explored as the main culprit and its early detection is crucial to control the exacerbation of diseases. This review aims to identify and summarise all clinical diseases that potentially developed due to the presence of P. gingivalis and discover all its detection methods that have been developed. MATERIALS AND METHODS: Full-text articles of case report, case control, cohort and cross-sectional studies that were published from 1st January 2012 until 30th June 2022, were searched using PubMed, CINAHL and Scopus. Periodontal related diseases were excluded in this review due to its wellknown associated disease with P. gingivalis. A comparison studies of detection methods were also excluded in this review. RESULTS: Out of 612 articles that were screened, only 106 met the eligibility criteria to be selected for further review. Risk of bias was performed using FEAT principles and reviewers' discussion. A total of 21 final articles that were reviewed showed significant correlation with P. gingivalis and were classified into several clinical domains. Twelve out of 13 detection methods showed high sensitivity and specificity with short duration analysis. CONCLUSION: Due to asymptomatic periodontal disease and the high prevalence of P. gingivalis-associated clinical diseases, this review suggests the need for oral public health awareness and early screening for the bacterium detection especially among elderly groups to maintain their quality of life.

Immunogenicity and In Vivo Protective Effects of Recombinant Nucleocapsid-Based SARS-CoV-2 Vaccine Convacell®.

The vast majority of SARS-CoV-2 vaccines which are licensed or under development focus on the spike (S) protein and its receptor binding domain (RBD). However, the S protein shows considerable sequence variations among variants of concern. The aim of this study was to develop and characterize a SARS-CoV-2 vaccine targeting the highly conserved nucleocapsid (N) protein. Recombinant N protein was expressed in Escherichia coli, purified to homogeneity by chromatography and characterized by SDS-PAGE, immunoblotting, mass spectrometry, dynamic light scattering and differential scanning calorimetry. The vaccine, formulated as a squalane-based emulsion, was used to immunize Balb/c mice and NOD SCID gamma (NSG) mice engrafted with human PBMCs, rabbits and marmoset monkeys. Safety and immunogenicity of the vaccine was assessed via ELISA, cytokine titer assays and CFSE dilution assays. The protective effect of the vaccine was studied in SARS-CoV-2-infected Syrian hamsters. Immunization induced sustainable N-specific IgG responses and an N-specific mixed Th1/Th2 cytokine response. In marmoset monkeys, an N-specific CD4+/CD8+ T cell response was observed. Vaccinated Syrian hamsters showed reduced lung histopathology, lower virus proliferation, lower lung weight relative to the body, and faster body weight recovery. Convacell® thus is shown to be effective and may augment the existing armamentarium of vaccines against COVID-19.

Murine model of steroid-resistant neutrophilic bronchial asthma as an attempt to simulate human pathology.

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the airways. The majority of patients with mild to moderate BA develop Th2-biased eosinophilic pulmonary inflammation and respond well to corticosteroid treatment. However up to 10% of BA patients develop severe pathology, which is associated with neutrophilic inflammation and resistant to conventional corticosteroid therapy. Contrary to eosinophil-predominant airway inflammation neutrophilic BA is developed through Th1- and Th17-immune responses. However, the etiology of corticoid insensitive neutrophilic BA is still remains unclear. Therefore, in the current study we developed a mouse model of BA with predominant neutrophilic rather than eosinophilic pulmonary inflammation. BALB/c mice were immunized with the mixture of the ovalbumin allergen and Freund's adjuvant, followed by aerosol challenge with the same allergen mixed with E. coli lipopolysaccharide. As a result, mice developed the main BA manifestations: production of allergen specific IgE, development of airway hyperreactivity, airway remodeling and pulmonary neutrophilic inflammation. Moreover, this pathology developed through Th1- and Th17-dependent mechanisms and mice with induced neutrophilic BA phenotype responded poorly to dexamethasone treatment, that coincide to clinical observations. The established mouse model could be useful both for studying the pathogenesis and for testing novel approaches to control neutrophilic BA.

