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Background: Limited information is available on patients' experience living with Huntington's disease (HD). The primary objective of this study was to assess the health-related quality of life and well being of patients with HD., Methods: A non-interventional, cross-sectional study was conducted in 17 hospitals-based movement disorders units in Spain. Patients aged ≥ 18 years, genetically HD diagnosed [with a diagnostic confidence level score of 4, and an Independence Scale (IS) score ≥ 70] were included. The primary variables were the Huntington's Disease Health-related Quality of Life (HDQLIFE) scores and results of the Satisfaction with Life Scale (SWLS). Secondary outcomes include the Unified HD Rating Scale (UHDRS), Beck Hopelessness Scale (BHS), Stigma Scale for Chronic Illness (SSCI-8), Beck Depression Inventory-Fast Screen (BDI-FS) and Problem Behaviours Assessment for HD short Version (PBA-S)., Results: A total of 102 patients were included. The mean age (SD) was 53.1 (12.1) years and 56% were male. Most of the patients (99.0%) showed motor symptoms (87.3%), behavioural and psychiatric disturbances (59.8%), or cognitive impairment (20.6%). HDQLIFE domain score means (SD) includes concern with death and dying 45.97 (9.60) end-of-life planning 37.91 (8.84), and meaning and purpose 44.74 (9.05). SWLS score mean was 24.25 (7.33). Depressive symptoms were found in 37.4% of patients and moderate-to-severe feelings of hopelessness in 32.9%. The prevalence of stigma was 55.9% (n = 57)., Conclusion: HD impacted quality of life, with prevalent motor, psychiatric symptoms and cognitive impairment. Patient perspectives may provide complementary information to implement specific interventions., Competing Interests: Declarations. Conflict of Interest: Sofía García-López, Carmen Álvarez and Jorge Maurino are Roche employees. Jesús Pérez Pérez, Tamara Fernández Valle, Cèlia Painous, María Rosa Querol Pascual, Pedro García-Ruiz Espiga, Elena Bellosta Diago, Esther Cubo Delgado, Bárbara Vives Pastor, María Carmen Peiró Vilaplana, Idaira Martín Santana, Marta Blázquez Estrada, Matilde Calopa Garride, Pablo Mir, Anna de Prado and José Luis López-Sendón declare no conflict of interest. JLS has served as a consultant or as an advisory committee member, unrelated to this research, from: La Roche ltd, Novartis ltd and UCB. Ethical Approval: The study was approved by the independent ethics committee CEIM of Hospital La Fe in Valencia. Code: ROC-HUN-2020-01 for Clinical Research and all patients provided written informed consent according to the Declaration of Helsinki., (© 2024. The Author(s).)

This article presents two cross-sectional studies that group the most relevant (and potential) factors contemplated in the bystander literature on Intimate Partner Violence Against Women, (IPVAW). We analyzed their relationship with the intention to respond to hypothetical scenarios with specific helping behaviors based on the witnesses' gender, political ideology and on the bystander effect (study 1). We also studied them as predictors of helping behaviors (study 2). In total, 1,563 Spanish people participated in study 1 and 755 Spanish people in study 2. Participants had to study an IPVAW vignette (with a single bystander or multiple bystanders) and a control scenario (a robbery with a woman as victim or a man) and assess the perceived severity of the situation, the perceived responsibility of the victim and the aggressor(s), the personal perceived responsibility of the bystander and the intention to perform 8 helping behaviors. They also fulfilled a social desirability scale (study 1 and 2), the Inventory of Distorted Thoughts about Women and Violence and the Scale on Gender Ideology (study 2). Women tend to assess the IPVAW scenario in a way that favors displaying active helping behaviors to a greater extent than men. An individual's political opinion has also shown to affect the assessment and, to a lesser extent, the intention to help an IPVAW victim. The bystander effect only takes place when negative attitudes are present. When analyzing the interaction between the type of violence (gender versus non-gender-based violence) and the above-mentioned variables, the results tend to confirm previous studies. Regarding the predictors of the helping behaviors, perceived personal responsibility is key, together with victim blaming attitudes or the perceived severity of the situation. This study expands the knowledge on bystander behaviors in IPVAW contexts and offers elements to work on awareness campaigns., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nardi-Rodríguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Bystander behaviors can be an important key for preventing all forms of violence against women. Identifying their facilitators and barriers becomes a priority. The aim of this research is to analyze the impact of the previous experiences of women (as sexual harassment victim or bystander) on their perceived responsibility to intervene as bystander in a case of workplace sexual harassment and to determine the possible mediating role of certain attitudinal and evaluative factors., Method: A non-probability convenience sample of 633 Spanish women answered a sociodemographic data questionnaire, a victimization questionnaire designed ad hoc, and the Questionnaire of Intention to Help in VAW Cases., Results: The results obtained indicate that previous victimization experiences as a victim or witness of sexual harassment impact the responsibility to intervene, mediated by the acceptance of sexual harassment myths and the perceived severity of workplace sexual harassment., Conclusions: These results may help to understand how to design prevention programs and which key variables to incorporate., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Victoria A. Ferrer-Perez reports article publishing charges, travel, and writing assistance were provided by State Research Agency (Agencia Estatal de Investigación, AEI) and the Ministry of Science, Innovation and Universities (Ministerio de Ciencia, Innovación y Universidades, MCIU). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Objective: Skin burns are associated with the presence of metallic components in transdermal drug delivery systems during Magnetic Resonance Imaging, cardioversion, or defibrillation procedures. The aim of the study was to review the presence of metallic components in marketed products of transdermal drug delivery systems in Spain., Method: For each pharmaceutical form, the summary of product characteristics was reviewed. If the information was not provided, manufacturers were contacted., Results: We identified 59 marketed products of transdermal drug delivery systems of 12 different active substances. 59.3% of patches contained metallic components or their presence could not be ruled out. Information regarding the need to remove the patch was only included in 8 summaries of product characteristics (13.6%) A table was elaborated and included the following aspects: product, active substance, manufacturer, need to remove the patch before the exposure to magnetic or electric fields, and references., Conclusion: More than a half of the patches at the time of the study contained metals or their absence could not be confirmed by the manufacturer. However, this information was only included in 13.6% of summaries of product characteristics., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: Skin burns are associated with the presence of metallic components in transdermal drug delivery systems during Magnetic Resonance Imaging, cardioversion or defibrillation procedures. The aim of the study was to review the presence of metallic components in marketed products of transdermal drug delivery systems in Spain., Method: For each presentation, the summary of product characteristics was reviewed. If the information was not provided, manufacturers were contacted., Results: We identified 59 marketed products of transdermal drug delivery systems of 12 different active substances. 59.3% of patches contained metallic components or their presence could not be ruled out. Information regarding the need to remove the patch was only included in 8 summaries of product characteristics (13.6%). A table was elaborated and included the following aspects: product, active substance, manufacturer, need to remove the patch before the exposure to magnetic or electric fields and references., Conclusion: More than a half of the patches at the time of the study contained metals or their absence could not be confirmed by the manufacturer. However, this information was only included in 13.6% of summaries of product characteristics., (Copyright © 2023 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

