Seasonal and Morphology Effects on Bioactive Compounds, Antioxidant Capacity, and Sugars Profile of Black Carrot (Daucus carota ssp. sativus var. atrorubens Alef.).

Black carrot (Daucus carota ssp. sativus var. atrorubens Alef.) is widely recognized for its bioactive compounds and antioxidant properties. The black carrot of Cuevas Bajas (Málaga) is a local variety characterized by a black/purple core, which differs from other black carrot varieties. Therefore, this autochthonous variety was characterized according to the root size and the harvesting season by means of a study of its antioxidant capacity analyzed by three methods, its total carotenoids content, and its sugars and phenolic compounds profile by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-MS). A total of 20 polyphenolic compounds were quantified in 144 samples analyzed. The anthocyanidins group was observed to be the most abundant, followed by the hydroxycinnamic acids group. Moreover, pelargonidin 3-sambubioside was observed in black carrot for the first time. The medium-sized carrots presented the highest content of phenolic compounds, largely due to their significantly higher anthocyanidins content. Comparatively, the small carrots showed a higher content of simple sugars than the large ones. Regarding the influence of season, significantly higher quantities of glucose and fructose were observed in the late-season carrots, while sucrose was the main sugar in early-season samples. No significant differences were observed in the total carotenoid content of black carrot.

WLB-87848, a Selective σ1 Receptor Agonist, with an Unusually Positioned NH Group as Positive Ionizable Moiety and Showing Neuroprotective Activity.

The synthesis and pharmacological activity of a new series of thieno[2,3-d]pyrimidin-4(3H)-one derivatives as sigma-1 receptor (σ1R) ligands are reported. A hit from a high-throughput screening program was evolved into a highly potent and selective σ1R agonist (14qR) that contains a free NH group as positive ionizable moiety, not fulfilling the usual pharmacophoric features of the σ1R. The compound shows good physicochemical and ADMET characteristics, displays an agonist profile in the binding immunoglobulin protein/σ1R association assay, induces neuron viability in an in vitro model of ß-amyloid peptide intoxication, and presents positive results against recognition memory impairment induced by hippocampal injection of Aß peptide in rats after oral treatment, altogether making 14qR (WLB-87848) an interesting candidate for neuroprotection.

Improved lipid-lowering treatment and reduction in cardiovascular disease burden in homozygous familial hypercholesterolemia: The SAFEHEART follow-up study.

AIM: We aimed to describe clinical and genetic characteristics, lipid-lowering treatment and atherosclerotic cardiovascular disease (ASCVD) outcomes over a long-term follow-up in homozygous familial hypercholesterolemia (HoFH). METHODS: SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is a long-term study in molecularly diagnosed FH. Data analyzed in HoFH were prospectively obtained from 2004 until 2022. ASCVD events, lipid profile and lipid-lowering treatment were determined. RESULTS: Thirty-nine HoFH patients were analyzed. The mean age was 42 ± 20 years and nineteen (49%) were women. Median follow-up was 11 years (IQR 6,18). Median age at genetic diagnosis was 24 years (IQR 8,42). At enrolment, 33% had ASCVD and 18% had aortic valve disease. Patients with new ASCVD events and aortic valve disease at follow-up were six (15%), and one (3%), respectively. Median untreated LDL-C levels were 555 mg/dL (IQ 413,800), and median LDL-C levels at last follow-up was 122 mg/dL (IQR 91,172). Most patients (92%) were on high intensity statins and ezetimibe, 28% with PCSK9i, 26% with lomitapide, and 23% with lipoprotein-apheresis. Fourteen patients (36%) attained an LDL-C level below 100 mg/dL, and 10% attained an LDL-C below 70 mg/dL in secondary prevention. Patients with null/null variants were youngers, had higher untreated LDL-C and had the first ASCVD event earlier. Free-event survival is longer in patients with defective variant compared with those patients with at least one null variant (p=0.02). CONCLUSIONS: HoFH is a severe life threating disease with a high genetic and phenotypic variability. The improvement in lipid-lowering treatment and LDL-C levels have contributed to reduce ASCVD events.

