Mechanisms modulating foam cell formation in the arterial intima: exploring new therapeutic opportunities in atherosclerosis.

In recent years, the role of macrophages as the primary cell type contributing to foam cell formation and atheroma plaque development has been widely acknowledged. However, it has been long recognized that diffuse intimal thickening (DIM), which precedes the formation of early fatty streaks in humans, primarily consists of lipid-loaded smooth muscle cells (SMCs) and their secreted proteoglycans. Recent studies have further supported the notion that SMCs constitute the majority of foam cells in advanced atherosclerotic plaques. Given that SMCs are a major component of the vascular wall, they serve as a significant source of microvesicles and exosomes, which have the potential to regulate the physiology of other vascular cells. Notably, more than half of the foam cells present in atherosclerotic lesions are of SMC origin. In this review, we describe several mechanisms underlying the formation of intimal foam-like cells in atherosclerotic plaques. Based on these mechanisms, we discuss novel therapeutic approaches that have been developed to regulate the generation of intimal foam-like cells. These innovative strategies hold promise for improving the management of atherosclerosis in the near future.

[Penicillin allergy: A label that is not forever]. / Alergia a la penicilina: una etiqueta que no es para siempre.

Self-reported penicillin allergy is highly prevalent. Different studies estimate that 10% of the population is labeled as such. This label, confirmed or suspected, forces us to take precautions and replace the antibiotic treatment of choice (frequently beta-lactams) with other 2nd or 3rd choice alternatives with worse overall results: side effects, resistance, costs, etc. The penicillin allergy label, once placed, remains in the medical record. It is only confirmed in less than 5% of patients, either because it has been placed inappropriately or because over time the sensitivity decreases and may disappear. Penicillin Allergy Decision Rule -PEN-FAST- is a validated and simple clinical prediction rule that estimates the risk of presenting an allergic reaction. Its use, together with algorithms that involve primary care in the study and delabeling of low-risk patients, can change our clinical practice.

Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease after Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide: A Study on Behalf of the Spanish Hematopoietic Stem Cell Transplantation and Cellular Therapy Group (GETH).

Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication after both autologous and allogeneic hematopoietic stem cell transplantation (HSCT). However, its characterization after haploidentical HSCT (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) is scarce. This study aimed to describe characteristics and outcomes of patients with SOS/VOD after haplo-HSCT with PT-Cy. We conducted a retrospective study of 797 patients undergoing a haplo-HSCT with PT-Cy between 2007 and 2019 in 9 centers in Spain. SOS/VOD was defined according to modified Seattle, Baltimore, or revised European Society for Blood and Marrow Transplantation (EBMT) criteria. Severity was graded retrospectively according to revised EBMT severity criteria into 4 categories: mild, moderate, severe, and very severe. From a total of 797 haplo-HSCTs performed, 46 patients (5.77%) were diagnosed with SOS/VOD at a median of 19 days (range, 4 to 84 days) after transplantation. Based on revised EBMT severity criteria, the SOS/VOD cases were classified as mild (n = 4; 8.7%), moderate (n = 10; 21.7%), severe (n = 12; 26.1%), and very severe (n = 20; 43.5%). Overall, 30 patients (65%) achieved SOS/VOD complete response, 25 (83%) of whom were treated with defibrotide. Twenty patients (43%) died before day +100 post-HSCT. Death was attributed to SOS/VOD in 11 patients, and 5 patients died of other causes without resolution of SOS/VOD. The incidence of SOS/VOD after haplo-HSCT with PT-Cy was comparable to those reported after HLA-identical HSCT series. Most of the patients developed very severe SOS/VOD according to revised EBMT severity criteria. Despite a promising SOS/VOD complete response (CR) rate (65%), 100-day mortality remained high (43%), indicating that further improvement in the management of this potentially fatal complication is needed.

Positive impact of Distintivo Soludable on implementation of sun protection policies and practices in schools of Andalusia, Spain.

