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Background: Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population. Methods: The validation of the neonatal DDD, Phase II of the research project, was carried out through a descriptive observational study. Periodic cut-offs were performed to collect antimicrobial prescriptions of neonates admitted to the neonatology and intensive care units of nine Spanish hospitals. The data collected included demographic variables (gestational age, postnatal age, weight and sex), antimicrobial dose, frequency and route of administration. The selection of the optimal DDD value takes into account power value, magnitude obtained from the differences in the DDD, statistical significance obtained by the Wilcoxon test and degree of agreement in the stipulated doses. Results: Set of 904 prescriptions were collected and finally 860 were analysed based on the established criteria. The antimicrobials were mostly prescribed in the intensive care unit (63.1%). 32 different antimicrobials were collected, and intravenous administration was the most commonly used route. Neonatal DDD were defined for 11 different antimicrobials. A potency > 80% was obtained in 7 antibiotics. The 57.1% of the selected DDD correspond to phase I and 21.4% from phase II. Conclusion: DDD validation has been achieved for the majority of intravenously administered antimicrobials used in clinical practice in the neonatal population. This will make it possible to have an indicator that will be used globally to estimate the consumption of antimicrobials in this population, thus confirming its usefulness and applicability.

The purpose of this paper is to verify whether the concentrations of caffeine in saliva are comparable to serum concentrations in preterm infants who are treated with caffeine for apnea of prematurity. This is a prospective observational study. Eligible participants were newborn infants < 37 weeks of gestational age treated with oral or intravenous caffeine for apnea of prematurity. Two paired samples of saliva and blood were collected per patient. Tube solid-phase microextraction coupled online to capillary liquid chromatography with diode array detection was used for analysis. A total of 47 infants with a median gestational age of 28 [26–30] weeks and a mean of 1.11 ± 0.4 kg of birth weight. Median postmenstrual age, when samples were collected, was 31 [29–33] weeks. Serum caffeine median levels of 19.30 μg/mL [1.9–53.90] and salivary caffeine median levels of 16.36 μg/mL [2.20–56.90] were obtained. There was a strong positive Pearson’s correlation between the two variables r  = 0.83 ( p  < 0.001). Conclusion : The measurement of salivary caffeine concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnea of prematurity. Measurement of salivary concentration minimizes blood draws, improves blood conservation, and subsequently minimizes painful procedures in premature infants. What is Known: • Salivary sampling may be useful when is applied to extremely low birth weight infant, in whom blood sampling must be severely restricted. What is New: • The measurement of caffeine salivary concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnoea of prematurity. • Salivary sampling may be a valid non-invasive alternative that could be used to individualize and optimize caffeine dose.

Niemann–Pick type C (NP-C) is a rare neurodegenerative disorder. Management is mainly supportive and symptomatic. The investigational use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a promising role in treating NP-C, although efficacy and safety have not been established. We conducted searches of MEDLINE, Cochrane, EMBASE, and other databases of reported cases of HP-β-CD compassionate use in NP-C disease. Sixteen reported cases were eligible, including evaluable information of 17 patients. The median onset age of HP-β-CD was 14 years (range 2–49 years). Intrathecal route was employed in 16 patients, in 3 patients simultaneously to IV infusions. Intracerebroventricular route was used in two patients. An objective improvement of clinical outcomes was measured in 14 patients, mainly by the NIH NP-C Clinical Severity Score and brainstem auditory evoked potential. Besides, an increase in metabolism and activities of the brain were observed in image tests and cholesterol biomarkers. Most patients showed some clinical benefit or a stabilization of NP-C progression. There were 17 adverse events (AEs) reported in 11 patients, 11 of them related to the drug and 6 to the route of administration. Loss of hearing was reported in four patients. The most severe AE were fever and chemical meningitis. Results suggest that efficacy may be partial and dependent on the early administration of the drug, the severity of the disease, and interpersonal variability. HP-β-CD could help stabilize NP-C with low toxicity potential, although some AEs have been reported. Moreover, controlled clinical trials would be necessary to evaluate the role of HP-β-CD in NP-C.

