Extracellular Vesicles from Adipose Tissue-Derived Stromal Cells Stimulate Angiogenesis in a Scaffold-Dependent Fashion.

BACKGROUND: The extracellular vesicles (EVs) secreted by adipose tissue-derived stromal cells (ASC) are microenvironment modulators in tissue regeneration by releasing their molecular cargo, including miRNAs. However, the influence of ASC-derived extracellular vesicles (ASC-EVs) on endothelial cells (ECs) and vascularisation is poorly understood. The present study aimed to determine the pro-angiogenic effects of ASC-EVs and explore their miRNA profile. METHODS: EVs were isolated from normoxic and hypoxic cultured ASC conditioned culture medium. The miRNA expression profile was determined by miRseq, and EV markers were determined by Western blot and immunofluorescence staining. The uptake dynamics of fluorescently labelled EVs were monitored for 24 h. ASC-EVs' pro-angiogenic effect was assessed by sprouting ex vivo rat aorta rings in left ventricular-decellularized extracellular matrix (LV dECM) hydrogel or basement membrane hydrogel (Geltrex®). RESULTS: ASC-EVs augmented vascular network formation by aorta rings. The vascular network topology and stability were influenced in a hydrogel scaffold-dependent fashion. The ASC-EVs were enriched for several miRNA families/clusters, including Let-7 and miR-23/27/24. The miRNA-1290 was the highest enriched non-clustered miRNA, accounting for almost 20% of all reads in hypoxia EVs. CONCLUSION: Our study revealed that ASC-EVs augment in vitro and ex vivo vascularisation, likely due to the enriched pro-angiogenic miRNAs in EVs, particularly miR-1290. Our results show promise for regenerative and revascularisation therapies based on ASC-EV-loaded ECM hydrogels.

Underground speciation: Unraveling the systematics and evolution of the highly diverse tuco-tucos (genus Ctenomys) with genomic data.

Subterranean rodents of the genus Ctenomys (tuco-tucos) are endemic to South America and have experienced relatively recent radiation. There are about 67 recognized species that originated in approximately 1-2 MY. They stand out for their species richness, extraordinary chromosomal diversity, and wide range of habitat they occupy in the continent. Phylogenetic relationships among species of tuco-tucos have been challenging to resolve. Groups of closely-related species have been suggested, but their relationships must be resolved. This study estimates the phylogeny of the genus using massive sequencing, generating thousands of independent molecular markers obtained by RADseq, with a taxonomic sampling that includes 66% of the recognized species. The sequences obtained were mapped against the C. sociabilis genome, recovering up to 1215 widely shared RAD loci with more than 19,000 polymorphic sites. Our new phylogenetic hypothesis corroborated the species groups previously proposed with cytochrome b gene sequences and provided a much greater resolution of the relationships among species groups. The frater group is sister to all other tuco-tucos, whereas some of the earlierliest proposals placed the sociabilis group as sister to all other tuco-tucos. Ctenomys leucodon, previously proposed as an independent lineage, is associated with the frater group with moderate statistical support. The magellanicus and mendocinus are sister groups in a major clade formed by the boliviensis, talarum, tucumanus, torquatus, and opimus groups. Ctenomys viperinus, included in the phylogeny for the first time, belongs to the tucumanus group. This multi-locus phylogenetic hypothesis provides insights into the historical biogeography of understanding this highly diverse genus.

Good clinical practice recommendations for the diagnosis and treatment of gastroesophageal reflux disease. An expert review from the Asociación Mexicana de Gastroenterología.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is very prevalent in the general population, with a broad spectrum of clinical manifestations, requiring accurate diagnosis and treatment. AIM: The aim of this expert review is to establish good clinical practice recommendations for the diagnosis and personalized treatment of GERD. METHODS: The good clinical practice recommendations were produced by a group of experts in GERD, members of the Asociación Mexicana de Gastroenterología (AMG), after carrying out an extensive review of the published literature and discussing each recommendation at a face-to-face meeting. This document does not aim to be a clinical practice guideline with the methodology such a document requires. RESULTS: Fifteen experts on GERD formulated 27 good clinical practice recommendations for recognizing the symptoms and complications of GERD, the rational use of diagnostic tests and medical treatment, the identification and management of refractory GERD, the overlap with functional disorders, endoscopic and surgical treatment, and GERD in the pregnant woman, older adult, and the obese patient. CONCLUSIONS: An accurate diagnosis of GERD is currently possible, enabling the prescription of a personalized treatment in patients with this condition. The goal of the good clinical practice recommendations by the group of experts from the AMG presented in this document is to aid both the general practitioner and specialist in the process of accurate diagnosis and treatment, in the patient with GERD.

