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Zebrafish is a popular toxicology model and provides an ethically acceptable small-scale analysis system with the complexity of a complete organism. Our goal is to further validate this model for its regulatory use for reproductive and developmental defects by testing the compounds indicated in the "Guideline on detection of reproductive and developmental toxicity for human pharmaceuticals" (ICH S5(R3) guideline.) To determine the embryotoxic and developmental risk of the 32 reference compounds listed in the ICH S5(R3) guideline, the presence of morphological alterations in zebrafish embryos was analyzed at two different stages to calculateLC50 and EC50 values for each stage. Teratogenic Indexes were established as the ratio between LC50 and EC50 critical for the proper compound classification as teratogenic when it is ≥ 2. A total of three biological replicates have been conducted to study the reproducibility of the assay. The chemicals' concentration in the medium and internally in the zebrafish embryos was evaluated. In this study, the 3 negative compounds were properly categorized while 23 compounds out of the 29 reference ones (sensitivity of 79.31%) were classified as teratogenic in zebrafish. The 6 that had false-negative results were classified 4 as inconclusive, 1 as not toxic, and 1 compound resulted toxic for zebrafish embryos under testing conditions. After the bioavailability experiments, some of the obtained inconclusive results were refined. The developmental defects assay in zebrafish gives an accuracy of 89.66%, sensitivity of 88.46%, specificity and repeatability of 100% compared to mammals; therefore, this is a well-integrated strategy using New Alternative Methods, to minimize the use of animals in developmental toxicity studies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Arantza Muriana reports equipment, drugs, or supplies and writing assistance were provided by GAIKER. Arantza Muriana reports a relationship with GAIKER that includes: consulting or advisory. The author is co-founder and R&D Director of BBD BioPhenix SLU, and all the coauthors except Sainz L and De Goñi F are nowadays employed or have been employed previously by BBD BioPhenix SLU, a CRO specialized in the use of zebrafish for efficacy, toxicity and ecotoxicity assays, including offering teratogenicity, reprotoxicity, neurotoxicity, or endocrine disruption assays for Pharma Industry, Cosmetic Industry, or Agrochemical Industry, including the assays described in the paper. Sainz L and De Goñi F work in GAIKER, a company that BBD BioPhenix SLU outsources to develop bioavailability assays for their clients, in this case, they offered their services to analyze the compounds inside the zebrafish for this paper., (Copyright © 2023. Published by Elsevier Inc.)

Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes of psoriatic skin, and we show that expression in keratinocytes is induced by limited glucose availability and enables increased survival under limiting glucose conditions by increasing glutamine metabolism. In addition, miR-31 expression results in not only secretion of specific metabolites (aspartate and glutamate) but also secretion of immunomodulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibitors of miR31-induced metabolic rewiring and metabolic crosstalk with immune cells alleviate psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Objective: Short-acting β 2 -agonist (SABA) over-reliance is associated with poor asthma outcomes. As part of the SABA Use IN Asthma (SABINA) III study, we assessed SABA prescriptions and clinical outcomes in patients from six Latin American countries., Methods: In this cross-sectional study, data on disease characteristics/asthma treatments were collected using electronic case report forms. Patients (aged ≥12 years) were classified by investigator-defined asthma severity (guided by the 2017 Global Initiative for Asthma) and practice type (primary/specialist care). Multivariable regression models analyzed the associations between SABA prescriptions and clinical outcomes., Results: Data from 1096 patients (mean age, 52.0 years) were analyzed. Most patients were female (70%), had moderate-to-severe asthma (79.4%), and were treated by specialists (87.6%). Asthma was partly controlled/uncontrolled in 61.5% of patients; 47.4% experienced ≥1 severe exacerbation in the previous 12 months. Overall, 39.8% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (considered over-prescription). SABA canisters were purchased over the counter (OTC) by 17.2% of patients, of whom 38.8% purchased ≥3 canisters in the 12 months prior. Of patients who purchased SABA OTC, 73.5% were prescribed ≥3 SABA canisters. Higher SABA prescriptions (vs. 1 - 2 canisters) were associated with an increased incidence rate of severe exacerbations (ranging from 1.31 to 3.08) and lower odds ratios of having at least partly controlled asthma (ranging from 0.63 to 0.15)., Conclusions: SABA over-prescription was common in Latin America, highlighting the need for urgent collaboration between healthcare providers and policymakers to align clinical practices with the latest evidence-based recommendations to address this public health concern.

