Is long-term follow-up solely by imaging tests safe in non-operated pancreatic neuroendocrine tumors?

INTRODUCTION: the diagnosis of asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has increased significantly due to the widespread use of high-resolution imaging tests, which is why the most appropriate management at the time of diagnosis is the subject of debate, as is how to follow-up patients. AIMS: the objective of this study was to analyze the frequency of imaging and endoscopic studies performed during long-term follow-up. METHODS: a retrospective review was performed of a database collected between January 2008 and December 2020 of patients with an incidental diagnosis of small NF-PNETs; follow-up was closed in March 2023. The imaging tests performed at the time of diagnosis and long-term follow-up were recorded. Growing less than 1 mm per year has not been considered as a worrisome feature. Follow-up was performed through imaging tests, considering endoscopic cytology for lesions with a faster grow rate. RESULTS: fifty-eight patients were included; the median age was 69 years. The initial mean size of the lesions studied was 12.79 mm (5-27). Follow-up was carried out only with computed tomography (CT) or magnetic resonance imaging (MRI). The initial size did not influence the behavior of the lesion in a statistically significant manner. Twenty-eight tumors (45 %) increased in size, with a growth equal to or less than 4 mm in 24 cases. The mean follow-up time was 82.41 months (12-164). No patient developed metastasis or died from PNET progression. CONCLUSIONS: the follow-up of neuroendocrine tumors of small size can be performed safely with only imaging tests.

Is long-term follow-up solely by imaging tests safe in non-operated pancreatic neuroendocrine tumors?

Introduction: the diagnosis of asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has increased significantly due to the widespread use of high-resolution imaging tests, which is why the most appropriate management at the time of diagnosis is the subject of debate, as is how to follow-up patients. Aims: the objective of this study was to analyze the frequency of imaging and endoscopic studies performed during long-term follow-up. Methods: a retrospective review was performed of a database collected between January 2008 and December 2020 of patients with an incidental diagnosis of small NF-PNETs; follow-up was closed in March 2023. The imaging tests performed at the time of diagnosis and long-term follow-up were recorded. Growing less than 1 mm per year has not been considered as a worrisome feature. Follow-up was performed through imaging tests, considering endoscopic cytology for lesions with a faster grow rate. Results: fifty-eight patients were included; the median age was 69 years. The initial mean size of the lesions studied was 12.79 mm (5-27). Follow-up was carried out only with computed tomography (CT) or magnetic resonance imaging (MRI). The initial size did not influence the behavior of the lesion in a statistically significant manner. Twenty-eight tumors (45 %) increased in size, with a growth equal to or less than 4 mm in 24 cases. The mean follow-up time was 82.41 months (12-164). No patient developed metastasis or died from PNET progression. Conclusions: the follow-up of neuroendocrine tumors of small size can be performed safely with only imaging tests. (AU)

Hypoalbuminemia and advanced age are risk factors for delayed gastric emptying after pancreaticoduodenectomy / La hipoalbuminemia y la edad avanzada son factores de riesgo de vaciamiento gástrico lento tras duodenopancreatectomía cefálica

Background: delayed gastric emptying (DGE) is one of the most common complications after pancreatoduodenectomy. It could be related to some baseline patient-related characteristics. This study aims to assess the predictive factors associated to DGE in the cohort of patients included in the PAUDA clinical trial. Methods: this study was a retrospective analysis based on the 80 patients included in a randomized clinical trial conducted and published by our group. A descriptive analysis and a bivariate regression model were carried out. Some factors were further scrutinized for associations using the Pearson correlation coefficient and, finally, a multiple regression model using a stepwise selection of variables was conducted. Results: DGE was diagnosed in 36 (45 %) out of 80 patients (DGE group). The number of patients older than 60 years old in the DGE group was greater than in the group without DGE (32 vs 28 patients, p = 0.009]. Likewise, the number of patients with a preoperative albumin < 35 g/L (18 vs 11 patients, p = 0.036); preoperative bilirubin > 200 µmol/L (14 vs 8 patients, p = 0.039); postoperative haemorrhage (7 vs 1 patients, p = 0.011); postoperative intraabdominal abscess (12 vs 5 patients, p = 0.017); and postoperative biliary fistula (5 vs 0 patients, p = 0.011), was also greater in the DGE group. Two risk factors were associated with DGE: the patient's age at the time of surgery and preoperative hypoalbuminemia (serum albumin concentration ≤ 35g/L). Conclusions: the patient's age at the time of surgery and the preoperative nutritional status are independent risk factors to the development of DGE after pancreatoduodenectomy. (AU)

