Glucose tolerance and insulin resistance/sensitivity associate with retinal layer characteristics: the LIFE-Adult-Study.

AIMS/HYPOTHESIS: As the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset. METHODS: The LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7-6.4% [39-47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings. RESULTS: In the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised ß=-0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; ß=-0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (ß=0.090; p<0.001 for eGDR) and MZ (ß=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis. CONCLUSIONS/INTERPRETATION: An impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.

Reactive oxygen species and aldehyde dehydrogenase 1A as prognosis and theragnostic biomarker in acute myeloid leukaemia patients.

Acute myeloid leukaemia (AML) remains a major unmet medical, despite recent progress in targeted molecular therapies. One aspect of leukaemic cell resistance to chemotherapy is the development of clones with increased capacity to respond to cellular stress and the production of reactive oxygen species (ROS), thanks in particular to a high aldehyde dehydrogenases (ALDH) 1A1/2 activity. At diagnosis, ROS level and ALDH1A1/2 activity in AML patients BM are correlated with the different ELN 2022 prognostic groups and overall survival (OS). A significant lower ALDH1A1/2 activity in BM was observed in the favourable ELN2022 subgroup compared to the intermediate and adverse group (p < 0.01). In the same way, the ROS levels were significantly lower in the favourable ELN 2022 subgroup compared to the intermediate group (p < 0.0001) and adverse group (p < 0.0002). ROShigh AML patients had a significantly lower median overall survival (OS) (8.2 months) than ROSlow patients (24.6 months) (p = 0.0368). After first-line therapy, a significant increase of ROS level (p = 0.015) and ALDH1A1/2 activity (0 = 0.0273) in leukaemic blasts was observed, especially in the refractory ones. ABD-3001, a competitive and irreversible inhibitor of ALDHs 1 and 3, can in vitro inhibit the proliferation of patient-derived leukaemic cells in accordance with redox balance. In multivariate analysis, ROS level was the most significant (p < 0.05) and the strongest predictive factor for the sensitivity of cells to ABD-3001. The safety profile of ABD-3001 is currently being assessed through the first inhuman multicenter phase 1 clinical trial "ODYSSEY" (NCT05601726) for patients with relapsed AML.

Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial.

BACKGROUND: The phase III PRIMA/ENGOT-OV26/GOG-3012 trial met its primary endpoint. Niraparib first-line maintenance significantly prolonged progression-free survival (PFS) among patients with newly diagnosed advanced ovarian cancer that responded to first-line platinum-based chemotherapy, regardless of homologous recombination deficiency (HRD) status. Final overall survival (OS) results are reported. PATIENTS AND METHODS: Patients were randomized 2:1 to niraparib or placebo, stratified by response to first-line treatment, receipt of neoadjuvant chemotherapy, and tumor HRD status. After reaching 60% target maturity, OS was evaluated via a stratified log-rank test using randomization stratification factors and summarized using Kaplan-Meier methodology. OS testing was hierarchical [overall population first, then the homologous recombination-deficient (HRd) population]. Other secondary outcomes and long-term safety were assessed; an updated, ad hoc analysis of investigator-assessed PFS was also conducted (cut-off date, 8 April 2024). RESULTS: The median follow-up was 73.9 months. In the overall population, the OS hazard ratio was 1.01 [95% confidence interval (CI) 0.84-1.23; P = 0.8834] for niraparib (n = 487) versus placebo (n = 246). In the HRd (n = 373) and homologous recombination-proficient (n = 249) populations, the OS hazard ratios were 0.95 (95% CI 0.70-1.29) and 0.93 (95% CI 0.69-1.26), respectively. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 11.7% and 15.8% of niraparib patients and 37.8% and 48.4% of placebo patients in the overall and HRd populations, respectively. The 5-year PFS rate numerically favored niraparib in the overall (niraparib, 22%; placebo, 12%) and HRd populations (niraparib, 35%; placebo, 16%). Myelodysplastic syndromes/acute myeloid leukemia incidence was <2.5% (niraparib, 2.3%; placebo, 1.6%). No new safety signals were observed. CONCLUSIONS: In patients with newly diagnosed advanced ovarian cancer at high risk of recurrence, there was no difference in OS between treatment arms. In the HRd population, patients alive at 5 years were two times as likely to be progression free with niraparib treatment than placebo. Long-term safety remained consistent with the established niraparib safety profile.

Speeding-up the Determination of Protein-Ligand Affinities by STD NMR: The Reduced Data Set STD NMR Approach (rd-STD NMR).

STD NMR spectroscopy is a powerful ligand-observed NMR tool for screening and characterizing the interactions of small molecules and low molecular weight fragments with a given macromolecule, identifying the main intermolecular contacts in the bound state. It is also a powerful analytical technique for the accurate determination of protein-ligand dissociation constants (KD) of medium-to-weak affinity, of interest in the pharmaceutical industry. However, accurate KD determination and epitope mapping requires a long series of experiments at increasing saturation times to carry out a full analysis using the so-called STD NMR build-up curve approach and apply the "initial slopes approximation". Here, we have developed a new protocol to bypass this important limitation, which allows us to obtain initial slopes by using just two saturation times and, hence, to very quickly determine precise protein-ligand dissociation constants by STD NMR.

The tale of two Ions Na+ and Cl-: unraveling onion plant responses to varying salt treatments.

BACKGROUND: Exploring the adaptive responses of onions (Allium cepa L.) to salinity reveals a critical challenge for this salt-sensitive crop. While previous studies have concentrated on the effects of sodium (Na+), this research highlights the substantial yet less-explored impact of chloride (Cl-) accumulation. Two onion varieties were subjected to treatments with different sodium and chloride containing salts to observe early metabolic responses without causing toxicity. RESULTS: The initial effects of salinity on onions showed increased concentrations of both ions, with Cl- having a more pronounced impact on metabolic profiles than Na+. Onions initially adapt to salinity by first altering their organic acid concentrations, which are critical for essential functions such as energy production and stress response. The landrace Birnförmige exhibited more effective regulation of its Na+/K+ balance and a milder response to Cl- compared to the hybrid Hytech. Metabolic alterations were analyzed using advanced techniques, revealing specific responses in leaves and bulbs to Cl- accumulation, with significant changes observed in organic acids involved in the TCA cycle, such as fumaric acid, and succinic acid, in both varieties. Additionally, there was a variety-specific increase in ethanolamine in Birnförmige and lysine in Hytech in response to Cl- accumulation. CONCLUSION: This comprehensive study offers new insights into onion ion regulation and stress adaptation during the initial stages of salinity exposure, emphasizing the importance of considering both Na+ and Cl- when assessing plant responses to salinity.

sp2-Iminosugar azobenzene O-glycosides: Light-sensitive glycosidase inhibitors with unprecedented tunability and switching factors.

The conventional approach to developing light-sensitive glycosidase activity regulators, involving the combination of a glycomimetic moiety and a photoactive azobenzene module, results in conjugates with differences in glycosidase inhibitory activity between the interchangeable E and Z-isomers at the azo group that are generally below one-order of magnitude. In this study, we have exploited the chemical mimic character of sp2-iminosugars to access photoswitchable p- and o-azobenzene α-O-glycosides based on the gluco-configured representative ONJ. Notably, we achieved remarkably high switching factors for glycosidase inhibition, favoring either the E- or Z-isomer depending on the aglycone structure. Our data also indicate a correlation between the isomeric state of the azobenzene module and the selectivity towards α- and ß-glucosidase isoenzymes. The most effective derivative reached over a 103-fold higher inhibitory potency towards human ß-glucocerebrosidase in the Z as compared with the E isomeric form. This sharp contrast is compatible with ex-vivo activation and programmed self-deactivation at physiological temperatures, positioning it as a prime candidate for pharmacological chaperone therapy in Gaucher disease. Additionally, our results illustrate that chemical tailoring enables the engineering of photocommutators with the ability to toggle inhibition between α- and ß-glucosidase enzymes in a reversible manner, thus expanding the versatility and potential therapeutic applications of this approach.

Allelic variants of the estrogen receptor genes and frailty phenotype in postmenopausal women.

