Design of two alternative routes for the synthesis of naftifine and analogues as potential antifungal agents

Two practical and efficient approaches have been implemented as alternative procedures for the synthesis of naftifine and novel diversely substituted analogues 16 and 20 in good to excellent yields, mediated by Mannich-type reactions as the key step of the processes. In these approaches, theγ-aminoalcohols 15 and 19 were obtained as the key intermediates and their subsequent dehydration catalyzed either by Brønsted acids like H2SO4 and HCl or Lewis acid like AlCl3, respectively, led to naftifine, along with the target allylamines 16 and 20. The antifungal assay results showed that intermediates 18 (bearing both a β-aminoketo- and N-methyl functionalities in their structures) and products 20 were the most active. Particularly, structures 18b, 18c, and the allylamine 20c showed the lowest MIC values, in the 0.5-7.8 μg/mL range, against the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. Interesting enough, compound 18b bearing a 4-Br as the substituent of the phenyl ring, also displayed high activity against Candida albicans and Cryptococcus neoformans with MIC80 = 7.8 μg/mL, being fungicide rather than fungistatic with a relevant MFC value = 15.6 μg/mL against C. neoformans.Fil: Abonia, Rodrigo. Universidad del Valle; ColombiaFil: Garay, Alexander. Universidad del Valle; ColombiaFil: Castillo, Juan C.. Universidad del Valle; Colombia. Universidad Pedagógica y Tecnológica de Colombia; ColombiaFil: Insuasty, Braulio. Universidad del Valle; ColombiaFil: Quiroga, Jairo. Universidad del Valle; ColombiaFil: Nogueras, Manuel. Universidad de Jaén; EspañaFil: Cobo, Justo. Universidad de Jaén; EspañaFil: Butassi, Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Zacchino, Susana Alicia Stella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Departamento de Química Orgánica. Área Farmacognosia; Argentin

Functional Massage of the Teres Major Muscle in Patients with Subacromial Impingement Syndrome. A Randomized Controlled Case Series Study.

Objective: the purpose of the present study was to analyze the concurrent validity and reliability of a force platform clinical COBS Feedback® for the estimation of the height of vertical jumps. Design: a cross-sectional correlational and comparative study. Setting: University Human Movement and Physiotherapy Laboratory. Participants: healthy university students (14 female and 13 male) aged between 18 and 25 years old (mean = 20.074 ±1.542). Main Outcome Measures: vertical jump heights, technical error and grade of agreement between methods of measurement. Results: after the 27 subjects performed a total of 135 vertical jumps on COBS Feedback®platform while simultaneously being recorded with a high-speed camera-based method, the intraclass correlation coefficient showed an almost perfect concordance between the two methods (ICC = 0.916, CI95%= 0.882 to 0.940, p<0.001). The technical error of the COBS Feedback® against HSC-Kinovea video analysis was at 0.310±0.223m, being higher in males than in females (t= -2.822, CI95%: -0.376 to -0.574, p=0.001). Conclusions: the COBS Feedback® method provided a valid measurement of the flight times for estimate the vertical jump height as a number of well-known tests and devices.Aims: Subacromial impingement syndrome is the most common shoulder condition. Myofascial trigger points in teres major muscle can be associated with this syndrome. Our objective is to determine whether adding manual therapy specifically for teres major trigger points can produce better results in these patients. Study Design: Randomized controlled case series. Place and Duration of Study: Public Primary Care Center in the Spanish National Health System (Cornellà de Llobregat - Barcelona) and the FREMAP Mutual Society for Work-related Injuries and Occupational Illness (Arnedo - La Rioja), between January and March 2014. Methodology: Fifty-eight people were recruited but 8 subjects were lost during the follow-up period. The sample consisted of 50 patients (17 male and 33 female, age range 23-80 years) randomly assigned to one of two groups: the intervention group or the control group. Both groups received a protocolized physical therapy treatment, while the intervention group also received manual therapy for teres major trigger points. Results: Pain intensity (p=.01) and function (p=.01) showed significant improvement in the control group, whereas pain intensity (p=.01), function (p=.01) and active range of motion (p=.01) showed significant improvement in the intervention group. Between-group differences were statistically significant for abduction (p=.01), extension (p=.02) and lateral rotation (p=.02), and clinically significant (Cohen’s d) for function, flexion, extension, lateral rotation and abduction. Conclusion: Although our findings must be considered as preliminary, they suggest that adding manual therapy to treat teres major trigger points achieves better results in the glenohumeral range of motion

Alert classification for the ALeRCE broker system: The real-time stamp classifier

