The BioMart community portal: an innovative alternative to large, centralized data repositories.

The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations.

Trypanosoma cruzi infection induces DNA double-strand breaks and activates DNA damage response pathway in host epithelial cells.

Trypanosoma cruzi, the etiological agent of Chagas disease, invades many cell types affecting numerous host-signalling pathways. During the T. cruzi infection, we demonstrated modulations in the host RNA polymerase II activity with the downregulation of ribonucleoproteins affecting host transcription and splicing machinery. These alterations could be a result of the initial damage to the host DNA caused by the presence of the parasite, however, the mechanisms are not well understood. Herein, we examined whether infection by T. cruzi coincided with enhanced DNA damage in the host cell. We studied the engagement of the DNA damage response (DDR) pathways at the different time points (0-24 h post-infection, hpi) by T. cruzi in LLC-MK2 cells. In response to double-strand breaks (DSB), maximum phosphorylation of the histone variant H2AX is observed at 2hpi and promotes recruitment of the DDR p53-binding protein (53BP1). During T. cruzi infection, Ataxia-telangiectasia mutated protein (ATM) and DNA-PK protein kinases remained active in a time-dependent manner and played roles in regulating the host response to DSB. The host DNA lesions caused by the infection are likely orchestrated by the non-homologous end joining (NHEJ) pathway to maintain the host genome integrity.

Impact of Adding a Rapid PCR-Based Blood Culture Identification Panel to the Antimicrobial Stewardship Program of Patients with Febrile Neutropenia in a Peruvian Referral Hospital.

The addition of Biofire® FilmArray® Blood Culture Identification panel 2 (BCID2) to the antimicrobial stewardship program (ASP) could improve outcomes in bloodstream infections (BSI) of patients with febrile neutropenia (FN). A pre- and post-quasi-experimental single-center study was conducted at a reference hospital in Peru. Three groups were considered: patients with BSI before ASP intervention (control group), patients with BSI after ASP intervention (group 1), and patients with BSI after ASP intervention plus BCID2 PCR Panel implementation (group 2). Overall, 93 patients were identified (32 control, 30 group 1, 31 group 2). The median time to effective therapy was significantly shorter in group 2 compared to group 1 and control group, respectively (3.75 vs. 10 h, p = 0.004; 3.75 vs. 19 h, p < 0.001). No significant differences in terms of relapse of bacteremia, in-hospital mortality (all cause), and 30-day-all-cause hospital readmission between the three study periods were found. The appropriateness of empirical antimicrobial use, adding or change, and the following de-escalation or discontinuation was significant when the two intervention periods were compared with the control group (p < 0.001). In addition to the lack of local studies documenting the microbiological profile of FN episodes, adding syndromic panels-based testing could allow for the consolidation of ASP strategies.

Modulation of the Host Nuclear Compartment by Trypanosoma cruzi Uncovers Effects on Host Transcription and Splicing Machinery.

Host manipulation is a common strategy for invading pathogens. Trypanosoma cruzi, the causative agent of Chagas Disease, lives intracellularly within host cells. During infection, parasite-associated modifications occur to the host cell metabolism and morphology. However, little is known about the effect of T. cruzi infection on the host cell nucleus and nuclear functionality. Here, we show that T. cruzi can modulate host transcription and splicing machinery in non-professional phagocytic cells during infection. We found that T. cruzi regulates host RNA polymerase II (RNAPII) in a time-dependent manner, resulting in a drastic decrease in RNAPII activity. Furthermore, host cell ribonucleoproteins associated with mRNA transcription (hnRNPA1 and AB2) are downregulated concurrently. We reasoned that T. cruzi may hijack the host U2AF35 auxiliary factor, a key regulator for RNA processing, as a strategy to affect the splicing machinery activities directly. In support of our hypothesis, we carried out in vivo splicing assays using an adenovirus E1A pre-mRNA splicing reporter, showing that intracellular T. cruzi directly modulates the host cells by appropriating U2AF35. For the first time, our results provide evidence of a complex and intimate molecular relationship between T. cruzi and the host cell nucleus during infection.

