Caracterización clínica y epidemiológica de la epidemia de Chikungunya en el Paraguay

Durante el verano del 2022 y 2023 ocurrió la mayor epidemia de Chikungunya en Paraguay, y una de las más grandes reportadas en la región. Estuvo centralizada en el área metropolitana de Asunción en una primera etapa, pero se expandió al resto del país durante los primeros meses del 2023. Este trabajo tiene el objetivo de describir epidemiológica y clínicamente la epidemia desde su inicio en la semana epidemiológica 40 del 2022 hasta la semana 20 del 2023. Metodología: es un estudio descriptivo que utiliza los datos públicos disponibles en la página de la Dirección General de Vigilancia de la Salud. Fueron confirmados 86.761 casos, 58% femenino, 8227 ingresos hospitalarios y 248 fallecidos. La letalidad global es de 2.8 por mil casos confirmados. Los grupos etarios más afectados corresponden a la franja de 0 a 4 años (9%), sin embargo, la mayor incidencia de casos se da en mayores de 80 años. Los principales desafíos de esta enfermedad son el abordaje multidisciplinario en la gestión del manejo del vector, la evaluación de las causas de esta alta letalidad y la necesidad de una vacuna de uso poblacional.

During the summer of 2022 and 2023, the largest Chikungunya epidemic occurred in Paraguay, and one of the largest reported in the region. It was centralized in the metropolitan area of Asunción in a first stage, but it expanded to the rest of the country during the first months of 2023. This work has the objective of describing the epidemic epidemiologically and clinically from its beginning in epidemiological week 40 of 2022 to week 20 of 2023. Methodology: it is a descriptive study that uses the public data available on the page of the General Directorate of Health Surveillance. 86,761 cases were confirmed, 58% female, 8,227 hospital admissions, and 248 deaths. The global lethality is 2.8 per thousand confirmed cases. The most affected age groups correspond to the 0 to 4-year-old group (9%), however, the highest incidence of cases occurs in people over 80 years of age. The main challenges of this disease are the multidisciplinary approach in the management of the vector, the evaluation of the causes of this high lethality and the need for a vaccine for population use.

Caracterización clínica y epidemiológica de la epidemia de Chikungunya en el Paraguay / Clinical and epidemiological characterization of the Chikungunya epidemic in Paraguay

Durante el verano del 2022 y 2023 ocurrió la mayor epidemia de Chikungunya en Paraguay, y una de las más grandes reportadas en la región. Estuvo centralizada en el área metropolitana de Asunción en una primera etapa, pero se expandió al resto del país durante los primeros meses del 2023. Este trabajo tiene el objetivo de describir epidemiológica y clínicamente la epidemia desde su inicio en la semana epidemiológica 40 del 2022 hasta la semana 20 del 2023. Metodología: es un estudio descriptivo que utiliza los datos públicos disponibles en la página de la Dirección General de Vigilancia de la Salud. Fueron confirmados 86.761 casos, 58% femenino, 8227 ingresos hospitalarios y 248 fallecidos. La letalidad global es de 2.8 por mil casos confirmados. Los grupos etarios más afectados corresponden a la franja de 0 a 4 años (9%), sin embargo, la mayor incidencia de casos se da en mayores de 80 años. Los principales desafíos de esta enfermedad son el abordaje multidisciplinario en la gestión del manejo del vector, la evaluación de las causas de esta alta letalidad y la necesidad de una vacuna de uso poblacional.

During the summer of 2022 and 2023, the largest Chikungunya epidemic occurred in Paraguay, and one of the largest reported in the region. It was centralized in the metropolitan area of Asunción in a first stage, but it expanded to the rest of the country during the first months of 2023. This work has the objective of describing the epidemic epidemiologically and clinically from its beginning in epidemiological week 40 of 2022 to week 20 of 2023. Methodology: it is a descriptive study that uses the public data available on the page of the General Directorate of Health Surveillance. 86,761 cases were confirmed, 58% female, 8,227 hospital admissions, and 248 deaths. The global lethality is 2.8 per thousand confirmed cases. The most affected age groups correspond to the 0 to 4-year-old group (9%), however, the highest incidence of cases occurs in people over 80 years of age. The main challenges of this disease are the multidisciplinary approach in the management of the vector, the evaluation of the causes of this high lethality and the need for a vaccine for population use.

