Labdanum Resin from Cistus ladanifer L. as a Source of Compounds with Anti-Diabetic, Neuroprotective and Anti-Proliferative Activity.

Labdanum resin or "gum" can be obtained from Cistus ladanifer L. by two different extraction methods: the Zamorean and the Andalusian processes. Although its main use is in the fragrance and perfumery sectors, ethnobotanical reports describe its use for medicinal purposes in managing hyperglycemia and mental illnesses. However, data concerning the bioactivities and pharmacological applications are scarce. In this work, it was found that the yield of labdanum resin extracted by the Andalusian process was 25-fold higher than the Zamorean one. Both resins were purified as absolutes, and the Andalusian absolute was purified into diterpenoid and flavonoid fractions. GC-EI-MS analysis confirmed the presence of phenylpropanoids, labdane-type diterpenoids, and methylated flavonoids, which are already described in the literature, but revealed other compounds, and showed that the different extracts presented distinct chemical profile. The potential antidiabetic activity, by inhibition of α-amylase and α-glucosidase, and the potential neuroprotective activity, by inhibition of acetylcholinesterase, were investigated. Diterpenoid fraction produced the higher α-amylase inhibitory effect (~30% and ~40% at 0.5 and 1 mg/mL, respectively). Zamorean absolute showed the highest α-glucosidase inhibitory effect (~14% and ~24%, at 0.5 and 1 mg/mL, respectively). Andalusian absolute showed the highest acetylcholinesterase inhibitory effect (~70% and ~75%, at 0.5 and 1 mg/mL, respectively). Using Caco-2 and HepG2 cell lines, Andalusian absolute and its purified fractions showed moderate cytotoxic/anti-proliferative activity at 24 h exposure (IC50 = 45-70 µg/mL, for Caco-2; IC50 = 60-80 µg/mL, for HepG2), whereas Zamorean absolute did not produce cytotoxicity (IC50 ≥ 200.00 µg/mL). Here we show, for the first time, that labdanum resin obtained by the Andalusian process, and its fractions, are composed of phytochemicals with anti-diabetic, neuroprotective and anti-proliferative potential, which are worth investigating for the pharmaceutical industry. However, toxic side-effects must also be addressed when using these products by ingestion, as done traditionally.

MRI Evaluation of Patients Before and After Interventions for Benign Prostatic Hyperplasia: An Update.

Transurethral resection of the prostate is the most commonly performed procedure for the management of patients with lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH). However, in recent years, various minimally invasive surgical therapies have been introduced to treat BPH. These include laser-based procedures such as holmium laser enucleation of the prostate and photoselective vaporization of the prostate as well as thermal ablation procedures such as water vapor thermal therapy (Rezum), all of which result in volume reduction of periurethral prostatic tissue. In comparison, a permanent metallic device (UroLift) can be implanted to pull open the prostatic urethra without an associated decrease in prostate size, and selective catheter-directed prostate artery embolization results in a global decrease in prostate size. The goal of this article is to familiarize radiologists with the underlying anatomic changes that occur in BPH as visualized on MRI and to describe the appearance of the prostate on MRI performed after these procedures. Complications encountered on imaging after these procedures are also discussed. Although MRI is not currently used in the routine preprocedural evaluation of BPH, emerging data support a role for MRI in predicting postprocedure outcomes.

Alpha-1 antitrypsin deficiency hidden in allegedly normal variants.

INTRODUCTION: Rare variants of Alpha-1 antitrypsin (AAT) deficiency (AATD) have been described by the Spanish registry of patients with AATD. The great majority of these rare variants are Mmalton alleles and many recent case series of them have been identified in the Canary Islands. The objective of this study was to analyze the distribution of Mmalton mutations in a Canarian population previously studied for the most common deficient alleles, namely PI*S (S) and PI*Z (Z), with PI*M (M) being the normal variant. METHODS: A cross-sectional study of 648 patients with allergic asthma was carried out. Mmalton mutation of the SERPINA1 gene was assayed by real-time PCR. RESULTS: Of the 648 patients, 3 (0.46%) were carriers of a Mmalton allele. All of them had low levels of AAT (53.9 mg/dL, 90 mg/dL, and 61 mg/dL, respectively) and were asymptomatic, showing normal lung function, radiological images, and levels of hepatic transaminases. CONCLUSION: In conclusion, although the most frequent AATD genotypes are Z and S alleles, it is important to consider other rare variants, particularly when low AAT serum levels are observed. Although individuals with the Mmalton mutation usually have a heterogenous clinical presentation and very low levels of AAT, all the patients in this study were asymptomatic.