[Intramedullary toxoplasmosis in HIV-tuberculosis co-infected patient]. / Toxoplasmosis intramedular en una paciente con coinfección por VIH y tuberculosis.

The most common clinical presentation of Toxoplasma gondii in HIV patients is encephalitis; however, the intramedullary involvement has been reported in a few cases. We report a case of intramedullary toxoplasmosis in a female patient diagnosed with HIV/tuberculosis co-infection, and history of poor adherence to antiretroviral therapy. The patient developed subacute paraparesis with compromise of sensory function and urinary sphincter. The nuclear magnetic resonance evaluation showed a single intramedullary ring-enhanced lesion at the T-8 level which was solved after an anti-Toxoplasma therapy with trimethoprim/sulfamethoxazole.

[Paracoccidiomicosis in the central nervous system: a case report]. / Paracoccidiomicosis en el sistema nervioso central: reporte de un caso.

Paracoccidioidomycosis is a fungal disease which can compromise the central nervous system (CNS).We present a case of an immunocompetent 45 year old man from Satipo, Peru who developed paracoccidioidomycosis in the CNS without any apparent point of entry or infection. The patient was diagnosed by imaging with a cerebellar granuloma, followed by a craniotomy where tissue and secretion of the granuloma abscess was obtained. Histological and microbiological diagnoses were performed on the tissue and secretion, respectively. Yeasts were observed in the histological section and growth of the fungus in the culture. The patient initially received antifungals, then acquired an intrahospital infection, received colistin and subsequently died. The case report emphasizes the importance of early and correct diagnosis for good outcomes of paracoccidioidomycosis cases.

Biofilm fúngico asociado a dispositivo intravascular de larga permanencia: Complicaciones y dificultades terapéuticas / Fungal biofilm associated with long-term central venous access device: Complications and therapeutic difficulties

Las infecciones fúngicas asociadas a biofilms en dispositivos biomédicos son refractarias al tratamiento antifúngico y habitualmente se requiere del retiro oportuno del dispositivo, así como la administración de antifúngicos sistémicos. Presentamos el caso de una paciente mujer de 36 años que recibe terapia para el dolor administrada por dispositivo intravascular de larga permanencia, catéter Port-A-Cath, y que desarrolló candidemia y endocarditis por Candida parapsilosis asociada al catéter; el cual tuvo que ser retirado mediante toracotomía por persistencia de la infección a pesar de la terapia antifúngica sistémica. Se evidenció extenso biofilm rodeando al catéter, con aislamiento de Candida parapsilosis y se completaron seis semanas de tratamiento antifúngico con evolución clínica favorable

Fungal infections associated with biofilms in biomedical devices are refractory to antifungal treatment and usually require the timely removal of the device, as well as the administration of systemic antifungals. We present the case of a 36-year- old female patient who received pain therapy administered by a Port-A-Cath long-term central venous access device. She developed catheter-related candidemi a and endocarditis caused by Candida parapsilosis. The catheter had to be removed by thoracotomy due to persistent infection despite the systemic antifungal therapy. An extensive biofilm surrounding the catheter was observed and Candida parapsilosis was isolated. Six weeks of antifungal treatment with a favorable clinical evolution were completed

Toxoplasmosis intramedular en una paciente con coinfección por VIH y tuberculosis / Intramedullary toxoplasmosis in HIV-tuberculosis co-infected patient

The most common clinical presentation of Toxoplasma gondii in HIV patients is encephalitis; however, the intramedullary involvement has been reported in a few cases. We report a case of intramedullary toxoplasmosis in a female patient diagnosed with HIV/tuberculosis co-infection, and history of poor adherence to antiretroviral therapy. The patient developed subacute paraparesis with compromise of sensory function and urinary sphincter. The nuclear magnetic resonance evaluation showed a single intramedullary ring-enhanced lesion at the T-8 level which was solved after an anti-Toxoplasma therapy with trimethoprim/sulfamethoxazole.

