The polarized expression of Na+,K+-ATPase in epithelia depends on the association between beta-subunits located in neighboring cells

The polarized distribution of Na+,K+-ATPase plays a paramount physiological role, because either directly or through coupling with co- and countertransporters, it is responsible for the net movement of, for example, glucose, amino acids, Ca2+, K+, Cl-, and CO3H- across the whole epithelium. We report here that the beta-subunit is a key factor in the polarized distribution of this enzyme. 1) Madin-Darby canine kidney (MDCK) cells (epithelial from dog kidney) express the Na+,K+-ATPase over the lateral side, but not on the basal and apical domains, as if the contact with a neighboring cell were crucial for the specific membrane location of this enzyme. 2) MDCK cells cocultured with other epithelial types (derived from human, cat, dog, pig, monkey, rabbit, mouse, hamster, and rat) express the enzyme in all (100%) homotypic MDCK/MDCK borders but rarely in heterotypic ones. 3) Although MDCK cells never express Na+,K+-ATPase at contacts with Chinese hamster ovary (CHO) cells, they do when CHO cells are transfected with beta(1)-subunit from the dog kidney (CHO-beta). 4) This may be attributed to the adhesive property of the beta(1)-subunit, because an aggregation assay using CHO (mock-transfected) and CHO-beta cells shows that the expression of dog beta(1)-subunit in the plasma membrane does increase adhesiveness. 5) This adhesiveness does not involve adherens or tight junctions. 6) Transfection of beta(1)-subunit forces CHO-beta cells to coexpress endogenous a-subunit. Together, our results indicate that MDCK cells express Na+,K+-ATPase at a given border provided the contacting cell expresses the dog P,-subunit. The cell-cell interaction thus established would suffice to account for the polarized expression and positioning of Na+,K+-ATPase in epithelial cells

Using the 3D Facial Norms Database to investigate craniofacial sexual dimorphism in healthy children, adolescents, and adults

Background: Although craniofacial sex differences have been extensively studied in humans, relatively little is known about when various dimorphic features manifest during postnatal life. Using cross-sectional data derived from the 3D Facial Norms data repository, we tested for sexual dimorphism of craniofacial soft-tissue morphology at different ages. Methods: One thousand five hundred fifty-five individuals, pre-screened for craniofacial conditions, between 3 and 25 years of age were placed in to one of six age-defined categories: early childhood, late childhood, puberty, adolescence, young adult, and adult. At each age group, sex differences were tested by ANCOVA for 29 traditional soft-tissue anthropometric measurements collected from 3D facial scans. Additionally, sex differences in shape were tested using a geometric morphometric analysis of 24 3D facial landmarks. Results: Significant (p < 0.05) sex differences were observed in every age group for measurements covering multiple aspects of the craniofacial complex. The magnitude of the dimorphism generally increased with age, with large spikes in the nasal, cranial, and facial measurements observed after puberty. Significant facial shape differences (p < 0.05) were also seen at each age, with some dimorphic features already present in young children (eye fissure inclination) and others emerging only after puberty (mandibular position). Conclusions: Several craniofacial soft-tissue sex differences were already present in the youngest age group studied, indicating that these differences emerged prior to 3 years of age. The results paint a complex and heterogeneous picture, with different groups of traits exhibiting distinct patterns of dimorphism during ontogeny. The definitive adult male and female facial shape was present following puberty, but arose from numerous distinct changes taking place at earlier stages

Intravitreal ranibizumab for myopic choroidal neovascularization: 12-month results

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intravitreal ranibizumab after 12 months in the treatment of choroidal neovascularization secondary to pathologic myopia. METHODS: This was a prospective, multicenter, consecutive, nonrandomized, interventional case series. The study included 34 eyes of 32 patients with choroidal neovascularization secondary to pathologic myopia; 13 eyes had previous photodynamic therapy, and 21 eyes had no previous treatment. The patients were followed for > or = 12 months. Best-corrected visual acuity, optical coherence tomography, and the presence of metamorphopsia were assessed monthly. RESULTS: Mean visual acuity improved 8 letters from baseline to 12-month follow-up, and the difference was statistically significant (P or = 3 lines, 44% improved > or = 2 lines, 65% improved > or = 1 line, and 79% improved > or = 0 lines. Central retinal thickness decreased significantly from baseline to the 12-month follow-up (P < 0.01). A mean of 3.6 treatments were performed during the 12-month follow-up, and no systemic or ocular side effects were registered during that time. CONCLUSION: One-year results of intravitreal ranibizumab for myopic choroidal neovascularization are very promising. Additional prospective studies are necessary to better determine long-term efficacy and safety

