Miracle-dz/UniFAR-FTUs huggingface dataset:
An Update on Resources, Procedures and Healthcare Provision in Pain Units: A Survey of Spanish Practitioners

Multidisciplinary pain treatment units are recommended to provide comprehensive diagnosis and treatment of chronic pain, a complex clinical syndrome and one of the leading causes of disability worldwide. The objective of this study was to provide updated results on the situation of pain treatment units in Spain and to determine compliance with recommendations proposed by de Spanish Ministry of Health (SMH). A cross-sectional, prospective, multicenter survey was performed, collecting data on resources, procedures and healthcare provision. Between March and May 2019, the Spanish Pain Society sent an invitation letter to 183 pain units with a link to the questionnaire. Sixty-nine units from 13 regions agreed to participate. According to the International Association for the Study of Pain criteria, only 12 units were classified as multidisciplinary pain centers. Most (95.7%) were in hospitals, 82.6% from the public sector, and 46.4% had protocols to coordinate with primary care. Interviewees rated the adequacy of facilities at 6.3 (from 0 to 10). Moreover, 67% of interviewees found that there were insufficient staff, with no mental health professionals, physical therapists or social workers in 49.3%, 87.0% and 97.1% units, respectively. Only 24 pain units had a day hospital, 44.9% offered psychological interventions, and 79.7% supported teaching and research activities. Results suggest that a small proportion of Spanish pain units meet the national standards for multidisciplinary pain units proposed by the SMH.
The Presence of Cholesteryl Ester Transfer Protein (CETP) in Endothelial Cells Generates Vascular Oxidative Stress and Endothelial Dysfunction

Endothelial dysfunction precedes atherosclerosis and is an independent predictor of cardiovascular events. Cholesterol levels and oxidative stress are key contributors to endothelial damage, whereas high levels of plasma high-density lipoproteins (HDL) could prevent it. Cholesteryl ester transfer protein (CETP) is one of the most potent endogenous negative regulators of HDL-cholesterol. However, whether and to what degree CETP expression impacts endothelial function, and the molecular mechanisms underlying the vascular effects of CETP on endothelial cells, have not been addressed. Acetylcholine-induced endothelium-dependent relaxation of aortic rings was impaired in human CETP-expressing transgenic mice, compared to their non-transgenic littermates. However, endothelial nitric oxide synthase (eNOS) activation was enhanced. The generation of superoxide and hydrogen peroxide was increased in aortas from CETP transgenic mice, while silencing CETP in cultured human aortic endothelial cells effectively decreased oxidative stress promoted by all major sources of ROS: mitochondria and NOX2. The endoplasmic reticulum stress markers, known as GADD153, PERK, and ARF6, and unfolded protein response effectors, were also diminished. Silencing CETP reduced endothelial tumor necrosis factor (TNF) α levels, intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expression, diminishing monocyte adhesion. These results support the notion that CETP expression negatively impacts endothelial cell function, revealing a new mechanism that might contribute to atherosclerosis.
Assessment of Physico-Chemical and Toxicological Properties of Commercial 2D Boron Nitride Nanopowder and Nanoplatelets