El compromiso encefálico por Toxoplasma gondii en pacientes con VIH es la localización más frecuente, no obstante, la localización intramedular ha sido escasamente reportada. Comunicamos un caso de toxoplasmosis intramedular en una mujer con diagnóstico de coinfección por VIH y tuberculosis, con mala adherencia a la terapia antirretroviral, que desarrolló de forma subaguda un cuadro de paraparesia con compromiso sensitivo y de esfínteres. La resonancia magnética mostró una lesión única intramedular con captación de contraste periférico en anillo a nivel T-8, que se resolvió tras recibir tratamiento anti-toxoplasmosis con cotrimoxazol.

Paracoccidiomicosis en el sistema nervioso central: reporte de un caso / Paracoccidiomicosis in the central nervous system: a case report

La paracoccidiomicosis es una enfermedad micótica que puede comprometer el sistema nervioso central (SNC). Se presenta el caso de un paciente varón de 45 años, inmunocompetente, de la ciudad de Satipo, que desarrollo paracoccidiomicosis en el SNC sin punto de entrada e infección aparente. El paciente fue diagnosticado por imágenes con un granuloma cerebelar, posteriormente, se realiza una craneotomía de donde se obtiene tejido y secreción del absceso del granuloma, se procedió al diagnóstico histológico y microbiológico, respectivamente, donde se observó la presencia de levaduras en el corte histológico y el crecimiento del hongo en el cultivo. El paciente, inicialmente, recibe antifúngicos, luego adquiere una infección intrahospitalaria, recibe colistina y posteriormente fallece. El caso reportado pone énfasis en la importancia del diagnóstico temprano y correcto para la buena evolución de los casos de paracoccidiomicosis.

Paracoccidioidomycosis is a fungal disease which can compromise the central nervous system (CNS).We present a case of an immunocompetent 45 year old man from Satipo, Peru who developed paracoccidioidomycosis in the CNS without any apparent point of entry or infection. The patient was diagnosed by imaging with a cerebellar granuloma, followed by a craniotomy where tissue and secretion of the granuloma abscess was obtained. Histological and microbiological diagnoses were performed on the tissue and secretion, respectively. Yeasts were observed in the histological section and growth of the fungus in the culture. The patient initially received antifungals, then acquired an intrahospital infection, received colistin and subsequently died. The case report emphasizes the importance of early and correct diagnosis for good outcomes of paracoccidioidomycosis cases.

Resultados preliminares del programa piloto de trasplante renal: Hospital Nacional Cayetano Heredia, Ministerio de Salud, Lima, Perú / Preliminary results of pilot program for renal transplantation Cayetano Heredia National Hospital, Ministry of Health, Lima, Peru