Introduction: Even though oral diseases are highly prevalent in people with visual impairment (VI) and this population faces access barriers to dental services and is exposed to risk factors that increase their vulnerability, the existing literature on oral health in this population is scarce., Objective: To conduct a literature review in order to describe studies on oral health in persons with VI and provide health care professionals who treat and educate these patients with relevant information., Methods: This is a literature review with a descriptive approach. A total of 26 original articles were included. The selected studies were published in the last six years (2014-March 2020) in English, Portuguese, and Spanish. The search was conducted in the Virtual Health Library, SciELO, PubMed, Scopus, and Clinical Key databases. Keywords combined with Boolean operators "AND" and "OR" were used., Results: Few studies address the use of dental services by people with VI. There is evidence of poor levels of knowledge on oral health and related practices, which increases vulnerability to risk factors for developing diseases compared to the general population. Caries and periodontal disease are reported as the most prevalent oral diseases. Health promotion and education intervention should involve parents, caregivers, and guardians to increase the success rate., Conclusions: People with VI may develop oral diseases easily; therefore, they require dental care and health promotion interventions adapted to their needs., (Universidad Nacional de Córdoba)

Objectives: To determine weight, height and body mass index (BMI) of schoolchildren from the La Mancha-Centro health area and compare them with those determined by the Spanish Cross-sectional Growth Study 2010 (SCGS-2010)., Methods: Cross-sectional study of 954 schoolchildren aged 6-12 years. Mean, standard deviation, and percentile distributions of weight, height, and BMI by gender and age were obtained. Differences in each 6-month age group were analyzed., Results: There was a progressive increase in BMI with age, which was significant in girls from nine years of age on and in boys from 8.5 years on. From age 10, average BMI was 2.3 kg/m 2 higher than at younger ages (p < 0.001). The biggest difference between genders occurred at age 12: 2 ± 0.98 kg/m 2 higher in boys (p = 0.042). Overall, no significant differences were found in weight, height and BMI vs. SCGS-2010, although mean weight of male children from La Mancha-Centro aged between 8.5 and 11.5 years was 3.9 kg higher than that of the rest of Spanish male children., Conclusions: Anthropometric parameters of schoolchildren from La Mancha-Centro do not significantly differ from national standards; however, preadolescent males from La Mancha-Centro weigh almost 4 kg more., (Copyright: © 2022 Permanyer.)

Differential WNT and Notch signaling regulates differentiation of Lgr5 + crypt-based columnar cells (CBCs) into intestinal cell lineages. Recently we showed that mitochondrial activity supports CBCs, while adjacent Paneth cells (PCs) show reduced mitochondrial activity. This implies that CBC differentiation into PCs involves a metabolic transition toward downregulation of mitochondrial dependency. Here we show that Forkhead box O (FoxO) transcription factors and Notch signaling interact in determining CBC fate. In agreement with the organoid data, Foxo1/3/4 deletion in mouse intestine induces secretory cell differentiation. Importantly, we show that FOXO and Notch signaling converge on regulation of mitochondrial fission, which in turn provokes stem cell differentiation into goblet cells and PCs. Finally, scRNA-seq-based reconstruction of CBC differentiation trajectories supports the role of FOXO, Notch, and mitochondria in secretory differentiation. Together, this points at a new signaling-metabolic axis in CBC differentiation and highlights the importance of mitochondria in determining stem cell fate., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Speech Analysis for Automatic Speech Recognition (ASR) systems typically starts with a Short-Time Fourier Transform (STFT) that implies selecting a fixed point in the time-frequency resolution trade-off. This approach, combined with a Mel-frequency scaled filterbank and a Discrete Cosine Transform give rise to the Mel-Frequency Cepstral Coefficients (MFCC), which have been the most common speech features in speech processing for the last decades. These features were particularly well suited for the previous Hidden Markov Models/Gaussian Mixture Models (HMM/GMM) state of the art in ASR. In particular they produced highly uncorrelated features of small dimensionality (typically 13 coefficients plus deltas and double deltas), which was very convenient for diagonal covariance GMMs, for dealing with the curse of dimensionality and for the limited computing resources of a decade ago. Currently most ASR systems use Deep Neural Networks (DNN) instead of the GMMs for modeling the acoustic features, which provides more flexibility regarding the definition of the features. In particular, acoustic features can be highly correlated and can be much larger in size because the DNNs are very powerful at processing high-dimensionality inputs. Also, the computing hardware has reached a level of evolution that makes computational cost in speech processing a less relevant issue. In this context we have decided to revisit the problem of the time-frequency resolution in speech analysis, and in particular to check if multi-resolution speech analysis (both in time and frequency) can be helpful in improving acoustic modeling using DNNs. Our experiments start with several Kaldi baseline system for the well known TIMIT corpus and modify them by adding multi-resolution speech representations by concatenating different spectra computed using different time-frequency resolutions and different post-processed and speaker-adapted features using different time-frequency resolutions. Our experiments show that using a multi-resolution speech representation tends to improve over results using the baseline single resolution speech representation, which seems to confirm our main hypothesis. However, results combining multi-resolution with the highly post-processed and speaker-adapted features, which provide the best results in Kaldi for TIMIT, yield only very modest improvements., Competing Interests: The authors have declared that no competing interests exist.