The rise in antifungal resistance and side effects of conventional treatments drive the search for innovative therapies like Photodynamic Therapy (PDT). This study explored the efficacy of PDT mediated by gutiferone, an isolated compound from red propolis, for candidiasis treatment. Multiple evaluation methods were employed, including determining the minimum inhibitory concentration (MIC) via broth microdilution, quantifying biomass using crystal violet detachment, and cell counting through total plate count. PDT mediated by gutiferone was also assessed in five groups of mice, followed by histopathological examination and agar plating of lingual tissue samples. Among the seven Candida species tested, gutiferone displayed efficacy against C. albicans, C. glabrata, and C. tropicalis, with MIC values of 1000 μg/mL. In C. tropicalis biofilms, exposure to gutiferone led to a reduction of 1.61 Log10 CFU/mL. PDT mediated by gutiferone achieved an average reduction of 3.68 Log10 CFU/mL in C. tropicalis biofilm cells, underscoring its potent fungicidal activity. Histopathological analysis revealed fungal structures, such as pseudohyphae and hyphae, in infected groups (G2) and irradiated mice. In contrast, groups treated with gutiferone or subjected to gutiferone-assisted PDT (G5) exhibited only few blastoconidia. Furthermore, CFU/mL assessments in lingual tissue post-treatment demonstrated a significantly lower count (0.30 Log10 CFU/mL) in the G5 group compared to G2 (2.43 Log10 CFU/mL). These findings highlight the potential of PDT mediated by gutiferone as a promising alternative for managing denture stomatitis. Future research and clinical investigations offer the promise of validating its clinical applicability and improving outcomes in the treatment of oral candidiasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Despite recent well-established kidney tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), usually presenting as acute kidney injury (AKI), there are few published cases with SARS-CoV-2-related tubulointerstitial nephritis (TIN). We report an adolescent with TIN and delayed association with uveitis (TINU syndrome), where SARS-CoV-2 spike protein was identified in kidney biopsy., Case-Diagnosis/treatment: A 12-year-old girl was assessed for a mild elevation of serum creatinine detected during the evaluation of systemic manifestations including asthenia, anorexia, abdominal pain, vomiting, and weight loss. Data of incomplete proximal tubular dysfunction (hypophosphatemia and hypouricemia with inappropriate urinary losses, low molecular weight proteinuria, and glucosuria) were also associated. Symptoms had initiated after a febrile respiratory infection with no known infectious cause. After 8 weeks, the patient tested positive in PCR for SARS-CoV-2 (Omicron variant). A subsequent percutaneous kidney biopsy revealed TIN and immunofluorescence staining with confocal microscopy detected the presence of SARS-CoV-2 protein S within the kidney interstitium. Steroid therapy was started with gradual tapering. Ten months after onset of clinical manifestations, as serum creatinine remained slightly elevated and kidney ultrasound showed mild bilateral parenchymal cortical thinning, a second percutaneous kidney biopsy was performed, without demonstrating acute inflammation or chronic changes, but SARS-CoV-2 protein S within the kidney tissue was again detected. At that moment, simultaneous routine ophthalmological examination revealed an asymptomatic bilateral anterior uveitis., Conclusions: We present a patient who was found to have SARS-CoV-2 in kidney tissue several weeks following onset of TINU syndrome. Although simultaneous infection by SARS-CoV-2 could not be demonstrated at onset of symptoms, since no other etiological cause was identified, we hypothesize that SARS-CoV-2 might have been involved in triggering the patient's illness., (© 2023. The Author(s).)

Alterations in plant metabolism play a key role in the complex plant-pathogen interactions. However, there is still a lack of knowledge about the connection between changes in primary and specialized metabolism and the plant defense against diseases that impact crops. Thus, we aim to study the metabolic reprograming in Brassica oleracea plants upon infection by Xanthomonas campestris pv. campestris ( Xcc ). To accomplish this, we utilized a combination of untargeted and targeted metabolomics, through UPLC-Q-TOF-MS/MS and 1 H-NMR, in two crop lines differing in resistance that were evaluated at two- and four-week intervals following inoculation (T1 and T2, respectively). Besides, to depict the physiological status of the plant during infection, enzymatic activities related to the carbohydrate pathway and oxidative stress were studied. Our results revealed different temporal dynamics in the responses of the susceptible vs. resistant crops lines. Resistant B. oleracea line suppresses carbohydrate metabolism contributing to limit nutrient supplies to the bacterium and prioritizes the induction of defensive compounds such as indolic glucosinolates, salicylic acid, phenylpropanoids and phytoalexins precursors at early infection stages. In contrast, the susceptible line invests in carbohydrate metabolism, including enzymatic activities related to the hexoses turnover, and activates defense signaling related to reactive oxygen species. Thus, each line triggers a different metabolic strategy that will affect how the plant overcomes the disease in terms of resistance and growth. This work provides first insights of a fine-tuned metabolic regulation during Xcc infection in B. oleracea that will contribute to develop new strategies for plant disease management., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Mother's milk contains a unique microbiome that plays a relevant role in offspring health. We hypothesize that maternal malnutrition during lactation might impact the microbial composition of milk and affect adequate offspring gut colonization, increasing the risk for later onset diseases. Then, Wistar rats were fed ad libitum (Control, C) food restriction (Undernourished, U) during gestation and lactation. After birth, offspring feces and milk stomach content were collected at lactating day (L)4, L14 and L18. The V3-V4 region of the bacterial 16S rRNA gene was sequenced to characterize bacterial communities. An analysis of beta diversity revealed significant disparities in microbial composition between groups of diet at L4 and L18 in both milk, and fecal samples. In total, 24 phyla were identified in milk and 18 were identified in feces, with Firmicutes, Proteobacteria, Actinobacteroidota and Bacteroidota collectively representing 96.1% and 97.4% of those identified, respectively. A higher abundance of Pasteurellaceae and Porphyromonas at L4, and of Gemella and Enterococcus at L18 were registered in milk samples from the U group. Lactobacillus was also significantly more abundant in fecal samples of the U group at L4. These microbial changes compromised the number and variety of milk-feces or feces-feces bacterial correlations. Moreover, increased offspring gut permeability and an altered expression of goblet cell markers TFF3 and KLF3 were observed in U pups. Our results suggest that altered microbial communication between mother and offspring through breastfeeding may explain, in part, the detrimental consequences of maternal malnutrition on offspring programming., Competing Interests: The authors declare no conflict of interest.

Plant responses against pathogens are influenced by growth immunity tradeoff, which ensure the best use of limited resources. We study how the immobilization of carbon resources and the induction of defensive responses (glucosinolates, phenolic compounds, stomatal closure) can influence the biomass of two Brassica oleracea lines, differing in their resistance, after infection with Xanthomonas campestris pv. campestris. Potentially, the growth immunity tradeoff can be influenced by the activation of all these processes. However, on the contrary of which is normally stated, our results suggest that the loss of biomass caused by pathogen infection is mainly due to the differential accumulation of starch and the immobilization of sugars rather than the reallocation of resources to synthesize secondary metabolites. Moreover, resistance may be related to the effectiveness of the tradeoff, since the resistant line immobilizes resources more efficiently than the susceptible one. Both inbred lines show a different phytohormones profile, which support the hypothesis that they are employing different strategies to defend themselves against the pathogen. This study emphasizes the key role of the primary metabolism in the defence strategies of plants against pathogens., (© 2022 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.)

A theoretical analysis of free Gibbs Energy and NMR 1H 13C chemical shifts of the effect of introduce methyl groups on diphenyl rings, to produce different isomers of (E)-1-(α,Ꞵ-dimethylbenzylidene)-2,2-diphenylhydrazine, is presented. IR vibrational frequencies, Mulliken charges, molecular electrostatic potential (MEP), Gibbs free energy (G) and 1H- and 13C-NMR chemical shifts were obtained by theoretical calculations. In this analysis it was found that the position of the methyl group affects the values of the 1H- and 13C-NMR chemical shifts and the ∆G and ∆H thermodynamic properties of formation and reaction, these properties vary with the same trend, for the isomers studied. Gibbs free energy calculations show that the theoretical (E)-1-(3,4-Dimethylbenzylidene)-2,2-diphenylhydrazine isomer is the most stable, which explains the success of the experimental synthesis of this compound among the other isomers. For this molecule, the C of the HC=N group is the most nucleophilic and the H is the least acidic. The 1H-NMR chemical shifts of protons show a strong correlation with the C=N distance. It was also observed that methyl affects the ν(C=N) frequencies, the C=N distance increases when the inductive effect of the methyl groups is in the structure.

