Virus-like particle-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice.

BACKGROUND: Neoantigens are patient- and tumor-specific peptides that arise from somatic mutations. They stand as promising targets for personalized therapeutic cancer vaccines. The identification process for neoantigens has evolved with the use of next-generation sequencing technologies and bioinformatic tools in tumor genomics. However, in-silico strategies for selecting immunogenic neoantigens still have very low accuracy rates, since they mainly focus on predicting peptide binding to Major Histocompatibility Complex (MHC) molecules, which is key but not the sole determinant for immunogenicity. Moreover, the therapeutic potential of neoantigen-based vaccines may be enhanced using an optimal delivery platform that elicits robust de novo immune responses. METHODS: We developed a novel neoantigen selection pipeline based on existing software combined with a novel prediction method, the Neoantigen Optimization Algorithm (NOAH), which takes into account structural features of the peptide/MHC-I interaction, as well as the interaction between the peptide/MHC-I complex and the TCR, in its prediction strategy. Moreover, to maximize neoantigens' therapeutic potential, neoantigen-based vaccines should be manufactured in an optimal delivery platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance. RESULTS: We generated a highly immunogenic vaccine platform based on engineered HIV-1 Gag-based Virus-Like Particles (VLPs) expressing a high copy number of each in silico selected neoantigen. We tested different neoantigen-loaded VLPs (neoVLPs) in a B16-F10 melanoma mouse model to evaluate their capability to generate new immunogenic specificities. NeoVLPs were used in in vivo immunogenicity and tumor challenge experiments. CONCLUSIONS: Our results indicate the relevance of incorporating other immunogenic determinants beyond the binding of neoantigens to MHC-I. Thus, neoVLPs loaded with neoantigens enhancing the interaction with the TCR can promote the generation of de novo antitumor-specific immune responses, resulting in a delay in tumor growth. Vaccination with the neoVLP platform is a robust alternative to current therapeutic vaccine approaches and a promising candidate for future personalized immunotherapy.

Nucleic Acid Vaccines Encoding Proteins and Virus-like Particles for HIV Prevention.

The development of HIV prophylactic vaccines is facing an impasse, since all phase IIb/III clinical trials were halted in 2023 without demonstrating efficacy. Thus, the field is in need of developing novel immunogens and vaccination strategies that induce broadly neutralising antibodies together with potent Fc-dependent effector functions, as well as protective cross-reactive CD4+ and CD8+ T cell responses. Nucleic acid vaccines, particularly mRNA vaccines, have been one of the major groundbreaking advances in the current decade. Nucleic acid vaccines may help recalibrate the HIV vaccine field towards the use of delivery systems that allow the proper expression of immunogens as a sole antigen (i.e., membrane-bound trimeric envelope glycoproteins) or even to be displayed in a multiantigen platform that will be synthesised by the host. In this review, we will summarise how the multiple HIV vaccine strategies pursued in the last 40 years of HIV research have driven current vaccine development, which are the most relevant immunogens identified so far to induce balanced adaptive immune responses, and how they can benefit from the acceptance of nucleic acid vaccines in the market by reducing the limitations of previous delivery systems. The incorporation of nucleic acid vaccines into the current heterogeneous repertoire of vaccine platforms may represent an invaluable opportunity to reignite the fight against HIV.

Production and Immunogenicity of FeLV Gag-Based VLPs Exposing a Stabilized FeLV Envelope Glycoprotein.

