Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease.

BACKGROUND: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs. METHODS: We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-ß precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction. RESULTS: Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS. LIMITATIONS: The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest. CONCLUSION: Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.

Impact of Continuous Estroprogestin Treatment on Circulating Microparticle Levels in Deep Endometriosis Patients.

There has been increasing interest in the study of new pathogenic mechanisms in endometriosis (END), including the coagulation/fibrinolysis system and its link with inflammation and tissue remodeling. It has been suggested that END patients, especially with deep-infiltrating (DE) forms, could present a hypercoagulable state revealing higher levels of proinflammatory and procoagulant markers, such as total circulating microparticles (cMPs) and cMP-TF (tissue factor), released by cells in response to damage, activation, or apoptosis. However, no previous study has assessed the effect of END hormonal treatments on cMP and cMP-TF levels. Therefore, the aim of this study was to evaluate the impact of these treatments on cMP and cMP-TF levels in DE patients. Three groups were compared: DE patients receiving a continuous combined oral contraceptive regimen (CCOCR) (n = 41), DE patients without CCOCR (n = 45), and a control group (n = 43). cMP and cMP-TF levels were evaluated in platelet-free plasma. A significant decrease in the total cMP levels was found in the DE group with CCOCR versus the group without CCOCR, reflecting a higher chronic inflammatory status in DE patients that decreased with the treatment. cMP-TF levels were higher in DE patients receiving CCOCR versus those not receiving CCOCR, suggesting that treatments containing estrogens play a predominant role in suppressing the inhibitory pathway of TF.

Chemical and Biological Characterization of Green and Processed Coffee Beans from Coffea arabica Varieties.

Coffee is one of the most consumed beverages in the world; its production is based mainly on varieties of the Coffea arabica species. Mexico stands out for its specialty and organic coffee. In Guerrero, the production is done by small indigenous community cooperatives that market their product as raw material. Official Mexico Standards stipulate the requirements for its commercialization within the national territory. In this work, the physical, chemical, and biological characterizations of green, medium, and dark roasted beans from C. arabica varieties were carried out. Analysis by HPLC showed higher chlorogenic acid (55 mg/g) and caffeine (1.8 mg/g) contents in the green beans of the Bourbon and Oro Azteca varieties. The caffeine (3.88 mg/g) and melanoidin (97 and 29 mg/g) contents increased according to the level of roasting; a dissimilar effect was found in the chlorogenic acid content (14.5 mg/g). The adequate nutritional content and the sensory evaluation allowed the classification of dark-roasted coffee as premium coffee (84.25 points) and medium-roasted coffee as specialty coffee (86.25 points). The roasted coffees presented antioxidant activity without cytotoxic effects; the presence of CGA and caffeine supports the beneficial effects of drinking coffee. The results obtained will serve as a basis for making decisions on improvements to the coffees analyzed.

Production of Two Isomers of Sphaeralcic Acid in Hairy Roots from Sphaeralcea angustifolia.

The Sphaeralcea angustifolia plant is used as an anti-inflammatory and gastrointestinal protector in Mexican traditional medicine. The immunomodulatory and anti-inflammatory effects have been attributed to scopoletin (1), tomentin (2), and sphaeralcic acid (3) isolated from cells in suspension cultures and identified in the aerial tissues of the wild plant. The hairy roots from S. angustifolia established by infecting internodes with Agrobacterium rhizogenes were explored to produce active compounds based on biosynthetic stability and their capacity to produce new compounds. Chemical analysis was resumed after 3 years in these transformed roots, SaTRN12.2 (line 1) produced scopoletin (0.0022 mg g-1) and sphaeralcic acid (0.22 mg g-1); instead, the SaTRN7.1 (line 2) only produced sphaeralcic acid (3.07 mg g-1). The sphaeralcic acid content was 85-fold higher than that reported for the cells in the suspension cultivated into flakes, and it was similar when the cells in suspension were cultivated in a stirring tank under nitrate restriction. Moreover, both hairy root lines produced stigmasterol (4) and ß-sitosterol (5), as well as two new naphthoic derivates: iso-sphaeralcic acid (6) and 8-methyl-iso-sphaeralcic acid (7), which turned out to be isomers of sphaeralcic acid (3) and have not been reported. The dichloromethane-methanol extract from SaTRN7.1 hairy root line had a gastroprotective effect on an ulcer model in mice induced with ethanol.