Literacy in the time of Coronavirus: an Italian perspective: Value of literacy in the context of a pandemic.

Background: COVID-19 pandemic, with its dramatic impact on society, poses a challenge to Health Pro-motion and to its principles of empowerment, social cohesion and citizens' democratic participation in health policies. In this pressing emergency, public health strategies aimed at preventing the spread of the pandemic have been primarily oriented towards restrictive measures (travel restrictions, use of PPE) in absence of an adequate educational communication, aimed at increasing citizens' knowledge and skills in regard to the emergency context. Aim: To offer a perspective on the Italian situation, in terms of health literacy and life skills in the context of COVID-19 pandemic, aimed not only at identifying deficits, but particularly at determining opportuni-ties and resources (assets) - offered by the peculiar context of crisis - useful to provide citizens with the necessary tools to comprehend the criticalities linked with the emergency and to shape their behaviour to new requirements, in absence of external obligations, as well as to promote future participation of the population - both effective and informed - in a social and political context. Methods: A non-systematic review of literature on the subject of health literacy and social cohesion in emergency contexts has been supported by a qualitative assessment, based on the model of assets and on the Italian condition in the last trimester of 2020. Results: The scarce ability of the population to independently adequate habits and behaviour to new criti-calities required by the risk of infection - as well as the necessity to suspend their empowerment and capa-bility from government authorities to protect public health - has been firstly traced back to a widespread lack of literacy and life skills at a general population level. The current situation of crisis offers a peculiar opportunity of tools, circumstances and receptiveness to highlight such deficits, as well as an intervention on multiple fronts, in order to increase literacy and capability, both on an individual and on a community level, through inclusive and sustainable initiatives. Conclusion: A prevention strategy based on the critical understanding of risk and risk-related criticalities is the only one which can aspire to last over time, while offering an effective tool for the safeguarding of public health, along with an opportunity of being prepared to contrast future emergencies more effectively. The development of such strategies represents one of the most significant contributions Health Promotion can offer in the time of Coronavirus.

Role of STAT3 Transcription Factor in Pathogenesis of Bronchial Asthma.

Bronchial asthma is a heterogeneous chronic inflammatory disease of airways. The studies of molecular and cellular mechanisms of bronchial asthma have established that a wide range of immune (T and B cells, eosinophils, neutrophils, macrophages, etc.) and structural (epithelial and endothelial) cells are involved in its pathogenesis. These cells are activated in response to external stimuli (bacteria, viruses, allergens, and other pollutants) and produce pro-inflammatory factors (cytokines, chemokines, metalloproteinases, etc.), which ultimately leads to the initiation of pathological processes in the lungs. Genes encoding transcription factors of the STAT family (signal transducer and activator of transcription), that includes seven representatives, are involved in the cell activation. Recent studies have shown that the transcription factor STAT3 plays an important role in the activation of the abovementioned cells, thus contributing to the development of asthma. In animal studies, selective inhibition of STAT3 significantly reduces the severity of lung inflammation, which indicates its potential as a therapeutic target. In this review, we describe the mechanisms of STAT3 activation and its role in polarization of Th2/Th17 cells and M2 macrophages, as well as in the dysfunction of endothelial cells, which ultimately leads to development of bronchial asthma symptoms, such as infiltration of neutrophils and eosinophils into the lungs, bronchial hyperreactivity, and the respiratory tract remodeling.

Naïve Regulatory T Cell Subset Is Altered in X-Linked Agammaglobulinemia.