Introducción: el vaciamiento gástrico lento (VGL) es una complicación frecuente tras la duodenopancreatectomía cefálica (DPC) y puede relacionarse con algunas características basales del paciente. El objetivo es evaluar los factores predictivos de VGL en la cohorte de pacientes incluidos en el ensayo clínico aleatorizado PAUDA. Métodos: se realizó un análisis retrospectivo basado en los 80 pacientes incluidos en el ensayo PAUDA. Se realizaron un análisis descriptivo y un modelo de regresión bivariante. Posteriormente, algunos factores se examinaron mediante el coeficiente de correlación de Pearson y, finalmente, se llevó a cabo un modelo de regresión multivariante. Resultados: se diagnosticó VGL en 36 (45 %) pacientes. El número de pacientes mayores de 60 años en el grupo VGL fue mayor que en el grupo sin VGL (p = 0,009). El número de pacientes con albúmina preoperatoria < 35 g/L (p = 0,036); bilirrubina preoperatoria > 200 µmol/L (p = 0,039); hemorragia (p = 0,011); absceso intraabdominal (p = 0,017); y fístula biliar (p = 0,011), fue mayor en el grupo VGL. Dos factores de riesgo se asociaron con el VGL: la edad del paciente y la hipoalbuminemia preoperatoria. Conclusiones: la edad del paciente en el momento de la cirugía y el estado nutricional preoperatorio son factores de riesgo independientes de VGL tras DPC. (AU)

Hypoalbuminemia and advanced age are risk factors for delayed gastric emptying after pancreaticoduodenectomy.

Introduction: Background: delayed gastric emptying (DGE) is one of the most common complications after pancreatoduodenectomy. It could be related to some baseline patient-related characteristics. This study aims to assess the predictive factors associated to DGE in the cohort of patients included in the PAUDA clinical trial. Methods: this study was a retrospective analysis based on the 80 patients included in a randomized clinical trial conducted and published by our group. A descriptive analysis and a bivariate regression model were carried out. Some factors were further scrutinized for associations using the Pearson correlation coefficient and, finally, a multiple regression model using a stepwise selection of variables was conducted. Results: DGE was diagnosed in 36 (45 %) out of 80 patients (DGE group). The number of patients older than 60 years old in the DGE group was greater than in the group without DGE (32 vs 28 patients, p = 0.009]. Likewise, the number of patients with a preoperative albumin < 35 g/L (18 vs 11 patients, p = 0.036); preoperative bilirubin > 200 µmol/L (14 vs 8 patients, p = 0.039); postoperative haemorrhage (7 vs 1 patients, p = 0.011); postoperative intraabdominal abscess (12 vs 5 patients, p = 0.017); and postoperative biliary fistula (5 vs 0 patients, p = 0.011), was also greater in the DGE group. Two risk factors were associated with DGE: the patient's age at the time of surgery and preoperative hypoalbuminemia (serum albumin concentration ≤ 35g/L). Conclusions: the patient's age at the time of surgery and the preoperative nutritional status are independent risk factors to the development of DGE after pancreatoduodenectomy.

