Beyond lectures and practical courses: Teaching pharmacology using imaginative pedagogical tools.

Pharmacology has broadened its scope considerably in recent decades. Initially, it was of interest to chemists, doctors and pharmacists. In recent years, however, it has been incorporated into the teaching of biologists, molecular biologists, biotechnologists, chemical engineers and many health professionals, among others. Traditional teaching methods, such as lectures or laboratory work, have been superseded by the use of new pedagogical approaches to enable a better conceptualization and understanding of the discipline. In this article, we present several new methods that have been used in Spanish universities. Firstly, we describe a teaching network that has allowed the sharing of pedagogical innovations in Spanish universities. A European experience to improve prescribing safety is described in detail. The use of popular films and medical TV series in biomedical students shows how these audiovisual resources can be helpful in teaching pharmacology. The use of virtual worlds is detailed to introduce this new approach to teaching. The increasingly important area of the social aspects of pharmacology is also considered in two sections, one devoted to social pharmacology and the other to the use of learning based on social services to improve understanding of this important area. Finally, the use of Objective Structured Clinical Evaluation in pharmacology allows to know how this approach can help to better evaluate clinical pharmacology students. In conclusion, this article allows to know new pedagogical methods resources used in some Spanish universities that may help to improve the teaching of pharmacology.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

Analysis of heart rate variability during emergency flight simulator missions in fighter pilots.

INTRODUCTION: Managing emergency situations in different simulated flight segments can entail a workload that could affect the performance of military pilots. The aim was to analyse the modifications in neurovegetative balance (using HR variability, HRV) of professional fighter pilots attending learning/training sessions on emergency situations in a flight simulator. METHODS: A total of 18 pilots from the Spanish Air and Space Force were included. HRV was recorded simultaneously during diverse simulated emergency situations in three different flight segments: take-off, in-flight and landing. RESULTS: The comparison between take-off and in-flight revealed a statistically significant increase (p<0.05) in percentage of consecutive RR intervals that differ by more than 50 ms from each other (pNN50), root mean square of the successive differences (rMSSD), standard desviation 1 and 2 (SD1 and SD2), and a statistically significant decrease (p<0.000) in stress score (SS) and in the sympathetic to parasympathetic ratio (S:PS). Between flight and landing, a statistically significant increase (p<0.05) in mean HR, minimum HR, maximum HR, SS and S:PS was shown, while experiencing a significant decrease (p<0.000) in pNN50, rMSSD and SD2. Finally, between take-off and landing, the variables which showed significant changes (p<0.05), with these changes being a significant increase, were mean HR, minimum HR, maximum HR, rMSSD, SD1 and SD2. SS and S:PS ratios showed a statistically significant decrease (p<0.000). CONCLUSIONS: An emergency situation in a flight simulator manoeuvre produced an anticipatory anxiety response in pilots, demonstrated by low HRV, which increased during the flight segment and decreased during the landing segment of the flight.Trial registration number NCT04487899.

Remote mental health care interventions during the COVID-19 pandemic: An umbrella review.

Mitigating the COVID-19 related disruptions in mental health care services is crucial in a time of increased mental health disorders. Numerous reviews have been conducted on the process of implementing technology-based mental health care during the pandemic. The research question of this umbrella review was to examine what the impact of COVID-19 was on access and delivery of mental health services and how mental health services have changed during the pandemic. A systematic search for systematic reviews and meta-analyses was conducted up to August 12, 2022, and 38 systematic reviews were identified. Main disruptions during COVID-19 were reduced access to outpatient mental health care and reduced admissions and earlier discharge from inpatient care. In response, synchronous telemental health tools such as videoconferencing were used to provide remote care similar to pre-COVID care, and to a lesser extent asynchronous virtual mental health tools such as apps. Implementation of synchronous tools were facilitated by time-efficiency and flexibility during the pandemic but there was a lack of accessibility for specific vulnerable populations. Main barriers among practitioners and patients to use digital mental health tools were poor technological literacy, particularly when preexisting inequalities existed, and beliefs about reduced therapeutic alliance particularly in case of severe mental disorders. Absence of organizational support for technological implementation of digital mental health interventions due to inadequate IT infrastructure, lack of funding, as well as lack of privacy and safety, challenged implementation during COVID-19. Reviews were of low to moderate quality, covered heterogeneously designed primary studies and lacked findings of implementation in low- and middle-income countries. These gaps in the evidence were particularly prevalent in studies conducted early in the pandemic. This umbrella review shows that during the COVID-19 pandemic, practitioners and mental health care institutions mainly used synchronous telemental health tools, and to a lesser degree asynchronous tools to enable continued access to mental health care for patients. Numerous barriers to these tools were identified, and call for further improvements. In addition, more high quality research into comparative effectiveness and working mechanisms may improve scalability of mental health care in general and in future infectious disease outbreaks.