The interplay between T- and B-cell compartments during naïve, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the thymic selection. Here we investigated characteristics of naïve and effector T cell subsets in XLA patients, revealing prominent alterations in the corresponding T-cell receptor (TCR) repertoires. We observed immunosenescence in terms of decreased diversity of naïve CD4+ and CD8+ TCR repertoires in XLA donors. The most substantial alterations were found within naïve CD4+ subsets, and we have investigated these in greater detail. In particular, increased clonality and convergence, along with shorter CDR3 regions, suggested narrower focused antigen-specific maturation of thymus-derived naïve Treg (CD4+CD45RA+CD27+CD25+) in the absence of B cells - normally presenting diverse self and commensal antigens. The naïve Treg proportion among naïve CD4 T cells was decreased in XLA patients, supporting the concept of impaired thymic naïve Treg selection. Furthermore, the naïve Treg subset showed prominent differences at the transcriptome level, including increased expression of genes specific for antigen-presenting and myeloid cells. Altogether, our findings suggest active B cell involvement in CD4 T cell subsets maturation, including B cell-dependent expansion of the naïve Treg TCR repertoire that enables better control of self-reactive T cells.

Psychometric properties of the Malay inventory for the perception of Muslims with hearing impairment.

OBJECTIVE: The aims of this study are to measure the psychometric properties of the newly developed preliminary version of hearing impairment inventory for religious duties for Muslim adults, i.e., the Inventori Persepsi Bagi Muslim Yang Memiliki Masalah Pendengaran (IPM3P), and to produce a final version of IPM3P. METHODS: The preliminary version of IPM3P that is used to investigate the perception of Muslim adults with hearing impairment towards Islamic understanding and practice has been tested in this study. The preliminary version of IPM3P consists of three domains (obligation, practice, and difficulty) with 59 items in total. Four phases of validity and reliability testing involved were: i) Content validation, ii) Pretesting, face validity and proofreading, iii) Pilot study, and iv) Psychometric evaluation. RESULTS: The final version of IPM3P consists of 36 items. The findings from the present study suggest that the final version of IPM3P has excellent psychometric properties manifested by: i) good content validity, ii) excellently pretested, iii) good face validity, iv) good construct validity shown by principal component analysis and convergent validity, and v) good discriminant validity showed by divergent validity. CONCLUSION: IPM3P shows good potential to be used as a tool in investigating perception of Muslim adults towards Islamic understanding and practice.

Translation, validation and cross-cultural adaptation of the Malay emotion regulation checklist (ERC-M): A preliminary study.

INTRODUCTION: Emotion Regulation Checklist (ERC) has been used globally and translated to several languages, including Brazilian Portuguese, Italian and Persian. The aim of this study is to translate and validate ERC to the Malay language and to measure the reliability and validity of the translated version of this scale among Malaysian parents. METHODS: This study involved forward and back translation method. The translated questionnaire was then pretested and piloted among 10 parents and 50 participants, respectively. The procedure was repeated using the same questionnaire to evaluate the test-retest reliability. RESULTS: The ERC-Malay (ERC-M) has excellent qualitative and quantitative measurements in both item-level content validation index (I-CVI) and scale-level content validation index (S-CVI). In addition, the ERC-M demonstrated good internal consistency from Cronbach's alpha and test-retest reliability based on the Intraclass Correlation Coefficient (ICC) in all domains. CONCLUSION: ERC-M can potentially be used as a tool to evaluate emotion for the population with emotional dysregulation issue, such as autism spectrum disorder.

Molecular and Cellular Mechanisms of Respiratory Syncytial Viral Infection: Using Murine Models to Understand Human Pathology.