Scaling properties of the action in the Riemann-Liouville fractional standard map.

The Riemann-Liouville fractional standard map (RL-fSM) is a two-dimensional nonlinear map with memory given in action-angle variables (I,θ). The RL-fSM is parameterized by K and α∈(1,2], which control the strength of nonlinearity and the fractional order of the Riemann-Liouville derivative, respectively. In this work we present a scaling study of the average squared action 〈I^{2}〉 of the RL-fSM along strongly chaotic orbits, i.e., for K≫1. We observe two scenarios depending on the initial action I_{0}, I_{0}≪K or I_{0}≫K. However, we can show that 〈I^{2}〉/I_{0}^{2} is a universal function of the scaled discrete time nK^{2}/I_{0}^{2} (n being the nth iteration of the RL-fSM). In addition, we note that 〈I^{2}〉 is independent of α for K≫1. Analytical estimations support our numerical results.

Lyophilized Avocado Paste Improves Corn Chips' Nutritional Properties and Sensory Acceptability.

Avocado paste (AP) is an industrial byproduct and a potential source of bioactive compounds, so there is great interest in its valorization. The objective of the present study was to evaluate the effects of adding AP to corn chips regarding their nutritional profile and sensory acceptability. Three AP-supplemented corn chip samples were prepared (C-2%, C-6%, and C-10%), along with a control chip (C), whose total phenolics, flavonoids, antioxidant capacity, proximate composition, minerals, fatty acids, and sensory acceptability were evaluated. Regarding the content of phenolic compounds and flavonoids, significant increases were found between all samples (p < 0.05), particularly between C and C-10% (from 0.93 to 3.56 mg GAE/g dw and 1.17 to 6.61 mg QE/g dw, respectively). Their antioxidant capacity also increased significantly (p < 0.05) with all methods used (FRAP, DPPH, ORAC, and TEAC). Regarding the sensory analysis, no significant differences were found (p > 0.05) between C and C-2% in the parameters of smell, color, flavor, and overall acceptability; however, the texture of C-2% was better evaluated. The C-2% sample also had the highest acceptability; 82% of the participants mentioned that they would buy the C-2%, higher than the rest of the samples. These results suggest the feasibility of adding 2% AP as a strategy to improve the nutritional properties of corn chips without compromising their sensory acceptability; therefore, AP may be used as a food ingredient.

The association between vitamin D binding protein levels and periodontal status: A systematic review.

BACKGROUND AND OBJECTIVES: Vitamin D binding protein (DBP) is biosynthesised in the liver and is predominantly expressed in serum. Its primary role centres on facilitating the systemic transportation of vitamin D and its metabolites, notably 25-hydroxyvitamin D, to specific target tissues where vitamin D exerts its biological functions. Due to the paucity of studies, it is unclear whether there is an association between DBP and periodontal status and thus its potential use as a diagnostic biomarker. Therefore, the aim of the systematic review is to investigate the association between DBP in periodontal disease. METHODS: Two independent reviewers (YD and RG) performed a systematic literature search of English publications using several databases including MEDLINE (OVID interface, 1946 onwards), EMBASE (OVID interface, 1974 onwards), and Global Health (OVID interface, 1973 onwards). This search strategy enabled the identification of relevant publications and the development of a comprehensive library of studies. Studies were included based on previously agreed eligibility criteria. Of the eight studies included as part of this systematic review, seven were case-control studies and one was a cross-sectional study. The quality assessment was based on the Newcastle-Ottawa Scale (NOS) for case-control studies and the modified NOS for the cross-sectional study. RESULTS: The NOS quality assessment was 'favorable' for 6 included case control studies; and 'fair' for one study. The modified NOS quality assessment for the single cross-sectional study demonstrated a medium risk of bias. The results of the majority of the included studies indicated a statistically significant higher concentration of DBP levels in individuals with periodontitis in comparison to those who were periodontally healthy. This trend held true irrespective of the sampling method employed for the assessment of DBP concentration. CONCLUSION: The results summarised in this systematic review indicate a positive association between DBP and periodontitis. Nonetheless, there is a need for longitudinal, prospective trials, to confirm the use of DBP as a potential biomarker for the diagnosis of periodontitis.