We present a real-time stamp classifier of astronomical events for the Automatic Learning for the Rapid Classification of Events broker, ALeRCE. The classifier is based on a convolutional neural network, trained on alerts ingested from the Zwicky Transient Facility (ZTF). Using only the science, reference, and difference images of the first detection as inputs, along with the metadata of the alert as features, the classifier is able to correctly classify alerts from active galactic nuclei, supernovae (SNe), variable stars, asteroids, and bogus classes, with high accuracy (~94%) in a balanced test set. In order to find and analyze SN candidates selected by our classifier from the ZTF alert stream, we designed and deployed a visualization tool called SN Hunter, where relevant information about each possible SN is displayed for the experts to choose among candidates to report to the Transient Name Server database. From 2019 June 26 to 2021 February 28, we have reported 6846 SN candidates to date (11.8 candidates per day on average), of which 971 have been confirmed spectroscopically. Our ability to report objects using only a single detection means that 70% of the reported SNe occurred within one day after the first detection. ALeRCE has only reported candidates not otherwise detected or selected by other groups, therefore adding new early transients to the bulk of objects available for early follow-up. Our work represents an important milestone toward rapid alert classifications with the next generation of large etendue telescopes, such as the Vera C. Rubin Observatory.The authors acknowledge support from the National Agency of Research and Development’s Millennium Science Initiative through grant IC12009, awarded to the Millennium Institute of Astrophysics (RC, ER, CV, FF, PE, GP, FEB, IR, PSS, GC, SE, Ja, EC, DR, DRM, MC) and from the National Agency for Research and Development (ANID) grants: BASAL Center of Mathematical Modelling AFB-170001 (CV, FF, IR, ECN, CS, ECI) and Centro de Astrofísica y Tecnologías Afines AFB170002 (FEB, PSS, MC); FONDECYT Regular #1171678 (PE), #1200710 (FF), #1190818(FEB), #1200495 (FEB), #1171273 (MC), #1201793(GP); FONDECYT Postdoctorado #3200250 (PSS); FONDECYT Iniciación #11191130 (CV); Magíster Nacional 2019 #22190947 (ER). This work was funded in part by project CORFO 10CEII-9157 Inria Chile (PS). The authors acknowledge financial support from the Spanish Ministry of Science, Innovation, and Universities (MICIU) under the 2019 Ramón y Cajal program RYC2019- 027683 (LG)

The Beneficial Effects of Antifreeze Proteins in the Vitrification of Immature Mouse Oocytes

Antifreeze proteins (AFPs) are a class of polypeptides that permit organismal survival in sub-freezing environments. The purpose of this study was to investigate the effect of AFP supplementation on immature mouse oocyte vitrification. Germinal vesicle-stage oocytes were vitrified using a two-step exposure to equilibrium and vitrification solution in the presence or absence of 500 ng/mL of AFP III. After warming, oocyte survival, in vitro maturation, fertilization, and embryonic development up to the blastocyst stage were assessed. Spindle and chromosome morphology, membrane integrity, and the expression levels of several genes were assessed in in vitro matured oocytes. The rate of blastocyst formation was significantly higher and the number of caspase-positive blastomeres was significantly lower in the AFP-treated group compared with the untreated group. The proportion of oocytes with intact spindles/chromosomes and stable membranes was also significantly higher in the AFP group. The AFP group showed increased Mad2, Hook-1, Zar1, Zp1, and Bcl2 expression and lower Eg5, Zp2, Caspase6, and Rbm3 expression compared with the untreated group. Supplementation of the vitrification medium with AFP has a protective effect on immature mouse oocytes, promoting their resistance to chilling injury. AFPs may preserve spindle forming ability and membrane integrity at GV stage. The fertilization and subsequent developmental competence of oocytes may be associated with the modulation of Zar1, Zp1/Zp2, Bcl2, Caspase6, and Rbm3

Between foraging and farming: Strategic responses to the Holocene Thermal Maximum in Southeast Asia

Large, ‘complex’ pre-Neolithic hunter-gatherer communities thrived in southern China and northern Vietnam, contemporaneous with the expansion of farming. Research at Con Co Ngua in Vietnam suggests that such hunter-gatherer populations shared characteristics with early farming communities: high disease loads, pottery, complex mortuary practices and access to stable sources of carbohydrates and protein. The substantive difference was in the use of domesticated plants and animals—effectively representing alternative responses to optimal climatic conditions. The work here suggests that the supposed correlation between farming and a decline in health may need to be reassessed

She\u27s So Bubbly

We introduce the Automatic Learning for the Rapid Classification of Events (ALeRCE) broker, an astronomical alert broker designed to provide a rapid and self-consistent classification of large etendue telescope alert streams, such as that provided by the Zwicky Transient Facility (ZTF) and, in the future, the Vera C. Rubin Observatory Legacy Survey of Space and Time (LSST). ALeRCE is a Chilean-led broker run by an interdisciplinary team of astronomers and engineers working to become intermediaries between survey and follow-up facilities. ALeRCE uses a pipeline that includes the real-time ingestion, aggregation, cross-matching, machine-learning (ML) classification, and visualization of the ZTF alert stream. We use two classifiers: a stamp-based classifier, designed for rapid classification, and a light curve–based classifier, which uses the multiband flux evolution to achieve a more refined classification. We describe in detail our pipeline, data products, tools, and services, which are made public for the community (see https://alerce.science). Since we began operating our real-time ML classification of the ZTF alert stream in early 2019, we have grown a large community of active users around the globe. We describe our results to date, including the real-time processing of 1.5 × 10⁸ alerts, the stamp classification of 3.4 × 10⁷ objects, the light-curve classification of 1.1 × 10⁶ objects, the report of 6162 supernova candidates, and different experiments using LSST-like alert streams. Finally, we discuss the challenges ahead in going from a single stream of alerts such as ZTF to a multistream ecosystem dominated by LSST

Role of age and comorbidities in mortality of patients with infective endocarditis

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015. Patients were stratified into three age groups:<65 years, 65 to 80 years, and = 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 = 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients =80 years who underwent surgery were significantly lower compared with other age groups (14.3%, 65 years; 20.5%, 65-79 years; 31.3%, =80 years). In-hospital mortality was lower in the <65-year group (20.3%, <65 years;30.1%, 65-79 years;34.7%, =80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%, =80 years; p = 0.003).Independent predictors of mortality were age = 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI = 3 (HR:1.62; 95% CI:1.39–1.88), and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared, the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. Conclusion: There were no differences in the clinical presentation of IE between the groups. Age = 80 years, high comorbidity (measured by CCI), and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO)

PURPOSE: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD. PARTICIPANTS: The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices. FINDINGS TO DATE: The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline. FUTURE PLANS: We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications