Publicaciones sobre sistemas de salud en el Perú entre 2000-2020: características bibliométricas / Publications on health systems in Peru between 2000-2020: bibliometric characteristics

RESUMEN Objetivo: Caracterizar las publicaciones sobre Sistemas de Salud producidas en el Perú entre 2000-2020. El estudio: Estudio bibliométrico de publicaciones científicas sobre sistemas de salud en el Perú en revistas indizadas en bases de datos de PubMed y SciELO. Se incluyó revisiones narrativas, artículos originales con diseños transversales, retrospectivos o prospectivos. Se describieron las redes de colaboración de autores y las instituciones. Hallazgos: Se identificaron 136 unidades bibliográficas. Las instituciones con mayor producción fueron la Universidad Peruana Cayetano Heredia (24,52%), Ministerio de Salud (14,19%) y la Universidad Peruana de Ciencias Aplicadas (7,74%). El componente más estudiado fue la provisión de servicios (50%), con diseños descriptivos. 65,44% fue publicado entre 2015-2020, 35,29% en la Revista Peruana de Medicina Experimental y Salud Pública, 51,47% en inglés. El abordaje predominante fue el cualitativo (52,94%). Conclusiones: Las publicaciones sobre sistemas de salud se enfocaron en la prestación de servicios y predominaron los estudios cualitativos.

ABSTRACT Objective: To characterize the publications on Health Systems produced in Peru between 2000-2020. Study: A bibliometric study of the scientific publications on health systems in Peru was carried out in journals indexed in the PubMed and SciELO databases. Narrative reviews, original articles with cross-sectional, and retrospective or prospective designs, were included. Collaboration networks of authors and institutions were described. Findings: 136 bibliographic units were identified. The institutions with the highest production were Universidad Peruana Cayetano Heredia (24.52%), the Ministry of Health (14.19%) and the Universidad Peruana de Ciencias Aplicadas (7.74%). The most studied component was the provision of services (50%), with descriptive designs. 65.44% were published between 2015-2020 and 35.29% in the Revista Peruana de Medicina Experimental y Salud Pública. 51.47% of the articles were written in English. The predominant approach was qualitative (52.94%). Conclusions: The publications on health systems in the period studied focused on the provision of services; they were predominantly qualitative articles.

Posibilidad de sesgo en estudio retrospectivo de ivermectina para COVID-19 / Bias Possibility in a Retrospective Study of Ivermectin for COVID-19

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Crystal Structure and Conformational Change Mechanism of a Bacterial Nramp-Family Divalent Metal Transporter.

The widely conserved natural resistance-associated macrophage protein (Nramp) family of divalent metal transporters enables manganese import in bacteria and dietary iron uptake in mammals. We determined the crystal structure of the Deinococcus radiodurans Nramp homolog (DraNramp) in an inward-facing apo state, including the complete transmembrane (TM) segment 1a (absent from a previous Nramp structure). Mapping our cysteine accessibility scanning results onto this structure, we identified the metal-permeation pathway in the alternate outward-open conformation. We investigated the functional impact of two natural anemia-causing glycine-to-arginine mutations that impaired transition metal transport in both human Nramp2 and DraNramp. The TM4 G153R mutation perturbs the closing of the outward metal-permeation pathway and alters the selectivity of the conserved metal-binding site. In contrast, the TM1a G45R mutation prevents conformational change by sterically blocking the essential movement of that helix, thus locking the transporter in an inward-facing state.

A mouse monoclonal antibody against Alexa Fluor 647.

Fluorophores are essential tools in molecular and cell biology. However, their application is mostly confined to the singular exploitation of their fluorescent properties. To enhance the versatility and expand the use of the fluorophore Alexa Fluor 647 (AF647), we generated a mouse monoclonal antibody against it. We demonstrate its use of AF647 for immunoblot, immunoprecipitation, and cytofluorimetry.

Dolor musculoesquelético y condiciones percibidas de trabajo en médicos y enfermeras de un hospital de Lima, Perú / Musculoskeletal Dolor y condiciones de trabajo en percibidas medical enfermeras y un hospital in Lima, Peru