Life-threatening idiopathic intracranial hypertension: the role of venous sinus stenting.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a clinical syndrome characterised by raised intracranial pressure with no discernible aetiology. It is relatively rare in children and its demographic features may differ from those of adults. The relationship between IIH and venous sinus stenosis (VSS) is well known. As VSS plays an important role in the pathophysiology, treatments have been developed aimed at improving venous blood outflow in refractory IIH. In the last two decades, venous sinus stenting has emerged as a treatment option in cases where stenosis is documented. METHODS AND RESULTS: The scientific literature on paediatric cases of IIH and its treatment with venous sinus stenting was analysed. We present the case of a 6-year-old girl with a life-threatening presentation of IIH, who was treated with transverse sinus stenting and a lumboperitoneal shunt. We summarise the characteristic of paediatric stenting cases reported and review the literature focusing on the main aspects of venous sinus stenting. CONCLUSION: VSS stenting could be a treatment tool for the acute presentation of IIH with severe symptoms and VSS plus an elevated trans-stenotic pressure gradient. However, in some cases, additional surgical treatment may be necessary.

Polyphasic identification of Penicillium spp. isolated from Spanish semi-hard ripened cheeses.

Fifteen samples of semi-hard ripened cheeses, both spoiled (10) and unspoiled (5), and obtained from cheese factories located in Northwest of Spain, were analysed by a dilution plating technique and direct sampling. A total of 32 isolates were identified at species level by a polyphasic approach (phenotypic characterization, partial extrolite analysis and molecular identification). Most isolates (65.6%) belonged to the species P. commune; other species found were P. solitum, P. chrysogenum, P. nordicum, P. expansum and P. cvjetkovicii. All of the P. commune isolates were able to produce cyclopiazonic acid, while the P. nordicum and the P. expansum isolates were producers of ochratoxin A and patulin respectively. Despite this, the role of P. commune as beneficial fungi in cheese ripening should be investigated. Molecular identification based on BenA sequence analysis was able to identify the majority of isolates. The three mycotoxins investigated can be considered key for identification. The polyphasic approach seems to be a very valuable tool for identification of isolates of this complex genus.

Combining evolutionary and metabolic engineering in Rhodosporidium toruloides for lipid production with non-detoxified wheat straw hydrolysates.

Improving the yield of carbohydrate to lipid conversion and lipid productivity are two critical goals to develop an economically feasible process to commercialize microbial oils. Lignocellulosic sugars are potential low-cost carbon sources for this process but their use is limited by the toxic compounds produced during biomass pretreatment at high solids loading, and by the pentose sugars (mainly xylose) which are not efficiently metabolized by many microorganisms. Adaptive laboratory evolution was used to select a Rhodosporidium toruloides strain with robust growth in non-detoxified wheat straw hydrolysates, produced at 20% solids loading, and better xylose consumption rate. An arabinose-inducible cre-lox recombination system was developed in this evolved strain that was further engineered to express a second copy of the native DGAT1 and SCD1 genes under control of the native xylose reductase (XYL1) promoter. Fed-batch cultivation of the engineered strain in 7-L bioreactors produced 39.5 g lipid/L at a rate of 0.334 g/Lh-1 and 0.179 g/g yield, the best results reported in R. toruloides with non-detoxified lignocellulosic hydrolysates to date.

[The Family Doctor and Nurse Program: development of the health care model in CubaO Programa de Médicos e Enfermeiras da Família: desenvolvimento do modelo de saúde em Cuba]. / El Programa del médico y enfermera de la familia: desarrollo del modelo de atención médica en Cuba.