Background: The use of molecular biomarkers for COVID-19 remains unconclusive. The application of a molecular biomarker in combination with clinical ones that could help classifying aggressive patients in first steps of the disease could help clinician and sanitary system a better management of the disease. Here we characterize the role of ACE2, AR, MX1, ERG, ETV5 and TMPRSS2 for trying a better classification of COVID-19 through knowledge of the disease mechanisms., Methods: A total of 329 blood samples were genotyped in ACE2, MX1 and TMPRSS2. RNA analyses were also performed from 258 available samples using quantitative polymerase chain reaction for genes: ERG, ETV5, AR, MX1, ACE2, and TMPRSS2. Moreover, in silico analysis variant effect predictor, ClinVar, IPA, DAVID, GTEx, STRING and miRDB database was also performed. Clinical and demographic data were recruited from all participants following WHO classification criteria., Results: We confirm the use of ferritin (p < 0.001), D-dimer (p < 0.010), CRP (p < 0.001) and LDH (p < 0.001) as markers for distinguishing mild and severe cohorts. Expression studies showed that MX1 and AR are significantly higher expressed in mild vs severe patients (p < 0.05). ACE2 and TMPRSS2 are involved in the same molecular process of membrane fusion (p = 4.4 × 10 -3 ), acting as proteases (p = 0.047)., Conclusions: In addition to the key role of TMPSRSS2, we reported for the first time that higher expression levels of AR are related with a decreased risk of severe COVID-19 disease in females. Moreover, functional analysis demonstrates that ACE2, MX1 and TMPRSS2 are relevant markers in this disease., (© 2023. The Author(s).)

Objective: To summarize the most recent scientific evidence on the usefulness and implementation of simulation training programs for health science students., Methods: A search and systematic review were conducted of the literature through the use of the PRISMA guidelines using the terms MESH Simulation AND healthcare AND Professional Training, including 42 articles., Results: The bibliometric analysis revealed that most of the studies were local in nature, that is, conducted in a single center, or in a few centers in the same region, from the English-speaking world, and using a mixed methodology with pre/post-test measurements. As for the educational aspects, most of the studies were conducted at universities or in the area of continuous education, used multidisciplinary teams as the student target, and used role-playing games as the simulation method. Also, these programs were especially successful in the acquisition of competencies, such as teamwork, communication, and trust., Conclusion: Clinical simulation is a teaching methodology implemented in the last twenty years, mainly in English-speaking countries; it utilizes techniques for its execution and assessment that have been validated in contrasted in many scientific studies, and lastly, it was also observed that it is useful for providing training on general competencies for multidisciplinary groups., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright� by the Universidad de Antioquia.)

Competing Interests: Conflicts of interest M.A.P. declares having received lecture fees and advisory board fees from Celgene, Gilead, Jansen, Kyowa Kirin, Millenium/Takeda and NanoString. P.L.O.-R. declares having received advisory fees from 4SC, Helsinn, Innate Pharma, Kyowa Kirin, Mallinckrodt, Recordati Rare Diseases and Takeda. The authors declare that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Background: A protective hepatitis B virus (HBV) vaccine has been available for four decades. Universal HBV vaccination of infants is recommended by the WHO since the 1990s. Furthermore, HBV immunization is advised for all adults with high-risk behaviours and no seroprotection. However, HBV vaccine coverage remains globally suboptimal. The advent of new more efficacious trivalent HBV vaccines has renewed the interest in HBV vaccination. At present, the extent of current HBV susceptibility in adults remains unknown in Spain., Methods: HBV serological markers were assessed on a large and representative sample of adults in Spain, including blood donors and individuals belonging to high-risk groups. Serum HBsAg, anti-HBc and anti-HBs were tested in specimens collected during the last couple of years., Results: From 13 859 consecutive adults tested at seven cities across the Spanish geography, overall 166 (1.2%) had positive HBsAg. Past HBV infection was recognized in 14% and prior vaccine immunization in 24%. Unexpectedly, 37% of blood donors and 63% of persons belonging to high-risk groups had no serum HBV markers and therefore were potentially HBV susceptible., Conclusion: Roughly 60% of adults living in Spain seem to be HBV susceptible. Waning immunity might be more common than expected. Hence, HBV serological testing should be performed at least once in all adults regardless of risk exposures. HBV vaccine full courses or boosters should be administered to all adults lacking serological evidence of HBV protection., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: We carried out a histological characterization analysis of the stromal layer of human heterotypic cornea substitutes generated with extra-corneal cells to determine their putative usefulness in tissue engineering. Methods: Human bioartificial corneas were generated using nanostructured fibrin-agarose biomaterials with corneal stromal cells immersed within. To generate heterotypical corneas, umbilical cord Wharton's jelly stem cells (HWJSC) were cultured on the surface of the stromal substitutes to obtain an epithelial-like layer. These bioartificial corneas were compared with control native human corneas and with orthotypical corneas generated with human corneal epithelial cells on top of the stromal substitute. Both the corneal stroma and the basement membrane were analyzed using histological, histochemical and immunohistochemical methods in samples kept in culture and grafted in vivo for 12 months in the rabbit cornea. Results: Our results showed that the stroma of the bioartificial corneas kept ex vivo showed very low levels of fibrillar and non-fibrillar components of the tissue extracellular matrix. However, in vivo implantation resulted in a significant increase of the contents of collagen, proteoglycans, decorin, keratocan and lumican in the corneal stroma, showing higher levels of maturation and spatial organization of these components. Heterotypical corneas grafted in vivo for 12 months showed significantly higher contents of collagen fibers, proteoglycans and keratocan. When the basement membrane was analyzed, we found that all corneas grafted in vivo showed intense PAS signal and higher contents of nidogen-1, although the levels found in human native corneas was not reached, and a rudimentary basement membrane was observed using transmission electron microscopy. At the epithelial level, HWJSC used to generate an epithelial-like layer in ex vivo corneas were mostly negative for p63, whereas orthotypical corneas and heterotypical corneas grafted in vivo were positive. Conclusion: These results support the possibility of generating bioengineered artificial corneas using non-corneal HWJSC. Although heterotypical corneas were not completely biomimetic to the native human corneas, especially ex vivo , in vivo grafted corneas demonstrated to be highly biocompatible, and the animal cornea became properly differentiated at the stroma and basement membrane compartments. These findings open the door to the future clinical use of these bioartificial corneas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Blanco-Elices, Morales-Álvarez, Chato-Astrain, González-Gallardo, Ávila-Fernández, Campos, Carmona, Martín-Piedra, Garzón and Alaminos.)

Background: Venous ulcers usually present a torpid evolution with a negative impact on patients' quality of life. In primary care, they account for 2.5% of nursing consultations and their treatment represents high costs for national health systems. These patients usually have a low level of physical activity, with muscle pump dysfunction of the lower limbs, which may improve with increased physical activity. The purpose of this study is to analyse the effectiveness of a structured intervention involving physical activity and exercise (Active Legs) as an adjuvant treatment in improving healing of chronic venous ulcers at 3 months follow-up., Methods: A randomized, multicentre clinical trial. A total of 224 individuals receiving primary nursing care with a diagnosis of venous ulcer, with a diameter of 1 cm or greater and an ankle-brachial index between 0.8 and 1.3, able to comply with the study requirements and consenting to participate, will be sequentially included (112 per group). Both groups will receive the standard treatment in primary care, with cleansing, debridement and healing in a moist environment together with multilayer compression therapy. The intervention group will also receive a structured educational intervention involving lower limb physical exercise and daily ambulation guidelines. The primary response variables will be complete healing -understood as complete and sustained epithelialisation for at least 2 weeks- and time to healing. The secondary variables will be degree of healing, ulcer area, quality of life, pain and variables related to the healing process, prognosis, and recurrences. Sociodemographic variables, adherence to treatment and satisfaction variables will also be recorded. Data will be collected at baseline, at 3 months and at 6 months follow-up. Survival analysis (Kaplan-Meier and Cox) will be performed to measure primary effectiveness. Intention-to-treat analysis., Discussion: If the intervention is effective, a cost-effectiveness analysis could be conducted and implemented as an additional intervention in the usual venous ulcer treatment in primary care., Trial Registration: NCT04039789. [ https://ClinicalTrials.gov ]. 07/11/2019., (© 2023. The Author(s).)

