Pediatric HIV+ Kaposi sarcoma exhibits clinical, virological, and molecular features different from the adult disease.

BACKGROUNDKaposi sarcoma (KS) is among the most common childhood cancers in Eastern and Central Africa. Pediatric KS has a distinctive clinical presentation compared with adult KS, which includes a tendency for primary lymph node involvement, a considerable proportion of patients lacking cutaneous lesions, and a potential for fulminant disease. The molecular mechanisms or correlates for these disease features are unknown.METHODSThis was a cross-sectional study. All cases were confirmed by IHC for KS-associated herpesvirus (KSHV) LANA protein. Baseline blood samples were profiled for HIV and KSHV genome copy numbers by qPCR and secreted cytokines by ELISA. Biopsies were characterized for viral and human transcription, and KSHV genomes were determined when possible.RESULTSSeventy participants with pediatric KS were enrolled between June 2013 and August 2019 in Malawi and compared with adult patients with KS. They exhibited high KSHV genome copy numbers and IL-6/IL-10 levels. Four biopsies (16%) had a viral transcription pattern consistent with lytic viral replication.CONCLUSIONThe unique features of pediatric KS may contribute to the specific clinical manifestations and may direct future treatment options.FUNDINGUS National Institutes of Health U54-CA-254569, PO1-CA019014, U54-CA254564, RO1-CA23958.

[Dioptric power of intraocular lens and dilatation in patients with cataract]. / Poder dióptrico del lente intraocular y dilatación en pacientes con catarata.

Background: Cataract surgery with intraocular lens implant is, nowadays, the most frequent surgical procedure in all the world. Its success depends on a lot of factors, one of the most important is the calculation of the exact dioptric power of intraocular lens. Objective: To compare the calculation of dioptric power of intraocular lens with and without dilatation in patients with cataract. Material and methods: Longitudinal study, the calculation of the dioptric power of the intraocular lens was determined in patients without and with pupillary dilation. The variables were age, gender, eye to study, keratometry, axial length, anterior chamber depth and dioptric power of the intraocular lens. Descriptive statistics and Student t test were performed. Results: There were 37 patients, 23 females and 14 males. The average age was 68 + 7.87 years. Sixty-four eyes were studied, 30 were right and 34 left. Statistically, there was only significant difference in K2 of the ocular biometry between patients without and with pupillary dilation when obtaining a value of p < 0.05. Conclusion: There are no changes in the calculation of the dioptric power of the Intraocular lens without and with pupillary dilation.

Introducción: la cirugía de catarata con implante de un lente intraocular es, hoy en día, el procedimiento quirúrgico más frecuente en todo el mundo. Su éxito depende de muchos factores, uno de los más importantes es el cálculo exacto del poder dióptrico del lente intraocular. Objetivo: comparar el cálculo del poder dióptrico del lente intraocular en los pacientes sin y con dilatación pupilar. Material y métodos: estudio longitudinal, en el que se determinó el cálculo del poder dióptrico del lente intraocular en pacientes con y sin dilatación pupilar. Las variables de estudio fueron: edad, género, ojo a estudiar, queratometría, longitud axial, profundidad de cámara anterior y poder dióptrico del lente intraocular. Se realizó estadística descriptiva y t de Student. Resultados: se estudiaron 37 pacientes, 23 mujeres y 14 hombres. La edad promedio fue de 68 ± 7.87 años. Se estudiaron 64 ojos, 30 fueron derechos y 34 izquierdos. Estadísticamente solo hubo diferencia significativa en K2 de la biometría ocular entre pacientes sin y con dilatación pupilar al obtenerse un valor de p ≤ 0.05. Conclusión: no existen cambios en el cálculo del poder dióptrico del LIO sin y con dilatación pupilar.

