Nanoparticle-and liposome-carried drugs: New strategies for active targeting and drug delivery across blood-brain barrier

The blood-brain barrier (BBB), the unusual microvascular endothelial interface between the central nervous system (CNS) and the circulatory system, is a major hindrance to drug delivery in the brain parenchyma. Besides the absence of fenestrations and the abundance of tight junctions, ATP-binding cassette (ABC) transporters critically reduce drug entry within the CNS, as they carry many drugs back into the bloodstream. Nanoparticle-and liposome-carried drugs, because of their increased cellular uptake and reduced efflux through ABC transporters, have been developed in recent times to circumvent the low drug permeability of the BBB. This review discusses the role of ABC transporters in controlling drug penetration into the brain parenchyma, the rationale for using nanoparticle-and liposome-based strategies to increase drug delivery across the BBB and new therapeutic strategies for using nanoparticle-and liposome-carried drugs in different conditions, ranging from CNS tumors and neurodegenerative diseases to viral infections and epilepsy. © 2013 Bentham Science Publishers

Utilidad de la relación aclaramiento de creatinina - índice de resistencia de la ecografía Doppler renal como predictor de rechazo agudo en riñones trasplantados

ResumenObjetivoAnalizar la utilidad de la asociación del índice de resistencia (IR) en las arterias arcuatas renales con el aclaramiento de creatinina (Cl Cr) para predecir el rechazo agudo del riñón trasplantado.Materiales y métodosSe realizó un estudio prospectivo de una cohorte de 87 pacientes que fueron sometidos a una biopsia renal por alteraciones clínicas de la función renal. Se les midió el IR junto con el Cl Cr mediante el método de modificación de la dieta en la enfermedad renal.ResultadosLa sensibilidad de la asociación IR mayor de 0,7 y Cl Cr 0-30 fue del 53,3% (intervalo de confianza [IC] de 95%: 34,3-71,7%) y la especificidad del 98,2% (95% IC: 90,4-100%). El área bajo la curva fue de 0,758 (95% IC: 0,665-0,85), el likelihood ratio positivo de 22,9 (95% IC: 4,16-214), el likelihood ratio negativo de 0,475 (95% IC: 0,324- 0,685), el odds ratio de 62,9, el valor predictivo positivo de 94,1% (95% IC: 71,3- 99,9%) y el valor predictivo negativo de 79,1% (95% IC: 68,3-88,4%).ConclusiónLa asociación IR mayor de 0,7 y Cl Cr 0-30 demostró ser útil para confirmar la posibilidad de rechazo renal agudo, al tener una buena especificidad (98,2%) a pesar de su baja sensibilidad (53%).AbstractObjectiveTo determine the usefulness of the association between the resistance index (RI) values in renal arcuate arteries and creatinine clearance (Cr Cl) levels in order to predict or detect acute rejection in a kidney transplant patient.Materials and methodsA prospective study was conducted on a cohort of 87 patients who were subjected to a kidney biopsy due to clinical changes in renal function. The RI was measured, and Cr Cl levels determined using the modification of diet in renal disease formula.ResultsThe sensitivity of an RI association higher than 0.7 and a Cr Cl 0-30 was 53.3% (95% confidence interval [CI]: 34.3-71.7%), with a specificity of 98.2% (95% CI: 90.4-100%). The area under the curve was 0.758 (95% CI: 0.665-0.85), the positive and negative likelihood ratio was 22.9 (95% CI: 4.16-214) and 0.475 (95% CI: 0.324-0.685), respectively. The odds ratio was 62.9, and the positive and negative predicted value was 94.1% (95% CI: 71.3-99.9%) and 79.1% (95% CI: 68.3-88.4%), respectively.ConclusionThe RI association higher than 0.7- Cr Cl 0-30 showed to be useful to detect the possibility of acute renal rejection, with its good specificity (98.2%), although with a low sensitivity (53%)

Infección por SARS-CoV-2 y obesidad

La pandemia por coronavirus 2019 (COVID-19) ha tenido diferentes efectos. Uno de ellos fue concentrar la atención de múltiples investigadores y clínicos para dedicarse a estudiar y tratar de entender los retos de esta infección en diferentes poblaciones, que se han determinado en riesgo de presentar una manifestación más grave de la infección. La obesidad ha sido recientemente identificada como una de las comorbilidades de mayor riesgo junto con la insuficiencia cardíaca, con una probabilidad siete veces mayor para el requerimiento de ventilación mecánica invasiva. La obesidad es un factor en la gravedad de la enfermedad del SARS-CoV-2, que tiene un mayor impacto en pacientes con un índice de masa corporal (IMC) ?35 kg/m2 . Los pacientes con obesidad, especialmente aquellos con grado severo, deben tomar medidas adicionales para evitar el contagio con SARS-CoV-2, mediante el cumplimiento de las medidas de prevención durante la pandemia actual, si se quiere, de forma más rigurosa

On the Rotation of Post-T Tauri Stars in Associations

Nearby associations are excellent objects for the study of the initial spin up phase during the PMS evolution. An empirical approach is adopted here to infer their rotations properties and relations to X-ray emission. Three nearby associations are considered. The TW Hya association with an age of 8 Myr, the Beta Pictoris moving group with 12 Myr and a combination of Tucana and Horologium associations (30 Myr). Two low and high rotation modes are considered for each association with stellar masses less than 1.5M and greater than 1.5M respectively. We infer representative equatorial rotation velocities Vo from the observed distribution of projected rotational velocities vsini. A spin up is found for the high rotation mode, whereas in the low rotation mode the Vo do not increase significantly. This insufficient increase of Vo is probably the cause of a decrease of the total mean specific angular momentum for the low mass stars between 8 and 30 Myr. However, for the high mass stars, where a sufficient spin up is present, the specific angular momentum is practically conserved in this same time interval. By supposing that the distribution of masses of these three associations follows a universal mass function, we estimate the number of members of these associations that remain to be detected. The analysis of rotation and stellar masses using luminosity X-rays indicators present similar properties, as the dependence on stellar mass and rotation, at least for the younger associations, to those obtained for T Tauri stars in the ONC. A strong desaturation effect appears at 30 Myr. This effect seems to be provoked by the minimum configuration of the stellar convection layers, attained for the first time for the higher mass stars at 30 Myr. The desaturation appears to be independent of rotation at this stage.Comment: 37 pages, 10 figures, 4 tables. Accepted by the Astronomical Journa