Impact of Pleural Lavage Cytology Positivity on Early Recurrence After Surgery for Non-Small Cell Lung Cancer / Impacto de la positividad de la citología del lavado pleural en la recurrencia temprana después de la cirugía por cáncer de pulmón de células no pequeñas

Objective: The aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). Methods: This is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. Results: Overall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06–2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04–2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14–2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27–3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25–16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25–5.36, p<0.001). Conclusions: Positive pleural lavage cytology was found to be the strongest predictor of early recurrence.(AU)

Impact of Pleural Lavage Cytology Positivity on Early Recurrence After Surgery for Non-Small Cell Lung Cancer.

OBJECTIVE: The aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). METHODS: This is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. RESULTS: Overall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06-2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04-2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14-2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27-3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25-16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25-5.36, p<0.001). CONCLUSIONS: Positive pleural lavage cytology was found to be the strongest predictor of early recurrence.

Towards Multitargeted Ligands as Pain Therapeutics: Dual Ligands of the Cavα2δ-1 Subunit of Voltage-Gated Calcium Channel and the µ-Opioid Receptor.

The synthesis and pharmacological activity of a new series of dual ligands combining activities towards the α2δ-1 subunit of voltage-gated calcium channels (Cavα2δ-1) and the µ-opioid receptor (MOR) as novel pain therapeutics are reported. A careful exploration of the pharmacophores related to both targets, which in principle had few common characteristics, led to the design of novel compounds exhibiting both activities. The construction of the dual ligands started from published Cavα2δ-1 ligands, onto which MOR ligand pharmacophoric elements were added. This exercise led to new amino-acidic substances with good affinities on both targets as well as good metabolic and physicochemical profiles and low potential for drug-drug interactions. A representative compound, (2S,4S)-4-(4-chloro-3-(((cis)-4-(dimethylamino)-4-phenylcyclohexyl)methyl)-5-fluorophenoxy)pyrrolidine-2-carboxylic acid, displayed promising analgesic activities in several in vivo pain models as well as a reduced side-effect profile in relation to morphine.

Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia: A multi-national study.

Objectives: Individuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline. Methods: We pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1-100, 101-400, >400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD). Results: Ninety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1-100, 160 (16%) had CAC 101-400, and 99 (10%) had CAC >400. Compared to males, female patients were more likely to have CAC=0 (48% [n = 262] vs 35% [n = 161]) and no plaque on CTA (39% [n = 215] vs 26% [n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1-100 (8% [n = 15] vs 18% [n = 26]), CAC 101-400 (32% [n = 22] vs 40% [n = 36]), and CAC >400 (52% [n = 16] vs 65% [n = 44]). Female patients aged 50-59 years were less likely to have obstructive CAD in CAC >400 (55% [n = 6] vs 70% [n = 19]). Conclusion: In this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population.

Genetic continuity and change among the Indigenous peoples of California.

Before the colonial period, California harboured more language variation than all of Europe, and linguistic and archaeological analyses have led to many hypotheses to explain this diversity1. We report genome-wide data from 79 ancient individuals from California and 40 ancient individuals from Northern Mexico dating to 7,400-200 years before present (BP). Our analyses document long-term genetic continuity between people living on the Northern Channel Islands of California and the adjacent Santa Barbara mainland coast from 7,400 years BP to modern Chumash groups represented by individuals who lived around 200 years BP. The distinctive genetic lineages that characterize present-day and ancient people from Northwest Mexico increased in frequency in Southern and Central California by 5,200 years BP, providing evidence for northward migrations that are candidates for spreading Uto-Aztecan languages before the dispersal of maize agriculture from Mexico2-4. Individuals from Baja California share more alleles with the earliest individual from Central California in the dataset than with later individuals from Central California, potentially reflecting an earlier linguistic substrate, whose impact on local ancestry was diluted by later migrations from inland regions1,5. After 1,600 years BP, ancient individuals from the Channel Islands lived in communities with effective sizes similar to those in pre-agricultural Caribbean and Patagonia, and smaller than those on the California mainland and in sampled regions of Mexico.

