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Manuel Diaz-Llopis,1–5 Maria Dolores Pinazo-Duran,2,3,6–9 Loreto Diaz-Guiñon,5 Miriam Rahhal-Ortuño,10 Mercedes Perez-Ramos,8,9 Rosabel Bosch,8,9 Roberto Gallego-Pinazo,11,12 Rosa Dolz-Marco,11,12 Teresa Diaz-Guiñon,5 María Diaz,1,5 Francisco Javier Romero,13 Angel Cisneros10 1University of Valencia, Valencia, Spain; 2Ophthalmology Unit, Faculty of Medicine, University of Valencia, Valencia, Spain; 3Molecular Ophthalmology Unit, Faculty of Medicine, University of Valencia, Valencia, Spain; 4Consellería de Sanitat (Valencian Regional Health Ministry), Valencian Autonomous Government, Valencia, Spain; 5IOVA – Valencia Ophthalmology Institute, Valencia, Spain; 6Hospital Universitario Doctor Peset, Valencia, Spain; 7Santiago Grisolía Eye Research Laboratory, FISABIO, Valencia, Spain; 8Specialised Medical Centre Alboraya, Valencia, Spain; 9Specialised Medical Centre Monteolivete, Valencia, Spain; 10Department of Ophthalmology, La Fe Hospital, Valencia, Spain; 11IMED Hospital, Valencia, Spain; 12Oftalvist Clinic, Valencia, Spain; 13European University of Valencia, Valencia, Spain Purpose: To investigate the safety and efficacy of sterile isotonic seawater washes vs standard treatment with carmellose artificial tears in dry eye syndrome (DES). Patients and methods: This is a randomized multicenter prospective study with 12 weeks of follow-up. A group of patients with DES (N=60) were treated with seawater spray (Quinton®) five times daily, and another similar group (N=60) were treated with carmellose artificial tears eyedrops (Viscofresh® 0.5%) five times a day. The parameters studied and measured were as follows: Ocular Surface Disease Index questionnaire score, Schirmer I test (without anesthesia) score, tear osmolarity (TearLab®), tear breakup time, tear meniscus height (meniscography OCT), fluorescein corneal staining score (National Eye Institute scale), lissamine green conjunctival staining score, and levels of IL-1 beta and IL-6 in tears (Luminex® 200). Results: In the group treated with seawater, symptoms decreased by 68%, and the decrease was 26% statistically superior to the group treated with carmellose artificial tears eyedrops (P

When breast milk extraction and storage is required before ingestion, it is important to establish the conditions that ensure the least losses in milk quality, like the antioxidant capacity. The present study evaluates glutathione peroxidase activity and malondialdehyde concentration of breast milk when stored frozen, comparing the effects of 2 temperatures (-20 degrees C and -80 degrees C) and different storage times (15, 30, and 60 days). The results indicate that freezing induces losses in the antioxidant properties of breast milk and that such losses increase with the duration of storage and differ in intensity according to the temperature. It is concluded that to maximally preserve the antioxidant properties of breast milk, it is advisable to store the latter at -80 degrees C for a period of less than 30 days, rather than for shorter time periods at the usual temperature of -20 degrees C. J Hum Lact. 26(1):35-41. [ABSTRACT FROM AUTHOR]

Purpose Diabetic retinopathy is a leading cause of visual loss and increased nitric oxide (NO) has been correlated with that. The aim of this study was to evaluate protective properties of Docosahexaenoic acid (DHA) at retinal pigment epithelial (RPE) cells exposed to high glucose concentration. Methods ARPE‐19 were cultured 4 days with normal blood glucose concentration (5,5 mM D‐glucose), followed by exposure to either normal (5,5 mM) or high (45 mM) concentration of D‐glucose during the next 5 days and DHA was added to the culture medium. Four different study groups were obtained: control group (5,5mM D‐glucose) (C), control+DHA group(5,5 mM D‐glucose+6,7 uM DHA)(CDHA), glucose group (45 mM D‐glucose)(G) and glucose+DHA group (45 mM D‐glucose+ 6,7 uM DHA)(GDHA). At the end of the experiment cells were washed, sonicated and lysed and the homogenates criopreserved. The total antioxidant capacity was measured with a commercial kit (Antioxidant Assay Kit, Cayman) and to measured the total nitrites a commercial kit was used (Parameter, Total Nitrite, R&D Systems). Results Antioxidant capacity in Ggroup was decreased significantly (0.97±0.10 mM/mg prot) when compared with the Cgroup (1.52±0.09 mM/mg prot). DHA administration reversed this alteration to normal values in the GDHA group (1.41 ± 0.16 mM/mg prot, p< 0.05 vs control). The total nitrites were significantly elevated in Ggroup (1.09±0.35 umol/L/mg prot) when compared to the Cgroup (0.53±0.08 umol/L/mg prot) and DHA administration reversed this alteration to normal values (0.49±0.12 umol/L/mg prot, p< 0.05 vs G). Conclusion DHA might be useful in protecting diabetic retina, though further studies are needed to better understand this mechanisms. [ABSTRACT FROM AUTHOR]

Purpose The aim of this work was to study oxidative stress markers in corneal limbal rings stored in Optisol at different preservation times. Methods Total Antioxidant capacity was measured with a commercial kit (Antioxidant Assay Kit, Cayman). Total nitrites were measured with a commercial kit where the amount of total nitrites was monitored spectofotometrically by reading the absorbance at 540 nm. Moreover, HNE (4‐hydroxy‐2‐nonenal) immunohistoquemistry was performed at 3 µm thick paraffin sections. Results The antioxidant capacity in corneal limbal rings preserved for 7 days were decreased significantly (0.5 ± 0.02 mM/mg prot) when compared to a fresh corneal limbal ring (1.1 ± 0.28 mM/mg prot) * p< 0.05. Moreover, the total nitrites were significantly elevated in corneal limbal rings preserved for 7 days (1.47 ± 0.18 umol/L/mg prot) when compared to fresh corneal limbal rings (0.89 ± 0.46 umol/L/mg prot) * p< 0.05. Immunohistoquemistry revealed that there exist an increase in HNE positive cells as conservation time increases. Conclusion Oxidative stress factors increases with time in corneal limbal rings preserved in Optisol. [ABSTRACT FROM AUTHOR]

