An Alzheimer's disease risk variant in TTC3 modifies the actin cytoskeleton organization and the PI3K-Akt signaling pathway in iPSC-derived forebrain neurons.

A missense variant in the tetratricopeptide repeat domain 3 (TTC3) gene (rs377155188, p.S1038C, NM_003316.4:c 0.3113C>G) was found to segregate with disease in a multigenerational family with late-onset Alzheimer's disease. This variant was introduced into induced pluripotent stem cells (iPSCs) derived from a cognitively intact individual using CRISPR genome editing, and the resulting isogenic pair of iPSC lines was differentiated into cortical neurons. Transcriptome analysis showed an enrichment for genes involved in axon guidance, regulation of actin cytoskeleton, and GABAergic synapse. Functional analysis showed that the TTC3 p.S1038C iPSC-derived neuronal progenitor cells had altered 3-dimensional morphology and increased migration, while the corresponding neurons had longer neurites, increased branch points, and altered expression levels of synaptic proteins. Pharmacological treatment with small molecules that target the actin cytoskeleton could revert many of these cellular phenotypes, suggesting a central role for actin in mediating the cellular phenotypes associated with the TTC3 p.S1038C variant.

Bacteremia by non-O1/non-O139 Vibrio cholerae: Case description and literature review / Bacteriemia por Vibrio cholerae no-O1/no-O139: descripción de un caso y revisión de la literatura

Bacteremia by non-O1/non-O139 Vibrio cholerae is a rare entity associated with high mortality rates. We report a case of non-O1/non-O139 V. cholerae bacteremia confirmed by polymerase chain reaction and agglutination tests. The clinicoepidemiological characteristics and therapeutic options for this infection are also described.

La bacteriemia por Vibrio cholerae no-O1/no-O139 es una entidad poco frecuente que se asocia con altas tasas de mortalidad. Se reporta un caso de bacteriemia por V. cholerae no-O1/no-O139 confirmado por reacción en cadena de la polimerasa y test de aglutinación. Se describen las características clinicoepidemiológicas y las opciones terapéuticas para esta infección.

Caracterización de ß-lactamasas de espectro extendido en aislamientos clínicos colombianos de Salmonella enterica no tifoidea de 1997 a 2022 / Characterization of extended spectrum ß-lactamases in Colombian clinical isolates of non-typhoidal Salmonella enterica between 1997 and 2022

Introducción. Salmonella spp. es un agente patógeno zoonótico transmitido al humano por el agua o los alimentos contaminados. La presencia de ß-lactamasas de espectro extendido es un creciente problema para la salud pública debido a que estas enzimas confieren resistencia contra las cefalosporinas de tercera y cuarta generación. Objetivo. Caracterizar las ß-lactamasas de espectro extendido en aislamientos de Salmonella spp. recibidos por el programa de vigilancia de enfermedad diarreica aguda o enfermedad transmitida por alimentos del Grupo de Microbiología del Instituto Nacional de Salud. Materiales y métodos. Entre enero de 1997 y junio de 2022, se recibieron 444 aislamientos de Salmonella spp. resistentes, por lo menos, a una de las cefalosporinas de tercera generación. El fenotipo de las ß-lactamasas de espectro extendido se identificó con la prueba de doble disco. El ADN se extrajo por ebullición y mediante PCR se amplificaron los genes bla CTX-M, bla SHVy : ' a ILM. Resultados. Todos los aislamientos fueron positivos para la prueba de ß-lactamasas de espectro extendido. Los resultados de la amplificación por PCR fueron: bla CTX-M + bla TLM (n=200), bla CTX-M (n=177), bla SHV(n=16), bla SHV + bla CTX-M (n=6), bla TLM (n=13) y bla SHV + bla CTX-M + bla TLM (n=3). Del total, 26 aislamientos fueron negativos para los genes evaluados. Los aislamientos positivos para ß-lactamasas de espectro extendido se identificaron en Bogotá y en 21 departamentos: Chocó, Magdalena, Meta, Bolívar, Casanare, Cesar, Córdoba, Quindío, Atlántico, Tolima, Cauca, Cundinamarca, Huila, Boyacá, Caldas, Norte de Santander, Risaralda, Antioquia, Nariño, Santander y Valle del Cauca. Conclusión. La resistencia a las cefalosporinas de tercera generación en aislamientos de Salmonella spp. fue generada principalmente por bla CTX-M. El 44 % (197/444) de los aislamientos presentó resistencia a ampicilina, tetraciclina, cloranfenicol y trimetoprim- sulfametoxazol Los serotipos portadores de ß-lactamasas de espectro extendido más frecuentes fueron S. Typhimurium y S. Infantis.

Introduction. Salmonella spp. is a zoonotic pathogen transmitted to humans through contaminated water or food. The presence of extended-spectrum ß-lactamases is a growing public health problem because these enzymes are resistant to third and fourth generation cephalosporins. Objective. To characterize extended-spectrum ß-lactamases in Salmonella spp. isolates received by the acute diarrheal disease/foodborne disease surveillance program of the Grupo de Microbiología of the Instituto Nacional de Salud. Materials and methods. A total of 444 Salmonella spp. isolates, resistant to at least one of the cephalosporins, were obtained between January 1997 and June 2022. The extended- spectrum ß-lactamases phenotype was identified by the double disk test. DNA extraction was carried out by the boiling method, and the bla CTX-M, bla SHV, and bla TLM genes were amplified by PCR. Results. All the isolates were positive for the extended-spectrum ß-lactamases test. The genes identified were: bla CTX-M + ba TLM (n=200), bla CTX-M (n=177), bla SHV(n=16), bla SHV + bla CTX-M (n=6), bla TLM (n=13) and bla SHV + bla CTX-M + bla TLM (n=3). Twenty-six isolates were negative for the evaluated genes. Positive extended-spectrum ß-lactamases isolates were identified in Bogotá and 21 departments: Chocó, Magdalena, Meta, Bolívar, Casanare, Cesar, Córdoba, Quindío, Atlántico, Tolima, Cauca, Cundinamarca, Huila, Boyacá, Caldas, Norte de Santander, Risaralda, Antioquia, Nariño, Santander y Valle del Cauca. Conclusion. Resistance to third generation cephalosporins in Salmonella spp. isolates was mainly caused by bla CTX-M. Isolates were resistant to ampicillin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole (44 %; 197/444). The most frequent extended-spectrum ß-lactamases-expressing serotypes were Salmonella Typhimurium and Salmonella Infantis.