Introducción: Los factores psicosociales y ergonómicos interactúan generando dolor musculoesquelético, frecuente en trabajadores de salud. Existen pocos estudios relacionando ambas condiciones, especialmente en médicos. Objetivo: Examinar la asociación entre factores psicosociales de estrés laboral (modelos demanda-control-apoyo (DC) y desequilibrio esfuerzo/recompensa (ERI)) y dolor musculoesquelético en médicos y enfermeras de un hospital público de Lima, Perú. Diseño: Estudio transversal con cuestionarios autorreportados anónimos: datos sociodemográficos, Cuestionario Nórdico (dolor musculoesquelético) y cuestionarios JCQ (Karasek) y ERI (Siegrist), en 54 médicos y 48 enfermeras del Hospital “San Juan Bautista” Huaral en el año 2013. Resultados: Los médicos varones presentaron un IMC medio de 28,45 y la media de horas trabajadas semanales fue de 66,86 (valores superiores a los de médicos mujeres y enfermeras). La prevalencia global de dolor musculoesquelético fue 93,1 por cento, más frecuente en cuello (72,5 por cento), hombros (46,1 por cento), muñecas y manos (44,1 por cento), dorso (52 por cento) y región lumbar (51 por cento). El dolor interfirió con las actividades en 53,9 por cento. Las enfermeras reportaron más regiones corporales afectadas por dolor (1,71 vs 0,98, p = 0,036). Hubo asociación entre dorsalgia y desequilibrio esfuerzo/recompensa (médicos: OR = 4,91, IC 95 por cento: 1,32-18,22; enfermeras: OR = 5,58 e IC 95 por cento: 1,09-28,45). Conclusiones: La prevalencia de dolor musculoesquelético, en especial cervical, dorsal y lumbar, es elevada, similar a otros reportes. Las dimensiones del modelo ERI se asociaron con dolor en cuello, hombros, dorsalgia y lumbago...

Background: Psychosocial and ergonomic factors interaction generates musculoskeletal pain, common in health care workers. There are few studies relating both conditions, especially in physicians. Objective: To evaluate the association between psychosocial factors of work stress (demand-control-support (DC) and effort-reward imbalance (ERI) models) and musculoskeletal pain on physicians and nurses from a public hospital at Lima, Peru. Design: Observational cross-sectional study employing anonymous questionnaires: socio-demographic data, Nordic Questionnaire (for musculoskeletal pain), and psychometric inventories for psychosocial factors: JCQ (Karasek) and ERI (Siegrist) on 54 physicians and 48 nurses from the Hospital San Juan Bautista Huaral at 2013. Results: Male physicians were overweight more frequently and worked more hours per week, without showing association with pain. Musculoskeletal pain prevalence was 93.1 per cent, with significant pain in 53.9 per cent of the cases. The most frequently affected sites were neck (72.5 per cent), shoulders (46.1 per cent), wrists and hands (44.1 per cent), upper back (52 per cent) and low back (51 per cent). Nurses reported more affected regions (1.71 vs. 0.98, p = 0.036). It was seen a significant association between upper back pain and the effort / reward coefficient (physicians: OR = 4.91, IC 95 per cent: 1.32-18.22; nurses: OR = 5.58, IC 95 per cent: 1.09-28.45). Conclusions: Reported prevalence of musculoskeletal pain, specially cervical, dorsal and lumbar is high and similar to other reports. The dimensions of the ERI model have shown a better association with neck pain, shoulder pain and upper/lower back pain presentation...

Introdução: Os fatores psicossociais e ergonômicos interagem gerando dor musculoesquelética, freqüente em trabalhadores de saúde. Existem poucos estudos que relacionam as duas condições, especialmente em médicos. Objetivo: Examinar a associação entre fatores psicossociais de estresse laboral (modelos demanda - controle - apoio (DC) e desequilíbrio esforço / recompensa (ERI)) e dor musculoesquelética em médicos e enfermeiras de um hospital público de Lima, Peru. Desenho: Estudo seccional com questionários auto-reportados anônimos: dados sócio-demográficos, Questionário Nórdico (dor musculoesquelética) e questionários JCQ (Karasek) e ERI (Siegrist), em 54 médicos e 48 enfermeiras do Hospital “San Juan Bautista” Huaral no ano 2013. Resultados: Os médicos varões apresentaram um IMC médio de 28,45 e a média de horas laboradas semanais foram 66,86 (valores superiores aos dos médicos mulheres e enfermeiras). A prevalência global da dor musculoesquelética foi 93,1 por cento, mais freqüente em pescoço (72,5 por cento), ombros (46,1 por cento), pulsos e mãos (44,1 por cento), coluna torácica (52 por cento) e coluna lombar (51 por cento). A dor atrapalhou as atividades em 53,9 por cento. As enfermeiras reportaram mais regiões corporais afetadas por dor (1,71 versus 0,98, p = 0,036). Houve associação entre dorsalgia e desequilíbrio esforço/recompensa (médicos: OR = 4,91, IC 95 por cento: 1,32-18,22; enfermeiras: OR = 5,58, IC 95 por cento: 1,09-28,45). Conclusões: A prevalência da dor musculoesquelética, especialmente cervical, dorsal e lombar é elevada, similar a outros reportes. As dimensões do modelo ERI se associaram com dor cervical, dor em ombros dorsalgia e dor lombar...