The envelope glycoprotein (Env) of retroviruses, such as the Feline leukemia virus (FeLV), is the main target of neutralizing humoral response, and therefore, a promising vaccine candidate, despite its reported poor immunogenicity. The incorporation of mutations that stabilize analogous proteins from other viruses in their prefusion conformation (e.g., HIV Env, SARS-CoV-2 S, or RSV F glycoproteins) has improved their capability to induce neutralizing protective immune responses. Therefore, we have stabilized the FeLV Env protein following a strategy based on the incorporation of a disulfide bond and an Ile/Pro mutation (SOSIP) previously used to generate soluble HIV Env trimers. We have characterized this SOSIP-FeLV Env in its soluble form and as a transmembrane protein present at high density on the surface of FeLV Gag-based VLPs. Furthermore, we have tested its immunogenicity in DNA-immunization assays in C57BL/6 mice. Low anti-FeLV Env responses were detected in SOSIP-FeLV soluble protein-immunized animals; however, unexpectedly no responses were detected in the animals immunized with SOSIP-FeLV Gag-based VLPs. In contrast, high humoral response against FeLV Gag was observed in the animals immunized with control Gag VLPs lacking SOSIP-FeLV Env, while this response was significantly impaired when the VLPs incorporated SOSIP-FeLV Env. Our data suggest that FeLV Env can be stabilized as a soluble protein and can be expressed in high-density VLPs. However, when formulated as a DNA vaccine, SOSIP-FeLV Env remains poorly immunogenic, a limitation that must be overcome to develop an effective FeLV vaccine.

VLPs generated by the fusion of RSV-F or hMPV-F glycoprotein to HIV-Gag show improved immunogenicity and neutralizing response in mice.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last decade, and the first RSV vaccines have finally been approved in older adults and pregnant individuals. These vaccines are based on recombinant stabilized pre-fusion F glycoproteins administered as soluble proteins. Multimeric antigenic display could markedly improve immunogenicity and should be evaluated in the next generations of vaccines. Here we tested a new virus like particles-based vaccine platform which utilizes the direct fusion of an immunogen of interest to the structural human immunodeficient virus (HIV) protein Gag to increase its surface density and immunogenicity. We compared, in mice, the immunogenicity of RSV-F or hMPV-F based immunogens delivered either as soluble proteins or displayed on the surface of our VLPs. VLP associated F-proteins showed better immunogenicity and induced superior neutralizing responses. Moreover, when combining both VLP associated and soluble immunogens in a heterologous regimen, VLP-associated immunogens provided added benefits when administered as the prime immunization.

Production and characterization of novel Anti-HIV Fc-fusion proteins in plant-based systems: Nicotiana benthamiana & tobacco BY-2 cell suspension.

Multifunctional anti-HIV Fc-fusion proteins aim to tackle HIV efficiently through multiple modes of action. Although results have been promising, these recombinant proteins are hard to produce. This study explored the production and characterization of anti-HIV Fc-fusion proteins in plant-based systems, specifically Nicotiana benthamiana plants and tobacco BY-2 cell suspension. Fc-fusion protein expression in plants was optimized by incorporating codon optimization, ER retention signals, and hydrophobin fusion elements. Successful transient protein expression was achieved in N. benthamiana, with notable improvements in expression levels achieved through N-terminal hydrophobin fusion and ER retention signals. Stable expression in tobacco BY-2 resulted in varying accumulation levels being at highest 2.2.mg/g DW. The inclusion of hydrophobin significantly enhanced accumulation, providing potential benefits for downstream processing. Mass spectrometry analysis confirmed the presence of the ER retention signal and of N-glycans. Functional characterization revealed strong binding to CD64 and CD16a receptors, the latter being important for antibody-dependent cellular cytotoxicity (ADCC). Interaction with HIV antigens indicated potential neutralization capabilities. In conclusion, this research highlights the potential of plant-based systems for producing functional anti-HIV Fc-fusion proteins, offering a promising avenue for the development of these novel HIV therapies.

A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity.

Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA+ memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in "up" position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions.

Immunisation efficacy of a stabilised SARS-CoV-2 spike glycoprotein in two geriatric animal models.

