Risk Factors for Relapse in People with Severe Mental Disorders during the COVID-19 Pandemic: A Multicenter Retrospective Study

Background: Evidence suggests that different variables associated with the COVID-19 pandemic may increase the risk of relapse in people with Severe Mental Disorders (SMDs). However, no studies have yet looked closely at the different risk factors involved to determine their influence on the worsening of these patients’ illnesses. Objective: To analyze which variables related to the COVID-19 pandemic have increased the risk of relapse in patients with SMDs. Method: A multicenter retrospective cohort study in which data were collected from 270 patients with mental disorders who had been under follow-up in day hospitals during the year 2020. Results: The proportion of full mental health inpatient admissions was significantly higher in those who lost their employment (40.7% vs. 18.1%; p = 0.01), in those who were not receiving psychotherapy interventions (33.9% vs. 16.6%; p = 0.006), and in those who were not receiving occupational therapy (25.7% vs. 13.6%: p = 0.013). Significant associations were detected between urgent mental health consultations, the number of COVID-19 symptoms (B = 0.274; p = 0.02), and the low-income group (1.2424 vs. 0.4583; p = 0.018). Conclusions: COVID-19 symptoms and certain consequences of the pandemic, such as loss of employment, economic hardship, and loss of interventions, have brought about clinical worsening in people with SMDs. Knowledge of these factors is important for health-related decision-making in future outbreaks or pandemics

JAZ2 controls stomata dynamics during bacterial invasion

Coronatine (COR) facilitates entry of bacteria into the plant apoplast by stimulating stomata opening. COR-induced signaling events at stomata remain unclear. We found that the COR and jasmonate isoleucine (JA-Ile) co-receptor JAZ2 is constitutively expressed in guard cells and modulates stomatal dynamics during bacterial invasion. We analyzed tissue expression patterns of AtJAZ genes and measured stomata opening and pathogen resistance in loss- and gain-of-function mutants. Arabidopsis jaz2 mutants are partially impaired in pathogen-induced stomatal closing and more susceptible to Pseudomonas. Gain-of-function mutations in JAZ2 prevent stomatal reopening by COR and are highly resistant to bacterial penetration. The JAZ2 targets MYC2, MYC3 and MYC4 directly regulate the expression of ANAC19, ANAC55 and ANAC72 to modulate stomata aperture. Due to the antagonistic interactions between the salicylic acid (SA) and JA defense pathways, efforts to increase resistance to biotrophs result in enhanced susceptibility to necrotrophs, and vice versa. Remarkably, dominant jaz2Δjas mutants are resistant to Pseudomonas syringae but retain unaltered resistance against necrotrophs. Our results demonstrate the existence of a COI1-JAZ2-MYC2,3,4-ANAC19,55,72 module responsible for the regulation of stomatal aperture that is hijacked by bacterial COR to promote infection. They also provide novel strategies for crop protection against biotrophs without compromising resistance to necrotrophs

Humanization of tumor stroma by tissue engineering as a tool to improve squamous cell carcinoma xenograft

The role of stroma is fundamental in the development and behavior of epithelial tumors. In this regard, limited growth of squamous cell carcinomas (SCC) or cell-lines derived from them has been achieved in immunodeficient mice. Moreover, lack of faithful recapitulation of the original human neoplasia complexity is often observed in xenografted tumors. Here, we used tissue engineering techniques to recreate a humanized tumor stroma for SCCs grafted in host mice, by combining CAF (cancer associated fibroblasts)-like cells with a biocompatible scaffold. The stroma was either co-injected with epithelial cell lines derived from aggressive SCC or implanted 15 days before the injection of the tumoral cells, to allow its vascularization and maturation. None of the mice injected with the cell lines without stroma were able to develop a SCC. In contrast, tumors were able to grow when SCC cells were injected into previously established humanized stroma. Histologically, all of the regenerated tumors were moderately differentiated SCC with a well-developed stroma, resembling that found in the original human neoplasm. Persistence of human stromal cells was also confirmed by immunohistochemistry. In summary, we provide a proof of concept that humanized tumor stroma, generated by tissue engineering, can facilitate the development of epithelial tumors in immunodeficient miceThis research was funded in part by SCIENCE AND INNOVATION MINISTRY OF SPAIN; grant number [SAF2017-86810-R], INSTITUTO DE SALUD CARLOS III [PI17/01747], both co-funded with European Regional Development Funds (ERDF). Additional funds come from COMUNIDAD DE MADRID [B2017/BMD-3692], and DEBRA International. AGM was supported by a research scholarship of the ASOCIACIÓN ESPAÑOLA CONTRA EL CANCER (AECC), Spain