Impact of conducting a genetic study on the management of familial hypercholesterolemia.

BACKGROUND: Clinically diagnosed familial hypercholesterolemia (FH) may require a genetic test (GT) to confirm diagnosis. GT availability/accessibility is resource-dependent and usually restricted to specialized clinics. While GT has a diagnostic value, it has not yet defined its impact on long-term management and prognosis of FH. OBJECTIVE: The aim was to identify the clinical characteristics associated with the request for a GT in suspected heterozygous FH. METHODS: Retrospective study including adult patients with clinically suspected to be FH. Positive GT (GT+) was defined as having a pathogenic/likely pathogenic variant. Patients were stratified based on whether they had a genetic study conducted, and among those with a genetic study, according to those who did or did not have a GT+. RESULTS: From 4854 patients included, 3090 were performed a GT (GT+: 2113). Median follow-up: 6.2 years. A younger age, FH-related physical signs, premature coronary disease, higher low-density lipoprotein cholesterol (LDLc) and lower body mass index and triglycerides, associated higher odds of being conducted a genetic study. These patients had higher baseline LDLc (252 mg/dL vs. 211 mg/dL among clinically diagnosed patients) and experienced larger reductions over the follow-up (157.7 mg/dL vs. 113.5 mg/dL, respectively). A similar pattern was observed among patients with GT+ (vs. negative GT). LDLc target attainment was low but increased to 66-95% when a triple combination with statin/ezetimibe/proprotein convertase subtilisin kexin type 9-inhibitor was used. Cardiovascular events occurred in 3.2% and 3.1% of patients who conducted/not conducted a genetic study. Patients conducted a genetic analysis and those with GT+ tended to present the events earlier. CONCLUSIONS: Genetic study, vs. having a clinical-only diagnosis, impacts the management of FH. Cardiovascular prognosis was similar in both groups, perhaps as a result of the more intensive management of patients with a genetic study.

Control de la hipercolesterolemia en España: una misma situación con diferentes realidades autonómicas / Hypercholesterolaemia control in Spain: The same situation with different regional realities

Introducción y objetivos: La estrategia de prevención cardiovascular en las comunidades autónomas (CCAA) puede ser variable, al estar transferidas las competencias en sanidad. El objetivo del estudio fue conocer el control de la dislipemia y la terapia hipolipemiante utilizada en pacientes de alto/muy alto riesgo cardiovascular (RCV) por CCAA. Métodos: Estudio descriptivo, transversal, multicéntrico no aleatorizado basado en una metodología de consenso. Se recogió información de práctica clínica en 145 áreas sanitarias de 17CCAA españolas mediante reuniones presenciales y cuestionarios realizados a los 435 médicos participantes. Se recopilaron datos agregados no identificables de 10 pacientes dislipémicos consecutivos que cada participante hubiera visitado recientemente. Resultados: De los 4.010 pacientes compilados, 649 (16%) eran de alto y 2.458 (61%) de muy alto RCV. La distribución de los 3.107 pacientes de alto/muy alto RCV fue equilibrada entre regiones, pero hubo diferencias interterritoriales (p<0,0001) en la consecución del objetivo de cLDL<70 e <55mg/dl, respectivamente. Las estatinas de alta intensidad en monoterapia o combinadas con ezetimiba y/o inhibidores PCSK9 se utilizaron en el 44, el 21 y el 4% de los pacientes de alto RCV, mientras que en los de muy alto RCV era del 38, del 45 y del 6%, respectivamente. El uso de estas terapias hipolipemiantes a nivel nacional fue significativamente diferente entre regiones (p=0,0079). Conclusiones: A pesar de que la distribución de los pacientes de alto/muy alto RCV fue similar entre CCAA, se identificaron diferencias interterritoriales en el grado de consecución del objetivo terapéutico en cLDL y de utilización de la terapia hipolipemiante. (AU)