Age is associated with reduced efficacy of vaccines and linked to higher risk of severe COVID-19. Here we determined the impact of ageing on the efficacy of a SARS-CoV-2 vaccine based on a stabilised Spike glycoprotein (S-29) that had previously shown high efficacy in young animals. Thirteen to 18-month-old golden Syrian hamsters (GSH) and 22-23-month-old K18-hCAE2 mice were immunised twice with S-29 protein in AddaVaxTM adjuvant. GSH were intranasally inoculated with SARS-CoV-2 either two weeks or four months after the booster dose, while all K18-hACE2 mice were intranasally inoculated two weeks after the second immunisation. Body weight and clinical signs were recorded daily post-inoculation. Lesions and viral load were investigated in different target tissues. Immunisation induced seroconversion and production of neutralising antibodies; however, animals were only partially protected from weight loss. We observed a significant reduction in the amount of viral RNA and a faster viral protein clearance in the tissues of immunized animals. Infectious particles showed a faster decay in vaccinated animals while tissue lesion development was not altered. In GSH, the shortest interval between immunisation and inoculation reduced RNA levels in the lungs, while the longest interval was equally effective in reducing RNA in nasal turbinates; viral nucleoprotein amount decreased in both tissues. In mice, immunisation was able to improve the survival of infected animals. Despite the high protection shown in young animals, S-29 efficacy was reduced in the geriatric population. Our research highlights the importance of testing vaccine efficacy in older animals as part of preclinical vaccine evaluation.

Immunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection.

Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are crucial to fight against the coronavirus disease 2019 pandemic. Most vaccines are based on a mutated version of the Spike glycoprotein [K986P/V987P (S-2P)] with improved stability, yield and immunogenicity. However, S-2P is still produced at low levels. Here, we describe the V987H mutation that increases by two-fold the production of the recombinant Spike and the exposure of the receptor binding domain (RBD). S-V987H immunogenicity is similar to S-2P in mice and golden Syrian hamsters (GSH), and superior to a monomeric RBD. S-V987H immunization confer full protection against severe disease in K18-hACE2 mice and GSH upon SARS-CoV-2 challenge (D614G or B.1.351 variants). Furthermore, S-V987H immunized K18-hACE2 mice show a faster tissue viral clearance than RBD- or S-2P-vaccinated animals challenged with D614G, B.1.351 or Omicron BQ1.1 variants. Thus, S-V987H protein might be considered for future SARS-CoV-2 vaccines development.

Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant.

Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production and immunogenicity of the recombinant S trimer, suggesting that these two parameters are related. Nevertheless, S-2P still shows some molecular instability and it is produced with low yield. Here we described a novel set of mutations identified by molecular modeling and located in the S2 region of the S-2P that increase its production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S-29 mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development.

Mapping of health services to urinary catheter users: challenges for the advanced nursing practice / Mapeo de servicios de salud a usuarios de cateterismo urinario: desafíos para la enfermería de práctica avanzada / Mapeamento dos serviços de saúde aos usuários de cateterismo urinário: desafios para a prática avançada de enfermagem

ABSTRACT Objective: To map and to identify the material distributed in the health care network to urinary catheter users in a municipality in the state of São Paulo, Brazil. Method: Quantitative, descriptive-exploratory study, carried out with supervisors and/or managers of health services and a unit of distribution of materials used by urinary catheter users. Data were collected using a questionnaire and an interview via electronic form and analyzed by descriptive statistics. Results: Health services to urinary catheter users were mapped in five health regions: health centers, family health units, outpatient clinics, specialized centers, hospitals, and emergency care units. Intermittent catheter and indwelling catheter were the distributed materials, along with other essential materials. Conclusion: The study shows the high number of distributed urinary catheters; primary health care was the service that directed the care from the materials distribution. It is concluded that mapping the provided care allows for understanding the provided care as well as fostering future studies addressing healthcare network strategies for users of urinary catheter.

