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 Traditional teaching methods, such as lectures or laboratory work, have been superseded by the use of new pedagogical approaches to enable a better conceptualization and understanding of the discipline.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.

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.

The efficacy of psychotherapy, pharmacotherapy and their combination on functioning and quality of life in depression: a meta-analysis.

BACKGROUND: There is growing recognition of the importance of both functioning and quality of life (QoL) outcomes in the treatment of depressive disorders, but the meta-analytic evidence is scarce. The objective of this meta-analysis of randomized controlled trials (RCTs) was to determine the absolute and relative effects of psychotherapy, pharmacotherapy and their combination on functioning and QoL in patients with depression. METHOD: One hundred and fifty-three outcome trials involving 29 879 participants with depressive disorders were identified through database searches in Pubmed, PsycINFO and the Cochrane Central Register of Controlled Trials. RESULTS: Compared to control conditions, psychotherapy and pharmacotherapy yielded small to moderate effect sizes for functioning and QoL, ranging from g = 0.31 to g = 0.43. When compared directly, initial analysis yielded no evidence that one of them was superior. After adjusting for publication bias, psychotherapy was more efficacious than pharmacotherapy (g = 0.21) for QoL. The combination of psychotherapy and medication performed significantly better for both outcomes compared to each treatment alone yielding small effect sizes (g = 0.32 to g = 0.39). Both interventions improved depression symptom severity more than functioning and QoL. CONCLUSION: Despite the small number of comparative trials for some of the analyses, this study reveals that combined treatment is superior, but psychotherapy and pharmacotherapy alone are also efficacious for improving functioning and QoL. The overall relatively modest effects suggest that future tailoring of therapies could be warranted to better meet the needs of individuals with functioning and QoL problems.

MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset.

Ulcerative colitis (UC) is one of the two major forms of inflammatory bowel disease, the aetiology of which remains unknown. Several studies have demonstrated the genetic basis of disease, identifying more than 130 susceptibility loci. The major histocompatibility complex class I chain-related gene A (MICA) is a useful candidate to be involved in UC pathogenesis, because it could be important in recognizing the integrity of the epithelial cell and its response to stress. The aim of this study was to analyse the relationship between polymorphisms in the transmembrane domain of MICA and susceptibility to develop UC. A total of 340 patients with UC and 636 healthy controls were genotyped for MICA transmembrane polymorphism using a polymerase chain reaction (PCR) combined with fluorescent technology. Different MICA alleles were determined depending on the PCR product size. The allele MICA*A4 was less frequent in patients than in controls (P = 0·003; OR = 0·643), and this protective role is higher when it forms haplotype with B*27 (P = 0·002; OR = 0·294). The haplotype HLA-B*52/MICA*A6 was also associated with UC [P = 0·001; odds ratio (OR) = 2·914]. No other alleles, genotypes or haplotypes were related with UC risk. Moreover, MICA*A5.1 is associated independently with abscesses (P = 0·002; OR = 3·096) and its frequency is lower in patients diagnosed between ages 17 and 40 years (P = 0·007; OR = 0·633), meaning an extreme age on onset. No association with location, extra-intestinal manifestations or need for surgery was found.

Examining Masculine Norms and Peer Support within a Sample of Incarcerated African American Males.

The adherence to masculine norms has been suggested to be influenced by social settings and context. Prisons have been described as a context where survival is dependent on adhering to strict masculine norms that may undermine reintegration back into the larger society. This study attempted to examine the relationship between masculine norms, peer support, and an individual's length of incarceration on a sample of 139 African American men taking part in a pre-release community re-entry program. Results indicate that peer support was associated with length of incarceration and the interaction between the endorsement of masculine norms and peer support significantly predicted the length of incarceration for African American men in this sample. Implications for incarcerated African American men and future research directions are discussed.

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.

Screening of Argentine native fungal strains for biocontrol of the grasshopper Tropidacris collaris: relationship between fungal pathogenicity and chitinolytic enzyme activity.

Tropidacris collaris (Orthoptera: Romaleidae) is a large and voracious grasshopper, which, in recent years, has become a recurrent pest in increasingly extensive areas of Argentina's northern provinces. In the present work chitinase activity was measured in 59 entomopathogenic fungal isolates native to Argentina, and the relationship between enzymatic activity and fungal virulence was assessed. Isolate LPSC 1067 caused the highest mortality on T. collaris nymphs (97.7 ± 1.22%). Nine isolates caused no mortality, while the remaining 49 caused mortalities ranging from 6.6 ± 0.3% (LPSC 770) to 91.06 ± 1.51% (LPSC 906). Several isolates revealed chitinolytic capabilities on test plates, although the activities differed with respect to the ratio of the chitin-decay-halo and fungal-colony diameters. A principal component analysis indicated that isolate LPSC 1067, obtained from a long-horned grasshopper (Orthoptera: Tettigoniidae), would be a potential candidate for T. collaris biocontrol because the strain exhibited the highest mortality, a shorter median lethal time, and a high enzymatic activity and growth rate.

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.

First record of Fusarium verticillioides as an entomopathogenic fungus of grasshoppers.