Delineation of cellular stages and identification of key proteins for reduction and biotransformation of Se(IV) by Stenotrophomonas bentonitica BII-R7.

The widespread use of selenium (Se) in technological applications (e.g., solar cells and electronic devices) has led to an accumulation of this metalloid in the environment to toxic levels. The newly described bacterial strain Stenotrophomonas bentonitica BII-R7 has been demonstrated to reduce mobile Se(IV) to Se(0)-nanoparticles (Se(0)NPs) and volatile species. Amorphous Se-nanospheres are reported to aggregate to form crystalline nanostructures and trigonal selenium. We investigated the molecular mechanisms underlying the biotransformation of Se(IV) to less toxic forms using differential shotgun proteomics analysis of S. bentonitica BII-R7 grown with or without sodium selenite for three different time-points. Results showed an increase in the abundance of several proteins involved in Se(IV) reduction and stabilization of Se(0)NPs, such as glutathione reductase, in bacteria grown with Se(IV), in addition to many proteins with transport functions, including RND (resistance-nodulation-division) systems, possibly facilitating Se uptake. Notably proteins involved in oxidative stress defense (e.g., catalase/peroxidase HPI) were also induced by Se exposure. Electron microscopy analyses confirmed the biotransformation of amorphous nanospheres to trigonal Se. Overall, our results highlight the potential of S. bentonitica in reducing the bioavailability of Se, which provides a basis both for the development of bioremediation strategies and the eco-friendly synthesis of biotechnological nanomaterials.

[Refeeding syndrome in a girl with cerebral palsy].

Refeeding syndrome is a serious and life-threatening complication associated with oral, enteral and parenteral nutritional therapy. It appears in severely malnourished patients or in those at risk of malnutrition, such as persons with cerebral palsy. We present the case of an 8-year-old girl with cerebral palsy who was admitted with severe hypoglycemia. After starting enteral nutrition by nasogastric tube, she developed refeeding syndrome. In children with cerebral palsy, it is essential to assess the presence of risk factors for refeeding syndrome before starting any nutritional support, and then start feeding progressively and monitor serum electrolytes.

The role of ageing in the wish to be dead: disentangling age, period and cohort effects in suicide ideation in European population.

AIMS: To investigate potential age, period and birth cohort effects in the prevalence of suicide ideation in European ageing population. METHODS: A total of 50 782 community-dwelling adults (aged + 50) from 20 different European countries were collected in the Survey Health Ageing and Retirement study. A multilevel logistic regression model of repeated measures was modelled to assess the effects of age and other variables, including the variability of observations over three levels: birth cohort groups, time period assessment and individual differences. RESULTS: The larger effect of variability was attributed to individual-level factors (57.8%). Youngest-old people (65-79 years) showed lower suicide ideation than middle-aged people (50-64 years). No significative differences were found for suicide ideation between middle-aged people and oldest-old (80 + years). Only 0.85% and 0.13% of the total variability of suicide ideation accounted for birth cohort and period effects, respectively. Cohorts born between 1941 and 1944 possessed the lowest estimates of suicide ideation. Conversely, suicide ideation started to rise with post-War generations and reached a significant level for people born from 1953-1957 to 1961-1964. Regarding the time period, participants assessed in 2006-2007 showed a lower likelihood of suicide ideation. The rest of the cohorts and period groups did not show any significant effect on the prevalence of suicide ideation. CONCLUSIONS: Our results suggest that age and suicide ideation relationship is not linear in middle and older age. The European Baby boomers born from 50s to mid-60s might report higher suicide ideation than their ancestors. This scenario would imply a greater need for mental healthcare services for older people in the future.

Multisystem combined uranium resistance mechanisms and bioremediation potential of Stenotrophomonas bentonitica BII-R7: Transcriptomics and microscopic study.