Background: The Zero Surgical Infection Project (ZSIP) in Spain is a nationwide programme to prevent surgical site infections (SSIs), sponsored by the Ministry of Health. The programme includes the application of a bundle of five key preventive measures (5PM): peri-operative antibiotic prophylaxis (PAP), skin antisepsis (SA), hair removal (HR), normothermia and normoglycaemia., Aim: To assess the effectiveness of the 5PM, applied in a set of Spanish public hospitals between 2017 and 2021, under standard conditions of surgical health care in Spain., Methods: This prospective cohort study of 33,240 patients from the ZSIP Registry (National Database Network) included surveillance of SSI data of selected surgical interventions, compliance data and other risk factors. Compliance with the 5PM bundle was verified through a specific checklist. The intervention and comparison groups were patients who were compliant with the 5PM bundle and patients who were not compliant with the 5PM bundle, respectively. Adjusted odds ratios (OR) and preventive fractions (PF) were calculated using logistic regression., Findings: The overall SSI rates for patients in the compliant group and non-compliant group were 4.77% and 6.90%, respectively. Overall compliance with the 5PM bundle was 35.9%, and the compliance rates were highest for PAP (87.2%), SA (82.2%) and HR (78.7%). Compliance with the 5PM bundle had a PF of 32% and adjusted OR of 0.68 (95% confidence interval 0.60-0.76)., Conclusion: The ZSIP, implemented between 2017 and 2021 in Spain, had a significant level of effectiveness against SSIs., Competing Interests: Conflict of interest statement None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

SARS-CoV-19 infection provokes a variety of symptoms; most patients present mild/moderate symptoms, whereas a small proportion of patients progress to severe illness with multiorgan failure accompanied by metabolic disturbances requiring ICU-level care. Given the importance of the disease, researchers focused on identifying severity-associated biomarkers in infected patients as well as markers associated with patients suffering long-COVID. However, little is known about the presence of biomarkers that remain a few years after SARS-CoV-2 infection once the patients fully recover of the symptoms. In this study, we evaluated the presence of persistent biomarkers in the nasopharyngeal tract two years after SARS-Cov-2 infection in fully asymptomatic patients, taking into account the severity of their infection (mild/moderate and severe infections). In addition to the direct identification of several components of the Coronavirus Infection Pathway in those individuals that suffered severe infections, we describe herein 371 proteins and their associated canonical pathways that define the different adverse effects of SARS-CoV-2 infections. The persistence of these biomarkers for up to two years after infection, along with their ability to distinguish the severity of the infection endured, highlights the surprising presence of persistent nasopharyngeal exudate changes in fully recovered patients.

Purpose: The Barcelona Clinic Liver Cancer (BCLC) staging schema is widely used for hepatocellular carcinoma (HCC) treatment. In the updated recommendations, HCC BCLC stage B can become candidates for transplantation. In contrast, hepatectomy is currently not recommended., Methods: This systematic review includes a multi-institutional meta-analysis of patient-level data. Survival, postoperative mortality, morbidity and patient selection criteria for liver resection and transplantation in BCLC stage B are explored. All clinical studies reporting HCC patients with BCLC stage B undergoing liver resection or transplantation were included., Results: A total of 31 studies with 3163 patients were included. Patient level data was available for 580 patients from 9 studies (423 after resection and 157 after transplantation). The overall survival following resection was 50 months and recurrence-free survival was 15 months. Overall survival after transplantation was not reached and recurrence-free survival was 45 months. The major complication rate after resection was 0.11 (95%-CI, 0.0-0.17) with the 90-day mortality rate of 0.03 (95%-CI, 0.03-0.08). Child-Pugh A (93%), minor resection (60%), alpha protein level less than 400 (64%) were common in resected patients. Resected patients were mostly outside the Milan criteria (99%) with mean tumour number of 2.9. Studies reporting liver transplantation in BCLC stage B were scarce., Conclusion: Liver resection can be performed safely in selected patients with HCC BCLC stage B, particularly if patients present with preserved liver function. No conclusion can done on liver transplantation due to scarcity of reported studies., (© 2024. The Author(s).)

In the evolution of pervasive electronics, it is imperative to significantly reduce the energy consumption of power systems and embrace sustainable materials and fabrication processes with minimal carbon footprint. Within this context, thermoelectric generators (TEGs) have garnered substantial attention in recent years because of the readily available thermal gradients in the environment, making them a promising energy-harvesting technology. Current commercial room-temperature thermoelectrics are based on scarce, expensive, and/or toxic V-VI chalcogenide materials, which limit their widespread use. Thermoelectric polymers partially address this issue, and as such, they have been intensively studied in the field in the past decade. However, less popular materials have recently appeared to respond to the challenges of room-temperature thermoelectrics in terms of sustainability and cost. In this contribution, we comprehensively review the latest advancements in emerging alternative materials with the potential to pave the way for the next generation of sustainable TEGs. This upcoming generation includes flexible and printed TEGs for applications like wearables or the Internet of Things., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