Introduction and objective: The cardiovascular prevention strategy by autonomous communities can be variable since the competences in health are transferred. The objective of the study was to determine the degree of dyslipidaemia control and the lipid-lowering pharmacological therapy used in patients at high/very high cardiovascular risk (CVR) by autonomous communities. Methods: Observational, cross-sectional, descriptive study based on a consensus methodology. Information on the clinical practice of 145 health areas belonging to 17 Spanish autonomous communities was collected through face-to-face meetings and questionnaires administered to the 435 participating physicians. Furthermore, aggregate non-identifiable data were compiled from 10 consecutive dyslipidaemic patients that each participant had recently visited. Results: Of the 4010 patients collected, 649 (16%) had high and 2458 (61%) very high CVR. The distribution of the 3107 high/very high CVR patients was balanced across regions, but there were inter-regional differences (P<.0001) in the achievement of target LDL-C <70 and <55mg/dL, respectively. High-intensity statins in monotherapy or in combination with ezetimibe and/or PCSK9 inhibitors were used in 44, 21 and 4% of high CVR patients, while in those at very high CVR it rose to 38, 45 and 6%, respectively. The use of these lipid-lowering therapies at national level was significantly different between regions (P=.0079). Conclusions: Even though the distribution of patients at high/very high CVR was similar between autonomous communities, inter-territorial differences were identified in the degree of achievement of LDL cholesterol therapeutic goal and use of lipid-lowering therapy. (AU)

Discovery of WLB-89462, a New Drug-like and Highly Selective σ2 Receptor Ligand with Neuroprotective Properties.

The synthesis and pharmacological activity of a new series of isoxazolylpyrimidines as sigma-2 receptor (σ2R) ligands are reported. Modification of a new hit retrieved in an HTS campaign allowed the identification of the compound WLB-89462 (20c) with good σ2R affinity (Ki = 13 nM) and high selectivity vs both the σ1R (Ki = 1777 nM) and a general panel of 180 targets. It represents one of the first σ2R ligands with drug-like properties, linked to a good physicochemical and ADMET profile (good solubility, no CYP inhibition, good metabolic stability, high permeability, brain penetration, and high oral exposure in rodents). Compound 20c shows neuroprotective activity in vitro and improves short-term memory impairment induced by hippocampal injection of amyloid ß peptide in rats. Together with the promising effects in the chronic models where 20c is currently being evaluated, these results pave the way toward its clinical development as a neuroprotective agent.

[Surgical management of primary spontaneous pneumothorax. A national survey of the Emerging Thoracic Surgery Group of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR)]. / Manejo quirúrgico del neumotórax espontáneo primario. Encuesta nacional del Grupo Emergente de Cirugía Torácica de la Sociedad Española de Neumología y Cirugía Torácica (SEPAR).

Introduction: In February 2022, the Emerging Thoracic Surgery Group of the Spanish Society of Pneumology and Thoracic Surgery initiated a multicenter study on the surgical management of primary spontaneous pneumothorax (PSP). As a preliminary step, this survey was developed with the aim of finding out the current situation in our country to specify and direct this project. Method: A descriptive study was carried out based on the results of this survey launched through the Google Docs® platform. The survey was sent to all active national thoracic surgeons, a total of 319. It consisted of 20 questions including demographic, surgical and follow-up data. Results: We obtained 124 responses (39% of all specialists and doctors in training in the national territory). The most consistent indications were: homolateral recurrence for 124 (100%), lack of resolution of the episode for 120 (96.7%), risk professions for 104 (84%) and bilateral pneumothorax for 93 (75%). The approach of choice for 100% of respondents was videothoracoscopy. Of these, 96 contemplated pulmonary resection of obvious lesions (77%). Regarding the pleurodesis technique, pleural abrasion was the technique most used by 70 respondents (56.7%) while 49 (40%) performed chemical pleurodesis with talc either alone or in combination with mechanical pleurodesis. Conclusions: While there is some consistency in some aspects of surgical management of PSP, this survey makes evident the variability in pleurodesis techniques applied among surgeons in our country.