IgG1+ ovalbumin-specific B-cell transnuclear mice show class switch recombination in rare allelically included B cells.

We used somatic cell nuclear transfer (SCNT) to generate a mouse from the nucleus of an IgG1(+) ovalbumin-specific B cell. The resulting OBI mice show generally normal B-cell development, with elevated percentages of marginal zone B cells and a reduction in B-1 B cells. Whereas OBI RAG1(-/-) mice have exclusively IgG1 anti-ovalbumin in their serum, OBI mice show elevated levels of anti-ovalbumin of nearly all isotypes 3' of the γ1 constant region in the IgH locus, indicating that class switch recombination (CSR) occurs in the absence of immunization with ovalbumin. This CSR is associated with the presence of IgM(+)IgG1(+) double producer B cells that represent <1% of total B cells, accumulate in the peritoneal cavity, and account for near-normal levels of serum IgM and IgG3.

Ubiquitin-dependent control of class II MHC localization is dispensable for antigen presentation and antibody production.

Controlled localization of class II MHC molecules is essential for proper class II MHC-restricted antigen presentation and the subsequent initiation of an adaptive immune response. Ubiquitination of class II MHC molecules on cytosolic lysine (K225) of the ß-chain has been shown to affect localization of the complex. We generated mice in which the endogenous ß-chain locus is replaced with a GFP tagged mutant version that lacks the cytosolic lysine residue (I-A-ß-K225R-EGFP). These mice have elevated levels of class II MHC as compared to I-A-ß-EGFP mice, and immature bone marrow-derived dendritic cells show redistribution of class II MHC to the cell surface. Nonetheless, in these same cells efficiency of antigen presentation is unaffected in I-A-ß-K225R-EGFP mice, as assayed for presentation of ovalbumin to appropriately specific T cells. The I-A-ß-K225R-EGFP animals have normal CD4 T cell populations and are capable of generating antigen-specific antibody in response to model antigens and viral infection. We therefore conclude that in our experimental system modulation of trafficking by ubiquitination of residue K225 of the ß-chain is not essential for the function of class II MHC products in antigen presentation or antibody production.

Screening individual hybridomas by microengraving to discover monoclonal antibodies.

The demand for monoclonal antibodies (mAbs) in biomedical research is significant, but the current methodologies used to discover them are both lengthy and costly. Consequently, the diversity of antibodies available for any particular antigen remains limited. Microengraving is a soft lithographic technique that provides a rapid and efficient alternative for discovering new mAbs. This protocol describes how to use microengraving to screen mouse hybridomas to establish new cell lines producing unique mAbs. Single cells from a polyclonal population are isolated into an array of microscale wells (approximately 10(5) cells per screen). The array is then used to print a protein microarray, where each element contains the antibodies captured from individual wells. The antibodies on the microarray are screened with antigens of interest, and mapped to the corresponding cells, which are then recovered from their microwells by micromanipulation. Screening and retrieval require approximately 1-3 d (9-12 d including the steps for preparing arrays of microwells).

Discovery of CD8+ T cell epitopes in Chlamydia trachomatis infection through use of caged class I MHC tetramers.

Class I MHC tetramers allow direct phenotypic identification of CD8(+) T cell populations, but their production remains laborious. A peptide exchange strategy that employs class I MHC products loaded with conditional ligands (caged MHC molecules) provides a fast and straightforward method to obtain diverse arrays of class I MHC tetramers and facilitates CD8(+) T cell epitope discovery. Here, we describe the development of photocleavable analogs of the FAPGNYPAL (SV9) epitope that bind H-2K(b) and H-2D(b) with full retention of their structural and functional integrity. We ranked all possible H-2K(b) octameric and H-2D(b) nonameric epitopes that span the genome of Chlamydia trachomatis and prepared MHC tetramers from approximately 2,000 of the highest scoring peptides by replacement of the SV9 analog with the peptide of choice. The resulting 2,000-member class I MHC tetramer array allowed the discovery of two variants of an epitope derived from polymorphic membrane protein I (PmpI) and an assessment of the kinetics of emergence and the effector function of the corresponding CD8(+) T cells.

Characterization of a mutation and an alternative splicing of UDP-galactose transporter in MDCK-RCAr cell line.