DNA damage represents a challenge for cells, as this damage must be eliminated to preserve cell viability and the transmission of genetic information. To reduce or eliminate unscheduled chemical modifications in genomic DNA, an extensive signaling network, known as the DNA damage response (DDR) pathway, ensures this repair. In this work, and by means of a proteomic analysis aimed at studying the STIM1 protein interactome, we have found that STIM1 is closely related to the protection from endogenous DNA damage, replicative stress, as well as to the response to interstrand crosslinks (ICLs). Here we show that STIM1 has a nuclear localization signal that mediates its translocation to the nucleus, and that this translocation and the association of STIM1 to chromatin increases in response to mitomycin-C (MMC), an ICL-inducing agent. Consequently, STIM1-deficient cell lines show higher levels of basal DNA damage, replicative stress, and increased sensitivity to MMC. We show that STIM1 normalizes FANCD2 protein levels in the nucleus, which explains the increased sensitivity of STIM1-KO cells to MMC. This study not only unveils a previously unknown nuclear function for the endoplasmic reticulum protein STIM1 but also expands our understanding of the genes involved in DNA repair., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Health literacy has a direct impact on the health of populations. It is related to education, capacity for self-care, and management of health resources. The Health Literacy Survey Questionnaire HLS-Q12 is one of the reference instruments but has not yet been adapted to Spanish. The aims of the study were to cross-culturally adapt and evaluate the psychometric properties of the Spanish version of the HLS-Q12., Methods: Data was collected from June 2020 to March 2022. The sample consisted of 60 patients who initiated cancer treatment for the first time within a clinical trial. Double direct translation, back-translation, cognitive debriefing with a 10-patient sample, and an expert committee were used for cross-cultural adaptation. For validation of the HLS-Q12, a psychometric analysis was performed to assess feasibility, reliability, sensitivity to change and construct validity with other measures such as health-related quality of life, empowerment, and health needs., Results: The HLS-Q12 is equivalent at the semantic, conceptual, and content level to the original version and its psychometric properties demonstrated good internal consistency with a Cronbach's alpha of 0.88 and a McDonald´s omega of 0.91, a high degree of fit for the confirmatory factor analysis, and a statistically significant sensitivity to change (p = 0.025)., Conclusions: Based on robust psychometric values, the Spanish version of HLS-Q12 was found to be a good cross-culturally adapted tool for collecting correct information on health literacy in cancer patients regardless of tumour type or stage. Although more studies are needed, this version of HLS-Q12 could be used in research for collecting data on the health literacy needs of Spanish-speaking patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Muñoz-Villaverde 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: During the COVID-19 pandemic, decentralised clinical trials incorporated self-monitoring, self-reporting, and telenursing tools to address health literacy and health empowerment of patients enrolled in clinical trials. We aimed to determine the impact of an educational intervention using telenursing consultations on health literacy, health empowerment, and health-related quality of life in cancer patients enrolled in clinical trials by measuring the level of satisfaction with the care received and assessing the views of healthcare professionals concerning the advanced practice nurse (APN) role in oncology clinical trials., Methods: In this pilot analytical, descriptive, longitudinal, quasi-experimental, and pre-post test study, an educational intervention was conducted by 5 visits with an APN using synchronous teleconsultation in patients starting cancer treatment for the first time in a clinical trial (n = 60), and health professionals working with the APN (n = 31). A descriptive analysis of the samples and questionnaires were utilised along with statistical comparisons., Results: After the intervention, patients' health literacy (31.7%), health empowerment (18.3%), and health-related quality of life (33.3%) increased (p < 0.05), with a decrease and trend towards resolution of care needs (p < 0.05). Satisfaction with the quality and care received in terms of perceived convenience, transition, and continuity of care showed positive results in 64.9 ± 20.7, 77.6 ± 19.5, and 72.1 ± 20.4 of respondents, respectively. On the overall assessment of the APN role, healthcare professionals expressed a high level of agreement with the statements related to their work performance., Conclusions: The data indicates that a clinical trial APN-led telenursing educational intervention results in an overall increase in health literacy, an improvement in health empowerment and health-related quality of life, and a decrease in care needs of oncology clinical trials patients. Patients stated that they received a high quality of care and health professionals indicated high levels of acceptance with APNs. Based on these results, we suggest that the APN role should gain more recognition in the Spanish healthcare system and their professional competencies should be aligned with those of other countries., (© 2024. The Author(s).)

This review focuses on the role of small extracellular vesicles in the pathophysiological mechanisms of retinal degenerative diseases. Many of these mechanisms are related to or modulated by the oxidative burden of retinal cells. It has been recently demonstrated that cellular communication in the retina involves extracellular vesicles and that their rate of release and cargo features might be affected by the cellular environment, and in some instances, they might also be mediated by autophagy. The fate of these vesicles is diverse: they could end up in circulation being used as markers, or target neighbor cells modulating gene and protein expression, or eventually, in angiogenesis. Neovascularization in the retina promotes vision loss in diseases such as diabetic retinopathy and age-related macular degeneration. The importance of micro RNAs, either as small extracellular vesicles' cargo or free circulating, in the regulation of retinal angiogenesis is also discussed.

Exosomes or small extracellular vesicles (sEVs) represent a pivotal component in intercellular communication, carrying a diverse array of biomolecules. Several factors can affect sEVs release dynamics, as occurs in hyperglycemia or inflammation. In fact, sEVs release has been associated with the promotion of physio-pathological processes. Among the sEVs cargo, microRNAs play an essential role in cell-to-cell regulation. More concretely, miR-205-5p is related to angiogenesis and cell proliferation. The aim of this study is to understand the specific role of sEVs containing miR-205-5p under high glucose conditions. ARPE-19 cells were cultured with high glucose (HG) for 5 days. sEVs were isolated and characterized. sEVs from ARPE-19 were used for angiogenesis and cell proliferation. HG increased sEVs release but downregulated miR-205-5p cargo expression compared to the control. sEVs from HG-treated ARPE-19 cells promoted tube formation and migration processes. In contrast, miR-205-5p overexpression (by mimic transfection) decreased angiogenesis and cell migration. Our results demonstrate how ARPE-19 cells respond to HG challenge by increasing sEVs with weak miR-205-5p cargo. The absence of this miRNA in sEVs is enough to promote angiogenesis. In contrast, restoring sEVs-miR-205-5p levels decreased it. These findings open new possibilities in sEVs-based therapies containing miR-205-5p against angiogenesis.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyze the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma., Methods: Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates., Results: The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflammatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analyzing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05., Conclusions: In this study, we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. Our results revealed a high CXCR4 expression in the tumor stroma, which is related to a poor tumor differentiation. On the contrary, we could not find an association between CXCR4 expression and survival and the rest of the clinicopathological variables. Focusing the study on the CXCR4 expression in the tumor stroma could generate more robust results. Therefore, we consider it key to develop more studies to enlighten the role of this receptor in PDAC and its implication as a possible biomarker., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background : Simultaneous liver resection and peritoneal cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial today. The aim of the study was to analyze the postoperative outcomes and survival of patients with advanced metastatic colon cancer (peritoneal and/or liver metastases). Methods: Retrospective observational study from a prospective maintained data base. Patients who underwent a simultaneous peritoneal cytoreduction and liver resection plus HIPEC were studied. Postoperative outcomes and overall and disease free survival were analyzed. Univariate and multivariate analyses were performed. Results: From January 2010 to October 2022, 22 patients operated with peritoneal and liver metastasis (LR+) were compared with 87 patients operated with peritoneal metastasis alone (LR-). LR+ group presented higher serious morbidity (36.4 vs. 14.9%; p: 0.034). Postoperative mortality did not reach statistical difference. Median overall and disease free survival was similar. Peritoneal carcinomatosis index was the only predictive factor of survival. Conclusions : Simultaneous peritoneal and liver resection is associated with increased postoperative morbidity and hospital stay, but with similar postoperative mortality and OS and disease free survival. These results reflect the evolution of these patients, considered inoperable until recently, and justify the trend to incorporate this surgical strategy within a multimodal therapeutic plan in highly selected patients.

