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Introduction: Spanish Governmen declared state of emergency in March 2020 to prevent coronavirus COVID-19 from spreading. During September and October 2020, at Child and Adolescent Psychiatry Unit we have attended patients who presented altered eating behaviors whose onset was during lockdown. We report a series of seven cases of adolescent girls between the ages of 11 and 16, who had no previous history of mental illness. During lockdown, they have presented restriction of food and increased physical exercise, with weight loss. Some of these patients have also presented food binges and purging behaviors. Objectives: Review the impact of lockdown on eating behavior, specially on weight loss. Methods: Literature review of scientific papers searching in Pubmed. Results: There are articles that study the variations in eating habits and exercise ocurred during confinement. Most focus on two trends: on the one hand, increased intake and the tendency to a more sedentary life; on the other hand, the worsening of people with a previous diagnosis of eating disorder. However, there is a third trend for which there are few studies: the new appearance of restrictive eating behaviors, together with increased physical exercise, bingeing and purging. This is the case of the patients we present. These studies describe as a possible cause of these alterations that confinement is a novel situation, which generates stress, social isolation, boredom, anxiety and a feeling of loneliness, which can influence self-concept and eating behaviors. Conclusions: Lockdown has favored a change in eating habits and exercise. More studies are needed on new-onset eating disorders. [ABSTRACT FROM AUTHOR]

Objectives: Vancomycin therapeutic drug monitoring is challenging, especially in the paediatric population where evidence is scarce. The main objective of this study was to analyse the achievement of therapeutic concentrations of vancomycin in paediatric patients and to evaluate the current monitoring method (trough levels), doses used, and the time required to achieve target concentrations., Methods: Paediatric patients on treatment and monitored with vancomycin from November 2019 to December 2021 were included. Those with only one determination of serum vancomycin concentration were excluded. Demographic variables, analytical and microbiological parameters and toxicity data were collected. Pharmacokinetic parameters were assessed at baseline and during treatment., Results: 225 patients (40.9% female; 108 neonates, 49 infants and 68 children or adolescents) were included in the study. The main indications for vancomycin treatment were sepsis (33.9%) and fever of unknown origin (29.3%). Microbiological cultures were positive in 71.1%, mostly with Gram-positive bacteria (60.4%). Therapeutic levels of vancomycin were reached in only 20.1% of the participants in the first determination. After pharmacokinetic monitoring, 81.7% of patients reached therapeutic concentrations, requiring a 23% increase in the initial dose, a 2-day lag time and 1-2 dosage adjustments until the therapeutic concentration was reached. Of the total patients, 13 developed nephrotoxicity, nine neutropenia and one patient developed red man syndrome., Conclusions: In our sample of paediatric patients, the recommended doses of vancomycin were insufficient to achieve therapeutic concentrations. Revision of the recommendations and/or a change in the method of pharmacokinetic monitoring is crucial to optimise treatment in this population., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The present study investigates the concentration of Delta (9)-tetrahidrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in 60 samples of cannabis resin acquired on the streets of Madrid region and its potential danger to consumers' health. Additionally, we study the possible correlation between the potency of samples and their organoleptic characteristics. The analysis of cannabinoids was carried out using a high performance liquid chromatography (RP-HPLC-UV). To classify samples, a strength scale based on THC content was established. THC content in 76.7% of the samples was higher than 15%. This potency allows these samples to be classified as Schedule I or drugs with "unacceptable risk" for human health. THC content in 36.7% of the samples was 28.8% on average, which means very high potency. The mean CBD content was 5%, while the correlation between the CBD/THC ratio and potency was negative. The mean content of CBN was 1.74% and the CBN/THC ratio also showed a negative correlation in respect to potency. When investigating the possible correlation between sample potency and organoleptic characteristics, those samples which simultaneously presented sticky texture, high elasticity and light brown colour had very high potency, with an average THC content of 28.7%. Our study shows that the THC content of most of the cannabis that can be purchased in Madrid region is over 15% and poses a health hazard. Additionally, we demonstrate for the first time that only those samples with very high potency can be directly associated with certain organoleptic characteristics.

