The potential for quality assurance systems to save costs and lives:the case of early infant diagnosis of HIV

OBJECTIVES: Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems. METHODS: We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses. RESULTS: The modelled 1-year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030. CONCLUSIONS: The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT

PATOGENICIDADE DE ESPÉCIES DE Macrophomina COLETADAS DE PLANTAS DANINHAS EM FEIJÃO-CAUPI

[PT] A podridão de carvão causada por Macrophomina phaseolina é uma das principais doenças do feijão-caupi, causando perdas substanciais para os produtores. Na região semiárida do Brasil, o feijão-caupi é uma das alternativas utilizadas para rotação de culturas durante a entressafra do melão. Isso favorece a multiplicação de Macrophomina, uma vez que ambas as culturas são hospedeiras desse patógeno. O objetivo deste estudo foi verificar a patogenicidade em caupi de Macrophomina phaseolina e M. pseudophaseolina em caupi. Isolados de Macrophomina spp. obtidos das raízes de Trianthema portulacastrum e Boerhavia diffusa, espécies de plantas daninhas prevalentes em áreas de produção de melão no Nordeste brasileiro foram utilizadas neste estudo. O experimento foi realizado em casa de vegetação. Plantas de feijão-caupi 'Paulistinha' foram inoculados com 30 isolados de M. phaseolina, 30 isolados de M. pseudophaseolina e um isolado de referência de M. phaseolina obtido de raízes de feijão-caupi. Todos os isolados de Macrophomina foram patogênicos ao feijão-caupi, não havendo diferenças estatísticas entre as duas espécies de Macrophomina em relação à incidência e severidade da doença. Além disso, 65,2 e 100,0% dos isolados de M. phaseolina, e 56,2 e 92,8% dos isolados de M. pseudophaseolina, obtidos de T. portulacastrum e B. diffusa, respectivamente, foram tão severos ao feijão-caupi quanto o isolado de referência. Esses resultados enfatizam a necessidade de estabelecer práticas de manejo visando o controle de T. portucalastrum e B. diffusa nas áreas de produção de feijão-caupi, pois podem atuar como fontes de inóculo e sobrevivência para Macrophomina spp.[EN] Charcoal rot caused by Macrophomina phaseolina is a major cowpea disease causing substantial losses to growers. In the semi-arid region of Brazil, cowpea is one of the most widely used alternatives for crop rotation during the off-season of melon. This favors Macrophomina multiplication because both crops are hosts of this pathogen. The objective of this study was to verify the pathogenicity of Macrophomina phaseolina and M. pseudophaseolina on cowpea. The Macrophomina spp. isolates used were obtained from the roots of Trianthema portulacastrum and Boerhavia diffusa, weed species prevalent in melon production areas in North-east Brazilian The experiment was carried out in a greenhouse. Cowpea plants cv. Paulistinha' were inoculated with 30 M. phaseolina isolates, 30 M. pseudophaseolina isolates and a reference isolate of H. phaseolina obtained from cowpea roots. All Macrophomina isolates were able to cause disease on cowpea and there were no statistical differences between both Macrophomina species regarding disease incidence and severity. Moreover, 65.2 and 100.0% of the M. phaseolina isolates, and 56.2 and 92.8% of the M. pseudophaseolina isolates, obtained from T. portulacastrum and B. diffusa, respectively, were as severe to cowpea as the M. phaseolina reference isolate from cowpea. These results emphasize the need to establish management practices aiming to control T. portucalastrum and B. diffusa from cowpea production areas, as they can act as potential sources of inoculum and survival for Macrophomina spp.This study was partially financed by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brazil (CAPES) -Finance Code 001 and by the Conselho Nacional de desenvolvimento Cientifico e Tecnologico (CNPq).Sales Jr., R.; Nogueira, A.; Mitsa Paiva Negreiros, A.; Rodrigues, T.; De Queiroz, M.; Armengol Fortí, J. (2020). PATHOGENICITY OF Macrophomina SPECIES COLLECTED FROM WEEDS IN COWPEA. Revista Caatinga. 