Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The properties such as clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the translation of siRNA is restricted by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.

Standardized Tests as Predictors of NCLEX-RN Success

@#PURPOSE: This study examined the predictive ability of Assessment Technologies Institute (ATI) standardized tests on Fundamentals of Nursing (FON), Pharmacology (PHARM), Medical-Surgical Nursing (MSN), and RN Comprehensive Predictor (RNCP) on the National Council Licensure Examination-Registered Nurses (NCLEX-RN) performance of nursing graduates. BACKGROUND: Various assessment tools in nursing education are used to predict the success of students in nursing licensure examinations. There are inconsistent findings on the predictive ability of course-specific standardized tests on NCLEX-RN success. METHODS: A retrospective correlation research design was used to determine the association between ATI standardized tests and NCLEX-RN success. Secondary data analysis of 141 ATI student scores from 2017 to 2018 from a Southeastern university in the United States were analyzed using descriptive and inferential statistics, set at 0.05 level of significance. Three models of logistic regression were used to determine the predictive ability of ATI standardized exams on NCLEX-RN success. RESULTS: ATI MSN standardized test is the strongest predictor of NCLEX-RN success, followed by ATI FON and ATI RNCP tests. ATI PHARM standardized test is not predictive of NCLEX-RN success. CONCLUSION: Standardized tests can help in identifying students who are at-risk for failing the NCLEX-RN prior to taking the examination. Understanding the impact of standardized testing on NCLEX-RN performance is essential in addressing the students' ability to become successful in the nursing program and NCLEX-RN.

Alergia ao glúten: série de nove casos / Gluten allergy: series of nine cases

Objetivos: Havendo poucos casos descritos de alergia ao gl�ten mediada por IgE, divulgamos uma s�rie de nove casos, com especial relevosobre o diagn�stico, vias de sensibiliza��o, manifesta��es cl�nicas e factores preditivos de progn�stico.M�todos: Nesta s�rie foram inclu�dos todos os casos de alergia ao gl�ten mediada por IgE, seguidos nos �ltimos 15 anos no ambulat�rio deAlergologia Pedi�trica de um hospital terci�rio. Foram analisadas idade de in�cio, manifesta��es iniciais, vias de sensibiliza��o, comorbidadese aquisi��o de toler�ncia.Resultados: Foram inclu�das nove crian�as com alergia ao gl�ten, com idades entre 1 e 14 anos, sendo oito meninos. A primeira manifesta��oocorreu entre os 5 e 9 meses. Em seis pacientes as primeiras manifesta��es foram cut�neas, dois apresentaram dist�rbios gastrointestinais e umamenina apresentou anafilaxia como manifesta��o inicial. A via de sensibiliza��o foi cut�nea ou por ingest�o. O valor de IgE espec�fica parao gl�ten variou entre 0,73-100 KUA/l. Todas as crian�as tinham outra doen�a at�pica. Oito apresentavam alergia alimentar m�ltipla. Quatrodesenvolveram alergia respirat�ria. Em dois casos ocorreu anafilaxia ap�s o diagn�stico. Tr�s resolveram a alergia ao gl�ten at� os seis anos.Conclus�es: A alergia ao gl�ten � rara, explicando o pequeno n�mero diagnosticado em 15 anos, em um hospital central de refer�ncia. Osnove casos tiveram in�cio no primeiro ano de vida, sendo as manifesta��es cut�neas as mais frequentes. O eczema foi uma apresenta��ofrequente e a sensibiliza��o foi por via cut�nea em alguns casos. A alergia alimentar m�ltipla tamb�m foi frequente nos casos descritos. Tr�sdas nove crian�as resolveram a alergia at� os seis anos, tendo em comum uma manifesta��o inicial cut�nea. Nestes nove casos, o valor de IgEespec�fica n�o foi preditivo da evolu��o cl�nica.

Aims: With few reported cases of IgE-mediated allergy to gluten, we report a series of nine cases, with special emphasis on diagnosis, processof sensitization, clinical manifestations and predictive factors of prognosis.Methods: In this series all cases of IgE-mediated allergy to gluten, followed the last 15 years at the Pediatric Allergology of a tertiary hospital,were included. Age of onset, initial symptoms, routes of sensitization, comorbidities and acquisition of tolerance were analyzed.Results: with gluten allergy, with ages ranging from 1 to 14 years, were included; eight were boys. The first manifestation took place between 5and 9 months. In six patients the initial symptoms were cutaneous, two patients had gastrointestinal disorders, and one girl showed anaphylaxisas the initial manifestation. The route of sensitization was cutaneous or by food ingestion. Serum specific IgE to gluten ranged from 0,73 to100KUA/l. All children exhibited other atopic diseases. Eight children had multiple food allergies and four developed respiratory allergy.Two patients suffered anaphylaxis after the diagnosis. Three cases resolved their gluten allergy up to eight years of age.Conclusions: Gluten allergy is rare, explaining the small number diagnosed in 15 years, in a central referral hospital. The nine cases began inthe first year of life, being cutaneous manifestations the most frequent. Eczema is a common presentation and there was dermal sensitizationin some cases. Multiple food allergy was also frequent in the cases described. Three of the nine children resolved allergy up to six years,having in common an initial cutaneous manifestation. In these nine cases, the value of specific IgE was not predictive of clinical outcome.