Background: Medical students frequently have depressive symptoms. Thus, the psychological impact of COVID-19 on them should be high., Aim: To conduct a systematic review and meta-analysis on the prevalence of depression in medical students during the COVID-19 pandemic., Material and Methods: MEDLINE via PubMed, Embase and Web of Science were searched for studies reporting the prevalence of depression in medical students, published from December 1, 2019 to December 27, 2020., Results: Eleven studies were included, most of them from Asia. The estimated overall prevalence of depression in medical students was 31% (95% CI: 23%-40%), with lower prevalence rates reported in studies from Asia in general, and China in particular., Conclusions: Our findings indicate that the proportion of medical students with depression during the pandemic was high, and comparable with that reported in other university students.

Objective: Comparative "real life" data on the effectiveness and safety of ceftolozane/tazobactam (C/T) versus other regimens (aminoglycosides/colistin/combination), in the treatment of multi-resistant (MDR) and extremely resistant (XDR) Pseudomonas aeruginosa (PA), are needed to establish positions., Methods: Observational, retrospective study of patients with microbiological confirmation of MDR and XDR PA from July 2016 up to December 2018 in a tertiary hospital. Variables: age, sex, comorbidities, risk factors for multidrug resistance, variables related to infection, source of infection, microorganism and type of sample, antibiotic treatment, clinical cure, microbiological cure, recurrence, mortality on admission and 30 days post-discharge. Patients were classified according to received antibiotic treatment, C/T or aminoglycosides/colistin/combination., Results: A total of 405 patients with PA MDR and XDR infection (73.1% men, mean age 63 ± 15 years) were studied. An 87.1% of PA XDR and a 12.9% MDR were observed. All patients received C/T as targeted therapy and in the aminoglycosides/colistin/combination group were 73.5%. Patients in the C/T group present worse prognostic factors: septic shock (30.0%) and catheterization (90.0%) (p<0.05). There were not statistically significant differences in microbiological cure (p=0.412), recurrence (p=0.880) and clinical cure (p=0.566). There were not statistically significant differences in mortality at admission (p=0.352) or at 30 days after discharge (p=0.231). A 17.2% of the patients with aminoglycosides/colistin/combination had acute kidney injury according to RIFLE criteria and 4.3% with C/T., Conclusions: The data obtained suggest that there have been no differences in effectiveness (clinical or microbiological cure) in favour of C/T, although, in the period studied, it was used in most cases in multitreated patients with a worse prognosis. Randomized and prospective studies would be needed to establish an adequate positioning., (©The Author 2021. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Background: Since the beginning of the COVID-19 pandemic, teachers have been accumulating adverse psychological symptoms due to the closure of educational centers and the need to adapt to different teaching modalities., Methods: Medline and PubMed were searched for studies on the prevalence of depression, anxiety, stress, and burn-out in teachers, published from 1 December 2019 to 15 June 2021., Results: In total, eight studies were included in this study. The results show that teachers report levels of anxiety (17%), depression (19%), and stress (30%). In Asia, there has been more anxiety compared to other continents. Overall, anxiety has been higher among teachers in schools compared to universities. However, stress levels have been higher among teachers in universities compared to schools. Statistically, there were no significant differences regarding gender and age in any of the symptoms., Conclusions: The results suggest that teachers at different educational levels are experiencing adverse psychological symptomatology during the COVID-19 pandemic, and that anxiety levels vary between different countries. However, more international studies are needed to fully understand the impact of the pandemic on teachers' mental health.

