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Recent studies have demonstrated that Sirtuin-1 (SIRT-1)-activating molecules exert a protective role in degenerative ocular diseases. However, these molecules hardly reach the back of the eye due to poor solubility in aqueous environments and low bioavailability after topical application on the eye’s surface. Such hindrances, combined with stability issues, call for the need for innovative delivery strategies. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for SIRT-1 delivery can represent a promising approach. The aim of the work was to design and optimize SNEDDS for the ocular delivery of two natural SIRT-1 agonists, resveratrol (RSV) and melatonin (MEL), with potential implications for treating diabetic retinopathy. Pre-formulation studies were performed by a Design of Experiment (DoE) approach to construct the ternary phase diagram. The optimization phase was carried out using Response Surface Methodology (RSM). Four types of SNEDDS consisting of different surfactants (Tween® 80, Tween® 20, Solutol® HS15, and Cremophor® EL) were optimized to achieve the best physico-chemical parameters for ocular application. Stability tests indicated that SNEDDS produced with Tween® 80 was the formulation that best preserved the stability of molecules, and so it was, therefore, selected for further technological studies. The optimized formulation was prepared with Capryol® PGMC, Tween® 80, and Transcutol® P and loaded with RSV or MEL. The SNEDDS were evaluated for other parameters, such as the mean size (found to be ˂50 nm), size homogeneity (PDI < 0.2), emulsion time (around 40 s), transparency, drug content (>90%), mucoadhesion strength, in vitro drug release, pH and osmolarity, stability to dilution, and cloud point. Finally, an in vitro evaluation was performed on a rabbit corneal epithelial cell line (SIRC) to assess their cytocompatibility. The overall results suggest that SNEDDS can be used as promising nanocarriers for the ocular drug delivery of RSV and MEL.

Background: The treatment of the third malleolus has evolved in recent years, and surgical treatment can be carried out with traditional percutaneous osteosynthesis using anteroposterior screws or ORIF with a posterolateral plate. Methods: Our study included 54 patients divided into two groups based on the intervention type (screw or plate). Instrumental assessments comprised pre- and post-operative X-rays and pre-operative CT scans to evaluate joint step-off. The mean follow-up duration was 1 year and 9 months. Results: Radiographic control revealed no loss of reduction or mobilization of the synthesis devices, and all patients achieved fracture healing. Articular step-off > 2 mm was observed in 21 patients (38.9%), including 4 in the plate group and 17 in the screw group, with a statistically significant likelihood of step-off presence in the latter. The mean AOFAS score was 90 points, negatively correlated with age, and lower in patients with joint step-off and a 15° reduction in ROM. Conclusions: The management of posterior malleolus fractures has changed with anatomical studies and an understanding of ankle stability through CT scans. ORIF with a posterior plate is advantageous for anatomical reduction of the tibial plafond but is disadvantageous in terms of surgical invasiveness and technical difficulty.

La organización en los servicios de medicina hospitalaria se caracteriza por su jerarquización, donde la diferencia de conocimientos y de estatus entre directores médicos, jefes de servicio, médicos especialistas y residentes conlleva implícitamente una dinámica de poder generadora de maltrato. Según la teoría simbólica de Bourdieu el entramado que subyace al maltrato está formado por la violencia simbólica que se materializa en unas relaciones complejas en las que cada uno conoce su posición jerárquica y no la cuestiona. Pero está violencia simbólica es experimentada de forma inconsciente, donde el maltrato se percibe como una actitud que forma parte de un orden establecido donde el maltratador y el maltratado actúan sin cuestionar el maltrato y perpetuando el modelo heredado históricamente. Para erradicar el maltrato a los residentes es preciso tomar conciencia de la fundamentación simbólica del maltrato que lo legitima y perpetua para desenmascarar la relación entre el maltratador y el maltratado, proponiendo un nuevo marco relacional basado en el respeto y el diálogo.

Summary: Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio

This paper characterizes the heat stress response (HSR) and explores the impact of temperatures on the immune response of larvae from two chironomid species, Prodiamesa olivacea and Chironomus riparius. Genes involved in crucial metabolic pathways were de novo identified in P. olivacea: Hsp27, Hsp60, Hsp70, Hsc70, Cdc37, and HSF for the heat stress response (HSR) and TOLL, PGRP, C-type lectin, and JAK/hopscotch for the immune system response (ISR). Quantitative real-time PCR was used to evaluate the expression levels of the selected genes in short-term treatments (up to 120') at high temperatures (35 °C and 39 °C). Exposing P. olivacea to elevated temperatures resulted in HSR induction with increased expression of specific heat shock genes, suggesting the potential of HSPs as early indicators of acute thermal stress. Surprisingly, we found that heat shock represses multiple immune genes, revealing the antagonist relation between the heat shock response and the innate immune response in P. olivacea. Our results also showed species-dependent gene responses, with more significant effects in P. olivacea, for most of the biomarkers studied, demonstrating a higher sensitivity in this species to environmental stress conditions than that of C. riparius. This work shows a multi-species approach that enables a deeper understanding of the effects of heat stress at the molecular level in aquatic dipterans.