OBJECTIVE: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) ERα and ERß genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women. METHODS: A cross-sectional study was performed in which we selected five SNPs, three in the ERα gene and two in the ERß. Linear regression was used to estimate the percentage of phenotypic variance after adjusting for confounding variables. RESULTS: A total of 470 women (mean ± standard deviation age 63.83 ± 8.16 years) were included, of whom 137 women were frail. The SNP rs3798577 of the ERα gene was the only variant associated with frailty, but this significance faded in the multivariant analysis. Body mass index (p = 0.012), number of comorbidities (0 vs. ≥2, p = 0.002) and two reproductive variables, number of miscarriages (none vs. ≥2, p = 0.036) and of childbirths (one vs. ≥3, p = 0.008), were independently related to frailty. CONCLUSION: The five SNPs of the ERα and ERß genes tested were not correlated with frailty. Other SNPs of the ER warrant analysis to clarify whether variance in the gene response affects frailty status.

Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population.

OBJECTIVES: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. METHODS: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. RESULTS: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. CONCLUSIONS: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.

Mast Cell Activation Profile and TFH13 Detection Discriminate Food Anaphylaxis Versus Sensitization.

BACKGROUND AND OBJECTIVE: The prevalence of food allergy (FA) has increased significantly, and the risk of developing anaphylaxis is unpredictable. Thus, discriminating between sensitized patients and those at risk of having a severe reaction is of utmost interest. To explore mast cell activation pattern and T follicular helper (TFH) 13 presence in sensitized and food anaphylaxis patients. METHODS: Patients sensitized to Lipid transfer protein (LTP) were classified as anaphylaxis or sensitized depending on the symptoms elicited by LTP-containing food. CD34+-derived MCs from patients and controls were obtained, sensitized with pooled sera, and challenged with Pru p 3 (peach LTP). Degranulation, PGD2, and cytokine/chemokine release were measured. The TFH13 population was examined by flow cytometry in the peripheral blood of all groups. In parallel, LAD2 cells were activated similarly to patients' MCs. RESULTS: A distinguishable pattern of mast cell activation was found in anaphylaxis compared to sensitized patients. Robust degranulation, PGD2, and IL-8 and GM-CSF secretion were higher in anaphylaxis, whereas TFG- and CCL2 secretion increased in sensitized patients. Concomitantly, anaphylaxis patients had a larger TFH13 population. MC activation profile was dependent on the sera rather than the MC source. In agreement with that, LAD2 cells reproduce the same pattern as MCs from anaphylactic and sensitized patients. CONCLUSION: The distinct profile of mast cell activation allows to discriminate between anaphylaxis and sensitized patients. Pooled sera may determine mast cell activation independently of mast cell origin. Besides, the presence of TFH13 cells in anaphylaxis patients points to an essential role of IgE affinity.

Evidence of castrations in fleas of small mammals (Chiroptera and Rodentia) from Argentina.

Morphological abnormalities in fleas seem to be common in nature and are under reported in Argentina. In this note, we describe anomalies in two males and one female of Alectopsylla unisetosa Mahnert (Ischnopsyllidae) and one of Polygenis sp. (Rhopalopsyllidae) male collected from small mammals in the provinces of Neuquen and Salta, Argentina. In all specimens, the anomalies were observed at the level of the genitalia recognized as partial castration. The structures mainly affected were the modified abdominal segments, the aedeagus (in male), and the spermatheca (in female). The present communication is the first one devoted exclusively to teratogenous fleas in Argentina.

Reproductive physiological outcomes of dairy cows with different genomic merit for fertility: Biomarkers, uterine health, endocrine status, estrus features, and response to ovarian synchronization.