Introduction and Objective: Headache is a frequent reason for consultation between primary care physicians, emergency services physicians, and neurology specialists; however, it is not always well managed. The Andalusian Society of Neurology's Headache Study Group (SANCE) aimed to analyse headache management at different levels of care., Material and Methods: We conducted a descriptive cross-sectional study with data gathered through a retrospective survey in July 2019. Participants completed a series of structured questionnaires on different social and work-related variables from 4 different groups of healthcare professionals (primary care [PC], emergency departments, neurology departments, headache units)., Results: A total of 204 healthcare professionals completed the survey: 35 emergency department physicians, 113 PC physicians, 37 general neurologists, and 19 neurologists specialising in headache. Eighty-five percent of PC physicians reported prescribing preventive drugs, which were maintained for at least 6 months (59%), with flunarizine and amitriptyline being the most commonly used. Most patients attended at neurology consultations (65%) are referred by PC physicians, with changes in the headache pattern being the main reason for referral (74%). Healthcare professionals across all levels of care showed great interest in headache and in receiving training in headache management (97% of PC physicians, 100% of emergency services physicians, 100% of general neurologists)., Conclusions: Migraine sparks great interest among healthcare professionals from different levels of care. Our results also reveal a lack of resources for headache management, which is reflected in the long waiting times. Other means of bilateral communication between different levels of care should be explored (eg, e-mail)., (Copyright © 2023 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: To evaluate the effect of faster aspart over glycaemic variability in type 1 diabetes (T1D) patients treated with sensor-augmented pump (SAP) in a real-world scenario., Methods: Observational study with SAP-treated adult T1D patients treated with faster aspart for three months. The primary endpoint was the mean amplitude of glucose excursions (MAGE)., Results: Fifty patients were treated with faster aspart. Eleven patients (23%) withdrew during the follow-up mainly due to worsening of diabetes control (9 patients). Mean age was 41.2 yrs. (range 21-59) and T1D duration 22.4±10.0 yrs. Mean SAP treatment duration was 3.6±3.1 yrs. We detected a reduction of -7.0 (95% CI -1.1, -12.9; p=0.021) in MAGE at the end of the study. Other glycemic variability indices were also improved: standard deviation of mean interstitial glucose (-3mg/dl; 95% CI, -1, -5; p=0.01), CONGA4 (-2.2; 95% CI -0.3, -4.2; p=0.029), CONGA6 (-2.6; 95% CI -0.6, -4.6; p=0.011), GRADE (-0.5; 95% CI -0.1, -0.9; p=0.022), HBGI (-0.7; 95% CI -0.2, -1.3; p=0.013), J-index (-2.9; 95% CI -0.7, -5.0; p=0.011) and MODD (-5.7; 95% CI -1.7, -9.7; p=0.006). A slight reduction in mean glucose management indicator was also detected (-0.14%; 95% CI, -0.02, -0.27; -1.4mmol/mol; 95% CI -0.1, -3.3; p=0.03)., Conclusions: In SAP-treated T1D patients, faster aspart insulin was associated with reduced glycaemic variability, but also a high percentage of dropouts due to worsened glycaemic control. NCT04233203., (Copyright © 2022 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo , ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo , in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor's body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes., Competing Interests: 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 © 2023 Insausti, Insausti, Muñoz López, Medina Lorenzo, Arroyo-Jiménez, Marcos Rabal, de La Rosa-Prieto, Delgado-González, Montón Etxeberria, Cebada-Sánchez, Raspeño-García, Iñiguez de Onzoño, Molina Romero, Benavides-Piccione, Tapia-González, Wisse, Ravikumar, Wolk, DeFelipe, Yushkevich and Artacho-Pérula.)

Dysregulation in calcium signaling pathways plays a major role in the initiation of Alzheimer's disease (AD) pathogenesis. Accumulative experimental evidence obtained with cellular and animal models, as well as with AD brain samples, points out the high cytotoxicity of soluble small oligomeric forms of amyloid-β peptides (Aβ) in AD. In recent works, we have proposed that Aβ-calmodulin (CaM) complexation may play a major role in neuronal Ca 2+ signaling, mediated by CaM-binding proteins (CaMBPs). STIM1, a recognized CaMBP, plays a key role in store-operated calcium entry (SOCE), and it has been shown that the SOCE function is diminished in AD, resulting in the instability of dendric spines and enhanced amyloidogenesis. In this work, we show that 2 and 5 h of incubation with 2 μM Aβ(1-42) oligomers of the immortalized mouse hippocampal cell line HT-22 leads to the internalization of 62 ± 11 nM and 135 ± 15 nM of Aβ(1-42), respectively. Internalized Aβ(1-42) oligomers colocalize with the endoplasmic reticulum (ER) and co-immunoprecipitated with STIM1, unveiling that this protein is a novel target of Aβ. Fluorescence resonance energy transfer measurements between STIM1 tagged with a green fluorescent protein (GFP) and Aβ(1-42)-HiLyte™-Fluor555 show that STIM1 can bind nanomolar concentrations of Aβ(1-42) oligomers at a site located close to the CaM-binding site in STIM1. Internalized Aβ(1-42) produced dysregulation of the SOCE in the HT-22 cells before a sustained alteration of cytosolic Ca 2+ homeostasis can be detected, and is elicited by only 2 h of incubation with 2 μM Aβ(1-42) oligomers. We conclude that Aβ(1-42)-induced SOCE dysregulation in HT-22 cells is caused by the inhibitory modulation of STIM1, and the partial activation of ER Ca 2+ -leak channels.

