A novel series of pyrazole derivatives toward biological applications: experimental and conceptual DFT characterization.

A new series of 13 pyrazole-derivative compounds with potential antifungal activity were synthetized with good yields. The series have the (E)-2-((1-(R)-3,5-dimethyl-1H-pyrazol-4-yl)diazenyl)phenol general structure and were characterized by means of X-ray diffraction, UV-Vis, FTIR, 1H-NMR, 13C-NMR, and two-dimensional NMR experiments. This experimental characterization was complemented by DFT simulations. A deep insight regarding molecular reactivity was accomplished employing a conceptual DFT approach. In this sense, dual descriptors were calculated at HF and DFT level of theory and GGV spin-density Fukui functions. The main reactive region within the molecules was mapped through isosurface and condensed representations. Finally, chemical descriptors that have previously shown to be close related to biological activity were compared within the series. Thus, higher values of chemical potential ω and electrophilicity χ obtained for compounds 10, 9, 8, 6 and 7, in this order, suggest that these molecules are the better candidates as biological agents.

Towards an Accurate Faults Detection Approach in Internet of Medical Things Using Advanced Machine Learning Techniques.

Remotely monitoring people's healthcare is still among the most important research topics for researchers from both industry and academia. In addition, with the Wireless Body Networks (WBANs) emergence, it becomes possible to supervise patients through an implanted set of body sensors that can communicate through wireless interfaces. These body sensors are characterized by their tiny sizes, and limited resources (power, computing, and communication capabilities), which makes these devices prone to have faults and sensible to be damaged. Thus, it is necessary to establish an efficient system to detect any fault or anomalies when receiving sensed data. In this paper, we propose a novel, optimized, and hybrid solution between machine learning and statistical techniques, for detecting faults in WBANs that do not affect the devices' resources and functionality. Experimental results illustrate that our approach can detect unwanted measurement faults with a high detection accuracy ratio that exceeds the 99.62%, and a low mean absolute error of 0.61%, clearly outperforming the existing state-of-art solutions.

Point-of-care ultrasound assessment with handheld ultrasound device attached to cell phone.

Recent advances in ultrasound technology have made modern handheld ultrasound devices and are contributing to make bedside ultrasound evaluation a practice available to all physicians. A 46-year-old woman with history of systemic erythematosus presented to our hospital with 14 days of COVID-19. The patient suddenly presented greater respiratory distress, tachycardia, hypotension, and increased supplemental oxygen requirements; so she required mechanical ventilation. Point-of-care ultrasound assessment with handheld ultrasound device was observed on the apical view an apical thrombus in the right ventricle, McConnell's sign. The patient underwent systemic thrombolysis with alteplase showing improvement in mechanical ventilation parameters and is currently continuing treatment for COVID-19 in the intensive care unit of our hospital. Emerging technologies such as handheld ultrasound devices can provide high-quality care to the patients. Routine screening of patients with COVID-19 using handheld ultrasound is feasible, may be able to define prognosis and treatment of cardiovascular complications.

[Amyloid angiopathy brain hemorrhage]. / Hemorragia encefálica por angiopatía amiloidea.

Amyloid angiopathy (AA) is a selective deposition of amyloid in the walls of the brain vessels. It is a form of sporadic and localized amyloidosis, constituted by the Aß4 protein, the same of Alzheimer's disease senile plaques. The most consistent clinical effect of AA is spontaneous brain hemorrhage (BH). It is the second most common cause of BH after arterial hypertension (HT). Other clinical manifestations are cognitive impairment and transient focal neurological episodes. AA BH is characteristically localized in the cerebral cortex and subcortical white matter (lobar hemorrhage), consistent with the preferential deposit of amyloid in the walls of leptomeningeal and intracortical small cerebral vessels. Other types of AA hemorrhagic complications are microbleeds (MB), cerebral convexity subarachnoid hemorrhage (cSAH) and superficial hemosiderosis (cSS). The diagnosis of AA BH is based on the Boston criteria. Using these criteria, several non-hemorrhagic biomarkers of AA have been identified that can be useful in its diagnosis. The principal AA BH risk factor is age, followed by cSS, MB, Apolipoprotein E gen ε2 and ε4 alleles, HT and the use of antithrombotics. This condition has a high recurrence rate that shares the same risk factors. There is no specific treatment for AA BH. It has a better prognosis than HT BH during the acute period, but worse on the long term, due to its high recurrence rate and cognitive impairment.