Boron nitride (BN) nanomaterials have been increasingly explored for potential applications in chemistry and biology fields (e.g., biomedical, pharmaceutical, and energy industries) due to their unique physico-chemical properties. However, their safe utilization requires a profound knowledge on their potential toxicological and environmental impact. To date, BN nanoparticles have been considered to have a high biocompatibility degree, but in some cases, contradictory results on their potential toxicity have been reported. Therefore, in the present study, we assessed two commercial 2D BN samples, namely BN-nanopowder (BN-PW) and BN-nanoplatelet (BN-PL), with the objective to identify whether distinct physico-chemical features may have an influence on the biological responses of exposed cellular models. Morphological, structural, and composition analyses showed that the most remarkable difference between both commercial samples was the diameter of their disk-like shape, which was of 200–300 nm for BN-PL and 100–150 nm for BN-PW. Their potential toxicity was investigated using adenocarcinomic human alveolar basal epithelial cells (A549 cells) and the unicellular fungus Saccharomyces cerevisiae, as human and environmental eukaryotic models respectively, employing in vitro assays. In both cases, cellular viability assays and reactive oxygen species (ROS) determinations where performed. The impact of the selected nanomaterials in the viability of both unicellular models was very low, with only a slight reduction of S. cerevisiae colony forming units being observed after a long exposure period (24 h) to high concentrations (800 mg/L) of both nanomaterials. Similarly, BN-PW and BN-PL showed a low capacity to induce the formation of reactive oxygen species in the studied conditions. Even at the highest concentration and exposure times, no major cytotoxicity indicators were observed in human cells and yeast. The results obtained in the present study provide novel insights into the safety of 2D BN nanomaterials, indicating no significant differences in the toxicological potential of similar commercial products with a distinct lateral size, which showed to be safe products in the concentrations and exposure conditions tested.
Extracellular Vesicles from Airway Secretions: New Insights in Lung Diseases

Lung diseases (LD) are one of the most common causes of death worldwide. Although it is known that chronic airway inflammation and excessive tissue repair are processes associated with LD such as asthma, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), their specific pathways remain unclear. Extracellular vesicles (EVs) are heterogeneous nanoscale membrane vesicles with an important role in cell-to-cell communication. EVs are present in general biofluids as plasma or urine but also in secretions of the airway as bronchoalveolar lavage fluid (BALF), induced sputum (IS), nasal lavage (NL) or pharyngeal lavage. Alterations of airway EV cargo could be crucial for understanding LD. Airway EVs have shown a role in the pathogenesis of some LD such as eosinophil increase in asthma, the promotion of lung cancer in vitro models in COPD and as biomarkers to distinguishing IPF in patients with diffuse lung diseases. In addition, they also have a promising future as therapeutics for LD. In this review, we focus on the importance of airway secretions in LD, the pivotal role of EVs from those secretions on their pathophysiology and their potential for biomarker discovery.
Spontaneous Eye Blink Rate Connects Missing Link between Aerobic Fitness and Cognition

Supplemental digital content is available in the text. ABSTRACT Purpose Higher aerobic fitness, a physiological marker of habitual physical activity, is likely to predict higher executive function based on the prefrontal cortex (PFC), according to current cross-sectional studies. The exact biological link between the brain and the brawn remains unclear, but the brain dopaminergic system, which acts as a driving force for physical activity and exercise, can be hypothesized to connect the missing link above. Recently, spontaneous eye blink rate (sEBR) was proposed and has been used as a potential, noninvasive marker of brain dopaminergic activity in the neuroscience field. To address the hypothesis above, we sought to determine whether sEBR is a mediator of the association between executive function and aerobic fitness. Methods Thirty-five healthy young males (18–24 yr old) had their sEBR measured while staring at a fixation cross while at rest. They underwent an aerobic fitness assessment using a graded exercise test to exhaustion and performed a color–word Stroop task as an index of executive function. Stroop task–related cortical activation in the left dorsolateral PFC (l-DLPFC) was monitored using functional near-infrared spectroscopy. Results Correlation analyses revealed significant correlations among higher aerobic fitness, less Stroop interference, and higher sEBR. Moreover, mediation analyses showed that sEBR significantly mediated the association between aerobic fitness and Stroop interference. In addition, higher sEBR was correlated with higher neural efficiency of the l-DLPFC (i.e., executive function was high, and the corresponding l-DLPFC activation was relatively low). Conclusion These results indicate that the sEBR mediates the association between aerobic fitness and executive function through prefrontal neural efficiency, which clearly supports the hypothesis that brain dopaminergic function works to connect, at least in part, the missing link between aerobic fitness and executive function.
Serum Response Factor (SRF) Drives the Transcriptional Upregulation of the MDM4 Oncogene in HCC