RESUMEN Objetivo: Mapear e identificar los dispositivos que disponen en la red de atención a usuarios de cateterismo urinario en una ciudad del estado de São Paulo. Método: Estudio cuantitativo, descriptivo exploratorio, realizado con supervisores y/o gestores de los servicios de salud y una unidad de distribución de materiales utilizados por los usuarios de cateterismo. Para la recolección de datos se utilizaron el cuestionario y la entrevista a través de un formulario electrónico; y para el análisis, la estadística descriptiva. Resultados: Se mapearon los servicios para usuarios de cateterismo urinario en cinco regiones de salud: unidades básicas, unidades de salud familiar, ambulatorios, clínicas especializadas, hospitales y unidades de urgencias. Los dispositivos urinarios que disponen fueron el catéter intermitente y el catéter permanente, además de otros materiales necesarios para el procedimiento. Conclusión: El estudio apunta al elevado número de catéteres urinarios distribuidos; la atención primaria de salud fue el servicio que más brindó cuidados a partir de la distribución de los materiales. Se concluye que la construcción de un mapa del cuidado posibilita identificar el cuidado ofrecido y el desarrollo de otros estudios con estrategias de cuidado en red para los usuarios de cateterismo urinario.

RESUMO Objetivo: Mapear e identificar os dispositivos dispensados na rede de atenção à saúde aos usuários de cateterismo urinário de um município do interior do Estado de São Paulo. Método: Estudo quantitativo, descritivo-exploratório, realizado com os supervisores e/ou gestores de serviços de saúde e uma unidade de distribuição de materiais utilizados por usuários de cateterismo. Os dados foram coletados utilizando-se questionário e entrevista via formulário eletrônico e analisados por estatística descritiva. Resultados: Foram mapeados os serviços aos usuários de cateterismo urinário em cinco regiões de saúde: unidades básicas, unidades de saúde da família, ambulatórios, centros especializados, hospitais e unidades de pronto atendimento. Os dispositivos urinários dispensados foram o cateter intermitente e o de demora, junto a outros materiais necessários para o procedimento. Conclusão: O estudo revela a alta quantidade de cateteres urinários distribuídos; a atenção primária à saúde foi o serviço que direcionou o cuidado a partir da distribuição de materiais. Conclui-se que a construção de um mapa do cuidado oferecido possibilita a compreensão do cuidado ofertado e o desenvolvimento de demais estudos com estratégias de cuidado em rede aos usuários de cateterismo urinário.

Qualidade de vida e cateterismo urinário no contexto da enfermagem em reabilitação: uma revisão integrativa / Quality of life and urinary catheterization in the rehabilitation nursing context: an integrative review

Objetivo: identificar as evidências científicas sobre a atuação de enfermagem na qualidade de vida de crianças e adultos em uso do cateterismo urinário e seus cuidadores no contexto de reabilitação. Método: revisão integrativa de literatura, através de questão norteadora "Qual a produção de conhecimento sobre a atuação de enfermagem na Qualidade de Vida de crianças e adultos em uso do cateterismo urinário e seus cuidadores no contexto de reabilitação?", em três bases de dados com os descritores cateterismo urinário, qualidade de vida e enfermagem. Foram incluídos 23 estudos, publicados no período de 2011 a 2020, realizados em mais de um país, em especial na população brasileira. Resultados: as principais atuações da enfermagem foram: educação em saúde, atividades de orientação em grupo, uso de simuladores e teleatendimentos. Conclusão: as contribuições do enfermeiro em reabilitação estão direcionadas ao cuidado integral e eficaz para promoção de melhores terapêuticas e uma maior qualidade de vida.

Objective: to identify the scientific evidence on nursing performance in the quality of life of children and adults undergoing urinary catheterization and their caregivers in the context of rehabilitation. Methods: integrative literature review adopting the guiding question "What is the production of knowledge about the nursing performance in the quality of life of children and adults undergoing urinary catheterization and their caregivers in the context of rehabilitation?" performed in three databases with use of the following descriptors: urinary catheterization, quality of life and nursing. Twenty-three studies published between 2011 and 2020, conducted in more than one country, especially in the Brazilian population, were included. Results: the main actions of nursing were: health education, group orientation activities, use of simulators and telenursing. Conclusion: the contributions of rehabilitation nurses are directed to comprehensive and effective care to promote better therapies and a higher quality of life.