New Sensitive and Selective Chemical Sensors for Ni2+ and Cu2+ Ions: Insights into the Sensing Mechanism through DFT Methods.

We report the synthesis and theoretical study of two new colorimetric chemosensors with special selectivity and sensitivity to Ni2+ and Cu2+ ions over other metal cations in the CH3CN/H2O solution. Compounds (E)-4-((2-nitrophenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)aniline (A) and (E)-4-((3-nitrophenyl)diazenyl)-N,N-bis(pyridin-2-ylmethyl)aniline (B) exhibited a drastic color change from yellow to colorless, which allows the detection of the mentioned metal cations through different techniques. The interaction of sensors with these metal ions induced a new absorption band with a hypsochromic shift to the characteristic signal of the free sensors. A theoretical study via time-dependent density functional theory (TD-DFT) was performed. This method has enabled us to reproduce the hypsochromic shift in the maximum UV-vis absorption band and explain the selective sensing of the ions. For all of the systems studied, the absorption band is characterized by a π → π* transition centered in the ligand. Instead of Ni2+ and Cu2+ ions, the transition is set toward the σ* molecular orbital with a strong contribution of the 3dx2-y2 transition (π → 3dx2-y2). These absorptions imply a ligand-to-metal charge transfer (LMCT) mechanism that results in the hypsochromic shift in the absorption band of these systems.

Antioxidant effect of resveratrol in single red blood cells measured by thermal fluctuation spectroscopy.

The human red blood cell (RBC) membrane has significant elastic capabilities which can be described measuring typical membrane edge fluctuations and mechanical properties by optical techniques. The RBC elastic properties can be affected by changes in the surrounding media. In an attempt to elucidate the molecular mechanisms of the interaction of resveratrol with the red cell membrane and of its antioxidant capacity the changes in mechanical properties of the RBC membrane were analyzed. These studies were carried out through measurements of RBC membrane fluctuations in the presence of the oxidant agent HClO using thermal fluctuation spectroscopy (TFS). The observed results showed that the elastic capabilities of RBC changed with low concentration of hypochlorous acid but without morphological changes. However, in the presence of resveratrol the deformation and decrease of elastic capabilities induced by HClO on RBC decreased. These in vitro results demonstrated the protective effect of RV against the detrimental effects triggered by HClO upon human erythrocytes.

Ectopic intestinal mucosa implanted on the perianal skin of a patient with Crohn disease.

Intestinal mucosa implanted in skin is an exceedingly rare occurrence. Implantations are thought to occur during the creation of ostomy sites or other surgical procedures in which suture goes through bowel mucosa and then skin. Current ostomy literature reports this as a very uncommon complication. We present a 54-year-old man diagnosed with Crohn disease with severe perianal involvement who was referred to our outpatient clinic because of two persistent perianal cutaneous ulcerations. He previously underwent several interventions to drain complex perianal fistulas and abscesses, the last of them involved placing seton stitches to ensure continuous draining during the healing process. Physical examination revealed two painful ulcerations with bleeding on contact. A skin biopsy was performed, revealing ectopic intestinal mucosa with crypts, villi, and goblet cells. Perianal ulcerations characteristic of Crohn disease might be difficult to differentiate from ectopic implant of bowel mucosa secondary to a surgical procedure in the perianal area. Therefore, we believe a high degree of suspicion and skin biopsy are key to the diagnosis.

Friendly-Sharing: Improving the Performance of City Sensoring through Contact-Based Messaging Applications.

Regular citizens equipped with smart devices are being increasingly used as "sensors" by Smart Cities applications. Using contacts among users, data in the form of messages is obtained and shared. Contact-based messaging applications are based on establishing a short-range communication directly between mobile devices, and on storing the messages in these devices for subsequent delivery to cloud-based services. An effective way to increase the number of messages that can be shared is to increase the contact duration. We thus introduce the Friendly-Sharing diffusion approach, where, during a contact, the users are aware of the time needed to interchange the messages stored in their buffers, and they can thus decide to wait more time in order to increase the message sharing probability. The performance of this approach is anyway closely related to the size of the buffer in the device. We therefore compare various policies either for the message selection at forwarding times and for message dropping when the buffer is full. We evaluate our proposal with a modified version of the Opportunistic Networking Environment (ONE) simulator and using real human mobility traces.

C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study.