Simple Summary Hepatocellular carcinoma (HCC) represents the most common type of liver cancer and has a poor prognosis. Therefore, there is an urgent need for the identification of new therapeutic options. The mouse double minute homolog 4 (MDM4) gene, a known p53 inhibitor, is upregulated in most HCCs. Here, we aimed to investigate the mechanisms leading to MDM4 transcriptional upregulation and to evaluate whether therapeutic targeting of these mechanisms might represent a suitable approach for future therapy. Using human HCC cell lines, a mouse model, and human HCC cohorts, we have identified serum response factor (SRF), ETS transcription factors ELK1 and ELK4 as transcription factors (TFs) driving MDM4 expression. Treatment of HCC cell lines with XI-011, a pharmaceutical inhibitor of MDM4 transcription, reduced the expression of both the TFs and MDM4 and impaired tumor growth, suggesting that targeting the MDM4 transcription may provide a rationale for future targeted therapy of HCC. Abstract Different molecular mechanisms support the overexpression of the mouse double minute homolog 4 (MDM4), a functional p53 inhibitor, in human hepatocellular carcinoma (HCC). However, the transcription factors (TFs) leading to its transcriptional upregulation remain unknown. Following promoter and gene expression analyses, putative TFs were investigated using gene-specific siRNAs, cDNAs, luciferase reporter assays, chromatin immunoprecipitation, and XI-011 drug treatment in vitro. Additionally, MDM4 expression was investigated in SRF-VP16iHep transgenic mice. We observed a copy-number-independent upregulation of MDM4 in human HCCs. Serum response factor (SRF), ELK1 and ELK4 were identified as TFs activating MDM4 transcription. While SRF was constitutively detected in TF complexes at the MDM4 promoter, presence of ELK1 and ELK4 was cell-type dependent. Furthermore, MDM4 was upregulated in SRF-VP16-driven murine liver tumors. The pharmacological inhibitor XI-011 exhibited anti-MDM4 activity by downregulating the TFs driving MDM4 transcription, which decreased HCC cell viability and increased apoptosis. In conclusion, SRF drives transcriptional MDM4 upregulation in HCC, acting in concert with either ELK1 or ELK4. The transcriptional regulation of MDM4 may be a promising target for precision oncology of human HCC, as XI-011 treatment exerts anti-MDM4 activity independent from the MDM4 copy number and the p53 status.
Role of Blood-Based Biomarkers in Ischemic Stroke Prognosis: A Systematic Review.

BACKGROUND AND PURPOSE Outcome prognostication in ischemic stroke patients remains challenging due to limited predictive properties of existing models. Blood-based biomarkers might provide additional information to established prognostic factors. We intended to identify the most promising prognostic biomarkers in ischemic stroke, their incremental prognostic value, and whether their predictive value differs among etiologies. METHODS We searched MEDLINE (Ovid) and Institute for Scientific Information Web of Knowledge for articles reporting the predictive performance of blood-based biomarkers measured up to 7 days after ischemic stroke and reporting functional outcome or death at least 7 days after stroke. This work updates a previous systematic review (up to January 2007), follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and was registered (International Prospective Register of Systematic Reviews PROSPERO 2018; https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42018094671). RESULTS Two hundred ninety-one articles published between January 2007 and August 2018 comprising 257 different biomarkers met inclusion criteria. Median sample size was 232 (interquartile range, 110-455); 260 (89%) articles reported regression analyses with 78% adjusting for stroke severity, 82% for age, 67% for both, and 9% for none of them; 37% investigated discrimination, 5% calibration, and 11% reclassification. Including publications from a previous systematic review (1960-January 2007), natriuretic peptides, copeptin, procalcitonin, mannose-binding lectin, adipocyte fatty acid-binding protein, and cortisol were the biomarkers most consistently associated with poor outcome in higher-quality studies showing an incremental value over established prognostic factors. Other biomarkers were less consistently associated with poor outcome or were reported in lower quality studies. High heterogeneity among studies precluded the performance of a meta-analysis. CONCLUSIONS The number of reports on prognostic blood-based biomarkers in ischemic stroke increased 3.5-fold in the period January 2007 to August 2018. Although sample size increased, methodological flaws are still common. Natriuretic peptides and markers of inflammation, atherogenesis, and stress response are the most promising prognostic biomarkers among identified studies.
Prevalence and nutrient composition of menu offerings targeted to customers with dietary restrictions at US fast casual and full-service restaurants

