Efficacy of the bumped kinase inhibitor BKI-1708 against the cyst-forming apicomplexan parasites Toxoplasma gondii and Neospora caninum in vitro and in experimentally infected mice.

Toxoplasma gondii and Neospora caninum are major worldwide morbidity-causing pathogens. Bumped kinase inhibitors (BKIs) are a compound class that has been optimized to target the apicomplexan calcium-dependent protein kinase 1 (CDPK1) - and several members of this class have proven to be safe and highly active in vitro and in vivo. BKI-1708 is based on a 5-aminopyrazole-4-carboxamide scaffold, and exhibited in vitro IC50 values of 120 nM for T. gondii and 480 nM for N. caninum ß-galactosidase expressing strains, and did not affect human foreskin fibroblast (HFF) viability at concentrations up to 25 µM. Electron microscopy established that exposure of tachyzoite-infected fibroblasts to 2.5 µM BKI-1708 in vitro induced the formation of multinucleated schizont-like complexes (MNCs), characterized by continued nuclear division and harboring newly formed intracellular zoites that lack the outer plasma membrane. These zoites were unable to finalize cytokinesis to form infective tachyzoites. BKI-1708 did not affect zebrafish (Danio rerio) embryo development during the first 96 h following egg hatching at concentrations up to 2 µM. Treatments of mice with BKI-1708 at 20 mg/kg/day during five consecutive days resulted in drug plasma levels ranging from 0.14 to 4.95 µM. In vivo efficacy of BKI-1708 was evaluated by oral application of 20 mg/kg/day from day 9-13 of pregnancy in mice experimentally infected with N. caninum (NcSpain-7) tachyzoites or T. gondii (TgShSp1) oocysts. This resulted in significantly decreased cerebral parasite loads and reduced vertical transmission in both models without drug-induced pregnancy interference.

Working towards the development of vaccines and chemotherapeutics against neosporosis-With all of its ups and downs-Looking ahead.

Neospora caninum is an apicomplexan and obligatory intracellular parasite, which is the leading cause of reproductive failure in cattle and affects other farm and domestic animals, but also induces neuromuscular disease in dogs of all ages. In cattle, neosporosis is an important health problem, and has a considerable economic impact. To date there is no protective vaccine or chemotherapeutic treatment on the market. Immuno-prophylaxis has long been considered as the best control measure. Proteins involved in host cell interaction and invasion, as well as antigens mediating inflammatory responses have been the most frequently assessed vaccine targets. However, despite considerable efforts no effective vaccine has been introduced to the market to date. The development of effective compounds to limit the effects of vertical transmission of N. caninum tachyzoites has emerged as an alternative or addition to vaccination, provided suitable targets and safe and efficacious drugs can be identified. Additionally, the combination of both treatment strategies might be interesting to further increase protectivity against N. caninum infections and to decrease the duration of treatment and the risk of potential drug resistance. Well-established and standardized animal infection models are key factors for the evaluation of promising vaccine and compound candidates. The vast majority of experimental animal experiments concerning neosporosis have been performed in mice, although in recent years the numbers of experimental studies in cattle and sheep have increased. In this review, we discuss the recent findings concerning the progress in drug and vaccine development against N. caninum infections in mice and ruminants.

In vitro and in vivo activities of a trithiolato-diRuthenium complex conjugated with sulfadoxine against the apicomplexan parasite Toxoplasma gondii.

Organometallic compounds, including Ruthenium complexes, have been widely developed as anti-cancer chemotherapeutics, but have also attracted much interest as potential anti-parasitic drugs. Recently hybrid drugs composed of organometallic Ruthenium moieties that were complexed to different antimicrobial agents were synthesized. One of these compounds, a trithiolato-diRuthenium complex (RU) conjugated to sulfadoxine (SDX), inhibited proliferation of Toxoplasma gondii tachyzoites grown in human foreskin fibroblast (HFF) monolayers with an IC50 < 150 nM, while SDX and the non-modified RU complex applied either individually or as an equimolar mixture were much less potent. In addition, conjugation of SDX to RU lead to decreased HFF cytotoxicity. RU-SDX did not impair the in vitro proliferation of murine splenocytes at concentrations ranging from 0.1 to 0.5 µM but had an impact at 2 µM, and induced zebrafish embryotoxicity at 20 µM, but not at 2 or 0.2 µM. RU-SDX acted parasitostatic but not parasiticidal, and induced transient ultrastructural changes in the mitochondrial matrix of tachyzoites early during treatment. While other compounds that target the mitochondrion such as the uncouplers FCCP and CCCP and another trithiolato-Ruthenium complex conjugated to adenine affected the mitochondrial membrane potential, no such effect was detected for RU-SDX. Evaluation of the in vivo efficacy of RU-SDX in a murine T. gondii oocyst infection model comprised of non-pregnant outbred CD1 mice showed no effects on the cerebral parasite burden, but reduced parasite load in the eyes and in heart tissue.