Sugar Content in Processed Foods in Spain and a Comparison of Mandatory Nutrition Labelling and Laboratory Values

To reduce the sugar content of processed foods through reformulation, the first step is to determine the content of the largest sources of sugars in each country’s diet. The aim of this work was to describe the sugar content in the most commonly consumed processed foods in Spain and to compare that sugar’s labelling and laboratory analysis values (LVs and AVs, respectively) to confirm its adequacy. A sample of the 1173 most commonly consumed processed foods in Spain (28 groups; 77 subcategories) was collected. For each product, the total sugar content was compared according to its AV and LV. The median (25th –75th percentiles, interquartile range) sugar content by group was calculated for the total sample, and the groups were classified as “high sugar content” when this value was above 22.5 g/100g of product. The adequacy of the LV, according to the European Union (EU) tolerance requirements, was then evaluated, and each subcategory median was compared with the AV to determine its appropriateness via a median test for independent samples (p < 0.05). In total, 10 out of 28 groups presented high sugar content. Moreover, 98.4% of the products met the EU tolerance ranges. Finally, only one subcategory (“cured ham”) presented significant differences between the AV and LV median values (0.4 g vs. 0.1 g sugar/100g, p < 0.05). The groups of food products whose sugar content reduction could have the greatest impact on public health were identified. In addition, our study showed the high adequacy of LV with the EU labeling tolerance requirements, as well as the LV’s appropriateness as a tool to implement actions aimed at reducing sugar consumption

Loss of smell and taste can accurately predict COVID-19 infection: a machine-learning approach

The COVID-19 outbreak has spread extensively around the world. Loss of smell and taste have emerged as main predictors for COVID-19. The objective of our study is to develop a comprehensive machine learning (ML) modelling framework to assess the predictive value of smell and taste disorders, along with other symptoms, in COVID-19 infection. A multicenter case-control study was performed, in which suspected cases for COVID-19, who were tested by real-time reversetranscription polymerase chain reaction (RT-PCR), informed about the presence and severity of their symptoms using visual analog scales (VAS). ML algorithms were applied to the collected data to predict a COVID-19 diagnosis using a 50-fold cross-validation scheme by randomly splitting the patients in training (75%) and testing datasets (25%). A total of 777 patients were included. Loss of smell and taste were found to be the symptoms with higher odds ratios of 6.21 and 2.42 for COVID-19 positivity. The ML algorithms applied reached an average accuracy of 80%, a sensitivity of 82%, and a specificity of 78% when using VAS to predict a COVID-19 diagnosis. This study concludes that smell and taste disorders are accurate predictors, with ML algorithms constituting helpful tools for COVID-19 diagnostic prediction.Junta de Andalucí

Clinically Relevant Correction of Recessive Dystrophic Epidermolysis Bullosa by Dual sgRNA CRISPR/Cas9-Mediated Gene Editing

Gene editing constitutes a novel approach for precisely correcting disease-causing gene mutations. Frameshift mutations inCOL7A1 causing recessive dystrophic epidermolysis bullosaare amenable to open reading frame restoration by non-homologous end joining repair-based approaches. Efficient targeteddeletion of faulty COL7A1 exons in polyclonal patient keratinocytes would enable the translation of this therapeutic strategy to the clinic. In this study, using a dual single-guide RNA(sgRNA)-guided Cas9 nuclease delivered as a ribonucleoprotein complex through electroporation, we have achieved veryefficient targeted deletion of COL7A1 exon 80 in recessivedystrophic epidermolysis bullosa (RDEB) patient keratinocytescarrying a highly prevalent frameshift mutation. This ex vivonon-viral approach rendered a large proportion of correctedcells producing a functional collagen VII variant. The effectivetargeting of the epidermal stem cell population enabled longterm regeneration of a properly adhesive skin upon graftingonto immunodeficient mice. A safety assessment by next-generation sequencing (NGS) analysis of potential off-target sitesdid not reveal any unintended nuclease activity. Our strategycould potentially be extended to a large number of COL7A1mutation-bearing exons within the long collagenous domainof this gene, opening the way to precision medicine for RDEB.The study was mainly supported by DEBRA International, funded by DEBRA Austria (grant termed as Larcher 1). Additional funds came from Spanish grants SAF2017-86810-R (to M.D.R.) and PI17/01747 (to F.L.) from the Ministry of Economy and Competitiveness and Instituto de Salud Carlos III, respectively, both co-funded with European Regional Development Funds (ERDF) ERA-NET E-RARE JTC 2017 (MutaEB) and CIBERER (grant termed as Murillas- TERAPIAS ER2017)