Efficacy and safety of mRNA1273 SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Single center experience

Background: COVID-19 represents a worldwide pandemic and vaccination remains the most effective preventive strategy. Among hematological patients, COVID-19 has been associated with a high mortality rate. Vaccination against SARS-CoV-2 has shown high efficacy in reducing community transmission, hospitalization and deaths related to severe COVID-19 disease. However, patients with impaired immunity may have lower sero-responsiveness to vaccination.MethodsThis study focuses on hematopoietic stem cell transplantation (HSCT) recipients. We performed a unicenter, prospective, observational study of a cohort of 31 allogeneic and 56 autologous-HSCT recipients monitored between March 2021 and May 2021 for serological response after COVID-19 vaccination with two doses of mRNA1273 vaccine (Moderna). In order to determine seroconversion, serological status before vaccination was studied.ResultsAt a median range of 75 days after the second vaccine dose, seroconversion rates were 84% and 85% for the autologous and allogeneic-HSCT groups, respectively. We confirmed some potential risk factors for a negative serological response, such as receiving anti-CD20 therapy in the previous year before vaccination, a low B-lymphocyte count and hypogammaglobulinemia. Neutralizing antibodies were quantified in 44 patients, with a good correlation with serological tests. Adverse events were minimal.ConclusionmRNA1273 vaccination is safe and effective in HSCT recipients, especially in those presenting recovered immunity. (AU)

Introducción: Entre los pacientes hematológicos, la COVID-19 se ha asociado a una mayor mortalidad. La vacunación frente a SARS-CoV-2 es la principal estrategia de prevención y ha demostrado eficacia en la reducción de la transmisión, de la hospitalización y de la tasa de mortalidad. Aun así, los pacientes oncohematológicos con un sistema inmunológico disfuncional podrían presentar una respuesta menor a la vacunación.MétodosEstudio unicéntrico, prospectivo y observacional, con una cohorte de 31 receptores de un trasplante alogénico de progenitores hematopoyéticos y de 56 receptores de un trasplante autólogo que recibieron la vacunación frente a SARS-CoV-2 entre marzo de 2021 y mayo de 2021, con 2 dosis de la vacuna mRNA1273 (Moderna). Para poder determinar la tasa de seroconversión, se determinó el estado serológico previamente a la vacunación y posteriormente se monitorizó la respuesta serológica.ResultadosCon un tiempo medio de seguimiento de 75 días después de la segunda vacuna, la tasa de seroconversión fue del 84%, y del 85% en el grupo receptor de trasplante autólogo y alogénico, respectivamente. Se confirmaron algunos potenciales factores de riesgo para la ausencia de respuesta serológica, como haber recibido terapias anti-CD20, un recuento bajo de linfocitos B y la hipogammaglobulinemia. En 44 pacientes se cuantificaron títulos de anticuerpos neutralizantes, con buena correlación con los test serológicos. Los efectos adversos de la vacuna fueron mínimos.ConclusiónLa vacunación con mRNA1273 es segura y efectiva en los pacientes receptores de un trasplante de progenitores hematopoyéticos, especialmente en los que presentan reconstitución inmune previa. (AU)

Violencia y embarazo en usuarias del sector salud en estados de alta marginación en México / Violence and pregnancy in female users of ministry of health care services in highly deprived states in Mexico