The Sequential Organ Failure Assessment (SOFA) could function as an effective risk stratification tool in the admission of critically ill patients with COVID-19 and would allow stratification based on a risk assessment. We aimed to examine whether the SOFA score is useful to define 2 severity profiles in COVID-19 patients admitted to ICU: mild with SOFA < 5, and severe with SOFA ≥ 5. A retrospective cohort, multicenter study was conducted from February 11 to May 11, 2020. We analyzed patients admitted to all ICUs of the 14 public hospitals of the Castilla-La Mancha Health Service at the beginning of the pandemic and with SARS-CoV-2 infection. Patients were divided in 2 groups according to the level of severity by SOFA at admission to the ICU. Cox regression was used to evaluate factors associated with survival and Kaplan-Meier test to examine survival probability. In total, 405 patients with a complete SOFA panel were recruited in the 14 participating ICUs. SOFA <5 group showed that age above 60 years and D-dimer above 1000 ng/mL were risk factors associated with lower survival. In SOFA ≥ 5 it was found that high blood pressure was a risk factor associated with shorter survival. Kaplan-Meier showed lower survival in SOFA ≥ 5 in combination with high blood pressure, time since viral symptom onset to admission in ICU < 7 days, D-dimer ≥1000 ng/mL and respiratory pathology. However, SOFA < 5 showed only higher age (≥60 years) associated with lower survival. Age over 60 years and D-dimer over 1000 ng/mL were risk factors reflecting lower survival in patients with SOFA < 5. Moreover, SOFA ≥ 5 patients within a week after COVID-19 onset and comorbidities such as high blood pressure and previous respiratory pathology showed lower survival., Competing Interests: Conflicts of interest: The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: SARS-CoV-2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two-step furin-mediated entry mechanism. Aprotinin is a broad-spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti-inflammatory properties for inhibiting the innate immunity contact system., Methods: This was a multicentre, double-blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID-19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length of hospital stay and ICU admission. The secondary endpoints were each of the primary efficacy outcomes and a composite of oxygen therapy, analytical parameters and death. Safety outcomes included adverse reactions to treatment during a 30-day follow-up period. Treatment was given for 11 days or till discharge., Results: With almost identical analytical profiles, significant differences were observed in treatment time, which was 2 days lower in the aprotinin group (p = .002), and length of hospital admission, which was 5 days shorter in the aprotinin group (p = .003). The incidence of discharge was 2.19 times higher (HR: 2.188 [1.182-4.047]) in the aprotinin group than in the placebo group (p = .013). In addition, the aprotinin-treated group required less oxygen therapy and had no adverse reactions or side effects., Conclusion: Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID-19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe., (© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

This case report presents a real example of a study which introduces the use of reconfigurable platforms in the teaching of electronics engineering to establish a bridge between theory and practice. This gap is one of the major concerns of the electronics engineering students. Different strategies, such as simulation tools or breadboard implementations, have been followed so far to make it easier for students to practice what they study in lectures. However, many students still claim to have problems when they face real practical implementations. The use of reconfigurable platforms as a teaching tool is proposed to provide the students the possibility of fast experimentation, reducing both development time and the learning curve. In addition, reconfigurable platforms available on the market make this methodology suitable to be applied throughout the different courses of their curricula. The feasibility of this approach is demonstrated in a course at the M.Eng. level, where the objective is the study, design and development of electronic sensor nodes. We firmly consider, based on the students' results and reflections collected during the course, that this methodology helps students to address the theoretical framework from a practical viewpoint, as well as to acquire some of the fundamental skills for their professional careers, such as the usage of communication protocols and embedded systems programming, in a more intuitive way when compared to traditional teaching methodologies.

Parafoveal circulation of the superficial retinal capillary plexus is usually measured with vessel density, which determines the length of capillaries with circulation, and perfusion density, which calculates the percentage of the evaluated area that has circulation. Perfusion density also considers the circulation of vessels larger than capillaries, although the contribution of these vessels to the first is not usually evaluated. As both measurements are automatically generated by optical coherence tomography angiography devices, this paper proposes a method for estimating the contribution of vessels larger than capillaries by using a coefficient of determination between vessel and perfusion densities. This method can reveal a change in the proportion of perfusion density from vessels larger than capillaries, even when mean values do not differ. This change could reflect compensatory arterial vasodilatation as a response to capillary dropout in the initial stages of retinal vascular diseases before clinical retinopathy appears. The proposed method would allow the estimation of the changes in the composition of perfusion density without the need for other devices.

Mastitis is the inflammation of one or several mammal lobes which can be accompanied by a mammary gland infection, and is the leading cause of undesired early weaning in humans. However, little information exists regarding the changes that this disease may induce in the biochemical composition of human milk, especially in terms of oxidative status. Given that newborns are subject to a significant increase in total ROS burden in their transition to neonatal life and that their antioxidant defense system is not completely developed, the aim of this study was to evaluate antioxidant defense (glutathione peroxidase (GPx), reduced glutathione (GSH), total polyphenol content (TPP), and total antioxidant capacity (TAC)) in milk samples from mothers suffering from mastitis and controls. We also measured the oxidative damage to lipids (malondyaldehyde (MDA)) and proteins (carbonyl group content (CGC)) in these samples. Finally, we tested whether dietary supplementation with cranberries (a product rich in antioxidants) in these breastfeeding mothers during 21 days could improve the oxidative status of milk. GPx activity, TPP, and TAC were increased in milk samples from mastitis-affected women, providing a protective mechanism to the newborn drinking mastitis milk. MDA concentrations were diminished in the mastitis group, confirming this proposal. Some oxidative damage might occur in the mammary gland since the CGC was increased in mastitis milk. Cranberries supplementation seems to strengthen the antioxidant system, further improving the antioxidative state of milk.

Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cocaine can induce severe neurobehavioral changes, among others, the ones involved in learning and memory processes. It is known that during drug consumption, cocaine-associated memory and learning processes take place. However, much less is known about the effects of this drug upon the mechanisms involved in forgetting.The present report focuses on the mechanisms by which cocaine affects memory consolidation of experiences acquired prior to drug administration. We also study the involvement of hippocampus in these processes, with special interest on the role of Nuclear factor kappa B (NF-κB), N-methyl-D-aspartate glutamate receptor 2B (GluN2B), and their relationship with other proteins, such as cyclic AMP response element binding protein (CREB). For this purpose, we developed a rat experimental model of chronic cocaine administration in which spatial memory and the expression or activity of several proteins in the hippocampus were assessed after 36 days of drug administration. We report an impairment in memory acquisition of experiences gathered prior to cocaine administration, associated to an increase in GluN2B expression in the hippocampus. We also demonstrate a decrease in NF-κB activity, as well as in the expression of the active form of CREB, confirming the role of these transcription factors in the cocaine-induced memory impairment., (© 2021. The Author(s).)

The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm 3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r =  - 0.27 to r =  - 0.46), and (2) tau with BA35 (r =  - 0.31) and SRLM thickness (r =  - 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r =  - 0.40), BA35 (r =  - 0.55), subiculum (r =  - 0.42) and CA1 thickness (r =  - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration., (© 2021. The Author(s).)