Respiratory syncytial virus (RSV) causes severe pathology of the lower respiratory tract in infants, immunocompromised people, and elderly. Despite decades of research, there is no licensed vaccine against RSV, and many therapeutic drugs are still under development. Detailed understanding of molecular and cellular mechanisms of the RSV infection pathology can accelerate the development of efficacious treatment. Current studies on the RSV pathogenesis are based on the analysis of biopsies from the infected patients; however deeper understanding of molecular and cellular mechanisms of the RSV pathology could be achieved using animal models. Mice are the most often used model for RSV infection because they exhibit manifestations similar to those observed in humans (bronchial obstruction, mucous hypersecretion, and pulmonary inflammation mediated by lymphocytes, macrophages, and neutrophils). Additionally, the use of mice is economically feasible, and many molecular tools are available for studying RSV infection pathogenesis at the molecular and cellular levels. This review summarizes new data on the pathogenesis of RSV infection obtained in mouse models, which demonstrated the role of T cells in both the antiviral defense and the development of lung immunopathology. T cells not only eliminate the infected cells, but also produce significant amounts of the proinflammatory cytokines TNFα and IFNγ. Recently, a new subset of tissue-resident memory T cells (TRM) was identified that provide a strong antiviral defense without induction of lung immunopathology. These cells accumulate in the lungs after local rather than systemic administration of RSV antigens, which suggests new approaches to vaccination. The studies in mouse models have revealed a minor role of interferons in the anti-RSV protection, as RSV possesses mechanisms to escape the antiviral action of type I and III interferons, which may explain the low efficacy of interferon-containing drugs. Using knockout mice, a significant breakthrough has been achieved in understanding the role of many pro-inflammatory cytokines in lung immunopathology. It was found that in addition to TNFα and IFNγ, the cytokines IL-4, IL-5, IL-13, IL-17A, IL-33, and TSLP mediate the major manifestations of the RSV pathogenesis, such as bronchial obstruction, mucus hyperproduction, and lung infiltration by pro-inflammatory cells, while IL-6, IL-10, and IL-27 exhibit the anti-inflammatory effect. Despite significant differences between the mouse and human immune systems, mouse models have made a significant contribution to the understanding of molecular and cellular mechanisms of the pathology of human RSV infection.

Development of hearing impairment inventory for religious duties of Muslim adult.

OBJECTIVE: This study is a preliminary work to develop a Malay version questionnaire named 'Inventori Persepsi bagi Muslim yang Memiliki Masalah Pendengaran (IPM3P)' to assess the perception on Islamic understanding and practice among Muslim adults with hearing impairment. METHODS: The scale development involved three phases: i) generation of domains based on the literature, ii) generation of sub-domains based on literature review and Islamic panel survey, and iii) generation of items. RESULTS: Preliminary version of IPM3P consists of 59 items was produced, representing three domains: Obligation (18 items), Practice (21 items), and Difficulty (20 items), and seven sub-domains ('Ibadah', 'Aqidah', 'Muamalat', 'Tasawwuf', 'Akhlak','Da'wah', and 'Sirah'). CONCLUSION: The preliminary version of IPM3P needs to be psychometrically tested. This pioneering study may become an impetus towards more research pertaining to understanding the effect of hearing loss towards religious life in the future in Malaysia.

Genotoxicity of cationic lipopeptide nanoparticles.

The genotoxicity of cationic lipopeptide nanoparticles (cLPNPs) was evaluated in vivo and in vitro comet assay and the in vivo chromosome aberrations test. In vitro comet assay, human blood cells were exposed to cLPNPs at the concentration of 2.5, 5, 10, 20, 40 and 100 µg/mL. Significant DNA damage was observed after 1 h exposure, but no effects were detected after 3 h. In vivo, cLPNPs were administered in single or five daily injection doses at 8, 20 and 40 mg/kg of body weight by subcutaneous injection to male mice. The cLPNPs caused DNA damage in the liver, lung and kidney, but not in the spleen. The kidney was more prone to genotoxic effects that persisted from 24 h to 14d after a single injection of cLPNPs. No statistically significant increase in the percentage of cells with chromosomal aberrations above the vehicle control was observed in mice bone marrow after a single or repeated injection of cLPNPs. In summary, cLPNPs shown to be genotoxic both in vivo and in vitro. The results suggest the importance of the use of highly sensitive methods, such as the comet assay, in order to determine the full genotoxic potential of nanoparticles.

Linear and dendrimeric antiviral peptides: design, chemical synthesis and activity against human respiratory syncytial virus.