Mapping the learning styles of medical students in Brazil.

BACKGROUND: Medical education has evolved based on the application of pedagogical actions that place the student as the protagonist of the learning process through the use of active teaching methodologies. Within this context, higher education teachers should use strategies that focus on the student and his/her context and avoid traditional teaching methods. Specifically in medical schools, there is an even greater challenge since the teaching methods of medical curricula differ from those used in previous schooling. Consequently, students acquire their own style of processing information that is often incompatible with the profile of medical schools. This may be one of the factors responsible for the lack of motivation among undergraduates. OBJECTIVE: The aim of this study was to characterize the learning styles of students enrolled in a Brazilian medical school using the Felder-Soloman Index of Learning Styles (ILS). METHODS: This was a cross-sectional, descriptive, quantitative study that included students from the 1st to the 6th year of a Brazilian medical school. The students participating in this study voluntarily answered 44 questions about learning styles of the Felder-Silverman instrument validated in Brazil. The instrument was divided so that each domain consisted of 11 questions with two response options in which only one could be selected. For each domain, a score (1 point) was assigned to the selected option (a, b) of the question and the learning style category was determined as the difference between these values. For data collection and tabulation, we used the Learning Syle Platform (EdA Platform) developed based on Felder's studies since this system processes information about the dimension analyzed, the preferred style, and the most striking characteristics of each style. RESULTS: The results showed that sensing was the preferred learning style of the students, followed by the sequential and visual styles. It was not possible to determine whether gender or age influences the choice of learning methods because of the homogeneity of the results. CONCLUSIONS: The present data will enable teachers of the institution involved in this study to plan pedagogical actions that improve the students' self-awareness, as well as their teaching-learning skills, by choosing the most adequate active methodologies for the medical education programs considering the individuality of each student and class.

Genetic alterations landscape in paediatric thyroid tumours and/or differentiated thyroid cancer: Systematic review.

Differentiated thyroid cancer (DTC) is a rare disease in the paediatric population (≤ 18 years old. at diagnosis). Increasing incidence is reflected by increases in incidence for papillary thyroid carcinoma (PTC) subtypes. Compared to those of adults, despite aggressive presentation, paediatric DTC has an excellent prognosis. As for adult DTC, European and American guidelines recommend individualised management, based on the differences in clinical presentation and genetic findings. Therefore, we conducted a systematic review to identify the epidemiological landscape of all genetic alterations so far investigated in paediatric populations at diagnosis affected by thyroid tumours and/or DTC that have improved and/or informed preventive and/or curative diagnostic and prognostic clinical conduct globally. Fusions involving the gene RET followed by NTRK, ALK and BRAF, were the most prevalent rearrangements found in paediatric PTC. BRAF V600E was found at lower prevalence in paediatric (especially ≤ 10 years old) than in adults PTC. We identified TERT and RAS mutations at very low prevalence in most countries. DICER1 SNVs, while found at higher prevalence in few countries, they were found in both benign and DTC. Although the precise role of DICER1 is not fully understood, it has been hypothesised that additional genetic alterations, similar to that observed for RAS gene, might be required for the malignant transformation of these nodules. Regarding aggressiveness, fusion oncogenes may have a higher growth impact compared with BRAF V600E. We reported the shortcomings of the systematized research and outlined three key recommendations for global authors to improve and inform precision health approaches, glocally.

Pooling Saliva Sample as an Effective Strategy for the Systematic CMV Screening of Newborns-A Multicentric Prospective Study.