Poder dióptrico del lente intraocular y dilatación en pacientes con catarata / Dioptric power of intraocular lens and dilatation in patients with cataract

ntroducción: la cirugía de catarata con implante de un lente intraocular es, hoy en día, el procedimiento quirúrgico más frecuente en todo el mundo. Su éxito depende de muchos factores, uno de los más importantes es el cálculo exacto del poder dióptrico del lente intraocular. Objetivo: comparar el cálculo del poder dióptrico del lente intraocular en los pacientes sin y con dilatación pupilar. Material y métodos: estudio longitudinal, en el que se determinó el cálculo del poder dióptrico del lente intraocular en pacientes con y sin dilatación pupilar. Las variables de estudio fueron: edad, género, ojo a estudiar, queratometría, longitud axial, profundidad de cámara anterior y poder dióptrico del lente intraocular. Se realizó estadística descriptiva y t de Student. Resultados: se estudiaron 37 pacientes, 23 mujeres y 14 hombres. La edad promedio fue de 68 ± 7.87 años. Se estudiaron 64 ojos, 30 fueron derechos y 34 izquierdos. Estadísticamente solo hubo diferencia significativa en K2 de la biometría ocular entre pacientes sin y con dilatación pupilar al obtenerse un valor de p ≤ 0.05. Conclusión: no existen cambios en el cálculo del poder dióptrico del LIO sin y con dilatación pupilar.

Background: Cataract surgery with intraocular lens implant is, nowadays, the most frequent surgical procedure in all the world. Its success depends on a lot of factors, one of the most important is the calculation of the exact dioptric power of intraocular lens. Objective: To compare the calculation of dioptric power of intraocular lens with and without dilatation in patients with cataract. Material and methods: Longitudinal study, the calculation of the dioptric power of the intraocular lens was determined in patients without and with pupillary dilation. The variables were age, gender, eye to study, keratometry, axial length, anterior chamber depth and dioptric power of the intraocular lens. Descriptive statistics and Student t test were performed. Results: There were 37 patients, 23 females and 14 males. The average age was 68 + 7.87 years. Sixty-four eyes were studied, 30 were right and 34 left. Statistically, there was only significant difference in K2 of the ocular biometry between patients without and with pupillary dilation when obtaining a value of p < 0.05. Conclusion: There are no changes in the calculation of the dioptric power of the Intraocular lens without and with pupillary dilation

Whole-genome sequencing of Kaposi sarcoma-associated herpesvirus (KSHV/HHV8) reveals evidence for two African lineages.

Kaposi sarcoma (KS)-associated herpesvirus (KSHV/HHV-8) was first sequenced from the body cavity (BC) lymphoma cell line, BC-1, in 1996. Few other KSHV genomes have been reported. Our knowledge of sequence variation for this virus remains spotty. This study reports additional genomes from historical US patient samples and from African KS biopsies. It describes an assay that spans regions of the virus that cannot be covered by short read sequencing. These include the terminal repeats, the LANA repeats, and the origins of replication. A phylogenetic analysis, based on 107 genomes, identified three distinct clades; one containing isolates from USA/Europe/Japan collected in the 1990s and two of Sub-Saharan Africa isolates collected since 2010. This analysis indicates that the KSHV strains circulating today differ from the isolates collected at the height of the AIDS epidemic. This analysis helps experimental designs and potential vaccine studies.

The ORF45 Protein of Kaposi Sarcoma-Associated Herpesvirus Is an Inhibitor of p53 Signaling during Viral Reactivation.

Kaposi sarcoma-associated herpesvirus (KSHV) is a carcinogenic double-stranded DNA virus and the etiological agent of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). To prevent premature apoptosis and support its replication cycle, KSHV expresses a series of open reading frames (ORFs) that regulate signaling by the p53 tumor suppressor protein. Here, we describe a novel viral inhibitor of p53 encoded by KSHV ORF45 and identify its mechanism of action. ORF45 binds to p53 and prevents its interactions with USP7, a p53 deubiquitinase. This results in decreased p53 accumulation, localization of p53 to the cytoplasm, and diminished transcriptional activity. IMPORTANCE Unlike in other cancers, the tumor suppressor protein p53 is rarely mutated in Kaposi sarcoma (KS). Rather, Kaposi sarcoma-associated herpesvirus (KSHV) inactivates p53 through multiple viral proteins. One possible therapeutic approach to KS is the activation of p53, which would result in apoptosis and tumor regression. In this regard, it is important to understand all the mechanisms used by KSHV to modulate p53 signaling. This work describes a novel inhibitor of p53 signaling and a potential drug target, ORF45, and identifies the mechanisms of its action.