Respiratory syncytial virus (RSV) is one of the most common viral pathogens. It is especially dangerous for newborns and young children. In some cases it could lead to severe bronchiolitis, pneumonia with hospitalization or even a lethal outcome. Despite decades of investigation of RSV biology, effective and safe therapeutics are still under development. Certain natural peptides have been found to exhibit antiviral activity against respiratory viruses, but their implementation is limited by low stability in biological media. One of the current approaches to enhance the peptide therapeutic opportunities is chemical synthesis of peptide dendrimers with hyperbranched structures. Taking into account the recent data of bioactive cationic and helical regions of natural peptides and the structure features of nucleolin identified as an RSV cellular receptor, the main goal of this study was to design relatively short linear and dendrimeric cationic peptides and to test their antiviral activity against RSV. As a result 3 linear cationic peptides and 4 peptide dendrimers were synthesized and compared with known LL-37 (cathelicidin family) and anti-F0 monoclonal antibodies in terms of cytotoxicity and antiviral activity. Their affinity to the supposed molecular target - nucleolin (C23) - was estimated in silico by molecular docking analysis. Four synthesized peptides demonstrated a cytotoxic effect, two of them were even more cytotoxic than LL-37, which could be explained by a combination of a high amount of positive charge and amphipathicity. Contrariwise, non-hydrophobic dendrimer peptides did not exhibit cytotoxicity in mammalian cells in the studied concentration range. Two of the seven synthesized peptides, LTP (dendrimer) and SA-35 (linear), used in this study had a stronger antiviral effect than natural peptide LL-37, and three others showed slightly lower activity than anti-F0 monoclonal antibodies. The data obtained in this study suggest that evenly distributed positive charge, and low or medium amphipathicity play a key role in the antiviral activity of the studied peptides. Moreover, the calculated free energy values of the peptide/nucleolin complex for the most active peptides supported the idea that the peptide ability of nucleolin interaction promotes the anti-RSV properties of the molecules.

Risk Factors for 3-Year-Mortality and a Tool to Screen Patient in Dialysis Population.

INTRODUCTION: Clinical parameters especially co-morbidities among end stage renal disease (ESRD) patients are associated with mortality. This study aims to determine the risk factors that are associated with mortality within three years among prevalent patients with ESRD. METHODS: This is a cohort study where prevalent ESRD patients' details were recorded between May 2012 and October 2012. Their records were matched with national death record at the end of year 2015 to identify the deceased patients within three years. Four models were formulated with two models were based on logistic regression models but with different number of predictors and two models were developed based on risk scoring technique. The preferred models were validated by using sensitivity and specificity analysis. RESULTS: A total of 1332 patients were included in the study. Majority succumbed due to cardiovascular disease (48.3%) and sepsis (41.3%). The identified risk factors were mode of dialysis (P < 0.001), diabetes mellitus (P < 0.001), chronic heart disease (P < 0.001) and leg amputation (P = 0.016). The accuracy of four models was almost similar with AUC between 0.680 and 0.711. The predictive models from logistic regression model and risk scoring model were selected as the preferred models based on both accuracy and simplicity. Besides the mode of dialysis, diabetes mellitus and its complications are the important predictors for early mortality among prevalent ESRD patients. CONCLUSIONS: The models either based on logistic regression or risk scoring model can be used to screen high risk prevalent ESRD patients.

Correlación entre el grado de hipertensión arterial y el índice de estrés oxidativo. Estudio de cohorte en una población de pacientes hipertensos sistémicos en República Dominicana / Correlation between the arterial hypertension degree and oxidative stress index. Cohort study in a population of systemic hypertensive patients in Dominican Republic