Synthesis of a novel magnetic nanomaterial for the development of a multielemental speciation method of lead, mercury, and vanadium via HPLC-ICP MS.

A new magnetic functionalized material based on graphene oxide magnetic nanoparticles named by us, M@GO-TS, was designed and characterized in order to develop a magnetic solid-phase extraction method (MSPE) to enrich inorganic and organic species of lead, mercury, and vanadium. A flow injection (FI) system was used to preconcentrate the metallic and organometallic species simultaneously, while the ultra-trace separation and determination of the selected species were achieved by high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC-ICP MS). Therefore, preconcentration and separation/determination processes were automated and conducted separately. To the best of our knowledge, this is the first method combining an online MSPE and HPLC-ICP MS for multielemental speciation. Under the optimized conditions, the enrichment factor obtained for PbII, trimethyllead (TML), HgII, methylmercury (MetHg), and VV was 27. The calculated LOD for all studied species were as follows: 5 ng L-1, 20 ng L-1, 2 ng L-1, 10 ng L-1, and 0.4 ng L-1, respectively. The RSD values calculated with a solution containing 0.5 µg L-1 of all species were between 2.5 and 4.5%. The developed method was validated by analyzing Certified Reference Materials TMDA 64.3 for total concentration and also by recovery analysis of the species in human urine from volunteers and a seawater sample collected in Málaga. The t statistical test showed no significant differences between the certified and found values for TMDA 64.3. All the recoveries obtained from spiked human urine and seawater samples were close to 100%. All samples were analyzed using external calibration. The developed method is sensitive and promising for routine monitoring of the selected species in environmental waters and biological samples.

A Pilot Study of Improving Self-Regulation and Social Interaction with Peers: An "Exciting School".

Social interaction skills are related to successful academic performance and mental health. One of the key elements of socio-emotional competence is self-regulation. The main aim of this study was to analyze the effect of a self-regulation program at a primary school on the social interactions of neurotypical children and children with special educational needs, from the teachers' and parents' perspectives. A pre-post study was conducted. The children (n = 107) followed 10 sessions, each one of 50 min, for ten weeks, between January and April 2021. To assess the changes in children's social interaction, the Peer Social Maturity Scale was administered to the teachers. After the intervention, parents completed a questionnaire designed ad hoc to understand the effectiveness of children's emotional self-regulation. The results showed a statistically significant improvement in peer interaction skills. The families were satisfied with the program, due to the improvement in their children's knowledge about their own emotions and those of the other people, and the learning strategies to regulate their emotions. Likewise, parents indicated that it would be necessary to complement the program with teaching and emotional regulation strategies for them. The "Exciting School" program could help improve the social skills of school-aged children.

Características epidemiológicas de los 190 pacientes internados con SARS-CoV2 en el Hospital General de Barrio Obrero periodo junio-diciembre 2020

RESUMEN El Hospital General de Barrio Obrero no es ajeno a la pandemia, teniendo pacientes hospitalizados con COVID-19 desde inicios de junio de 2020 con un impacto alto en los servicios. Se analizaron 190 pacientes internados en los distintos servicios. Se encontró predominio del sexo masculino 52%. En cuanto a la edad, se observó un claro predominio de gerontes con el 51% del total de pacientes170 (89%) fueron internados en el servicio de clínica médica, a pesar de eso, aún un bajo porcentaje se detectó en servicios como gineco-obstetricia y cirugía general. Según la evolución clínica de los pacientes, 138 (73%) fueron dados de alta, 29 (15%) fueron trasladados a un centro de mayor complejidad por complicación de la enfermedad y 23 (12%) fallecieron, 16 (70%) eran de sexo masculino, según el rango etario, los pacientes que obitaron eran gerontes 17 (74%), adultos mayores 4 (17%) y adultos jóvenes 2 (9%). Octubre fue el mes con más muertes en pacientes internados con SARS-CoV-2. .En cuanto a la comorbilidad, 91% presentaba al menos una comorbilidad, entre las que predominó la hipertensión arterial (25%)

