A FRET-based cGMP biosensor in Drosophila

CUTie2 is a FRET-based cGMP biosensor tested so far only in cells. To expand its use to multicellular organisms we generated two transgenic Drosophila melanogaster strains that express the biosensor in a tissue-dependent manner. CUTie2 expression and subcellular localization was verified by confocal microscopy. The performance of CUTie2 was analyzed on dissected larval brains by hyperspectral microscopy and flow cytometry. Both approaches confirmed its responsivity, and the latter showed a rapid and reversible change in the fluorescence of the FRET acceptor upon cGMP treatment. This validated reporter system may prove valuable for studying cGMP signaling at organismal level.Agencia Nacional de Investigación e InnovaciónDirección Nacional de Innovación, Ciencia y Tecnologí

Interventions Reducing Racial/Ethnic Disparities Across the Cancer Care Continuum: A Scoping Review

https://openworks.mdanderson.org/sumexp23/1126/thumbnail.jp

The Market for Organic Black Tea in Germany and the United States

This market research paper has been prepared under the supervision of Prof. Dr. Wolfgang Veit of TH Köln and Prof. Dr. Carol Scovotti of University of Wisconsin-Whitewater in the course of the inter-university cross-border collaboration student research project “Export Opportunity Surveys (EOS)”. This study explores organic black tea export opportunities to the German and US markets

New heterobimetallic ferrocenyl derivatives are promising antitrypanosomal agents

In the search for a more effective chemotherapy for the treatment of Chagas´ disease and human African trypanosomiasis, caused by Trypanosoma cruzi and Trypanosoma brucei parasites, respectively, the use of organometallic compounds may be a promising strategy. In this work, eight new heterobimetallic compounds are described including four 5-nitrofuryl containing thiosemicarbazones as bioactive ligands (HL1-HL4) and dppf = 1,1′-bis(diphenylphosphino) ferrocene as an organometallic co-ligand. Complexes of the formula [MII(L)(dppf)](PF6) with M = Pd or Pt were synthesized and fully characterized in the solid state and in solution, including the determination of the molecular structure of four of them by single crystal X-ray diffraction methods. Most compounds showed activity in the low micromolar or submicromolar range against both parasites, with the platinum compounds being more active than the palladium analogues. Activity was significantly increased by generation of the M-dppf compounds (3-24 fold increase with respect to free ligands HL for T. cruzi and up to 99 fold increase with respect to HL for T. brucei). The inclusion of the organometallic co-ligand also led to lower toxicity in mammalian cells and higher selectivity towards both parasites when compared to the free HL compounds. The complexes interact with DNA and affect the redox metabolism of the parasites. Furthermore, the most active and selective compound of the new series showed no in vivo toxicity in zebrafish embryos.Fil: Rodríguez Arce, Esteban. Universidad de la República; UruguayFil: Putzu, Eugenia. Universidad de la República; UruguayFil: Lapier, Michel. Universidad de Chile; ChileFil: Maya, Juan Diego. Universidad de Chile; ChileFil: Olea Azar, Claudio. Universidad de Chile; ChileFil: Echeverría, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Piro, Oscar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Medeiros, Andrea. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Sardi, Florencia. Instituto Pasteur de Montevideo; UruguayFil: Comini, Marcelo. Instituto Pasteur de Montevideo; UruguayFil: Risi, Gastón. Instituto Pasteur de Montevideo; UruguayFil: Salinas, Gustavo. Instituto Pasteur de Montevideo; UruguayFil: Abad Villamor, Ana Isabel. Instituto Superior Técnico; PortugalFil: Pessoa, João Costa. Instituto Superior Técnico; PortugalFil: Otero, Lucía. Universidad de la República; UruguayFil: Gambino, Dinorah. Universidad de la República; Urugua

Mitochondrial Redox Metabolism in Trypanosomatids Is Independent of Tryparedoxin Activity