Angiogenesis is promoted by hypoxic cervical carcinoma-derived extracellular vesicles depending on the endothelial cell environment.

INTRODUCTION: Cancer needs perfusion for its growth and metastasis. Cancer cell-derived extracellular vesicles (CA-EVs) alter the tumor microenvironment (TME), potentially promoting angiogenesis. We hypothesize that conditions in the tumor, e.g., hypoxia, and in the target cells of the TME, e.g., nutrient deprivation or extracellular matrix, can affect the angiogenic potential of CA-EVs, which would contribute to explaining the regulation of tumor vascularization and its influence on cancer growth and metastasis. METHODS: CA-EVs were isolated and characterized from cervical carcinoma cell lines HeLa and SiHa cultured under normoxia and hypoxia, and their angiogenic potential was evaluated in vitro in three endothelial cells (ECs) lines and aortic rings, cultured in basal (growth factor-reduced) or complete medium. RESULTS: Hypoxia increased EV production 10-100 times and protein content 2-4 times compared to normoxic CA-EVs. HeLa-EVs contained six times more RNA than SiHa-EVs, and this concentration was not affected by hypoxia. Treatment with CA-EVs increased tube formation and sprouting in ECs and aortic rings cultured in basal medium and long-term stabilized the stablished vascular networks formed by ECs cultured in complete medium. CONCLUSION: Hypoxia differentially affects CA-EVs in a cell line-dependent manner. The cellular environment (nutrient availability and extracellular matrix scaffold) influences the effect of CA-EV on the angiogenic potential of ECs.

Remote Delivery of the Cuidándome Telehealth Intervention for Self-Management of Depression and Anxiety Among Latina Immigrant Women: Randomized Controlled Trial.

BACKGROUND: Growing evidence suggests that Latina immigrant survivors of adverse childhood experiences (ACEs) are at increased risk for developing and remaining with either depression or anxiety or both symptoms. This study examined the feasibility and acceptability of a telehealth intervention-Cuidándome (quee-DAN-doh-meh, "taking care of myself"). Cuidándome is a 10-week, patient-centered, trauma-informed intervention delivered by a trained facilitator that promotes self-management of depression and anxiety symptoms through improved problem-solving skills and strategies. OBJECTIVE: The aim of this study was to examine the feasibility and acceptability of Cuidándome delivered remotely (via Zoom) with Latina immigrant ACE survivors with either depression or anxiety or both symptoms. We also estimated the effect sizes associated with the intervention on decreasing depression and anxiety symptoms and improving social problem-solving styles. METHODS: We evaluated Cuidándome using a randomized controlled trial design. Latina immigrants (N=47) who had experienced at least 1 ACE and had at least mild depression or anxiety symptoms were randomized to Cuidándome or a comparison group delivered by trained facilitators. We assessed for changes in depression and anxiety symptoms as well as social problem-solving styles at baseline, post intervention, and 3- and 6-month follow-up. RESULTS: Analyses indicated significant decreases over time within both Cuidándome and comparison groups for depression and anxiety symptoms and maladaptive problem-solving. The intervention effect was largest for anxiety; at 6-month follow-up, Cuidándome participants had significantly lower anxiety scores than the comparison group. In addition, we observed a greater average point reduction in depression symptoms at 6 months among Cuidándome participants (5.7 points) than in the comparison group (3.7 points). CONCLUSIONS: A mental health program delivered via Zoom by a trained facilitator was feasible and acceptable to Latina immigrant women and can be beneficial for reducing anxiety and depression symptoms. More research is needed to assess the effectiveness of Cuidándome among a powered sample size of Latina immigrants. TRIAL REGISTRATION: ISRCTN Registry ISRCTN16668518; https://www.isrctn.com/ISRCTN16668518.