ABSTRACT The Barrio Obrero General Hospital is no stranger to the pandemic, having hospitalized patients with COVID-19 since the beginning of June 2020 with a high impact on services. 190 patients admitted to the different services were analyzed. 52% male predominance was found. Regarding age, a clear predominance of elderly was observed with 51% of all patients170 (89%) were admitted to the medical clinic service, despite this, a low percentage was still detected in services such as gynecology. obstetrics and general surgery. According to the clinical evolution of the patients, 138 (73%) were discharged, 29 (15%) were transferred to a more complex center due to complications of the disease and 23 (12%) died, 16 (70%) were of male sex, according to age range, the patients who obtained were elderly 17 (74%), older adults 4 (17%) and young adults 2 (9%). October was the month with the most deaths in patients hospitalized with SARS-CoV-2. Regarding comorbidity, 91% had at least one comorbidity, among which arterial hypertension predominated (25%).

Serie de Casos de Leishmaniasis Detectados en Centros Hospitalarios del Departamento de Caaguazú, Paraguay en 2019

Resumen La leishmaniasis es la tercera de las enfermedades de transmisión vectorial a humanos en importancia por el número de casos y la población en riesgo. En Paraguay la leishmaniasis cutánea es una enfermedad endémica atribuida en casi todos los casos a Leishmania (Viannia) braziliensis. El objetivo del artículo es describir las características demográficas y clínicas de una serie de casos de pacientes con leishmaniasis en el V departamento de Caaguazú y departamentos cercanos, epidemiológicamente endémicos. Se reportan casos diagnosticados en los meses enero a diciembre del año 2019. Los casos se presentaron en el departamento de Caaguazú, abarcando los diferentes distritos que componen y departamentos cercanos como Canindeyú, Alto Paraná y Guaira. De los casos registrados (9 casos) fueron hombres y (6 casos) tuvieron entre 50 a 70 años de edad. La lesión estuvo situada mayormente en el tabique nasal en 8 casos, con una evolución de menos de 10 años (6 casos) y en 4 casos dejo cicatriz. Solo 3 casos completaron su tratamiento. Se sugiere realizar el reporte de casos para tener un panorama de los casos de leishmaniasis en Paraguay como vigilancia sanitaria de la enfermedad y localizar focos de contagio.

Abstract Leishmaniasis is the third most important vector-borne diseases in humans due to the number of cases and the population at risk. In Paraguay, cutaneous leishmaniasis is an endemic disease attributed in almost all cases to Leishmania (Viannia) braziliensis. The objective of the article was to describe the demographic and clinical characteristics of a series of cases of patients with leishmaniasis in the V department of Caaguazú and nearby departments, epidemiologically endemic. Cases diagnosed in the months of January to December of the year 2019 are reported. The cases occurred in the department of Caaguazú, covering the different districts that make up and nearby departments such as Canindeyú, Alto Paraná and Guaira. Of the registered cases (9 cases) were men and (6 cases) were between 50 and 70 years of age. The lesion was located mainly in the nasal septum in 8 cases, with an evolution of less than 10 years (6 cases) and in 4 cases it left a scar. Only 3 cases completed their treatment. It is suggested to carry out the case report to have an overview of Leishmania cases in Paraguay as a health surveillance of the disease and to locate sources of contagion.