The potential use of microorganisms in the bioremediation of U pollution has been extensively described. However, a lack of knowledge on molecular resistance mechanisms has become a challenge for the use of these technologies. We reported on the transcriptomic and microscopic response of Stenotrophomonas bentonitica BII-R7 exposed to 100 and 250 µM of U. Results showed that exposure to 100 µM displayed up-regulation of 185 and 148 genes during the lag and exponential phases, respectively, whereas 143 and 194 were down-regulated, out of 3786 genes (>1.5-fold change). Exposure to 250 µM of U showed up-regulation of 68 genes and down-regulation of 290 during the lag phase. Genes involved in cell wall and membrane protein synthesis, efflux systems and phosphatases were up-regulated under all conditions tested. Microscopic observations evidenced the formation of U-phosphate minerals at membrane and extracellular levels. Thus, a biphasic process is likely to occur: the increased cell wall would promote the biosorption of U to the cell surface and its precipitation as U-phosphate minerals enhanced by phosphatases. Transport systems would prevent U accumulation in the cytoplasm. These findings contribute to an understanding of how microbes cope with U toxicity, thus allowing for the development of efficient bioremediation strategies.

Monopolar dielectric diathermy by emission of radiofrequency in Patellofemoral pain. A single-blind-randomized clinical trial.

Despite the high incidence of patellofemoral pain syndrome (PFPS), few studies show the effects of radiofrequency on pain and functionality in these patients. For this reason, the aim of this study was to determine the efficacy of monopolar dielectric diathermy by emission of radiofrequency (MDR) in dynamic applications aimed at treating pain and improving function in patients with PFPS. For this purpose, a single-blind randomized clinical trial was conducted. Eighty-four participants with PFPS were evenly divided into an experimental group (EG) and a control group (CG). All subjects receive 10 min of daily home exercises along 3 weeks, and in addition, the subjects of the EG received 10 sessions based on the dynamic application of MDR. Variables measured included Visual Analogue Scale (VAS), DN4 questionnaire, Lower Extremity Functionality Scale (LEFS), Kujala scale, Range of Movement (ROM) in knee flexion and extension and drug intake. The EG showed a statistically significant reduction in pain (VAS = 4.8 [5.5-4.1] [p < .001]; DN4 = 3.8 [4.4-3.2] [p < .001]), and an increase in functionality (LEFS = 16 [19-13] [p < .001]; Kujala = 19 [23-14] [p < .001]) and in ROM (flexion 18º [21º-16º] [p < .001]). No statistically significant changes in drug intake were found. Based on this data, the dynamic application of MDR seems effective in reducing pain and increasing functionality and flexion in patients with PFPS. Diathermy by emission of radiofrequency could be recommended as complement or main therapy in the treatment of PFPS.

Numerical simulation of knotted solutions for Maxwell equations.

In this work, we use the finite differences in time domain (FDTD) numerical method to compute and assess the validity of Hopf solutions, or hopfions, for the electromagnetic field equations. In these solutions, field lines form closed loops characterized by different knot topologies which are preserved during their time evolution. Hopfions have been studied extensively in the past from an analytical perspective but never, to the best of our knowledge, from a numerical approach. The implementation and validation of this technique eases the study of more complex cases of this phenomena; e.g., how these fields could interact with materials (e.g., anisotropic or nonlinear), their coupling with other physical systems (e.g., plasmas), and also opens the path on their artificial generation by different means (e.g., antenna arrays or lasers).

Food waste from restaurant sector - Characterization for biorefinery approach.

The aim of this study is the analysis of food waste (FW) composition from local catering services to assess potential biorefinery development. Moisture content of different FW samples showed that 27-47% (w/w) was organic material. Main components were lipids (25.7-33.2, w/w), starch (16.2-29.4%, w/w) and proteins (23.5-18.3%, w/w) on a dry basis. A metal profile with Na and Mg as main components, followed by trace elements, i.e. Zn or Fe, was also found in food waste samples. Statistical tests in combination with principal component analysis provides an efficient methodology to establish specific composition variations between FW from different catering services, while relating them to FW typology. The combination of chemical characterization with statistical study constitutes a promising decision-making tool for FW processing and valorization. The innovative methodology presented in this study provides systematic evaluation of FW composition and variability to allow selection of the most appropriate valorization paths.

[Current diagnosis and management of toddler's fracture]. / Manejo diagnóstico y terapéutico actual de la fractura de los primeros pasos.