BACKGROUND: Cytomegalovirus is the most common cause of congenital infections worldwide. Screening all newborns in the first 2 weeks of life is the only way to detect all cases of congenital infection, allowing the monitoring of children with asymptomatic infection at birth and early intervention. AIM: In this multicenter study, we aimed to evaluate the feasibility of using a saliva pool strategy for mass screening in 7 Portuguese hospitals, and to estimate the current prevalence of this congenital infection in these hospitals. METHODS: A total of 7033 newborns were screened between June 2020 and June 2022, and 704 pools of 10 saliva samples were analyzed by polymerase chain reaction (PCR). RESULTS: Of the 704 pools analyzed, 685 were negative and 19 had positive PCR results for cytomegalovirus. After individual PCR testing, 26 newborns had positive saliva results, of which 15 were confirmed by urine testing. Thus, this study's prevalence of congenital infection was 0.21% (95% confidence interval: 0.12%-0.35%). CONCLUSIONS: In this study, the pooling strategy proved to be effective for the systematic screening of newborns, although this low prevalence raises questions regarding the cost-effectiveness of implementing universal screening. However, this prevalence is probably the result of the control measures taken during the pandemic; therefore, the rates are expected to return to prepandemic values, but only a new study after the pandemic will be able to confirm this.

HER2 Status in RAS and BRAF Wild-Type Metastatic Colorectal Cancer: A Portuguese Study.

INTRODUCTION: Colorectal cancer (CRC) is the second-most deadly cancer worldwide. However, there remains a scarcity of precision treatments available for this type of cancer. Amplification or overexpression of human epidermal growth factor receptor 2 (HER2+) is a well-established therapeutic target in gastric and breast cancer. HER2 is positive in approximately 5% of CRC cases and has been implicated in resistance to therapy with anti-epidermal growth factor receptor antibodies. The aim of this study was to evaluate HER2 status in RAS and BRAF wild-type metastatic CRC (mCRC) and its correlation with survival outcomes. MATERIALS AND METHODS: A single-center retrospective analysis of RAS and BRAF wild-type mCRC patients undergoing systemic treatment was conducted from July 2014 to September 2020. Tissue HER2 status was determined by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) and/or chromogenic in situ hybridization (CISH). HER2+ was defined as IHC3 (+) or IHC2 (+) through FISH or CISH (+). RESULTS: Fifty-nine patients were included. The median age of all the included patients was 64 years (33-82). Four patients had HER2+ tumors (7%). Four patients had HER2+ tumors (7%). The majority of HER2+ mCRC cases were males (n=3) and left-sided CRC (n=3). All patients received FOLFIRI plus cetuximab as first-line treatment. At the median follow-up of 24.0 months, patients with HER2-negative mCRC presented with a median overall survival (mOS) of 39.4 months (95% confidence interval (CI) 32.7-46.0) and the four patients with HER2+ mCRC had a mOS of 20.4 months (95% CI; 9.5-31.3; p=0.07). In HER2-negative patients, the median PFS (mPFS) was 11.3 months (95% CI; 9.2-13.4) vsHER2-positive patients with a mPFS of 10.9 months (95% CI; 1.3-20.4; p=0.47). CONCLUSIONS: To our knowledge, this is the first study reporting HER2+ in mCRC patients in a Portuguese population and the HER2+ rate was consistent with previous studies. Our study suggests that HER2+ may potentially be a marker that is able to predict poor prognosis in RAS and BRAF wild-type mCRC.

Intensity-Dependent Influence of Interoceptive Accuracy on Psychophysiological Responses During Aerobic Exercise in Physically Inactive Men.

We aimed to investigate the influence of interoceptive accuracy on affective valence, arousal, and ratings of perceived exertion (RPE) during 20 minutes of aerobic exercise at both moderate and heavy intensity among physically inactive men. We divided our participant sample into men with poor heartbeat perception (PHP, n = 13) and good heartbeat perception (GHP, n = 15), based on their cardioceptive accuracy. We measured their heart rate reserve (%HRreserve), perceived affective valence (Feeling Scale; +5/-5), perceived arousal (Felt Arousal Scale, 0-6), and ratings of perceived effort (RPE; Borg scale 6-20) every five minutes during an exercise session on a bicycle ergometer. During moderate-intensity aerobic exercise, the GHP group presented a greater decline in affective valence (p = 0.010; d = 1.06) and a greater increase in RPE (p = 0.004; d = 1.20) compared to the PHP group, with no group differences in %HRreserve (p = 0.590) and arousal (p = 0.629). Psychophysiological and physiological responses to the heavy-intensity aerobic exercise were not different between groups. We concluded that the influence of interoceptive accuracy on psychophysiological responses during submaximal fixed-intensity aerobic exercise was intensity-dependent in these physically inactive men.