The UDP-galactose (UDP-Gal) transporter present in the Golgi apparatus is a member of a transporter family comprising hydrophobic proteins with multiple transmembrane domains. Co-immunoprecipitation experiments showed that the full-length UDP-Gal transporter protein forms oligomeric structures in the MDCK cell. A ricin-resistant mutant of the MDCK cell line (MDCK-RCA(r)) is deficient in galactose linked to macromolecules because of a lower UDP-Gal transport rate into the Golgi apparatus. We cloned this mutated protein and found that it contains a stop codon close to the 5' terminus of its open reading frame. We also detected a shorter splicing variant of the UDP-Gal transporter which contains a 183-nt in-frame deletion in both the wild-type and the mutant mRNA. We showed that the protein, when overexpressed, is localized in the Golgi apparatus and could partially correct the phenotype of the MDCK-RCA(r) and CHO-Lec8 mutant cell lines. The level of mRNA of the UDP-Gal transporter is much lower (25-30 copies per cell) than those of the CMP-sialic acid transporter (100 copies per cell), UDP-N-acetylglucosamine transporter (80 copies per cell), and GDP-fucose transporter (65 copies per cell). The transcript level of the shorter splicing variant of the UDP-Gal transporter is extremely rare in wild-type MDCK cells (a few copies per cell), but it is significantly increased in the mutant, RCA-resistant cells.

Uso del cariograma en la determinación de niveles de riesgo de caries dental en escolares de una población urbana de Zacatecas México / The use of cariogram in caries risk level determination in schoolchildren in Zacatecas Mexico

Existen herramientas que permiten evaluar el riesgo a caries dental, considerando factores como la dieta, la experiencia de caries dental, parámetros fisiológicos del huésped, la flora microbiana de carbohidratos. El objetico es determinar los niveles de riesgo de caries dental utilizando el cariograma en una población escolar. Se estudiaron 150 niños de 10 a 13 años de edad, seleccionados aleatoriamente de una escuela primaria en una zona urbana de Zacatecas, México. Se recolectaron muestras de saliva para determinar: UFC de S. mutans y lactobasillus; capacidad buffer y tasa de flujo salival. Para la evaluación clínica se utilizó el índice CPOD y el IHOS. Mediante un cuestionario se recolectó información referida a la ingesta de carbohidratos y uso de agentes fluorados. Los datos de cada paciente fueron incorporados al software para la determinación de los niveles de riesgo. El índice de CPOD promedio fue 1.55 ± 1.8 dientes, el 45 por ciento de los niños estaban libres de caries. De acuerdo con el cariograma el 50 por ciento presentó bajo riesgo de caries y solamente 8.66 por ciento alto riesgo. El cariograma es una herramienta para la prevención, control y seguimiento en pacientes libres de caries dental afectados por la enfermedad.

Multiple intracellular routes in the cross-presentation of a soluble protein by murine dendritic cells.

Soluble heat shock fusion proteins (Hsfp) stimulate mice to produce CD8+ CTL, indicating that these proteins are cross-presented by dendritic cells (DC) to naive CD8 T cells. We report that cross-presentation of these proteins depends upon their binding to DC receptors, likely belonging to the scavenger receptor superfamily. Hsfp entered DC by receptor-mediated endocytosis that was either inhibitable by cytochalasin D or not inhibitable, depending upon aggregation state and time. Most endocytosed Hsfp was transported to lysosomes, but not the small cross-presented fraction that exited early from the endocytic pathway and required access to proteasomes and TAP. Naive CD8 T cell (2C and OT-I) responses to DC incubated with Hsfp at 1 microM were matched by incubating DC with cognate octapeptides at 1-10 pM, indicating that display of very few class I MHC-peptide complexes per DC can be sufficient for cross-presentation. With an Hsfp (heat shock protein-OVA) having peptide sequences for both CD4+ (OT-II) and CD8+ (OT-I) cells, the CD4 cells responded far more vigorously than the CD8 cells and many more class II MHC-peptide than class I MHC-peptide complexes were displayed.

Niveles de Streptococcus mutans y prevalencia de caries dental en una población de escolares de la zona urbana de la ciudad de Zacatecas / Streptococcus mutans levels and caries prevalence in schoolchildren population from the urban zone of Zacatecas

El estado de salud bucal, el papel que juega el Streptococcus mutans y la acumulación de placa dental en el desarrollo de caries son factores importantes de análisis para determinar la importancia que tienen como factores de riesgo. Se ha demostrado que los niños en edades preescolares y de educación primaria no tienen buenos hábitos de higiene, de igual forma es importante la utilización de procedimientos microbiológicos que permitan evaluar en forma cuantitativa y cualitativa las condiciones de la placa dental. El objetivo de este estudio es determinar la prevalencia de caries dental en un grupo de estudiantes de educación primaria de 10-13 años de la zona urbana de la ciudad de Zacatecas y determinar la presencia y cantidad de S. mutans en saliva para establecer una correspondencia con el CPOD. Se determinó el IHOS, CPOD y el ufc/mL de S. mutans a 150 niños de ambos sexos de una escuela primaria de la zona urbana de la ciudad de Zacatecas y se encontró una prevalencia de caries dental del 56 por ciento, asimismo se detectó una correspondencia entre los niveles de S. mutans y el CPOD, por lo que es importante establecer mecanismos de control en la proliferación de este microorganismo

A role for Toll-like receptor 4 in dendritic cell activation and cytolytic CD8+ T cell differentiation in response to a recombinant heat shock fusion protein.