Recomendaciones nutricionales en la prevención y tratamiento de la dislipemia aterogénica. Grupo de Trabajo Dislipemia Aterogénica, Sociedad Española de Arteriosclerosis / Nutritional recommendations in the prevention and treatment of atherogenic dyslipidemia

La incorporación de una dieta saludable, ejercicio físico regular junto a la supresión del hábito tabáquico son las primeras medidas para reducir el riesgo cardiovascular en los pacientes con dislipemia aterogénica. En estas personas se debe mejorar la calidad nutricional de su alimentación, sustituyendo los alimentos con mayor efecto aterogénico, por otros de efecto más saludable. Hay una sólida evidencia de que los patrones alimentarios de base vegetal, bajos en ácidos grasos saturados, colesterol y sodio, con un alto contenido en fibra, potasio y ácidos grasos insaturados, son beneficiosos y reducen la expresión de los factores de riesgo cardiovascular. Este documento se centra en el papel que juega la nutrición en la prevención y tratamiento de la dislipemia aterogénica, aportando las evidencias actuales que sirvan de herramienta a los profesionales de la salud en su manejo clínico. Para facilitar su lectura dichas recomendaciones se expondrán en un formato de tablas amigable, jerarquizando por diferentes niveles de evidencia.(AU)

The incorporation of a healthy diet, regular physical exercise and smoking cessation are the initial measures to reduce cardiovascular risk in patients with atherogenic dyslipidemia. In these patients, the nutritional quality of their diet should be improved, replacing foods with a greater atherogenic effect for others with a healthier effect. There is strong evidence that plant-based dietary patterns, low in saturated fatty acids, cholesterol and sodium, with a high content of fiber, potassium and unsaturated fatty acids, are beneficial and reduce the expression of cardiovascular risk factors. This document focuses on the role of nutrition in the prevention and treatment of atherogenic dyslipidemia, providing current evidence to serve as a tool for health professionals in its clinical management. To facilitate the reading of these recommendations, they are presented in a user-friendly table format, with a hierarchy of different levels of evidence.(AU)

Impact of physician's perception about LDL cholesterol control in clinical practice when treating patients in Spain.

BACKGROUND AND AIMS: We aimed to understand the impact of physicians' perception about LDL-cholesterol (LDLc) control on the management of patients with dyslipidemia in Spain. METHODS: We performed a cross-sectional and multicenter study, in which 435 healthcare professionals participated in face-to-face meetings, collecting qualitative and quantitative information related to hypercholesterolemia management. Additionally, aggregated anonymized data of the last 10 patients with hypercholesterolemia attended by each physician were collected. RESULTS: A total of 4,010 patients (8%, 13%, 16% and 61% with low, moderate, high, and very high cardiovascular [CV] risk) were included. Physicians' perception was that 62% of their patients attained LDLc goals (66%, 63%, 61% and 56%, for low, moderate, high and very high CV risk, respectively). However, when looking into the data only 31% (vs 62% p<0.01) of patients attained the LDLc goals (47%, 36%, 22% and 25%, respectively). Overall, 33% of patients were taking high intensity statins, 32% statin/ezetimibe, 21% low/moderate intensity statins and 4% PCSK9 inhibitors. These numbers were 38%, 45%, 8% and 6% for very high risk patients and 44%, 21%, 21% and 4% for high CV risk patients. In 32% of patients, a change in lipid lowering therapy was performed after the visit, mainly combining statins/ezetimibe (55%). CONCLUSIONS: In Spain, most patients with dyslipidemia do not achieve the recommended LDLc goals because of an insufficient intensification of lipid lowering therapy. On the one hand, this is in part due to physicians misperception on preventive LDLc control and the need for repeated advice to patient, and, on the other, to the lack of patient adherence.

Impact of the pre-drying process on the volatile profile of on-farm processed Ecuadorian bulk and fine-flavour cocoa varieties.

Aiming to improve the quality of cocoa, preconditioning of cocoa after harvesting and before fermentation has become an on-farm processing step of great interest in recent times. The present work aimed to evaluate the influence of a pre-drying process on the volatile composition of Ecuadorian bulk (Forastero and CCN-51) and fine-flavour (ETT103 and LR14) cocoa at the end of primary processing. A total of 63 volatile compounds including aldehydes, alcohols, acids, ketones, esters, terpenes, lactones and other miscellaneous compounds were identified in cocoa samples by HS-SPME-GC-MS. The use of a pre-drying step revealed a varietal homogenization and a reduction in the fermentation time, making this preconditioning step an inexpensive and attractive option for farmers. Moreover, different varietal behaviour was observed after pre-drying, the fine-flavour varieties obtaining a clear improvement in aromatic quality with higher levels of compounds imparting positive notes.