The Cuban family medicine model has been developed, for more than three decades, as the third model of medical care of the revolutionary period in Cuba. It is the complete expression of the application of the primary health care strategy. However, it is still possible to improve the organization, quality and efficiency of health services in the first level of health care. The objective of this article is to describe the model, its singularities, distinctive elements, main achievements, and challenges. A documentary review was made from journal articles, books and official documents of the Ministry of Public Health of Cuba on the creation and development of the model; documents were selected and analyzed by experts for the preparation of this report. Conceptual elements of the model are presented, as well as indicators supporting the information. The main characteristics of family medicine in Cuba, its fundamental achievements, and challenges are presented. Based on its results, Cuba's family medicine model is a reference for the Region of the Americas. It is still a model in development, however, perfectible and susceptible to transformations to face new challenges, more importantly to renew the model keeping and strengthening the foundational ideas of the program.

O modelo cubano de medicina familiar foi desenvolvido, há mais de três décadas, como o terceiro modelo de assistência médica do período revolucionário em Cuba. É a expressão mais completa da aplicação da estratégia de atenção primária à saúde. Ainda mostra potencial de melhoria na organização, qualidade e eficiência dos serviços de saúde no primeiro nível de cuidados de saúde. O objetivo essencial deste trabalho é descrever o modelo, suas singularidades, elementos distintivos, principais conquistas, e desafios. Para isso, foi feita uma revisão documental em artigos de revistas, livros e documentos oficiais do Ministério da Saúde Pública de Cuba sobre a criação e desenvolvimento do modelo, selecionados e analisados por especialistas para a elaboração deste relatório. Os elementos conceituais do modelo são apresentados, bem como indicadores que suportam a informação. Identificamos as principais características da medicina familiar em Cuba, suas conquistas fundamentais, e desafios. Com base em seus resultados, conclui-se que o modelo de medicina familiar de Cuba é uma referência para a Região das Américas. Ainda é um modelo em desenvolvimento, perfeitável e susceptível a transformações para enfrentar novos desafios, o maior dos quais será renovar o modelo com a manutenção e fortalecimento das idéias fundamentais do programa.

Quantitative Variation of Flavonoids and Diterpenes in Leaves and Stems of Cistus ladanifer L. at Different Ages.

The compounds derived from secondary metabolism in plants perform a variety of ecological functions, providing the plant with resistance to biotic and abiotic factors. The basal levels of these metabolites for each organ, tissue or cell type depend on the development stage of the plant and they may be modified as a response to biotic and/or abiotic stress. As a consequence, the resistance state of a plant may vary in space and time. The secondary metabolites of Cistus ladanifer have been quantified in leaves and stems throughout autumn, winter, spring and summer, and at different ages of the plant. This study shows that there are significant differences between young leaves, mature leaves and stems, and between individuals of different ages. Young leaves show significantly greater synthesis of flavonoids and diterpenes than mature leaves and stems, with a clear seasonal variation, and the differences between leaves at different growth stages and stems is maintained during the quantified seasons. With respect to age, specimens under one year of age secreted significantly lower amounts of compounds. The variation in the composition of secondary metabolites between different parts of the plant, the season and the variations in age may determine the interactions of Cistus ladanifer with the biotic and abiotic factors to which it is exposed.

Intra-Population Variation of Secondary Metabolites in Cistus ladanifer L.

In previous studies, secondary metabolites in the leaf exudate of Cistus ladanifer, specifically aglycone flavonoids and diterpenes, were demonstrated to play an ecophysiological role. They protect against ultraviolet radiation, have antiherbivore activity, and are allelopathic agents. Their synthesis in the plant was also found to vary quantitatively and qualitatively in response to various environmental factors. In view of these findings, the present work was designed to clarify whether within a single population there are differences among individuals subject to the same environmental conditions. To this end, we analyzed the leaves of 100 individuals of C. ladanifer. The results showed the existence of intrapopulational variation, since, although all the individuals had the same composition of secondary chemistry, the amounts were different. The individuals of a given population of C. ladanifer differ from each other even when growing under similar conditions. According to the ammount of flavonoids and diterpenes observed in each individual, it was possible to distinguish four different groups of individuals. Most individuals, evenly distributed within the population, had low concentrations of the studied compounds, whilst other individuals synthesized greater amounts and were randomly distributed among the former. Given the functions of flavonoids and diterpenes in this species, the quantified intra-population variation may involve greater plasticity for the species in the face of environmental changes.

