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In this work we introduce Target Fisher, a consensus structure-based target prediction tool that integrates molecular docking and machine learning with the aim to aid in the identification of potential biological targets and the optimization of the use of bioassays. Target Fisher uses per-residue energy decomposition profiles extracted from docking poses as fingerprints to train target-specific machine learning models. It provides predictions for a curated set of 37 protein targets, covering a diverse range of biological entities, and offers a user-friendly interface accessible via a web server (https://gqc.quimica.unlp.edu.ar/targetfisher/). In this sense, Target Fisher is a valuable tool to aid organic and medicinal chemistry groups in target identification, drug discovery and drug repurposing. As a case study, we demonstrate the efficacy of Target Fisher by screening a small library of assorted natural products for targets relevant to neurodegenerative diseases, which resulted in the identification and experimental validation of selective inhibitors of monoamine oxidase B (MAO-B)., (© 2024 Wiley-VCH GmbH.)

Although the two drugs currently available for the treatment of Chagas disease, Benznidazole and Nifurtimox, have proven to be effective in the acute phase of the disease, the 60-90-day treatment leads to high toxicity and unwanted side effects, presenting, in addition, a low efficacy in the chronic phase of the disease. For this reason, new therapies that are more effective are needed. In this regard, we have recently shown that the inhibition of the Epac-Rap1b pathway suppressed the cAMP-mediated host cell invasion by Trypanosoma cruzi . Interestingly, it has been described that vitexin, a natural flavone that protects against ischemia-reperfusion damage, acts by inhibiting the expression of Epac and Rap1 proteins. Vitexin can be found in plants of the genus Crataegus spp., traditionally known as hawthorn, which are of great interest considering their highly documented use as cardio-protectors. Pre-treating cells with an extract of Crataegus oxyacantha produced levels of T. cruzi invasion comparable to the ones observed for the commercially available Epac1-specific inhibitor, ESI-09. In addition, extract-treated cells exhibited a decrease in the activation of Rap1b, suggesting that the effects of the extract would be mediated by the inhibition of the cAMP-Epac-Rap1 signaling pathway. Using HPLC-HRMS 2 , we could confirm the presence of vitexin, and other flavones that could act as inhibitors of Epac/Rap1b, in the extracts of C. oxyacantha. Most significantly, when cells were treated with the extract of C. oxyacantha in conjunction with Nifurtimox, an increased modulation of invasion was observed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ferri, Fernández, Di Mario, Musikant, Palermo and Edreira.)

Introduction: Pneumothorax in neonates can be life-threatening. In neonates without respiratory distress, spontaneous pneumothorax can also develop under certain conditions., Objectives: To determine the incidence of ultrasonographic signs of pneumothorax in asymptomatic neonates using lung ultrasound as the diagnostic tool., Methods: This was an observational prospective study conducted at the Basurto University Hospital (Bilbao, Spain) between January 2018 and December 2020. Lung ultrasound was performed during routine examination of asymptomatic neonates admitted to the maternity ward., Results: Of a total of 204 asymptomatic neonates included in the study, 21 (10.3%) presented ultrasound signs of pneumothorax (Group A), and 183 (89.7%) had a normal lung ultrasound (Group B). Lung ultrasound was performed after a mean of 19 h of life (range 9-34). The presence of A-lines behind the sternum in the anterior transverse plane, at the intermammillary level, was observed in 100% of patients in Group A compared to no cases in Group B (p < 0.0001). The neonates of Group A presented the lung point located in the midclavicular line, indicative of a mild air leak., Conclusions: Lung ultrasound allows precise detection of suspected small-sized air leaks that can be detected in asymptomatic neonates. The true incidence of pneumothorax in asymptomatic neonates may be substantially higher than previously described in the literature., (© 2023 Wiley Periodicals LLC.)

