Transcriptional re-programming of insulin B-chain epitope-specific T-follicular helper cells into anti-diabetogenic T-regulatory type-1 cells.

Systemic delivery of nanoparticles (NPs) coated with mono-specific autoimmune disease-relevant peptide-major histocompatibility complex class II (pMHCII) molecules can resolve organ inflammation in various disease models in a disease-specific manner without impairing normal immunity. These compounds invariably trigger the formation and systemic expansion of cognate pMHCII-specific T-regulatory type 1 (TR1) cells. By focusing on type 1 diabetes (T1D)-relevant pMHCII-NP types that display an epitope from the insulin B-chain bound to the same MHCII molecule (IAg7) on three different registers, we show that pMHCII-NP-induced TR1 cells invariably co-exist with cognate T-Follicular Helper (TFH)-like cells of quasi-identical clonotypic composition and are oligoclonal, yet transcriptionally homogeneous. Furthermore, these three different TR1 specificities have similar diabetes reversal properties in vivo despite being uniquely reactive against the peptide MHCII-binding register displayed on the NPs. Thus, pMHCII-NP treatment using nanomedicines displaying different epitope specificities results in the simultaneous differentiation of multiple antigen-specific TFH-like cell clones into TR1-like cells that inherit the fine antigenic specificity of their precursors while acquiring a defined transcriptional immunoregulatory program.

Endoparasites Infecting Domestic Animals and Spectacled Bears (Tremarctos ornatus) in the Rural High Mountains of Colombia.

This research described the co-infection prevalence of endoparasites in Tremartus ornatus and domestic animals in the rural high mountains of Colombia by copro-parasitological examination. Some parasites have a zoonotic potential in wild endangered species and domestic animals in Colombian regions. T. ornatus had a notable infection with Eimeria spp., Ascaris spp., Ancylostoma spp., and Baylisascaris spp. Cryptosporidium spp., Balantidium coli, Anoplocephala spp., and Acanthamoeba spp. In B. taurus, Eimeria spp. is coinfecting with Cryptosporidium spp. (6.6%) and represents 18% of the total parasitism. In E. caballus and B. taurus. Eimeria spp. coinfecting (34.7%), with the Strongylus spp. (21.9-25%). In T. ornatus, Eimeria spp. is coinfecting with Ancylostoma spp. (36.2%), Cryptosporidium spp., Ascaris spp., Baylisascaris spp., and B. coli.

Immunomodulatory and immunoregulatory nanomedicines for autoimmunity.

Autoimmune diseases, caused by cellularly and molecularly complex immune responses against self-antigens, are largely treated with broad-acting, non-disease-specific anti-inflammatory drugs. These compounds can attenuate autoimmune inflammation, but tend to impair normal immunity against infection and cancer, cannot restore normal immune homeostasis and are not curative. Nanoparticle (NP)- and microparticle (MP)-based delivery of immunotherapeutic agents affords a unique opportunity to not only increase the specificity and potency of broad-acting immunomodulators, but also to elicit the formation of organ-specific immunoregulatory cell networks capable of inducing bystander immunoregulation. Here, we review the various NP/MP-based strategies that have so far been tested in models of experimental and/or spontaneous autoimmunity, with a focus on mechanisms of action.

Diagnosis of Community-acquired Pneumonia in Hospitalized Children: A Multicenter Experience in Bolivia.

BACKGROUND: Community-acquired pneumonia (CAP) represents a major cause of hospitalization, especially among young children. In the third world countries, information about CAP etiology is scarce. Therefore, rapid and highly sensitive diagnostic methods are crucial to determine etiologic agents. METHODS: Between March 2016 and March 2017, we have prospectively studied the clinical, radiologic, laboratory, and molecular aspects of patients with CAP at 2 tertiary-level hospitals in Santa Cruz de la Sierra, using a multiplex real-time polymerase chain reaction (RT-PCR). RESULTS: A total of 274 children were evaluated, with a median age of 13 months. An etiologic agent was identified in 187 patients (68.2%): 54% (n = 148) were viruses and 14.2% (n = 39) were bacteria. CAP prevalence was highest among children under 2 years (71%; 195/274); respiratory syncytial virus (RSV) was the most frequent cause in 22% (60/274), especially among infants, followed by influenza (14.5%; 40/274). Streptococcus pneumoniae accounted for 7% of the total (19/274), followed by Staphylococcus aureus (3%;8/274) and Haemophilus influenzae (1.4%;4/274). Together, these cases accounted for 79.5% (31/39) of all bacterial CAP. Pleural effusion (PE) complicated CAP in 13.8% (38/274), of which 29 were of bacterial etiology. RT-PCR increased the detection rate of pneumococcus by 47%. Coinfection occurred in 28 patients (10%); 26 (9.5%) required intensive care and 9 patients (3%) died. CONCLUSIONS: RT-PCR provided additional diagnostic value to conventional, clinical, and laboratory methods. The higher prevalence of RSV, influenza, and Streptococcus pneumoniae reveals the need for preventive measures with better vaccine uptake and future research for RSV vaccines.