The presence of venous leg ulcers (VLU) is associated with emotional disorders in individuals who have conditions, such as depression, anxiety, and sleeping problems, which result in a reduced perceived quality of life by these individuals. The study aim was to describe the perceived quality of life and associated factors for individuals with VLU. We conducted a cross-sectional study in 22 primary care health centers with a sample of 93 individuals with VLU. The variables collected were the following: perceived quality of life measured with Spanish version of the Charing Cross Venous Ulcer Questionnaire (CCVUQ-e), ulcer severity measured with the RESVECH 2.0 Score, demographic variables, and those related to the healing process. The results showed a mean CCVUQ-e score of 47.4 ± 11.8 points (Mean ± SD), with the most affected dimension being the emotional status, followed by cosmesis, social interaction, and domestic activities. The mean RESVECH 2.0 score was 11.1 ± 3.7 points. An association was found between ulcer-related pain and poorer quality of life ( P < .05, t test) and between erythema in perilesional skin and poorer quality life ( P < .05, t test). The signs of infection and inflammation in the VLUs were as follows: increasing exudate, friable tissue, and biofilm-compatible tissue, which were associated with a poorer quality of life ( P < .05, t test). The multivariate model was statistically significant and explained a variability of 26% in the CCVUQ-e score. This study confirms that wound severity, pain, and signs of infection in VLU decrease the perceived quality of life of individuals with these wounds.

Fusarium fujikuroi, a model organism for secondary metabolism in fungi, produces carotenoids, terpenoid pigments with antioxidant activity. Previous results indicate that carotenoid synthesis in F. fujikuroi is stimulated by light or by different stress conditions and downregulated by a RING finger protein encoded by carS gene. Here, we have analyzed the effects of three stressors, nitrogen scarcity, heat shock, and oxidative stress. We compared them with the effect of light in the wild type, a carS mutant that overproduces carotenoids, and its complemented strain. The assayed stressors increase the synthesis of carotenoids in the three strains, but mRNA levels of structural genes of carotenogenesis, carRA and carB , are only enhanced in the presence of a functional carS gene. In the wild-type strain, the four conditions affect in different manners the mRNA levels of carS : greater in the presence of light, without significant changes in nitrogen starvation, and with patent decreases after heat shock or oxidative stress, suggesting different activation mechanisms. The spores of the carS mutant are more resistant to H 2 O 2 than those of the wild type; however, the mutant shows a greater H 2 O 2 sensitivity at the growth level, which may be due to the participation of CarS in the regulation of genes with catalase domains, formerly described. A possible mechanism of regulation by heat stress has been found in the alternative splicing of the intron of the carS gene, located close to its 3' end, giving rise to the formation of a shorter protein. This action could explain the inducing effect of the heat shock, but not of the other inducing conditions, which may involve other mechanisms of action on the CarS regulator, either transcriptionally or post-transcriptionally., Competing Interests: SN is employed by the Symrise AG Chemicals company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ruger-Herreros, Nordzieke, Vega-Álvarez, Avalos and Limón.)

Cocoa constitutes one of the richest sources of dietary flavonoids with demonstrated anti-diabetic potential. However, the metabolic impact of cocoa intake in a diabetic context remains unexplored. In this study, metabolomics tools have been used to investigate the potential metabolic changes induced by cocoa in type 2 diabetes (T2D). To this end, male Zucker diabetic fatty rats were fed on standard (ZDF) or 10% cocoa-rich diet (ZDF-C) from week 10 to 20 of life. Cocoa supplementation clearly decreased serum glucose levels, improved glucose metabolism and produced significant changes in the urine metabolome of ZDF animals. Fourteen differential urinary metabolites were identified, with eight of them significantly modified by cocoa. An analysis of pathways revealed that butanoate metabolism and the synthesis and degradation of branched-chain amino acids and ketone bodies are involved in the beneficial impact of cocoa on diabetes. Moreover, correlation analysis indicated major associations between some of these urine metabolites (mainly valine, leucine, and isoleucine) and body weight, glycemia, insulin sensitivity, and glycated hemoglobin levels. Overall, this untargeted metabolomics approach provides a clear metabolic fingerprint associated to chronic cocoa intake that can be used as a marker for the improvement of glucose homeostasis in a diabetic context., Competing Interests: The authors declare no conflicts of interest.

Background: Background: Perinatal malnutrition seems to provoke important neurochemical alterations in the brain that lead to higher vulnerability to develop neuropsychiatric disorders in the adulthood., Objectives: We have examined the persistence and reversibility of the changes induced by perinatal undernourishment on the expression of fumarate hydratase in the rat nucleus accumbens, bearing in mind that this expression has been previously linked with addictive disorders. Clusterin, a multifunctional protein known to be neuroprotective and possibly related to addiction in humans, was studied in parallel., Methods: Female Wistar rats underwent a severe restriction of food during gestation and lactation. Upon weaning, a subgroup of undernourished animals was switched to normal chow and another one continued under food restriction. Control rats and their mothers were fed on chow along the experiment. Fumarate hydratase and clusterin were quantified by western blot after five months of postnatal life in the three experimental groups., Results: Food restriction along the whole experimental period provoked a marked upregulation of both clusterin and fumarate hydratase in the mitochondrial fraction of the nucleus accumbens. In the case of clusterin, this upregulation was also observed in the cytosolic fraction of the nucleus accumbens. When undernourishment was limited to gestation and lactation the two proteins appeared downregulated with respect to controls., Conclusion: The results are consistent with the idea that perinatal malnutrition provokes marked changes in brain neurochemistry that are not fully corrected by the rehabilitation of normal feeding and could be linked to behavioural disturbances in the adulthood, that is, increased vulnerability to addiction.