Introducción: El Seguro Integral de Salud ha iniciado un programa de apoyo para financiar las Terapias de Reemplazo Renal. Objetivo: Presentar resultados preliminares del Programa Piloto de Trasplante Renal, Hospital Nacional Cayetano Heredía-Ministerio de Salud. Material y método: Es una serie de casos del periodo 2007 - 2009. Resultados: Se realizaron 32 trasplantes renales, 30 (93,75%) de donantes vivos relacionados, 1 (3,13%) no relacionado, 1 (3,13%) cadavérico, 14 (43,75%) fueron varones, 18 (56,25%) mujeres, 18 (56,25%) niños y 14 (43,75%) adultos. La edad promedio fue: 21,5 ± 12,14 años (9,3 û 65,3), el promedio de espera en diálisis fue: 2,04 ± 1,79 (0,3 û 6,36) años. El tiempo de anastomosis arterial, venosa, isquemia caliente y fría fue: 32,28 ± 15,52 (15 - 79) min, 31 ± 9,7 (20 - 60) min, 1,72 ± 1,02 (0,83 û 3,28) min, 2,5 ± 0,56 (1 û 16) horas respectivamente. La terapia de inducción fue: Globulina Antitimocítica en 20 casos y la de mantenimiento, fue: Tacrolimus, Ciclosporina, Micofenolato de Mofetil y Prednisona. Las complicaciones quirúrgicas: linfocele (4), linforragia (1), fístula ureteral (1), falla de anastomosis primaria con doble arteria (1) y trombosis arterial (1). Las médicas: infección del tracto urinario (12), necrosis tubular aguda (5), rechazo agudo (6), nefrotoxicidad (2), recidiva de la enfermedad primaria (1) y neumonía AH1N1 (1). Tiempo promedio de seguimiento: 11,25 ± 7,03 (2,4 û 27,4) meses y la tasa de filtración glomerular promedio es de 76,47 ± 22,52 (30 û 140) ml/ min./1,73 m2sc. Conclusión: Es factible realizar trasplante renal con resultados comparables a estándares internacionales en un hospital del Ministerio de Salud, implementando un programa con financiamiento público, dirigido a la población pobre y de extrema pobreza.

Introduction: The Integral Health Insurance started a support program to finance renal replacement therapies. Objetive: We present preliminary results of the Pilot Program Renal Transplantation of Cayetano Heredía National Hospital û Public Health. Material and method: Case series of renal transplantation period 2007 to 2009. Results: we performed 32 living-related donor 30 (93.75%), unrelated 1 (3.13%), cadáver 1 (3.13%), 14 (43.75%) men, 18 (56.25%) women, 18 (56.25%) children and 14 (43.75%) adults. The average age was 21.5 ± 12.14 years (9.3 û 65.3), average waiting time on díalysis was 2.04 ± 1.79 (0.3 û 6.36) years. Time of arterial and venous anastomosis, warm ischemia and cold was 32.28 ± 15.52 (15-79) min, 31 ± 9.7 (20 - 60) min, 1.72 ± 1.02 (0.83 û 3.28) min, 2.5 ± 0.56 (1 û 16) hours respectively. Induction therapy it was Antithymocyte Globulin in 20 cases and maintenance therapy: it was Tacrolimus, Cyclosporine, mycophenolate mofetil and prednisone. Surgical complications: lymphocele (4), lymphatic leakage (1), ureteral fistula (1), primary anastomosis failure with double renal artery (1) and arterial thrombosis (1). Medical: urinary tract infection (12), acute tubular necrosis (5), acute rejection (6), nephrotoxicity (2), recurrence of primary disease (1) and AH1N1 pneumonia (1). The mean time of follow-up was: 11.25 ± 7.03 (2.4 û27.4) months; the glomerular filtration rate average is 76.47 ± 22.52 (30 û 140) ml/min./1.73 m2sc. Conclusion: Renal transplantation in a public hospital is feasible with good results comparable to international standards, implementing a public health financing program and targeting poor populations and in extreme poverty.

Nuevas fronteras en hipertensión arterial: mecanismos, evolución, tratamiento y pronóstico / New frontier in arterial hypertension mechanisms, evolution, therapy and prognostic

Trabajos presentados en el symposiom sobre nuevas fronteras en Hipertensión Arterial. Investigadosres de España, Estados Unidos, Italia y Venezuela desarrollan sus ponencias teniendo como objetivos: a) actualizar los principales macanismos que se han involucrado en la etiología y la patología de la hipertensión arterial promaría, b) asentar criterios conceptuales y practicos en la evaluación del paciente hipertenso, c) revisar criticamente las bases sobre los cuales se sustenta el tratamiento del paciente hipertenso, d) discutir desde el punto de vista epidemiológico y clínico, como podemos enfocar y mejorar el pronóstico de esos pacientes