Crosstalk between dihydroceramides produced by Porphyromonas gingivalis and host lysosomal cathepsin B in the promotion of osteoclastogenesis.

Emerging studies indicate that intracellular eukaryotic ceramide species directly activate cathepsin B (CatB), a lysosomal-cysteine-protease, in the cytoplasm of osteoclast precursors (OCPs) leading to elevated RANKL-mediated osteoclastogenesis and inflammatory osteolysis. However, the possible impact of CatB on osteoclastogenesis elevated by non-eukaryotic ceramides is largely unknown. It was reported that a novel class of phosphoglycerol dihydroceramide (PGDHC), produced by the key periodontal pathogen Porphyromonas gingivalis upregulated RANKL-mediated osteoclastogenesis in vitro and in vivo. Therefore, the aim of this study was to evaluate a crosstalk between host CatB and non-eukaryotic PGDHC on the promotion of osteoclastogenesis. According to a pulldown assay, high affinity between PGDHC and CatB was observed in RANKL-stimulated RAW264.7 cells in vitro. It was also demonstrated that PGDHC promotes enzymatic activity of recombinant CatB protein ex vivo and in RANKL-stimulated osteoclast precursors in vitro. Furthermore, no or little effect of PGDHC on the RANKL-primed osteoclastogenesis was observed in male and female CatB-knock out mice compared with their wild type counterparts. Altogether, these findings demonstrate that bacterial dihydroceramides produced by P. gingivalis elevate RANKL-primed osteoclastogenesis via direct activation of intracellular CatB in OCPs.

Sentinel surveillance for bacterial pneumonia and meningitis in children under the age of 5 in a tertiary pediatric hospital in Colombia - 2016 / Vigilancia centinela de neumonías y meningitis bacterianas en menores de 5 años en un hospital pediátrico de tercer nivel en Colombia - 2016

Abstract | Introduction: Bacterial pneumonia and meningitis are vaccine-preventable diseases. Sentinel surveillance provides relevant information about their behavior. Objective: To present the data from sentinel surveillance carried out at the Fundación HOMI, Fundación Hospital Pediátrico La Misericordia in 2016. Materials and methods: We conducted a descriptive study from January 1 to December 31, 2016, on the daily surveillance of patients under 5 years of age diagnosed with pneumonia or bacterial meningitis according to PAHO's definitions. We identified the microorganisms using the automated VITEKTM 2 system. Bacterial isolates were sent to the Microbiology Group at the Colombian Instituto Nacional de Salud for confirmation, serotyping, phenotypic, and genotypic characterization. Antimicrobial susceptibility profiles were established. Results: From 1,343 suspected cases of bacterial pneumonia, 654 (48.7%) were probable, 84% had complete Hib vaccination schedules, and 87% had complete pneumococcal vaccination schedules for age. Blood culture was taken in 619 (94.6%) and 41 (6.6%) were positive while S. pneumoniae was isolated in 17 (41%) of them. The most frequent serotype was 19A in five cases (29.4%), and four 19A serotypes were associated with the reference isolate ST320. The incidence rate of probable bacterial pneumonia was 7.3 cases/100 hospitalized patients, and lethality was 2.1%. As for bacterial meningitis, 22 suspected cases were reported, 12 (54%) were probable, four (33%) were confirmed: two by Escherichia coli and two by group C N. meningitidis. The incidence of probable bacterial meningitis was 0.14 cases/100 hospitalized patients. Conclusion: Streptococcus pneumoniae serotypes 19A and 3 were the most frequent cause of pneumonia. Spn19A is related to the multi-resistant clone ST320. Strengthening and continuing this strategy will allow understanding the impact of vaccination.

Resumen | Introducción. La neumonía y la meningitis bacterianas son enfermedades inmunoprevenibles; la vigilancia centinela aporta información relevante acerca de su comportamiento. Objetivo. Presentar los resultados de la vigilancia centinela de neumonía y meningitis llevada a cabo en la HOMI, Fundación Hospital Pediátrico La Misericordia. Materiales y métodos. Se hizo un estudio descriptivo entre el 1 de enero y el 31 diciembre del 2016, de la vigilancia diaria de pacientes menores de 5 años con diagnóstico de neumonía o meningitis bacteriana, según las definiciones de la Organización Panamericana de la Salud (OPS). Los microorganismos fueron identificados usando el sistema automatizado VITEK TM2. Los aislamientos se enviaron al grupo de microbiología del Instituto Nacional de Salud para confirmación, serotipificación, y caracterización genotípica y fenotípica. Asimismo, se establecieron los perfiles de sensibilidad antimicrobiana. Resultados. De 1.343 casos sospechosos de neumonía bacteriana, 654 (48,7 %) fueron probables, el 84 % tenía el esquema de vacunación completo para la edad contra Haemophilus influenzae de tipo b, y el 87 %, contra neumococo. En 619 (94,6 %) pacientes se hizo hemocultivo y 41 (6,6 %) fueron positivos. S. pneumoniae se aisló en 17 (41 %) casos. El serotipo más frecuente fue el 19A, en cinco pacientes (29,4 %), en tanto que cuatro aislamientos de spn19A fueron relacionados con el clon ST320. La tasa de incidencia de neumonía bacteriana probable fue de 7,3 casos/100 pacientes hospitalizados. La letalidad fue de 2,1 %. Hubo 22 casos sospechosos de meningitis bacteriana, 12 (54 %) probables, y cuatro (33 %) confirmados: dos por Escherichia coli y dos por Neisseria meningitidis del grupo C. La incidencia de meningitis bacteriana probable fue de 0,14/100 pacientes hospitalizados. Conclusión. Los serotipos 19A y 3 de S. pneumoniae fueron la causa más frecuente de neumonía. El Spn19A se relacionó con el clon ST320 mulitirresistente. El fortalecimiento continuo de la vigilancia centinela permitirá entender el impacto de la vacunación.