The incidence of skin cancer is increasing worldwide even though its main risk factor is preventable. This study evaluated the impact of the Distintivo Soludable pilot intervention on implementation of photoprotection policies and practices in preschool and primary schools in Andalusia, Spain. We completed two rounds of a Sun Protection Policies and Practices Survey (SPPPS) nine months apart. At baseline, 67 Andalusian schools earned a median score of 3/12 points (range 0-8; IQR: 2). Ten schools involved in Distintivo Soludable intervention group significantly increased their scores from 4 to 7.5/12 points (p = 0.014). We also detected a modest positive effect in 57 control group schools, an increase from 2 to 3 points (p = 0.002). This pilot study demonstrated that the main achievement of the Distintivo Soludable intervention was implementation of organizational policies regarding sun protection, an essential starting point for establishing positive attitudes toward sun protection in school communities.

Ecophysiological responses of Ostreopsis towards temperature: A case study of benthic HAB facing ocean warming.

Reports of the benthic dinoflagellate Ostreopsis spp. have been increasing in the last decades, especially in temperate areas. In a context of global warming, evidences of the effects of increasing sea temperatures on its physiology and its distribution are still lacking and need to be investigated. In this study, the influence of temperature on growth, ecophysiology and toxicity was assessed for several strains of O. cf. siamensis from the Bay of Biscay (NE Atlantic) and O. cf. ovata from NW Mediterranean Sea. Cultures were acclimated to temperatures ranging from 14.5 °C to 32 °C in order to study the whole range of each strain-specific thermal niche. Acclimation was successful for temperatures ranging from 14.5 °C to 25 °C for O. cf. siamensis and from 19 °C to 32 °C for O. cf. ovata, with the highest growth rates measured at 22 °C (0.54-1.06 d-1) and 28 °C (0.52-0.75 d-1), respectively. The analysis of cellular content of pigments and lipids revealed some aspects of thermal acclimation processes in Ostreopsis cells. Specific capacities of O. cf. siamensis to cope with stress of cold temperatures were linked with the activation of a xanthophyll cycle based on diadinoxanthin. Lipids (neutral reserve lipids and polar ones) also revealed species-specific variations, with increases in cellular content noted under extreme temperature conditions. Variations in toxicity were assessed through the Artemia franciscana bioassay. For both species, a decrease in toxicity was observed when temperature dropped under the optimal temperature for growth. No PLTX-like compounds were detected in O. cf. siamensis strains. Thus, the main part of the lethal effect observed on A. franciscana was dependent on currently unknown compounds. From a multiclonal approach, this work allowed for defining specificities in the thermal niche and acclimation strategies of O. cf. siamensis and O. cf. ovata towards temperature. Potential impacts of climate change on the toxic risk associated with Ostreopsis blooms in both NW Mediterranean Sea and NE Atlantic coast is further discussed, taking into account variations in the geographic distribution, growth abilities and toxicity of each species.

3-Acetylpyridine-induced ataxic-like motor impairments are associated with plastic changes in the Purkinje cells of the rat cerebellum.

Ataxias are characterized by aberrant movement patterns closely related to cerebellar dysfunction. Purkinje cell axons are the sole outputs from the cerebellar cortex, and dysfunctional activity of Purkinje cells has been associated with ataxic movements. However, the synaptic characteristics of Purkinje cells in cases of ataxia are not yet well understood. The nicotinamide antagonist 3-acethylpyridine (3-AP) selectively destroys inferior olivary nucleus neurons so it is widely used to induce cerebellar ataxia. Five days after 3-AP treatment (65mg/kg) in adult male Sprague-Dawley rats, motor incoordination was revealed through BBB and Rotarod testing. In addition, in Purkinje cells from lobules V-VII of the cerebellar vermis studied by the Golgi method, the density of dendritic spines decreased, especially the thin and mushroom types. Western blot analysis showed a decrease in AMPA and PSD-95 content with an increase of the α-catenin protein, while GAD-67 and synaptophysin were unchanged. Findings suggest a limited capacity of Purkinje cells to acquire and consolidate afferent excitatory inputs and an aberrant, rigid profile in the movement-related output patterns of Purkinje neurons that likely contributes to the motor-related impairments characteristic of cerebellar ataxias.