O uso de academias da terceira idade por idosos modifica parâmetros morfofuncionais? / Does the use of third age fitness centers by the elderly modify morphofunctional parameters?

O objetivo do estudo foi analisar as características morfofuncionais de usuários de Academias da Terceira Idade (ATIs) na cidade de Maringá, Estado do Paraná. O estudo contou com 86 indivíduos (28 homens (67,8 ± 5,4 anos) e 58 mulheres (67,6 ± 6,0 anos)). Os parâmetros morfofuncionais foram divididos em antropométricos (Índice de Massa Corporal - IMC e a Relação Cintura-Quadril - RCQ) e funcionais (níveis pressóricos - PA). Foi usada a estatística descritiva para tratamento dos dados. Em relação ao estado nutricional, homens apresentaram valores maiores de IMC em comparação às mulheres. Quanto à distribuição regional de gordura, as mulheres apresentaram RCQ mais alto quando separados pelos diferentes estratos, embora em valores absolutos a média masculina tenha sido maior. Quanto a PA, homens mostraram tendência de valores mais elevados, mas ambos os gêneros tiveram reduções nos valores de PA na reavaliação, especialmente as mulheres. É possível concluir que o período de três a seis meses de prática nas ATIs não foi capaz de produzir mudanças significativas nos parâmetros morfológicos de indivíduos acima de 60 anos, independente do gênero. Modificações na função cardiovascular sinalizam importantes reduções nos níveis pressóricos, indicando que a prescrição individualizada e a regularidade de atividade física são essenciais para a obtenção de melhoras mais expressivas.

The objective of the study was to analyze the morphofunctional characteristics from users of Third Age Fitness Centers (TAFC) in the city of Maringá, Parana State. The study involved 86 individuals ­ 28 men (67.8 ± 5.4 years of age old) and 58 women (67.6 ± 6.0 years old). The morphofunctional parameters were divided into anthropometric (Body Mass Index ­ BMI and Waist-Hip Ratio ­ WHR) and functional (blood pressure ­ BP). The method used for data processing was descriptive statistics. With regard to nutritional status, men showed higher BMI values compared to women. As for regional body fat distribution, women had higher WHR when separated by different strata, although in absolute values the male average was higher. As for BP, men showed a trend for higher values, but both genders had reductions in BP values in the reassessment, especially women. We can conclude that the three to six-month period of practice at ATA was not able to produce significant changes in the morphologic parameters of individuals over 60 years of age old, regardless of gender. Changes in cardiovascular function indicate important reductions in blood pressure levels, indicating that individualized prescription and regular physical activity are essentials to achieving most significant improvements.

Advances in the study of arrhythmogenic mechanisms / 国际药学研究杂志

Arrhythmia is a common complication of cardiovascular diseases and a risk factor for human health. Especially, ventricular tachycardia and ventricular fibrillation may not only exacerbate original heart diseases, but also cause cardiac sudden death which has been an mportant death reason in China. However, anti-arrhythmic drugs nowadays cannot effectively treat these arrhythmias, with an efficiency of only 30%-60%, which indicates that our knowledge about arrhythmias is limited. Hence, to explore the potential mechanism, look for novel targets, and develop drugs with multiple-channel action are the focus of the research direction. Recent studies displayed that the atrial-specific potassium channels such as IKur and IKAch were involved in atrial fibrillation, which provided a prospective target for atrial fibrillation treatment. Calcium leak, gap junction protein and autoantibody against ICaL channel were shown to participate in arrhythmogenesis. These findings provided a theoretical basis for the development of more effective anti-arrhythmic drugs. Remarkably, as a kind of mportant RNA regulating gene expression, microRNA (miRNA) was shown to possess anti-arrhythmic activities which may prevent cardiac sudden death. miR-1, miR-133 and miR-590 regulated the arrhythmia in various types of animal models. Because of the multiple-gene regulation actions of miRNA, it has the potential to be developed as novel anti-arrhythmic target.