Streptococcus pneumoniae serotype 3 genotypes in invasive isolates from Colombia / Genotipos del serotipo 3 de Streptococcus pneumoniae en aislamientos invasivos en Colombia

Abstract | Introduction: Streptococcus pneumoniae serotype 3 is an important cause of pneumonia, bacteremia, and meningitis. Objective: To establish the circulating genotypes of S. pneumoniae serotype 3 isolates recovered from the invasive disease between 1994 to 2015 in Colombia. Materials and methods: Of the 365 S. pneumoniae serotype 3 isolates recovered through the laboratory national surveillance program, 117 isolates were analyzed. Pulsed-field gel electrophoresis was used for genotyping, and multilocus sequence typing was determined in representative isolates. Results: The frequency of this serotype increased from 2.7% between 1994 and 1998 to 9.1% between 2011 and 2015 (p=0.000); 91.7% of the isolates showed a genetic similarity greater than 77% and were related to the Netherlands3-31(PMEN31) clone CC180. Several subtypes were identified, two of which showed antimicrobial resistance. Conclusion: In Colombia, the pneumococcal population of the capsular type 3 shows a continuous and homogeneous circulation relating to the clonal group ST-180.

Resumen | Introducción. El serotipo 3 de Streptococcus pneumoniae es una causa importante de neumonía, bacteriemia y meningitis. Objetivo. Establecer los genotipos circulantes de aislamientos del serotipo 3 de S. pneumoniae recuperados de muestras de enfermedad invasiva de 1994 a 2015 en Colombia. Materiales y métodos. Se analizaron 117 de los 365 aislamientos del serotipo 3 de S. pneumoniae recuperados del programa nacional de vigilancia por el laboratorio. El genotipo se estableció con electroforesis en gel de campo pulsado y la tipificación se llevó a cabo mediante secuenciación multilocus en aislamientos representativos. Resultados. La frecuencia de este serotipo aumentó de 2,7 % entre 1994 y 1998 a 9,1 % entre 2011 y 2015 (p=0,000). El 91,7 % de los aislamientos evidenció una similitud genética superior al 77 % y se relacionó con el clon CC180 de Netherlands3-31 (PMEN31). Se identificaron varios subtipos, dos de los cuales mostraron resistencia a los antimicrobianos. Conclusión. En Colombia, la población neumocócica del tipo capsular 3 tiene una circulación continua y homogénea relacionada con el grupo clonal ST-180.

Brote de Salmonella entérica subsp. entérica serovar Give asociado con enfermedad transmitida por alimentos en Vichada, Colombia, 2015 / An outbreak of Salmonella entérica subsp. entérica serovar Give associated with foodborne illness in the department of Vichada, Colombia, 2015

Resumen | Introducción. Salmonella entérica subsp. entérica serovar Give se encuentra en mamíferos rumiantes, cerdos, aves y ambientes acuáticos, pero rara vez en humanos. En Colombia este serotipo ocupó el decimoprimer lugar en frecuencia en la vigilancia por laboratorio de la enfermedad diarreica aguda entre el 2000 y el 2013. Objetivo. Caracterizar el fenotipo y el genotipo de S. Give en aislamientos relacionados con un brote de enfermedad transmitida por alimentos en el departamento de Vichada en la quinta semana epidemiológica del 2015. Materiales y métodos. Se buscó Salmonella spp. en 37 muestras de materia fecal con el método de estudio del Instituto Nacional de Salud. La muestra de sardinas enlatadas fue procesada según la norma ISO6579:2002 Cor.1:2004. Se determinó el serotipo en los aislamientos confirmados mediante serología o PCR en tiempo real, y se hicieron pruebas de sensibilidad a antimicrobianos y electroforesis en gel de campo pulsado con las enzimas Xbal y BlnI. Resultados. Todos los aislamientos de origen humano (11) y el aislamiento del alimento (1), se identificaron como S. Give y este último presentó resistencia a la tetraciclina. El análisis por PFGE-XbaI agrupó bajo el patrón COIN15JEXX01.0005 diez aislamientos de origen humano y a los restantes bajo el COIN15JEXX01.0006, con un 96,3 % de similitud. Los resultados de todos los aislamientos se confirmaron con la enzima BlnI; cuatro de ellos (tres humanos y el del alimento) se agruparon bajo el patrón COIN15JEXA26.002, con un porcentaje de similitud del 95,65 %. Conclusión. El estudio confirmó que las sardinas enlatadas se relacionaron con la transmisión de S. Give en el brote, que es el tercero ocasionado por este serotipo en Colombia.

Abstract | Introduction: Salmonella enterica subsp. enterica serovar Give is found in ruminants, pigs, poultry, and aquatic environments, but rarely in humans. In Colombia, this serotype was ranked 11th. in the laboratory surveillance of acute diarrheal disease between 2000 and 2013. Objective: To characterize phenotypic and genotypic isolates of Salmonella related to an outbreak of foodborne Illness in the department Vichada in the fifth epidemiological week of 2015. Materials and methods: Following the Instituto Nacional de Salud method, we tested 37 fecal samples for Salmonella spp. while the sample of canned sardines was processed according to the ISO 6579:2002 Cor.1:2004 standard. The isolates were confirmed by serology and/or real-time PCR, antimicrobial susceptibility tests, and pulsed-field gel electrophoresis with the XbaI and BlnI enzymes. Results: All human isolates (11) and that from food (1) were identified as S. Give. The food isolate exhibited tetracycline resistance. PFGE analysis with XbaI grouped ten isolates from samples of human origin in pattern COIN15JEXX01.0005 and the remaining isolates in COIN15JEXX01.0006 with 96.3% similarity. All isolates were confirmed with the BlnI enzyme, and four (three human isolates and the one from food) were matched to the pattern COIN15JEXA26.002 with 95.65% similarity. Conclusion: Our study confirmed that canned sardines were related to the transmission of S. Give in the outbreak, which is the third one caused by this serotype in Colombia.