Comparison of dehydration systems in quality and chemical effects on sunflower seeds.

The present work investigates the quality and the chemical effects of dehydration, using a novel dehydration system based on an electromagnetic induction and low pressures technique, comparing it with the thermo-solar drying system. High oleic sunflower seeds, which are an important oil seed crop, were used due to the fact that they have a special place in the food industry. The seed samples were exposed to electromagnetic induction and low pressures by 0.5 and 1 h, then several chemical characterizations were carried out, in the electrophoresis study, it was found that most proteins in the hull were degraded or denatured, some of them were lost during the time in the thermosolar dryer while in kernel keeps 94.9% of the concentration in control proteins. Otherwise, the electromagnetic induction dryer did not lose the most of proteins in the kernel keeping 99.1% in 0.5 h and 98.4% in 1 h, just degrading its concentration. Germination viability results did not show changes after 0.5 h in the electromagnetic fields, but they decreased in 1 h from 66 to 40% until the thermosolar method fell to 24% in 4 h, both analysis results change proportionally with the treatment time and moisture content and the amount of the oxygen.

Transient loss of Polycomb components induces an epigenetic cancer fate.

Although cancer initiation and progression are generally associated with the accumulation of somatic mutations1,2, substantial epigenomic alterations underlie many aspects of tumorigenesis and cancer susceptibility3-6, suggesting that genetic mechanisms might not be the only drivers of malignant transformation7. However, whether purely non-genetic mechanisms are sufficient to initiate tumorigenesis irrespective of mutations has been unknown. Here, we show that a transient perturbation of transcriptional silencing mediated by Polycomb group proteins is sufficient to induce an irreversible switch to a cancer cell fate in Drosophila. This is linked to the irreversible derepression of genes that can drive tumorigenesis, including members of the JAK-STAT signalling pathway and zfh1, the fly homologue of the ZEB1 oncogene, whose aberrant activation is required for Polycomb perturbation-induced tumorigenesis. These data show that a reversible depletion of Polycomb proteins can induce cancer in the absence of driver mutations, suggesting that tumours can emerge through epigenetic dysregulation leading to inheritance of altered cell fates.

Management of patients with endometriosis and infertility: laparoscopic treatment and spontaneous pregnancy rate.

OBJECTIVE: To evaluate factors involved in spontaneous pregnancy rate after surgery for endometriosis in patients with endometriosis and infertility. METHODS: This retrospective study spanned from 2014 to 2020 and included a follow-up period of two years of patients with endometriosis-related infertility who underwent laparoscopic surgery. Women aged 25 to 43 years with patent tubes, no/mild male factor and no other infertility factors were selected and grouped according to fertility management as follows: patients immediately prescribed ART (16.5%, ART-p); patients who chose not to undergo ART (83.5%) and achieved spontaneous pregnancy (71.8% SP-p); and patients who first chose not to undergo ART but had it subsequently (28.2%, NSP-p). RESULTS: A total of 200 patients were analyzed. Of the 167 patients who waited for spontaneous pregnancy, 71.8% achieved it. We observed a tendency of higher endometriosis ASRM scores in the ART-p group compared with patients who waited for spontaneous pregnancy, and lower scores in individuals that achieved spontaneous pregnancy. When we looked at how long it took to achieve pregnancy, we found that individuals in the SP-p group achieved pregnancy in 5.7 months, while subjects in the NSP-p group took 1.8 times longer than their peers in the SP-p group (p<0.001). However, once prescribed ART, the individuals in the NSP-p group achieved pregnancy within a similar time when compared with subjects in the SP-p group. In order to identify individuals that might benefit from ART early on, we performed a multivariable analysis and developed a decision tree (81.3% accuracy and 53.3% sensitivity). CONCLUSIONS: The present results indicated that, after surgery, the majority of patients achieved spontaneous pregnancy. The decision tree proposed in this study allows the early identification of patients who might require ART, thus decreasing the time between surgery and pregnancy and improving overall outcomes.