33(2):395-401. https://doi.org/10.1590/1983-21252020v33n212rcS395401332Ambrósio, M. M. Q., Dantas, A. C. A., Martínez-Perez, E., Medeiros, A. C., Nunes, G. H. S., & Picó, M. B. (2015). Screening a variable germplasm collection of Cucumis melo L. for seedling resistance to Macrophomina phaseolina. Euphytica, 206(2), 287-300. doi:10.1007/s10681-015-1452-xFreitas, F. C. L., Medeiros, V. F. L. P., Grangeiro, L. C., Silva, M. G. O., Nascimento, P. G. M. L., & Nunes, G. H. (2009). Interferência de plantas daninhas na cultura do feijão-caupi. Planta Daninha, 27(2), 241-247. doi:10.1590/s0100-83582009000200005Gomes-Silva, F., Almeida, C. M. A., Silva, A. G., Leão, M. P. C., Silva, K. P., Oliveira, L. G., … Lima, V. L. M. (2017). Genetic Diversity of Isolates of Macrophomina phaseolina Associated with Cowpea from Brazil Semi-Arid Region. Journal of Agricultural Science, 9(11), 112. doi:10.5539/jas.v9n11p112Gupta, G. K., Sharma, S. K., & Ramteke, R. (2012). Biology, Epidemiology and Management of the Pathogenic Fungus Macrophomina phaseolina (Tassi) Goid with Special Reference to Charcoal Rot of Soybean (Glycine max (L.) Merrill). Journal of Phytopathology, 160(4), 167-180. doi:10.1111/j.1439-0434.2012.01884.xKaur, S., Dhillon, G. S., Brar, S. K., Vallad, G. E., Chand, R., & Chauhan, V. B. (2012). Emerging phytopathogenMacrophomina phaseolina: biology, economic importance and current diagnostic trends. Critical Reviews in Microbiology, 38(2), 136-151. doi:10.3109/1040841x.2011.640977Machado, A. R., Pinho, D. B., Soares, D. J., Gomes, A. A. M., & Pereira, O. L. (2018). Bayesian analyses of five gene regions reveal a new phylogenetic species of Macrophomina associated with charcoal rot on oilseed crops in Brazil. European Journal of Plant Pathology, 153(1), 89-100. doi:10.1007/s10658-018-1545-1Mbaye, N., Mame, P. S., Ndiaga, C., & Ibrahima, N. (2015). Is the recently described Macrophomina pseudophaseolina pathogenically different from Macrophomina phaseolina? African Journal of Microbiology Research, 9(45), 2232-2238. doi:10.5897/ajmr2015.7742Negreiros, A. M. P., Sales Júnior, R., León, M., Melo, N. J., Michereff, S. J., Ambrósio, M. M., … Armengol, J. (2019). Identification and pathogenicity of Macrophomina species collected from weeds in melon fields in Northeastern Brazil. Journal of Phytopathology, 167(6), 326-337. doi:10.1111/jph.12801Negreiros, A. M. P., Júnior, R. S., Rodrigues, A. P. M. S., León, M., & Armengol, J. (2019). Prevalent weeds collected from cucurbit fields in Northeastern Brazil reveal new species diversity in the genusMonosporascus. Annals of Applied Biology, 174(3), 349-363. doi:10.1111/aab.12493Ramos, H. M. M., Bastos, E. A., Andrade Júnior, A. S. de, & Marouelli, W. A. (2012). Estratégias ótimas de irrigação do feijão‑caupi para produção de grãos verdes. Pesquisa Agropecuária Brasileira, 47(4), 576-583. doi:10.1590/s0100-204x2012000400014Reis, E. M., Boaretto, C., & Danelli, A. L. D. (2014). Macrophomina phaseolina: density and longevity of microsclerotia in soybean root tissues and free on the soil, and competitive saprophytic ability. Summa Phytopathologica, 40(2), 128-133. doi:10.1590/0100-5405/1921Rocha, M. de M., Carvalho, K. J. M. de, Freire Filho, F. R., Lopes, Â. C. de A., Gomes, R. L. F., & Sousa, I. da S. (2009). Controle genético do comprimento do pedúnculo em feijão-caupi. Pesquisa Agropecuária Brasileira, 44(3), 270-275. doi:10.1590/s0100-204x2009000300008Sales Junior, R., Oliveira, O. F. de, Medeiros, É. V. de, Guimarães, I. M., Correia, K. C., & Michereff, S. J. (2012). Ervas daninhas como hospedeiras alternativas de patógenos causadores do colapso do meloeiro. Revista Ciência Agronômica, 43(1), 195-198. doi:10.1590/s1806-66902012000100024Sales Júnior, R., Rodrigues, A. P. M. dos S., Negreiros, A. M. P., Ambrósio, M. M. de Q., Barboza, H. da S., & Beltrán, R. (2019). WEEDS AS POTENTIAL HOSTS FOR FUNGAL ROOT PATHOGENS OF WATERMELON. Revista Caatinga, 32(1), 1-6. doi:10.1590/1983-21252019v32n101rcFrancisco, de A. S. e S., & Carlos, A. V. de A. (2016). The Assistat Software Version 7.7 and its use in the analysis of experimental data. African Journal of Agricultural Research, 11(39), 3733-3740. doi:10.5897/ajar2016.11522Silva, M. G. O. da, Freitas, F. C. L. de, Negreiros, M. Z. de, Mesquita, H. C. de, Santana, F. A. O. de, & Lima, M. F. P. de. (2013). Manejo de plantas daninhas na cultura da melancia nos sistemas de plantio direto e convencional. Horticultura Brasileira, 31(3), 494-499. doi:10.1590/s0102-05362013000300025Zhao, L., Cai, J., He, W., & Zhang, Y. (2019). Macrophomina vaccinii sp. nov. causing blueberry stem blight in China. MycoKeys, 55, 1-14. doi:10.3897/mycokeys.55.3501