Análisis de datos basados en evidencia para la caracterización epidemiológica de leishmaniasis en Paraguay: I - Leishmaniasis tegumentaria

Resumen La leishmaniasis es una enfermedad desatendida, transmitida por dípteros de los géneros Phlebotomus y Lutzomyia. Existen tres formas clínicas principales de leishmaniasis: una visceral, y dos tegumentarias, las cuales se dividen en leishmaniasis cutánea (LC) y leishmaniasis mucocutánea (LM), todas presentes en Paraguay. El objetivo de este trabajo es describir las características epidemiológicas de la leishmaniasis tegumentaria en Paraguay. Aquí analizamos datos epidemiológicos de leishmaniasis tegumentaria (incluyendo LC y ML), tomados desde el 2006 hasta el 2017. La identidad de los pacientes se mantuvo confidencial. Un total de 2.918 casos positivos de leishmaniasis fueron estudiados. El pico de casos reportados se dio en el 2007. Una vista general muestra una disminución en la tendencia de leishmaniasis tegumentaria, donde los varones son más afectados que las mujeres, y el área endémica está localizada en las zonas este y noreste de Paraguay. Los casos en el Chaco (al oeste del Río Paraguay) están en aumento. La incidencia de leishmaniasis tegumentaria para el país es de 4 personas por 100.000 habitantes. Esta es considerada una enfermedad ocupacional ya que el 67% de los pacientes infectados fueron trabajadores rurales. Durante el periodo de estudio, la LC fue más común que la LM, excepto en los años 2010, 2014 y 2017. La mayoría de los pacientes afectados por LM son de avanzada edad. Conclusión. Remarcamos que la leishmaniasis no está restringida a las áreas húmedas del este de Paraguay, debido a que está también presente en zonas xerofíticas de Paraguay y Bolivia. Los trabajadores rurales de sexo masculino comprenden el grupo más susceptible. La alta frecuencia de LM en algunos años indica que es necesario que las agencias nacionales lleven a cabo más programas de educación en salud para prevenir o reducir la carga de LC (y por consiguiente también de LM) en el país.

Abstract Leishmaniasis is a neglected disease transmitted by sandflies of the genera Phlebotomus and Lutzomyia. There are three main clinical forms of leishmaniasis: one visceral and two tegumentary, differentiated between cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (ML), all present in Paraguay. The objective of this work is to describe the epidemiologic characteristics of tegumentary leishmaniasis in Paraguay. Here we analyzed epidemiological data of tegumentary leishmaniasis (including CL and ML), taken from 2006 to 2017. Patients' identities were kept confidential. A total of 2,918 cases of positive leishmaniasis infection were studied. The peak of reported cases was in 2007. An overview shows a decrease in the trend of tegumentary leishmaniasis, where males are more affected than females, and the endemic area located on the east and north-eastern parts of Paraguay. Cases in the Chaco (west of Paraguay river) are increasing. The incidence of tegumentary leishmaniasis for the country is 4 persons per 100,000 inhabitants. This is considered an occupational disease since 67% of the infected patients were rural workers. During the period of study CL was more common than ML, except for the years 2010, 2014, and 2017. Most of the patients affected by ML are elders. Conclusion. We remark that leishmaniasis is not only restricted to the humid area of eastern Paraguay, since it is also present in xerophytic areas of Paraguay and Bolivia. Male rural workers are the most susceptible group. The high frequency of ML in some years indicates that more educational programs have to be carried out by national agencies to prevent and reduce the burden of CL (and thus also ML) in the country.

Randomly branching θ-polymers in two and three dimensions: Average properties and distribution functions.