Dose-Effect Determination of a Neuroprotector Fraction Standardized in Coumarins of Tagetes lucida and Bioavailability.

Neurodegeneration has been associated with chronic inflammation states in the brain. For this reason, attention has been directed to drugs indicated as anti-inflammatory as possible therapies for the treatment of said conditions. Tagetes lucida has been widely used as a folk remedy in illnesses associated with the central nervous system and inflammatory ailments. Among the compounds that stand out in the plant against these conditions are coumarins, such as 7-O-prenyl scopoletin, scoparone, dimethylfraxetin, herniarin, and 7-O-prenylumbelliferone. Therefore, the relationship between the therapeutic effect and the concentration was evaluated through pharmacokinetic and pharmacodynamic studies, including vascular permeability evaluation by blue Evans and pro- and anti-inflammatory cytokines quantification, under a neuroinflammation model induced by lipopolysaccharide by the oral administration of three different doses (5, 10, and 20 mg/kg) of a bioactive fraction of T. lucida. In the present study, it was found that all doses showed a neuroprotective and immunomodulatory effect, although the doses of 10 and 20 mg/kg were able to exert their effect for a longer time and to a greater extent. The protective effects of the fraction may be mainly associated with the DR, HR, and SC coumarins due to their structural profile and plasmatic and brain tissue bioavailability.

Clinical and sonographic impact of oral contraception in patients with deep endometriosis and adenomyosis at 2 years of follow-up.

Nowadays, combined oral contraceptives (COCs) are successfully employed for the treatment of endometriosis (END) and adenomyosis (AD) in a large proportion of patients. However, literature focusing on the clinical and sonographic response to treatment in the long-term follow-up of patients with deep endometriosis (DE) and AD is scarce. The aim of this study was to evaluate the changes in the symptoms and the sonographic exams at 12 and 24 months of follow-up in patients who had received a flexible extended COC regimen containing 2 mg of dienogest/30 µg ethinyl estradiol. This prospective, longitudinal, observational study included women diagnosed with DE and AD presenting no surgical indication and were candidates to treatment with COCs. The presence and severity of dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria were evaluated using the Numerical Rating Scale (NRS) at baseline, and at 12 and 24 months of treatment. Transvaginal ultrasound was also performed at these check points searching for criteria of AD and reporting the size of the DE nodules and ovarian endometriomas (OE). Sixty-four patients were included. A significant decrease in the number of patients with severe dysmenorrhea and non-menstrual pelvic pain was reported during follow-up. The mean NRS score for dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria was also significantly lower at follow-up. There was a significant reduction in the sonographic number and type of AD criteria during follow-up after treatment. Similarly, a significant decrease in the size of OE and uterosacral ligament involvement in DE was observed at the 12-month follow-up, with a further, albeit not statistically significant, decrease in the 12- to 24-month follow-up. Additionally, torus and rectosigmoid DE decreased in size, although the reduction was not statistically significant at any study point. This prospective study suggests a clinical and sonographic improvement after a flexible extended COC regimen in DE and AD patients, which was significant at 12 months of follow-up. The improvement was more evident in AD and OEs compared with DE. Further research with a longer follow-up, larger sample size and comparison with other treatments is needed.

Intracranial Self-stimulation of the Medial Forebrain Bundle Ameliorates Memory Disturbances and Pathological Hallmarks in an Alzheimer's Disease Model by Intracerebral Administration of Amyloid-ß in Rats.

No curative or fully effective treatments are currently available for Alzheimer's disease (AD), the most common form of dementia. Electrical stimulation of deep brain areas has been proposed as a novel neuromodulatory therapeutic approach. Previous research from our lab demonstrates that intracranial self-stimulation (ICSS) targeting medial forebrain bundle (MFB) facilitates explicit and implicit learning and memory in rats with age or lesion-related memory impairment. At a molecular level, MFB-ICSS modulates the expression of plasticity and neuroprotection-related genes in memory-related brain areas. On this basis, we suggest that MFB could be a promising stimulation target for AD treatment. In this study, we aimed to assess the effects of MFB-ICSS on both explicit memory as well as the levels of neuropathological markers ptau and drebrin (DBN) in memory-related areas, in an AD rat model obtained by Aß icv-injection. A total of 36 male rats were trained in the Morris water maze on days 26-30 after Aß injection and tested on day 33. Results demonstrate that this Aß model displayed spatial memory impairment in the retention test, accompanied by changes in the levels of DBN and ptau in lateral entorhinal cortex and hippocampus, resembling pathological alterations in early AD. Administration of MFB-ICSS treatment consisting of 5 post-training sessions to AD rats managed to reverse the memory deficits as well as the alteration in ptau and DBN levels. Thus, this paper reports both cognitive and molecular effects of a post-training reinforcing deep brain stimulation procedure in a sporadic AD model for the first time.

The Journey of a Medicinal Plant throughout Science: Sphaeralcea angustifolia (Cav.) G. Don (Malvaceae).

Using herbal medicine is an ancestral cultural practice among Mexicans. A broad sector of society turns to plants to treat priority health problems, a reality that leads scientists to explore the healing value attributed to them. Advances in the experimental research of Sphaeralcea angustifolia confirmed the anti-inflammatory activity of the species; therefore, an analysis of the scope of these studies is now warranted. As such, this paper is a compendium of the advances published in the scientific literature (from 2004 to 2021) on the anti-inflammatory properties of this plant. The promise offered by the species as a potential therapeutic agent is also considered, without dismissing aspects necessary for the preservation of this resource and its cultural and physical environment. The chemical-pharmacological aspects of the wild plant and its in vitro culture are highlighted. The plant's anti-inflammatory properties support its clinical application as an anti-inflammatory phytopharmaceutical to treat arthritic conditions. The sustained therapeutic potential of S. angustifolia is reinforced by the biotechnological processes designed to conserve the resource, thus contributing to the protection of biodiversity and cultural diversity, aspects distinctive of a megadiverse country such as Mexico.

ICT efficacy and response to different needs in university classrooms: effects on attitudes and active behaviour towards technology.

Digital competence is considered to be a crucial learning outcome in education in the 21st century. In this context, research highlights the fact that the perceptions that instructors manifest about different aspects of Information and Communication Technologies (ICTs) condition these professionals' behaviour towards these learning resources. In the same line, this study aims to analyse the effects that exist between a series of dimensions related to the perception of university teaching staff on the capacity of ICTs to respond to different needs of students, on perceived efficacy and attitudes towards these tools and, lastly, on active behaviour towards their use. To do so, 345 university instructors from the Spanish educational system filled in an online questionnaire. The application of a Structural Equation Model underscores the fact that the ability of ICTs to respond to the different needs of students in the university classroom and their perceived efficacy in the teaching-learning process both exert a positive effect on attitudes in favour of their incorporation into the classroom. In turn, these attitudes also have a significant effect on active behaviour with ICT resources. In addition, various mediating effects are seen to influence an active behaviour. All this gives rise to a discussion on the implications of these results to encourage the training of university teaching staff in the knowledge and management of ICTs. Increasing confidence in ICTs as effective tools to respond to different needs could significantly favour positive attitudes and behaviour so that these resources are actively integrated into the classroom.

One-year efficacy and safety of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: KYONAL study.

OBJECTIVES: Naloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study. METHODS: This one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L). RESULTS: A total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment. CONCLUSION: The results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.

Pharmacokinetics and Tissue Distribution of Coumarins from Tagetes lucida in an LPS-Induced Neuroinflammation Model.

Tagetes lucida has been widely used as a folk remedy in illnesses associated with the central nervous system and inflammatory ailments. Among the chemical compounds that stand out in the plant against these conditions are coumarins, such as 7-O-prenylscopoletin (PE), scoparone (SC), dimethylfraxetin (DF), herniarin (HR), and 7-O-prenylumbelliferone (PU), considered potential anti-neuroinflammatory compounds. Therefore, the relationship between the therapeutic effect and the dose can be evaluated through pharmacokinetic-pharmacodynamic (PK-PD) studies under a model of neuroinflammation induced by lipopolysaccharide (LPS). Nonetheless, accomplishing those studies requires an accurate and robust analytical method for the detection of these compounds in different biological matrices of interest. Due to the above, in the present study, a bioanalytical method was established by HPLC-DAD-UV for the simultaneous quantification of the coumarins present in the hexane extract of T. lucida, which was able to determine the temporal concentration profiles of each of the coumarins in the plasma, brain, kidney, and spleen samples of healthy and damaged mice. Coumarins showed an increase in plasma concentrations of up to three times in the neuroinflammation model, compared to healthy mice, so it was possible to quantify the therapeutic agents in the main target organ, the brain. The ability of compounds to cross the blood-brain barrier is an advantage in the treatment of diseases associated with neuroinflammation processes that can be studied in future PK-PD evaluations.