Background: There is evidence of a high psychological toll from the COVID-19 pandemic in healthcare workers. This paper was aimed at conducting a systematic review and meta-analysis of studies reporting levels of depression among healthcare workers during the COVID-19 and estimating the pooled prevalence of depression., Methods: We searched for cross-sectional studies listed on PubMed from 1 December 2019 to 15 September 2020 that reported prevalence of depression in healthcare workers, nurses, medical doctors, and COVID-19 frontline professionals. The pooled proportions of depression were calculated with random effects models., Results: We identified 57 studies from seventeen countries. The pooled prevalence of depression in healthcare workers was 24% (95% CI: 20-28%), 25% for nurses (95% CI: 18-33%), 24% for medical doctors (95% CI: 16-31%), and 43% for frontline professionals (95% CI: 28-59%)., Conclusions: The proportion of depression in nurses and medical doctors during the COVID-19 pandemic was similar to that found in the general population as previously reported in other meta-analyses conducted with smaller numbers of studies. Importantly, almost half of the frontline healthcare workers showed increased levels of depression. There is need for a comprehensive, international response to prevent and treat common mental health problems in healthcare workers.

Background: The unprecedented worldwide crisis caused by the rapid spread of COVID-19 and the restrictive public health measures enforced by some countries to slow down its transmission have severely threatened the physical and mental wellbeing of communities globally., Methods: We conducted a systematic review and meta-analysis to determine the prevalence of anxiety in the general population during the COVID-19 pandemic. Two researchers independently searched for cross-sectional community-based studies published between December 1, 2019 and August 23, 2020, using PubMed, WoS, Embase, and other sources (e.g., grey literature, manual search)., Results: Of 3049 records retrieved, 43 studies were included. These studies yielded an estimated overall prevalence of anxiety of 25%, which varied significantly across the different tools used to measure anxiety. Consistently reported risk factors for the development of anxiety included initial or peak phase of the outbreak, female sex, younger age, marriage, social isolation, unemployment and student status, financial hardship, low educational level, insufficient knowledge of COVID-19, epidemiological or clinical risk of disease and some lifestyle and personality variables., Conclusions: As the overall global prevalence of anxiety disorders is estimated to be 7.3% normally, our results suggest that rates of anxiety in the general population could be more than 3 times higher during the COVID-19 pandemic. These findings suggest a substantial impact on mental health that should be targeted by individual and population-level strategies., (Copyright © 2020. Published by Elsevier Inc.)

Capecitabine-induced hand-foot syndrome (CiHFS) is a common dermatological adverse reaction affecting around 30% of patients with capecitabine-treated cancer, and the main cause of dose reductions and chemotherapy delays. To identify novel genetic factors associated with CiHFS in patients with cancer, we carried out an extreme-phenotype genomewide association study in 166 patients with breast and colorectal capecitabine-treated cancer with replication in a second cohort of 85 patients. We discovered and replicated a cluster of four highly correlated single-nucleotide polymorphisms associated with susceptibility to CiHFS at 20q13.33 locus (top hit = rs6129058, hazard ratio = 2.40, 95% confidence interval = 1.78-3.20; P = 1.2 × 10 -8 ). Using circular chromosome conformation capture sequencing, we identified a chromatin contact between the locus containing the risk alleles and the promoter of CDH4, located 90 kilobases away. The risk haplotype was associated with decreased levels of CDH4 mRNA and the protein it encodes, R-cadherin (RCAD), which mainly localizes in the granular layer of the epidermis. In human keratinocytes, CDH4 downregulation resulted in reduced expression of involucrin, a protein of the cornified envelope, an essential structure for skin barrier function. Immunohistochemical analyses revealed that skin from patients with severe CiHFS exhibited low levels of RCAD and involucrin before capecitabine treatment. Our results uncover a novel mechanism underlying individual genetic susceptibility to CiHFS with implications for clinically relevant risk prediction., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

The alterations in carbohydrate metabolism that fuel tumor growth have been extensively studied. However, other metabolic pathways involved in malignant progression, demand further understanding. Here we describe a metabolic acyl-CoA synthetase/stearoyl-CoA desaturase ACSL/SCD network causing an epithelial-mesenchymal transition (EMT) program that promotes migration and invasion of colon cancer cells. The mesenchymal phenotype produced upon overexpression of these enzymes is reverted through reactivation of AMPK signaling. Furthermore, this network expression correlates with poorer clinical outcome of stage-II colon cancer patients. Finally, combined treatment with chemical inhibitors of ACSL/SCD selectively decreases cancer cell viability without reducing normal cells viability. Thus, ACSL/SCD network stimulates colon cancer progression through conferring increased energetic capacity and invasive and migratory properties to cancer cells, and might represent a new therapeutic opportunity for colon cancer treatment.