Prevalence and associated risk factors of Intestinal parasites in rural high-mountain communities of the Valle del Cauca-Colombia.

The aim of this study was to measure the prevalence of gastrointestinal parasites (GI) in domestic animals and children in high mountain populations in the districts of Combia and Toche, Valle del Cauca-Colombia. These communities have been affected by the armed conflict in Colombia and are susceptible to health risk factors related to the Colombian post-conflict. Prevalence and risk factors were measured using Bayesian methods on 45 structured interviews applied to 29 families in Combia and 16 in Toche. This inquire aimed to analyze the socio-economic and demographic factors associated with the presence of parasites. This interview was conducted with 50 children: 40 (80%) from Rita Sabogal school district of Toche, and 10 (20%) from Tablones-Atanasio Girardot schools. 23 faecal samples from asymtomatic children from these schools were collected. Subsequently, 308 animals were characterized through the analysis of 64 faecal samples from asymptomatic individuals (20,8%); 18/41 from dogs (43,9%), 18/175 from poultry (10,3%), 7/13 from cats 56,84%, 6/20 from equines (30%) and from 15/59 cattle (25,43%). The prevalence of intestinal parasites among children under six years was 60% [95% PI = 41%-78%]; Endolimax nana, 24% [95% PI = 9,8%-42%]; Iodamoeba buetschlii, 16% [95% PI = 4,7%-32%]; Entamoeba coli, 35% [95% PI = 18%-55%]; Giardia lamblia, 12% [95% PI = 2,7%-27%]. In Equids the presence of Strongylus spp was 37% [95% PI = 10%-71%]; Parascaris equorum, 37% [95% PI = 10%-71%]; in dogs, Dipylidium caninum was 20% [95% PI = 6%-39%]; Trichuris trichiura, 9% [95% PI = 1,3%-26%]; Toxocara canis, 25% [95% PI = 9%-46%]; in cats, Toxocara cati had a prevalence of 44% [95% PI = 16%-75%]; cyst of Eimeria spp, 15% [95% PI = 3,4%-33%]; in poultry and Eimeria zuernii in cattle, 50% [95% PI = 23%-77%]. There was no association with exposure of humans to animal parasites. However, we conclude that female and children under 6 years of age are more likely OR (6,72-2,3) to get parasites.

Yersinia pestis Resists Predation by Acanthamoeba castellanii and Exhibits Prolonged Intracellular Survival.

Plague is a flea-borne rodent-associated zoonotic disease caused by Yersinia pestis The disease is characterized by epizootics with high rodent mortalities, punctuated by interepizootic periods when the bacterium persists in an unknown reservoir. This study investigates the interaction between Y. pestis and the ubiquitous soil free-living amoeba (FLA) Acanthamoeba castellanii to assess if the bacterium can survive within soil amoebae and whether intracellular mechanisms are conserved between infection of mammalian macrophages and soil amoebae. The results demonstrate that during coculture with amoebae, representative Y. pestis strains of epidemic biovars Medievalis, Orientalis, and Antiqua are phagocytized and able to survive within amoebae for at least 5 days. Key Y. pestis determinants of the intracellular interaction of Y. pestis and phagocytic macrophages, PhoP and the type three secretion system (T3SS), were then tested for their roles in the Y. pestis-amoeba interaction. Consistent with a requirement for the PhoP transcriptional activator in the intracellular survival of Y. pestis in macrophages, a PhoP mutant is unable to survive when cocultured with amoebae. Additionally, induction of the T3SS blocks phagocytic uptake of Y. pestis by amoebae, similar to that which occurs during macrophage infection. Electron microscopy revealed that in A. castellanii, Y. pestis resides intact within spacious vacuoles which were characterized using lysosomal trackers as being separated from the lysosomal compartment. This evidence for prolonged survival and subversion of intracellular digestion of Y. pestis within FLA suggests that protozoa may serve as a protective soil reservoir for Y. pestisIMPORTANCEYersinia pestis is a reemerging flea-borne zoonotic disease. Sylvatic plague cycles are characterized by an epizootic period during which the disease spreads rapidly, causing high rodent mortality, and an interepizootic period when the bacterium quiescently persists in an unknown reservoir. An understanding of the ecology of Y. pestis in the context of its persistence in the environment and its reactivation to initiate a new epizootic cycle is key to implementing novel surveillance strategies to more effectively predict and prevent new disease outbreaks. Here, we demonstrate prolonged survival and subversion of intracellular digestion of Y. pestis within a soil free-living amoeba. This suggests the potential role for protozoa as a protective soil reservoir for Y. pestis, which may help explain the recrudescence of plague epizootics.