LUBAC prevents lethal dermatitis by inhibiting cell death induced by TNF, TRAIL and CD95L

The linear ubiquitin chain assembly complex (LUBAC), composed of HOIP, HOIL-1 and SHARPIN, is required for optimal TNF-mediated gene activation and to prevent cell death induced by TNF. Here, we demonstrate that keratinocyte-specific deletion of HOIP or HOIL-1 (E-KO) results in severe dermatitis causing postnatal lethality. We provide genetic and pharmacological evidence that the postnatal lethal dermatitis in HoipE-KO and Hoil-1E-KO mice is caused by TNFR1-induced, caspase-8-mediated apoptosis that occurs independently of the kinase activity of RIPK1. In the absence of TNFR1, however, dermatitis develops in adulthood, triggered by RIPK1-kinase-activity-dependent apoptosis and necroptosis. Strikingly, TRAIL or CD95L can redundantly induce this disease-causing cell death, as combined loss of their respective receptors is required to prevent TNFR1-independent dermatitis. These findings may have implications for the treatment of patients with mutations that perturb linear ubiquitination and potentially also for patients with inflammation-associated disorders that are refractory to inhibition of TNF alone

Defining Major Surgery: A Delphi Consensus Among European Surgical Association (ESA) Members

Background: Major surgery is a term frequently used but poorly defined. The aim of the present study was to reach a consensus in the definition of major surgery within a panel of expert surgeons from the European Surgical Association (ESA). Methods: A 3-round Delphi process was performed. All ESA members were invited to participate in the expert panel. In round 1, experts were inquired by open- and closed-ended questions on potential criteria to define major surgery. Results were analyzed and presented back anonymously to the panel within next rounds. Closed-ended questions in round 2 and 3 were either binary or statements to be rated on a Likert scale ranging from 1 (strong disagreement) to 5 (strong agreement). Participants were sent 3 reminders at 2-week intervals for each round. 70% of agreement was considered to indicate consensus. Results: Out of 305 ESA members, 67 (22%) answered all the 3 rounds. Significant comorbidities were the only preoperative factor retained to define major surgery (78%). Vascular clampage or organ ischemia (92%), high intraoperative blood loss (90%), high noradrenalin requirements (77%), long operative time (73%) and perioperative blood transfusion (70%) were procedure-related factors that reached consensus. Regarding postoperative factors, systemic inflammatory response (76%) and the need for intensive or intermediate care (88%) reached consensus. Consequences of major surgery were high morbidity (>30% overall) and mortality (>2%). Conclusion: ESA experts defined major surgery according to extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes

Quantitative Analysis of Vasodilatory Action of Quercetin on Intramural Coronary Resistance Arteries of the Rat In Vitro

Background: Dietary quercetin improves cardiovascular health, relaxes some vascular smooth muscle and has been demonstrated to serve as a substrate for the cyclooxygenase enzyme. Aims: 1. To test quantitatively a potential direct vasodilatory effect on intramural coronary resistance artery segments, in different concentrations. 2. To scale vasorelaxation at different intraluminal pressure loads on such vessels of different size. 3. To test the potential role of prostanoids in vasodilatation induced by quercetin. Methods: Coronary arterioles (70-240 mu m) were prepared from 24 rats and pressurized in PSS, using a pressure microangiometer. Results: The spontaneous tone that developed at 50 mmHg was relaxed by quercetin in the 10(-9) moles/lit concentration (p<0.05), while 10(-5) moles/lit caused full relaxation. Significant relaxation was observed at all pressure levels (10-100 mmHg) at 10(-7) moles/lit concentration of quercetin. The cyclooxygenase blocker indomethacin (10(-5) moles/lit) induced no relaxation but contraction when physiological concentrations of quercetin were present in the tissue bath (p<0.02 with Anova), this contraction being more prominent in smaller vessels and in the higher pressure range (p<0.05, Pearson correlation). A further 2-8% contraction could be elicited by the NO blocker L-NAME (10(-4) moles/lit). Conclusion: These results demonstrate that circulating levels of quercetin (10(-7) moles/lit) exhibit a substantial coronary vasodilatory effect. The extent of it is commeasurable with that of several other physiological mechanisms of coronary blood flow control. At least part of this relaxation is the result of an altered balance toward the production of endogenous vasodilatory prostanoids in the coronary arteriole wall