We report the synthesis of 16 new compounds obtained from kokusaginine and flindersiamine, the main alkaloids isolated from the bark of Balfourodendron riedelianum. The activity of the compounds against axenic cultures of Trypanosoma cruzi epimastigtotes and trypomastigotes, as well as intracellular amastigotes, is described, together with their cytotoxic activity against three different human cell lines. The synthetic strategy for the preparation of the new compounds was based on the reactivity at the C4 position of the furoquinoline core towards nucleophiles. The new derivatives were synthesized by a Buchwald-Hartwig reaction, in most cases under green, solvent-free conditions. Compounds 1 c and 1 e displayed better in-vitro activity against trypomastigotes than benznidazole and nifurtimox (positive controls) with IC 50 <4 μM. In addition, both compounds were not cytotoxic against the three human cell lines K562 (erytroleukimia), LM2 (breast cancer), and HaCat (keratinocyte). Interestingly, when evaluated against intracellular amastigotes, compound 1 c was able to significantly reduce the number of this parasite form, compared to the negative control., (© 2022 Wiley-VCH GmbH.)

Objective: Lung ultrasound is a useful tool for diagnosis and follow-up of diseases in critically ill neonates. Its use is increasingly widespread thanks to its advantages over other imaging tests and the rapidly growing body of evidence to support it, and "point-of-care ultrasound" (POCUS) has become a key component in neonatal guidelines. The objective of this special article is to present the foundations and the established diagnostic and therapeutic applications of lung ultrasonography as well as introducing new applications., Methods and Results: The Lung Ultrasound Section of the Neonatal Ultrasonography Working Group of the Spanish Neonatology Society has summarised the current scientific evidence. The article describes the sonographic features of the most common respiratory diseases, discusses some of the applications of ultrasound in neonatal care (such as prediction of admission and need of surfactant, ultrasound-guided procedures or monitoring of lung development in premature infants) and proposes its introduction in other scenarios in which its use is not quite established at present, such as resuscitation or respiratory management. This article reaffirms the usefulness of lung ultrasound in guiding diagnosis, clinical decision-making and prognosis and facilitating procedures., Conclusions: Lung ultrasound should be established as the gold standard for diagnosis of respiratory diseases in neonates. Therefore, training in lung ultrasound should be included in the educational curriculum of neonatologists and in diagnostic and therapeutic care protocols. Research on the subject should continue to be pursued with performance of rigorous multicentre studies to increase the quality of the evidence., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Protein-protein interactions (PPIs) play central roles in most molecular mechanisms underlying cellular and biological processes. Within the methods developed to study PPIs is bioluminescence resonance energy transfer (BRET). Taking advantage of this technique, we have set a BRET-based assay that enables the screening of modulators of essential PPIs for Trypanosoma cruzi survival. Considering the complexity of the evaluated mixture, pure chemical compounds or natural extracts, two approaches are described, BRET in living cells or from lysates., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objective: Dermatophytes are fungi that cause infections in hair, skin, and nails. Potassium Hydroxide (KOH) microscopy is the most frequently used method for identifying dermatophytes. KOH helps in the visualization of the hyphae as it clears the debris present in the specimen but needs a trained eye for final diagnosis of the infection. Fluorescence microscopy