Optimal Fast Integral Decontamination of Bacillus thuringiensis Aerosols and Fast Disinfection of Contaminated Surfaces.

Aerosolized anthrax (Bacillus anthracis) spores are of extreme health concern and can remain airborne for hours and contaminate all kinds of surfaces, constituting reservoirs from which resuspension is easily produced. The assessment of decontamination techniques must therefore consider both air and surfaces. In the present study, several kinds of disinfecting fogs were experimentally tested against Bacillus thuringiensis spores, which served as a surrogate for Bacillus anthracis, both as aerosols released into the air and spread on porous and non-porous surfaces with different positions and orientations. This technology removed Bacillus thuringiensis spores from the air in 20 min with just a 1 min application of fog. The dynamics and characteristics of the fog, related to aerosol and surface interactions, proved to be critical for optimal performance and decontamination. An optimal configuration could provide effective disinfection even on indirectly reached surfaces. In all cases, 8% hydrogen peroxide (H2O2) provided a higher disinfection rate than 2% glutaraldehyde.

Hypercholesterolaemia control in Spain: The same situation with different regional realities. / Control de la hipercolesterolemia en España: una misma situación con diferentes realidades autonómicas.

INTRODUCTION AND OBJECTIVE: The cardiovascular prevention strategy by autonomous communities can be variable since the competences in health are transferred. The objective of the study was to determine the degree of dyslipidaemia control and the lipid-lowering pharmacological therapy used in patients at high/very high cardiovascular risk (CVR) by autonomous communities. METHODS: Observational, cross-sectional, descriptive study based on a consensus methodology. Information on the clinical practice of 145 health areas belonging to 17 Spanish autonomous communities was collected through face-to-face meetings and questionnaires administered to the 435 participating physicians. Furthermore, aggregate non-identifiable data were compiled from 10 consecutive dyslipidaemic patients that each participant had recently visited. RESULTS: Of the 4010 patients collected, 649 (16%) had high and 2458 (61%) very high CVR. The distribution of the 3107 high/very high CVR patients was balanced across regions, but there were inter-regional differences (P<.0001) in the achievement of target LDL-C <70 and <55mg/dL, respectively. High-intensity statins in monotherapy or in combination with ezetimibe and/or PCSK9 inhibitors were used in 44, 21 and 4% of high CVR patients, while in those at very high CVR it rose to 38, 45 and 6%, respectively. The use of these lipid-lowering therapies at national level was significantly different between regions (P=.0079). CONCLUSIONS: Even though the distribution of patients at high/very high CVR was similar between autonomous communities, inter-territorial differences were identified in the degree of achievement of LDL cholesterol therapeutic goal and use of lipid-lowering therapy.

Efecto de la inmunidad celular en el tratamiento de las úlceras del pie diabético con Heberprot-P® / Effect of cellular immunity in the treatment of diabetic foot ulcers with Heberprot-P®

Introducción: Los diabéticos muestran una disminuida función del sistema inmune. Su complicación más temida es la aparición de las úlceras del pie. El Heberprot-P® tiene efectos beneficiosos en la curación de estas úlceras. Objetivo: Evaluar el efecto de la inmunidad celular en el tratamiento de las úlceras del pie diabético con Heberprot-P®. Métodos: Se realizó un estudio observacional, prospectivo, de serie de casos, en 30 pacientes con úlcera de pie diabético, ingresados en el Instituto Nacional de Angiología y Cirugía Vascular. Se administraron 75 µg de Heberprot-P®, tres veces por semana, a través de vías peri- e intralesional, durante ocho semanas. Se evaluaron las variables edad, sexo, glucemia en ayunas, creatinina, urea, ácido úrico, prueba de hipersensibilidad retardada, porcentaje de granulación, tiempo de cierre de la lesión y localización de la úlcera, antes de comenzar el tratamiento, a las 4 y 8 semanas. Resultados: Se precisó un predominio del 60 por ciento en el sexo femenino y del color de piel blanca. Los niveles de glucemia y creatinina se comportaron más elevados en los anérgicos; la urea fue similar tanto en anérgicos como en reactivos; y el ácido úrico resultó mayor en hombres reactivos y en mujeres anérgicas. Hubo mayor proporción de reactivos (63,6 por ciento), que en la cuarta semana presentaron un tejido de granulación igual o mayor al 50 por ciento; y a la octava, igual o mayor al 70 por ciento. Conclusiones: La condición en los pacientes diabéticos de ser reactivo a las pruebas de hipersensibilidad retardada con úlcera de pie diabético de tipo neuropática, tratados con Heberprot-P®, está asociada directamente con una mejor respuesta en la cicatrización de sus lesiones, mediante la formación del tejido de granulación, que favorece el cierre total o parcial de la lesión. Esto no ocurrió con los pacientes anérgicos a dicha prueba(AU)

Introduction: Diabetics show decreased immune system function. Its most feared complication is the appearance of foot ulcers. Heberprot-P® has beneficial effects in healing these ulcers. Objective: To assess the effect of cellular immunity in the treatment of diabetic foot ulcers with Heberprot-P®. Methods: An observational, prospective, case series study was conducted in 30 patients with diabetic foot ulcer admitted to the National Institute of Angiology and Vascular Surgery. 75 µg of Heberprot-P®, three times a week, were administered through peri- and intralesional routes, during eight weeks. The variables age, sex, fasting blood glucose, creatinine, urea, uric acid, delayed hypersensitivity test, percentage of granulation, time of closure of the lesion and location of the ulcer, before starting treatment, at 4 and 8 weeks were evaluated. Results: A predominance of 60 % in females and white skin color were specified. Blood glucose and creatinine levels behaved higher in the anergics; urea was similar in both anergics and reagents; and uric acid was higher in reactive men and anergic women. There was a higher proportion of reagents (63.6 por ciento), which in the fourth week presented a granulation tissue equal to or greater than 50 por ciento; and at the eighth week, it was equal to or greater than 70 por ciento. Conclusions: The condition of being reactive to delayed hypersensitivity tests in diabetic patients with diabetic foot ulcer of neuropathic type, treated with Heberprot-P® is directly associated with a better response in the healing of their lesions, through the formation of granulation tissue, which favors the total or partial closure of the lesion. This did not occur with patients who were anergic to this test(AU)

Effect of In Vitro Gastrointestinal Digestion and Colonic Fermentation on the Stability of Polyphenols in Pistachio (Pistacia Vera L.).

The aim of this study was to evaluate the impact of in vitro gastrointestinal digestion and colonic fermentation on the polyphenol compounds from different varieties of pistachio by UHPLC-HRMS analysis. The total polyphenol content decreased significantly, mostly during oral (recoveries of 27 to 50%) and gastric digestion (recoveries of 10 to 18%), with no significant changes after the intestinal phase. After in vitro digestion, the hydroxybenzoic acids and the flavan-3-ols were the main compounds found in pistachio, with respective total polyphenol contents of 73 to 78% and 6 to 11%. More specifically, the main compounds determined after in vitro digestion were 3,4,5-trihydroxybenzoic acid, vanillic hexoside and epigallocatechin gallate. The colonic fermentation affected the total phenolic content of the six varieties studied, with a recovery range of 11 to 25% after 24 h of fecal incubation. A total of twelve catabolites were identified after fecal fermentation, the main compounds being the 3-(3'-hydroxyphenyl)propanoic, 3-(4'-hydroxyphenyl)propanoic, 3-(3',4'-dihydroxyphenyl)propanoic, 3-hydroxyphenylacetic acids and 3,4-dihydroxyphenyl-É£-valerolactone. Based on these data, a catabolic pathway for colonic microbial degradation of phenolic compounds is proposed. The catabolites identified at the end of the process are potentially responsible for the health properties attributed to pistachio consumption.