OBJETIVO: Caracterizar la violencia de pareja e identificar los principales factores que se asocian a la violencia en el embarazo en cuatro estados de alta marginación en México. MATERIAL Y MÉTODOS: La fuente de información fueron los datos de la Encuesta Nacional sobre Violencia contra las Mujeres 2003. Con base en ésta se realizó un estudio transversal, donde se incluyeron 1 949 mujeres entre 15 y 50 años de edad, que alguna vez estuvieron embarazadas y que demandaron atención en los servicios de primer y segundo nivel de atención de la SSA, IMSS e ISSSTE de los estados de Guerrero, Hidalgo, Oaxaca y Chiapas durante el periodo noviembre 2002- marzo 2003. Mediante regresión logística simple y múltiple, se evaluó la asociación entre las variables de interés y la violencia en el embarazo. RESULTADOS: Del total de mujeres, 250 (13 por ciento) informaron haber sufrido violencia (física, psicológica, sexual y económica) durante alguno de sus embarazos; una de cada tres refirió haber recibido golpes en el abdomen durante el embarazo. En la mayor parte de los casos (91.4 por ciento) el agresor fue el cónyuge. Las variables que se asociaron positivamente con violencia en algún embarazo fueron: a) nivel de escolaridad de la mujer: las analfabetas, comparadas con las mujeres que tenían escolaridad superior a primaria completa, presentaron la asociación más fuerte (RM 2.2; IC 95: por ciento 1.1, 4.4); b) antecedentes de violencia en la niñez (RM 3.2; IC 95 por ciento 1.9, 5.4); c) antecedentes de abuso sexual antes de los 15 años (RM 2.4, IC95 por ciento 1.3, 4.4) y d) consumo diario de alcohol por la pareja (RM 6.5; IC 95 por ciento 3.3, 12.9). CONCLUSION: Los resultados de este estudio muestran que la violencia durante el embarazo es un hecho frecuente en contextos de alta marginación, además de que su expresión tiende a ser más severa. Los resultados sustentan la necesidad de seguir estudiando el problema de la violencia en el embarazo en México, además de identificarlo durante el proceso de atención prenatal a mujeres violentadas.

OBJECTIVE: To characterize intimate partner abuse and identify the main factors associated with violence in pregnancy in four highly deprived States in Mexico. MATERIAL AND METHODS: The data were taken from the National Survey on Violence against Women 2003 (ENVIM per its abbreviation in Spanish). Based on it a cross-sectional study was conducted on 1 949 women between 15 and 50 years of age, who were once pregnant and who utilized primary and secondary health care services from the Ministry of Health, Mexican Institute of Social Security, and the Institute for Social Security and Services for State Workers in Guerrero, Hidalgo, Oaxaca and Chiapas states, between November 2002 and March 2003. Logistic regression was used to assess the association between independent variables and violence during pregnancy. RESULTS: 250 women (13 percent) suffered a type of violence (physical, psychological, sexual or economical) during any of their pregnancies. Of these women 76 (30.40 percent) were battered on their abdomen. In most of these cases (91.39 percent) the husband was the aggressor. The variables significantly associated with violence in pregnancy were: woman's illiteracy (OR 2.2; CI 95: percent .1, 4.4); history of violence in childhood (OR 3.2; CI 95 percent 1.9, 5.4) as well as sexual abuse in her childhood (OR 2.4, CI 95 percent 1.3, 4.4) and her partner's daily alcohol consumption (OR 6.5; CI 95 percent 3.3, 12.9). CONCLUSIONS: The results show that violence during pregnancy is a regular event in the impoverished context and that its expression is more severe. These results point to the importance of continued study of the problem of violence against pregnant women in Mexico and the importance of identifying battered women in prenatal care.