Intracranial Self-Stimulation and Memory in Rats: A Sistematic Review.

BACKGROUND: Intracranial self-stimulation (ICSS) is a technique by which rats press a lever to stimulate their brains through an electrode chronically implanted in brain reward areas. Currently only two laboratories in the world, one in India and one in Spain, are intensively studying the effect of this kind of deep brain stimulation on learning and memory. This paper will present the main findings. METHODS: Different groups of young and old healthy and brain-damaged rats with electrodes implanted in the medial forebrain bundle received a treatment of ICSS after being trained in several paradigms of implicit and explicit learning. Memory was tested over short and long-term periods. Structural and molecular post-mortem analyses of their brains were examined in relation to memory results. RESULTS: ICSS enhances implicit and explicit memory, especially in animals showing poor performance in the learning tasks, such as brain-damaged subjects. At the structural and molecular level, ICSS enhances size and dendritic arborization and promotes neurogenesis in specific hippocampal areas. ICSS also regulates the expression of genes related to learning and memory. CONCLUSIONS: Through activating reward and neural plasticity mechanisms, ICSS in the medial forebrain bundle is a promising technique for memory-enhancing treatments.

Spontaneous Regeneration of Plantlets Derived from Hairy Root Cultures of Lopezia racemosa and the Cytotoxic Activity of Their Organic Extracts.

A histological analysis was performed with the aim of elucidating the spontaneous regeneration process of the hairy root lines LRT 2.3 and LRT 6.4, derived from Lopezia racemosa leaf explants and genetically transformed with the Agrobacterium rhizogenes strain ATCC15834/pTDT. The analysis showed both lines regenerate via indirect somatic embryogenesis; LRT 6.4 also regenerated by direct organogenesis. The morphogenic characteristics of the regenerated plantlets from both lines showed the typical characteristics, described previously, including a higher number of axillary shoot formation, short internodes, and plagiotropic roots compared with wild-type seedlings. The regeneration process occurred without the addition of plant growth regulators and was linked to the sucrose concentration in the culture medium. Reducing the sucrose concentration from 3% to 2%, 1%, and 0.5% increased the regeneration rate in LRT 6.4; the effect was less pronounced in LRT 2.3. The cytotoxic activity of different organic extracts obtained from roots and shoots were evaluated in the cancer cell lines HeLa (cervical carcinoma), HCT-15 (colon adenocarcinoma), and OVCAR (ovary carcinoma). The hexane and dichloromethane extracts from roots of both lines showed cytotoxic activity against the HeLa cell line. Only the dichloromethane extract from the roots of PLRT 2.3 showed cytotoxic activity against the OVCAR cell line. None of the methanol extracts showed cytotoxic activity, nor the shoot extracts from any solvent.

Protocol to assess rewarding brain stimulation as a learning and memory modulating treatment: Comparison between self-administration and experimenter-administration.

Intracranial electrical self-stimulation (ICSS) is a useful procedure in animal research. This form of administration ensures that areas of the brain reward system (BRS) are being functionally activated, since the animals must perform an operant response to self-administer an electrical stimulus. Rewarding post-training ICSS of the medial forebrain bundle (MFB), an important system of the BRS, has been shown to consistently improve rats' acquisition and retention in several learning tasks. In the clinical setting, deep brain stimulation (DBS) of different targets is currently being used to palliate the memory impairment that occurs in some neurodegenerative diseases. However, the stimulation of the MFB has only been used to treat emotional alterations, not memory disorders. Since DBS stimulation treatments in humans are exclusively administered by external sources, studies comparing the efficacy of that form of application to a self-administered stimulation are key to the translationality of ICSS. This protocol compares self-administered (ICSS) and experimenter-administered (EAS) stimulation of the MFB on the spatial Morris Water Maze task (MWM). c-Fos immunohistochemistry procedure was carried out to evaluate neural activation after retention. Results show that the stimulation of the MFB improves the MWM task regardless of the form of administration, although some differences in c-Fos expression were found. Present results suggest that MFB-ICSS is a valid animal model to study the effects of MFB electrical stimulation on memory, which could guide clinical applications of DBS. The present protocol is a useful guide for establishing ICSS behavior in rats, which could be used as a learning and memory-modulating treatment.