using staining agents, such as calcofluor white (CFW) or blankophor, is a better method for identification of dermatophytes but is not used in clinics due to the cost and complexity of fluorescence microscopes. The objective of the present work is to develop a simple low-cost mobile phone-based device for the identification of fungal pathogens in skin samples., Materials and Methods: A fluorescence spectrometer was used to establish the excitation/emission peaks of fluorescence intensity of CFW and KOH and Methyl Cellulose, a surrogate of fungi used for system development. A transillumination microscopy prototype was fabricated using off-the-shelf components, 3D printing and a mobile phone. The system was optically characterized using contrast resolution targets and verified using fungi isolate samples. An isolate of Trichophyton (T) rubrum was grown for 10-14 days for formation of fungal colonies. The surface of a single colony was gently scraped with a sterile loop and transferred to a glass slide. CFW with KOH was added to the T. rubrum and covered with cover slip for microscopic examination. The images of T. rubrum obtained with the prototype device were compared to those obtained using a commercial microscope., Results: The excitation/emission wavelength pair for CFW was found to be 370/430 nm. The proposed device design is a transillumination microscopy setup using a mobile phone. It consists of a 365 nm LED as the excitation source, a 3V battery to power the LED, a slide to hold the sample, a lens for magnification and a phone to capture and store the images of the sample. The fabricated prototype has a resolution of 70 to 99 µm, a 2% to 30% distortion, and 60% contrast value for well illuminated samples. Images of T. rubrum samples obtained under brightfield illumination clearly show the long septate hyphae of the dermatophyte. As expected, images of the same samples with CFW and KOH show blue fluorescence, which results from the binding of the CFW to the chitin and cellulose in the fungal hyphae. These images are similar to those obtained with a commercial microscope., Summary and Conclusions: The concept and design of a mobile phone-based fluorescence microscope to identify dermatophytes has been demonstrated in a prototype and laboratory samples. The concept and design offer a simple, low-cost, compact but robust method for identification of fungal pathogens. This method is shown to be feasible for detecting fluorescence accurately and imaging the fungal structure at a resolution of 100 µm or better. Lasers Surg. Med. 51:201-207, 2019. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Complete development of Orius majusculus Reuter (Heteroptera: Anthocoridae) at nine constant temperatures, between 12 and 34°C, was evaluated under laboratory conditions. The maximum developmental period of 90.75 d occurred at 12°C, whereas the minimum of 11.34 d occurred at 30°C. From 30 to 34°C, the developmental period increased to 13.50 d. Between 21 and 33°C the survival rate was more than 80%. The optimal temperature when considering developmental rate and survival was between 24 and 30°C. At constant temperatures, four models were developed, one of which was linear and three nonlinear (Logan type III, Lactin, and Brière). All models were validated under field conditions and diel temperature variations. The values of the adjusted determination coefficients of the linear (>0.77) and nonlinear models (>0.93) were high. The thermal requirement for complete development, from egg to adult, was 284.5 degree-days (DD). In all nonlinear models, elevated levels of accuracy (≥90.31%) in field validation were also obtained, especially in the Brière model. With the results obtained herein, the optimization of O. majusculus mass rearing, its ideal use, and field management in biological control strategies can be improved., (© The Author(s) 2018. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

