Synthesis, biological evaluation, and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis: Part 2. Synthesis of rigid pyrazolones

Two series of novel rigid pyrazolone derivatives were synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis. Two of these compounds showed a high activity against MTB (MIC = 4 μg/mL). The newly synthesized pyrazolones were also computationally investigated to analyze if their properties fit the pharmacophoric model for antitubercular compounds previously built by us. The results are in agreement with those reported by us previously for a class of pyrazole analogues and confirm the fundamental role of the p-chlorophenyl moiety at C4 in the antimycobacterial activity

Radionuclide Determination In Surface Water Samples By Inductively Coupled Plasma With Sector Field Mass Spectrometry (ICP-SFMS)

The determination of naturally occurring radionuclides in the environment by inductively coupled plasma mass spectrometry of high resolution (ICP-SFMS) has gained recognition over the last fifteen years, relative to the radiometric techniques, as the result of improvement in instrumental performance, sample introduction equipment and sample preparation. With the increase in instrumental sensitivity, it is now possible to measure ultratrace levels of many radioisotopes.The aim of this work was to determined the natural radionuclides (232Th, 234U, 235U and 238U) in surface water using Inductively Coupled Plasma-Sector Field Mass Spectrometry (ICP-SFMS). The samples were sampling from Lerma river, State of Mexico at february to april 2015. The process of treatment of sample consisted in perform an acid digestion according to the 3015A USEPA method followed of the direct measurement in ICP-SFMS. Results obtained were: a) identify the presence of 232Th, 234U, 235U and 238U isotopes in water, b) isotopic ratios were for 234U/238U=1.133 ± 0.016. ICP-SFMS has gained popularity in the field of radiochemistry, particularly as a method of detection for long lived-actinides

Place of Preoperative Treatment of Acromegaly with Somatostatin Analog on Surgical Outcome: A Systematic Review and Meta-Analysis

Context: Transsphenoidal neurosurgery is the accepted first-line treatment of acromegaly in the majority of patients. Previous studies addressing preoperative somatostatin analog (SSA) treatment and subsequent surgical cure rates are conflicting, reporting either benefits or no significant differences. Objective: The aim of this study, based on a meta-analysis of all published reports, was to investigate whether treatment with SSA before surgery improves the surgical outcome of acromegaly. Data sources: All studies of preoperative treatment of acromegaly with SSA were systematically reviewed up to December 2011. We searched the Medline, Embase, Cochrane and Google Scholar electronic databases. Study selection: The primary endpoint was the biochemical postoperative cure rate. We identified 286 studies, out of which 10 studies (3.49%) fulfilling the eligibility criteria were selected for analysis; five retrospective studies with a control group, two prospective non-randomized trials, and three prospective controlled trials. The meta-analysis was conducted using the random-effects model. Data extraction: Data were extracted from published reports by two independent observers. Data synthesis: A borderline effect was detected in the analysis of all of the trials with control groups, with a pooled odds ratio (OR) for biochemical cure with SSA treatment of 1.62 (95% CI, 0.93-2.82). In the analysis of the three prospective controlled trials, a statistically significant effect was identified OR: 3.62 (95% CI, 1.88-6.96). Conclusions: Preoperative treatment with SSA og GH-secreting pituitary adenomas shows a significant improvement on surgical results. This meta-analysis suggests that in centers without optimal results all patients with a GH-secreting pituitary macroadenoma should be treated with a long-acting SSA prior to surgical treatment

Ten years of preanalytical monitoring and control: Synthetic Balanced Score Card Indicator