Abstract Objective: To examine the prevalence and nutrient composition of menu offerings targeted to customers with dietary restrictions at US fast casual and full-service chain restaurants. Design: We used 2018 data from MenuStat, a database of nutrient information for menu items at large US chain restaurants. Five alternative diets were examined: gluten-free, low-calorie, low-carbohydrate, low-fat and vegetarian. Diet offerings were identified by searching MenuStat item descriptions and reviewing online menus. For each diet, we reported counts and proportions. We used bootstrapped multilevel models to examine differences in predicted mean kilojoules, saturated fat, Na and sugars between diet and non-diet menu items. Setting: Forty-five US fast casual and full-service chain restaurants in 2018 (including 6419 items in initial analytic sample across small plates, salads and main dishes). Participants: None. Results: The most prevalent diets were gluten-free (n 631, 9·8 % of menu items), low-calorie (n 306, 4·8 %) and vegetarian (n 230, 3·6 %). Compared with non-diet counterparts, low-calorie main dishes had significantly lower levels of all nutrients examined and vegetarian main dishes had significantly lower levels of all nutrients except saturated fat. Gluten-free small plates had significantly fewer kilojoules, grams of saturated fat and milligrams of Na compared with non-diet small plates. Conclusions: A small proportion of fast casual and full-service restaurant menus are targeted towards customers with dietary restrictions. Compared with non-diet items, those classified as gluten-free, low-calorie or vegetarian generally have healthier nutrient profiles, but overall nutrient values are still too high for most menu items, regardless of dietary label.
Effects of Mesenchymal Stem Cell‐Derived Paracrine Signals and Their Delivery Strategies

Mesenchymal stem cells (MSCs) have been widely studied as a versatile cell source for tissue regeneration and remodeling due to their potent bioactivity, which includes modulation of inflammation response, macrophage polarization toward proregenerative lineage, promotion of angiogenesis, and reduction in fibrosis. This review focuses on profiling the effects of paracrine signals of MSCs, commonly referred to as the secretome, and highlighting the various engineering approaches to tune the MSC secretome. Recent advances in biomaterials‐based therapeutic strategies for delivery of MSCs and MSC‐derived secretome in the form of extracellular vesicles are discussed, along with their advantages and challenges.
Unpicking the Secrets of African Swine Fever Viral Replication Sites

African swine fever virus (ASFV) is a highly contagious pathogen which causes a lethal haemorrhagic fever in domestic pigs and wild boar. The large, double-stranded DNA virus replicates in perinuclear cytoplasmic replication sites known as viral factories. These factories are complex, multi-dimensional structures. Here we investigated the protein and membrane compartments of the factory using super-resolution and electron tomography. Click IT chemistry in combination with stimulated emission depletion (STED) microscopy revealed a reticular network of newly synthesized viral proteins, including the structural proteins p54 and p34, previously seen as a pleomorphic ribbon by confocal microscopy. Electron microscopy and tomography confirmed that this network is an accumulation of membrane assembly intermediates which take several forms. At early time points in the factory formation, these intermediates present as small, individual membrane fragments which appear to grow and link together, in a continuous progression towards new, icosahedral virions. It remains unknown how these membranes form and how they traffic to the factory during virus morphogenesis.
Hypertensive Crisis in Acute Cerebrovascular Diseases Presenting at the Emergency Department: A Narrative Review