Age-dependent effects of the recombinant spike protein/SARS-CoV-2 on the M-CSF- and IL-34-differentiated macrophages in vitro.

The SARS-CoV-2 virus causes elevated production of senescence-associated secretory phenotype (SASP) markers by macrophages. SARS-CoV-2 enters macrophages through its Spike-protein aided by cathepsin (Cat) B and L, which also mediate SASP production. Since M-CSF and IL-34 control macrophage differentiation, we investigated the age-dependent effects of the Spike-protein on SASP-related pro-inflammatory-cytokines and nuclear-senescence-regulatory-factors, and CatB, L and K, in mouse M-CSF- and IL-34-differentiated macrophages. The Spike-protein upregulated SASP expression in young and aged male M-CSF-macrophages. In contrast, only young and aged male IL-34-macrophages demonstrated significantly reduced pro-inflammatory cytokine expression in response to the Spike-protein in vitro. Furthermore, the S-protein elevated CatB expression in young male M-CSF-macrophages and young female IL-34-macrophages, whereas CatL was overexpressed in young male IL-34- and old male M-CSF-macrophages. Surprisingly, the S-protein increased CatK activity in young and aged male M-CSF-macrophages, indicating that CatK may be also involved in the COVID-19 pathology. Altogether, we demonstrated the age- and sex-dependent effects of the Spike-protein on M-CSF and IL-34-macrophages using a novel in vitro mouse model of SARS-CoV-2/COVID-19.

Identificación de aislamientos de Candida auris recuperados a través de la vigilancia por laboratorio en Colombia: un reto para el diagnóstico / Identification of Candida auris isolates recovered through laboratory surveillance in Colombia: a challenge for diagnostic

Resumen Objetivo: Comparar los resultados obtenidos de diferentes sistemas de identificación de C. auris. Métodos: Análisis descriptivo con datos recopilados durante 2016-19 mediante la vigilancia nacional. Se evaluaron los resultados generados por los sistemas MicroScan, Phoenix BD, VITEK 2 y MALDI-TOF MS de instituciones hospitalarias de 843 aislamientos clínicos sospechosos de C. auris remitidos al INS y se compararon con los resultados generados de confirmación a través de MALDI- TOF MS (Bruker Daltonics) o PCR. Resultados: De los 843 aislamientos clínicos remitidos al INS, el 81,7% fueron confirmados como C. auris mediante MALDI- TOF MS o PCR en el INS y el resto, 18,3%, fueron identificados como otras especies de Candida spp. Las identificaciones correctas enviadas por los laboratorios representaron el 42,4%. MicroScan identificó C. auris principalmente como C. haemulonii, C. guilliermondii, C. albicans y C. famata; Phoenix BD, VITEK 2 y MALDI-TOF MS identificó C. auris como C. haemulonii. Discusión: Estudios señalan que C. auris exhibe una estrecha relación filogenética con C. haemulonii. Las identificaciones discrepantes pueden darse debido a que las bases de datos de los sistemas de diagnóstico son limitadas para este patógeno. Las deficiencias de los sistemas comerciales para la identificación de C. auris deben ser complementados con otros sistemas como MALDI-TOF MS o pruebas moleculares.

Abstract Objective: To compare the identification results obtained by different identification systems of C. auris isolates. Methods: A descriptive study with data collected during the years 2016-19 through surveillance. The results generated by the MicroScan, Phoenix BD, VITEK 2 and MALDI-TOF MS systems of 843 clinical isolates of C. auris submitted to the INS were evaluated and compared with the results generated from confirmation through MALDI-TOF MS (Bruker Daltonics) or PCR. Results: Out of 843 clinical isolates submitted to the INS, 81.7% were confirmed as C. auris by MALDITOF MS or PCR in the INS and the rest, 18.3%, were identified as other species of Candida spp. The correct identifications sent by the laboratories was 42.4%. MicroScan identified C. auris as C. haemulonii, C. guilliermondii, C. albicans and C. famata; Phoenix BD, VITEK 2 and MALDI-TOF MS identified C. auris as C. haemulonii. Discussion: Studies indicate that C. auris exhibits a close phylogenetic relationship with C. haemulonii. In addition, discrepant identifications may occur because the databases of diagnostic systems are limited with reference to this pathogen. The deficiencies of commercial systems for the identification of C. auris must be complemented with other systems such as MALDI-TOF MS or molecular tests.

Elusive Roles of the Different Ceramidases in Human Health, Pathophysiology, and Tissue Regeneration.

Ceramide and sphingosine are important interconvertible sphingolipid metabolites which govern various signaling pathways related to different aspects of cell survival and senescence. The conversion of ceramide into sphingosine is mediated by ceramidases. Altogether, five human ceramidases-named acid ceramidase, neutral ceramidase, alkaline ceramidase 1, alkaline ceramidase 2, and alkaline ceramidase 3-have been identified as having maximal activities in acidic, neutral, and alkaline environments, respectively. All five ceramidases have received increased attention for their implications in various diseases, including cancer, Alzheimer's disease, and Farber disease. Furthermore, the potential anti-inflammatory and anti-apoptotic effects of ceramidases in host cells exposed to pathogenic bacteria and viruses have also been demonstrated. While ceramidases have been a subject of study in recent decades, our knowledge of their pathophysiology remains limited. Thus, this review provides a critical evaluation and interpretive analysis of existing literature on the role of acid, neutral, and alkaline ceramidases in relation to human health and various diseases, including cancer, neurodegenerative diseases, and infectious diseases. In addition, the essential impact of ceramidases on tissue regeneration, as well as their usefulness in enzyme replacement therapy, is also discussed.