INTRODUCTION: Toddler's fracture is an accidental spiral tibial fracture, characteristic of the early childhood. The objective of this study is to determine the incidence and current diagnosis and management of this disorder. PATIENTS AND METHODS: A retrospective study was conducted on a sample of patients aged 0-3 years diagnosed with a toddler's fracture in a tertiary hospital between years 2013 and 2017. RESULTS: A total of 53 patients were registered (10.6 cases per year). The median age was 2 years, with a slight male predominance. The initial radiograph was normal in 24.5% of patients. With the initial approach, 69.8% of patients were diagnosed with fracture, 11.3% with suspected fracture, and 18.9% with contusion. A follow-up was required in 22% required a control test, using radiographs in 10 patients (pathological 90%), and ultrasound in 5 (pathological 80%, 3 of them with normal initial radiography). The large majority (80.8%) of the patients were immobilised with a cast, while flexible immobilisation or non-immobilisation was used in 19.2%. Complications were found in a 21.4% of patients immobilised with splint, mainly skin injuries (19%). These were more frequent in this group than in those that were not immobilised (21.4% vs. 0%, P=.006); with no significant differences in time to weight-bearing. CONCLUSIONS: Radiography has a limited sensitivity for the diagnosis of toddler's fracture. In the group of patients with normal radiography, the use of ultrasound can be helpful to the diagnosis and avoid additional radiation. Even though the most common treatment continues to be immobilisation with a splint, the alternative without rigid immobilisation does not seem to give worse results, even with lower morbidity associated with the treatment.

Vigilancia intensificada de eventos de salud pública en comunidades desplazadas por inundaciones en Paraguay, 2015-2016 / Intensified surveillance of public health events in communities displaced by floods in Paraguay, 2015-2016

Introducción: La vigilancia epidemiológica de la morbilidad y la mortalidad relacionadas a los desastres, es fundamental para organizar y gestionar los recursos, equipos y personal necesarios para responder efectivamente a las situaciones de emergencia. Se describe la implementación del sistema de vigilancia intensificada en poblaciones desplazadas por inundaciones en Paraguay, período 2015/2016. Materiales y métodos: Estudio descriptivo de corte trasversal, entre el 28/12/2015 y 12/07/2016, en todo el territorio nacional. Como fuentes de datos se utilizaron la planilla de notificación diaria de enfermedades, el consolidado de situación de albergues. Se diseñó un sistema de carga de datos por la web. Para el análisis de datos se utilizó el programa informático Epi Info 7.1.5, con medidas estadísticas de tendencia central como medias, medianas, proporciones. Resultados: Se registraron 68.699 personas afectadas. De las cuales, 32,4% eran menores de 5 años. Un 48,0 % se alojaron en refugios formales y 36,7% en campamentos informales, en ambos se identificó déficit de condiciones sanitarias básicas. Se registraron 23.877 consultas. Las enfermedades más frecuentes: Infección respiratoria aguda no neumonía (33%), hipertensión arterial (19%), enfermedad tipo influenza (14%), lesiones de la piel (6%) y diarreas (6%). Un 3% correspondió al síndrome febril agudo, dos casos confirmados de leptospirosis. No se registraron brotes de enfermedades infecciosas. Conclusión: La aplicación de la vigilancia intensificada durante el evento de inundación permitió la identificación de grupos de riesgo y sus problemas de salud más frecuentes. Esto fue fundamental en la orientación de los esfuerzos de prevención y control durante del desastre. Palabras claves: Desastres naturales, inundaciones, vigilancia en salud pública, epidemiología, Paraguay.

Introduction: The importance of epidemiological surveillance of morbidity and mortality related to disasters is that it is essential to organize and manage resources, equipment and personnel necessary to respond effectively to emergencies. The implementation of an intensified surveillance system in populations displaced by flooding in the affected regions of Paraguay during the 2015/2016 period is described. Materials and methods: Descriptive study of cross section, between 12/28/2015 and 7/12/2016, throughout the national territory. As data sources, the planning of the daily notifications of diseases is used, the consolidation of the situation of the shelters. A web data loading system was designed. For the analysis of the data, it is the Epi Info 7.1.5 computer program, with measures of central tendency such as means, medians, and proportions. Results: 68,699 affected people were registered. Of which, 32.4% were under 5 years old; 48.0% were housed in formal shelters and 36.7% in informal camps, both of which identified a deficit of basic sanitary conditions. There were 23,877 queries. The most frequent diseases: Acute respiratory infection, pneumonia (33%), hypertension (19%), influenza-like illness (14%), skin lesions (6%) and diarrhea (6%). 3% corresponded to the acute febrile syndrome, two confirmed cases of leptospirosis. There were no outbreaks of infectious diseases. Conclusion: The implementation of intensified surveillance during the flooding event allowed a better understanding of the general situation of the displaced population, as well as the identification of risk groups and their most frequent health problems. This was instrumental in guiding the prevention and control efforts during the disaster. Keywords: Natural disasters, floods, public health surveillance, epidemiology, Paraguay.