Acciones de endotelina 1 y angiotensina II en embarazos complicados con preeclampsia / Endothelin 1 and angiotensin II in preeeclampsia

Introduction. It is generally thought that development of hypertension in preeclampsia (PE) is due to generalized endothelial dysfunction and/or results from an imbalance in the production and/or action of vasoactive factors, resulting in higher citosolic Ca2+ concentration which in turn leads to vasoconstriction and decreased blood pressure perfusion in organs, including the fetoplacental unit. Among vasoactive factors involved in blood pressure regulation, endothelin 1 (ET-1) and angiotensin II (Ang II) regulate citosolic Ca2+ concentrations and therefore are considered in this review. PE is associated with higher circulating and placental ET-1 levels, observation that explains, at least in part, vasoconstriction and oxidative stress. Higher and lower Ang II sensitivity seen in PE and normal pregnancy, respectively, could not be explained by changes in renin-angiotensin system components, including Ang II receptors (ATI). During normal pregnancy, ATI receptors are found as monomers and are inactivated by reactive oxygen species (ROS) leading to lower Ang II sensitivity. In contrast, PE is associated with increased ATl/bradicinin receptors (B2) heterodimers which are resistant to inactivation by ROS, maintaining increased ATI-receptor stimulated signaling in PE. In adittion, AT-1 agonistic antibodies (AT1-AA) obtained from PE women increases intracellular Ca2+, NADPH oxidase components and ROS, effects not observed with normal pregnancy AT1-AA. Conclusion. High ET-1 levels, the presence of AT1/B2 receptor heterodimers and increased AT1-AA are involved, at least in part, in the hypertensive and oxidative stress states in PE.

Introducción. Se reconoce que el desarrollo de la hipertensión en la preeclampsia (PE) resulta del daño endotelial generalizado y/o de la falta de equilibrio en la producción y/o acción de agentes vasoactivos, lo que conlleva al incremento en la concentración citosólica de Ca2+ que resulta en vasoconstricción y disminución de la perfusión sanguínea en los órganos, incluyendo la unidad fetoplacentaria. Dentro de los factores vaso-activos que regulan la presión arterial, en la presente revisión se consideró a la endotelina 1 (ET-1) y a la angiotensina II (Ang II), factores que regulan la concentración citosólica de Ca2+. En comparación con el embarazo normal, la PE se asocia con mayor concentración en suero y placenta de ET-1, lo que explica en parte la vasoconstricción y el estado de estrés oxidativo. La respuesta exagerada en la PE y el estado de refractariedad en el embarazo normal a la Ang II no pueden explicarse por componentes del sistema renina-angiotensina, incluyendo a los receptores de Ang II (ATI). Durante el embarazo normal los receptores AT-1 se encuentran en forma de monómeros y son inactivados por las especies reactivas de oxígeno (ROS), lo que se asocia con menor respuesta a Ang II. En cambio, la respuesta exagerada a la Ang II durante la PE puede deberse a la heterodimerizacion de los receptores ATI con los de bradicinina (B2), estado que les confiere resistencia a la inactivación por las especies reactivas de oxígeno (ROS), lo que explica el incremento en la concentración del Ca2+ intracelular. Además, los anticuerpos agonistas del receptor ATI (AT1-AA) de mujeres PE aumenta la concentración de Ca2+ intracelular, de la NADPH oxidasa y de ROS, efectos que no se presentan al utilizar AT1-AA de embarazadas normotensas. Conclusión. Las altas concentraciones de ET-1, la presencia de receptores ATI en forma de heterodimeros ATI/ B2 y el aumento en los AT1-AA explican en parte, el estado de hipertensión y de estrés oxidativo de la PE.

Otoscopic and audiologic findings in an ati community in Boracay

Background: Certain indigenous populations have been noted by the World Health Organization (WHO) to havethe highest prevalence ratesforchronicsuppurativeotitis media (CSOM), including the Australian Aborigines (28-43%), Greenlanders (2-10%) and Alaskan Eskimos (2-10%). Objectives: To determine the prevalence of common ear problems, particularly CSOM, among the indigenous Ati or Aeta community in Bolabog, Boracay, and to determine their hearing sensitivity using screening audiometry. Methods: Study Design - Descriptive cross-sectional study. Setting - A small Ati community in Bolabog, Boracay. Population - A total of 63 adults and children underwent medical interview and otoscopy. Additionally 24 had their hearing screened by audiometry. Results: About a quarter of the population participated in the study, including 41 children (40 percent of all children) and 22 adults (18 percent of all adults). Forty-six percent of children and 23 percent of adults who were examined had previous history of ear discharge, while 22 percent of children and 45 percent of adults who were examined had history of hearing loss. Seventeen percent of children had history of hearing loss in the family. CSOM was found in 18 (43.90 percent) children and 8 (36.36 percent) adults. Impacted cerumen was found in 17.1 percent of children. Eleven female children underwent screening audiometry. Of these, eight had normal hearing and three had abnormal findings. Thirteen adults were also tested, five of whom were male and had normal hearing bilaterally. Four of eight female adults had abnormal hearing, of which three were unilateral. Conclusions: The Ati population in Bolabog, Boracay belongs to a group with the highest prevalence rates for CSOM (27.0 percent). A bigger sample for screening audiometry is required for proper estimation of hearing loss prevalence. Both environmental and genetic factors may have increased the prevalence of CSOM in the Ati population of Boracay. (Author)