Objective: To assess the dietary pattern of the school population from La Mancha-Centro Health Area (Ciudad Real)., Methodology: A cross-sectional study conducted on a representative sample of schoolchildren aged 6 to 12 years, using a questionnaire to determine their general dietary habits and a record of their 24-hour intake., Results: A total of 1142 schoolchildren were included, with 612 boys (53.6%) and 530 girls (46.4%), and a mean age of 9.3 ± 1.7 years of age. The frequency of food intake was 4.62 ± 0.6 times a day, which decreased with the age of the schoolchildren (P=.044), and increased with the educational level of parents (P=.004). Food preference influenced the choice in the meals consumed. The level of appetite was related directly with weight and body mass index (BMI) (P<.001), age (P=.02), and number of daily food intakes by the children (P=.038). The food groups most frequently consumed were cereals and their derivatives (92.8%), milk and dairy products (90.45%), while vegetables were the least consumed (35.46%). Over 70% of the sample usually consumed olive oil., Conclusion: The dietary pattern of the school population maintains some of the features of traditional Mediterranean dietary pattern, such as the habit of daily breakfast, the greater consumption of olive oil and cereals. On the other hand, other characteristics are remarkable, such as the low consumption of fruit and vegetables and the high consumption of meat., (Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: this study aimed to estimate prevalence of metabolic syndrome and all its components to know the cardiovascular risk and metabolic control of the main risk factors in postmenopausal women aged over 45 years in the province of Cuenca (Castilla-La Mancha, Spain)., Methods: in this cross-sectional study, we randomly selected 716 postmenopausal women from 3,108 women aged over 45. Metabolic syndrome was identified according to the National Cholesterol Education Program Adult Treatment Panel III definition. Cardiovascular risk was calculated by the Systematic Coronary Risk Evaluation ( < 65 years). The American Diabetes Association´s standards of medical care in diabetes were used to estimate metabolic control. The statistical analysis was done with SPPS.19 RESULTS: prevalence of metabolic syndrome was 61.7% (95%CI: 56.9-66.4). Prevalence of each component was: high blood pressure: 95.8% (95%CI: 95.7-95.8), abdominal obesity: 91% (95%CI: 90.9-91.0), low high-density lipoproteins cholesterol (HDLc) levels: 70% (95%CI: 69.8-69.9), high triglyceride levels: 56.9% (95%CI: 56.4- 56.9), high glucose levels: 54.3% (95%CI: 54.2-54.3). Cardiovascular risk was moderate until 65 years, but was high after this age. Metabolic control in postmenopausal women was very good for glucose, bad for systolic blood pressure and worse for lipid levels. Bad blood pressure control was associated with being over 65 years, being hypertensive and taking treatment for diabetes, but it reduced when being physically limited to do moderate exercise and anxiety increased., Conclusions: prevalence of metabolic syndrome in postmenopausal women in the province of Cuenca is the highest in Spain. High blood pressure and abdominal obesity are the commonest components. Cardiovascular risk was moderate-high in postmenopausal women, but systolic blood pressure and lipid profile were unsatisfactorily controlled. Early intervention is necessary to achieve a better risk profile., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Objective: To know the consumption of alcohol in Toledo schoolchildren, to find out the reasons which cause them to drink and the alternatives proposed., Design: Descriptive, transverse study., Location: 2 zones in the Toledo health area., Participants: A total of 625 adolescents between 13 and 18 years, in the third and fourth years of Obligatory Secondary Education and first year in High School (Bachillerato) of 2 secondary education institutions in Torrijos and 1 in Toledo capital., Main Measurements: Using an ad hoc designed anonymous questionnaire, with 32 items, the following data was collected: age, sex, alcohol consumption (personal, family, and friends), how much (standard drink units), knowledge and sources of information on alcohol, taking of other drugs, reasons for consuming, and the alternatives., Results: 47.27% of those questioned were male. The mean age was 15.4 +/- (-)1.3 years. 93.4% had tried alcohol (95% CI, 91.1-95.2). 52.0% had been drunk at some time, which was more frequent in rural areas than in the city. 58.1% considered alcohol as a drug. Among the reasons mentioned for drinking, the main ones were "enjoyment" (46.3%), "to forget problems" (30.7%), and "curiosity" (24.6%). The alternatives to drinking which were proposed were related to computers and sport., Conclusions: The consumption of alcohol is a common habit among adolescents and its pattern differs between urban and rural areas, where it is much earlier and more intense in the latter. It forms part of their lifestyle, they use it as a means of enjoyment and a large percentage consider that alcohol is a drug. Against "street binge drinking," their proposals are computer activities and sport.