BACKGROUND AND PURPOSE: Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. METHODS: Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. RESULTS: Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP>4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30-4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15-4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14-3.67). There was no interaction with randomized antiplatelet treatment. CONCLUSIONS: Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Ovarian cancer cell invasiveness is associated with discordant exosomal sequestration of Let-7 miRNA and miR-200.

BACKGROUND: The role of exosomes in the pathogenesis and metastatic spread of cancer remains to be fully elucidated. Recent studies support the hypothesis that the release of exosomes from cells modifies local extracellular conditions to promote cell growth and neovascularisation. In addition, exosomes may modify the phenotype of parent and/or target cell. For example, sequestration of signaling mediators into exosomes may reduce their intracellular bioavailability to the parent cell thereby altering cell phenotype and metastatic potential. The fusion of released exosomes with target cell and delivery may also modify cell function and activity. In this study, to further elucidate the role of exosomes in ovarian cancer, the release of exosomes from two ovarian cancer cell lines of different invasive capacity and their miRNA content of exosomes were compared. The hypothesis to be tested was that ovarian cancer cell invasiveness is associated with altered release of exosomes and discordant exosomal sequestration of miRNA. METHODS: High (SKOV-3) and low (OVCAR-3) invasive ovarian cancer cell lines were used to characterize their exosome release. SKOV-3 and OVCAR-3 cells were cultured (DMEM, 20% exosome-free FBS) under an atmosphere of 8% O2 for 24 hours. Cell-conditioned media were collected and exosomes were isolated by differential and buoyant density centrifugation and characterised by Western blot (CD63 and CD9). Exosomal microRNA (let-7a-f and miR-200a-c) content was established by real-time PCR. RESULTS: Exosomes were identified with by the presence of typical cup-shaped spherical vesicle and the expression of exosome markers: CD63, CD9. SKOV-3 cells released 2.7-fold more exosomes (1.22 ± 0.11 µg/106 cells) compared to OVCAR-3 (0.44 ± 0.05 µg/106 cells). The let-7 family miRNA transcripts were identified in both ovarian cancer cell lines and their exosomes. The let-7 family transcripts were more abundant in OVCAR-3 cell than SKOV-3 cells. In contrast, let-7 family transcripts were more abundant in exosomes from SKOV-3 than OVCAR-3. miR-200 family transcripts were only identified in OVCAR-3 cells and their exosomes. CONCLUSIONS: The data obtained in this study are consistent with the hypothesis that the releases of exosomes varies significantly between ovarian cancer cell lines and correlates with their invasive potential.

[Charles Miller Fisher: a giant of neurology]. / Charles Miller Fisher, un grande de la neurología.

C. Miller Fisher MD, one of the great neurologists in the 20th century, died in April 2012. Born in Canada, he studied medicine at the University of Toronto. As a Canadian Navy medical doctor he participated in World War II and was a war prisoner from 1941 to 1944. He did a residency in neurology at the Montreal Neurological Institute between 1946 and 1948, and later on was a Fellow in Neurology and Neuropathology at the Boston City Hospital. In 1954 he entered the Massachusetts General Hospital as a neurologist and neuropathologist, where he remained until his retirement, in 2005. His academic career ended as Professor Emeritus at Harvard University. His area of special interest in neurology was cerebrovascular disease (CVD). In 1954 he created the first Vascular Neurology service in the world and trained many leading neurologists on this field. His scientific contributions are present in more than 250 publications, as journal articles and book chapters. Many of his articles, certainly not restricted to CVD, were seminal in neurology. Several concepts and terms that he coined are currently used in daily clinical practice. The chapters on CVD, in seven consecutive editions of Harrison's Internal Medicine textbook, are among his highlights. His death was deeply felt by the neurological community.

Hyperspectral Microscopy Technology to Detect Syrups Adulteration of Endemic Guindo Santo and Quillay Honey Using Machine-Learning Tools.

Honey adulteration is a common practice that affects food quality and sale prices, and certifying the origin of the honey using non-destructive methods is critical. Guindo Santo and Quillay are fundamental for the honey production of Biobío and the Ñuble region in Chile. Furthermore, Guindo Santo only exists in this area of the world. Therefore, certifying honey of this species is crucial for beekeeper communities-mostly natives-to give them advantages and competitiveness in the global market. To solve this necessity, we present a system for detecting adulterated endemic honey that combines different artificial intelligence networks with a confocal optical microscope and a tunable optical filter for hyperspectral data acquisition. Honey samples artificially adulterated with syrups at concentrations undetectable to the naked eye were used for validating different artificial intelligence models. Comparing Linear discriminant analysis (LDA), Support vector machine (SVM), and Neural Network (NN), we reach the best average accuracy value with SVM of 93% for all classes in both kinds of honey. We hope these results will be the starting point of a method for honey certification in Chile in an automated way and with high precision.