Our overarching objective was to characterize associations between genomic merit for fertility and the reproductive function of lactating dairy cows in a prospective cohort study. In this manuscript, we present results of the association between genomic merit for fertility and indicators of metabolic status and inflammation, uterine health, endocrine status, response to synchronization, and estrous behavior in dairy cows. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation were enrolled at parturition and fitted with an ear-attached sensor for automated detection of estrus. Ear-notch tissue samples were collected from all cows and submitted for genotyping using a commercial genomic test. Based on genomic PTA values for daughter pregnancy rate (gDPR), cows were classified into a high (Hi-Fert; gDPR >0.6; n = 36), medium (Med-Fert; gDPR -1.3 to 0.6; n = 45), or low (Lo-Fert; gDPR <-1.3; n = 38) group. At 33 to 39 DIM, cohorts of cows were enrolled in the Presynch-Ovsynch protocol for synchronization of estrus and ovulation. Body weights, BCS, and uterine health measurements (i.e., vaginal discharge, uterine cytology) were collected from parturition to 60 DIM, and milk yield was collected through 90 DIM. Blood samples were collected weekly through 3 wk of lactation for analysis of BHB, nonesterified fatty acids (NEFA), and haptoglobin plasma concentrations. Body weight, BCS, NEFA, BHB, and haptoglobin were not associated with fertility groups from 1 to 9 wk after parturition. The proportion of cows classified as having endometritis at 33 to 36 DIM tended to be greater for the Lo-Fert than the Hi-Fert group. The proportion of cows that resumed cyclicity did not differ at any time point evaluated, and there were no significant associations between probability or duration and intensity of estrus with fertility group. Cows of superior genetic merit for fertility were more likely to ovulate, have a functional corpus luteum, have greater circulating progesterone, and have larger ovulatory size than cows of inferior fertility potential at key time points during synchronization of estrus and ovulation. Despite observing numerical differences with potential performance consequences for the proportion of cows that responded to synchronization of ovulation and were both cyclic and responded to the Ovsynch portion of the synchronization protocol, we did not observe significant differences between fertility groups. Although not consistent and modest in magnitude, the collective physiological and endocrine differences observed suggested that cows of superior genetic fertility potential might have improved reproductive performance, at least in part, because of modestly improved endocrine status, uterine health, and ability to ovulate.

Delaying induction of ovulation and timed AI in a Double-Ovsynch protocol increased expression of estrus and altered first service reproductive outcomes of lactating dairy cows.

The objective of this randomized controlled experiment was to evaluate the effect of delaying induction of ovulation and timed artificial insemination (TAI) on expression of estrus before AI and first service reproductive outcomes. A secondary objective was to evaluate the effects of delaying induction of ovulation in a Double-Ovsynch protocol on ovarian function. Lactating Holstein cows (n = 4,672) from 2 commercial dairy farms fitted with sensors for automated detection of estrus were synchronized with a Double-Ovsynch protocol up to the first PGF2α (PGF-L) of the Breeding-Ovsynch portion of the protocol (Pre-Ovsynch: GnRH, 7 d later PGF2α, 3 d later GnRH, 7 d later Breeding-Ovsynch: GnRH, 7 d later PGF2α, 1 d later PGF2α). At PGF-L, cows blocked by parity (primiparous vs. multiparous) and semen used for first service (sex-sorted dairy vs. conventional beef) were randomly assigned to the G56 (n = 2,338) or G80 (n = 2,334) treatments. Cows in G56 had 56 h whereas cows in G80 had 80 h from PGF-L to induction of ovulation with the last GnRH (GnRH2) before AI. For both treatments, TAI occurred ∼16 h after GnRH2. All cows with automated estrus alerts between PGF-L and TAI were inseminated at detected estrus (AIE) without GnRH. Ovarian function and responses to synchronization were monitored based on circulating concentrations of progesterone and examination of the ovaries by ultrasonography. Data for binary outcomes were analyzed by logistic and continuous outcomes with lineal regression. More cows in G80 received AIE and had estrus before AI. Overall, pregnancies per AI (P/AI) did not differ for the G80 and G56 treatments. Cows in G80 that received TAI and had no estrus had fewer P/AI than cows with estrus that received AIE or TAI in G80, and fewer P/AI than cows AIE and cows that received TAI and had or did not have estrus in the G56 treatment. No differences were observed between treatments or for cows with and without estrus for pregnancy loss. Unlike some minor differences between treatments for concentrations of progesterone at GnRH2, the most notable differences in ovarian function were for cows in both treatments with or without estrus that received TAI. Cows with estrus, were more likely to have follicles > 16 mm, had larger follicles before ovulation, and had a greater ovulation risk after AI. Likewise, within the G80 treatment only, cows with estrus that received AIE or TAI had larger follicles, were more likely to have complete luteal regression, had greater ovulation risk, were more likely to have a functional corpus luteum, and had more circulating progesterone after AI. We concluded that delaying induction of ovulation and TAI was effective for allowing more cows to express estrus before AI which had different ovarian function outcomes and greater P/AI than cows that did not express estrus. However, the greater P/AI of cows that expressed estrus was insufficient to compensate for the reduced P/AI of cows that did not express estrus, and thus increase overall P/AI compared with the treatment without delayed induction of ovulation. Detection of estrus before AI in cows undergoing synchronization of ovulation could help identify cows with different likelihoods of pregnancy after insemination.