Background and Objective: The Pharmacy and Therapeutics Committee (PTC) evaluates the requests for off-label uses with an abbreviated report format. The aim of this study is to perform a descriptive analysis of this activity and to study the rate of approvals., Material and Methods: A descriptive study was performed on the PTC reports in a tertiary hospital between September 2009 and April 2011. The type of drug by treatment group and by type of dispensing, indication and requesting department was analysed. The final decision adopted was studied as the primary outcome, and the percentage of requests approved according to the characteristics of the drug evaluated, indication requested, alternatives used, evidence and cost, as secondary outcomes., Results: A total of 51 applications were analysed, of which 60.8% were drugs for hospital use and 54.9% cytostatic. The most requested indications were the onco-haematological (43.2%) and autoimmune (35.3%). Haematology was the department that made most requests (11 requests with 72.7% approved), Oncology and Paediatrics (both with 10 requests, with 50% approved). Almost two-thirds (60.8%) of the requests were approved. Of those that were not approved, 11 had not used up the therapeutic alternatives, and 8 had no evidence. Just under half (47.1%) of the drugs requested had a cost/patient between 10,000-100,000 euros,of which 58.3% were approved (cost per course of treatment if it had a defined period, or cost of treatment per year for chronic treatment)., Conclusion: There is an increase in the activity of the PTC that is growing over the years. Most applications focus on drugs for hospital use and cytostatic drugs by Onco-haematology. There is a high rate of approval by the PTC, and high variability in the percentage of approval depending on the department and the evidence of use. The difference between approved and unapproved requests followed a logic of cost-effectiveness., (Copyright © 2012 SECA. Published by Elsevier Espana. All rights reserved.)

Tumour development comprises a complex succession of events that prompt incipient cancer cells to proliferate out of control and to acquire migratory and invasive capabilities. Over the past decades, cancer research has produced a wealth of knowledge about the intrinsic alterations of neoplastic cells within tumours. However, tumours now have come to be understood to function as complex tissues in which numerous cells, collectively termed the tumour microenvironment, play a critical role. These include inflammatory cells, blood vessels, fibroblasts and changes in their secreted extracellular matrix. This is revealing additional mechanisms of tumorigenesis that has spawned a new era of therapeutic strategies aimed at eradicating tumours.

Objective: To assess the frequency of class 1 integrons among isolates of Salmonella enterica producing different types of beta-lactamases from the health region of Tortosa, and to attempt to establish the resistance genes located within their variable regions., Methods: The presence of class 1 integrons and of aadA1, aadA2, dfrA1, tem-1, oxa-1 and pse-1 resistance genes within their variable regions was investigated by PCR in 100 ampicillin-resistant isolates of S. enterica (30 S. enteritidis, 56 S. Typhimurium and 14 from other serotypes) consecutively recovered in our laboratory between 2000 and 2001. Beta-lactamases were characterized by isoelectric focusing and PCR., Results: a) 6/57 TEM-1 producing isolates carried integrons: 1 S. ser Panama, 2 S. ser Enteritidis and 1 S. ser Typhimurium (1600 pb/aadA1-dfrA1); 1 S. ser Panama (1600 pb/aadA2-dfrA1); 1 S. ser Grumpensis (1500 pb 1 1700 pb; aadA2 and ??) b) All OXA-1 producing isolates (20 S. ser Typhimurium) bore an integron of 2000 pb/aadA1-oxa-1; c) All PSE-1 producing isolates (22 S. ser Typhimurium, most of them 104 phage type, and 1 S. enterica immobile [4,12:-:-]) harbored 2 integrons (1000 pb/aadA1 and 1,00 pb/pse-1)., Conclusion: The presence of class 1 integrons carrying oxa-1 or pse-1 resistance genes in all the OXA-1-producing and PSE-1-producing isolates investigated could have contributed to their spread and explain the increase in frequency of multiresistant S. ser Typhimurium isolates harboring these enzymes seen in the health region of Tortosa. In addition, we report the first isolate of S. ser enterica serotype Grumpensis harboring integrons.