Associations between physical activity and cardiorespiratory fitness with vascular health phenotypes in older adults: a cross-sectional study.

Objective: We investigated the associations between physical activity (PA) and cardiorespiratory fitness (CRF) with vascular health phenotypes in community-dwelling older adults. Methods: This cross-sectional study included 82 participants (66.8 ± 5.2 years; 81% females). Moderate-to-vigorous physical activity (MVPA) was assessed using accelerometers, and CRF was measured using the distance covered in the 6-min walk test (6MWT). The vascular health markers were as follows: i) arterial function measured as aortic pulse wave velocity (aPWV) estimated using an automatic blood pressure device; and ii) arterial structure measured as the common carotid intima-media thickness (cIMT). Using a combination of normal cIMT and aPWV values, four groups of vascular health phenotypes were created: normal aPWV and cIMT, abnormal aPWV only, abnormal cIMT only, and abnormal aPWV and cIMT. Multiple linear regression was used to estimate the beta coefficients (ß) and their respective 95% confidence intervals (95% CI) adjusting for BMI, and medication for diabetes, lipid, and hypertension, sex, age, and blood pressure. Results: Participants with abnormal aPWV and normal cIMT (ß = -53.76; 95% CI = -97.73--9.78 m; p = 0.017), and participants with both abnormal aPWV and cIMT (ß = -71.89; 95% CI = -125.46--18.31 m; p = 0.009) covered less distance in the 6MWT, although adjusting for age, sex and blood pressure decreased the strength of the association with only groups of abnormal aPWV and cIMT covering a lower 6MWT distance compared to participants with both normal aPWV and cIMT (ß = -55.68 95% CI = -111.95-0.59; p = 0.052). No associations were observed between MVPA and the vascular health phenotypes. Conslusion: In summary, poor CRF, but not MVPA, is associated with the unhealthiest vascular health phenotype (abnormal aPWV/cIMT) in older adults.

Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP.

OBJECTIVES: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA). METHODS: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "Autoimmunity Testing"; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP). RESULTS: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations. CONCLUSIONS: These recommendations are an important step to achieve high quality ANA testing.

Analytical aspects of the antinuclear antibody test by HEp-2 indirect immunofluorescence: EFLM report on an international survey.

OBJECTIVES: Detection of antinuclear antibodies (ANA) by indirect immunofluorescence assay using HEp-2 cells (HEp-2 IFA) is used to screen for various autoimmune diseases. HEp-2 IFA suffers from variability, which hampers harmonization. METHODS: A questionnaire was developed to collect information on HEp-2 IFA methodology, computer-assisted diagnosis (CAD) systems, training, inter-observer variability, quality assessment, reagent lot change control, and method verification. The questionnaire was distributed to laboratories by Sciensano (Belgium), national EASI groups (Italy, Croatia, Portugal, Estonia, Greece) and ICAP (worldwide). Answers were obtained by 414 laboratories. The results were analysed in the framework of the recent EFLM/EASI/ICAP ANA recommendations (companion paper). RESULTS: Laboratories used either HEp-2, HEp-2000, or HEp-20-10 cells and most laboratories (80%) applied the same screening dilution for children and adults. The conjugate used varied between laboratories [IgG-specific (in 57% of laboratories) vs. polyvalent]. Sixty-nine percent of CAD users reviewed the automatic nuclear pattern and 53% of CAD users did not fully exploit the fluorescence intensity for quality assurance. Internal quality control was performed by 96% of the laboratories, in 52% of the laboratories only with strongly positive samples. Interobserver variation was controlled by 79% of the laboratories. Limited lot-to-lot evaluation was performed by 68% of the laboratories. Method verification was done by 80% of the respondents. CONCLUSIONS: Even though many laboratories embrace high-quality HEp-2 IFA, substantial differences in how HEp-2 IFA is performed and controlled remain. Acting according to the EFLM/EASI/ICAP ANA recommendations can improve the global performance and quality of HEp-2 IFA and nurture harmonization.

Fasting and prolonged food restriction differentially affect GH secretion independently of GH receptor signaling in AgRP neurons.