Intracranial Self-Stimulation and Memory in Rats: A Sistematic Review / Autoestimulación Eléctrica Intracraneal y Memoria en Ratas: una Revisión Sistemática

Background: Intracranial self-stimulation (ICSS) is a technique by which rats press a lever to stimulate their brains through an electrode chronically implanted in brain reward areas. Currently only two laboratories in the world, one in India and one in Spain, are intensively studying the effect of this kind of deep brain stimulation on learning and memory. This paper will present the main findings. Methods: Different groups of young and old healthy and brain-damaged rats with electrodes implanted in the medial forebrain bundle received a treatment of ICSS after being trained in several paradigms of implicit and explicit learning. Memory was tested over short and long-term periods. Structural and molecular post-mortem analyses of their brains were examined in relation to memory results. Results: ICSS enhances implicit and explicit memory, especially in animals showing poor performance in the learning tasks, such as brain-damaged subjects. At the structural and molecular level, ICSS enhances size and dendritic arborization and promotes neurogenesis in specific hippocampal areas. ICSS also regulates the expression of genes related to learning and memory. Conclusions: Through activating reward and neural plasticity mechanisms, ICSS in the medial forebrain bundle is a promising technique for memory-enhancing treatments.(AU)

Antecedentes: La autoestimulación eléctrica intracraneal (AEIC) es un tipo de estimulación cerebral profunda autoadministrada a través de un electrodo implantado de forma crónica en áreas cerebrales de la recompensa. Actualmente, dos laboratorios en el mundo, uno en India y otro en España, están estudiando intensivamente el efecto de este tipo de estimulación cerebral reforzante sobre el aprendizaje y la memoria. Aquí se presentan los principales hallazgos. Métodos: Diferentes grupos de ratas sanas y con daño cerebral, jóvenes y viejas, con electrodos implantados en el haz prosencefálico medial recibieron un tratamiento de AEIC después de ser entrenados en diferentes paradigmas de aprendizaje. La memoria se evaluó a corto y largo plazo. Resultados: La AEIC mejora la memoria implícita y explícita, especialmente en animales con un bajo rendimiento o con daño cerebral. A nivel estructural y molecular, la AEIC estimula del desarrollo de la arborización dendrítica, promueve la neurogénesis en el hipocampo y regula la expresión de genes relacionados con plasticidad, aprendizaje y memoria. Conclusiones: La AEIC en el haz prosencefálico medial, al activar mecanismos de recompensa y de plasticidad neural, constituye un tratamiento prometedor para la mejora de la memoria.(AU)

Pharmacokinetic Study of Anti-osteoarthritic Compounds of a Standardized Fraction from Sphaeralcea Angustifolia.

Sphaeralcea angustifolia has been widely used in inflammatory conditions such as blows, bruises, fractures, and wounds. The compounds identified as active in plants and suspension cell culture of S. angustifolia were tomentin, scopoletin, and sphaeralcic acid. To consolidate the integral use of knowledge about the S. angunstifolia and strengthen its pharmacological use in patients with knee osteoarthritis, the pharmacokinetic behavior of the active compounds was characterized. The SaTSS (S. angustifoloia standardized in Tomentin, Scopoletin, and Sphaeralcic acid) anti-ostearthritic fraction was obtained from cell suspension. The analytical method of High-Performance Liquid Chromatography (HPLC) for tomentin, scopoletin, and sphaeralcic acid were validated determining the accuracy, precision linearity, sensibility, specificity, detection limits, and quantification time-range parameters, as well as extraction efficiency and stability of compounds. The pharmacokinetic assay was performed with ICR mice strain, in which the mice were administrated with a single oral or intravenous dose (400 mg/kg with 7.1 mg/kg of scopoletin and tomentin in mixture and 34.6 mg/kg of sphaeralcic acid) of the SaTSS standardized active fraction. The results of the validated analytical methods allowed establishing, in a validated manner, that a coumarin mixture and sphaeralcic acid present in the SaTES fraction were detected in plasma. According to the values of Akaike Information Criteria (AIC), Sum of Squares (SS), Schwarz Criteria (SC), and by the determination coefficient (R2), the compounds follow a two-compartment model.