Síndrome de tako-tsubo. Una presentación atípica / Tako-Tsubo syndrome. Atypical presentation

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Mortalidad por envenenamiento en niños / Child mortality by poisoning

Objetivo. Conocer el panorama de las muertes por envenenamiento en niños de 0-14 años ocurridas en la República mexicana, entre 1979 y 1994. Material y métodos. Se utilizaron fuentes secundarias. Las variables analizadas fueron: edad, sexo, año, causa externa de traumatismo y envenenamientos, de la IX Clasificación Internacional de Enfermedades: E850-E858, E860-E869 y E905, Mediante un modelo de regresión Poisson se analizaron tendencias por causa específica y se obtuvieron riesgos relativos según edad, sexo y entidad federativa. Resultados. Hubo un total de 11 272 defunciones en menores de 15 años; las principales causas fueron el envenenamiento y las reacciones tóxicas causadas por plantas y animales venenosos (E905), el envenenamiento accidental por otras drogas (E858). El grupo de edad que presentó los mayores riesgos, para las causas mencionadas, fue el de menores de un año con un riesgo relativo (RR) de 29.6, IC95 por ciento 29.2-33.4; RR 3.47, IC95 por ciento 2.86-4.22, y RR 31.86, IC95 por ciento 24.8-40.9. El riesgo fue similar en ambos sexos, salvo para la causa E905. El estado de Aguascalientes se situó sistemáticamente entre los de mayor riesgo para todas las causas analizadas, mientras que Nuevo León siempre se ubicó entre los de riesgo más bajo. Conclusiones. El envenenamiento constituye una importante causa de muerte en los niños; el riesgo se incrementa al disminuir la edad. Considerando que esas muertes son potencialmente evitables y que la mayor parte de los envenenamientos ocurren en el hogar, para prevenirlos, se recomienda a los familiares vigilar y mantener fuera de peligro al niño. Por otra parte, la multicausalidad del fenómeno requiere que su prevención se realice desde una perspectiva multidisciplinaria que genera una cultura y un ambiente de seguridad en la sociedad

Atención médica de lesiones intencionales provocadas por la violencia familiar / Medical care of injuries caused intentionally by domestic violence

OBJETIVO: Describir y analizar las características de la demanda provocada por lesiones intencionales, en especial las provocadas por violencia familiar en los servicios de urgencias de hospitales públicos de la Ciudad de México. MATERIAL Y MÉTODOS: Se realizó un estudio transversal, en el cual se incluyeron variables relacionadas con el agresor, el agredido y con la atención médica. Se diseñó un cuestionario, que se aplicó durante los meses de enero a abril de 1998 en cuatro hospitales seleccionados. Se realizó un análisis con base en frecuencias simples, ji cuadrado, razón de momios con sus respectivos intervalos de confianza de 95 por ciento, y se aplicó modelo de regresión logística ajustado por las variables asociadas con este tipo de demanda. RESULTADOS: De los 598 casos que presentaron lesiones intencionales, 16 por ciento correspondió a violencia familiar. Los más afectados fueron el sexo femenino (76 por ciento), y jóvenes entre 15 y 29 años de edad (46 por ciento). Las variables que se encontraron asociadas con la demanda por lesiones provocadas por violencia familiar, en comparación con otro tipo de violencia, fueron: edad mayor de 30 años (RM 2.36, IC 95 por ciento 1.13-4.90), sexo femenino (RM 8.60, IC 95 por ciento/4.25-17.40) antecedentes de lesiones previas (RM 4.93, IC 95 por ciento 2.03-11.95), el hogar como lugar de ocurrencia (RM 36.25, IC 95 por ciento 16.598-79.18) y escolaridad primaria o menos (RM 2.33, IC 95 por ciento 1.03-5.26). CONCLUSIONES: Los resultados encontrados coinciden con reportes de otros estudios sobre el tema, y son de gran utilidad como antecedentes para la aplicación de la Norma Oficial Mexicana para la Atención Médica de la Violencia Familiar, que entró en vigencia en marzo de 2000

Vibrio cholerae O1 en Venezuela 1997-1999: sensibilidad a los antibióticos / Vidrio cholerae 01 in Venezuela 1997-1999: sensitivity of antibiotics