Resultados de la vigilancia nacional de la resistencia antimicrobiana de enterobacterias y bacilos Gram negativos no fermentadores en infecciones asociadas a la atención de salud, Colombia, 2012-2014 / Results of the national surveillance of antimicrobial resistance of Enterobacteriaceae and Gram negative bacilli in health care-associated infections in Colombia, 2012-2014

Resumen Introducción. En el tercer trimestre de 2012, comenzó a operar el Sistema Nacional de Vigilancia de Resistencia Antimicrobiana en las infecciones asociadas a la atención en salud, con el fin de recabar y analizar la información referente al problema en Colombia. Objetivo. Describir los perfiles de resistencia y los resultados de la vigilancia por el laboratorio con base en los datos recolectados en el Sistema. Materiales y métodos. Se hizo un estudio descriptivo y retrospectivo con base en la información del Sistema Nacional de Vigilancia en Salud Pública, Sivigila, 1 de septiembre de 2012 a 31 de diciembre de 2014, así como de las bases de datos Whonet con los datos notificados por las unidades primarias generadoras de datos y los resultados de la confirmación por el laboratorio de la caracterización fenotípica y genotípica de la resistencia a carbapenemasas en 1.642 aislamientos (927 de enterobacterias, 614 de Pseudomonas spp. y 101 de Acinetobacter spp.). Resultados. La resistencia de Escherichia coli a las cefalosporinas de tercera generación presentó un incremento significativo, alcanzando 26,3 % en unidades de cuidados intensivos y 22,5 % en otras áreas de hospitalización. La resistencia a ertapenem de Klebsiella pneumoniae registró un incremento y alcanzó 14,6 % en unidades de cuidados intensivos. La resistencia de Acinetobacter baumannii a los carbapenémicos superó el 50 % en dichas unidades, en tanto que en Pseudomonas aeruginosa se presentaron porcentajes más bajos (38,8 %). Las carbapenemasas más frecuentes en enterobacterias fueron la KPC (n=574), seguida de la NDM (n=57); en P. aeruginosa, la VIM (n=229) y la KPC (n=114), y en A. baumannii, la OXA-23 (n=87). Se detectaron varias combinaciones de carbapenemasas, siendo la de KPC y VIM la más frecuente en Pseudomonas spp., y en enterobacterias. Conclusión. La información obtenida a partir del Sistema Nacional de Vigilancia ha permitido conocer los perfiles y los mecanismos de resistencia a carbapenémicos de las cepas que están circulando en las instituciones de salud del país.

Abstract Introduction: The Colombian National Antimicrobial Resistance Monitoring System for the surveillance of healthcare-associated infections was set up to meet this problem in the third quarter of 2012. Objective: To describe resistance profiles and laboratory-based surveillance based on the information collected by the System. Materials and methods: We conducted a retrospective and descriptive study of the information notified to the Colombian Public Health Surveillance System (Sivigila), and in the Whonet databases covering the period from July 2012 to December 2014 provided by the primary data-generating units in the country, as well as laboratory surveillance results from 1,642 phenotypic and genotypic tests on carbapenemase isolates (927 from Enterobacteriaceae, 614 from Pseudomonas spp. and 101 from Acinetobacter spp.). Results: There was a significant increase in Escherichia coli resistance to third-generation cephalosporins (reaching 26.3% in ICUs and 22.5% in other hospital wards), and Klebsiella pneumoniae resistance to ertapenem also increased (reaching 14.6% in ICUs). Acinetobacter baumannii carbapenem resistance exceeded 50% in ICUs whereas Pseudomonas aeruginosa had lower carbapenem resistance (38.8%). KPC (n = 574) and NDM (n=57) were the most frequently occurring carbapenemases in Enterobacteriaceae, VIM (n=229) and KPC (n=114) in P. aeruginosa, and OXA-23 in A. baumannii (n=87); several carbapenemase combinations were identified, KPC + VIM being the most common in Pseudomonas spp. and Enterobacteriaceae. Conclusion: The data from the surveillance of healthcare-associated infections revealed significant carbapenem resistance profiles and antimicrobial resistance mechanisms circulating in Colombian healthcare institutions.

Molecular characterization of non-vaccine Streptococcus pneumoniae serotypes 11A, 15 B/C and 23A recovered from invasive isolates in Colombia / Caracterización molecular de los serotipos no vacunales 11A, 15 B/C y 23A de Streptococcus pneumoniae recuperados de aislamientos invasivos en Colombia

Resumen Introduction: A total of 192 invasive Streptococcus pneumoniae isolates, from serotypes 11A, 15B/C and 23A (not included in the conjugated vaccines), were collected in Colombia between 1994 and 2014 as part of the activities of the Network surveillance system for the causative agents of pneumonia and meningitis (SIREVA II). Objective: To determine the molecular characteristics ofinvasive S. pneumoniaeisolates from serotypes 11A, 15B/C and 23A in Colombia from 1994 to 2014. Materials and methods: The molecular characterization of the isolates was carried out through Pulse-Field Gel Electrophoresis (PFGE) and Multilocus Sequence Typing (MLST). Results: Serotype 11A showed one clonal group represented by ST62. Serotype 15B/C was composed of three groups associated with Netherlands15B-37 ST199 (28.75%), ST8495 (18.75%), and SLV (Single-Locus Variant) of ST193 (21.25%). Isolates from serotype 23A were gathered in three clonal groups, with70.21% closely related toST42, 17.02% to Colombia23F-ST338, and6.38% to Netherlands15B-37 ST199. Conclusion: Clones Colombia23F-ST338 andNetherlands15B-ST199 covered more serotypes than those previously found by other authors, including serotype 23A. These analyses reveal the importance of capsular switching in the spreading of successful clones among non-vaccine serotypes causing invasive pneumococcal disease.