Objective: The aim of this study was to explore the influence of an enrolled degree course on health and eating habits in a population of Spanish university students (17-26 y of age)., Methods: A cross-sectional observational study was carried out with 648 students. Volunteers were stratified into biomedical (medicine and nursing, 48%) and non-biomedical students (other fields of study, 52%). Data were collected using previously self-reported questionnaires focused on anthropometric and sociodemographic profile, lifestyle practices, body image perception, health consciousness, eating habits, physical activity, and food addiction. Mann-Whitney U tests and Pearson's χ 2 tests were applied to identify associations between the two groups., Results: Self-reported body mass index was higher for the non-biomedical group (22.1 ± 3.1 versus 23 ± 5 kg/m 2 ; P < 0.05), which also reported less regularity in taking meals (91 versus 95%; P < 0.05), eating fewer colored vegetables and fruits (65 versus 77%; P < 0.001) and a higher alcohol intake (27 versus 20%; P < 0.001). In contrast, the proportion of students that showed more interest in the diet-health duality (92 versus 85%; P < 0.001) and a desire to adopt healthier habits (80 versus 78%; P < 0.05) was larger in the biomedical group. Dietary habits, obtained by means of a food frequency questionnaire, suggested that biomedical students make healthier food choices. Additionally, the group of biomedical students took more walks per week (5.8 ± 1.8 versus 5.5 ± 1.9; P < 0.05)., Conclusions: Healthier lifestyle factors cluster into the biomedical group in various components of the study, except food addiction where no differences were observed. The data presented here suggest the necessity to develop health promotion strategies targeting university students., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Spain is one of the countries with the highest number of COVID-19 patients. Unfortunately, few data for regions are available., Objectives: This study aimed to describe the characteristics and independent risk factors associated with COVID-19 mortality in Castilla-La Mancha, Spain., Methods: Cohort and multicenter study in all 14 public hospitals of the Castilla-La Mancha Health Service. Baseline characteristics, preexisting comorbidities, symptoms, clinical features and treatments were included. Multivariable logistic regression was used to evaluate factors associated with death and Kaplan-Meier test to examine survival probability. Statistical significance was considered with p  < 0.05 (95% CI). SPSS (version 24.0 for Windows) and R 4.0.2 (R Statistics) software were used., Results: The cohort comprised 12,126 patients sequentially attended between February 11 and May 11, 2020. The mean age of patients was 66.4 years; 5667 (46.7%) were women. Six protective factors against exitus were defined: female sex, anosmia, cough, chloroquine and azithromycin. The risk factors were: age over 50, obesity, cardiac pathology, fever, dyspnea, lung infiltrates, lymphopenia, D-dimer above 1000 ng/mL, and mechanical ventilation requirement. Survival analysis showed higher survival rate in women (75.7%) than men (72.1%). Cumulative survival was 87.5% for non-hospitalized patients, 70.2% for patients admitted to hospital and 61.2% in ICU patients. Additionally, survival probability decreased with increasing age range., Conclusion: Determination of protective or death-promoting factors could be useful to stratify patients by severity criteria and to improve COVID-19 care management., (© 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: To evaluate the long-term clinical effect of continuous subcutaneous insulin infusion (CSII) in adult type 1 diabetes mellitus (T1DM) patients in a regional public healthcare system real-world scenario., Methods: All adult T1DM patients on CSII for ≥10 years subjected to follow-up in the regional Castilla-La Mancha Public Health Service were included. The primary efficacy outcome was the variation in HbA 1c during follow-up. Direct patient data were compiled through the web-based Spanish national registry on CSII therapy., Results: A total of 69 T1DM adult patients were treated with insulin pumps for ≥10 years in our region. The mean age was 45.0±10.5 years, with a T1DM duration of 13.9±8.5 years. The mean duration of CSII therapy was 11.4±2.1 years. The main indications for treatment were high glucose variability (39%), problematic hypoglycemia (26%), and HbA 1c >53mmol/mol (7%) on multiple daily injections (20%). Sensor-augmented pump therapy was used by 31% of the patients. Glycosylated hemoglobin did not change during follow-up (58±11mmol/mol vs. 58±11mmol/mol; 7.5±1.0 vs. 7.5±1.0; p=0.66). However, the percentage of patients with at least one episode of severe hypoglycemia during the last year and unnoticed hypoglycemia decreased from 36% to 7% (p=0.006) and from 38% to 32% (p<0.001), respectively. The proportion of subjects with ≥1 episode of diabetic ketoacidosis in the last year decreased from 30% to 6% (p=0.045)., Conclusions: The reduction of severe hypoglycemia without deterioration of glycemic control can be sustained over long-term CSII therapy., (Copyright © 2020 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Stromal interaction molecule 1 (STIM1) plays a pivotal role in store-operated Ca 2+ entry (SOCE), an essential mechanism in cellular calcium signaling and in maintaining cellular calcium balance. Because O -GlcNAcylation plays pivotal roles in various cellular function, we examined the effect of fluctuation in STIM1 O -GlcNAcylation on SOCE activity. We found that both increase and decrease in STIM1 O -GlcNAcylation impaired SOCE activity. To determine the molecular basis, we established STIM1-knockout HEK293 (STIM1-KO-HEK) cells using the CRISPR/Cas9 system and transfected STIM1 WT (STIM1-KO-WT-HEK), S621A (STIM1-KO-S621A-HEK), or T626A (STIM1-KO-T626A-HEK) cells. Using these cells, we examined the possible O -GlcNAcylation sites of STIM1 to determine whether the sites were O -GlcNAcylated. Co-immunoprecipitation analysis revealed that Ser 621 and Thr 626 were O -GlcNAcylated and that Thr 626 was O -GlcNAcylated in the steady state but Ser 621 was not. The SOCE activity in STIM1-KO-S621A-HEK and STIM1-KO-T626A-HEK cells was lower than that in STIM1-KO-WT-HEK cells because of reduced phosphorylation at Ser 621 Treatment with the O -GlcNAcase inhibitor Thiamet G or O -GlcNAc transferase (OGT) transfection, which increases O -GlcNAcylation, reduced SOCE activity, whereas treatment with the OGT inhibitor ST045849 or siOGT transfection, which decreases O -GlcNAcylation, also reduced SOCE activity. Decrease in SOCE activity due to increase and decrease in O -GlcNAcylation was attributable to reduced phosphorylation at Ser 621 These data suggest that both decrease in O -GlcNAcylation at Thr 626 and increase in O -GlcNAcylation at Ser 621 in STIM1 lead to impairment of SOCE activity through decrease in Ser 621 phosphorylation. Targeting STIM1 O -GlcNAcylation could provide a promising treatment option for the related diseases, such as neurodegenerative diseases., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (© 2020 Nomura et al.)