El presente estudio reporta los resultados de la vigilancia de la sensibilidad antibióticos en 202 cepas de V.cholerae O1 aisladas en Venezuela, desde enero de 1997 hasta diciembre de 1999. Se muestran los registros de las primeras cepas con resistencia a algunos antibióticos en Venezuela (12,2 por ciento), cefotaxima (15,4 por ciento), ceftriaxona (3,2 por ciento) y tetraciclina (0,6 por ciento), las cuales fueron aisladas en el brote detectado en el estado Zulia y que expandió por 14 entidades federales en 1997. También se demuestra el surgimiento de multiresistencia a los antibióticos en cepas aisladas en un segundo brote que inició en el estado Delta Amacuro y se extendió a los estados Sucre, Nueva Esparta, Monagas, Anzoátegui y Miranda. Los aislamientos resultaron resistentes a la ampicilina, ampicilina-sulbactam, co-trimoxazol y al agente vibriostático 0129, permaneciendo sensibles al ácido nalidíxico, cefotaxima, cetriaxona, ciprofloxacina, cloranfenicol, doxiciclina, gentamicina, norfloxacina, tetraciclina y tobramicina. Posteriores estudios deberán realizarse para determinar los mecanismos genéticos para la adquisición de esta resistencia a antibióticos.

Patología renal en vasculitis sistémicas. Problemas diagnósticos e en la biopsia renal / Renal pathology in systemic vasculitis. Diagnostic problem in kidney biopsy

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La dieta mediterránea mejora la resistencia a la oxidación de las lipoproteínas de baja densidad / Mediterranean diet improves low density lipoprotein susceptibility to oxidative modifications

Fundamento: Numerosos paneles de expertos, en especial de países anglosajones, recomiendan la dieta pobre en grasa para la prevención de enfermedades cardiovasculares. Sin embargo, la tasa de muerte por cardiopatía isquémica es baja en los países del área mediterránea, lo que puede ser debido al alto porcentaje de grasa monoinsaturada proporcionada por el aceite de oliva en la dieta. Por ello hemos comparado el efecto de ambas dietas sobre la susceptibilidad in vitro a la oxidación de las lipoproteínas de baja densidad (LDL), pieza clave en el inicio y desarrollo de la arteriosclerosis. Sujetos y métodos: Cuarenta y un sujetos varones sanos normolipémicos fueron sometidos a tres períodos de dieta, de 4 semanas de duración cada uno, consistentes en una dieta rica en grasa saturada (SAT: 38 por ciento grasa, 20 por ciento saturada), otra pobre en grasa (NCEP-I: 28 por ciento grasa, 10 por ciento saturada) y una dieta medi-terránea (38 por ciento grasa, 22 por ciento de grasa monoinsaturada). Al final de cada período dietético se determinaron las concentraciones plasmáticas de colesterol total, cLDL, cHDL, triglicéridos, apoproteínas A-I y B, *-tocoferol y la susceptibilidad a la oxidación de las LDL in vitro. Resultados: Ambas dietas hipolipemiantes produjeron un descenso significativo de las concentraciones plasmáticas de colesterol total, cLDL y apo B, mientras que sólo la dieta NCEP-I disminuyó el cHDL. La sustitución de una dieta rica en grasa saturada o de una dieta rica en hidratos de carbono por una dieta mediterránea aumentó la resistencia a la oxidación de las LDL al prolongarse el tiempo de latencia (p < 0,038) e inducir un descenso (p < 0,001) en la tasa de progresión de la curva de cinética de oxidación de las LDL. Conclusión: Nuestros resultados indican que el consumo de una dieta mediterránea rica en aceite de oliva, además de mejorar el índice aterogénico (colesterol total/cHDL), aumenta la resistencia a la oxidación de las LDL en comparación con la dieta pobre en grasa. Ello nos hace aconsejar el modelo de dieta mediterránea para la prevención de las enfermedades cardiovasculares. (AU)