Abstract Introducción. En Colombia se recolectaron 192 aislamientos invasivos de Streptococcus pneumoniae de los serotipos 11A, 15B/C y 23A (no incluidos en las vacunas conjugadas) entre 1994 y 2014, como parte de las actividades del Sistema de Redes de Vigilancia de los Agentes Responsables de Neumonías y MeningitisBacterianas (SIREVA II). Objetivo. Determinar las características moleculares de aislamientosinvasivos de los serotipos11A, 15B/C y 23A de S. pneumoniae recolectados en Colombia entre 1994 y 2014. Materiales y métodos. La caracterización molecular de los aislamientos se hizo medianteelectroforesis en gel de campo pulsado (Pulse-Field Gel Electrophoresis, PFGE) y por tipificación de secuencias multilocus (Multilocus Sequence Typing, MLST). Resultados. El serotipo 11A mostró un grupo clonal representadopor el ST62, en tanto que el serotipo15B/C se distribuyó en tres grupos asociados conlos clones Netherlands15B-37 ST199 (28,75 %), ST8495 (18,75 %) y SLV (variante en un solo locus) de ST193 (21,25 %). Los aislamientos con serotipo 23A se agruparon en tres gruposclonales; 70,21 % de ellos estaban estrechamente relacionadoscon elST42, 17,02 % con elColombia23F-ST338, y 6,38 % con el Netherlands15B-37 ST199. Conclusión. Los clones Colombia23F-ST338 y Netherlands15B-ST199 encontrados en este estudio abarcaronmás serotipos de los reportados previamente por otros autores, incluido el serotipo23A. Estos análisis revelan laimportancia de la conmutación(switching) capsular en la expansión de clones exitosos entre los serotipos no vacunales como causa de enfermedad invasiva neumocócica.

Whole-Genome Sequencing to Determine Origin of Multinational Outbreak of Sarocladium kiliense Bloodstream Infections.

We used whole-genome sequence typing (WGST) to investigate an outbreak of Sarocladium kiliense bloodstream infections (BSI) associated with receipt of contaminated antinausea medication among oncology patients in Colombia and Chile during 2013-2014. Twenty-five outbreak isolates (18 from patients and 7 from medication vials) and 11 control isolates unrelated to this outbreak were subjected to WGST to elucidate a source of infection. All outbreak isolates were nearly indistinguishable (<5 single-nucleotide polymorphisms), and >21,000 single-nucleotide polymorphisms were identified from unrelated control isolates, suggesting a point source for this outbreak. S. kiliense has been previously implicated in healthcare-related infections; however, the lack of available typing methods has precluded the ability to substantiate point sources. WGST for outbreak investigation caused by eukaryotic pathogens without reference genomes or existing genotyping methods enables accurate source identification to guide implementation of appropriate control and prevention measures.

Aislamientos invasivos de Haemophilus influenzae en menores de 5 años: distribución de los serotipos y de la sensibilidad antimicrobiana, SIREVA II Colombia 2002-2013 / Invasive Haemophilus influenzae isolates in children younger than 5 years: Distribution of serotypes and antimicrobial sensitivity, SIREVA II Colombia 2002-2013

Objetivo: Analizar del 2002 al 2013 los datos de la vigilancia de los serotipos y sensibilidad antimicrobiana de los aislamientos invasivos de Haemophilus influenzae ( H. influenzae ) en niños menores de 60 meses. Materiales y métodos: Se analizaron los datos demográficos, fuente y enfermedad asociada de los aislamientos invasivos de H. influenzae recibidos entre 2002 y 2013. Todos los aislamientos habían sido confirmados bacteriológicamente, tenían el dato del serotipo, el cual fue determinado por el método de aglutinación en lámina y PCR y los patrones de sensibilidad antimicrobiana por concentración inhibitoria mínima a ampicilina, SXT, cloranfenicol, cefuroxima y ceftriaxona. El análisis se realizó por periodos de 3 años. Resultados: Por enfermedad invasiva el 50,5% eran de pacientes con meningitis, 23,5% de neumonías, 19,5% de sepsis y bacteriemia, 2,0% de otros y 4,5% sin dato. Por procedencia se recibieron de Bogotá y Antioquia 55 aislamientos de cada uno, de Risaralda 24, de Valle 15, de Santander 11 y 40 de 14 departamentos. El serotipo predominante fue el Hib (40,5%), seguido de HiNT (38,0%), Hia (17,5%), Hid (2,0%), Hif (1,5%) y Hie (0,5%). Del total de los aislamientos, 12,0% eran resistentes a ampicilina; 16,5% a SXT; 1,0% a cloranfenicol y 0,5% a ceftriaxona. Todos los aislamientos fueron sensibles a cefuroxima y a rifampicina. Conclusiones: La vigilancia por el laboratorio es una vigilancia pasiva voluntaria pero, no obstante el número reducido de aislamientos, permite determinar que Hib continúa circulando en esta población y que hay otros serotipos de H. influenzae que causan enfermedad invasiva. Por tanto es necesario mantener y fortalecer la vigilancia de este patógeno.

Objective: To analyze 2002-2013 surveillance data on the serotypes and antimicrobial sensitivity of invasive Haemophilus influenzae ( H. influenzae ) isolates in children younger than 60 months. Materials and methods: We analyzed the demographic data, source and associated diseases ofinvasive HI isolates from cases recorded from 2002-2013. All isolates had been bacteriologically confirmed and had data on their serotype, which was determined by the slide agglutination method and polymerase chain reaction. The antimicrobial sensitivity patterns were determined by minimum inhibitory concentration of ampicillin, trimethoprim-sulfamethoxazole, chloramp-henicol, cefuroxime and ceftriaxone. The analysis was conducted in 3-year periods. Results: According to invasive disease, 50.5% of patients had meningitis, 23.5% had pneumonia,19.5% had sepsis and bacteremia, 2.0% had other diseases and 4.5% lacked data. By origin, 55 isolates each were received from Bogota and Antioquia, 24 were from Risaralda, 15 were from Valle, 11 were from Santander and 40 came from 14 departments. The predominant serotype was Hib (40.5%), followed by HiNT (38.0%), Hia (17.5%), Hid (2.0%), Hif (1.5%) and Hie (0.5%). Ofthe total isolates, 12.0% were resistant to ampicillin; 16.5% to trimethoprim-sulfamethoxazole,1.0% to chloramphenicol and 0.5% to ceftriaxone. All isolates were sensitive to cefuroxime andrifampicin. Conclusions: Laboratory surveillance is a voluntary passive surveillance; however, the low number of isolates helped determine that Hib continues to circulate in this population and that there are other H. influenzae serotypes that cause invasive disease. Therefore, surveillance of this pathogen needs to be maintained and reinforced.