Hypertensive crisis, defined as an increase in systolic blood pressure >179 mmHg or diastolic blood pressure >109 mmHg, typically causes end-organ damage; the brain is an elective and early target, among others. The strong relationship between arterial hypertension and cerebrovascular diseases is supported by extensive evidence, with hypertension being the main modifiable risk factor for both ischemic and hemorrhagic stroke, especially when it is uncontrolled or rapidly increasing. However, despite the large amount of data on the preventive strategies and therapeutic measures that can be adopted, the management of high BP in patients with acute cerebrovascular diseases presenting at the emergency department is still an area of debate. Overall, the outcome of stroke patients with high blood pressure values basically depends on the occurrence of hypertensive emergency or hypertensive urgency, the treatment regimen adopted, the drug dosages and their timing, and certain stroke features. In this narrative review, we provide a timely update on the current treatment, debated issues, and future directions related to hypertensive crisis in patients referred to the emergency department because of an acute cerebrovascular event. This will also focus greater attention on the management of certain stroke-related, time-dependent interventions, such as intravenous thrombolysis and mechanic thrombectomy.
The effect of a fresh produce incentive paired with cooking and nutrition education on healthy eating in low-income households: a pilot study

Abstract Objective: This study pilot-tested combining financial incentives to purchase fruits and vegetables with nutrition education focused on cooking to increase the consumption of fruits and vegetables and improve attitudes around healthy eating on a budget among low-income adults. The goal of the pilot study was to examine implementation feasibility and fidelity, acceptability of the intervention components by participants and effectiveness. Design: The study design was a pre-post individual-level comparison without a control group. The pilot intervention included two components, a scan card providing free produce up to a weekly maximum dollar amount for use over a 2-month period, and two sessions of tailored nutrition and cooking education. Outcomes included self-reported attitudes about healthy eating and daily fruit and vegetable consumption from one 24-h dietary recall collected before and after the intervention. Setting: Greater Minneapolis/St. Paul area in Minnesota. Participants: Adults (n 120) were recruited from five community food pantries. Results: Findings indicated that the financial incentive component of the intervention was highly feasible and acceptable to participants, but attendance at the nutrition education sessions was moderate. Participants had a statistically significant increase in the consumption of fruit, from an average of 1·00 cup/d to 1·78 cups/d (P < 0·001), but no significant change in vegetable consumption or attitudes with respect to their ability to put together a healthy meal. Conclusions: While combining financial incentives with nutrition education appears to be acceptable to low-income adult participants, barriers to attend nutrition education sessions need to be addressed in future research.
A Meta-Analysis of Hippocampal and Amygdala Volumes in Patients Diagnosed With Dissociative Identity Disorder

ABSTRACT Dissociative Identity Disorder (DID), an illness characterized by multiple personality states, has long been a controversial diagnosis within the psychiatric community. Demonstrating a neuroanatomical basis for the disorder may help to resolve the controversy. Current literature on the neuroanatomy associated with DID has focused on the hippocampus and amygdala and are inconclusive. This meta-analysis pools the results from n = 3 studies to compare the mean size of these two structures between DID patients, non-DID patients, and healthy controls. Patients diagnosed with both DID & PTSD were found to have smaller hippocampi bilaterally (p< .001) compared to healthy controls; no significant difference was seen in the amygdala. When comparing DID to PTSD patients, the left hippocampus was smaller (p< .001), with a trend for a smaller right hippocampus (p = .06). A comparison of the amygdala was not possible due to a lack of data. These findings suggest that a smaller hippocampus is seen in DID patients beyond what is seen for PTSD, provides neuroanatomical evidence for the memory impairment often seen in DID patients (i.e., amnesia experienced by the host and alters), and presents a potentially novel means to understand this disorder.