Effect of olive oil consumption on cardiovascular disease, cancer, type 2 diabetes, and all-cause mortality: A systematic review and meta-analysis

Background: Some large prospective studies on olive oil consumption and risk of chronic disease sug- gested protective effects. Objective: We conducted an outcome-wide systematic review and meta-analysis of prospective cohort studies and randomized controlled trials (RCT) assessing the association between olive oil consumption and the primary risk of 4 different outcomes: cardiovascular disease (CVD), cancer, type 2 diabetes (T2D) or all-cause mortality through January 2022. Methods: Thirty-six studies were included in the systematic review and twenty-seven studies (24 pro- spective cohorts and 3 different reports from one RCT) were assessed in 4 quantitative random-effects meta-analyses. They included a total of 806,203 participants with 49,223 CVD events; 1,285,064 par- ticipants with 58,892 incident cases of cancer; 680,239 participants with 13,389 incident cases of T2D; and 733,420 participants with 174,081 deaths. Olive oil consumption was most frequently measured with validated food frequency questionnaires. Studies follow-up ranged between 3.7 and 28 years. Results: A 16% reduced risk of CVD (relative risk [RR]: 0.84; 95% confidence interval [CI]: 0.76 to 0.94), standardized for every additional olive oil consumption of 25 g/d was found. No significant association with cancer risk was observed (RR: 0.94; 95% CI: 0.86 to 1.03, per 25 g/d). Olive oil consumption was associated with a 22% lower relative risk of T2D (RR: 0.78; 95% CI: 0.69 to 0.87, per 25 g/d) without evidence of heterogeneity. Similarly, it was inversely associated with all-cause mortality (RR: 0.89; 95% CI: 0.85 to 0.93, per 25 g/d). Only the results for T2D were homogeneous. Specific sources of hetero- geneity for the other 3 outcomes were not always apparent. Conclusions: Prospective studies supported a beneficial association of olive oil consumption with CVD, T2D and all-cause mortality, but they did not show any association with cancer risk

A nation-wide analysis of socioeconomic and geographical disparities in the prevalence of obesity and excess weight in children and adolescents in Spain: Results from the ENE-COVID study

Objective: To estimate national and provincial prevalence of obesity and excess weight in the child and adolescent population in Spain by sex and sociodemographic characteristics, and to explore sources of inequalities in their distribution, and their geographical patterns. Methods: ENE-COVID is a nationwide representative seroepidemiological survey (68 287 participants) stratified by province and municipality size (April-June 2020). Participants answered a questionnaire which collected self-reported weight and height, that allowed estimating crude and model-based standardized prevalences of obesity and excess weight in the 10 543 child and adolescent participants aged 2-17 years. Results: Crude prevalences (WHO growth reference) were higher in boys than in girls (obesity: 13.4% vs. 7.9%; excess weight: 33.7% vs. 26.0%; severe obesity: 2.9% vs. 1.2%). These prevalences varied with age, increased with the presence of any adult with excess weight in the household, while they decreased with higher adult educational and census tract average income levels. Obesity by province ranged 1.8%-30.5% in boys and 0%-17.6% in girls; excess weight ranged 15.2%-49.9% in boys and 10.8%-40.8% in girls. The lowest prevalences of obesity and excess weight were found in provinces in the northern half of Spain. Sociodemographic characteristics only partially explained the observed geographical variability (33.6% obesity; 44.2% excess weight). Conclusions: Childhood and adolescent obesity and excess weight are highly prevalent in Spain, with relevant sex, sociodemographic and geographical differences. The geographic variability explained by sociodemographic variables indicates that there are other potentially modifiable factors on which to focus interventions at different geographic levels to fight this problem.Instituto de Salud Carlos III; Ministerio de SanidadS