Motivated by renewed interest in the physics of branched polymers, we present here a detailed characterization of the connectivity and spatial properties of 2- and 3-dimensional single-chain conformations of randomly branching polymers under θ-solvent conditions obtained by Monte Carlo computer simulations. The first part of the work focuses on polymer average properties, such as the average polymer spatial size as a function of the total tree mass and the typical length of the average path length on the polymer backbone. In the second part, we move beyond average chain behavior and we discuss the complete distribution functions for tree paths and tree spatial distances, which are shown to obey the classical Redner-des Cloizeaux functional form. Our results were rationalized first by the systematic comparison to a Flory theory for branching polymers and next by generalized Fisher-Pincus relationships between scaling exponents of distribution functions. For completeness, the properties of θ-polymers were compared to their ideal (i.e., no volume interactions) as well as good-solvent (i.e., above the θ-point) counterparts. The results presented here complement the recent work performed in our group [A. Rosa and R. Everaers, J. Phys. A: Math. Theor. 49, 345001 (2016); J. Chem. Phys. 145, 164906 (2016); and Phys. Rev. E 95, 012117 (2017)] in the context of the scaling properties of branching polymers.

Detección molecular de Leishmania (Viannia) lainsoni Silveira, Shaw, Braga & Ishikawa, 1987 (Kinetoplastida: Trypanosomatidae) en humanos de Paraguay

RESUMEN La leishmaniasis es una de las enfermedades tropicales más desatendidas, causada por el parásito Leishmania. En Paraguay, la especie responsable de la leishmaniasis cutánea es (LC) es L. (Viannia) braziliensis. Aquí se reporta un caso diagnosticado de Leishmaniasis, y análisis moleculares empleando reacción en cadena de la polimerasa - polimorfismos de restricción de fragmentos de restricción (PCR-RFLP) demostraron que el caso fue causado por L. (V.) lainsoni. Este es el primer registro de esta especie para Paraguay, con lo cual se extiende el rango de distribución conocido de la especie, unos 1.430 km al sur de localidades previamente conocidas. Se necesitan más estudios para conocer la incidencia real de esta especie en casos de LC en Paraguay, y para identificar reservorios naturales del parásito en la naturaleza.

ABSTRACT Leishmaniasis is one of the most neglected tropical diseases worldwide caused by the parasite Leishmania. In Paraguay the species responsible for cutaneous leishmaniasis (CL) is L. (Viannia) braziliensis. Here we report a case diagnosed with Leishmaniasis, and molecular analyses using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) demonstrate that the case was caused by L. (V.) lainsoni. This is the first record of this species for Paraguay, with which we extend the distribution range of the parasite 1,430 km southwards from the southernmost previous known locality. More studies are needed to know the actual incidence of this species in cases of CL in Paraguay, and to identify natural reservoirs in the wild.

Nonequilibrium Uptake Kinetics of Molecular Cargo into Hollow Hydrogels Tuned by Electrosteric Interactions.

Hollow hydrogels represent excellent nano- and microcarriers due to their ability to encapsulate and release large amounts of cargo molecules (cosolutes) such as reactants, drugs, and proteins. In this work, we use a combination of a phenomenological effective cosolute-hydrogel interaction potential and dynamic density functional theory to investigate the full nonequilibrium encapsulation kinetics of charged and dipolar cosolutes by an isolated charged hollow hydrogel immersed in a 1:1 electrolyte aqueous solution. Our analysis covers a broad spectrum of cosolute valences ( zc) and electric dipole moments (µc), as well as hydrogel swelling states and hydrogel charge densities. Our calculations show that, close to the collapsed state, the polar cosolutes are predominantly precluded and the encapsulation process is strongly hindered by the excluded-volume interaction exerted by the polymer network. Different equilibrium and kinetic sorption regimes (interface versus interior) are found depending on the value and sign of zc and the value of µc. For cosolutes of the same sign of charge as the gel, the superposition of steric and electrostatic repulsion leads to an "interaction-controlled" encapsulation process, in which the characteristic time to fill the empty core of the hydrogel grows exponentially with zc. On the other hand, for cosolutes oppositely charged to the gel, we find a "diffusion-controlled" kinetic regime, where cosolutes tend to rapidly absorb into the hydrogel membrane and the encapsulation rate depends only on the cosolute diffusion time across the membrane. Finally, we find that increasing µc promotes the appearance of metastable and stable surface adsorption states. For large enough µc, the kinetics enters an "adsorption-hindered diffusion", where the enhanced surface adsorption imposes a barrier and slows down the uptake. Our study represents the first attempt to systematically describe how the swelling state of the hydrogel and other leading physical interaction parameters determine the encapsulation kinetics and the final equilibrium distribution of polar molecular cargo.