Alcohol Marketing on Twitter and Instagram: Evidence of Directly Advertising to Youth/Adolescents.

AIMS: Assess whether alcohol companies restrict youth/adolescent access, interaction, and exposure to their marketing on Twitter and Instagram. METHODS: Employed five fictitious male and female Twitter (n = 10) and Instagram (n = 10) user profiles aged 13, 15, 17, 19 and/or 21. Using cellular smartphones, we determined whether profiles could (a) interact with advertising content-e.g. retweet, view video or picture content, comment, share URL; and/or (b) follow and directly receive advertising material updates from the official Instagram and Twitter pages of 22 alcohol brands for 30 days. RESULTS: All user profiles could fully access, view, and interact with alcohol industry content posted on Instagram and Twitter. Twitter's age-gate, which restricts access for those under 21, successfully prevented underage profiles from following and subsequently receiving promotional material/updates. The two 21+ profiles collectively received 1836 alcohol-related tweets within 30 days. All Instagram profiles, however, were able to follow all alcohol brand pages and received an average of 362 advertisements within 30 days. The quantity of promotional updates increased throughout the week, reaching their peak on Thursday and Friday. Representatives/controllers of alcohol brand Instagram pages would respond directly to our underage user's comments. CONCLUSION: The alcohol industry is in violation of their proposed self-regulation guidelines for digital marketing communications on Instagram. While Twitter's age-gate effectively blocked direct to phone updates, unhindered access to post was possible. Everyday our fictitious profiles, even those as young as 13, were bombarded with alcohol industry messages and promotional material directly to their smartphones.

Yersinia pseudotuberculosis IP32953 survives and replicates in trophozoites and persists in cysts of Acanthamoeba castellanii.

Yersinia pseudotuberculosis is a foodborne enteric pathogen that causes a mild self-limiting diarrhea in humans. Yersinia pseudotuberculosis is able to persist in soil and water and in association with fresh produce, but the mechanism by which it persists is unknown. It has been shown that Y. pseudotuberculosis co-occurs with protozoans in these environments; therefore, this study investigates if bacterivorous free-living amoeba (FLA) are able to support persistence of Y. pseudotuberculosis. Coculture studies of Y. pseudotuberculosis and the prototype FLA, Acanthamoeba castellanii revealed that bacteria had an enhanced capacity to survive in association with amoeba and in the absence of any cytotoxic effects. Yersinia pseudotuberculosis is able to survive and replicate in trophozoites specifically localized within vacuoles, and persists within cysts over a period of at least a week. These data present the first evidence that Y. pseudotuberculosis is able to resist the bacterivorous nature of FLA and instead exhibits an enhanced ability to replicate and persist in coculture with amoeba. This study sheds light on the potential role of FLA in the ecology of Y. pseudotuberculosis which may have implications for food safety.

Unraveling a three-step spatiotemporal mechanism of triggering of receptor-induced Nipah virus fusion and cell entry.

Membrane fusion is essential for entry of the biomedically-important paramyxoviruses into their host cells (viral-cell fusion), and for syncytia formation (cell-cell fusion), often induced by paramyxoviral infections [e.g. those of the deadly Nipah virus (NiV)]. For most paramyxoviruses, membrane fusion requires two viral glycoproteins. Upon receptor binding, the attachment glycoprotein (HN/H/G) triggers the fusion glycoprotein (F) to undergo conformational changes that merge viral and/or cell membranes. However, a significant knowledge gap remains on how HN/H/G couples cell receptor binding to F-triggering. Via interdisciplinary approaches we report the first comprehensive mechanism of NiV membrane fusion triggering, involving three spatiotemporally sequential cell receptor-induced conformational steps in NiV-G: two in the head and one in the stalk. Interestingly, a headless NiV-G mutant was able to trigger NiV-F, and the two head conformational steps were required for the exposure of the stalk domain. Moreover, the headless NiV-G prematurely triggered NiV-F on virions, indicating that the NiV-G head prevents premature triggering of NiV-F on virions by concealing a F-triggering stalk domain until the correct time and place: receptor-binding. Based on these and recent paramyxovirus findings, we present a comprehensive and fundamentally conserved mechanistic model of paramyxovirus membrane fusion triggering and cell entry.

Detection of receptor-induced glycoprotein conformational changes on enveloped virions by using confocal micro-Raman spectroscopy.

Conformational changes in the glycoproteins of enveloped viruses are critical for membrane fusion, which enables viral entry into cells and the pathological cell-cell fusion (syncytia) associated with some viral infections. However, technological capabilities for identifying viral glycoproteins and their conformational changes on actual enveloped virus surfaces are generally scarce, challenging, and time-consuming. Our model, Nipah virus (NiV), is a syncytium-forming biosafety level 4 pathogen with a high mortality rate (40 to 75%) in humans. Once the NiV attachment glycoprotein (G) (NiV-G) binds the cell receptor ephrinB2 or -B3, G triggers conformational changes in the fusion glycoprotein (F) that result in membrane fusion and viral entry. We demonstrate that confocal micro-Raman spectroscopy can, within minutes, simultaneously identify specific G and F glycoprotein signals and receptor-induced conformational changes in NiV-F on NiV virus-like particles (VLPs). First, we identified reproducible G- and F-specific Raman spectral features on NiV VLPs containing M (assembly matrix protein), G, and/or F or on NiV/vesicular stomatitis virus (VSV) pseudotyped virions via second-derivative transformations and principal component analysis (PCA). Statistical analyses validated our PCA models. Dynamic temperature-induced conformational changes in F and G or receptor-induced target membrane-dependent conformational changes in F were monitored in NiV pseudovirions in situ in real time by confocal micro-Raman spectroscopy. Advantageously, Raman spectroscopy can identify specific protein signals in relatively impure samples. Thus, this proof-of-principle technological development has implications for the rapid identification and biostability characterization of viruses in medical, veterinary, and food samples and for the analysis of virion glycoprotein conformational changes in situ during viral entry.

[Intestinal damage by non-steroidal anti-inflammatory drugs]. / Daõ intestinal por antiinflamatorios no esteroideos.

BACKGROUND: Nonsteroidal antiinflammatory Drugs (NSAIDS) are the most widely prescribed medication in the world, with a high complication rate including gastrointestinal damage. OBJECTIVE: To present two clinical cases of intestinal damage associated to the chronic ingestion of NSAIDs. METHOD: A clinical case with inflammatory bowel disease and jejunum enteropathy and another case associated with clinical symptoms of digestive hemorrhage and endoscopic demostration of ulcers in the right colon. CONCLUSION: Patients with previous ingestion of NSAIDs presenting diarrhea, gastrointestinal bleeding, malnutrition or anemia need to discard intestinal damage.

Megacolon tóxico secundario a colitis pseudomembranosa / eee

Antecedentes: el megacolon tóxico es una complicación rara de la colitis pseudomembranosa. Objetivo: presentar un caso de megacolon tóxico secundario a colitis pseudomembranosa. Método: se revisó el caso de un paciente de 75 años, quien desarrolló un cuadro de megacolon tóxico secundario a colitis pseudomembranosa y el tratamiento efectuado. Resultados: se informa el caso de un paciente con diagnóstico de colitis pseudomembranosa cuyas principales manifestaciones clínicas fueron fiebre, distensión abdominal y síndrome disenteriforme, integrándose el diagnóstico de megacolon tóxico, por lo que se realizó colectomía total con ileostomia terminal y cierre proximal del recto, el paciente falleció 24 horas posterior al procedimiento. Conclusiones: el megacolon tóxico es una complicación rara de la colitis pseudomembranosa y se debe sospechar cuando se presenta dilatación colónica acompañada de signos de toxicidad sistémica, debiendo adoptar una conducta quirúrgica agresiva.