Therapeutic hypothermia (TH) initiated within 6 h from birth is the most effective therapeutic approach for moderate to severe hypoxic-ischemic encephalopathy (HIE). However, underlying mechanisms and effects on the human metabolism are not yet fully understood. This work aims at studying the evolution of several energy related key metabolites in newborns with HIE undergoing TH employing gas chromatography – mass spectrometry. The method was validated following stringent FDA requirements and applied to 194 samples from a subgroup of newborns with HIE (N = 61) enrolled in a multicenter clinical trial (HYPOTOP) for the determination of lactate, pyruvate, ketone bodies and several Krebs cycle metabolites at different sampling time points. The analysis of plasma samples from newborns with HIE revealed a decrease of lactate, pyruvate and β-hydroxybutyrate concentrations, whereas rising malate concentrations were observed. In healthy control newborns (N = 19) significantly lower levels of pyruvate and lactate were found in comparison to age-matched newborns with HIE undergoing TH, whereas acetoacetate and β-hydroxybutyrate levels were clearly increased. Access to a validated analytical method and a controlled cohort of newborns with HIE undergoing hypothermia treatment for the first time allowed the in-depth study of the evolution of key metabolites of metabolic junctions in this special population.

Background: Own mother’s milk (OMM) is the optimal nutrition for preterm infants. However, pasteurized donor human milk (DHM) is a valid alternative. We explored the differences of the transcriptome in exfoliated epithelial intestinal cells (EEIC) of preterm infants receiving full feed with OMM or DHM. Methods: The prospective observational study included preterm infants ≤ 32 weeks’ gestation and/or ≤1500 g birthweight. Total RNA from EEIC were processed for genome-wide expression analysis. Results: Principal component analysis and unsupervised hierarchical clustering analysis revealed two clustered groups corresponding to the OMM and DHM groups that showed differences in the gene expression profile in 1629 transcripts. The OMM group overexpressed lactalbumin alpha gene (LALBA), Cytochrome C oxidase subunit I gene (COX1) and caseins kappa gene (CSN3), beta gene (CSN2) and alpha gene (CSN1S1) and underexpressed Neutrophil Cytosolic Factor 1 gene (NCF1) compared to the DHM group. Conclusions: The transcriptomic analysis of EEIC showed that OMM induced a differential expression of specific genes that may contribute to a more efficient response to a pro-oxidant challenge early in the postnatal period when preterm infants are at a higher risk of oxidative stress. The use of OMM should be strongly promoted in preterm infants.

Background and aims This field-base study evaluates the long-term effectiveness of in-situ remediation measures applied to soils residually polluted by potentially toxic elements (PTEs) in an area affected by a mining spill in SW Spain. Methods To evaluate the remediation treatments success, their influence on key soil properties and on the development of spontaneous vegetation in the treated soils was investigated. The treatments were based on human derived by-products valorization, and consisted of: biopiles, marble sludge and gypsum mining spoil addition, and their combination with an organic amendment (vermicompost). Results Amendments application improved the soil properties and reduced PTEs availability. As a result, an enhancement in spontaneous development of vegetation cover and diversity of plant species in the treated soils was followed. Spergularia rubra and Lamarckia aurea , two primary plant species growing in the studied area and that exhibit strong association to soils with the highest levels of pollution, showed high Pb and As accumulation in shoots ande in roots. Exceptionally, accumulation of these pollutants occurred in L. aurea roots, which can explain its high presence in soils with more limited vegetation development and in which no additional plant species can thrive. Conclusions The occurrence of S. rubra and L. aurea in the amended soils may be indicative of improved soil conditions and reduced toxicity induced by the remediation measures implemented. They may also be considered key species in the area since their presence can promote the recolonization of the degraded soils by species less tolerant to their residual pollution.