This work demonstrates a cost-effective manufacturing method of flexible and fully printed microheaters, using carbon nanotubes (CNTs) as the heating element. Two different structures with different number of CNT layers have been characterized in detail. The benchmarking has been carried out in terms of maximum operating temperature, as well as nominal resistance and input power for different applied voltages. Their performances have been compared with previous reports for similar devices, fabricated with other technologies. The results have shown that the heaters presented can achieve high temperatures in a small area at lower voltages and lower input power. In particular, the fully printed heaters fabricated on a flexible substrate covering an area of 3.2 mm 2 and operating at 9.5 V exhibit a maximum temperature point above 70 °C with a power consumption below 200 mW. Therefore, we have demonstrated that this technology paves the way for a cost-effective large-scale fabrication of flexible microheaters aimed to be integrated in flexible sensors.

STIM1 is an endoplasmic reticulum (ER) protein that modulates the activity of a number of Ca 2+ transport systems. By direct physical interaction with ORAI1, a plasma membrane Ca 2+ channel, STIM1 activates the I CRAC current, whereas the binding with the voltage-operated Ca 2+ channel Ca V 1.2 inhibits the current through this latter channel. In this way, STIM1 is a key regulator of Ca 2+ signaling in excitable and non-excitable cells, and altered STIM1 levels have been reported to underlie several pathologies, including immunodeficiency, neurodegenerative diseases, and cancer. In both sporadic and familial Alzheimer's disease, a decrease of STIM1 protein levels accounts for the alteration of Ca 2+ handling that compromises neuronal cell viability. Using SH-SY5Y cells edited by CRISPR/Cas9 to knockout STIM1 gene expression, this work evaluated the molecular mechanisms underlying the cell death triggered by the deficiency of STIM1, demonstrating that STIM1 is a positive regulator of ITPR3 gene expression. ITPR3 (or IP3R3) is a Ca 2+ channel enriched at ER-mitochondria contact sites where it provides Ca 2+ for transport into the mitochondria. Thus, STIM1 deficiency leads to a strong reduction of ITPR3 transcript and ITPR3 protein levels, a consequent decrease of the mitochondria free Ca 2+ concentration ([Ca 2+ ] mit ), reduction of mitochondrial oxygen consumption rate, and decrease in ATP synthesis rate. All these values were normalized by ectopic expression of ITPR3 in STIM1-KO cells, providing strong evidence for a new mode of regulation of [Ca 2+ ] mit mediated by the STIM1-ITPR3 axis.

The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELISA, qPCR and Western blot. The highest EtOH concentration used stimulated a large increase in ROS levels, upregulating the cytochrome P450-2E1 (CYP2E1) and promoting cell death. The use of antioxidants such as N-acetylcysteine (NAC) and diallyl sulfide (DAS), which is also a CYP2E1 inhibitor, reverted cell death and oxidative stress, modulating also the upstream angiogenesis and inflammation regulators. Because oxidative stress plays a central role in most frequent ocular diseases, the results herein support the proposal that CYP2E1 upregulation could aggravate retinal degeneration, especially in those patients with high baseline oxidative stress levels due to their ocular pathology and should be considered as a risk factor.

Herein, we present, for the first time, a 2D-MOF based on copper and 4-hydroxypyrimidine-5-carbonitrile as the linker. Each MOF layer is perfectly flat and neutral, as is the case for graphene. High pressure X-ray diffraction measurements reveal that this layered structure can be modulated between 3.01 to 2.78 Å interlayer separation, with an evident piezochromism and varying conductive properties. An analysis of the band structure indicates that this material is conductive along different directions depending on the application of pressure or H doping. These results pave the way for the development of novel layered materials with tunable and efficient properties for pressure-based sensors.

Objective: To know the epidemiological, clinical and therapeutic characteristics of patients with a diagnosis of HF treated in primary care of 2Health Areas of Albacete, Zone 5 A (characteristics of the Urban Center) and Casas Ibañez (characteristics of the Rural Center) as well as to highlight The main differences between the two., Method: Descriptive and cross-sectional study, corresponding to the first phase of the ALBAPIC study. All patients in the area who met the inclusion criteria have been registered: Having a diagnosis of HF in the TURRIANO program (consultation program in Primary Care of Castilla la Mancha). Demographic-anthropometric and clinical characteristics, analytical data, complementary diagnostic examinations, therapeutic guidelines and hospitalizations were recorded for 12 months prior to inclusion. A physical examination and electrocardiographic and biochemical controls were performed at the inclusion visit., Results: 384 patients diagnosed with HF in both Health Zone (161 in urban areas and 223 in rural areas) have participated. Average age 82.24±10.51 years (81.24±9.59 years in urban areas and 83.37±11 years in rural areas with significant differences P<.005, 54.3% are women (54% in urban areas and 54.7% in rural areas) We have an incidence of CI of 1% in urban areas and 1.8% in rural areas. The prevalence of CVRF has that hypertension above all and dyslipidemia are the most frequent, with differences depending on the environment in which they live. In the rural environment there are higher rates of heart disease. Patients with HF have a high number of concomitant chronic diseases, being between 4 and 6 more than 60% of cases in the urban environment and between 1 and 4 in the rural environment. Approximately 14% also have an oncological disease in the urban environment compared to 21% in the rural. According to the exploration and analytical data, the main variables are acceptably controlled, the lipid parameters in the rural center being worse controlled. The average number of drugs prescribed by each patient was 6.3 in rural and 7.2 urban. As for the treatments they are taking, it is observed that diuretics and statins., Conclusions: There is an acceptable control of cardiovascular risk factors in both media, there being differences in the diagnostic methods and treatments used., (Copyright © 2020 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Sexual dimorphism in lizards is determined by ecological and environmental factors. Broadly distributed species may show variation in patterns of sexual dimorphism toward either sex, as well as exhibiting variation in morphological dimensions. In the present study, sexual dimorphism in size and shape attributes was evaluated in three populations of the lizard Sceloporus variabilis from different environments in Mexico. We evaluated the size attributes of 10 morphological variables: snout-vent length (SVL), tibia length (TL), femur length (FeL), forearm length (FoL), interaxial distance (ID), head length (HL), head width (HW), head height (HH), jaw length (JL), and jaw width (JW). We also evaluated the attributes of shape (relative dimensions of the 10 morphological variables). In the size attribute, sexual dimorphism was found, with males being larger than females. In the case of shape, sexual dimorphism was found, with the females being larger in relative dimensions of ID and JW. Also, the males showed larger relative dimensions in TL, FeL and FoL. Differences were found between populations in the dimension of the variables analyzed in each sex. The pattern in size can be explained by sexual selection, where the males of each population maintain larger dimensions to compete for territory and access to females. In shape, females can be favored if they have larger relative ID and JW, as it promotes maintenance of clutch sizes, and use of microhabitats and different consumption of prey types than males. In the case of males, relative dimensions of TL, FeL and FoL may be functioning as important traits for escape from predators. The present study shows the importance of incorporating size and shape variables into analyses of sexual dimorphism among populations of a single species with a wide distribution. These types of studies help to identify the causes that promote sexual dimorphism, as well as the degree of difference among populations that inhabit different environments., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