Histoplasmosis diseminada con lesiones cutáneas y osteomielitis en un niño con Leucemia Linfoblastica Aguda en mantenimiento / Disseminated histoplasmosis with skin lesions and osteomyelitis in a child with acute Lymphoblastic Leukemia Undergoing maintenance treatment

La histoplasmosis es una micosis causada por el hongo Histoplasma capsulatum y generalmente se manifiesta como una infección diseminada en pacientes inmunocomprometidos. La osteomielitis por H. capsulatum es rara y difícil de diagnosticar. Presentamos un caso inusual de histoplasmosis diseminada, causada por H. capsulatum, con lesiones en piel, mucosas y osteomielitis en un niño de 10 años de edad con Leucemia Linfoblastica Aguda en tratamiento con metotrexato vía oral a dosis baja, con adecuada respuesta a Anfotericina b y mantenimiento con Itraconazol.

Histoplasmosis is a mycosis caused by the fungus Histoplasma capsulatum and usually manifests as a disseminated infection in immunocompromised patients. Osteomyelitis due to H. capsulatum is rare and difficult to diagnose. We present an unusual case of disseminated histoplasmosis, caused by H. capsulatum, with lesions in skin, mucous membranes and osteomyelitis in a 10-yearold boy with acute Lymphoblastic Leukemia Undergoing low-dose oral methotrexate treatment, who had an adequate response to Amphotericin B and maintenance treatment with Itraconazole.

Frecuencia de colonización y sensibilidad de Staphylococcus aureus en un grupo de niños sanos en Asunción

Introducción: La portación nasal de Staphylococcus aureus (SA) en individuos sanos constituye una fuente potencial de infección. La prevalencia de infecciones por SA adquiridas en la comunidad ha aumentado entre los niños sanos. Aunque la epidemiología de la colonización e infección por SA en otros países se ha estudiado ampliamente, los datos son limitados en el Paraguay. Objetivos: Determinar la prevalencia de la portación nasal por SA y su susceptibilidad antimicrobiana en una población de escolares sanos en Asunción, y evaluar factores de riesgo asociados a la colonización. Material y métodos: Estudio multicéntrico, prospectivo, descriptivo y analítico, sobre la colonización nasal por SA en niños de 5 a 16 años, durante el periodo comprendido entre junio y julio del 2016. Previa autorización de los padres y la escuela, se recogieron datos demográficos y factores de riesgo para la colonización. La determinación de SA se realizó mediante muestras de hisopado de las narinas de los niños. Se realizaron pruebas de susceptibilidad antimicrobiana en Agar Mueller y la sensibilidad a la vancomicina se realizó mediante tiras de E-Test®. Los datos fueron registrados en planillas Excel y analizados con el software R v.3.4.2 Resultados: 299 niños fueron incluidos en el estudio. De estos, 58%(173) eran mujeres con una media de edad de 10,6 (±2,5) años. El 79,9% procedía de Asunción y vivía con una media de 5,1 (±1,8) habitantes en el domicilio. Se determinó la presencia de SA en el 30,8% (92/299) de los niños. El 63% de los niños refirió algún factor de riesgo para la colonización por SA. Se objetivo que el antecedente de una enfermedad previa OR=1,92 (95%IC 0,88-4,28), el uso de antibióticos previos OR=1,51 (95%IC 0,89-2,55), la convivencia con mascotas OR=1,42(95%IC 0,81-2,50) y los tratamientos crónicos OR=1,20 (95%IC 0,55-2,61) fueron las variables asociadas a un mayor riesgo de presentar colonización por SA. Conclusión: En el presente estudio se objetivó que el 30,8% de los niños incluidos en el estudio presentaba colonización por SA y que los factores asociados a un mayor riesgo de colonización han sido el antecedente de una enfermedad previa, el uso de antibióticos, la convivencia con mascotas y los tratamientos crónicos.

Introduction: Staphylococcus aureus (SA) nasal carriage in healthy individuals is a potential source of infection. The prevalence of SA infections acquired in the community has increased among healthy children. Although the epidemiology of colonization and infection by SA in other countries has been studied extensively, data are limited in Paraguay. Objectives: To determine the prevalence of nasal carriage by SA and its antimicrobial susceptibility in a population of healthy schoolchildren in Asunción, and to evaluate risk factors associated with colonization. Material and methods: This was a multicenter, prospective, descriptive and analytical study on nasal colonization by SA in children aged 5 to 16 years between June and July 2016. After obtaining authorization from parents and the school, we collected data on demographics and on risk factors for colonization. The SA colonization determination was made by swabbing samples from the children's nostrils. Antimicrobial susceptibility tests were performed on Mueller Agar and the sensitivity to vancomycin was made using E-Test® strips. The data were recorded in Excel spreadsheets and analyzed with the R v.3.4.2 software. Results: 299 children were enrolled in the study. Of these, 58% (173) were female with an average age of 10.6 (± 2.5) years. 79.9% came from Asunción and lived with an average of 5.1 (± 1.8) inhabitants at home. The presence of SA was detected in 30.8% (92/299) of the children. 63% of children reported some risk factor for colonization by SA. We found that a history of a previous disease OR = 1.92 (95% CI 0.88-4.28), the use of previous antibiotics OR = 1.51 (95% CI 0.89-2.55), cohabitation with pets OR = 1.42 (95% CI 0.81-2.50) and chronic treatments OR = 1.20 (95% CI 0.55-2.61) were the variables associated with an increased risk for colonization by SA. Conclusion: In the present study it was found that 30.8% of the children enrolled in the study were colonized by SA and that factors associated with an increased risk of colonization were a history of a previous disease, the use of antibiotics, coexistence with pets and chronic treatments.

Conformation change of an isotactic poly (N-isopropylacrylamide) membrane: Molecular dynamics.

In this work, isotactic Poly (N-Isopropylacrylamide)-PNIPAM-in neat water and in electrolyte solutions is studied by means of molecular dynamics simulations. This is done for an infinitely diluted oligomer and for an assembly of several PNIPAM chains arranged into a planar membrane configuration with a core-shell morphology. We employed two different force fields, AMBER (assisted model building with energy refinement) and OPLS-AA (all atom - optimized potentials for liquid simulations) in combination with extended simple point charge water. Despite the more water insoluble character of isotactic oligomers, our results support the existence of a coil to globule transition for the isolated 30-mer. This may imply the existence of an oligomer rich phase of coil-like structures in equilibrium with a water rich phase for temperatures close but below the coil to globule transition temperature, TΘ. However, the obtained coil structure is much more compact than that corresponding to the syndiotactic chain. Our estimations of TΘ are (308±5) K and (303±5) K for AMBER and OPLS-AA, respectively. The membrane configuration allows one to include chain-chain interactions, to follow density profiles of water, polymer, and solutes, and accessing the membrane-water interface tension. Results show gradual shrinking and swelling of the membrane by switching temperature above and below TΘ, as well as the increase and decrease of the membrane-water interface tension. Finally, concentration profiles for 1M NaCl and 1M NaI electrolytes are shown, depicting a strong salting-out effect for NaCl and a much lighter effect for NaI, in good qualitative agreement with experiments.

Sorption and Spatial Distribution of Protein Globules in Charged Hydrogel Particles.

We have theoretically studied the uptake of a nonuniformly charged biomolecule suitable for representing a globular protein or a drug by a charged hydrogel carrier in the presence of a 1:1 electrolyte. On the basis of the analysis of a physical interaction Hamiltonian including monopolar, dipolar, and Born (self-energy) contributions derived from linear electrostatic theory of the unperturbed homogeneous hydrogel, we have identified five different sorption states of the system, from complete repulsion of the molecule to its full sorption deep inside the hydrogel, passing through metastable and stable surface adsorption states. The results are summarized in state diagrams that also explore the effects of varying the electrolyte concentration, the sign of the net electric charge of the biomolecule, and the role of including excluded-volume (steric) or hydrophobic biomolecule-hydrogel interactions. We show that the dipole moment of the biomolecule is a key parameter controlling the spatial distribution of the globules. In particular, biomolecules with a large dipole moment tend to be adsorbed at the external surface of the hydrogel, even if like-charged, whereas uniformly charged biomolecules tend to partition toward the internal core of an oppositely charged hydrogel. Hydrophobic attraction shifts the states toward the internal sorption of the biomolecule, whereas steric repulsion promotes surface adsorption for oppositely charged biomolecules or for the total exclusion of likely charged ones. Our results establish a guideline for the spatial partitioning of proteins and drugs in hydrogel carriers, tunable by the hydrogel charge, pH, and salt concentration.

Competition between excluded-volume and electrostatic interactions for nanogel swelling: effects of the counterion valence and nanogel charge.

In this work the equilibrium distribution of ions around a thermo-responsive charged nanogel particle in an electrolyte aqueous suspension is explored using coarse-grained Monte Carlo computer simulations and the Ornstein-Zernike integral equation theory. We explicitly consider the ionic size in both methods and study the interplay between electrostatic and excluded-volume effects for swollen and shrunken nanogels, monovalent and trivalent counterions, and for two different nanogel charges. We find good quantitative agreement between the ionic density profiles obtained using both methods when the excluded repulsive force exerted by the cross-linked polymer network is taken into account. For the shrunken conformation, the electrostatic repulsion between the charged groups provokes a heterogeneous polymer density profile, leading to a nanogel structure with an internal low density hole surrounded by a dense corona. The results show that the excluded-volume repulsion strongly hinders the ion permeation for shrunken nanogels, where volume exclusion is able to significantly reduce the concentration of counterions in the more dense regions of the nanogel. In general, we demonstrate that the thermosensitive behaviour of nanogels, as well as their internal structure, is strongly influenced by the valence of the counterions and also by the charge of the particles. On the one hand, an increase of the counterion valence moves the swelling transition to lower temperatures, and induces a major structuring of the charged monomers into internal and external layers around the crown for shrunken nanogels. On the other hand, increasing the particle charge shifts the swelling curve to larger values of the effective radius of the nanogel.

Size-exclusion partitioning of neutral solutes in crosslinked polymer networks: a Monte Carlo simulation study.

In this work, the size-exclusion partitioning of neutral solutes in crosslinked polymer networks has been studied through Monte Carlo simulations. Two models that provide user-friendly expressions to predict the partition coefficient have been tested over a wide range of volume fractions: Ogston's model (especially devised for fibrous media) and the pore model. The effects of crosslinking and bond stiffness have also been analyzed. Our results suggest that the fiber model can acceptably account for size-exclusion effects in crosslinked gels. Its predictions are good for large solutes if the fiber diameter is assumed to be the effective monomer diameter. For solutes sizes comparable to the monomer dimensions, a smaller fiber diameter must be used. Regarding the pore model, the partition coefficient is poorly predicted when the pore diameter is estimated as the distance between adjacent crosslinker molecules. On the other hand, our results prove that the pore sizes obtained from the pore model by fitting partitioning data of swollen gels are overestimated.