Growth hormone (GH) receptor (GHR) is abundantly expressed in neurons that co-release the agouti-related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). Since ARHAgRP/NPY neurons regulate several hypothalamic-pituitary-endocrine axes, this neuronal population possibly modulates GH secretion via a negative feedback loop, particularly during food restriction, when ARHAgRP/NPY neurons are highly active. The present study aims to determine the importance of GHR signaling in ARHAgRP/NPY neurons on the pattern of GH secretion in fed and food-deprived male mice. Additionally, we compared the effect of two distinct situations of food deprivation: 16 h of fasting or four days of food restriction (40% of usual food intake). Overnight fasting strongly suppressed both basal and pulsatile GH secretion. Animals lacking GHR in ARHAgRP/NPY neurons (AgRP∆GHR mice) did not exhibit differences in GH secretion either in the fed or fasted state, compared to control mice. In contrast, four days of food restriction increased GH pulse frequency, basal GH secretion, and pulse irregularity/complexity (measured by sample entropy), whereas pulsatile GH secretion was not affected in both control and AgRP∆GHR mice. Hypothalamic Ghrh mRNA levels were unaffected by fasting or food restriction, but Sst expression increased in acutely fasted mice, but decreased after prolonged food restriction in both control and AgRP∆GHR mice. Our findings indicate that short-term fasting and prolonged food restriction differentially affect the pattern of GH secretion, independently of GHR signaling in ARHAgRP/NPY neurons.

Implicit motor imagery performance and cortical activity throughout the menstrual cycle.

Studies show that female motor and visuospatial skills are modulated by the menstrual cycle. Implicit motor imagery, meaning the involuntary imagination of movements during a task, involves kinesthetic, visual, and spatial aspects of the corresponding action and can be investigated by using the hand laterality judgment task (HLJT). In this study we aimed to investigate whether implicit motor imagery performance and cortical activity are altered throughout the menstrual cycle, as demonstrated by motor skills in females. Thus, 31 healthy women underwent HLJT during the menstrual, follicular and luteal phases of their menstrual cycles. Right-handed participants had to recognize the laterality (right or left) of hands presented in different views (palm or back) and orientations on a computer screen. Test performance and EEG event-related potentials were analyzed. Participants performed better in the test in the follicular and luteal phases when compared to the menstrual phase, and the accuracy of the test was positively correlated with estradiol levels in the follicular phase. The difference between medial and lateral hand orientations for rotation-related negativity was significant in the medial and left parieto-occipital regions only in the follicular phase. These findings suggest positive modulating action of estradiol in performing implicit motor imagery.

Aplicativos móveis direcionados aos idosos para autogerenciamento do cuidado: revisão de escopo / Mobile apps aimed at the elderly for self-management of care: scoping review / Aplicaciones móviles dirigidas a personas mayores para la autogestión del cuidado: revisión del alcances

Introdução: o uso de aplicativos móveis pode facilitar o autogerenciamento em saúde e oportunizar a autonomia dos idosos no seu autocuidado. Objetivo: mapear a produção científica sobre aplicativos móveis para autogerenciamento do cuidado direcionados aos idosos. Materiais e Métodos: revisão de escopo realizada no período de setembro de 2020 a janeiro de 2021, a partir das bases de dados: MEDLINE, SciELO, Scopus, Web of Science e Science Direct, mediante a estratégia de busca: ("Self-management" OR "Self-care") AND (Elderly OR "Old man") AND ("Mobile Applications" OR Smartphone OR "Cell phone"), com a inclusão de artigos que tratassem do uso de aplicativos móveis por idosos para o autogerenciamento do cuidado, sem delimitação de tempo e idioma. Resultados: a amostra final compôs-se de 14 artigos, categorizados em três vertentes de gerenciamento, a saber: medicamentos, comorbidades e práticas saudáveis. Na maioria dos estudos, os aplicativos foram direcionados ao autogerenciamento dos medicamentos, seguidos dos cuidados de condições crônicas e por último a autoavaliação do risco de quedas e tratamentos não-farmacológicos da dor. Discussão: esta revisão contribui para a prática clínica e pesquisa em enfermagem, uma vez que seus resultados apontam o que há publicado sobre o desenvolvimento e uso de aplicativos móveis por idosos para o autogerenciamento do cuidado. Conclusões: o uso de aplicativos móveis facilita o autocuidado da população idosa, principalmente, na gestão de medicamentos para condições crônicas.