Cirugía anorrectal en pacientes infectados por el virus de la inmunodeficiencia humana / Anorectal surgery in patients infected with the human immunodeficiency virus

Objetivo: describir las características de los pacientes infectados por el virus de la inmunodeficiencia humana (VIH), sometidos a cirugía anorrectal con énfasis en el tiempo de cicatrización. Método: se evaluaron prospectivamente de julio de 1998 a julio de 1999 un total de 23 pacientes VIH (+) (grupo I) sometidos a cirugía anorrectal. Fueron comparados con un grupo control de pacientes VIH (-) (grupo II), escogidos al azar para establecer las características de cada grupo, la morbilidad, y el tiempo de cicatrización. El Análisis estadístico fue mediante la prueba de t de Student. Resultados: en el grupo I los diagnósticos fueron fístula perianal, fisura anal, absceso anorrectal, condiloma acuminado, úlcera anal y colgajo cutáneo hipertrófico. A siete pacientes se les realizó fistulotomía, drenaje de absceso en uno, resección de diferentes lesiones perineales en 12, electrofulguración de condilomas en dos, fisurectomía en tres y biopsia únicamente en tres. El tiempo de cicatrización en el grupo I fue de 26.087 días mientras que en el grupo II fue de 23.21 días. Se comparó tiempo de cicatrización y complicaciones de estos dos grupos, para determinar si existe diferencia en estos parámetros. No se encontró diferencia significativa entre cada grupo pero se encontraron márgenes desiguales de tiempo de cicatrización (26.087, DE ñ 10.778 días vs 23.21, DE ñ 6.259 días, p = n.s.) y complicaciones para procedimientos similares. Conclusiones: el tiempo de cicatrización en pacientes VIH (+) sometidos a cirugía anorrectal no varía en forma importante cuando se compara con pacientes VIH (-).

poder de la palabra en la construccion sexual de los cuerpos / sss

La conceptualizacion de los roles de hombres y mujeres en nuestra sociedad esta en base a una construccion historica patriarcal que se refleja en la cotidianeidad de las charlas y la vida social de las personas, se habla y se piensa de la mujer desde parametros estereotipados. En efecto el discurso que toma como instrumento la palabra, va a construir las categorias de genero a apartir del valor simbolico que se le da a ese cuerpo dentro del orden del lenguaje. Pero el efecto de la palabra va mucho mas alla, no solo va asignar funciones y roles a los hombres y mujeres, sino tambien va estructurar el psiquismo de las personas determinando su identidad sexual...

Púrpura trombocitopénica autoinmune crónica en adultos: análisis de 80 pacientes observados durante una década

En el período 1982-1990 se estudiaron y trataron 80 pacientes adultos con Púrpura Trombocitopénica Autoinmune Crónica (PTAC) en el Hospital Universitario San Vicente de Paúl de Medellín. Desde el punto de vista clínico, la púrpura fue la manifestación más frecuente y las hemorragias en órganos vitales raras. El laboratorio mostró trombocitopenia promedio de 13.513 por mm3 y cuando se detectó anemia, ésta fue ferropriva y secundaria a sangrado crónico. Los 80 pacientes recibieron glucocorticoides comno tratamiento inicial, obteniéndose remisión continua en 21 (26.3 por ciento) de los casos; los 40 (50 por ciento) dependientes de glucocorticoides fueron esplenectomizados y 31 (94 por ciento) entraron en remisión continua contra sólo 2/15 (13 por ciento) que no respondieron a los glucocorticoides (p<0.001). La edad (menores de 40 años), (p<0.001), la calidad de respuesta a los esteroides (p<0.001) y la trombocitosis postesplenectomía (p<0.005) se asociaron con una respuesta permanente. Se concluye que la PTAC del adulto con el tratamiento usual de glucocorticoides y esplenectomía puede llevar a remisión continua a 78.3 por ciento de los pacientes

Manifestación de acidosis tubular renal tipo I (distal) como insuficiencia respiratoria

Describimos tres casos de acidosis tubular renal del adulto (ATR), asociada a hipocalemia e insuficiencia respiratoria. Este es el primer informe de esta asociación reportado en la literatura colombiana. Recomendamos en cualquier paciente que se presente con parálisis e insuficiencia respiratoria aguda una evaluación del potasio sérico