Is there life beyond the Spanish government's aid to furloughed employees by COVID-19?

This paper examines the perceptions of firms in April 2020, one month after the Spanish Government declared the state of alarm, about how the COVID-19 pandemic will affect their business activity in the following months, and what employment decisions they expect to make in response. The data for the study was collected by the Government of the region of Aragon (Spain) through a survey of a non-randomly selected sample of firms located in the region. In addition to prospects and intended actions, firms were asked whether or not they had applied for ERTE aid (the Spanish job retention scheme to contain the pandemic crisis). We find that firms participating (voluntarily and anonymously) in the survey anticipated rather well the severity of the effects of the pandemic in the following months. The ERTE aid helped firms to maintain the jobs of their inactive employees, while firms that did not ask for aid responded by laying off employees. Further, the ERTE aid helped to maintain the jobs of furloughed employees, but the firms receiving ERTE aid expected to lay off the same proportion of employees as firms without that aid, controlling for the different anticipated effects of the pandemic in the two groups of firms.

Psychometry and estimation of cutoff points of Jefferson Scale of empathy in dental students.

OBJECTIVE: The objective of this study was to determine the psychometric properties of the 3-dimensional latent model of empathy on the Jefferson Scale of Physician Empathy instrument (version S), and to verify the existence of cutoff points capable of differentiating empathy measures classified as: "high," "medium," and "low" using data collected from observations of students from 11 dental faculties of 5 Central American and Caribbean countries (n = 3082) between 2015 and 2019. METHODS: This is an exploratory, "a posteriori," and non-experimental study. Factor structure and factor invariance by country and gender were analyzed. Hierarchical cluster analysis and bifactorial analysis were applied, and the data were normalized by cluster and by percentiles within them. RESULTS: Confirmatory factor analysis showed that the original model was replicable and fit the data, while multigroup analysis allowed assuming an invariant factor structure by country and by gender. There is reliability in the measurement made by the scale and its dimensions. CONCLUSIONS: The instrument has adequate psychometric properties, and cutoff values obtained allow people with lower or higher levels of empathy and its components to be classified. Therefore, these results solve the problem of comparing the scores and observed levels of empathy between dental schools within and between countries and between genders. Such comparisons were only possible since the original data of each study were made available for traditional statistical methods.

Efficacy of naloxegol on symptoms and quality of life related to opioid-induced constipation in patients with cancer: a 3-month follow-up analysis.

OBJECTIVES: Opioid-induced constipation (OIC) can affect up to 63% of all patients with cancer. The objectives of this study were to assess quality of life as well as efficacy and safety of naloxegol, in patients with cancer with OIC. METHODS: An observational study was made of a cohort of patients with cancer and with OIC exhibiting an inadequate response to laxatives and treated with naloxegol. The sample consisted of adult outpatients with a Karnofsky performance status score ≥50. The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) and the Patient Assessment of Constipation Symptoms (PAC-SYM) were applied for 3 months. RESULTS: A total of 126 patients (58.2% males) with a mean age of 61.3 years (range 34-89) were included. Clinically relevant improvements (>0.5 points) were recorded in the PAC-QOL and PAC-SYM questionnaires (p<0.0001) from 15 days of treatment. The number of days a week with complete spontaneous bowel movements increased significantly (p<0.0001) from 2.4 to 4.6 on day 15, 4.7 after 1 month and 5 after 3 months. Pain control significantly improved (p<0.0001) during follow-up. A total of 13.5% of the patients (17/126) presented some gastrointestinal adverse reaction, mostly of mild (62.5%) or moderate intensity (25%). CONCLUSIONS: Clinically relevant improvements in OIC-related quality of life, number of bowel movements and constipation-related symptoms were recorded as early as after 15 days of treatment with naloxegol in patients with cancer and OIC, with a good safety profile.