This study explores the growth of bacterial, fungal, and interkingdom biofilms under aerobiosis or microaerobic conditions and the effect of ozonated sunflower oil on these biofilms. Candida species and Streptococcus mutans were used to study this interaction due to their importance in oral health and disease as these microorganisms display a synergistic relationship that manifests in the onset of caries and tooth decay. Biofilms were developed in a 96-well microtiter plate at 37ºC for 24 h, under aerobiosis or microaerobic conditions, and treated with ozonated oil for 5 to 120 min. All the microorganisms formed biofilms in both oxygenation conditions. Scanning electron microscopy was used to visualize biofilm morphology. Rodent experiments were performed to verify the oil-related toxicity and its efficacy in oral candidiasis. The growth of all Candida species was increased when co-cultured with S. mutans, whilst the growth of bacterium was greater only when co-cultured with C. krusei and C. orthopsilosis under aerobiosis and microaerobic conditions, respectively. Regardless of the oxygenation condition, ozonated oil significantly reduced the viability of all the tested biofilms and infected mice, showing remarkable microbicidal activity as corroborated with confocal microscopy and minimal toxicity. Thus, ozonated oil therapy can be explored as a strategy to control diseases associated with these biofilms especially in the oral cavity., Lay Summary: We demonstrated that ozonated sunflower oil is effective at killing the biofilms formed by Candida species, by the bacterium Streptococcus mutans, or by both micoorganisms that can interact in the oral cavity, making it a potential therapeutic option for the treatment of these infections., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: The therapeutic landscape for spinal muscular atrophy has changed in the last few years, encompassing respiratory/motor function and life expectancy benefits. However, physicians still have the challenge of tailoring individuals' treatment to therapeutic goals, disease progression, patient/caregiver's preferences, and personal experience to achieve an optimal risk/benefit balance. This study aims to provide insight into the preferred treatment choices of pediatric neurologists managing spinal muscular atrophy in their daily practice and to recognize behavioral factors that may influence decision-making., Methods: This is a noninterventional, cross-sectional pilot study involving 50 pediatric neurologists managing spinal muscular atrophy in Spain. We designed an online platform that contains 13 simulated case scenarios of common presentations of patients with spinal muscular atrophy. The primary study outcome will be treatment preferences according to the percentages of participants who select treatment initiation when recommended, switch therapies when there is evidence of disease progression, and select treatment discontinuation when disease progression puts patients outside treatment recommendation (11 case scenarios). Secondary outcomes include therapeutic inertia prevalence (11 case scenarios), herding phenomenon prevalence (2 case scenarios), care-related regret prevalence (specific questions) and intensity (10-item Regret Intensity Scale), occupational burnout prevalence (nonproprietary single-item measure), and risk preferences (uncertainty test and risk aversion assessment)., Conclusions: The study findings will contribute to better understand relevant factors associated with therapeutic decisions of pediatric neurologists in spinal muscular atrophy, identifying treatment preferences and evaluating the role of behavioral aspects such as therapeutic inertia, herding, regret, and workplace burnout., Competing Interests: The study was funded by Roche Medical Department, Spain (SL42765). This does not alter our adherence to PLoS ONE policies on sharing data and materials. Gustavo Saposnik received unrestricted grants and personal fees from Hoffman La Roche (Canada) and Roche Farma (Spain), and reported being supported by the Heart and Stroke Foundation of Canada Scientist Award following an open peer-reviewed competition. Paola Díaz-Abós, Victoria Sánchez-Menéndez, Carmen Álvarez, Jorge Maurino, and María Brañas-Pampillón are employees of Roche Farma Spain. María Terzaghi and Ignacio Málaga declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Several studies have shown a relationship between the distribution of fat mass around the organism, metabolic disorders, and an increased risk of morbidity and mortality. It has been demonstrated that in obese animals there is a big rise in the white fat deposits due to hyperplasia and hypertrophy of the adipocytes. Studies related to weight and health have been more popular regarding obesity rather than extreme caquexia or calorico-proteic deficiencies, but these states are interesting from the point of view of the preferential atrophy of certain organs that may help us in the understanding of undernourishment. Moreover, the discovery of beige adipose tissue has instigated thoughts around the roles played by the different cells in the adipose tissue as well as its adaptability in pathological states. In our study we carried out morphometric, morphological, and quantitative measurements of the adipose tissue in an animal model based on a 40-50% diet restriction in comparison to control animals. We have found a decrease in the size of white adipocytes together with a variation in the lipid droplet size of brown adipocytes in undernourished animals, what may be considered as possible transformations between the types of adipose tissues, and that could be caused by an adaptive phenomenon to the undernourished state., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To evaluate if the two-layer bandage is more effective than the crepe bandage in the healing of venous ulcers after 12 weeks of follow-up., Design: Randomized multicentre controlled clinical trial., Location: 22 Primary Health Centers of Madrid., Participants: Over 18 years old, with diagnosis of venous ulcers. 93 patients were randomized, 56 in the double layer group and 37 in the crepe group. Withdrawals: 16 in double layer group, 7 in crepe group., Interventions: Control group: usual clinical practice: treatment of the wound and bandage with crepe. Experimental group: same usual clinical practice for wound treatment and bandage with double layer., Main Measurements: Primary outcome: complete healing at 12 weeks., Secondary Outcomes: severity of ulceration, health-related quality of life, adverse events. Blind evaluation of the response variable., Results: Complete healing: in crepe group, 25, 67.5% (95% CI 50.2-81.9) and in double layer group, 32, 57.1% (95% CI 43.2-70.3). No evidence of a difference in both groups, RR=1.10 (95% CI 0.864-1.424). The basal severity of the ulcers is associated with the healing time. HR=0.86 (95% CI 0.78-0.94). Our data showed a significant improvement in health-related quality of life, total and in the of cosmesis and emotional dimensions. No evidence of a difference in both groups. We didn't find serious adverse events in any of the groups., Conclusions: We didn't find significant differences in the healing between the two bandages evaluated. Both are appropriate for ulcer healing and to improve the health-related quality of life., (Copyright © 2020 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.)

Attitudes play a central role in intimate partner violence against women and are related to its origin, to the responses of women who suffer violence, and to the settings where it occurs. In fact, these attitudes are recognized as one of the risk factors linked to violent perpetration and to public, professional, and victim responses to this type of violence. However, even though available research generally shows a broad rejection of this violence, it remains a serious social and health problem that has reached epidemic proportions. This suggests that the information available about these attitudes (obtained through explicit and direct measures, i.e., self-reports) may be distorted or influenced by factors such as social desirability. In this context, the overall objective of our research project is to provide multi-method measures (explicit and implicit) of attitudes toward intimate partner violence against women, and the main goal of this paper is to propose an instrument for the implicit measurement of these attitudes. In this regard, the Implicit Association Test (IAT) is the most common procedure used, providing a superior predictive validity compared to explicit measures for socially sensitive topics. We will present an exploratory study that describes its adaptation for our purposes, and the development of the Gender Violence - Implicit Association Test (GV-IAT) to use among Spanish-speaking populations, and discuss the strengths and limitations of this proposal.

Maternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liver glycogen autophagy in the programming of glucose metabolism disturbances. To this end, newborns were obtained from pregnant Wistar rats fed ad libitum with a standard diet or 65% food-restricted during the last week of gestation. We found that newborns from undernourished mothers showed markedly high basal insulin levels whereas those of glucagon were decreased. This unbalance led to activation of the mTORC1 pathway and inhibition of hepatic autophagy compromising the adequate handling of glycogen in the very early hours of extrauterine life. Restoration of autophagy with rapamycin but not with glucagon, indicated no defect in autophagy machinery per se, but in signals triggered by glucagon. Taken together, these results support the notion that hyperinsulinemia is an important mechanism by which mobilization of liver glycogen by autophagy is defective in food-restricted animals. This early alteration in the hormonal control of liver glycogen autophagy may influence the risk of developing metabolic diseases later in life.

Cocoa supplementation improves glucose metabolism in Zucker diabetic fatty (ZDF) rats via multiple mechanisms. Furthermore, cocoa rich-diets modify the intestinal microbiota composition both in humans and rats in healthy conditions. Accordingly, we hypothesized that cocoa could interact with the gut microbiota (GM) in ZDF rats, contributing to their antidiabetic effects. Therefore, here we investigate the effect of cocoa intake on gut health and GM in ZDF diabetic rats. Male ZDF rats were fed with standard (ZDF-C) or 10% cocoa-rich diet (ZDF-Co) during 10 weeks. Zucker Lean animals (ZL) received the standard diet. Colon tissues were obtained to determine the barrier integrity and the inflammatory status of the intestine and faeces were analysed for microbial composition, short-chain fatty acids (SCFA) and lactate levels. We found that cocoa supplementation up-regulated the levels of the tight junction protein Zonula occludens-1 (ZO-1) and the mucin glycoprotein and reduced the expression of pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 (MCP-1) in the colon of ZDF diabetic animals. Additionally, cocoa modulated the microbial composition of the ZDF rats to values similar to those of the lean group. Importantly, cocoa treatment increased the relative abundance of acetate-producing bacteria such as Blautia and prevented the increase in the relative amount of lactate-producing bacteria (mainly Enterococcus and Lactobacillus genera) in ZDF diabetic animals. Accordingly, the total levels of SCFA (mainly acetate) increased significantly in the faeces of ZDF-Co diabetic rats. Finally, modified GM was closely associated with improved biochemical parameters related to glucose homeostasis and intestinal integrity and inflammation. These findings demonstrate for the first time that cocoa intake modifies intestinal bacteria composition towards a healthier microbial profile in diabetic animals and suggest that these changes could be associated with the improved glucose homeostasis and gut health induced by cocoa in ZDF diabetic rats., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We generalize the notion of λ-superstrings, presented in a previous paper, to the notion of weighted λ-superstrings. This generalization entails an important improvement in the applications to vaccine designs, as it allows epitopes to be weighted by their immunogenicities. Motivated by these potential applications of constructing short weighted λ-superstrings to vaccine design, we approach this problem in two ways. First, we formalize the problem as a combinatorial optimization problem (in fact, as two polynomially equivalent problems) and develop an integer programming (IP) formulation for solving it optimally. Second, we describe a model that also takes into account good pairwise alignments of the obtained superstring with the input strings, and present a genetic algorithm that solves the problem approximately. We apply both algorithms to a set of 169 strings corresponding to the Nef protein taken from patiens infected with HIV-1. In the IP-based algorithm, we take the epitopes and the estimation of the immunogenicities from databases of experimental epitopes. In the genetic algorithm we take as candidate epitopes all 9-mers present in the 169 strings and estimate their immunogenicities using a public bioinformatics tool. Finally, we used several bioinformatic tools to evaluate the properties of the candidates generated by our method, which indicated that we can score high immunogenic λ-superstrings that at the same time present similar conformations to the Nef virus proteins., Competing Interests: The authors have declared that no competing interests exist.