Male infant patient with a mesenteric cyst in the greater and lesser omenta: a case report

Background: Mesenteric cysts are intra-abdominal masses of congenital origin, which most frequently occur in children, with an incidence of approximately 1 case per 20,000 pediatric admissions. Its progression can be asymptomatic, and its diagnosis can be incidental. However, it usually occurs with symptoms such as nausea, vomiting, constipation, sensation of a mass, and/or diarrhea. The diagnostic imaging method of choice is abdominal ultrasound. Case presentation: Below, we present the case of a previously healthy 1-year-old male patient with nonspecific symptoms, who was referred to a tertiary hospital. The presence of a mesenteric cyst was detected at the end of the diagnostic approach. Conclusion: It is important to know these pathologies even though they are infrequent, because although they are benign masses by definition, they can lead to complications such as intestinal torsion, intestinal obstruction, and even peritonitis. © 2020 The Author(s)

Coping Strategies Used by Female Victims of the Colombian Armed Conflict: The Women in the Colombian Conflict (MUCOCO) Program

The effects of armed conflict on women in post-conflict situations are an area of analysis for social disciplines. This study will analyze the situation in Colombia, currently involved in a peace restoration process. The aim is to verify the efficacy of a coping and emotion regulation program analyzing victimization as well as the coping strategies employed in response to these violent acts. The program focuses on 62 women contacted through the Ruta Pacífica de las Mujeres, a nongovernmental organization. The program had a positive effect on women, reporting lower levels of posttraumatic stress, more functional coping strategies, and less use of dysfunctional strategies. All emotional cognitive and social indicators improved. Women felt emotionally better, perceiving greater social support and more trust in institutions. Survivors had more self-confidence to achieve their goals and solve their problems. The implications in a context of peace reconstruction and search for social cohesion are discussed.project (Proyectos CUD 2017) funded by the Oficina de Cooperación al Desarrollo (Development Cooperation Office) of the Universidad del País Vasco/Euskal Herriko Unibertsitatea (University of the Basque Country, Spain) and the University of Burgos funding for the research group SIQoL (Y133GI)

Factors associated with viremia in people living with HIV on antiretroviral therapy in Guatemala

INTRODUCTION: Viral suppression prevents HIV transmission and disease progression, but socio-economic and clinical factors can hinder the goal of suppression. We evaluated factors associated with viral non suppression (VNS) and persistent viremia (PV) in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Guatemala. METHODS: We conducted a cross sectional analysis using data from an ongoing cohort of PLHIV attending the largest HIV clinic in Guatemala. Univariable and multivariable analyses were conducted between PLHIV with viral suppression and detectable viremia. VNS was defined as most recent HIV RNA ≥ 200 copies/ml and PV as two consecutive HIV RNA ≥ 200 copies/ml. RESULTS: Of 664 participants, 13.3% had VNS and 7.1% had PV. In univariable analysis disaggregated by gender, low income, poor education, perceived difficulty attending healthcare, and alcohol use were associated with VNS in men while low CD4 at diagnosis, multiple prior ART regimens and treatment interruptions were significant in both genders. Multiple prior ART regimens (adjusted Odds Ratio (aOR) 2.82, [95% confidence interval (CI) 1.59, 4.99], p \u3c 0.01), treatment interruptions (aOR 4.51, [95% CI 2.13, 9.58], p \u3c 0.01), excessive alcohol consumption (aOR 2.56, [95% CI 1.18, 5.54], p \u3c 0.05) perceived difficulty attending healthcare (aOR 2.07, [ 95% CI 1.25, 3.42], p \u3c 0.01) and low CD4 at diagnosis (aOR 2.34, 95% [CI 1.30, 4.20], p \u3c 0.01) were independently associated with VNS on multivariable regression. CONCLUSIONS: We conclude that socio-economic and clinical factors influence viral suppression in our cohort and vary between men and women. Gender specific approaches are necessary to achieve the 90% suppression goal

Automated laser-transfer synthesis of high-density microarrays for infectious disease screening

Abstract Laser-induced forward transfer (LIFT) is a rapid laser-patterning technique for high-throughput combinatorial synthesis directly on glass slides. A lack of automation and precision limited LIFT applications to simple proof-of-concept syntheses of fewer than 100 compounds. Here, we report an automated synthesis instrument that combines laser transfer and robotics for parallel synthesis in a microarray format with up to 10000 individual reactions/cm2. An optimized pipeline for amide bond formation is the basis for preparing complex peptide microarrays with thousands of different sequences in high yield with high reproducibility. The resulting peptide arrays are of higher quality than commercial peptide arrays. More than 4800 15-residue peptides resembling the entire Ebola virus proteome on a microarray were synthesized to study the antibody response of an Ebola virus infection survivor. We identified known and unknown epitopes that serve now as a basis for Ebola diagnostic development. The versatility and precision of the synthesizer is demonstrated by in situ synthesis of fluorescent molecules via Schiff base reaction and multi-step patterning of precisely definable amounts of fluorophores. This automated laser transfer synthesis approach opens new avenues for high-throughput chemical synthesis and biological screening