Introducción: Introducción: el vaciamiento gástrico lento (VGL) es una complicación frecuente tras la duodenopancreatectomía cefálica (DPC) y puede relacionarse con algunas características basales del paciente. El objetivo es evaluar los factores predictivos de VGL en la cohorte de pacientes incluidos en el ensayo clínico aleatorizado PAUDA. Métodos: se realizó un análisis retrospectivo basado en los 80 pacientes incluidos en el ensayo PAUDA. Se realizaron un análisis descriptivo y un modelo de regresión bivariante. Posteriormente, algunos factores se examinaron mediante el coeficiente de correlación de Pearson y, finalmente, se llevó a cabo un modelo de regresión multivariante. Resultados: se diagnosticó VGL en 36 (45 %) pacientes. El número de pacientes mayores de 60 años en el grupo VGL fue mayor que en el grupo sin VGL (p = 0,009). El número de pacientes con albúmina preoperatoria < 35 g/L (p = 0,036); bilirrubina preoperatoria > 200 µmol/L (p = 0,039); hemorragia (p = 0,011); absceso intraabdominal (p = 0,017); y fístula biliar (p = 0,011), fue mayor en el grupo VGL. Dos factores de riesgo se asociaron con el VGL: la edad del paciente y la hipoalbuminemia preoperatoria. Conclusiones: la edad del paciente en el momento de la cirugía y el estado nutricional preoperatorio son factores de riesgo independientes de VGL tras DPC.

Treatment of early borderline lesions in low immunological risk kidney transplant patients: a Spanish multicenter, randomized, controlled parallel-group study protocol: the TRAINING study.

BACKGROUND: Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function. METHODS: The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression. DISCUSSION: This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL. TRIAL REGISTRATION: clinicaltrials.gov : NCT04936282. Registered June 23, 2021, https://clinicaltrials.gov/ct2/show/NCT04936282?term=NCT04936282&draw=2&rank=1 . Protocol Version 2 of 21 January 2022. SPONSOR: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). mgomez@fciisc.org .

Transcriptional response of a target plant to benzoxazinoid and diterpene allelochemicals highlights commonalities in detoxification.

BACKGROUND: Plants growing in proximity to other plants are exposed to a variety of metabolites that these neighbors release into the environment. Some species produce allelochemicals to inhibit growth of neighboring plants, which in turn have evolved ways to detoxify these compounds. RESULTS: In order to understand how the allelochemical-receiving target plants respond to chemically diverse compounds, we performed whole-genome transcriptome analysis of Arabidopsis thaliana exposed to either the benzoxazinoid derivative 2-amino- 3H-phenoxazin-3-one (APO) or momilactone B. These two allelochemicals belong to two very different compound classes, benzoxazinoids and diterpenes, respectively, produced by different Poaceae crop species. CONCLUSIONS: Despite their distinct chemical nature, we observed similar molecular responses of A. thaliana to these allelochemicals. In particular, many of the same or closely related genes belonging to the three-phase detoxification pathway were upregulated in both treatments. Further, we observed an overlap between genes upregulated by allelochemicals and those involved in herbicide detoxification. Our findings highlight the overlap in the transcriptional response of a target plant to natural and synthetic phytotoxic compounds and illustrate how herbicide resistance could arise via pathways involved in plant-plant interaction.

Extracellular Vesicles in Trypanosoma cruzi Infection: Immunomodulatory Effects and Future Perspectives as Potential Control Tools against Chagas Disease.

Chagas disease, caused by the protozoa parasite Trypanosoma cruzi, is a neglected tropical disease and a major public health problem affecting more than 6 million people worldwide. Many challenges remain in the quest to control Chagas disease: the diagnosis presents several limitations and the two available treatments cause several side effects, presenting limited efficacy during the chronic phase of the disease. In addition, there are no preventive vaccines or biomarkers of therapeutic response or disease outcome. Trypomastigote form and T. cruzi-infected cells release extracellular vesicles (EVs), which are involved in cell-to-cell communication and can modulate the host immune response. Importantly, EVs have been described as promising tools for the development of new therapeutic strategies, such as vaccines, and for the discovery of new biomarkers. Here, we review and discuss the role of EVs secreted during T. cruzi infection and their immunomodulatory properties. Finally, we briefly describe their potential for biomarker discovery and future perspectives as vaccine development tools for Chagas Disease.

Anti-Trypanosoma cruzi activity of alkaloids isolated from Habranthus brachyandrus (Amaryllidaceae) from Argentina.

BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi, affects over six million people worldwide, mainly in Latin American countries. Currently available drugs have variable efficacy in the chronic phase and significant side effects, so there is an urgent need for safer chemotherapeutic treatments. Natural products provide privileged structures that could serve as templates for the synthesis of new drugs. Among them, Amaryllidaceae plants have proved to be a potential natural source of therapeutical agents due to their rich diversity in alkaloids. PURPOSE: To identify alkaloids with anti-T. cruzi activity from Habranthus brachyandrus (Baker) Sealy (Amaryllidaceae, subfamily Amaryllidoideae) collected in Argentina. METHODS: An H. brachyandrus alkaloid extract was tested against T. cruzi, and its cytotoxicity profile was evaluated against two mammalian cell lines to ascertain its selectivity against the parasite and potential liver toxicity. It was also assessed by a stage-specific anti-amastigote assay and analysed by GC/MS to determine its alkaloid profile. The isolated alkaloids were also tested using the aforementioned assays. RESULTS: The extract showed high and specific activity against T. cruzi. The alkaloids lycoramine, galanthindole, 8-O-demethylmaritidine, 8-O-demethylhomolycorine, nerinine, trisphaeridine, deoxytazettine, and tazettamide were identified by means of GC-MS. In addition, hippeastidine (also named aulicine), tazzetine, ismine, and 3-epimacronine were isolated. The alkaloid ismine was specifically active against the parasite and had low toxicity against HepG2 cells, but did not show anti-amastigote activity. CONCLUSION: The extract had specific anti-T. cruzi activity and the isolated alkaloid ismine was partially responsible of it. These results encourage further exploration of H. brachyandrus alkaloids in search of novel starting points for Chagas disease drug development.

C3 glomerulopathy associated with monoclonal gammopathy: impact of chronic histologic lesions and beneficial effects of clone-targeted therapies.

BACKGROUND: C3 glomerulopathy associated with monoclonal gammopathy (C3G-MIg) is a rare entity. Herein we analysed the clinical and histologic features of a cohort of C3G-MIg patients. METHODS: We conducted a retrospective, multicentre, observational study. Patients diagnosed with C3G-MIg between 1995 and 2021 were enrolled. All had genetic studies of the alternative complement pathway. The degree of disease activity and chronicity were analysed using the C3G histologic index. Descriptive statistics and propensity score matching (PSM) analysis were used to evaluate the main outcome of the study [kidney failure (KF)]. RESULTS: The study group included 23 patients with a median age 63 of years [interquartile range (IQR) 48-70], and 57% were males. Immunoglobulin G kappa was the most frequent MIg (65%). The diagnosis of C3G-MIg was made in transplanted kidneys in seven patients (30%). Five (22%) patients had C3 nephritic factor and five (22%) had anti-factor H antibodies. One patient carried a pathogenic variant in the CFH gene. During a follow-up of 40 months (IQR 14-69), nine patients (39%) reached KF and these patients had a significantly higher total chronicity score on kidney biopsy. Patients who received clone-targeted therapy had a significantly higher survival compared with other management. Those who achieved haematological response had a significantly higher kidney survival. Outcome was remarkably poor in kidney transplant recipients, with five of them (71%) reaching KF. By PSM (adjusting for age, kidney function, proteinuria and chronicity score), no significant differences were observed in kidney survival between C3G patients with/without MIg. CONCLUSIONS: The C3G histologic index can be used in patients with C3G-MIg to predict kidney prognosis, with higher chronicity scores being associated with worse outcomes. Clone-targeted therapies and the development of a haematological response are associated with better kidney prognosis.

"Hemosuccus pancreaticus:" an uncommon form of presentation of pancreatic intraductal papillary mucinous neoplasm.

"Hemosuccus pancreaticus" (HP), "wirsungorrhagia" or "pseudohemobilia" is a rare cause of upper gastrointestinal bleeding consisting of blood loss along the duct of Wirsung with exteriorization through the ampulla of Vater. Due to its rarity, the literature on HP is limited to retrospective studies, case reports, and case series.

Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is a promising strategy to break COVID-19 transmission. Although hydroxychloroquine was evaluated for treatment and post-exposure prophylaxis, it is not evaluated for COVID-19 PrEP yet. The aim of this study was to evaluate the efficacy and safety of PrEP with hydroxychloroquine against placebo in healthcare workers at high risk of SARS-CoV-2 infection during an epidemic period. METHODS: We conducted a double-blind placebo-controlled randomized clinical trial in three hospitals in Barcelona, Spain. From 350 adult healthcare workers screened, we included 269 participants with no active or past SARS-CoV-2 infection (determined by a negative nasopharyngeal SARS-CoV-2 PCR and a negative serology against SARS-CoV-2). Participants allocated in the intervention arm (PrEP) received 400 mg of hydroxychloroquine daily for the first four consecutive days and subsequently, 400 mg weekly during the study period. Participants in the control group followed the same treatment schedule with placebo tablets. RESULTS: 52.8% (142/269) of participants were in the hydroxychloroquine arm and 47.2% (127/269) in the placebo arm. Given the national epidemic incidence decay, only one participant in each group was diagnosed with COVID-19. The trial was stopped due to futility and our study design was deemed underpowered to evaluate any benefit regarding PrEP efficacy. Both groups showed a similar proportion of participants experiencing at least one adverse event (AE) (p=0.548). No serious AEs were reported. Almost all AEs (96.4%, 106/110) were mild. Only mild gastrointestinal symptoms were significantly higher in the hydroxychloroquine arm compared to the placebo arm (27.4% (39/142) vs 15.7% (20/127), p=0.041). CONCLUSIONS: Although the efficacy of PrEP with hydroxychloroquine for preventing COVID-19 could not be evaluated, our study showed that PrEP with hydroxychloroquine at low doses is safe. TRIAL REGISTRATION: ClinicalTrials.gov NCT04331834 . Registered on April 2, 2020.

Novel Purine Chemotypes with Activity against Plasmodium falciparum and Trypanosoma cruzi.

Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 µM) and progressed those compounds that kept the growth of the parasites < 30% at 100 µM to dose-response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC50 = 19.19 µM) and 76 (IC50 = 18.27 µM) were the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 µM) and 34 (IC50 = 4.24 µM) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.

Amaryllidaceae plants: a potential natural resource for the treatment of Chagas disease.

BACKGROUND: Chagas disease is a neglected zoonosis caused by the parasite Trypanosoma cruzi. It affects over six million people, mostly in Latin America. Drugs available to treat T. cruzi infection have associated toxicity and questionable efficacy at the chronic stage. Hence, the discovery of more effective and safer drugs is an unmet medical need. For this, natural products represent a pool of unique chemical diversity that can serve as excellent templates for the synthesis of active molecules. METHODS: A collection of 79 extracts of Amaryllidaceae plants were screened against T. cruzi. Active extracts against the parasite were progressed through two cell toxicity assays based on Vero and HepG2 cells to determine their selectivity profile and discard those toxic to host cells. Anti-T. cruzi-specific extracts were further qualified by an anti-amastigote stage assay. RESULTS: Two extracts, respectively from Crinum erubescens and Rhodophiala andicola, were identified as highly active and specific against T. cruzi and its mammalian replicative form. CONCLUSIONS: The results retrieved in this study encourage further exploration of the chemical content of these extracts in search of new anti-T. cruzi drug development starting points.

Evaluación de una intervención para mejora en la administración segura de medicación en el turno de noche / An Intervention to Improve Safe Administration of Medication in the Night Shift