For optimal application of Nesidiocoris tenuis as a biological control agent, adequate field management and programmed mass rearing are essential. Mathematical models are useful tools for predicting the temperature-dependent developmental rate of the predator. In this study, the linear model and nonlinear models Logan type III, Lactin and Brière were estimated at constant temperatures and validated at alternating temperatures and under field conditions. N. tenuis achieved complete development from egg to adult at constant temperatures between 15 and 35°C with high survivorship (>80%) in the range 18-32°C. The total developmental time decreased from a maximum at 15°C (76.74 d) to a minimum at 33°C (12.67 d) and after that, increased to 35°C (13.98 d). Linear and nonlinear developmental models all had high accuracy (R a 2 >0.86). The maximum developmental rate was obtained between 31.9°C (Logan type III and Brière model for N1) and 35.6°C (for the egg stage in the Brière model). Optimal survival and the highest developmental rate fell within the range 27-30°C. The field validation revealed that the Logan type III and Lactin models offered the best predictions (95.0 and 94.5%, respectively). The data obtained on developmental time and mortality at different temperatures are useful for mass rearing this predator, and the developmental models are valuable for using N. tenuis as a biological control agent.

Peracetylated bile acids (1a-g) were used as starting materials for the preparation of fourteen new derivatives bearing an oxazole moiety in their side chain (6a-g, 8a-g). The key step for the synthetic path was a Dakin-West reaction followed by a Robinson-Gabriel cyclodehydration. A simpler model oxazole (12) was also synthesized. The antifungal activity of the new compounds (6a-g) as well as their starting bile acids (1a-g) was tested against Candida albicans. Compounds 6e and 6g showed the highest percentages of inhibition (63.84% and 61.40% at 250 μg/mL respectively). Deacetylation of compounds 6a-g, led to compounds 8a-g which showed lower activities than the acetylated derivatives., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A detailed chemical study of the aerial parts and rhizomes of Hyalis argentea var. latisquama yielded a variety of sesqui- and diterpenes. In total, 26 compounds were isolated and identified, of which four are new, namely, two ent-kaurenes (1 and 2), a diterpene lactone (3), and a lindenanolide (4). The previously reported compounds included a series of lindenanolides, guaianolides, elemanolides, and additional diterpenes. The antifungal activity of the isolated compounds was tested against Cryptococcus neoformans and Candida albicans. Among the isolated compounds, the lindenanolides were the only structural class that showed strong antifungal activity, and onoseriolide acetate (5) was the most active. On the other hand, the isolated guaianolides were only moderately active, while the diterpenes did not show significant antifungal activity.

Five new neolignans with a bicyclo[2.2.2]octene framework were isolated from an ethanolic extract of the bark of Cordia americana. The structures and relative configurations of the compounds were elucidated by a combination of spectroscopic methods. All the isolated compounds showed good antioxidant activities in the DPPH radical scavenging (0.5-100 µg/mL) and Ferric-reducing antioxidant power (FRAP, 1-100 µg/mL) assays. One of the compounds displayed mild fungistatic activity at 0.1 µmol/spot against Fusarium virguliforme while, at the same time, all compounds were inactive against several strains of Gram (+) and Gram (-) bacteria at all assayed concentrations (10-1,000 µg/mL)., (Georg Thieme Verlag KG Stuttgart · New York.)

The investigation of the ethanol extract of fresh aerial parts of the Patagonian shrub Nardophyllum bryoides collected in the province of Chubut, Argentina, yielded eleven terpenoids. These include: three seco-ent-halimane diterpenoids (1-3), two ent-halimanes (4-5) and six pentacyclic oleanane and ursane triterpenoids (6-11). Four of these compounds (2, 6, 8 and 11) are hitherto unknown, while two others (1 and 4) have been previously reported but only as synthetic products. Several of these compounds showed moderate cytotoxicity against a human pancreatic adenocarcinoma cell line while compounds 4 and 5 were active at micromolar concentrations. The main component, seco-chiliolidic acid (1), could be isolated from this extract in large amounts, turning N. bryoides into a sustainable source of this bioactive compound., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Osseous hemangioma in the maxillofacial region (OHMF) was first reported in the literature as a clinical entity in the middle of last century. Several fatal cases of accidental hemorrhage following tooth extraction were attributed to OHMF. The discovery of X-rays and image diagnosis should have facilitated identification of the lesion and contributed to establishing differential diagnosis with other entities. However, our review of case-reports suggests that this lesion has been misdiagnosed and mistaken for other neoplastic and non-neoplastic hemorrhagic bone lesions. The aim of this study was to analyze clinical and radiographic data obtained from our review in order to determine the diagnostic criteria for OHMF over the last twenty years. Our case study showed that OHMF occurred at a mean age of 27.3 years, and appeared at a later age in women (30.4 years). OHMF was more frequent in women with a female to male ratio of 1.6:1, although a higher ratio has been reported in the literature. The site of predilection was the premolar and molar region of the mandible (65%). Clinical diagnosis of hemangioma was performed in 7 cases only (35%); diagnosis of the remaining cases was less accurate. The most frequent radiographic feature was mixed radiodensity (70%) and radiolucency (30%). A honeycombed appearance predominated (35%). In addition, 8 cases of OHMF involved the teeth which exhibited resorption and displacement. The present study shows that image diagnosis of OHMF must be based on the critical application of increasingly complex techniques in order to define the lesion.