Analysis of oncological drugs authorised in Spain in the last decade: association between clinical benefit and reimbursement.

BACKGROUND: Our study aimed to assess whether there was a relationship between clinical benefits and reimbursement decisions as well as the inclusion of economic evaluations in  therapeutic positioning reports (IPTs) and to explore factors influencing reimbursement decisions. MATERIALS AND METHODS: We analysed all anti-cancer drugs approved in Spain from 2010 to September 2022. The clinical benefit of each drug were evaluated using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) 1.1. The characteristics of these drugs were obtained from the Spanish Agency of Medicines and Medical Devices. Reimbursement status information was obtained using BIFIMED, a web resource available in Spanish and consulted the agreements of the Interministerial Committee on Pricing of Medicines (CIPM). RESULTS: In total, 73 drugs were included involving 197 indications. Almost half of the indications had substantial clinical benefit (49.8% yes vs. 50.3% no). Of the 153 indications with a reimbursement decision, 61 (56.5%) reimbursed indications had substantial clinical benefit compared to 14 (31.1%) of the non-reimbursed (p < 0.01). The median gain of overall survival was 4.9 months (2.8-11.2) for reimbursed indications and 2.9 months (1.7-5) in non-reimbursed (p < 0.05). Only six (3%) indications had an economic evaluation in the IPT. CONCLUSION: Our study revealed that there is a relationship between substantial clinical benefit and the reimbursement decision in Spain. However, we also found that the overall survival gain was modest, and a significant proportion of the reimbursed indications had no substantial clinical benefit. Economic evaluations in IPTs are infrequent and cost-effectiveness analysis is not provided by CIPM.

Nuclear Charge Radius of

Collinear laser spectroscopy was performed on the isomer of the aluminium isotope ^{26m}Al. The measured isotope shift to ^{27}Al in the 3s^{2}3p ^{2}P_{3/2}^{○}→3s^{2}4s ^{2}S_{1/2} atomic transition enabled the first experimental determination of the nuclear charge radius of ^{26m}Al, resulting in R_{c}=3.130(15) fm. This differs by 4.5 standard deviations from the extrapolated value used to calculate the isospin-symmetry breaking corrections in the superallowed ß decay of ^{26m}Al. Its corrected Ft value, important for the estimation of V_{ud} in the Cabibbo-Kobayashi-Maskawa matrix, is thus shifted by 1 standard deviation to 3071.4(1.0) s.

Diagnostic accuracy of lumbar CT and MRI in the evaluation of chronic low back pain without red flag symptoms.

BACKGROUND: Low back pain (LBP) is one of the most frequent reasons for medical consultation. Most of the patients will have nonspecific LBP, which usually are self-limited episodes. It is unclear which of the diagnostic imaging pathways is most effective and costeffective and how the imaging impacts on patient treatment. Imaging techniques are usually indicated if symptoms remain after 6 weeks. Magnetic resonance imaging (MRI) is the diagnostic imaging examination of choice in lumbar spine evaluation of low back pain; however, availability of MRI is limited. OBJECTIVES: To evaluate the diagnostic accuracy of computed tomography (CT) with MRI (as standard of reference) in the evaluation of chronic low back pain (LBP) without red flags symptoms. To compare the results obtained by two radiologists with different grades of experience. MATERIALS AND METHODS: Patients with chronic low back pain without red flags symptoms were retrospectively reviewed by two observers with different level of experience. Patients included had undergone a lumbar or abdominal CT and an MRI within a year. Once the radiological information was collected, it was then statistically reviewed. The aim of the statistical analysis is to identify the equivalence between both diagnostic techniques. To this end, sensitivity, specificity and validity index were calculated. In addition, intra and inter-observer reliability were measured by Cohen's kappa values and also using the McNemar test. RESULTS: 340 lumbar levels were evaluated from 68 adult patients with chronic low back pain or sciatica. 63.2% of them were women, with an average age of 60.3 years (SD 14.7). CT shows high values of sensitivity and specificity (>80%) in most of the items evaluated, but sensitivity was low for the evaluation of density of the disc (40%) and for the detection of disc herniation (55%). Moreover, agreement between MRI and CT in most of these items was substantial or almost perfect (Cohen's kappa-coefficient > 0'8), excluding Modic changes (kappa = 0.497), degenerative changes (kappa0.688), signal of the disc (kappa = 0.327) and disc herniation (kappa = 0.639). Finally, agreement between both observers is mostly high (kappa > 0.8). Foraminal stenosis, canal stenosis and the grade of the canal stenosis were overdiagnosed by the inexperienced observer in the evaluation of CT images. CONCLUSIONS AND SIGNIFICANCE: CT is as sensitive as lumbar MRI in the evaluation of most of the items analysed, excluding Modic changes, degenerative changes, signal of the disc and disc herniation. In addition, these results are obtained regardless the experience of the radiologist. The rising use of diagnostic medical imaging and the improvement of image quality brings the opportunity of making a second look of abdominal CT in search of causes of LBP. Thereby, inappropriate medical imaging could be avoided (2). In addition, it would allow to reduce MRI waiting list and prioritize other patients with more severe pathology than LBP.

Printed Digital Wax-up Model as a Blueprint for Layered Pressed-ceramic Laminate Veneers: Technique Description and Case Report.

This article presents a clinical technique for transferring Digital Smile Design (DSD) information and a digital wax-up to fabricate highly personalized ceramic laminate veneers. The hybrid workflow of digitally designed wax-up and conventional hand-crafted veneers is showcased in a female adult who sought to improve her smile due to maxillary anterior incisal wear. The ceramic veneers, layered by feldspathic porcelain, followed the contours and shade blueprint planned with the digital wax-up. The DSD improved the harmony of the facial-and-smile relationship, and the ceramic restorations fulfilled the patient's esthetic and functional demands. Guides based on the printed model with the digitally designed wax-up can provide a reference for pressed lithium disilicate veneers layered with feldspathic porcelain.

Incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infection in European hospitals: the COMBACTE-NET ARTHR-IS multi-centre study.

BACKGROUND: The aim of this study was to estimate the incidence, associated disease burden and healthcare utilization due to Staphylococcus aureus prosthetic joint infections (SA-PJI) after primary hip and knee arthroplasty in European centres. METHODS: This study was conducted in patients who underwent primary hip and knee arthroplasty in 19 European hospitals between 2014 and 2016. The global incidence of PJI and SA-PJI was calculated. The associated disease burden was measured indirectly as infection-related mortality plus loss of function. For healthcare utilization, number and duration of hospitalizations, number and type of surgical procedures, duration of antibiotic treatments, and number of outpatient visits were collected. Subgroup and regression analyses were used to evaluate the impact of SA-PJI on healthcare utilization, controlling for confounding variables. RESULTS: The incidence of PJI caused by any micro-organism was 1.41%, and 0.40% for SA-PJI. Among SA-PJI, 20.7% were due to MRSA with substantial regional differences, and were more frequent in partial hip arthroplasty (PHA). Related deaths and loss of function occurred in 7.0% and 10.2% of SA-PJI cases, respectively, and were higher in patients with PHA. Compared with patients without PJI, patients with SA-PJI had a mean of 1.4 more readmissions, 25.1 more days of hospitalization, underwent 1.8 more surgical procedures, and had 5.4 more outpatient visits, controlling for confounding variables. Healthcare utilization was higher in patients who failed surgical treatment of SA-PJI. CONCLUSIONS: This study confirmed that the SA-PJI burden is high, especially in PHA, and provided a solid basis for planning interventions to prevent SA-PJI.

Dose assesment with fast Monte Carlo codes in interventional radiology.

This study presents the performance of two fast Monte Carlo codes, PENELOPE/penEasyIR and MCGPU-IR in order to assess operator doses in interventional radiology. In particular, it aims to validate the calculations when workers are protected with shielding located between the patient and the operator. The experiments are performed in a calibration laboratory and measurements are gathered using Thermo EPD and Mirion DMC personal active dosemeters. Calculation efficiency of the fast Monte Carlo codes is approximately four orders of magnitude greater than for a standard Monte Carlo code. Satisfactory agreement between measurements and calculations is shown.