Background: Some attitudes serve to justify violence against women, to blame women for the violence they experience, and to perpetuate levels of this violence. These attitudes often stem from traditional norms and beliefs which are important to identify. The purpose of this study is to compare beliefs about intimate partner violence against women (IPVAW) between two time points, examining the effect of the respondents&ndash; sex and previous academic-training., Method: Two opportunity samples of undergraduates took part in this study: 1,392 in 2006 (34.4% men and 65.6% women) and 730 in 2018 (36.3% men and 63.7% women). A four-factor model from the Inventory of Distorted Thoughts on Women and Violence (IPDMV) was used after assessing fit through CFA., Results: Significant differences between 2006 and 2018 in all factors were found using MANCOVA (covariable: age). Differences were also found by sex and previous academic-training, and effects of interaction in the first factor between these variables and the time point., Conclusions: The beliefs and distorted thoughts about women and violence fell between the two time points analysed, with less acceptance of these beliefs among women and people with prior IPVAW academic-training.

In the dwarf hamster (Phodopus campbelli), activational effects of testosterone (T) and estradiol (E 2 ) in the regulation of paternal behavior have been repeatedly rejected because peripheral concentrations of E 2 do not change across the reproductive cycle of males. Further, castration no affected paternal behavior despite that both T and E 2 concentrations decreased significantly. However, the role of these hormones has not been evaluated in models of castration and hormonal replacement in virgin males. Here, we analysed the effects of E 2 and T in paternal behavior in virgin male dwarf hamster (Phodopus campbelli). Thirty paternal (PAT) males were bilaterally castrated; of them, 10 were implanted with T, 10 with E 2 and 10 males received no treatment. Other 10 PAT males underwent sham-castration. Seventeen aggressive (AGG) males were also bilaterally castrated; of these, 10 AGG received E 2 replacement, 7 were not treated. Other 7 AGG males were submitted to sham-castration. Following treatments, paternal behavior tests were conducted again. T and E 2 levels in plasma were quantified by radioimmunoassay (RIA). The results showed that the treatments did not affect the paternal behavior of males that were initially paternal. Neither castration nor sham-castration surgery affected the behavior of AGG males. However, when these males were treated with E 2 and the concentrations of this hormone increase significantly they became paternal. Our data suggest that an increase in E 2 levels shifted infanticidal behavior to paternal behavior in dwarf hamster., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Review of the experience of a tertiary care centre for almost 10 years in the CT diagnosis of non-occlusive mesenteric ischaemia (NOMI). Analysis of CT findings, correlation with clinical outcomes and evaluation of the usefulness of measuring the superior mesenteric artery (SMA) diameter for the diagnosis of NOMI., Methods: 106 patients were diagnosed with NOMI in a biphasic CT examination from 2008 to 2017 in our hospital. Clinical outcomes and CT findings were reviewed. In 55 patients, the diameter of the SMA was compared with a previous CT scan where NOMI was not the diagnosis, and statistical analysis using paired t-test was performed., Results: 81 patients (76%) had findings consistent with small bowel ischaemia and the ileum was the segment most commonly involved (47%). Lack of wall enhancement, pneumoperitoneum, pneumatosis intestinalis and portal venous gas were all considered signs of bowel necrosis and surgery was performed promptly. 70 patients had signs of vascular narrowing of the SMA branches and in the 55 cases with a previous CT scan, there were statistically significant differences regarding the SMA diameter with a mean reduction of the artery calibre and standard deviation of 1.93 ± 1.1 mm between the NOMI and non-NOMI scans (p < 0.001)., Conclusion: Acknowledgment of characteristic bowel necrosis CT findings is crucial for determining the therapeutic attitude and the use of previous CT scans to compare the SMA diameter may help the radiologist to achieve an early diagnosis of NOMI in an often critically ill patient population. Advances in knowledge: Diagnosis of NOMI can be difficult in cases of partial mural ischaemia, thus objective data (diameter of the SMA) should be useful for the radiologist to include NOMI as the first diagnostic option in the differential diagnosis.

Background: Immediate hypersensitivity reactions (IHRs) to iodinated contrast media (ICMs) remain a common clinical concern. Positive skin test and basophil activation test results suggest a specific IgE-mediated mechanism in some cases. Skin test and controlled challenge test (CCT) are useful to manage these patients., Objective: To study clinical and allergologic features of IHRs to ICMs in a Spanish tertiary hospital during a 7-year period., Methods: Demographic and clinical data concerning the reaction were recorded. Patients treated at the Allergy Department of Hospital General Universitario Gregorio Marañón, Madrid, Spain, underwent skin tests. In those with positive results, CCTs with an alternative skin-test-negative ICM was performed. Global reaction rate was calculated and compared for each ICM., Results: A total of 342 reactions occurred in 329 patients. Cutaneous symptoms were the most common (87.7%). A total of 196 patients underwent an allergy workup, 15 (7.6%) of whom had positive skin test results. Reactions were more severe in patients with positive vs negative skin test results (grade 1, 46.7% vs 73.6%; grade 2, 33.3% vs 20.9%; grade 3, 20% vs 5.46%; P < .05). Three patients had cross-reactivity to 3 ICMs, all including ioversol and iomeprol. Six patients allergic to iopamidol tolerated ioversol and 1 tolerated iomeprol. Four patients allergic to ioversol and 1 allergic to iomeprol tolerated iopamidol. The global reaction rate was 0.2%, differing for each ICM (iopamidol, 0.14%; ioversol, 0.2%; and iomeprol, 0.4%; P < .001). Positive skin test results were found in a low percentage of patients in whom skin test-based CCT identified an alternative non-cross-reactive ICM. Low-grade cross-reactivity was found, especially between iopamidol and ioversol. Reactions were more severe in patients with positive skin test results. The reaction rate was greater for iomeprol compared with iopamidol (reaction rate, 2.8%) and ioversol (reaction rate, 2%)., Conclusion: This study identified a possible underlying specific IgE-mediated mechanism by positive skin test result in a low percentage of patients with IHRs to ICMs. In these patients, the CCT based on skin test results was useful for identifying an alternative non-cross-reactive ICM. More studies are needed to investigate the underlying mechanism in patients with IHRs and negative skin test results., (Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Endometriosis can affect up to 10% of women of reproductive age, in a wide range of clinical presentations that vary from mild to severe or deep endometriosis. Deep endometriosis can affect the urinary tract in 1-5% to 15-25% cases. Even though deep endometriosis' surgeries are usually complex with higher rate of complications, conservative management is not always considered as an option because of its high failure rates. This paper describes two cases of deep endometriosis with ureteric involvement (hydronephrosis) treated conservatively with a double-pigtail stent plus a Levonorgestrel intrauterine device, after conservative surgery, who remained symptom free with no evidence of recurrence at 3 years follow-up, avoiding radical high-risk surgery. Impact statement Several treatments have been described for endometriosis. From a symptomatic perspective, conservative medical management has been proposed with a variable response. Concerning deep endometriosis (affecting the urinary or digestive tract), the definitive treatment has always been thought to be radical surgery. However, this can lead to several complications. To illustrate a possible more conservative approach this paper describes two cases of deep infiltrating endometriosis affecting the ureter, treated conservatively with a temporary pigtail ureter stent plus a Levonorgestrel intrauterine device. The management demonstrates that, in a selected population, conservative treatment solves the urinary disease avoiding the surgical complications and, what is more, improving patients' symptoms in a permanent way. Further prospective studies are needed to confirm whether the introduction of this management in clinical practice would reduce the need for surgery thereby, avoiding high-risk surgery and improving the success rate of conservative management.