Novel Peptides with Dual Properties for Treating Pseudomonas aeruginosa Keratitis: Antibacterial and Corneal Wound Healing

The corneal epithelium is a layer in the anterior part of eye that contributes to light refraction onto the retina and to the ocular immune defense. Although an intact corneal epithelium is an excellent barrier against microbial pathogens and injuries, corneal abrasions can lead to devastating eye infections. Among them, Pseudomonas aeruginosa-associated keratitis often results in severe deterioration of the corneal tissue and even blindness. Hence, the discovery of new drugs able not only to eradicate ocular infections, which are often resistant to antibiotics, but also to elicit corneal wound repair is highly demanded. Recently, we demonstrated the potent antipseudomonal activity of two peptides, Esc(1-21) and its diastereomer Esc(1-21)-1c. In this study, by means of a mouse model of P. aeruginosa keratitis and an in vivo corneal debridement wound, we discovered the efficacy of these peptides, particularly Esc(1-21)-1c, to cure keratitis and to promote corneal wound healing. This latter property was also supported by in vitro cell scratch and ELISA assays. Overall, the current study highlights Esc peptides as novel ophthalmic agents for treating corneal infection and injury, being able to display a dual function, antimicrobial and wound healing, rarely identified in a single peptide at the same micromolar concentration range

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Abstract:&nbsp; The aging of the population constitutes a major challenge for services that interact in an interdisciplinary way with the elderly. We carried out a descriptive cross-sectional study to evaluate opinions of young people regarding the elderly in students of the Department&nbsp;of Community Health III FCM UNC. Anonymous online self-administered survey was conducted using Chi2 and Fisher, designed by Lic. Luis Parodi, and approved by Master\u27s Degree in Gerontology. Chi2 values ​​less than 12.6, p less than 0.023 were obtained. Inclusion Criteria: students of the subject from the year 2021. 384 students participated, response rate 85%. 87% between 19 and 21 years old, 64.6% Female and 35.4% Male 16.2% do not have a grandparent, of those who have 84.3% do not live with them, 36% see them daily, 79.3% have an affectionate relationship. 65.7% consult in problem situations. 73.6% do not consult in personal aspects. 86.2% know the elderly and live nearby. 52.14% is related to affection, 35.3% with respect and 14.7% does not maintain any relationship. 48.2% do not know the beginning of old age and 51.8% are over 60 years old. When requesting aspects that are related to old age regardless of age, 22.5% indicated hopelessness. 18.3% do not love life, 24% feel sick and lonely. young people who visualize the elderly in the framework of society neither rejected nor accepted 33.5%, more respected than not respected in 36.2%, more sedentary than laborious 35.6%, more polite than rude 46.9%, more loving than indifferent in 33.9%, which is equally considered more pleasant than unpleasant in 46%, who is socially more abandoned than protected 31.7% is considered wiser than ignorant 46.1%, it is equally annoying than useful 38.2%, equally boring than active by 40.4% and more ignored than heard by 29.3%. 77.3% believe that the main obstacle that stands between the young-old is the time, 15.2% that the young marginalize the old and 6.4% that the old self-marginalize. 92.4% propose meetings and encounters between young and old, 49% think that the young generations reject the old and 51% think that they do not. This work opens new lines of research to consider the Elderly as a subject integrated in society with opportunities and quality of life.Resumen:&nbsp; El envejecimiento de la población constituye un desafío importante para los servicios que interactúan en forma interdisciplinaria con el adulto mayor. Realizamos estudio descriptivo de corte transversal, para evaluar opiniones de&nbsp;jóvenes respecto al adulto mayor en estudiantes&nbsp;de la cátedra de Salud Comunitaria III FCM UNC, . Se realizó encuesta anónima online autoadministrada usando&nbsp;Chi2 y Fisher, diseñada por Lic. Luis Parodi, y&nbsp;aprobado por Maestría en Gerontología. Se obtuvieron valores de Chi2 menor a 12.6,&nbsp;p&nbsp;menor a 0.023. Criterios de Inclusión:&nbsp;estudiantes de la materia del año 2021. Participaron&nbsp;384 alumnos, tasa de respuesta 85%.&nbsp;87% entre 19 y 21 años, 64.6% Femenino y 35.4% Masculino&nbsp;16.2% no tienen abuelo, de los que tienen 84,3% no vive con ellos, 36% los ve diariamente, 79.3% relación afectuosa.&nbsp;65,7% consulta ante situaciones problemas. 73.6% no consultan en aspectos personales. 86.2% conocen ancianos y viven cerca. 52.14% se relaciona con afecto.35.3% con respeto y 14.7% no mantiene ninguna relación.&nbsp;48.2% desconocen edad comienzo&nbsp;de&nbsp;vejez y 51.8% mas de&nbsp;60 años.&nbsp;Al solicitar aspectos que se relacionan con la vejez independiente de la edad, el 22.5% indicaron la desesperanza. 18.3% no amar la vida, 24% sentirse enfermo y soledad. los jóvenes que visualizan al anciano en el marco de la sociedad ni rechazado ni aceptado un 33.5%, mas respetado que no respetado en un 36.2%, mas sedentario que laborioso un 35.6%, mas educado que grosero un 46.9%, mas amoroso que indiferente en un 33.9%, que es igualmente considerado mas agradable que desagradable en un 46%, que socialmente esta mas abandonado que amparado 31,7% es considerado mas sabio que ignorante 46.1%,&nbsp; es igualmente estorbo que útil 38.2%, igualmente aburrido que activo en un 40,4% y mas ignorado que escuchado un 29.3%. 77.3% opinan que el principal obstáculo que se interpone entre joven- viejo es la época, un 15.2% que el joven margina al viejo y un 6.4% que el viejo se auto margina. 92.4% proponen reuniones y encuentros entre jóvenes y viejos,&nbsp;49% opinan que las generaciones jóvenes rechazan a los viejos y el 51% opina que no.&nbsp;&nbsp;Este trabajo abre nuevas líneas de investigación&nbsp;para considerar&nbsp;al Adulto Mayor como sujeto integrado en sociedad&nbsp;con oportunidades y calidad de vida.