Protección de la Spirulina maxima sobre la citotoxicidad de la hidroxiurea en células embrionarias de ratón / Protection of Spirulina maxima on cytotoxicity of hydroxyurea in mouse embryonic cells / Proteção de Spirulina maxima em citotoxicidade de hidroxiureia em células embrionárias de camundongo

La Spirulina maxima (SP) tiene efectos farmacológicos protectores por su contenido de ficobiliproteínas que están relacionados con su actividad antioxidante. La hidroxiurea (HU) es un fármaco antineoplásico, citotóxico y teratógeno que implica la inducción del estrés oxidativo. El objetivo de este trabajo fue determinar si la SP y su extracto acuoso de proteína (SPE) protegen contra el efecto citotóxico de HU en cultivos celulares primarios a partir de embriones de ratón de once días. Los efectos de SP, SPE e HU sobre la viabilidad celular se determinaron por el ensayo de fluorescencia de resazurina en cultivos celulares de embriones completos de ratones de once días, de encéfalo y de brotes de extremidades anteriores. Se demostró que ni SP ni su extracto provocaron efectos citotóxicos en ninguna concentración ensayada, por lo que se aumentaba la viabilidad celular. Se encontró que las células expuestas a HU de embriones completos y encéfalo mostraron mayor toxicidad que las células de los miembros anteriores. La SP y el SPE protegieron contra la citotoxicidad de HU de una manera dependiente de la concentración hasta 48 h después de la exposición al fármaco. Este efecto podría ser adecuado para prevenir la muerte celular que deriva en un proceso teratogénico, atribuido a sus propiedades antioxidantes.

Spirulina maxima (SP) has protective pharmacological effects that are related to the antioxidant activity due to its phycobiliprotein content. Hydroxyurea (HU) is an antineoplastic, cytotoxic and teratogenic drug, which involves the induction of oxidative stress. The aim of this study was to determine whether SP and its aqueous protein extract (SPE) protect against the cytotoxic effect of HU in primary cell cultures from mouse embryos. The effects of SP, SPE, and HU on cell viability were determined by resazurin fluorescence assay in whole embryo cell cultures, encephalon, and eleven-day-old forehead bud outbreaks. It was shown that neither SP nor its extract caused cytotoxic effects at any concentration tested, increasing cell viability. It was found that cells exposed to HU of whole embryos and encephalon showed higher toxicity than cells of the previous limbs. SP and SPE protected HU cytotoxicity in a concentration-dependent manner up to 48 hours after exposure to the drug. This effect could be adequate to prevent cell death resulting in a teratogenic process attributed to its antioxidant properties.

Spirulina maxima (SP) tem efeitos farmacológicos protetores devido a seu conteúdo de ficobiliproteínas, que estão relacionadas com sua atividade antioxidante. A hidroxiureia (HU) é uma droga antineoplásica, citotóxica e teratogênica, que envolve a indução do estresse oxidativo. O objetivo deste estudo foi determinar se a SP e seu extrato aquoso de proteína (SPE) protegem contra o efeito citotóxico da HU em culturas celulares primárias a partir de embriões de camundongo de onze dias. Os efeitos de SP, SPE e HU na viabilidade celular foram determinados pelo ensaio de fluorescência de resazurina em culturas celulares de embriões inteiros de camundongos de onze dias, de encéfalo e de surtos de extremidades anteriores. Demonstrou-se que nem a SP nem seu extrato causaram efeitos citotóxicos em qualquer concentração testada, aumentando a viabilidade celular. Verificou-se que as células expostas à HU de embriões completos e encéfalo mostraram maior toxicidade do que as células dos membros anteriores. SP e SPE protegem contra a citotoxicidade de HU de forma dependente da concentração até 48 h após a exposição ao medicamento. Esse efeito poderia ser adequado para prevenir a morte celular, que resulta em um processo teratogênico atribuído a suas propriedades antioxidantes.