The clinical evidence of dietary polyphenols as colorectal cancer (CRC) chemopreventive compounds is very weak. Verification in humans of tissue-specific molecular regulation by the intake of polyphenols requires complex clinical trials that allow for the procurement of sufficient pre- and postsupplementation tissue samples. Ellagitannins (ETs), ellagic acid (EA) and their gut microbiota-derived metabolites, the urolithins, modify gene expression in colon normal and cancer cultured cells. We conducted here the first clinical trial with 35 CRC patients daily supplemented with 900 mg of an ET-containing pomegranate extract (PE) and evaluated the expression of various CRC-related genes in normal and cancerous colon tissues before (biopsies) and after (surgical specimens) 5-35 days of supplementation. Tissues were also obtained from 10 control patients (no supplementation) that confirmed a large, gene- and tissue-specific interindividual variability and impact of the experimental protocol on gene expression, with some genes induced (MYC, CD44, CDKN1A, CTNNB1), some repressed (CASP3) and others not affected (KRAS). Despite these issues, the consumption of the PE was significantly associated with a counterbalance effect in the expression of CD44, CTNNB1, CDKN1A, EGFR and TYMs, suggesting that the intake of this PE modulated the impact of the protocol on gene expression in a gene- and tissue-specific manner. These effects were not associated with the individuals' capacity to produce specific urolithins (i.e., metabotypes) or the levels of urolithins and EA in the colon tissues and did not reproduce in vitro effects evidencing the difficulty of demonstrating in vivo the in vitro results., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Alzheimer’s disease is one of the most prevalent neurodegenerative dementia in developed world. This fact, coupled with the lack cure, makes new no pharmacological therapeutic strategies such as nutrient management to investigate. In this regard, it stresses the possible influence of coconut oil as alternative energy source capable of stopping the progressively neuronal death that occurs in this disease. Objectives: To assess the cognitive impact of coconut oil in Alzheimer’s patients, and specifically in orientation, language-building, fixing, calculation-concentration and memory areas. Methods: Prospective, longitudinal, qualitative, analytical and experimental study through a clinical trial where 44 patients with Alzheimer’s in region of Ribera (Valencia), of which half was selected to receive during 21 days, 40 ml coconut oil daily divided between breakfast (20 ml) and food (20 ml). Before and after administration of the oil, they were evaluated through cognitive test Mini-Mental State Examination to determine possible changes. Results: It was observed in patients who received coconut oil, that cognitive improvement after completion of the intervention, statistically significant improved in the orientation and language-construction areas. Conclusions: Coconut oil appears to improve cognitive abilities of Alzheimer’s patients, with different intensity depending on the cognitive area.

Because nonalcoholic steatohepatitis (NASH) is associated with impaired liver regeneration, we investigated the effects of G49, a dual glucagon-like peptide-1/glucagon receptor agonist, on NASH and hepatic regeneration. C57Bl/6 mice fed chow or a methionine and choline-deficient (MCD) diet for 1 week were divided into 4 groups: control (chow diet), MCD diet, chow diet plus G49, and M+G49 (MCD diet plus G49). Mice fed a high-fat diet (HFD) for 10 weeks were divided into groups: HFD and H+G49 (HFD plus G49). Following 2 (MCD groups) or 3 (HFD groups) weeks of treatment with G49, partial hepatectomy (PH) was performed, and all mice were maintained on the same treatment schedule for 2 additional weeks. Analysis of liver function, hepatic regeneration, and comprehensive genomic and metabolic profiling were conducted. NASH was ameliorated in the M+G49 group, manifested by reduced inflammation, steatosis, oxidative stress, and apoptosis and increased mitochondrial biogenesis. G49 treatment was also associated with replenishment of intrahepatic glucose due to enhanced gluconeogenesis and reduced glucose use through the pentose phosphate cycle and oxidative metabolism. Following PH, G49 treatment increased survival, restored the cytokine-mediated priming phase, and enhanced the proliferative capacity and hepatic regeneration ratio in mice on the MCD diet. NASH markers remained decreased in M+G49 mice after PH, and glucose use was shifted to the pentose phosphate cycle and oxidative metabolism. G49 administered immediately after PH was also effective at alleviating the pathological changes induced by the MCD diet. Benefits in terms of liver regeneration were also found in mice fed HFD and treated with G49., Conclusion: Dual-acting glucagon-like peptide-1/glucagon receptor agonists such as G49 represent a novel therapeutic approach for patients with NASH and particularly those requiring PH. (Hepatology 2017;65:950-968)., (© 2016 by the American Association for the Study of Liver Diseases.)

The Wnt signaling pathway is critical for a number of functions in the central nervous system, including regulation of the synaptic cleft structure and neuroprotection against injury. Deregulation of Wnt signaling has been associated with several brain pathologies, including Alzheimer's disease. In recent years, it has been suggested that the Wnt pathway might act as a central integrator of metabolic signals from peripheral organs to the brain, which would represent a new role for Wnt signaling in cell metabolism. Energy metabolism is critical for normal neuronal function, which mainly depends on glucose utilization. Brain energy metabolism is important in almost all neurological disorders, to which a decrease in the capacity of the brain to utilize glucose has been linked. However, little is known about the relationship between Wnt signaling and neuronal glucose metabolism in the cellular context. In the present study, we found that acute treatment with the Wnt3a ligand induced a large increase in glucose uptake, without changes in the expression or localization of glucose transporter type 3. In addition, we observed that Wnt3a treatment increased the activation of the metabolic sensor Akt. Moreover, we observed an increase in the activity of hexokinase and in the glycolytic rate, and both processes were dependent on activation of the Akt pathway. Furthermore, we did not observe changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose phosphate pathway. The effect of Wnt3a was independent of both the transcription of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte--specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8 weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus., Competing Interests: The authors declare no competing or financial interests., (© 2016. Published by The Company of Biologists Ltd.)

Background: Chronic venous insufficiency, in its final stage can cause venous ulcers. Venous ulcers have a prevalence of 0.5 % to 0.8 % in the general population, and increases starting at 60 years of age. This condition often causes increased dependency in affected individuals, as well as a perceived reduced quality of life and family overload. Local Treating chronic venous ulcers has 2 components: topically healing the ulcer and controlling the venous insufficiency. There is evidence that compressive therapy favours the healing process of venous ulcers. The studies we have found suggest that the use of multilayer bandage systems is more effective than the use of bandages with a single component, these are mostly using in Spain. Multilayer compression bandages with 2 layers are equally effective in the healing process of chronic venous ulcers as 4-layer bandages and are better tolerated and preferenced by patients. More studies are needed to specifically compare the 2-layer bandages systems in the settings where these patients are usually treated., Method/design: Randomised, controlled, parallel, multicentre clinical trial, with 12 weeks of follow-up and blind evaluation of the response variable. The objective is to assess the efficacy of multilayer compression bandages (2 layers) compared with crepe bandages, based on the incidence of healed venous ulcers in individuals treated in primary care nursing consultations, at 12 weeks of follow-up. The study will include 216 individuals (108 per branch) with venous ulcers treated in primary care nursing consultations. The primary endpoint is complete healing at 12 weeks of follow-up. The secondary endpoints are the degree of healing (Resvech.2), quality of life (CCVUQ-e), adverse reactions related to the healing process. Prognosis and demographic variables are also recorder. Effectiveness analysis using Kaplan-Meier curves, a log-rank test and a Cox regression analysis. The analysis was performed by intention to treat., Discussion: The study results can contribute to improving the care and quality of life of patients with venous ulcers, decreasing healing times and healthcare expenditure and contributing to the consistent treatment of these lesions., Trial Registration: This study has been recorded in the Clinical Trials.gov site with the code NCT02364921. 17 February 2015.

Introducción: la composición lipídica de las fórmulas de nutrición parenteral (NP) se postula como posible factor de evolución clínica.Objetivo: evaluar las diferencias en eficacia y seguridad de dos emulsiones lipídicas en NP.Material y métodos: estudio clínico prospectivo de pacientes posquirúrgicos sometidos a NP durante más de 7 días en un periodo de 2 años. Se administraron de forma indistinta 2 tipos de emulsiones lipídicas: enriquecida con ácidos grasos omega 3 (SMOFlipid Fresenius Kabi®) o con ácido oleico omega 9 (Clinoleic Baxter®). Se analizaron variables epidemiológicas, analíticas, complicaciones infecciosas y mortalidad.Resultados: se estudió un total de 154 pacientes con edad media de 64,36 ± 13,73 años, de los que 95 eran hombres (61%), 78 (51%) recibieron SMOFlipid® y 76 (49%) Clinoleic®. La estancia media fue de 16,91 ± 4,23 días, la duración de la NP 9,68 ± 3,25 días y la mortalidad del 11%. Se diagnosticaron 58 (37%) infecciones. No existieron diferencias significativas en cuanto a los parámetros analíticos lipídicos, hepáticos o nutricionales (medidos al inicio y al 7.º día) ni en su evolución (estancia media, complicaciones infecciosas ni mortalidad) entre los dos grupos de pacientes.Conclusión: los pacientes sometidos a NP presentan similares características evolutivas con independencia de la emulsión lipídica utilizada. La bibliografía actual apunta a un beneficio de la disminución del aporte de ácidos grasos omega 9, pero no se han encontrado diferencias significativas entre las fórmulas comparadas.