The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development. Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin. Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene. Epithelial cells that ectopically express Snail adopt a fibroblastoid phenotype and acquire tumorigenic and invasive properties. Endogenous Snail protein is present in invasive mouse and human carcinoma cell lines and tumours in which E-cadherin expression has been lost. Therefore, the same molecules are used to trigger epithelial-mesenchymal transitions during embryonic development and in tumour progression. Snail may thus be considered as a marker for malignancy, opening up new avenues for the design of specific anti-invasive drugs.

The mechanisms underlying downregulation of the cadherin/catenin complexes and beta-catenin signaling during tumor progression are not fully understood. We have analyzed the effect of oncogenic H-Ras on E-cadherin/catenin complex formation/stabilization and beta-catenin distribution in epidermal keratinocytes. Microinjection or stable expression of V12Ras into keratinocytes promotes the loss of E-cadherin and alpha-catenin and relocalization of beta-catenin to the cytoplasm and nucleus. Moreover, these effects are dependent on PI3K (phosphoinositide 3-OH kinase) activity. Interestingly, a strong association of p85alpha and p110alpha subunits of PI3K with beta-catenin is induced in V12Ras-expressing keratinocytes, and in vitro binding assays show a direct interaction between beta-catenin and p85alpha. Overexpression of either V12Ras or constitutively active p110alpha induces metabolic stabilization of beta-catenin and promotes its accumulation in cytoplasmic and nuclear pools. In addition, the interaction of beta-catenin with the adenomatous polyposis coli protein is blocked in V12Ras and p110alpha transformants though no changes in glycogen synthase kinase 3 beta activity could be detected. Nevertheless, in V12Ras transformants the in vivo phosphorylation of beta-catenin in Ser residues is strongly decreased. These results indicate that H-Ras activation induces the relocalization and cytoplasmic stabilization of beta-catenin by a mechanism involving its interaction with PI3K.

Background: The aim of this study was to characterize resistance of Escherichia coli in our environment to four associations of beta-lactams and beta-lactamase inhibitors (beta Lac) studying the influence of the type and level of beta Lac production., Methods: The minimum inhibitory concentration (MIC) to ampicillin/sulbactam (A/S), amoxycillin/clavulanic acid (A/C), ticarcillin/clavulanic acid (T/C) and piperacillin/tazobactam (P/T) assessed was in 245 strains of E. coli resistant to ampicillin, consecutively isolated in our laboratory from September 1995 to March 1996. The beta Lac produced by these isolates were identified by isoelectrofocusing and spectrophotometrically quantified., Results: The sensitivity to A/S, A/C, T/C and P/T was of 9.4, 86.9, 64.5 and 89.4%, respectively. The strains with only one beta Lac which cofocused with TEM-1 were the most frequent (215/245), followed by those producing a cofocusing enzyme with SHV-1 (7/245). A significant correlation was observed between beta Lact activity of the 215 TEM-1 strains and their MIC at A/S (r = 0.53; p < 0.001), A/C (r = 0.46; p < 0.001), T/TC (r = 0.58; p < 0.001), and P/T (r = 0.42; p < 0.001). The comparison between enzyme activity of the isolates of the different categories of susceptibility showed significant differences (p < 0.05) for the four associations studied., Conclusion: TEM-1 production is the main cause of resistance to beta-lactams in E. coli in our environment. The inhibitory efficacy of sulbactam, clavulanic acid and tazobactam over TEM-1 is inversely proportional to the amounts of enzyme produced. The high rate of resistance to A/S and T/C E. coli presents in our environment is mainly due to a hyperproduction of TEM-1.