Ovarian function and endocrine phenotypes of lactating dairy cows during the estrous cycle are associated with genomic-enhanced predictions of fertility potential.

The objectives of this prospective cohort study were to characterize associations among genomic merit for fertility with ovarian and endocrine function and the estrous behavior of dairy cows during an entire nonhormonally manipulated estrous cycle. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation had ear-notch tissue samples collected for genotyping using a commercial genomic test. Based on genomic predicted transmitting ability values for daughter pregnancy rate (gDPR), cows were classified into high (Hi-Fert; gDPR > 0.6, n = 36), medium (Med-Fert; gDPR -1.3 to 0.6, n = 45), and low fertility (Lo-Fert; gDPR < -1.3, n = 38) groups. At 33 to 39 DIM, cohorts of cows were enrolled in the Presynch-Ovsynch protocol for synchronization of ovulation and initiation of a new estrous cycle. Thereafter, the ovarian function and endocrine dynamics were monitored daily until the next ovulation by transrectal ultrasonography and concentrations of progesterone (P4), estradiol, and FSH. Estrous behavior was monitored with an ear-attached automated estrus detection system that recorded physical activity and rumination time. Overall, we observed an association between fertility group and the ovarian and hormonal phenotype of dairy cows during the estrous cycle. Cows in the Hi-Fert group had greater circulating concentrations of P4 than cows in the Lo-Fert group from d 4 to 13 after induction of ovulation and from day -3 to -1 before the onset of luteolysis. The frequency of atypical estrous cycles was 3-fold greater for cows in the Lo-Fert than the Hi-Fert group. We also observed other modest associations between genomic merit for fertility with the follicular dynamics and estrous behavior. We found several associations between milk yield and parity with ovarian, endocrine, and estrous behavior phenotypes as cows with greater milk yield and in the second lactation were more likely to have unfavorable phenotypes. These results demonstrate that differences in reproductive performance between cows of different genomic merit for fertility classified based on gDPR may be partially associated with circulating concentrations of P4, the incidence of atypical phenotypes during the estrous cycles, and, to a lesser extent, the follicular wave dynamics. The observed physiological and endocrine phenotypes might help explain part of the differences in reproductive performance between cows of superior and inferior genomic merit for fertility.

Self-perceived body weight and weight status: analysis of concordance by age group and sex.

OBJECTIVES: Previous studies suggest that there is discordance between actual weight status and body-weight perception. This fact has implications when it comes to designing public health interventions. The aim of this study was to estimate the prevalence of the different categories of weight status and body-weight perception and to analyse their concordance in a representative Spanish population sample. STUDY DESIGN: Cross-sectional study. METHODS: Data were sourced from the 2018 Galician Risk Behaviour Data System, with the target population being all persons aged 16 years and above. We collected data on self-perceived body weight and assessed weight status on the basis of body mass index (BMI). BMI was estimated using self-reported measures of weight and height. To estimate concordance, Cohen's kappa coefficient, both unweighted and weighted with Cicchetti weights, was calculated. RESULTS: Data were obtained for 7853 individuals aged 16 years and above, whereas the overall unweighted concordance was 0.393 (95%CI: 0.377-0.409), with an agreement percentage of 61.6%, weighted concordance was 0.503 (0.490-0.517), with an agreement percentage of 86.6%. The highest concordance between self-perceived body weight and weight status was observed in women. By age group, the highest concordance was observed in the youngest group (16-24 years) for the BMI categories of underweight and overweight, and in the 45-64 age group for the category of obesity. CONCLUSIONS: The results highlight the existence of differences between self-perceived body weight and weight status, according to sex and age.