In a scenario of global climate change, water scarcity is a major threat for agriculture, severely limiting crop yields. Therefore, alternatives are urgently needed for improving plant adaptation to drought stress. Among them, gene expression reprogramming by microRNAs (miRNAs) might offer a biotechnologically sound strategy. Drought-responsive miRNAs have been reported in many plant species, and some of them are known to participate in complex regulatory networks via their regulation of transcription factors involved in water stress signaling. We explored the role of miR159 in the response of Solanum lycopersicum Mill. plants to drought stress by analyzing the expression of sly-miR159 and its target SlMYB transcription factor genes in tomato plants of cv. Ailsa Craig grown in deprived water conditions or in response to mechanical damage caused by the Colorado potato beetle, a devastating insect pest of Solanaceae plants. Results showed that sly-miR159 regulatory function in the tomato plants response to distinct stresses might be mediated by differential stress-specific MYB transcription factor targeting. sly-miR159 targeting of SlMYB33 transcription factor transcript correlated with accumulation of the osmoprotective compounds proline and putrescine, which promote drought tolerance. This highlights the potential role of sly-miR159 in tomato plants’ adaptation to water deficit conditions.

The incidences of Citrus leprosis virus C (CiLV-C) and Orchid fleck dichorhavirus Citrus strain (OFV-citrus) were determined in field populations of Brevipalpus mites from 15 citrus-producing states in Mexico. Mites were collected from orange, grapefruit, mandarin, lime, and sweet lime orchards. Brevipalpus yothersi (Baker) (Trombidiformes: Tenuipalpidae) was the most abundant species followed by Brevipalpus californicus (Banks) (Trombidiformes: Tenuipalpidae), which confirmed previous reports. The viruses CiLV-C and OFV-citrus were found in both mite species. The incidence of CiLV-C, OFV-citrus and both viruses simultaneously (CiLV-C and OFV-citrus) was 17.2, 10.3, and 3.4% (n = 116) for B. yothersi, and 12.5, 20.8, and 4.1% (n = 24) for B. californicus, respectively. No significant difference was found when the incidence of these viruses was compared between both mite species. The importance of our results in relation to the epidemiology of leprosis is discussed.

Objective The objective was to determine and compare demographic features, professional activities and adversities, physical health conditions, and self-care behaviors related to the most frequently self-reported mental health problems among psychiatrists and psychiatry trainees. Methods A cross-sectional, retrospective, comparative study was conducted on a total of 330 (48.2%) psychiatry trainees and 355 (51.8%) psychiatrists from Mexico through an online survey. Demographic features, professional activities and adversities, physical and mental health problems, self-care behaviors, and social support were examined. Comparative analyses and multiple logistic regression models were performed. Results Major depression, anxiety, and burnout were the most common mental health problems reported with a higher frequency of anxiety disorders in psychiatry trainees. Being a woman, having a physical health problem, and lack of restful sleep were the main risk factors in both groups. Consultation in the government sector and having patients with severe suicidal ideation affected more psychiatry trainees. Perceived discrimination and inadequate eating schedules were risk factors for mental health problems for psychiatrists. Conclusion Psychiatry trainees constitute a vulnerable group for anxiety disorders. Particular attention should be paid to how students cope with the training experience to determine whether additional support is required. These professionals face major stressors leading to a high prevalence of depression, burnout, and anxiety. Encouraging psychiatrists to have better health habits is a step in the right direction, which must be accompanied by tangible organizational avenues to do so and creating a culture that truly promotes self-care.

The concept of psychopathy has shifted from people who commit crimes to those with a particular personality and deviant behaviors. Although antisocial personality disorder is associated with psychopathy, it also seems common in individuals with narcissistic personality traits. Psychopathy may be the expression of earlier, persistent patterns of individual characteristics as personality. The psychobiological model of personality can be useful for determining whether the expression of psychopathy differs in accordance with personality dimensions and specific personality disorders. The aim was to compare temperament and character dimensions between individuals with psychopathy with comorbid predominant antisocial or narcissistic personality traits and control subjects and to determine which dimensions distinguish these groups. Control subjects (n = 80) and individuals with psychopathy (n = 80) were assessed using the Psychopathy Checklist-Reviewed, the Structured Clinical Interview for DSM-IV Axis II disorders and the Temperament and Character Inventory-Revised. Reward dependence and Self-Directedness distinguish psychopathic individuals with predominant narcissistic personality traits whereas Novelty Seeking and Self-Transcendence characterize those with antisocial personality traits. Individuals with antisocial or narcissistic psychopathy could be identified by their temperament and character traits. The expression of psychopathy differed in accordance with biologically based, environmentally shaped personality traits.