In this paper, we present a comparative study of a cost-effective method for the mass fabrication of electrodes to be used in thin-film flexible supercapacitors. This technique is based on the laser-synthesis of graphene-based nanomaterials, specifically, laser-induced graphene and reduced graphene oxide. The synthesis of these materials was performed using two different lasers: a CO 2 laser with an infrared wavelength of λ = 10.6 µm and a UV laser (λ = 405 nm). After the optimization of the parameters of both lasers for this purpose, the performance of these materials as bare electrodes for flexible supercapacitors was studied in a comparative way. The experiments showed that the electrodes synthetized with the low-cost UV laser compete well in terms of specific capacitance with those obtained with the CO 2 laser, while the best performance is provided by the rGO electrodes fabricated with the CO 2 laser. It has also been demonstrated that the degree of reduction achieved with the UV laser for the rGO patterns was not enough to provide a good interaction electrode-electrolyte. Finally, we proved that the specific capacitance achieved with the presented supercapacitors can be improved by modifying the in-planar structure, without compromising their performance, which, together with their compatibility with doping-techniques and surface treatments processes, shows the potential of this technology for the fabrication of future high-performance and inexpensive flexible supercapacitors.

A portable reconfigurable platform for hemoglobin determination based on inner filter quenching of room-temperature phosphorescent carbon dots (CDs) in the presence of H 2 O 2 is described. The electronic setup consists of a light-emitting diode (LED) as the carbon dot optical exciter and a photodiode as a light-to-current converter integrated in the same instrument. The reconfigurable feature provides adaptability to use the platform as an analytical probe for CDs coming from different batches with some variations in luminescence characteristics. The variables of the reaction were optimized, such as pH, concentration of reagents, and response time; as well as the variables of the portable device, such as LED voltage, photodiode sensitivity, and adjustment of the measuring range by a reconfigurable electronic system. The portable device allowed the determination of hemoglobin with good sensitivity, with a detection limit of 6.2 nM and range up to 125 nM.

Tumor invasion requires efficient cell migration, which is achieved by the generation of persistent and polarized lamellipodia. The generation of lamellipodia is supported by actin dynamics at the leading edge where a complex of proteins known as the WAVE regulatory complex (WRC) promotes the required assembly of actin filaments to push the front of the cell ahead. By using an U2OS osteosarcoma cell line with high metastatic potential, proven by a xenotransplant in zebrafish larvae, we have studied the role of the plasma membrane Ca 2+ channel ORAI1 in this process. We have found that epidermal growth factor (EGF) triggered an enrichment of ORAI1 at the leading edge, where colocalized with cortactin (CTTN) and other members of the WRC, such as CYFIP1 and ARP2/3. ORAI1-CTTN co-precipitation was sensitive to the inhibition of the small GTPase RAC1, an upstream activator of the WRC. RAC1 potentiated ORAI1 translocation to the leading edge, increasing the availability of surface ORAI1 and increasing the plasma membrane ruffling. The role of ORAI1 at the leading edge was studied in genetically engineered U2OS cells lacking ORAI1 expression that helped us to prove the key role of this Ca 2+ channel on lamellipodia formation, lamellipodial persistence, and cell directness, which are required for tumor cell invasiveness in vivo.

In this paper, we present a simple, fast, and cost-effective method for the large-scale fabrication of high-sensitivity humidity sensors on flexible substrates. These sensors consist of a micro screen-printed capacitive structure upon which a sensitive layer is deposited. We studied two different structures and three different sensing materials by modifying the concentration of poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate (PEDOT:PSS) in a graphene oxide (GO) solution. The results show that the aggregation of the PEDOT:PSS to the GO can modify its electrical properties, boosting the performance of the capacitive sensors in terms of both resistive losses and sensitivity to relative humidity (RH) changes. Thus, in an area less than 30 mm 2 , the GO/PEDOT:PSS-based sensors can achieve a sensitivity much higher (1.22 nF/%RH at 1 kHz) than other similar sensors presented in the literature which, together with their good thermal stability, time response, and performance over bending, demonstrates that the manufacturing approach described in this work paves the way for the mass production of flexible humidity sensors in an inexpensive way., Competing Interests: The authors declare no conflicts of interest.

The retina is subjected to oxidative stress due to its high vascularization, long time light exposition and a high density of mitochondria. Oxidative stress can lead to pathological processes, like cell apoptosis, angiogenesis and inflammation ending in retinal pathologies. Curcumin, a major bioactive component obtained from the spice turmeric ( Curcuma longa ) rhizome has been used for centuries in Asian countries for cooking and for curing all kinds of diseases like dysentery, chest congestion and pain in general, due to its antioxidant effects. Curcumin prevents the formation of reactive oxygen species and so it is a good protective agent. Curcumin has shown also anti-inflammatory, and antitumor properties. Curcumin is a natural product, which can be a therapeutic option in a variety of retinal diseases due to its pleiotropic properties. Some drawbacks are its poor solubility, bioavailability and lack of stability at physiological conditions; which have been shown in curcumin skeptical publications. In this review, we provide some lights and shadows on curcumin administration on the major retinal pathologies.