A Catastrophic Complication of Thoracic Endovascular Aortic Repair: Aortoesophageal Fistula.

A 62-year-old man was admitted to the hospital due to sepsis secondary to a hemodialysis catheter-related infection that, upon diagnostic evaluation, demonstrated to be caused by P. aeruginosa and was treated with meropenem. Eradication of the infectious episode was confirmed by blood workup, including cultures. One month after the initial episode, the patient was readmitted due to a symptomatic penetrating aortic ulcer, which was classified as a cardiovascular emergency. The patient underwent an aortic stent-graft placement. Four weeks later, he presented to the emergency department with a 2-hour onset of thoracic pain and massive hematemesis. The esophagus and aortic segment with aortic stent graft were resected en bloc after an aortoesophageal fistula was diagnosed.

International multicentre observational study to evaluate the association between perioperative red blood cell transfusions and 1-year mortality after major cancer surgery (ARCA-1): study design, statistical analysis plan and study protocol.

INTRODUCTION: Blood transfusion is still common in patients undergoing major cancer surgery. Blood transfusion can be associated with poor prognosis in patients with cancer. Perioperative Care in the Cancer Patient -1 (ARCA-1) aims to assess in a large cohort of patients the current incidence, pattern of practice and associations between perioperative blood transfusions and 1-year survival in patients undergoing major cancer surgery. METHODS AND ANALYSIS: ARCA-1 is a prospective international multicentre observational study that will include adult patients scheduled to have major cancer surgical procedures with the intention to cure, and an overnight planned hospital admission. The study will be opened for 1 year for enrolment (7 January 2020-7 February 2021). Each centre will enrol patients for 30 days. The primary endpoint of this study is all-cause mortality 1 year after major cancer surgery. Secondary endpoints are rate of perioperative blood product use, cancer-specific mortality at 1 year and PFSs and 30-day morbidity and mortality. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board at The University of Texas-MD Anderson Cancer Center. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT04491409.

Obstructive sleep apnea as an independent stroke risk factor: possible mechanisms.

Obstructive Sleep Apnea (OSA) is a prevalent disease that has emerged as a new cerebrovascular disease (CVD) risk factor, which is independent of its association to hypertension, age and other known conditions that increase CVD. The mechanisms involved in this relation are most likely induced by the periodic hypoxia/reoxygenation that characteristically occurs in OSA, which results in oxidative stress, endothelial dysfunction and activation of the inflammatory cascade, all of which favor atherogenesis. Numerous markers of these changes have been reported in OSA patients, including increased circulating free radicals, increased lipid peroxidation, decreased antioxidant capacity, elevation of tumor necrosis factor and interleukines, increased levels of proinflammatory nuclear transcription factor kappa B, decreased circulating nitric oxide, elevation of vascular adhesion molecules and vascular endothelial growth factor. In addition, several authors have described that Continuous Positive Airway Pressure, the standard OSA therapy, reverts these abnormalities. Further research is needed in order to better clarify the complex mechanisms that underlie the relation between OSA, atherogenesis and CVD which most likely will have significant clinical impact.

Two New Hygroline and Tropane Alkaloids Isolated from Schizanthus hookeri and S. tricolor (Solanaceae).

Two new hygroline and tropane alkaloids, 4-hydroxybenzenepropanoylhygroline (1) and 3α,4ß-dihydroxy-6ß-angeloyoxytropane (2) have been isolated from the aerial parts of Schizanthus hookeri and S. tricolor, respectively, two plants indigenous from Chile. Their structures were elucidated by spectroscopic methods and high resolution mass spectrometry. Their antiparasitic activity and cytotoxicity were measured.

Infrared light field imaging system free of fixed-pattern noise.