RELAXIN enhances differentiation and matrix mineralization through Relaxin/insulin-like family peptide receptor 2 (Rxfp2) in MC3T3-E1 cells in vitro.

RELAXIN (RLN) is a polypeptide hormone of the insulin-like hormone family; it facilitates birth by softening and widening the pubic symphysis and cervix in many mammals, including humans. The role of RLN in bone metabolism was recently suggested by its ability to induce osteoclastogenesis and activate osteoclast function. RLN binds to RELAXIN/INSULIN-LIKE FAMILY PEPTIDE 1 (RXFP1) and 2 (RXFP2), with varying species-specific affinities. Young men with mutated RXFP2 are at high risk for osteoporosis, as RXFP2 influences osteoblast metabolism by binding to INSULIN-LIKE PEPTIDE 3 (INSL3). However, there have been no reports on RLN function in osteoblast differentiation and mineralization or on the functionally dominant receptors for RLN in osteoblasts. We previously described Rxfp1 and 2 expression patterns in developing mouse oral components, including the maxillary and mandibular bones, Meckel's cartilage, tongue, and tooth primordia. We hypothesized that Rln/Rxfp signaling is a key mediator of skeletal development and metabolism. Here, we present the gene expression patterns of Rxfp1 and 2 in developing mouse calvarial frontal bones as determined by in situ hybridization. In addition, RLN enhanced osteoblastic differentiation and caused abnormal mineralization and extracellular matrix metabolism through Rxfp2, which was predominant over Rxfp1 in MC3T3-E1 mouse calvarial osteoblasts. Our data suggest a novel role for Rln in craniofacial skeletal development and metabolism through Rxfp2.

Molecular characterization of Streptococcus pneumoniae serotype 1 invasive isolates in Colombia / Caracterización molecular de cepas invasoras de Streptococcus pneumoniae serotipo 1 aisladas en Colombia

OBJECTIVE: To determine the genetic relationship between Streptococcus pneumoniae serotype 1 Colombian isolates recovered from invasive disease between 1994 and 2011 and recognized serotype 1 international clones. METHODS: A total of 135 S. pneumoniae serotype 1 isolates with epidemiological and antimicrobial susceptibility data (Clinical and Laboratory Standards Institute, 2012) were studied. The genetic relationship with recognized international clones was established by pulsed-field gel electrophoresis (PFGE) with SmaI restriction enzyme. Multilocus sequence typing (MLST) was standardized to determine the sequence type (ST) in seven isolates representing different clonal groups. Control and reference strain R6, and clones Sweden¹ ST217, Sweden¹ ST304, Sweden¹ ST306, and USA¹ ST615, were used. RESULTS: PFGE revealed that 89.7% of the isolates were associated with Sweden¹ ST306, 3.7% were associated with Sweden¹ ST304, and 6.6% were not clonally related. Using MLST, ST306 was confirmed in six isolates and ST304 in one. CONCLUSIONS: In contrast to Brazil and the United States, where clones Sweden¹ ST304 and ST227 prevail, invasive disease caused by S. pneumoniae serotype 1 in Colombia is principally associated with the dispersion of isolates related to clone Sweden¹ ST306.

OBJETIVO: Determinar la relación genética entre las cepas de Streptococcus pneumoniae serotipo 1 aisladas en Colombia en casos de enfermedad invasora entre 1994 y 2011 y los clones internacionales reconocidos del serotipo 1. MÉTODOS: Se estudiaron un total de 135 cepas de S. pneumoniae serotipo 1 de las que se tenían datos epidemiológicos y de sensibilidad a los antimicrobianos (Clinical and Laboratory Standards Institute, 2012). Se estableció su relación genética con los clones internacionales reconocidos mediante electroforesis en gel de campo pulsátil (PFGE) utilizando la enzima de restricción SmaI. Se estandarizó la tipificación de secuencias mulitlocus (MLST) para determinar el tipo de secuencia (ST) en siete cepas que representaban diferentes grupos clonales. Se utilizaron la cepa de control y referencia R6 y los clones Sweden¹ ST217, Sweden¹ ST304, Sweden¹ ST306, y USA¹ ST615. RESULTADOS: La PFGE reveló que 89,7% de las cepas se asociaban con Sweden¹ ST306, 3,7% con Sweden¹ ST304, y 6,6% no mostraron relación clonal. Mediante MLST, se confirmó la relación con ST306 en seis cepas y con ST304 en una. CONCLUSIONES: A diferencia de Brasil y Estados Unidos, donde prevalecen los clones Sweden¹ ST304 y ST227, la enfermedad invasora causada por S. pneumoniae serotipo 1 en Colombia se asocia principalmente con la dispersión de cepas relacionadas con el clon Sweden¹ ST306.

Actividad física y sedentarismo en jóvenes universitarios de Colombia: prácticas, motivos y recursos para realizarlas / Physical activity and sedentary behavior in college youth from Colombian cities: practices, motivations, and resources

Objetivo: Describir las prácticas de actividad física (AF) en jóvenes universitarios de algunas ciudades colombianas, eidentificar la relación de las prácticas con los motivos para realizarlas y modificarlas, así como con los recursos disponiblespara llevarlas a cabo.Método: Participaron 1,811 estudiantes, entre 15 y 24 años, de seis universidades colombianas. Se utilizó la subescalade actividad física del ®Cuestionario de estilos de vida en jóvenes universitarios¼.Resultados: Del total de jóvenes universitarios 22.2% realiza AF. Los principales motivos para hacer AF fueron®beneficiar la salud¼ (45.8%) y ®mejorar la figura¼ (32%) y para no hacerla la ®pereza¼ (61.5%). La AF es mayor en quienesestán satisfechos con los cambios logrados en este sentido y piensan mantenerlos (66%), y en quienes informan tener a sudisposición recursos como implementos deportivos, tiempo, habilidades, cualidades físicas, buen estado de salud, espaciosy oferta de actividades físicas y deportivas en la universidad, y conocimientos para la realización adecuada de las prácticas.Conclusiones: Pocos jóvenes universitarios realizan AF y para la prevención y modificación del sedentarismo esnecesario considerar aspectos de la motivación para el cambio y cómo ampliar o conseguir los recursos que necesitan para realizar AF.