Fusarium verticillioides (Saccardo) Nirenberg (Ascomycota: Hypocreales) is the most common fungus reported on infected corn kernels and vegetative tissues, but has not yet been documented as being entomopathogenic for grasshoppers. Grasshoppers and locusts represent a large group of insects that cause economic damage to forage and crops. Tropidacris collaris (Stoll) (Orthoptera: Acridoidea: Romaleidae) is a large and voracious grasshopper that in recent years has become an increasingly recurrent and widespread pest in progressively more greatly extended areas of some of in Argentina's northern provinces, with chemical insecticides being currently the only means of control. During February and March of 2008-09, nymphs and adults of T. collaris were collected with sweep nets in dense woodland vegetation at a site near Tres Estacas in western Chaco Province, Argentina, and kept in screened cages. F. verticillioides was isolated from insects that died within 10 days and was cultured in PGA medium. Pathogenicity tests were conducted and positive results recorded. Using traditional and molecular-biological methods, an isolate of F. verticillioides was obtained from T. collaris, and its pathogenecity in the laboratory was shown against another harmful grasshopper, Ronderosia bergi (Stål) (Acridoidea: Acrididae: Melanoplinae). The mortality caused by F. verticillioides on R. bergi reached 58 ± 6.53% by 10 days after inoculation. This is the first record of natural infection caused by F. verticillioides in grasshoppers.

[Community antibiotic consumption in Chile, 2000-2008]. / Consumo comunitario de antimicrobianos en Chile, 2000-2008.

BACKGROUND: The Chilean Ministry of Health has implemented regulatory rules for the consumption of anti-biotics since September 1999, with sales restriction limited only with medical prescription. AIM: To analyze the impact of established regulatory measures from 2000 to 2008. MATERIAL AND METHODS: A retrospective analysis of antibiotics sales in pharmacies from 2000 to 2008 was performed. The information was obtained from the International Marketing System (IMS Health), an auditing system of pharmacy sales. The consumption unit used was the Defined Daily Dose per 1000 inhabitants/day (DDD). RESULTS: From 2000 to 2002 the regulatory rules had a great impact, but since 2002 the antibiotic consumption increased, especially amoxicillin, returning to similar levéis observed in 1998. CONCLUSIONS: The regulatory measures had an initial impact, but there was not reinforcement in the time and there was no further control. It is necessary to assume a permanent task and support of the authorities of health to edúcate the population about the implications of the inadequate use of antimicrobials and his effect on the microbial ecology.

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.

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.

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.

[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.

Arbuscular mycorrhizal fungal propagules from tillage and no-tillage systems: possible effects on Glomeromycota diversity.

Arbuscular mycorrhizal fungi (AMF) can use different types of propagules to colonize new roots. In this work we tested different types of AMF inocula obtained from a field experiment with tilled and no-tilled soils planted with wheat as well as from nondisturbed treatments with spontaneous vegetation. AMF trap cultures were carried out with soil, mycelium, segments of roots and wheat plants from the field as sources of inocula. Then after the senescence of the trap plants Glomeromycota species that had been established from each type of propagule in the substrate from the pots were identified. In field soils the proportions of Acaulosporaceae and Gigasporaceae were relatively similar to that of Glomeraceae, mainly in conventional tillage, whereas in all trap cultures investigated the percentages of members of the Glomeraceae family were higher than 90%. Because most of the trap cultures were based on intra- and/or extraradical mycelium our results show that members of Glomeraceae have advantages in the use of these propagules over Acaulosporaceae and Gigasporaceae species. We suggest that the higher contribution of Glomeraceae previously found in no-tillage systems could be related partially to the lack of disruption of the hyphal network and the composition of the soil propagules in this system.

Normal values in ambulatory oesophageal pH monitoring at two levels in Spain.

AIM: Upper oesophageal pH monitoring may play a significant role in the study of extra-oesophageal GERD, but limited normal data are available to date. Our aim was to develop a large series of normal values of proximal oesophageal acidification. METHODS: 155 healthy volunteers (74 male) participated in a multi-centre national study including oesophageal manometry and 24 hours oesophageal pH monitoring using two electrodes individually located 5 cm above the LOS and 3 cm below the UOS. RESULTS: 130 participants with normal manometry completed all the study. Twelve of them were excluded for inadequate pH tests. Twenty-seven subjects had abnormal conventional pH. The remaining 91 subjects (37 M; 18-72 yrs age range) formed the reference group for normality. At the level of the upper oesophagus, the 95th percentile of the total number of reflux events was 30, after eliminating the meal periods 22, and after eliminating also the pseudo-reflux events 18. Duration of the longest episodes was 5, 4 and 4 min, respectively (3.5 min in upright and 0.5 min in supine). The upper limit for the percentage of acid exposure time was 1.35, 1.05 and 0.95%, respectively. No reflux events were recorded in the upper oesophagus in 8 cases. CONCLUSION: This is the largest series of normal values of proximal oesophageal reflux that confirm the existence of acid reflux at that level in healthy subjects, in small quantity and unrelated to age or gender. Our data support the convenience of excluding pseudo-reflux events and meal periods from analysis.

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).