Last twenty-years activity of cardiovascular tissue banking in Barcelona.

The Barcelona Tissue Bank was established from the merge of two previous multi-tissue banks. Potential donors are screened by Donor Center staff and multi-tissue retrieval is performed by specialized own teams. Tissue processing and preservation is performed in clean room facilities by specialised personnel. After quality control of both donor and all tissues results, the heart valves and vascular segments are stored until medical request. The aim of this report is to present the cardiovascular tissue activity and retrospectively evaluate the outcomes of the changes performed in last 20 years. Cardiovascular tissue from 4088 donors was received, specifically 3115 hearts and 2095 vascular segments were processed and evaluated. A total of 48% of the aortic valves, 68% of the pulmonary valves and 75% of the vascular segments were suitable for transplant. The main reason for discarding tissue was macroscopic morphology followed by microbiological results, for both valves and arteries. Altogether, 4360 tissues were distributed for transplantation: 2032 (47%) vascular segments, 1545 (35%) pulmonary valves and 781 (18%) aortic valves. The most common indication for aortic valve surgery was the treatment of endocarditis, while for pulmonary valves, it was congenital malformation reconstruction. Vascular segments were mainly used for reconstruction after ischemia. During this period, a number of changes were made with the goal of enhancing tissue quality, safety and efficacy. These improvements were achieved through the use of a new antibiotic cocktail, increasing of donor age criteria and changing the microbiological control strategy.

Ideational Praxis, Play, and Playfulness: A Cross-Sectional Study of Autistic Children.

IMPORTANCE: Assessment of praxis skills is an essential aspect of understanding autistic children's development of play and playfulness. OBJECTIVE: To assess the relationship and influence of ideational praxis skills on play skills and playfulness among autistic children. DESIGN: A cross-sectional study. SETTINGS: Homes, schools, and early care centers across Spain. PARTICIPANTS: Children ages 4 yr 6 mo to 6 yr 11 mo (45 typically developing [TP] and 45 with autism spectrum disorder [ASD]). OUTCOMES AND MEASURES: Student's t tests were used to compare means between the two groups. Pearson's correlation and multiple linear regression were used to determine possible effects of ideational skills on play and playfulness. RESULTS: Scores for the TP group were significantly higher than those of the ASD group on all play dimensions-space management, t(88) = 4.58; material management, t(88) = 5.86; pretense-symbolism, t(88) = 8.12; and participation, t(88) = 7.31-and on the Test of Playfulness (ToP), t(88) = 10.18, and Test of Ideational Praxis (TIP), t(88) = 4.38 (all ps < .001). Multiple linear regression revealed a statistically significant effect of TIP dimensions-space management, F(3, 41) = 4.83, p < .042; material management, F(3.41) = 8.49. p < .001; pretense-symbolism, F(3, 41) = 5.66. p < .002; and participation, F(3.41) = 7.81. p < .001-and on the ToP, F(3, 41) = 5.96. p < .002. CONCLUSIONS AND RELEVANCE: Ideational praxis skills combined with diagnostic information significantly predicted play skills and playfulness, highlighting the influence of ideation on play. Plain-Language Summary: This article provides data supporting the influence of ideational praxis skills on the play skills and playfulness of autistic children. Understanding how ideational praxis skills affect the ability to recognize and act on object affordances might promote greater possibilities for play interactions among autistic children.

[Translated article] Bioethical Conflicts in Current Dermatology: A Narrative Review.

Both the functions and equipment of dermatologists have increased over the past few years, some examples being cosmetic dermatology, artificial intelligence, tele-dermatology, and social media, which added to the pharmaceutical industry and cosmetic selling has become a source of bioethical conflicts. The objective of this narrative review is to identify the bioethical conflicts of everyday dermatology practice and highlight the proposed solutions. Therefore, we conducted searches across PubMed, Web of Science and Scopus databases. Also, the main Spanish and American deontological codes of physicians and dermatologists have been revised. The authors recommend declaring all conflicts of interest while respecting the patients' autonomy, confidentiality, and privacy. Cosmetic dermatology, cosmetic selling, artificial intelligence, tele-dermatology, and social media are feasible as long as the same standards of conventional dermatology are applied. Nonetheless, the deontological codes associated with these innovations need to be refurbished.