Introduction: Preanalytical control and monitoring continue to be an important issue for clinical laboratory professionals. The aim of the study was to evaluate a monitoring system of preanalytical errors regarding not suitable samples for analysis, based on different indicators; to compare such indicators in different phlebotomy centres; and finally to evaluate a single synthetic preanalytical indicator that may be included in the balanced scorecard management system (BSC). Materials and methods: We collected individual and global preanalytical errors in haematology, coagulation, chemistry, and urine samples analysis. We also analyzed a synthetic indicator that represents the sum of all types of preanalytical errors, expressed in a sigma level. We studied the evolution of those indicators over time and compared indicator results by way of the comparison of proportions and Chi-square. Results: There was a decrease in the number of errors along the years (P < 0.001). This pattern was confirmed in primary care patients, inpatients and outpatients. In blood samples, fewer errors occurred in outpatients, followed by inpatients. Conclusion: We present a practical and effective methodology to monitor unsuitable sample preanalytical errors. The synthetic indicator results summarize overall preanalytical sample errors, and can be used as part of BSC management system

AmericasNLI: Machine translation and natural language inference systems for Indigenous languages of the Americas

Little attention has been paid to the development of human language technology for truly low-resource languages—i.e., languages with limited amounts of digitally available text data, such as Indigenous languages. However, it has been shown that pretrained multilingual models are able to perform crosslingual transfer in a zero-shot setting even for low-resource languages which are unseen during pretraining. Yet, prior work evaluating performance on unseen languages has largely been limited to shallow token-level tasks. It remains unclear if zero-shot learning of deeper semantic tasks is possible for unseen languages. To explore this question, we present AmericasNLI, a natural language inference dataset covering 10 Indigenous languages of the Americas. We conduct experiments with pretrained models, exploring zero-shot learning in combination with model adaptation. Furthermore, as AmericasNLI is a multiway parallel dataset, we use it to benchmark the performance of different machine translation models for those languages. Finally, using a standard transformer model, we explore translation-based approaches for natural language inference. We find that the zero-shot performance of pretrained models without adaptation is poor for all languages in AmericasNLI, but model adaptation via continued pretraining results in improvements. All machine translation models are rather weak, but, surprisingly, translation-based approaches to natural language inference outperform all other models on that task

Clima escolar, inteligencia emocional y psicología educativa en los espacios de aprendizaje

Desde hace un tiempo se vienen detectando niveles de estrés, fracaso escolar, en niveles más elevados y en etapas educativas ansiedades más tempranas. Este suceso viene derivado de factores como el aumento de responsabilidad y autonomía, carga de trabajo académico, así como falta de habilidades para gestionar las emociones. De ahí que, en las últimas décadas, la Inteligencia Emocional haya adquirido una mayor importancia en el ámbito educativo, puesto que actúa como medio para promover el bienestar psicológico del alumnado, facilitándoles la comprensión del entorno que los rodea, así como dotándolos de las competencias. necesarios para hacer frente a las diversas situaciones que se presentan. De esta manera, este constructo se constituye como un proceso educativo que ha de ser permanente y continúo favoreciendo el desarrollo integral de los estudiantes

Antimicrobial, Antioxidant and Cytotoxic Activities and Phytochemical Screening of Some Yemeni Medicinal Plants

The traditional medicine still plays an important role in the primary health care in Yemen. The current study represents the investigation of 16 selected plants, which were collected from different localities of Yemen. The plants were dried and extracted with two different solvents (methanol and hot water) to yield 34 crude extracts. The obtained extracts were tested for their antimicrobial activity against three Gram-positive bacteria, two Gram-negative bacteria, one yeast species and three multiresistant Staphylococcus strains using agar diffusion method, for their antioxidant activity using scavenging activity of DPPH radical method and for their cytotoxic activity using the neutral red uptake assay. In addition, a phytochemical screening of the methanolic extracts was done. Antibacterial activity was shown only against Gram-positive bacteria, among them multiresistant bacteria. The highest antimicrobial activity was exhibited by the methanolic extracts of Acalypha fruticosa, Centaurea pseudosinaica, Dodonaea viscosa, Jatropha variegata, Lippia citriodora, Plectranthus hadiensis, Tragia pungens and Verbascum bottae. Six methanolic extracts especially those of A. fruticosa, Actiniopteris semiflabellata, D. viscosa, P. hadiensis, T. pungens and V. bottae showed high free radical scavenging activity. Moreover, remarkable cytotoxic activity against FL-cells was found for the methanolic extracts of A. fruticosa, Iris albicans, L. citriodora and T. pungens. The phytochemical screening demonstrated the presence of different types of compounds like flavonoids, terpenoids and others, which could be responsible for the obtained activities

Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL)-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study)

BACKGROUND: Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for the treatment of this form of dyslipidemia and to identify factors associated with better treatment response. METHODS: Multicenter, international, open-label study. Four hundred and thirty seven patients were included. The plasma lipid levels at inclusion were fasting triglyceride concentrations between 1.6–3.9 mM/l and HDL cholesterol ≤ 1.05 mM/l for women and ≤ 0.9 mM/l for men. The LDL cholesterol was below 4.2 mM/l. All patients received ciprofibrate 100 mg/d. Efficacy and safety parameters were assessed at baseline and at the end of the treatment. The primary efficacy parameter of the study was percentage change in triglycerides from baseline. RESULTS: After 4 months, plasma triglyceride concentrations were decreased by 44% (p < 0.001). HDL cholesterol concentrations were increased by 10% (p < 0.001). Non-HDL cholesterol was decreased by 19%. A greater HDL cholesterol response was observed in lean patients (body mass index < 25 kg/m(2)) compared to the rest of the population (8.2 vs 19.7%, p < 0.001). In contrast, cases with excess body weight had a larger decrease in non-HDL cholesterol levels (-20.8 vs -10.8%, p < 0.001). There were no significant complications resulting from treatment with ciprofibrate. CONCLUSIONS: Ciprofibrate is efficacious for the correction of hypertriglyceridemia / low HDL cholesterol. A greater decrease in non-HDL cholesterol was found among cases with excess body weight. The mechanism of action of ciprofibrate may be influenced by the pathophysiology of the disorder being treated

Reimplantable Microdrive for Long-Term Chronic Extracellular Recordings in Freely Moving Rats

Extracellular recordings of electrical activity in freely moving rats are fundamental to understand brain function in health and disease. Such recordings require a small-size, lightweight device that includes movable electrodes (microdrive) to record either a new set of neurons every day or the same set of neurons over time. Ideally, microdrives should be easy to implant, allowing precise and smooth displacement of electrodes. The main caveat of most commercially available microdrives is their relatively short half-life span, in average ranging from weeks to a month. For most experiments, recording days–weeks is sufficient, but when the experiment depends on training animals for several months, it is crucial to develop new approaches. Here, we present a low-cost, reusable, and reimplantable device design as a solution to extend chronic recordings to long-term. This device is composed of a baseplate that is permanently fixed to the rodent’s skull, as well as a reusable and replaceable microdrive that can be attached and detached from the baseplate, allowing its implantation and reimplantation. Reimplanting this microdrive is particularly convenient when no clear neuronal signal is present, or when the signal gradually decays across days. Our microdrive incorporates a mechanism for moving a 16 tungsten-wire bundle within a small (∼15 mm3) lightweight device (∼4 g). We present details of the design, manufacturing, and assembly processes. As a proof of concept, we show that recordings of the nucleus accumbens core (NAcc) in a freely behaving rat are stable over a month. Additionally, during a lever-press task, we found, as expected, that NAc single-unit activity was associated with rewarded lever presses. Furthermore, we also show that NAc shell (NAcSh) responses evoked by freely licking for sucrose, consistent with our previously published results, were conserved from a first implant to a second microdrive reimplant in the same rat, notably showing reimplantation is possible without overtly affecting the functional responses of the area of interest. In sum, here we present a novel microdrive design (low-cost, small size, and light weight) that can be used for long-term chronic recordings and reimplanted in freely behaving rats