Pine needle abortions in cattle due to consumption of Pinus ponderosa in Argentina: Case reports.

Two outbreaks of pine needle abortions in cattle are here reported for the first time in Argentina. The cases occurred in Chubut and Neuquén provinces in the Patagonia region, causing 29.6% and 9% of abortions in each herd respectively. In both outbreaks, the dams were in the last third of gestation, and, due to a period of cold, snow and lack of available forage, they gained access to Pinus ponderosa and Pinus contorta forests. No pathological lesions, serological, molecular, or microbiological evidence of infectious causes were observed in any of the six fetuses analyzed. Microhistological analysis of feces confirmed higher presence of fragments of Pinus spp. needles in the diet of affected dams than in that of non-affected ones (12.2 vs 3.0%). Moreover, toxicological analysis showed higher tetrahydroagathic acid in the sera of affected dams than in that of non-affected ones (10.05 vs 2.81 ppm). In addition, this acid was detected in different fetal fluids (3.6-8.1 ppm) of the six fetuses analyzed. Interestingly, isocupressic acid was detected only in needles of P. ponderosa, and its content was lower than that found in other areas of the world (0.31 and 0.5% in Chubut and Neuquén respectively). These results confirm that the consumption of P. ponderosa by dams could have been the cause of these abortion outbreaks, a fact that should be considered as differential diagnosis in abortions of cattle, especially in silvopastoral systems of Argentina.

Bocconia frutescens L. induces neurological defects in rat offspring.

Nearly 80% of the world's population trusts traditional medicine and plant-based drug compounds to improve health, and more than 50% of women who participated in a study have used herbal remedies during pregnancy. Bocconia frutescens L. is a plant native to tropical America, where infusion of its leaves has been widely used for the treatment of several gastrointestinal disorders. We have already shown that orogastric consumption of B. frutescens L. during the organogenesis period at concentrations equivalent to human consumption produces teratogenic effects in rats, but effects on progeny development have not yet been studied. In this study, we aimed to investigate the possible association between the consumption of B. frutescens L. at a dose equivalent to that consumed by humans and the neurological development of rat progeny. Pregnant Wistar rats were administered lyophilized B. frutescens L. extract at 300 mg/kg/day or vehicle via the orogastric route during the organogenesis period (gestation days 7-13). The physical development and sensory and motor maturation of their offspring during lactation were analyzed with a battery of reflex and physical tests. B. frutescens L. produced a significant delay in physical development and sensorimotor maturation, compared to the control group. Proton nuclear magnetic resonance spectroscopy analysis showed signals for both flavonoids and alkaloids in the B. frutescens L. extract. We conclude that the delay in physical and neurological development could be interpreted as alterations in the maturation of some neuronal circuitries induced by B. frutescens L.

Hybrid wind-solar energy resources mapping in the European Atlantic.

The complementarity of offshore wind and solar resources can enhance the energy output of a hybrid farm and reduce its variability relative to a stand-alone, conventional offshore wind farm. In this work offshore wind and solar resources are characterised and mapped in a large study area covering the European Atlantic, the North and Baltic Seas, and the Canary Islands. The intra-annual and overall variabilities of wind power density and solar irradiance are investigated, and their complementarity is evaluated on the basis of their correlation. Negatively correlated regions include the seas around Ireland and Great Britain, with vast wind resources (mean wind power density ~1500 Wm-2 off W Ireland) and comparatively limited solar resources (mean solar irradiance ~100 Wm-2). Positively correlated regions include notably the Canary Islands, with the highest values of solar irradiance in the study area (mean values of ~280 Wm-2). Two study sites are chosen for more detailed investigation - one with a negative correlation, off W Ireland; the other with a positive correlation, off the Canary Islands. Even in the positively correlated regions, it is found that the correlation coefficient is never large (always under 0.2), which signals an opportunity for reducing power output variability through hybrid or co-located wind-solar farms. This, along with the other advantages of hybrid or co-located wind-solar farms (optimised use of scarce marine space, shared electrical infrastructure, shared O&M crews and vessels, etc.), attests to their potential in the European Atlantic. This potential could be realised through new hybrid or co-located wind-solar farms, or by retrofitting floating solar PV into existing offshore wind farms.