Hyperthermia is defined as a temperature of at least 1.5 degrees C over the normal core body temperature. It is a proven teratogen in animals and in humans. The type of defects induced by hyperthermia in experimental animals are: anencephaly/exencephaly, encephalocele, microphthalmia, arthrogryposis, abdominal wall defects, limb deficiencies, embryonic death, and resorption. In humans it has been observed that infants prenatally exposed to hyperthermia presented with spina bifida, encephalocele, microphthalmia, micrognathia, external ear anomalies, cardiac defects, hypospadias, gastrointestinal defects, cleft lip and/or cleft palate, abdominal wall defects, diaphragmatic hernia, Hirschsprung disease, Möbius syndrome, oromandibular-limb hypogenesis spectrum, and spontaneous abortions. We describe an additional case with severe limb deficiencies whose mother had fever over 39 degrees C for 2 days in the second and in the fourth month of amenorrhoea. We conclude that, based on the degree of development of the humeri and the femora and the type of limb deficiencies, this case presents a disruption that most probably occurred in the fourth month of gestation., (Copyright 2001 Wiley-Liss, Inc.)

Tuberous sclerosis is characterized by the potential for hamartomatous growth in multiple organs. Common manifestations are hypomelanotic spots, facial angiofibromas, subependymal hamartomas, cortical tubers, cardiac rhabdomyomas, retinal hamartomas, and so on. Seizures and mental retardation are frequent. It is an autosomal dominant disease but there is a high percentage of spontaneous mutations. Neonatal diagnosis is exceptional. We report a case of a female term newborn who presented partial motor seizures at the third day of life. Physical examination revealed only a disturbance of cardiac rhythm. Echocardiography showed ventricular intramural rhabdomyomas. Magnetic resonance imaging disclosed periventricular subependymal nodules and cortical tubers. A retinal hamartoma was found in the right eye. At the age of 1 month, hypomelanotic spots were evident on the back skin. The patient had infantile spasms, followed by poorly controlled partial complex seizures together with severe psychomotor retardation. Examination of both parents was normal. We discuss the uncommon diagnosis of tuberous sclerosis during the neonatal period, as well as the exceptional mode of presentation of our patient, with seizures in the early neonatal period, a phenomenon rarely reported in the literature.