Recombinant heat shock fusion proteins (Hsfp) injected into mice without added adjuvants can stimulate production of CD8 cytolytic T cells. Because initiation of productive immune responses generally requires dendritic cell (DC) activation, the question arises as to whether the Hsfp can activate DC independently of contaminating LPS. Using microarray analyses of DC from LPS-insensitive mice having a point mutation in Toll-like receptor 4 (Tlr4) (C3H/HeJ), or lacking Tlr4 (B10/ScNCr), we show here that unlike a LPS standard, Hsfp activated DC from HeJ mice almost as well as DC from wild-type mice. Consistent with the microarray analysis, the Hsfp's ability to activate DC was not eliminated by polymyxin B but was destroyed by proteinase K. The Hsfp did not, however, stimulate DC from mice lacking Tlr4. In vivo the CD8 T cell response to the Hsfp in mice lacking Tlr4 was impaired: the responding CD8 cells initially proliferated vigorously but their development into cytolytic effector cells was diminished. Overall, the results indicate that this Hsfp can activate DC independently of LPS but still requires Tlr4 for an optimal CD8 T cell response.

Comparative studies of erythroid growth factors

Se evaluó la aparición de factores séricos capaces de estimular la proliferación de progenitores eritroides mamíferos. Sueron anémicos y normales de ambos e jemplares, fraccionados por tratamiento alcohólico, se ensayaron por el método del ratón post-hipóxico, no detectándose incorporación de 59Fe. Al ser ensayados en cultivos semisólidos de médula ósea murina a diferentes tiempos de incubación (colonias CFU-E y BFU-E), el suero anémico aviario mostró alta actividad estimulatória, mientras que el suero anémico anfibio resultó incapaz de incrementar la proliferación eritroide. La muestra aviaria parcialmente purificada por tratamiento alcohólico fue cromatografiada en Sephadex G-150 revelando tres entidades moleculares respondables de la actividad biológica in vitro, con pesos moleculares aparentes de 29, 14 y 10 KD respectivamente. Los factores séricos aviarios estimulantes de la línea eritroide fueron sometidos a diversos tratamientos físico-químicos y luego se evaluó la conservación de su actividad biológica. Todos ellos resultaron termoestables, sensibles al tratamiento con neuraminideasa, mientras que el ditiotreitol provocó la pérdida de la actividad biológica de las proteínas de bajo peso molecular. Estos resultados sugieren, al menos bajo estas condiciones experimentales, la presencia de factores análogos estimulantes del crecimiento eritroideo entre amniotas homeotermos

Comparative studies of erythroid growth factors

Se evaluó la aparición de factores séricos capaces de estimular la proliferación de progenitores eritroides mamíferos. Sueron anémicos y normales de ambos e jemplares, fraccionados por tratamiento alcohólico, se ensayaron por el método del ratón post-hipóxico, no detectándose incorporación de 59Fe. Al ser ensayados en cultivos semisólidos de médula ósea murina a diferentes tiempos de incubación (colonias CFU-E y BFU-E), el suero anémico aviario mostró alta actividad estimulatória, mientras que el suero anémico anfibio resultó incapaz de incrementar la proliferación eritroide. La muestra aviaria parcialmente purificada por tratamiento alcohólico fue cromatografiada en Sephadex G-150 revelando tres entidades moleculares respondables de la actividad biológica in vitro, con pesos moleculares aparentes de 29, 14 y 10 KD respectivamente. Los factores séricos aviarios estimulantes de la línea eritroide fueron sometidos a diversos tratamientos físico-químicos y luego se evaluó la conservación de su actividad biológica. Todos ellos resultaron termoestables, sensibles al tratamiento con neuraminideasa, mientras que el ditiotreitol provocó la pérdida de la actividad biológica de las proteínas de bajo peso molecular. Estos resultados sugieren, al menos bajo estas condiciones experimentales, la presencia de factores análogos estimulantes del crecimiento eritroideo entre amniotas homeotermos (AU)