CXCR3+ Monocytes Increase Significantly in Graft Blood Compared to Peripheral Blood in Patients With Stable Kidney Graft Function.

INTRODUCTION: We have recently reported that some lymphocyte populations do not maintain the same proportion in kidney graft blood as in peripheral blood, despite a stable function of the transplanted kidney. These results suggest that a comparative study between leukocyte cells from graft blood and those obtained from peripheral blood could provide information about the inflammatory state of the transplanted organ. In this work we selected the population of CD4+ lymphocytes and monocytes expressing CXCR3 to test this hypothesis. MATERIAL AND METHODS: The study was performed by flow cytometry during month 3, 6, and 12 after transplantation in 58 patients who received an isolated kidney transplant and the same immunosuppressive regimen. The peripheral blood sample was obtained by venipuncture and the graft blood by fine needle aspiration. RESULTS: We found a significant percentage decrease in CXCR3+ monocytes throughout the first year of transplantation in peripheral blood (15.9 ± 20.7 vs. 12.6 ± 12.4 vs. 6.3 ± 9.0, at 3, 6, and 12 months, respectively; P = .001), whereas the percentage of CXCR3+ monocytes in graft blood did not change over this period. This situation resulted in a significant percentage difference between the CXCR3+ monocytes from the graft blood and those from the peripheral blood at the sixth (15.8 ± 8.1 vs. 12.6 ± 12.4, respectively; P = .008) and 12th months (12.9 ± 8.1 vs. 6.3 ± 9.0, respectively; P < .001). CONCLUSIONS: Therefore, we can conclude that the significant percentage increase of CXCR3+ monocytes in graft blood with respect to peripheral blood suggests the presence of inflammatory activity despite renal function being stable during the second half of the first year post-transplantation.

Knowledge, availability, and use of ambulatory and home blood pressure monitoring in primary care in Spain: the MAMPA study.

OBJECTIVE: To examine the degree of knowledge and management of automated devices for office blood pressure measurement (AD), home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM) in primary care in Spain. METHODS: Online self-administered survey sent between May 2016 and February 2017 to 2221 primary-care physicians working across Spain. Clinicians were mostly identified through national primary-care scientific societies (20% overall response rate). RESULTS: Participants' mean age was 47.7 years, 55% were women, and 54% reported at least 20 years of primary-care practice. Among them, 47.5% considered ABPM the best diagnostic method for hypertension, 23% chose HBPM, and 7.1% chose office blood pressure. Also, 78.2% had AD available at their centers and 49.0% had ABPM, with slight urban/rural differences. HBPM was recommended in daily practice for hypertension diagnosis by 67% of participants, whereas 30% recommended ABPM. Cost to the patients was the main reason for not using HBPM (42.7%) as was lack of accessibility for not using ABPM (69.8%). Lack of specific training was also reported as an important reason in both cases. CONCLUSION: Even in the possibly best primary care scenario presented by highly motivated physicians (respondents to a voluntary anonymous survey), enormous gaps were observed between current guidelines' recommendations on ABPM and HBPM use for confirming hypertension and the modest degree of knowledge, availability, and use of these technologies.

7Be, 210Pb and 40K depositions over 11 years in Málaga.

The monthly bulk depositional fluxes of three natural radionuclides (7Be, 210Pb and 40K) were measured at a Mediterranean coastal station (Málaga) over an 11-year period from 2005 to 2015. The mean annual depositional fluxes of 7Be, 210Pb and 40K were 1215, 144 and 67 Bq m-2 year-1 respectively, showing a clear seasonal trend with minimum values recorded during summer and maximum values in winter. The rainfall regime with dry summers allows estimating the dry deposition. Assuming constant dry deposition through each year, 7Be, 210Pb and 40K would account for 12.5, 26.5 and 33% of the bulk fallout respectively which indicates that deposition for 210Pb and 40K are significantly higher than 7Be. The precipitation-normalized enrichment factor alpha used to explain seasonal variations in the depositional fluxes of radionuclides with respect the rainfall, indicates higher depositional fluxes during spring and summer than expected from the amount of rainfall. Despite their different origin, 210Pb and 7Be monthly depositional fluxes have strong correlation. The atmospheric deposition fluxes of 7Be, 210Pb and 40K were controlled mainly by the amount of rainfall (r = 0.89, 0.91 and 0.66 respectively). Moreover, principal component analysis was applied to the datasets and deposition of radionuclides and rainfall in the same component highlighting the importance of the washout mechanism. The mean depositional velocity of aerosols evaluated using 7Be and 210Pb are similar and are compared to other published values.