Management of Massive Arterial Hemorrhage After Pancreatobiliary Surgery: Does Embolotherapy Contribute to Successful Outcome?

Massive arterial hemorrhage is, although unusual, a life-threatening complication of major pancreatobiliary surgery. Records of 351 patients who underwent major surgery for malignant pancreatobiliary disease were reviewed in this series. Thirteen patients (3.7%) experienced massive hemorrhage after surgery. Complete hemostasis by transcatheter arterial embolization (TAE) or re-laparotomy was achieved in five patients and one patient, respectively. However, 7 of 13 cases ended in fatality, which is a 54% mortality rate. Among six survivors, one underwent selective TAE for a pseudoaneurysm of the right hepatic artery (RHA). Three patients underwent TAE proximal to the proper hepatic artery (PHA): hepatic inflow was maintained by successful TAE of the gastroduodenal artery in two and via a well-developed subphrenic artery in one. One patient had TAE of the celiac axis for a pseudoaneurysm of the splenic artery (SPA), and hepatic inflow was maintained by the arcades around the pancreatic head. One patient who experienced a pseudoaneurysm of the RHA after left hemihepatectomy successfully underwent re-laparotomy, ligation of RHA, and creation of an ileocolic arterioportal shunt. In contrast, four of seven patients with fatal outcomes experienced hepatic infarction following TAE proximal to the PHA or injury of the common hepatic artery during angiography. One patient who underwent a major hepatectomy for hilar bile duct cancer had a recurrent hemorrhage after TAE of the gastroduodenal artery and experienced hepatic failure. In the two patients with a pseudoaneurysm of the SPA or the superior mesenteric artery, an emergency re-laparotomy was required to obtain hemostasis because of worsening clinical status. Selective TAE distal to PHA or in the SPA is usually successful. TAE proximal to PHA must be restricted to cases where collateral hepatic blood flow exists. Otherwise or for a pseudoaneurysm of the superior mesenteric artery, endovascular stenting, temporary creation of an ileocolic arterioportal shunt, or vascular reconstruction by re-laparotomy is an alternative

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd

Antibody-Mediated Growth Inhibition of Plasmodium falciparum: Relationship to Age and Protection from Parasitemia in Kenyan Children and Adults

BACKGROUND: Antibodies that impair Plasmodium falciparum merozoite invasion and intraerythrocytic development are one of several mechanisms that mediate naturally acquired immunity to malaria. Attempts to correlate anti-malaria antibodies with risk of infection and morbidity have yielded inconsistent results. Growth inhibition assays (GIA) offer a convenient method to quantify functional antibody activity against blood stage malaria. METHODS: A treatment-time-to-infection study was conducted over 12-weeks in a malaria holoendemic area of Kenya. Plasma collected from healthy individuals (98 children and 99 adults) before artemether-lumefantrine treatment was tested by GIA in three separate laboratories. RESULTS: Median GIA levels varied with P. falciparum line (D10, 8.8%; 3D7, 34.9%; FVO, 51.4% inhibition). The magnitude of growth inhibition decreased with age in all P. falciparum lines tested with the highest median levels among children \u3c4 years compared to adults (e.g. 3D7, 45.4% vs. 30.0% respectively, p = 0.0003). Time-to-infection measured by weekly blood smears was significantly associated with level of GIA controlling for age. Upper quartile inhibition activity was associated with less risk of infection compared to individuals with lower levels (e.g. 3D7, hazard ratio = 1.535, 95% CI = 1.012-2.329; p = 0.0438). Various GIA methodologies had little effect on measured parasite growth inhibition. CONCLUSION: Plasma antibody-mediated growth inhibition of blood stage P. falciparum decreases with age in residents of a malaria holoendemic area. Growth inhibition assay may be a useful surrogate of protection against infection when outcome is controlled for age