Polyphosphates and pyrophosphates of pentopyranoses and pentofuranoses as allosteric effectors of human hemoglobin: synthesis, molecular recognition, and oxygen release.

Perphosphorylated pentopyranoses and pentofuranoses were synthesized from parent carbohydrates as potential allosteric effectors of hemoglobin (Hb). The construction of seven- and eight-membered cyclic pyrophosphates was also carried out successfully on most of the pentoses. All final compounds were tested for their efficiency on oxygen release from human Hb. Most proved to be efficient allosteric effectors, some of them with an affinity toward Hb and an effect on oxygen release from Hb approaching that of myo-inositol hexakisphosphate, which is one of the most active allosteric effectors of Hb. The efficacy was higher for free phosphates than for pyrophosphates.

Incremento de la resistencia a eritromicina de Streptococcus pneumoniae, Colombia, 1994-2008 / Increase in erythromycin-resistant Streptococcus pneumoniae in Colombia, 1994-2008

Introducción. Streptococcus pneumoniae es un agente comúnmente implicado en enfermedad invasora. Los macrólidos constituyen un tratamiento alternativo para las infecciones por S. pneumoniae resistente a los beta-lactámicos. Sin embargo, la resistencia a macrólidos se ha incrementado a nivel mundial. Objetivo. Determinar la frecuencia de la resistencia a la eritromicina de S. pneumoniae en 15 años de vigilancia y caracterizar fenotípica y genotípicamente los aislamientos resistentes. Materiales y métodos. Se analizaron los datos demográficos de los pacientes, la sensibilidad antimicrobiana y los serotipos de los aislamientos resistentes a la eritromicina, recuperados entre 1994 y 2008. Se determinaron los fenotipos por la técnica del doble disco, y los genotipos, por PCR y PFGE. Todos los aislamientos se recuperaron de enfermedad invasiva y fueron proporcionados por los laboratorios nacionales de salud pública. Resultados. Se recuperaron 3.241 aislamientos invasores; 136 (4,2 %) presentaron resistencia a la eritromicina. La resistencia a la eritromicina se incrementó entre 1994-1996 y 2006-2008, de 2,4 % a 6,9 % en menores de 6 años y, de 3,3 % a 5,7 %, en adultos. Los serotipos más frecuentes fueron 6B (36,8 %), 14 (16,9 %) y 6A (17,6 %). El fenotipo constitutivo cMLSB se determinó en 87 aislamientos; 82 tenían el gen ermB. El fenotipo M se determinó en 46; 45 tenían el gen mefA, tres aislamientos expresaron fenotipo inducible (iMLSB) y un aislamiento presentaba el gen ermB. Por PFGE, se determinó que 50 aislamientos estaban relacionados con clones internacionales, de los cuales, 58 % eran España6B ST90, 26 % eran España9V ST156, 8 % eran Colombia23F-ST338 y 8 % eran España23F-ST81. Conclusiones. Se observó incremento en la resistencia a la eritromicina, relacionada principalmente con el mecanismo de metilación ribosómica y con el clon España6B-ST90 que ha circulado en Colombia desde 1994.

Introduction. Streptococcus pneumoniae is a commonly implicated agent in invasive disease. For infections of S. pneumoniae resistant to beta-lactam, macrolides are an alternative treatment. However, resistance to macrolides has increased worldwide as well. Objective. The frequency of resistance to erythromycin was determined for S. pneumoniae over a 15-year surveillance period, and the resistant isolates were characterized phenotypically and genotypically. Materials and methods. Demographic data of the patients, antimicrobial susceptibility and serotypes were analyzed for 3,241 S. pneumoniae isolates recovered between 1994 and 2008. The phenotypes were determined by the double-disc technique and genotypes by PCR (polymerase chain reaction) and PFGE (pulsed field gel electrophoresis). Isolates were recovered from invasive diseases and were provided by national public health laboratories. Results. Of the 3,241 isolates, 136 were resistant to erythromycin. In the 12-year period between 1994-1996 and 2006-2008, resistance in each 2-year sampling had increased from 2.4% to 6.9% in children under 6 years and from 3.3% to 5.7% in adults. The most common serotypes were 6B (36.8%), 14 (16.9%) and 6A (17.6%). Constitutive phenotype cMLSB was determined in 87 isolates; 82 of these expressed the ermB gene. Phenotype M was determined in 46 isolates; 45 had the mefA gene. An additional three isolates expressed the inducible phenotype (iMLSB), and one expressed the ermB gene. By PFGE, 50 of the isolates were found to be related to international clones--58% were Spain6B-ST90, 26% Spain9V-ST156, 8% Colombia23F-ST338 and 8% Spain23F-ST81. Conclusion. The increase in erythromycin resistance was primarily related to the mechanism of ribosomal methylation. More than half the cases were congeneric with the clone Spain6B-ST90 that has been circulating in Colombia since 1994.

Polyphosphates and pyrophosphates of hexopyranoses as allosteric effectors of human hemoglobin: synthesis, molecular recognition, and effect on oxygen release.

Polyphosphorylated and perphosphorylated hexopyranose monosaccharides and disaccharides were synthesized from parent or partially protected carbohydrates as potential allosteric effectors of hemoglobin. A study toward the construction of seven- and eight-membered cyclic pyrophosphates was also performed on the sugars which had the proper orientation, protection, and number of phosphates. All final compounds were tested for their efficiency on oxygen release from human hemoglobin. Several compounds presented higher potency than myo-inositol hexakisphosphate, which is the most efficient of the known allosteric effectors of hemoglobin. Structure-activity relationships were analyzed. The affinity and efficiency depend on the number of phosphates attached to the carbohydrate skeleton and are related primarily to the number of negative charges present. Other effects operate, but play a lesser role.