Fungal microbiota from rain water and pathogenicity of Fusarium species isolated from atmospheric dust and rainfall dust

In order to determine the presence of Fusarium spp. in atmospheric dust and rainfall dust, samples were collected during September 2007, and July, August, and October 2008. The results reveal the prevalence of airborne Fusarium species coming from the atmosphere of the South East coast of Spain. Five different Fusarium species were isolated from the settling dust: Fusarium oxysporum, F. solani, F. equiseti, F. dimerum, and F. proliferatum. Moreover, rainwater samples were obtained during significant rainfall events in January and February 2009. Using the dilution-plate method, 12 fungal genera were identified from these rainwater samples. Specific analyses of the rainwater revealed the presence of three species of Fusarium: F. oxysporum, F. proliferatum and F. equiseti. A total of 57 isolates of Fusarium spp. obtained from both rainwater and atmospheric rainfall dust sampling were inoculated onto melon (Cucumis melo L.) cv. Piñonet and tomato (Lycopersicon esculentum Mill.) cv. San Pedro. These species were chosen because they are the main herbaceous crops in Almeria province. The results presented in this work indicate strongly that spores or propagules of Fusarium are able to cross the continental barrier carried by winds from the Sahara (Africa) to crop or coastal lands in Europe. Results show differences in the pathogenicity of the isolates tested. Both hosts showed root rot when inoculated with different species of Fusarium, although fresh weight measurements did not bring any information about the pathogenicity. The findings presented above are strong indications that long-distance transmission of Fusarium propagules may occur. Diseases caused by species of Fusarium are common in these areas. They were in the past, and are still today, a problem for greenhouses crops in Almería, and many species have been listed as pathogens on agricultural crops in this region. Saharan air masses dominate the Mediterranean regions. The evidence of long distance dispersal of Fusarium spp. by atmospheric dust and rainwater together with their proved pathogenicity must be taken into account in epidemiological studies

Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009

BACKGROUND: In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. METHODS: We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. RESULTS: This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. CONCLUSION: This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans