Red de formación y de cuidados para la transición de adolescentes con inmunodeficiencias primarias / Care and training network for the transition of adolescents with primary immunodeficiencies

En este escrito nos proponemos relatar y sistematizar los aspectos centrales de la estrategia de gestión, formación y atención diseñada por el Servicio de Inmunología y Psicología Institucional del Hospital Garrahan junto a los Hospitales Durand y Posadas para la transición de adolescentes con inmunodeficiencias primarias a la atención de adultos. La formalización de las primeras transiciones comenzó en 2007 con el Hospital Durand y progresivamente se fueron complejizando y expandiendo los procesos y actores participantes, sumándose el Hospital Posadas y otros centros de atención que reciben un porcentaje menor de pacientes. El eje central de la estrategia fue la implementación de un sistema de rotaciones para los residentes del último año de la especialidad de adultos por el servicio de pediatría. La formalización de la estrategia también readecuó de manera gradual aspectos internos de la atención de los adolescentes en el hospital pediátrico. En una etapa posterior se implementaron encuentros por videoconferencia con centros de adultos para redefinir acuerdos entre los servicios. Además, la asociación civil de pacientes (Asociación de Ayuda al Paciente con Inmunodeficiencias Primarias - AAPIDP) cumplió un rol relevante desde los primeros años de la estrategia. Estas acciones propiciaron la creación de una red de formación y cuidados en inmunodeficiencias primarias para la transición (AU)

In this article, we aim to describe and systematize the central aspects of the management, training, and care strategy designed by the Departments of Immunology and Institutional Psychology of the Garrahan Hospital, in collaboration with the Durand and Posadas Hospitals, for the transition of adolescents with primary immunodeficiencies to adult care. The first transitions were formalized in 2007 with the Durand Hospital. Over time, the processes and actors involved have become more complex and expanded, incorporating the Posadas Hospital and other care centers that receive a smaller percentage of patients. The central axis of the strategy was the implementation of a rotation system for residents in their final year of the adult specialty in the Department of Pediatrics. The formalization of the strategy also led to gradual readjustments in the internal aspects of adolescent care within the pediatric hospital. In a later stage, videoconference meetings with adult centers were implemented to redefine agreements between departments. Additionally, the patient association (Asociación de Ayuda al Paciente con Inmunodeficiencias Primarias - AAPIDP) has played a significant role since the early years of the strategy. These actions have led to the creation of a network for training and care in primary immunodeficiencies for the transition (AU)

Three mutations at a Y-STR haplotype defy a paternal half-brothers kinship case analysis.

This work presents the results of a DNA test aimed to determine a possible biological link of paternal half brotherhood of two males. The combined use of biparentally inherited markers (autosomal STRs) and a panel of 27 Y-STRs allowed us to determine the existence of a biological relationship of kinship, even after detecting three mutations at their Y-STR haplotypes along the analyses, constituting an infrequent multiple mutation situation. This case is an example illustrating the importance of having different analytical markers sets and strategies for clarifying complex kinship cases where mutations occur.

A simple and rapid approach for human herpesvirus type 8 subtype characterization using single base extension.

Sequence analysis of the ORFK1 of human herpesvirus type 8 (HHV-8) allows the identification of six major subtypes (A-F), which are related to human migrations and the clinical progression of Kaposi's sarcoma. Sequencing and subsequent phylogenetic analysis of ORFK1 is considered to be the most reliable method for HHV-8 genotyping. However, it exhibits challenges and limitations. Herein, we designed and validated a single base extension (SBE) protocol for characterization of HHV-8 ORFK1 subtypes. A nested polymerase chain reaction (PCR) protocol was carried out to amplify a small 294-bp PCR product encompassing four single nucleotide polymorphisms at positions 360, 406, 465 and 527 of the HHV-8 genome. Finally, a multiplex SBE technique was developed and validated in 20 samples previously genotyped by phylogenetic analysis. The patterns obtained in this reaction could successfully discriminate between ORFK1 subtypes. The typing results obtained completely matched with those of the 'gold standard' method in all analysed samples. This method can reliably identify HHV-8 subtypes A, B and C, which are the most prevalent ones worldwide, and the remaining subtypes (D, E and F). SBE can be useful as an efficient, rapid and low-cost screening method for viral genotyping in a single tube, particularly samples with low-quality DNA, and with easy data interpretation.

Ancestral genetic legacy of the extant population of Argentina as predicted by autosomal and X-chromosomal DIPs.

Aiming to determine their ancestry diagnostic potential, we selected two sets of nuclear deletion/insertion polymorphisms (DIPs), including 30 located on autosomal chromosomes and 33 on the X chromosome. We analysed over 200 unrelated Argentinean individuals living in urban areas of Argentina. As in most American countries, the extant Argentinean population is the result of tricontinental genetic admixture. The peopling process within the continent was characterised by mating bias involving Native American and enslaved African females and European males. Differential results were detected between autosomal DIPs and X-DIPs. The former showed that the European component was the largest (77.8%), followed by the Native American (17.9%) and African (4.2%) components, in good agreement with the previously published results. In contrast, X-DIPs showed that the European genetic contribution was also predominant but much smaller (52.9%) and considerably larger Native American and African contributions (39.6% and 7.5%, respectively). Genetic analysis revealed continental genetic contributions whose associated phenotypic traits have been mostly lost. The observed differences between the estimated continental genetic contribution proportions based on autosomal DIPs and X-DIPs reflect the effects of autosome and X-chromosome transmission behaviour and their different recombination patterns. This work shows the ability of the tested DIP panels to infer ancestry and confirm mating bias. To the best of our knowledge, this is the first study focusing on ancestry-informative autosomal DIP and X-DIP comparisons performed in a sample representing the entire Argentinean population.

Distribution of genetic polymorphisms associated with hepatitis C virus (HCV) antiviral response in a multiethnic and admixed population.

The prevalence of genetic polymorphisms identified as predictors of therapeutic-induced hepatitis C virus (HCV) clearance differs among ethnic groups. However, there is a paucity of information about their prevalence in South American populations, whose genetic background is highly admixed. Hence, single-nucleotide polymorphisms rs12979860, rs1127354 and rs7270101 were characterized in 1350 healthy individuals, and ethnicity was assessed in 259 randomly selected samples. The frequency of rs12979860CC, associated to HCV treatment response, and rs1127354nonCC, related to protection against hemolytic anemia, were significantly higher among individuals with maternal and paternal Non-native American haplogroups (64.5% and 24.2%), intermediate among admixed samples (44.1% and 20.4%) and the lowest for individuals with Native American ancestry (30.4% and 6.5%). This is the first systematic study focused on analyzing HCV predictors of antiviral response and ethnicity in South American populations. The characterization of these variants is critical to evaluate the risk-benefit of antiviral treatment according to the patient ancestry in admixed populations.

NMR chemical shielding and spin-spin coupling constants of liquid NH3: a systematic investigation using the sequential QM/MM method.

The NMR spin coupling parameters, (1)J(N,H) and (2)J(H,H), and the chemical shielding, sigma((15)N), of liquid ammonia are studied from a combined and sequential QM/MM methodology. Monte Carlo simulations are performed to generate statistically uncorrelated configurations that are submitted to density functional theory calculations. Two different Lennard-Jones potentials are used in the liquid simulations. Electronic polarization is included in these two potentials via an iterative procedure with and without geometry relaxation, and the influence on the calculated properties are analyzed. B3LYP/aug-cc-pVTZ-J calculations were used to compute the (1)J(N,H) constants in the interval of -67.8 to -63.9 Hz, depending on the theoretical model used. These can be compared with the experimental results of -61.6 Hz. For the (2)J(H,H) coupling the theoretical results vary between -10.6 to -13.01 Hz. The indirect experimental result derived from partially deuterated liquid is -11.1 Hz. Inclusion of explicit hydrogen bonded molecules gives a small but important contribution. The vapor-to-liquid shifts are also considered. This shift is calculated to be negligible for (1)J(N,H) in agreement with experiment. This is rationalized as a cancellation of the geometry relaxation and pure solvent effects. For the chemical shielding, sigma((15)N) calculations at the B3LYP/aug-pcS-3 show that the vapor-to-liquid chemical shift requires the explicit use of solvent molecules. Considering only one ammonia molecule in an electrostatic embedding gives a wrong sign for the chemical shift that is corrected only with the use of explicit additional molecules. The best result calculated for the vapor to liquid chemical shift Delta sigma((15)N) is -25.2 ppm, in good agreement with the experimental value of -22.6 ppm.

Electric quadrupole polarizabilities of nuclear magnetic shielding in some small molecules.

Computational procedures, based on (i) the Ramsey common origin approach and (ii) the continuous transformation of the origin of the quantum mechanical current density-diamagnetic zero (CTOCD-DZ), were applied at the Hartree-Fock level to determine electric quadrupole polarizabilities of nuclear magnetic shielding for molecules in the presence of a nonuniform electric field with a uniform gradient. The quadrupole polarizabilities depend on the origin of the coordinate system, but values of the magnetic field induced at a reference nucleus, determined via the CTOCD-DZ approach, are origin independent for any calculations relying on the algebraic approximation, irrespective of size and quality of the (gaugeless) basis set employed. On the other hand, theoretical estimates of the induced magnetic field obtained by single-origin methods are translationally invariant only in the limit of complete basis sets. Calculations of electric quadrupole polarizabilities of nuclear magnetic shielding are reported for H(2), HF, H(2)O, NH(3), and CH(4) molecules.

Calculation of the electric hypershielding at the nuclei of molecules in a strong magnetic field.

The third-rank electric hypershielding at the nuclei of 14 small molecules has been evaluated at the Hartree-Fock level of accuracy, by a pointwise procedure for the geometrical derivatives of magnetic susceptibilities and by a straightforward use of its definition within the Rayleigh-Schrodinger perturbation theory. The connection between these two quantities is provided by the Hellmann-Feynman theorem. The magnetically induced hypershielding at the nuclei accounts for distortion of molecular geometry caused by strong magnetic fields and for related changes of magnetic susceptibility. In homonuclear diatomics H(2), N(2), and F(2), a field along the bond direction squeezes the electron cloud toward the center, determining shorter but stronger bond. It is shown that constraints for rotational and translational invariances and hypervirial theorems provide a natural criterion for Hartree-Fock quality of computed nuclear electric hypershielding.

Nonlinear response of the benzene molecule to strong magnetic fields.

The fourth-rank hypermagnetizability tensor of the benzene molecule has been evaluated at the coupled Hartree-Fock level of accuracy within the conventional common-origin approach, adopting gaugeless basis sets of increasing size and flexibility. The degree of convergence of theoretical tensor components has been estimated allowing for two different coordinate systems. It is shown that a strong magnetic field perpendicular to the plane of the molecule causes a distortion of the electron charge density, which tends to concentrate in the region of the C-C bonds. This charge contraction has a dynamical origin, and can be interpreted as a feedback effect in terms of the classical Lorentz force acting on the electron current density.

Genotipificacion del gen HLA DQB1 en diabetes autoinmune del adulto ( LADA ) / HLA DQB1 genotyping in latent autoimmune diabetes of adults ( LADA )

La diabetes autoinmune es una enfermedad multifactorial causada por factores genéticos predisponentes y ambientales desencadenantes. Se manifiesta en la edad infantojuvenil (diabetes tipo 1, DMID) y en la edad adulta (diabetes autoinmune latente del adulto, LADA). La predisposición genética es de tipo poligénico, se ha establecido asociación con alelos polimórficos del gen DQB del sistema HLA, VNTR del gen de insulina y polimorfismos en el gen CTLA4. En el presente trabajo se analizaron las frecuencias de los alelos polimórficos del gen HLA DQB1 en 63 pacientes LADA, 70 pacientes DMID y 79 individuos normales. La tipificación de los alelos del gen DQB1 se llevó a cabo mediante el Kit SSPTM DQ Olerup. Se observó una mayor frecuencia del genotipo *0201-*0302 y *0201-*0201 en ambas poblaciones diabéticas con respecto a normales (p<0.05). La presencia del genotipo *0201-*0302 fue mayor en DMID que en LADA (p<0.05). Por otra parte, el análisis del alelo protector *0602 muestra una alta prevalencia en individuos normales con respecto a la población diabética. El alelo de susceptibilidad más frecuente en pacientes LADA y DMID de nuestro país fue el *0201. En conclusión, LADA presenta susceptibilidad genética dada por alelos del gen HLA DQB1 pero en forma menos determinante que en diabetes tipo 1. A su vez, el hallazgo del aumento en la frecuencia del alelo *0201, tanto en frecuencias alélicas como genotípicas permite caracterizar nuestra población de pacientes tanto LADA como DMID a diferencia de otras poblaciones en las que el alelo más frecuente es el *0302. (AU)

Genotipificacion del gen HLA DQB1 en diabetes autoinmune del adulto ( LADA ) / HLA DQB1 genotyping in latent autoimmune diabetes of adults ( LADA )

La diabetes autoinmune es una enfermedad multifactorial causada por factores genéticos predisponentes y ambientales desencadenantes. Se manifiesta en la edad infantojuvenil (diabetes tipo 1, DMID) y en la edad adulta (diabetes autoinmune latente del adulto, LADA). La predisposición genética es de tipo poligénico, se ha establecido asociación con alelos polimórficos del gen DQB del sistema HLA, VNTR del gen de insulina y polimorfismos en el gen CTLA4. En el presente trabajo se analizaron las frecuencias de los alelos polimórficos del gen HLA DQB1 en 63 pacientes LADA, 70 pacientes DMID y 79 individuos normales. La tipificación de los alelos del gen DQB1 se llevó a cabo mediante el Kit SSPTM DQ Olerup. Se observó una mayor frecuencia del genotipo *0201-*0302 y *0201-*0201 en ambas poblaciones diabéticas con respecto a normales (p<0.05). La presencia del genotipo *0201-*0302 fue mayor en DMID que en LADA (p<0.05). Por otra parte, el análisis del alelo protector *0602 muestra una alta prevalencia en individuos normales con respecto a la población diabética. El alelo de susceptibilidad más frecuente en pacientes LADA y DMID de nuestro país fue el *0201. En conclusión, LADA presenta susceptibilidad genética dada por alelos del gen HLA DQB1 pero en forma menos determinante que en diabetes tipo 1. A su vez, el hallazgo del aumento en la frecuencia del alelo *0201, tanto en frecuencias alélicas como genotípicas permite caracterizar nuestra población de pacientes tanto LADA como DMID a diferencia de otras poblaciones en las que el alelo más frecuente es el *0302.

Modeling solid-state effects on NMR chemical shifts using electrostatic models.

This paper presents a comparison of the embedded ion method (EIM) and the surface charge representation of the electrostatic embedding potential (SCREEP) method, two methods which can be used to calculate solid-state effects on NMR chemical shifts. The results in a selected group of compounds with known single-crystal solid-state NMR data and neutron diffraction structures, confirm that these effects are important in both (13)C and (15)N chemical shifts. The solid-state effects calculated by both methods are similar and of equal statistical quality when compared with the experimental data.

Calculation of the fourth-rank molecular hypermagnetizability of some small molecules.

A computational scheme has been developed within the framework of Rayleigh-Schrödinger perturbation theory to evaluate nonlinear interaction energy contributions for a molecule in the presence of an external spatially uniform, time-independent magnetic field. Terms connected with the fourth power of the perturbing field, representing the fourth-rank hypermagnetizabilities of five small molecules, have been evaluated at the coupled Hartree-Fock level of accuracy within the conventional common-origin approach. Gaugeless basis sets of increasing size and flexibility have been employed in a numerical test, adopting two different coordinate systems to estimate the degree of convergence of theoretical tensor components.

Purificación parcial de interferón humano tipo alfa para su uttilización en productos farmacéuticos / Partial purification of Hu-IFN-* for pharmaceutical purposes

La purificación parcial del Hu-IFN-* se logra en un solo paso por adsorción y elución sobre ácido silícico. La recuperación de la actividad antiviral es del 80-100 por ciento, con un aumento de la actividad específica de aproximadamente 20-80 veces. El producto obtenido por este método es estable y apropiado para ser utilizado en terapéuticas locales