La investigación de las trayectorias interculturales en las comunidades indígenas migrantes en el Distrito Federal / Researching of intercultural paths in indigenous migrants communities in Distrito Federal

The migrant indigenous population living all over Mexico City is increasing. The settlement of families in a single piece of land has magnified their visibility and political participation in the city based on their kinship and <>* relationships. This family settlement has given the indigenous migrant population the opportunity to maintain its cultural patterns and to speak its mother tongue; but this collective coexistence often creates serious problems and conflicts among its members. However, these communities must concur with institutional criteria and with local social programs' requirements for gaining access to resources (mostly coming from welfare) such as land regulation, medical assistance, grants, groceries, house building, and so on. Those criteria and requirements are usually established from the outside, without a proper knowledge of the communities they attempt to benefit. They do not have enough sensitivity towards the community's social organization, this situation has created conflicts and breaking-offs among the allegedly favored communities, as well as alterations in their traditional forms of organization. Urban resources, for instance, tend to promote group organization among indigenous with a community leader who has to be an agent for getting resources; but he often acts on his own rather than as the traditional guide originally in charge of maintaining the community life inside the limits of the public agreements reached through assemblies. Another troublesome experience that indigenous people face in the city is the frequent inter-ethnic links they have with the academic community, which approaches them to <>. Migrant Triquis, Otomies, Mazahuas, and other groups have a negative opinion of the academic community; they do not see it as an inter-ethnic link but as an inquiring one. Interviewers and pollsters from academic, government, ecclesiastic, news, and school agencies have asked them the same questions for many years: their school history, eating habits, income, occupation, and their reasons for migrating. Apparently researchers tend to believe that this population has an <> for these questions. The use indigenous groups make of the <> underlines their demands before the State about their right to work, to have a house, to medical attention, and to education and constitutes one of the few channels they have to be heard, though a lot remains unheard or in the dark. Even though they have received some attention, many of the places where they live in the city still are in dreadful health and living conditions, lacking the most basic services. After ten years, many of these indigenous camps have nothing but the poorest houses. On the other hand, recent non-indigenous migrants already have much better conditions. Indigenous communities living in the city often think that organizations use them, that they do nothing or very little to understand and benefit them, but that they can make things worse for them (for instance, breaking off their camps and generating more violence and alcohol use among their families). Although in the present there is a paradigm of egalitarian coexistence and multicultural tolerance in the urban centers, being part of an indigenous group still means disadvantage in comparison to a mixed race person. The idea that indigenous people are barbarians or savages still exists in the usual representations of mixed race society and their attention policy is filled with an integration thinking which considers indigenous societies as lower and incapable, as well as prone to be absorbed by the higher culture to finish the civilization process. The fundamental frame for knowing and understanding indigenous communities as well as their experiences in the way they experience them, is through the intercultural paths they are following in the city, their contact with resources, the inter-ethnic relationships they have from the moment they leave their homes until they arrive to the city. Achieving this goal implies that sponsors, researchers, and services providers stop looking at themselves as external observers and the communities as <> and start training informants in professional skills to become collaborators in the researches or in the social programs. Thus members of these <> could be part of the knowledge production in the enclosing culture without sacrificing neither their identity, nor their cultural values but revitalizing them instead. It is also needed that researchers do something more than just tackling indigenous communities' knowledge from the perspective of informants to capture their voice in the final reports, even being cautious not to publish material that could hurt them. The people who get involved in a research as subjects have very little influence on what is published so they do not feel represented. Even though using a classical research model helps to save time and to simplify responsibilities in managing funds and reporting research results, the challenge to access informants and gaining their trust still exists. Generally this approach creates skeptical reactions among participants who do not believe neither in the results nor in the purposes and products of a study because they do not feel part of the planning. It is necessary to practice alternative ways to relate to informants and to make more inclusive participant research projects. That way it would be possible to gradually involve subjects in every step of the research process to found a cooperative model where informants are trained during research to participate in designing, performing, analyzing, and reporting research results. This new team is the one that would present and conduct the research. Such new approach would guarantee that subjects' needs are covered and their experiences recognized. It would also help the researcher to access informants, to gain their trust, and to consider ethical aspects in treating them. This article describes some of the present problems involved in assisting and researching indigenous groups that live in Mexico City. The nature of the socio-cultural organization of indigenous groups living in the city is analyzed, as well as the transformation their communities experience when they contact with urban resources. A brief count of the elements involved in the meeting between indigenous people and the academic staff interested in studying them is presented. The usual failure in setting egalitarian inter-ethnic relationships, which has often resulted in damaging indigenous groups, is exposed. Finally, the need for alternative approaches in assisting and researching cultural minorities is discussed, especially from the perspective that there is an interest in creating equality, renewing their identities and their socio-cultural life, and improving their general living conditions based on the inter-cultural paths these groups follow in the big cities.