Utility of artificial intelligence for detection of pneumothorax on chest radiopgraphs done after transthoracic percutaneous transthoracic biopsy guided by computed tomography.

OBJETIVE: To assess the ability of an artificial intelligence software to detect pneumothorax in chest radiographs done after percutaneous transthoracic biopsy. MATERIAL AND METHODS: We included retrospectively in our study adult patients who underwent CT-guided percutaneous transthoracic biopsies from lung, pleural or mediastinal lesions from June 2019 to June 2020, and who had a follow-up chest radiograph after the procedure. These chest radiographs were read to search the presence of pneumothorax independently by an expert thoracic radiologist and a radiodiagnosis resident, whose unified lecture was defined as the gold standard, and the result of each radiograph after interpretation by the artificial intelligence software was documented for posterior comparison with the gold standard. RESULTS: A total of 284 chest radiographs were included in the study and the incidence of pneumothorax was 14.4%. There were no discrepancies between the two readers' interpretation of any of the postbiopsy chest radiographs. The artificial intelligence software was able to detect 41/41 of the present pneumothorax, implying a sensitivity of 100% and a negative predictive value of 100%, with a specificity of 79.4% and a positive predictive value of 45%. The accuracy was 82.4%, indicating that there is a high probability that an individual will be adequately classified by the software. It has also been documented that the presence of Port-a-cath is the cause of 8 of the 50 of false positives by the software. CONCLUSIONS: The software has detected 100% of cases of pneumothorax in the postbiopsy chest radiographs. A potential use of this software could be as a prioritisation tool, allowing radiologists not to read immediately (or even not to read) chest radiographs classified as non-pathological by the software, with the confidence that there are no pathological cases.

Vitamin D and risk of developing type 2 diabetes in the SUN project: a prospective cohort study.

PURPOSE: Vitamin D deficiency has been associated with multiple chronic diseases, including metabolic disorders such as insulin resistance and type 2 diabetes (T2D). The aim of the study was to analyze the association between validated predicted serum vitamin D status and the risk of developing T2D in a large prospective cohort based on a Mediterranean population. METHODS: The SUN project is a prospective and dynamic Spanish cohort that gathers university graduates who have answered lifestyle questionnaires, including a validated Food Frequency Questionnaire. The association between predicted serum vitamin D and the risk of T2D was assessed through Cox regression models according to quartiles (Q) of predicted vitamin D at baseline. The models were adjusted for potential confounders and sensitivity analyses were performed to ensure the robustness of our findings. RESULTS: Our study included a total of 18,594 participants and after a total follow-up of 238,078 person-years (median follow-up of 13.5 years), 209 individuals were diagnosed with incident T2D. We found a significant inverse association between predicted levels of serum vitamin D and the risk of developing T2D, after adjusting for potential confounders and performing different sensitivity analyses (hazard ratio Q4 vs. Q1: 0.48, 95% CI 0.26-0.88; p for trend = 0.032). CONCLUSION: The outcomes suggest that higher levels of vitamin D at baseline may be associated with a reduced risk of developing T2D.

Effect of pre-season and in-season training on anthropometric variables, somatotype, body composition and body proportion in elite basketball players.