Digital photonic sensors have greatly evolved to maximize sensitivity and spatial, spectral, and temporal imaging resolution. For low-energy photons, new designs have generated new types of noise that degrade the formed-image signal-to-noise ratio to values lower than 1. Fixed-pattern noise (FPN), which is produced by the non-uniform focal-plane-array optoelectronics response, is an ill-posed problem in infrared and hyperspectral imaging science. Here, we experimentally show that the FPN behaves as an object at a depth of infinity when a light field is captured by an imaging system. The proposed method is based on the capture of the light field of a scene and digital refocusing to any nearby objects in the scene. Unlike standard techniques for FPN reduction, our method does not require knowledge of the physical parameters of the optoelectronic transducer, the motion scene, or the presence of off-line blackbody sources. The ability of the proposed method to reduce FPN is measured by evaluating the structural similarity (SSIM) index employing a blackbody-based FPN reduction technique as a reference. This new interpretation of the FPN opens avenues to create new cameras for low-energy photons with the ability to perform denoising by digital refocusing.

Hemorragia encefálica por angiopatía amiloidea / Amyloid angiopathy brain hemorrhage

Amyloid angiopathy (AA) is a selective deposition of amyloid in the walls of the brain vessels. It is a form of sporadic and localized amyloidosis, constituted by the Aβ4 protein, the same of Alzheimer's disease senile plaques. The most consistent clinical effect of AA is spontaneous brain hemorrhage (BH). It is the second most common cause of BH after arterial hypertension (HT). Other clinical manifestations are cognitive impairment and transient focal neurological episodes. AA BH is characteristically localized in the cerebral cortex and subcortical white matter (lobar hemorrhage), consistent with the preferential deposit of amyloid in the walls of leptomeningeal and intracortical small cerebral vessels. Other types of AA hemorrhagic complications are microbleeds (MB), cerebral convexity subarachnoid hemorrhage (cSAH) and superficial hemosiderosis (cSS). The diagnosis of AA BH is based on the Boston criteria. Using these criteria, several non-hemorrhagic biomarkers of AA have been identified that can be useful in its diagnosis. The principal AA BH risk factor is age, followed by cSS, MB, Apolipoprotein E gen ε2 and ε4 alleles, HT and the use of antithrombotics. This condition has a high recurrence rate that shares the same risk factors. There is no specific treatment for AA BH. It has a better prognosis than HT BH during the acute period, but worse on the long term, due to its high recurrence rate and cognitive impairment.

Ventilación en posición prona en el manejo de pacientes con síndrome de dificultad respiratoria aguda / Prone ventilation in the management of patients with acute respiratory distress syndrome

INTRODUCCIÓN. El posicionamiento prono es una de las estrategias ventilatorias más estudiadas y difundidas de la medicina intensiva, forma parte del manejo de ventilación protectiva con impacto en disminución de la mortalidad en pacientes con síndrome de dificultad respiratoria aguda. OBJETIVO. Revisar la evidencia disponible acerca de ventilación en posición prona en pacientes con síndrome de dificultad respiratoria aguda, enfocada en el análisis fisiopatológico y clínico. MATERIALES Y MÉTODOS. Se realizó una revisión bibliográfica en la base de datos de buscadores académicos como PubMed, Google Scholar y Elsevier, en los idiomas español e inglés, en el período comprendido entre los años 1970-2020; se seleccionaron 16 publicaciones en texto completo: 3 metaanálisis, 10 estudios randomizado, 3 revisiones sistemáticas. CONCLUSIÓN. En base a la evidencia y percepción recopilada de la experiencia de los autores, la ventilación en posición prona es una estrategia de manejo de primera línea, fiable, que no requiere para su empleo equipamiento costoso ni complejo y ha demostrado mejoría en desenlaces relevantes en el tratamiento del paciente crítico respiratorio como disminución en la mortalidad y optimización de los parámetros ventilatorios y de oxigenación.

INTRODUCTION. Prone positioning is one of the most studied and widespread ventilatory strategies in intensive medicine, it is part of protective ventilation management with an impact on mortality reduction in patients with acute respiratory distress syndrome. OBJECTIVE. To review the available evidence about ventilation in the prone position in patients with acute respiratory distress syndrome, focused on the pathophysiological and clinical analysis. MATERIALS AND METHODS. A bibliographic review was carried out in the databases of academic search engines such as PubMed, Google Scholar and Elsevier, in the Spanish and English languages, in the period between the years 1970-2020, 16 full text publications were selected: 3 meta-analyses, 10 randomized studies, 3 systematic reviews. CONCLUSION. Based on the evidence and perception gathered from the authors' experience, prone ventilation is a reliable first-line management strategy that does not require costly or complex equipment for its use and has demonstrated improvements in relevant outcomes in the treatment of the critically ill respiratory patient, such as decreased mortality and optimization of ventilatory and oxygenation parameters.