Cada vez más frecuentemente, una población indígena migrante reside en todas las unidades territoriales del Distrito Federal. Gracias a sus relaciones de parentesco y compadrazgo -el asentamiento por familias en un solo predio- se ha hecho más notoria su presencia y politización en el área urbana. Sin embargo, estas comunidades deben ajustarse a los criterios institucionales y administrativos de los programas sociales que se ofrecen en la ciudad para hacerse acreedores a recursos (predominantemente asistencialistas) como la regularización de los predios, el otorgamiento de servicios médicos, becas, despensas y construcción de viviendas, etc. Tales criterios son establecidos regularmente de forma externa sin incluir un conocimiento pertinente del funcionamiento de las comunidades a quienes intentan beneficiar. No se es sensible a las formas propias de organización social, lo que ha desencadenado entre los supuestos beneficiados, rupturas y conflictos al interior de las propias comunidades, así como una alteración de sus formas tradicionales de organización. Entre los triquis que migran a la Ciudad de México, al igual que sucede con otomíes, mazahuas y otras comunidades, existe una percepción negativa hacia la comunidad académica, a la que no se le ve como un vínculo interétnico sino como formada por interrogadores. Han sido muchos años en los que encuestadores y entrevistadores de instituciones académicas, de gobierno, eclesiásticas, reporteros y estudiantes, se les han aproximado para preguntarles "siempre lo mismo": su escolaridad, su alimentación, el monto de sus ingresos, su ocupación y las razones de su emigración entre otras cosas. Aun cuando algunos indígenas han conseguido hacerse oír, muchos predios urbanos donde habitan diversas etnias del país presentan aún condiciones deplorables de salud y subsistencia, careciendo de lo más elemental. Actualmente se tiende al paradigma de convivencia igualitaria de la multiplicidad de culturas en los grandes centros urbanos, sin embargo pertenecer a la categoría indígena aún coloca a quienes portan esa identidad en condiciones de desventaja respecto de los mestizos. El imaginario sobre el indígena como bárbaro o salvaje aún prevalece implícito en las representaciones comunes de la sociedad mestiza, y en su política de atención indigenista todavía priva el integracionismo que considera a las sociedades indígenas como incapaces e inferiores, susceptibles de ser asimiladas a la cultura mayoritaria para completar en ellas el proceso de "civilización del bárbaro". Los trayectos interculturales que los indígenas migrantes están recorriendo en la Ciudad, en el contacto con recursos, en las relaciones interétnicas que establecen desde que migran y se instalan en la urbe, es el marco fundamental para conocer y comprender en lo posible a las comunidades indígenas, sus experiencias y significados, tal como son sentidos por sus propios integrantes. En el presente trabajo se describen algunos de los problemas presentes en la atención y la investigación que han merecido grupos indígenas que residen en la Ciudad de México. Se aborda también la naturaleza de la organización social cultural de estos grupos indígenas y la transformación que sufren sus comunidades al vincularse con los recursos citadinos. Posteriormente se hace un breve recuento de los elementos que han caracterizado el encuentro entre indígenas y académicos que intentan aproximárseles para su estudio. Se evidencia el frecuente fracaso para un establecimiento de relaciones interétnicas propicias y equitativas entre ambos sectores, lo que ha resultado en perjuicio de esos grupos étnicos. Finalmente se discute la necesidad y la naturaleza de los abordajes alternativos hacia las minorías culturales, tanto para la prestación de servicios que requieren como cuando son tema de estudio o de conocimiento para los investigadores, reporteros, estudiantes o financiadores, etc., sobre todo si se pretende que las trayectorias interculturales que cursan tales minorías en los grandes centros urbanos de nuestra entidad, nutran y permitan, en igualdad de condiciones, la reelaboración de sus identidades, de su vida cultural social y el potenciamiento de sus condiciones de vida en general.