The aims of the study were: 1) to evaluate the changes in anthropometric variables, body composition, somatotype and body proportions of elite basketball players throughout the pre-season period; 2) to evaluate the changes in anthropometric variables, body composition, somatotype and body proportions of elite basketball players throughout the in-season period; and 3) to observe if the age and position influenced the variables analyzed. A total of 17 players belonging to the men's ACB league team competing in the Euroleague (age = 23.42 ± 5.28 years-old) participated in the study. The players underwent an anthropometric measurement before and after the pre-season, as well as four evaluations throughout the in-season. Anthropometric indices, somatotype components according to Heath and Carter, and adiposity were calculated. The results show that during the pre-season, body mass, BMI, sum of 6 and 8 skinfolds, waist/hip ratio, adipose tissue (kg), adipose tissue percentage, and endomorphy decreased, while ectomorphy increased. However, no significant changes were found in the variables analyzed throughout the season; except for endomorphy, which increased along the in-season. Playing position and age did not have a significant influence on the changes in the anthropometric variables throughout the pre-season and the in-season. In conclusion, while changes in the anthropometric variables in the pre-season were observed, these remained the same during the in-season.

Association between socioeconomic status and hospitalisation requirement in older patients attended at the emergency department: A retrospective cohort study.

INTRODUCTION AND OBJECTIVE: A low socioeconomic status (SES) has been associated with poor health results. The present study aimed to investigate if SES of older patients attending the emergency department is associated with the use of healthcare resources and outcomes. PATIENTS AND METHODS: Observational, retrospective study including consecutive patients 65 years or older admitted to the emergency department. Variables at baseline, index episode, and follow-up were recorded. SES was measured using an indirect theoretical index and patients were categorised into two groups according to whether they lived in a neighbourhood with a low or high SES. Primary outcomes included hospitalisation after the emergency department visit and prolonged hospitalisation (>7 days) at index episode. Secondary outcomes included emergency department re-consultant and hospital admission in the following 3 months after the index episode, and all-cause mortality after long-term follow-up. Logistic regression and cumulative hazards regression models were used to investigate associations between SES and outcomes. RESULTS: The cohort included 553 patients (80 years [73-85], 50.5% female, 55.9% with low SES). After the emergency department visit, 234 patients (42.3%) required hospital admission. A low SES was inversely associated with hospitalisation with an adjusted odds ratio=0.654 (95% CI 0.441-0.970). Among hospitalised patients, a low SES was associated with prolonged hospitalisation (adjusted odds ratio=2.739; 95% CI 1.470-5.104). Follow-up outcomes, including all-cause mortality, were not associated with SES. CONCLUSIONS: Older patients living in more deprived urban areas were hospitalised less often after emergency department care, but hospital stays were longer. Understanding the effect of social determinants in healthcare use is mandatory to tailor resources to patient needs.

Clinical practice guidelines for the diagnosis and management of Charcot-Marie-Tooth disease.

INTRODUCTION: Charcot-Marie-Tooth disease (CMT) is classified according to neurophysiological and histological findings, the inheritance pattern, and the underlying genetic defect. The objective of these guidelines is to offer recommendations for the diagnosis, prognosis, follow-up, and treatment of this disease in Spain. MATERIAL AND METHODS: These consensus guidelines were developed through collaboration by a multidisciplinary panel encompassing a broad group of experts on the subject, including neurologists, paediatric neurologists, geneticists, physiatrists, and orthopaedic surgeons. RECOMMENDATIONS: The diagnosis of CMT is clinical, with patients usually presenting a common or classical phenotype. Clinical assessment should be followed by an appropriate neurophysiological study; specific recommendations are established for the parameters that should be included. Genetic diagnosis should be approached sequentially; once PMP22 duplication has been ruled out, if appropriate, a next-generation sequencing study should be considered, taking into account the limitations of the available techniques. To date, no pharmacological disease-modifying treatment is available, but symptomatic management, guided by a multidiciplinary team, is important, as is proper rehabilitation and orthopaedic management. The latter should be initiated early to identify and improve the patient's functional deficits, and should include individualised exercise guidelines, orthotic adaptation, and assessment of conservative surgeries such as tendon transfer. The follow-up of patients with CMT is exclusively clinical, and ancillary testing is not necessary in routine clinical practice.