Bioethical Conflicts in Current Dermatology: A Narrative Review. / Conflictos bioéticos en la dermatología actual: una revisión narrativa.

Both the functions and equipment of dermatologists have increased over the past few years, some examples being cosmetic dermatology, artificial intelligence, tele-dermatology, and social media, which added to the pharmaceutical industry and cosmetic selling has become a source of bioethical conflicts. The objective of this narrative review is to identify the bioethical conflicts of everyday dermatology practice and highlight the proposed solutions. Therefore, we conducted searches across PubMed, Web of Science and Scopus databases. Also, the main Spanish and American deontological codes of physicians and dermatologists have been revised. The authors recommend declaring all conflicts of interest while respecting the patients' autonomy, confidentiality, and privacy. Cosmetic dermatology, cosmetic selling, artificial intelligence, tele-dermatology, and social media are feasible as long as the same standards of conventional dermatology are applied. Nonetheless, the deontological codes associated with these innovations need to be refurbished.

Bibliometric Study of the Advances Made in Clinical Dermatological Research in Spain from 2015 through 2021: Update of the MaIND Project and Interactive Online Map. / Estudio bibliométrico sobre la evolución de la investigación clínica dermatológica española entre 2015 y 2021: actualización del proyecto MaIND y mapa interactivo en línea.

INTRODUCTION: A clinical dermatological research was conducted in Spain from 2005 through 2014 as part of the MaIND project with the provinces or centers with the highest number of published articles. However, a low level of evidence in scientific production was confirmed as the overall result. The aim of this study is to update the Spanish clinical dermatological research in bibliometric terms from 2015 through 2021 with comparisons between both periods of time. MATERIAL AND METHODS: We conducted a bibliometric study to replicate the methodology used in the article to be updated. We included articles whose corresponding authors' affiliation was a Spanish dermatological center, which met the criteria for clinical research in dermatology, including a level of evidence ≤4. RESULTS: A total of 1,674 out of the 10,199 articles met the inclusion criteria. An interactive map representing quantitative and qualitative indicators calculated for the 2005-2021 is presented here. In the study period, we found an increasing trend both in the number of published articles (P<.002) and in the mean number of citation-years per article (P<.01). A total of 22 of the articles had a level of evidence >4, with a positive trend towards more articles having a higher level of evidence (P<.03). ACTAS DERMOSIFILOGRÁFICAS still maintains its position as the journal with the highest number of articles received (18%, a total of 302 articles). CONCLUSIONS: The results of this study show that, in Spain, the scientific production of dermatology represents an upward trend in quantity, impact, and level of evidence.

[Translated article] Bibliometric Study of the Advances Made in Clinical Dermatological Research in Spain from 2015 through 2021: Update of the MaIND Project and Interactive Online Map.

INTRODUCTION: A clinical dermatological research was conducted in Spain from 2005 through 2014 as part of the MaIND project with the provinces or centers with the highest number of published articles. However, a low level of evidence in scientific production was confirmed as the overall result. The aim of this study is to update the Spanish clinical dermatological research in bibliometric terms from 2015 through 2021 with comparisons between both periods of time. MATERIAL AND METHODS: We conducted a bibliometric study to replicate the methodology used in the article to be updated. We included articles whose corresponding authors' affiliation was a Spanish dermatological center, which met the criteria for clinical research in dermatology, including a level of evidence ≤4. RESULTS: A total of 1,674 out of the 10,199 articles met the inclusion criteria. An interactive map representing quantitative and qualitative indicators calculated for the 2005-2021 is presented here. In the study period, we found an increasing trend both in the number of published articles (P<.002) and in the mean number of citation-years per article (P<.01). A total of 22 of the articles had a level of evidence >4, with a positive trend towards more articles having a higher level of evidence (P<.03). ACTAS DERMOSIFILOGRÁFICAS still maintains its position as the journal with the highest number of articles received (18%, a total of 302 articles). CONCLUSIONS: The results of this study show that, in Spain, the scientific production of dermatology represents an upward trend in quantity, impact, and level of evidence.