In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. The brain has a high demand for glucose, which is mainly used for energy production. Neurons use energy for highly specific processes that require a high energy level, such as maintaining the electrical potential and synthesizing neurotransmitters. Moreover, an important metabolic impairment has been described in all neurodegenerative disorders. Despite the key role of glucose metabolism in the brain, little is known about the cellular pathways involved in regulating this process. We report here that Wnt5a induces an increase in glucose uptake and glycolytic rate and an increase in the activity of the pentose phosphate pathway; the effects of Wnt5a require the intracellular generation of nitric oxide. Our data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect that could be important for the reported neuroprotective role of Wnt signaling in neurodegenerative disorders.

Objetive: to determine the prevalence of malnutrition in patients aged 65 years or more at admission and factors associated with its presence. Analyze excess hospital stay (EHS), economic impact and premature readmission rate associated with hospital malnutrition in elderly patient., Material and Method: retrospective study conducted at the University Hospital Reina Sofía. All patients aged 65 years or older admitted to internal medicine in 2011. The sample size was calculated taking into account the income of the previous year, and considering a prevalence of malnutrition of 50% with a 95% and included error of 5%. To define the degree of malnutrition nutritional control tool (CONUT), which establishes a score based on albumin, total cholesterol and lymphocyte determination was used. To determine the factors associated with the presence of moderate to severe malnutrition analysis of multivariate logistic regression was performed. For each patient the EHS, premature readmissions and the associated cost to EHS was calculated. A threshold of statistical significance of 0.05 was used for all analyzes and were performed with SPSS v15.0., Results: 310 patients, of whom 54.2% were women were included, the mean age was 80.1 years (SD: 6.8), ranging between 65 and 95 years. Regarding diagnosis at admission 27.4% were respiratory diseases, 22.6% of the circulatory and digestive 11.6%. The median Charlson index was 2.0, found that 36.8% of patients had high comorbidity. The most prevalent chronic diseases were diabetes mellitus (44.2%), chronic kidney disease (25.2%) and dementia (10.6). Regarding the CONUT, 75.8% of patients met the criteria of malnutrition: 42.6% mild, 28.7% moderate and severe 4.5%, of which only 46.6% had some nutritional support during admission. Factors associated with the presence of moderate to severe malnutrition were female gender (OR: 1.7; 95%: 1.1 - 2.8), age over 80 years (OR: 2.0, IC 95%: 1.2 - 3.5), and dementia (OR: 2.4; IC 95%:1.2 - 5.2). No association with comorbidity or with other chronic diseases was found. Regarding the EHS (days) differences between patients with moderate to severe malnutrition (4.7; IC 95%: 2.3 - 7.1) and normally nourished (-0.1; IC 95%: -1.4 - 1.2) (p = 0.001) were found, but were not for cases of mild malnutrition (1.6, 95%: 0.5-2.8) (p = 0.07).Regarding the rate of premature readmission in malnourished patients was 28/235 (11.9%). The cost associated with EHS / 100 patients was € 195 479.4 for moderate malnutrition, mild malnutrition € 73 484.8, and normally nourished patients represented a saving of € 12 353., Conclusions: hospital malnutrition in elderly patients remains an unsolved problem, given the high prevalence found, associated to an excess of hospital stay and increased hospital costs, especially in patients with moderate to severe malnutrition. The CONUT is a nutritional screening tool very useful for the speed and validity of their results, and allows detecting patients at risk or nutritional alert without lead to increased costs., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Scope: MicroRNAs (miRs) are proposed as colorectal cancer (CRC) biomarkers. Pomegranate ellagic acid and their microbiota metabolites urolithins exert anticancer effects in preclinical CRC models, and target normal and malignant colon tissues in CRC patients. Herein, we investigated whether the intake of pomegranate extract (PE) modified miRs expression in surgical colon tissues versus biopsies from CRC patients., Methods and Results: We conducted a randomized, double-blind, controlled trial. Thirty-five CRC patients consumed 900 mg PE daily before surgery. Control CRC patients (no PE intake, n = 10) were included. Our results revealed: (1) significant differences for specific miRs between malignant and normal tissues modifiable by the surgical protocols; (2) opposed trends between -5p and -3p isomolecules; (3) general induction of miRs attributable to the surgery; (4) moderate modulation of various miRs following the PE intake, and (5) no association between tissue urolithins and the observed miRs changes., Conclusion: PE consumption appears to affect specific colon tissue miRs but surgery critically alters miRs levels hindering the discrimination of significant changes caused by dietary factors and the establishment of genuine differences between malignant and normal tissues as biomarkers. The components responsible for the PE effects and the clinical relevance of these observations deserve further research., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: HELLP syndrome is a serious hypertensive disorder of pregnancy with important neonatal problems in the newborn. The objective of this work was to determine the characteristics of these infants and its neonatal evolution., Methods: A retrospective observational study of all newborns of mothers with HELLP syndrome born in a university hospital between January 1, 2008 and December 31, 2013 was carried out. Thirty-three infants from 28 pregnancies (five twin gestations) were studied. A descriptive and comparative analysis between groups and a multivariate analysis of factors associated with mortality in the series took place., Results: Of 33 newborns studied (2.2 newborns/1,000 infants total), two were stillbirths (6.1% of the total) and four died after birth (12.9% of live neonates) with overall perinatal mortality of 18.2%. Pregnancies in 28 infants ended before 37 weeks (84.8%) and 11 pregnancies ended before week 32 (33.3%). Seven infants weighed<1500g (four weighed <1000g). Of the 31 live births, 13 infants were in a <10th percentile weight for gestational age (41.9%), 20 needed neonatal resuscitation (64.5%) and 14 had leukopenia at birth (45.2%). In the final logistic regression, neonatal mortality was associated with extreme prematurity regardless of underweight, leukopenia and/or need for neonatal resuscitation., Conclusions: Children of mothers with HELLP syndrome have a high mortality associated with extreme prematurity, independent of the presence of leukopenia, low weight for gestational age and need for neonatal resuscitation., (Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.)

Scope: Mice with deletion of insulin receptor substrate (IRS) 2 develop hyperglycaemia, impaired hepatic insulin signaling and elevated gluconeogenesis. Protein tyrosine phosphatase 1B (PTP1B) inhibition by resveratrol improves peripheral insulin sensitivity of these mice. Although resveratrol activates Sirtuin1 (Sirt1), the mechanisms underlying its beneficial effects are not totally elucidated. In this study, we have investigated whether Sirt1 mediates the effects of resveratrol in controlling insulin resistance in diabetic mice., Methods and Results: We attempted to ameliorate peripheral insulin resistance in two diabetic models, Irs2-deficient (Irs2(-/-)) mice and streptozotocin (STZ)-injected mice by resveratrol treatment or Sirt1 overexpression. Resveratrol improved systemic insulin sensitivity of Irs2-deficient mice. Irs2-deficient mice are characterized by high levels of PTP1B expression in liver and muscle. Interestingly, resveratrol decreased PTP1B in both tissues, thereby restoring IRS1-mediated insulin signaling. Moreover, resveratrol also restored insulin sensitivity and hepatic insulin signaling in STZ-diabetic mice. In contrast, moderate overexpression of Sirt1 neither normalized PTP1B levels nor restored insulin signaling in Irs2-deficient mice or STZ-diabetic mice., Conclusion: Resveratrol improves peripheral insulin signaling independently of Sirt1 in diabetic mice in association with the inhibition of PTP1B and, therefore, this polyphenol could be an effective adjuvant for the treatment of diabetes., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)