Introducción: la hipertensión arterial (HTA) es una de las mayores cargas de enfermedad y riesgo para infarto cardíaco, la insuficiencia cardíaca y el fallo renal. Se reconoce que el estrés oxidativo (EO) es un determinante en el desarrollo de complicaciones y el progreso de la HTA. Se determinó el índice de EO (IEO) en individuos con HTA y en un grupo sano control, para evaluar su posible correlación. Materiales y métodos: se midió IEO en una población de 112 individuos con HTA de distintos grados entre 50 y 70 años escogidos al azar y se comparó con los valores de un grupo control de voluntarios sanos, con la intención de definir el grado de correlación entre los niveles del IEO y la severidad de HTA, mediante la medición de biomarcadores para el EO en lisado de eritrocitos. Resultados: a pesar de que los beneficios de la terapia antioxidante (TAO) no han sido definitivamente probadas, en gran parte porque las enfermedades complejas no dependen de un solo componente fisiopatogénico, el EO sigue siendo una piedra angular en el desarrollo de complicaciones y el empeoramiento de los cuadros clínicos de muchos padecimientos. La demostración de biomarcardores específicos mejora la posibilidad de una TAO dirigida. El presente ensayo demostró que la edad, el género y la etnia no influyen en el IEO y que el EO fue severo en los casos de HTA iii, moderado en HTA ii y estuvo ausente en el subgrupo con HTA grado i. Conclusiones: estos resultados sugieren una relación entre los niveles de EO y severidad de HTA y sustenta evidencias para diseñar nuevos ensayos clínicos que evalúen la eficacia de una TAO adyuvante en el manejo de la HTA

Introduction: Arterial hypertension (AHT) is one of the major burdens of disease and risk for cardiac infarction, heart failure and renal failure. It is recognized that the oxidative stress (OS) is a determining factor in the development of complications and the progress of the AHT. OS Index (OSI) in individuals with AHT and a healthy control group, was determined to assess their possible correlation. Methods: OSI was measured in a population of 112 individuals with AHT of different levels between 50 and 70 years old, chosen at random and compared with the values of healthy volunteers control group with the aim of defining the degree of correlation between the levels of the OSI and the AHT severity, by measuring biomarkers for OS in a red cell lysate. Discussion: Despite the benefits of an antioxidant therapy (AOT) have not been definitely proven, largely because the complex diseases do not depend on a single pathophysiological component, OS remains as a cornerstone in the development of complications and the worsening of the clinical pictures of many ailments. The demonstration of specific biomarkers improve the possibility of an addressed AOT. This trial showed th at the age, gender and ethnicity do not influence the OSI and that OS was severe in HTA iii cases, moderate in HTA ii cases and was absent in the subgroup with HTA i. Conclusions: These results suggest a relationship between levels of EO and severity of hypertension and support evidence to design new clinical trials assessing the efficacy of an adjuvant AOT in the management of HTA

A novel computer-based simulated learning environment in audiology with learning assistance: Preliminary findings.

INTRODUCTION: This paper describes the development and the evaluation of a new Two-dimensional (2D) computer-based (CB) Simulated Learning Environment (SLE) software for routine audiology tests that comes with learning assistance for audiology students. The aim of the study was to serve as preliminary evaluation on the effectiveness of the new 2D CB SLE audiology software among audiology students. MATERIALS AND METHODS: The development process of the new 2D CB SLE includes, (i) the identification of common errors made by students in the audiology clinic, (ii) the development of five case simulations that include four routine audiology tests incorporating learning assistance derived from the errors commonly made by audiology students and, (iii) the development of 2D CB SLE from a technical perspective. A preliminary evaluation of the use of the 2D CB SLE software was conducted among twenty-six second-year undergraduate audiology students. RESULTS: The pre-analysis evaluation of the new 2D CB SLE showed that the majority of the students perceived the new 2D CB SLE software as realistic and helpful for them in achieving the course learning outcomes and in improving their clinical skills. The mean overall scores among the twenty-six students using the self-reported questionnaire were significantly higher when using the 2D CB SLE software than with the existing software typically used in their SLE training. CONCLUSIONS: This new 2D CB SLE software has the potential for use by audiology students for enhancing their learning.