Trombofilia primaria en México: parte VI: falta de asociación estadística entre las condiciones trombofílicas heredadas / Primary thrombophilia in México: VI: lack of statistical association among the inherited thrombophilic conditions

Objetivo: En un periodo de 70 meses estudiamos de manera prospectiva a 100 pacientes mestizos mexicanos con algún marcador clínico de trombofilia: a) Trombosis antes de los 40 años, b) Historia familiar de trombosis, c) Trombosis recurrente sin la presencia de un factor precipitante aparente, d) Trombosis en sitios anatómicos inusuales, o e) Resistencia a la terapia antitrombótica convencional. Métodos: En estos pacientes, investigamos el síndrome de las plaquetas pegajosas, la mutación 677 C —>T del gen de la 5,10-metilentetrahidrofolato reductasa (MTHFR), el fenotipo de resistencia a la proteína C activada (RPCa), la presencia de anticuerpos antifosfolípidos, las mutaciones Leiden, Cambridge, Liverpool y Hong Kong del gen del factor V, el haplotipo HR2 del mismo gen del factor V, el polimorfismo G20210A de la región 3´-no traducida del gen de la protrombina y las deficiencias de proteínas C y S y de antitrombina III. Resultados: En el 94 % de los casos encontramos por lo menos alguna alteración; de estos casos con alteración, la mayoría (81 %) tuvo dos o más condiciones trombofílicas asociadas. El análisis multivariado de todas estas variables sólo mostró asociación estadística entre la mutación tipo Leiden del gen del factor V y el fenotipo de RPCa (r = .495; p < 0.001). Conclusiones: Se concluye que, realizando este grupo de estudios, es posible identificar alguna alteración trombofílica en la mayoría de los pacientes mestizos mexicanos con algún marcador clínico de trombofilia y que las alteraciones no se asocian entre sí.

OBJECTIVE: Over a 70-month period, 100 consecutive Mexican mestizo individuals with a clinical marker associated with a primary hypercoagulable state were studied. METHODS: We prospectively assessed: the sticky platelet syndrome (SPS), the activated protein C resistance (aPCR) phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, IgG and IgM isotypes of antiphospholipid antibodies, homocysteine levels, the factor V gene Leiden, Cambridge, Hong Kong, and Liverpool mutations, the 677 C-->T mutation in the 5,10-methylenetetrahydrofolatereductase (MTHFR), and the G20210A polymorphism in the 3'-untranslated region of the prothrombin gene. RESULTS: Of the 100 consecutive patients prospectively accrued in the study, only 29% were males. In only 6 individuals could we not record any abnormality, whereas in most individuals (81%), two to five co-existing abnormalities were identified. In a multivariate analysis of the association of all these assesments, the only significant association was found between the factor V Leiden mutation and the aPCR phenotype (r = .495; p < 0.001). CONCLUSIONS: These results confirm previous observations on thrombophilia in Mexico underlining that it is a multifactorial disease. They also suggest that the abnormalities detected are not associated to each other.