Determining the mineral composition in Cucurbita pepo fruit using near infrared reflectance spectroscopy.

BACKGROUND: Efforts through conventional breeding to improve the mineral content in horticultural crops have not always been successful mainly due to the fact that standard analytical methods are both costly and time-consuming. We investigated the feasibility of applying near infrared reflectance spectroscopy (NIRS) to the estimation of essential mineral composition in the skin and flesh of summer squash fruits (Cucurbita pepo subsp. pepo) using a 200-sample set from diverse morphotypes. RESULTS: The coefficients of determination in the external validation (R(2) VAL) obtained for the skin and flesh of the fruit were: total mineral content, 0.84 and 0.70; P, 0.74 and 0.62; K, 0.83 and 0.67; Ca, 0.57 and 0.60; Mg, 0.78 and 0.45; Fe, 0.78 and 0.65; Cu, 0.67 and 0.66; Mn, 0.67 and 0.64; Zn, 0.80 and 0.79 and Na, 0.33 and 0.33; respectively. CONCLUSIONS: NIRS combined with different spectral transformations by modified partial least-squares (MPLS) regression has shown to be useful in determining the mineral composition of summer squash fruit, being a fast and low-cost analytical technique. Components such as chlorophyll, starch and lipids were used by MPLS for modelling the predicting equations. The promotion of micronutrient-rich summer squash varieties could have a significant long-term beneficial impact on the health of mineral deficient human populations.

[Human resources in the National Health System. Medical education. SESPAS Report 2024]. / Recursos humanos del Sistema Nacional de Salud. Formación. Informe SESPAS 2024.

The problems posed by medical education in Spain are diverse. This paper analyzes the system currently used to select candidates who will be admitted to a public faculty of medicine in Spain and some issues arising from the unprecedented increase in both public and private medical schools in our country. The importance of generic competencies in today's medicine and the need to return to a core design in specialist training are other aspects that are discussed. The degree of development of advanced accreditation diplomas and areas of specific competence is also subject to analysis. Finally, the authors emphasize the importance of continuous professional development and the idea of professional recertification as a system that guarantees patients the quality of the care they receive.

Angiographic patterns in spontaneous coronary artery dissection: novel diagnostic insights.

INTRODUCTION: Spontaneous coronary artery dissection (SCAD) is a rare but well-recognized cause of acute coronary syndrome, especially important in women. Invasive coronary angiography (ICA) is the fundamental diagnostic technique for the confirmation of SCAD. Knowing the angiographic patterns suggestive of SCAD is essential for the correct identification of patients with this entity. AREAS COVERED: In this narrative review, the main angiographic characteristics of SCAD lesions as detected by ICA are presented and discussed. EXPERT OPINION: In addition to the specific angiographic classification of SCAD, several authors have described complementary angiographic patterns suggestive of SCAD. Knowledge and correct identification of these angiographic patterns is essential for the correct diagnosis of patients with clinical suspicion of SCAD.

Exploring the sheep (Ovis aries) immunoglobulin repertoire by next generation sequencing.

Next-generation sequencing (NGS) has revolutionized the way we determine the antibody repertoires encoded by B cells in the blood or lymphoid organs and transformed our understanding of adaptive immune responses in many species. Sheep (Ovis aries) have been widely used as a host for therapeutic antibody production since the early 1980s, however, little is known about their immune repertoires or immunological processes affecting the antibody generation. The objective of this study was to employ NGS for a comprehensive analysis of immunoglobulin heavy and light chain repertoires in four healthy sheep. We obtained > 90 % complete antibody sequences and nearly 130,000, 48,000 and 218,000 unique CDR3 reads for the heavy chain (IGH), kappa chain (IGK), and lambda chain (IGL) loci, respectively. Consistent with other species, we observed biased usage of germline variable (V), diversity (D) and joining (J) genes in the heavy and kappa loci, but not in the lambda loci. Moreover, the enormous diversity of CDR3 sequences was observed through sequence clustering and convergent recombination. These data will build a foundation for future studies investigating immune repertoires in health and disease as well as contribute to further refinement of ovine-derived therapeutic antibody drugs.

Isolation and characterization of new bacteriophages active against Clostridium tyrobutyricum and their role in preventing the late blowing defect of cheese.

Lytic bacteriophages (phages) offer a great potential as biocontrol agents for spoilage Clostridium tyrobutyricum, responsible for butyric acid fermentation in semi-hard and hard ripened cheeses, resulting in late gas blowing defect. With this aim, we have isolated, identified and characterized new lytic phages of C. tyrobutyricum, and have evaluated their efficacy to control cheese late blowing by adding them to manufacture milk. Silage, soil, milk and cheese from dairy farms were screened for anti-clostridial phages, obtaining 96 isolates active against C. tyrobutyricum. According to host range, source and plaque morphology, we obtained 20 phage profiles, 8 of them (represented by phages FA3, FA21, FA29, FA52, FA58, FA67, FA70 and FA88) showing a wider host range and high quality lysis, which were further characterized. Selected isolates showed a non-contractile tail, belonging to the Siphoviridae family, and were grouped into 3 restriction profiles. Viable phages were detected after storage in sodium-magnesium buffer (SM buffer), skim milk and acidified skim milk (pH 5) for 7 d at 4 °C, 12 °C and 37 °C, although a decline in infectivity was observed in some cases. Good phage survival was also detected during semi-hard cheese manufacture and ripening (60 d), and cheese lactococci counts, pH, dry matter values, and volatile compounds were not affected by phage addition. In semi-hard cheese, phage FA67 impaired the early germination of C. tyrobutyricum spores and caused a significant decrease in clostridial vegetative cells counts at 14 d of ripening, delaying by 2 weeks the consumption of lactic acid, formation of butyric acid and appearance of late blowing symptoms, compared to the spoilt control cheese without the phage. This is the first report on the application of phage to control C. tyrobutyricum in cheese.

Real-Life Effectiveness of Mepolizumab in Refractory Chronic Rhinosinusitis with Nasal Polyps.

The aim of this study was to evaluate the efficacy of mepolizumab in patients affected by chronic rhinosinusitis with nasal polyps (CRSwNP) in real-life. A single-center retrospective observational study was conducted on severe CRSwNP patients treated with mepolizumab. Nasal endoscopic polyp score (NPS), visual analogue scale (VAS) symptom score, sinonasal outcome test (SNOT-22), asthma control test (ACT) score, fractional exhaled nitric oxide (FeNO), eosinophils blood cells and prednisone intake were assessed at baseline and after 6 months. A total of 55 patients were included; 49 patients (89%) presented with asthma; aspirin exacerbated respiratory disease (AERD) in 28 patients (51%). A statistically significant decrease in the SNOT-22 score was observed (median difference -63; 95% CI: -68; -58; p < 0.001) with median t0 76 and IQR (61;90) to t6 10 (5;15). A reduction in NPS, median t0 NPS 4; (IQR:4;6), median t6 NPS 1; (IQR:0;1) p < 0.001, was greater in patients with AERD. The median baseline VAS score was 6 (IQR:6;7) and the differences between t0 and t6 were statistically significant p < 0.001. Significant changes in blood eosinophils cells, median t0 500 cell/mcl (IQR:340;830), median t6 97 cell/mcl (IQR:60;160) p < 0.001, were greater in patients with AERD. Mepolizumab treatment effects have been demonstrated with significantly reduced symptoms, polyp scores, blood eosinophils and systemic corticosteroid use, resulting in an increased health-related quality of life in patients with severe CRSwNP, regardless of the presence or absence of asthma or AERD.

Genetic polymorphisms of the Wnt receptor LRP5 are differentially associated with trochanteric and cervical hip fractures.