Introducción: Uno de cada siete pacientes hospitalizados experimenta un evento adverso relacionado con la administración de medicación. Los errores de medicación son una de las causas más importantes de mortalidad y morbilidad prevenible. Objetivo: Evaluar la eficacia de una intervención formativa sobre la población de enfermeras de turno de noche de un hospital de agudos para mejorar el cumplimiento del protocolo de administración segura de medicación. Métodos: Ensayo experimental, pre-post intervención formativa, realizado en Hospital Clínic de Barcelona, durante 2015-2016. Población: 268 enfermeras en dos turnos de noche, muestra: 177 participantes (88 Grupo Control y 89 Grupo Experimental). La intervención consistió en sesiones informativas y acceso a Procedimiento escrito. El instrumento de medida fue el Procedimiento Normalizado de Trabajo de la institución mediante check-list de cumplimiento. Se realzó estudio uni-bivariable, mediante Chi2 y test de Fisher con significancia para p < 0,05. Resultados: Se realizaron 219 observaciones en Grupo Control y 207 en Grupo Experimental. De 17 variables analizadas, solo tres mostraron diferencias significativas: en Grupo Experimental mejoró el conocimiento del Procedimiento; se incrementó el uso del agua y jabón sobre la solución hidroalcohólica; y empeoró la identificación normalizada de fármacos pendientes de administrar. Ninguna de las 14 variables restantes mostró diferencias significativas. De 426 observaciones, solo se produjeron 3 errores de medicación en Grupo control, subsanados antes de su administración, y 0 en Grupo Experimental. Conclusiones: Las intervenciones formativas clásicas con receptores pasivos pueden no ser eficaces para mejorar la práctica enfermera en administración segura de medicación(AU)

Introduction: One in seven hospitalized patients experiences an adverse event related to administration of medication. Medication errors are one of the most important causes of preventable mortality and morbidity. Objective: To assess the efficacy of a training intervention with the population of night shift nurses in an acute care hospital, in order to improve compliance with the protocol for the safe administration of medication. Methods: Experimental trial, pre-post training intervention, carried out at Hospital Clínic of Barcelona, during 2015-2016. The population consisted of 268 nurses in two night shifts. The sample consisted of 177 participants (88 from the control group and 89 from the experimental group). The intervention consisted in information sessions and access to a written procedure. The measurement instrument was the Institution's Standard Work Procedure by means of a compliance check-list. Uni-bivariate study was performed, using chi-square and Fisher's test with a significance of P < 0.05. Results: 219 observations were carried out in the control group and 207, in the experimental group. Of seventeen variables analyzed, only three showed significant differences: in the experimental group, knowledge of the procedure improved, increase in the use of soap and water over hydroalcoholic solution, and worsening of standardized identification of drugs pending from being administered. None of the fourteen remaining variables showed significant differences. Of 426 observations, only three medication errors occurred in the control group, corrected before its administration, and zero occurred in the experimental group. Conclusions: Classic training interventions with passive receptors may not be effective to improve nursing practice in safe administration of medication(AU)

Identification of Trypanosoma cruzi Growth Inhibitors with Activity In Vivo within a Collection of Licensed Drugs.

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), affects more than six million people worldwide, with its greatest burden in Latin America. Available treatments present frequent toxicity and variable efficacy at the chronic phase of the infection, when the disease is usually diagnosed. Hence, development of new therapeutic strategies is urgent. Repositioning of licensed drugs stands as an attractive fast-track low-cost approach for the identification of safer and more effective chemotherapies. With this purpose we screened 32 licensed drugs for different indications against T. cruzi. We used a primary in vitro assay of Vero cells infection by T. cruzi. Five drugs showed potent activity rates against it (IC50 < 4 µmol L-1), which were also specific (selectivity index >15) with respect to host cells. T. cruzi inhibitory activity of four of them was confirmed by a secondary anti-parasitic assay based on NIH-3T3 cells. Then, we assessed toxicity to human HepG2 cells and anti-amastigote specific activity of those drugs progressed. Ultimately, atovaquone-proguanil, miltefosine, and verapamil were tested in a mouse model of acute T. cruzi infection. Miltefosine performance in vitro and in vivo encourages further investigating its use against T. cruzi.

Electrophysiological Responses of the Mediterranean Fruit Fly, Ceratitis capitata, to the Cera Trap® Lure: Exploring Released Antennally-Active Compounds.