Introduction: the use of mobile applications can facilitate self-management in health and provide opportunities for the autonomy of the elderly in their self-care. Objective: to map the scientific production on mobile applications for self-management of care aimed at the elderly. Materials and Methods: scope review carried out from September 2020 to January 2021, based on the following databases: MEDLINE, SciELO, Scopus, Web of Science and Science Direct, using the search strategy: ("Self-management" OR "Self-care") AND (Elderly OR "Old man") AND ("Mobile Applications" OR Smartphone OR "Cell phone"), with the inclusion of articles dealing with the use of mobile applications by the elderly for self-management of care, without time and language limitations. Results: the final sample consisted of 14 articles, categorized into three aspects of management, namely: medications, comorbidities and healthy practices. In most studies, applications were aimed at self-management of medications, followed by care for chronic conditions and finally self-assessment of the risk of falls and non-pharmacological pain treatments. Discussion: this review contributes to clinical practice and nursing research, as its results point to what has been published about the development and use of mobile applications by the elderly for self-management of care. Conclusions: the use of mobile applications facilitates self-care for the elderly population, especially in the management of medication for chronic conditions.

Introducción: el uso de aplicaciones móviles puede facilitar la autogestión en salud y brindar oportunidades para la autonomía de las personas mayores en su autocuidado. Objetivo: mapear la producción científica en aplicaciones móviles para la autogestión del cuidado dirigido a las personas mayores. Materiales y Métodos: revisión de alcance realizada desde septiembre de 2020 a enero de 2021, con base en las siguientes bases de datos: MEDLINE, SciELO, Scopus, Web of Science y Science Direct, utilizando la estrategia de búsqueda: ("Self-management" OR "Self-care") AND (Elderly OR "Old man") AND ("Mobile Applications" OR Smartphone OR "Cell phone"), con la inclusión de artículos que tratan sobre el uso de aplicaciones móviles por parte de los ancianos para la autogestión de cuidado, sin limitaciones de tiempo e idioma. Resultados: la muestra final constó de 14 artículos, categorizados en tres aspectos del manejo, a saber: medicamentos, comorbilidades y prácticas saludables. En la mayoría de los estudios, las aplicaciones estuvieron dirigidas al autocontrol de los medicamentos, seguido de la atención de las condiciones crónicas y finalmente la autoevaluación del riesgo de caídas y los tratamientos no farmacológicos del dolor. Discusión: esta revisión contribuye a la práctica clínica y la investigación en enfermería, ya que sus resultados apuntan a lo publicado sobre el desarrollo y uso de aplicaciones móviles por parte de los ancianos para la autogestión del cuidado. Conclusiones: el uso de aplicaciones móviles facilita el autocuidado de la población anciana, especialmente en el manejo de la medicación para enfermedades crónicas.

Prophylactic action of ayahuasca in a non-human primate model of depressive-like behavior.

Observational studies of long-term users of ayahuasca, an Amazonian psychedelic brew, suggest an increase in resilience via improvements in emotion and cognition. Ayahuasca has also demonstrated clinical antidepressant effects in human and animal studies; however, its potential prophylactic action in depression has not been previously studied. Therefore, this experimental study sought to evaluate the potential prophylactic effects of repeated and long-term ayahuasca use, via the modulation of resilience, in a non-human primate animal model, Callithrix jacchus, subjected to a protocol for induction of depressive-like behavior. For the formation of the study groups, some juvenile marmosets were kept in their family groups (GF = 7), while for the two experimental groups, the animals were removed from the family and kept socially isolated. Then, part of the isolated animals made up the group in which ayahuasca was administered (AG, n = 6), while for others, no intervention was made (IG, n = 5). AG animals took ayahuasca (1.67 mL/300g body weight) at weeks 4 (before isolation), 8, and 12 (during isolation) of the study. More adaptive stress response was observed for the AG when compared to the IG. The AG showed higher cortisol reactivity and fecal cortisol levels than IG, while both measures were similar to FG. Moreover, AG animals showed no signs of anhedonia and no increase in chronic stress-related behaviors, which were expressed by the IG. Thus, ayahuasca seems to promote the expression of resilient responses, indicating a prophylactic action, buffering the emergence of depressive-like behaviors and cortisol alterations associated with major depression. These results are encouraging for further research on the prophylactic use of psychedelics to prevent psychopathologies associated with chronic stress.

The bank robbery analogy as a first approach for understanding basic concepts of synthesis, transport, and mechanism of action of hormones.