Epidemiological studies suggest that cervical and trochanteric hip fractures have different pathogenesis. We tested the hypothesis that genetic factors have different influences on both types of fractures. Ten polymorphisms of genes known to play an important role in skeletal homeostasis [estrogen receptor alpha (ESR1), aromatase (CYP19A1), type I collagen (COL1A1), and lipoprotein receptor-related protein 5 (LRP5)] were analyzed in 471 Spanish patients with fragility hip fractures. Two polymorphisms of the LRP5 gene (rs7116604 and rs3781600) were associated with the type of fracture (P = 0.0085 and 0.0047, respectively). The presence of rare alleles at each locus was associated with trochanteric fractures over cervical fractures (OR = 1.7 in individuals with at least one rare allele at rs7116604 or rs3781600 loci in comparison with the common homozygotes). Considering individuals bearing the four common alleles as reference, the OR for trochanteric fractures was 1.6 in those with one or two rare alleles and 7.5 in those with three or four rare alleles (P for trend = 0.0074), which is consistent with an allele-dosage effect. There were no significant differences in the frequency distributions of the ESR1, CYP19A1, and COL1A1 genotypes between trochanteric and cervical fractures in either the original group or an extended group of 818 patients. These results suggest that LRP5 alleles influence the type of hip fractures. They support the view that different genetic factors are involved in cervical and trochanteric fractures, which should be taken into consideration in future genetic association studies.

Microchip electrophoresis with amperometric detection for a novel determination of phenolic compounds in olive oil.

The relevance of the development of microchip electrophoresis applications in the field of food analysis is considered in this work. A novel method to determine important phenolic compounds in extra virgin olive oil samples using a miniaturized chemical analysis system is presented in this paper. Three interesting phenolic compounds in olive oil and fruit (tyrosol, hydroxytyrosol and oleuropein glucoside) were studied by end-channel amperometric detection using a 100 µm gold wire as working electrode in glass microchip electrophoresis. The electrochemical behavior of these compounds was studied and the medium to carry out their detection was selected (0.1 M aqueous sulfuric acid). The best conditions for the separation were achieved in sodium tetraborate (10% methanol, pH 9.50) with different concentrations for the sample and the running buffer in order to allow the sample stacking phenomenon. The injection was carried out using 600 V for 3 s and the separation voltage was set at 1000 V. The quality of the method was evaluated through its analytical figures of merit and by its performance on real extra virgin olive oil samples. Determination of these compounds was carried out using the standard addition calibration method with good recoveries.

Simple and fast determination of phenolic compounds from different varieties of olive oil by nonaqueous capillary electrophoresis with UV-visible and fluorescence detection.

In this article, we proposed very simple procedures to analyze important phenolic compounds in olive oil samples from different olive varieties. A nonaqueous CE method has been employed. The main phenolic alcohols in virgin olive oil (tyrosol and hydroxytyrosol) and some among the most abundant secoiridoid aglycone derivatives (dialdehydic form of decarboxymethyl elenoic acid linked to hydroxytyrosol, an isomer of oleuropein aglycone and the dialdehydic form of decarboxymethyl elenoic acid linked to tyrosol) were determined by a direct injection into the capillary of the olive oil dissolved in 1-propanol 1:1 v/v. For the determination of compounds present at lower concentrations, a very simple liquid-liquid extraction method with ethanol has been proposed. The extraction was performed using a relationship 5:1 w/v olive oil/ethanol to achieve the necessary preconcentration of the analytes and the ethanolic extracts were directly injected into the capillary to obtain a very important time reduction. Good recoveries were obtained with both the procedures, using an internal standard. Finally, these procedures were applied to the analysis of these compounds in extra virgin olive oil samples from different varieties of olive.

Research Software vs. Research Data I: Towards a Research Data definition in the Open Science context.

Background: Research Software is a concept that has been only recently clarified. In this paper we address the need for a similar enlightenment concerning the Research Data concept. Methods: Our contribution begins by reviewing the Research Software definition, which includes the analysis of software as a legal concept, followed by the study of its production in the research environment and within the Open Science framework. Then we explore the challenges of a data definition and some of the Research Data definitions proposed in the literature. Results: We propose a Research Data concept featuring three characteristics: the data should be produced (collected, processed, analyzed, shared & disseminated) to answer a scientific question, by a scientific team, and has yield a result published or disseminated in some article or scientific contribution of any kind. Conclusions: The analysis of this definition and the context in which it is proposed provides some answers to the Borgman's conundrum challenges, that is, which Research Data might be shared, by whom, with whom, under what conditions, why, and to what effects. They are completed with answers to the questions: how? and where?