Tryparedoxins (TXNs) are oxidoreductases unique to trypanosomatids (including Leishmania and Trypanosoma parasites) that transfer reducing equivalents from trypanothione, the major thiol in these organisms, to sulfur-dependent peroxidases and other dithiol proteins. The existence of a TXN within the mitochondrion of trypanosomatids, capable of driving crucial redox pathways, is considered a requisite for normal parasite metabolism. Here this concept is shown not to apply to Leishmania. First, removal of the Leishmania infantum mitochondrial TXN (LiTXN2) by gene-targeting, had no significant effect on parasite survival, even in the context of an animal infection. Second, evidence is presented that no other TXN is capable of replacing LiTXN2. In fact, although a candidate substitute for LiTXN2 (LiTXN3) was found in the genome of L. infantum, this was shown in biochemical assays to be poorly reduced by trypanothione and to be unable to reduce sulfur-containing peroxidases. Definitive conclusion that LiTXN3 cannot directly reduce proteins located within inner mitochondrial compartments was provided by analysis of its subcellular localization and membrane topology, which revealed that LiTXN3 is a tail-anchored (TA) mitochondrial outer membrane protein presenting, as characteristic of TA proteins, its N-terminal end (containing the redox-active domain) exposed to the cytosol. This manuscript further proposes the separation of trypanosomatid TXN sequences into two classes and this is supported by phylogenetic analysis: i) class I, encoding active TXNs, and ii) class II, coding for TA proteins unlikely to function as TXNs. Trypanosoma possess only two TXNs, one belonging to class I (which is cytosolic) and the other to class II. Thus, as demonstrated for Leishmania, the mitochondrial redox metabolism in Trypanosoma may also be independent of TXN activity. The major implication of these findings is that mitochondrial functions previously thought to depend on the provision of electrons by a TXN enzyme must proceed differently

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Devolução dos resultados de exames sorológicos de HIV/IST entre pacientes psiquiátricos nos serviços de saúde mental

OBJECTIVE: To assess individual and/or health service factors associated with patients returning for results of HIV or sexually transmitted infection (STI) tests in mental health centers. METHODS: Cross-sectional national multicenter study among 2,080 patients randomly selected from 26 Brazilian mental health centers in 2007. Multilevel logistic regression was used to assess the effect of individual (level 1) and mental health service characteristics (level 2) on receipt of test results. RESULTS: The rate of returning HIV/STI test results was 79.6%. Among health service characteristics examined, only condom distribution was associated with receiving HIV/STI test results, whereas several individual characteristics were independently associated including living in the same city where treatment centers are; being single; not having heard of AIDS; and not having been previously HIV tested. CONCLUSIONS: It is urgent to expand HIV/STI testing in health services which provide care for patients with potentially increased vulnerability to these conditions, and to promote better integration between mental health and health services.OBJETIVO: Analizar factores asociados a la recepción de resultados de exámenes serológicos para VIH y otras infecciones de transmisión sexual (ITS) entre pacientes psiquiátricos. MÉTODOS: Estudio de corte transversal multicéntrico nacional de 2.080 participantes seleccionados aleatoriamente entre 26 instituciones brasileñas de salud mental en 2007. El efecto del individuo (nivel 1) y de los servicios de salud mental (nivel 2) en la recepción de los resultados de los exámenes fue evaluado utilizándose regresión logística multinivel. RESULTADOS: La proporción de retorno de los resultados de exámenes VIH/ITS fue 79,6%. Entre las características individuales, hubo asociación del desenlace con: vivir en la misma ciudad donde se encontraban los servicios, ser soltero, no haber escuchado hablar sobre el sida, y no haber sido previamente evaluado para VIH. Entre las características de los servicios de salud, sólo la distribución de preservativos estuvo asociada a la recepción de los resultados de los exámenes. CONCLUSIONES: El retorno de los resultados de exámenes indicó que es urgente promover una mejor integración entre los servicios de salud, así como expandir la oferta de examen anti-VIH y otras ITS, en especial en servicios de atención a pacientes psiquiátricos potencialmente más vulnerables a estas condiciones.OBJETIVO: Analisar fatores associados ao recebimento de resultados de exames sorológicos para HIV e outras infecções sexualmente transmissíveis (IST) entre pacientes psiquiátricos. MÉTODOS: Estudo de corte transversal multicêntrico nacional de 2.080 participantes selecionados aleatoriamente dentre 26 instituições de saúde mental brasileiras em 2007. O efeito do indivíduo (nível 1) e dos serviços de saúde mental (nível 2) no recebimento dos resultados dos exames foi avaliado utilizando-se regressão logística multinível. RESULTADOS: A proporção de retorno dos resultados de exames HIV/IST foi de 79,6%. Entre as características individuais, houve associação do desfecho com: viver na mesma cidade onde se encontravam os serviços, ser solteiro, não ter ouvido falar sobre aids e não ter sido previamente testado para HIV. Entre as características dos serviços de saúde, apenas distribuição de preservativos esteve associada ao recebimento dos resultados de exames. CONCLUSÕES: É urgente promover melhor integração entre os serviços de saúde, além de expandir a oferta de exame anti-HIV e outras IST, em especial em serviços de atenção a pacientes psiquiátricos potencialmente mais vulneráveis a essas condições