The Mediterranean fruit fly (medfly), Ceratitis capitata, is a worldwide pest of agriculture able to use olfactory cues to locate habitat, food sources, mates and oviposition sites. The sensitivity of medfly olfaction has been exploited to develop olfactory-based attractants that are currently important tools for detection, control and eradication of its populations. Among these is Cera Trap® (BIOIBERICA, S.A.U.), a cost-effective bait. Here we used coupled gas chromatography/electroantennographic detection (GC-EAD) and GC/mass spectrometry (GC-MS) approaches to characterize the medfly antennally-active compounds released by this lure. We identified GC peaks corresponding to chemicals belonging to six different classes including heterocyclic aromatic compounds, aliphatic alcohols, aldehydes, esters, sesquiterpene hydrocarbons, and aromatic alcohols. We tested ten potential candidate volatiles belonging to these classes and predicted to be emitted by the lure and found that they were eliciting electroantennographic responses in medfly adults. These results will help in unravelling the physiological mechanisms of odor perception in both sexes, especially in relation to Cera Trap® attractant activity, which in the field has been shown to be female-specific. These findings and their developments will ultimately expand the toolbox for medfly control in the field.

Allelopathy in rice: a story of momilactones, kin recognition, and weed management.

In the struggle to secure nutrient access and to outperform competitors, some plant species have evolved a biochemical arsenal with which they inhibit the growth or development of neighbouring plants. This process, known as allelopathy, exists in many of today's major crops, including rice. Rice synthesizes momilactones, diterpenoids that are released into the rhizosphere and inhibit the growth of numerous plant species. While the allelopathic potential of rice was recognized decades ago, many questions remain unresolved regarding the biosynthesis, exudation, and biological activity of momilactones. Here, we review current knowledge on momilactones, their role in allelopathy, and their potential to serve as a basis for sustainable weed management. We emphasize the gaps in our current understanding of when and how momilactones are produced and of how they act in plant cells, and outline what we consider the next steps in momilactone and rice allelopathy research.

Anti-Trypanosoma cruzi Activity of Metabolism Modifier Compounds.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and affects over 6 million people worldwide. Development of new drugs to treat this disease remains a priority since those currently available have variable efficacy and frequent adverse effects, especially during the long regimens required for treating the chronic stage of the disease. T. cruzi modulates the host cell-metabolism to accommodate the cell cytosol into a favorable growth environment and acquire nutrients for its multiplication. In this study we evaluated the specific anti-T. cruzi activity of nine bio-energetic modulator compounds. Notably, we identified that 17-DMAG, which targets the ATP-binding site of heat shock protein 90 (Hsp90), has a very high (sub-micromolar range) selective inhibition of the parasite growth. This inhibitory effect was also highly potent (IC50 = 0.27 µmol L-1) against the amastigote intracellular replicative stage of the parasite. Moreover, molecular docking results suggest that 17-DMAG may bind T. cruzi Hsp90 homologue Hsp83 with good affinity. Evaluation in a mouse model of chronic T. cruzi infection did not show parasite growth inhibition, highlighting the difficulties encountered when going from in vitro assays onto preclinical drug developmental stages.

Benznidazole for the treatment of Chagas disease.

INTRODUCTION: Chagas disease affects 6-7 million people, mainly in the Americas, and benznidazole is one of the two therapeutic options available. Trypanocide treatment aims to eliminate the parasite from the body to prevent the establishment or progression of visceral damage, mainly cardiac and/or digestive. Remarkably, it helps interrupt vertical transmission when administered to women of childbearing age. AREAS COVERED: We discuss the basic and scarce data regarding chemical, pharmacokinetic, and pharmacodynamic structure. We also collect the most important data from previous phase II and III studies, as well as studies currently underway and upcoming. We reflect on the main indications for treatment and its challenges, such as the profile of adverse effects in adults, the pharmaceutical formulations, the search for reliable biomarkers, as well as regulatory aspects and access barriers. Alternative strategies such as shorter regimens, lower doses, and fixed doses are currently being evaluated to improve access and the safety profile of this treatment. EXPERT OPINION: Benznidazole is likely to continue to be the drug of choice for Chagas disease in the coming years. However, it would probably be with a different treatment scheme.