Learning endocrine physiology can be challenging. Some physiological concepts are abstract, making the process of learning more difficult for students. The comprehension of basic concepts, such as chemical hormone classification, is essential to understand the differences in synthesis, secretion, transport, and mechanism of action of hormones. To assist the students on this subject, we developed an analogy between the basic concepts of hormone synthesis, transport, and mechanism of action and a bank robbery as a first approach to engage and stimulate their learning process. In the analogy, the students are asked to help identify and characterize two bank robbery crews based on a set of evidence collected by the police. The goal is to identify the general profile of lipid- and water-soluble hormones synthesis, transport, and mechanism of action on target cells. When applying the activity, the students showed a great deal of interest in solving the crime and they seemed to understand the similarities between the analogy and the subject.NEW & NOTEWORTHY Two endocrine bank robbery crews are being searched by the police. As an endocrine system student, you have been summoned to help the police solve the robberies.

Criterion validity of 14-item Health Literacy Scale (HLS-14) questionnaire in Brazilian adults and older people.

The objective of this study was to evaluate the criterion validity of the 14-item Health Literacy Scale (HLS-14) in Brazilian adults and older adults. The cross-sectional study performed in an oral health (OH) prospective cohort was conducted in 2017 in Piracicaba, Brazil. The HLS-14 questionnaire was applied to evaluate Health Literacy (HL) by dimensions: Functional literacy (FunL), Communicative literacy (ComL) and Critical literacy (CriL). An evaluation protocol (EP) was proposed to evaluate the criterion validity of HLS-14 considering HL dimensions (FunL: reading of the drug information leaflets; ComL: reading of the medical prescription and CriL: identification of OH conditions). HL (total) was dichotomized by the median in high (≥35 point) or low (<35 point) HL. Kendall's rank correlation coefficient (p < 0.05) and chi-squared test (p < 0.05) were applied. There was agreement between EP and HLS-14 for FunL (p < 0.01). There was association between high HL, measured through the HLS-14 questionnaire, assessing the reading of the drug information leaflets (p < 0.01) and the need for help to read them (p < 0.01). EP showed association between high HL and being able to read the drug information leaflet (p < 0.01), not needing help to read (p < 0.01), having found in the prescription all the information to take the medicine (p < 0.01) and knowing two or more health and OH information in the educational material (p < 0.01). The HSL-14 questionnaire showed criterion validity to measure FunL, and for some items of ComL and CriL evaluation. HL evaluation in a practical and multidimensional way could have an effect on the communication between health professional and patient, motivation and health outcomes.

Increased GH Secretion and Body Growth in Mice Carrying Ablation of IGF-1 Receptor in GH-releasing Hormone Cells.

Growth hormone (GH) secretion is controlled by short and long negative feedback loops. In this regard, both GH (short-loop feedback) and insulin-like growth factor 1 (IGF-1; long-loop feedback) can target somatotropic cells of the pituitary gland and neuroendocrine hypothalamic neurons to regulate the GH/IGF-1 axis. GH-releasing hormone (GHRH)-expressing neurons play a fundamental role in stimulating pituitary GH secretion. However, it is currently unknown whether IGF-1 action on GHRH-expressing cells is required for the control of the GH/IGF-1/growth axis. In the present study, we investigated the phenotype of male and female mice carrying ablation of IGF-1 receptor (IGF1R) exclusively in GHRH cells. After weaning, both male and female GHRHΔIGF1R mice exhibited increases in body weight, lean body mass, linear growth, and length of long bones (tibia, femur, humerus, and radius). In contrast, the percentage of body fat was similar between control and GHRHΔIGF1R mice. The higher body growth of GHRHΔIGF1R mice can be explained by increases in mean GH levels, GH pulse amplitude, and pulse frequency, calculated from 36 blood samples collected from each animal at 10-minute intervals. GHRHΔIGF1R mice also showed increased hypothalamic Ghrh mRNA levels, pituitary Gh mRNA expression, hepatic Igf1 expression, and serum IGF-1 levels compared with control animals. Furthermore, GHRHΔIGF1R mice displayed significant alterations in the sexually dimorphic hepatic gene expression profile, with a prevailing feminization in most genes analyzed. In conclusion, our findings indicate that GHRH neurons represent a key and necessary site for the long-loop negative feedback that controls the GH/IGF-1 axis and body growth.