IntroductionThe availability of a human-like chronic heart failure (HF) animal model was critical for affiliating development of novel therapeutic drug treatments. With the close physiology relatedness to humans, the non-human primate (NHP) HF model would be valuable to better understand the pathophysiology and pharmacology of HF. The purpose of this work was to present preliminary cardiac image findings using echocardiography and cardiovascular magnetic resonance (CMR) in a HF-like cynomolgus macaque model.MethodsThe NHP diet-induced model developed cardiac phenotypes that exhibited diastolic dysfunction with reduced left ventricular ejection fraction (LVEF) or preserved LVEF. Twenty cynomolgus monkeys with cardiac dysfunction were selected by echocardiography and subsequently separated into two groups, LVEF

BackgroundA major barrier to a healthy diet may be the higher price of healthy foods compared to low-quality foods.ObjectivesThis study aimed to assess the association between the monetary cost of food and diet quality in Spanish older adults at high risk of cardiovascular disease.MethodsCross-sectional analysis was carried out in Spanish older adults (n = 6,838; 48.6% female). A validated food frequency questionnaire was used to assess dietary intake. Metabolic syndrome severity, adherence to the Mediterranean diet (MedDiet), adherence to a provegetarian dietary pattern, and dietary inflammatory index were assessed. The economic cost of the foods was obtained from the Spanish Ministry of Agriculture Fisheries and Food database (2015–2017, the period of time when the participants were recruited). The total cost of diet adjusted per 1,000 kcal was computed.ResultsThe healthier dietary pattern was associated with a higher cost of the diet. Higher adherence to the MedDiet, anti-inflammatory diet, and the healthy version of the provegetarian dietary pattern were related to higher costs of the diet.ConclusionHigher diet quality was associated with a higher dietary cost of the diet per 1,000 kcal/day. Food prices can be an important component of interventions and policies aimed at improving people's diets and preventing diet-related chronic diseases.Clinical trial registry numberThe trial was registered in 2014 at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870) with the number 89898870.

Abstract Background Genetic risk factors impact around 15% of Parkinson's disease (PD) patients and at least 23 variants have been identified including Glucocerebrosidase (GBA) gene variants. Using different clinical and instrumental qualitative‐based data, various studies have been published on GBA‐PD cohorts which suggested possible differences in dopaminergic nigrostriatal denervation pattern, particularly in caudate and putamen nuclei. Methods This retrospective study included two consecutive homogenous cohorts of GBA‐PD and idiopathic (I‐PD) patients. Each consecutive GBA‐PD patient has been matched with a 1:1 pairing method with a consecutive I‐PD subject according to age, age at disease onset, sex, Hoehn & Yahr (H&Y) staging scale and comorbidity level (CCI). Semiquantitative volumetric data by the DaTQUANTTM software integrated in the DaTSCAN exam performed at time of the diagnosis (SPECT imaging performed according to current guidelines of I‐123 FPCIT SPECT imaging) were extrapolated. Bilateral specific binding ratios (SBR) at putamen and caudate levels were calculated, using the occipital lobes uptake. The Mann–Whitney test was performed to compare the two cohorts while the Spearman's test was used to find correlations between motor and volumetric data in each group. Bonferroni correction was used to account for multiple comparisons. Results Two cohorts of 25 patients each (GBA‐PD and I‐PD), were included. By comparing GBA‐PD and I‐PD patients, lower SBR values were found in the most affected anterior putamen and left caudate of the GBA‐PD cohort. Furthermore, in the GBA‐PD cohort the SBR of the most affected posterior putamen negatively correlated with the H&Y scale. However, none of these differences or correlations remained significant after Bonferroni correction for multiple comparisons. Conclusions We observed differences in SBR values in GBA‐PD patients compared with I‐PD. However, these differences were no longer significant after Bonferroni multiple comparisons correction highlighting the need for larger, longitudinal studies.

Abstract Understanding the responses of insect herbivores to plant chemical defences is pivotal for the management of crops and pests. However, the mechanisms of interaction are not entirely understood. In this study, we compared the whole transcriptome gene expression of the aphid Macrosiphum euphorbiae grown on two different varieties of tomato that differ in their inducible chemical defences. We used two isogenic lines of tomato with a shared genetic background that only differ in the presence of type IV glandular trichomes and their associated acylsucrose excretions. This works also reports a de novo transcriptome of the aphid M. euphorbiae. Subsequently, we identified a unique and distinct gene expression profile for the first time corresponding to aphid´s exposure to type IV glandular trichomes and acylsugars. The analysis of the aphid transcriptome shows that tomato glandular trichomes and their associated secretions are highly efficient in triggering stress-related responses in the aphid, and demonstrating that their role in plant defence goes beyond the physical impediment of herbivore activity. Some of the differentially expressed genes were associated with carbohydrate, lipid and xenobiotic metabolisms, immune system, oxidative stress response and hormone biosynthesis pathways. Also, the observed responses are compatible with a starvation syndrome. The transcriptome analysis puts forward a wide range of genes involved in the synthesis and regulation of detoxification enzymes that reveal important underlying mechanisms in the interaction of the aphid with its host plant and provides a valuable genomic resource for future study of biological processes at the molecular level using this aphid.

We compared hospital-acquired catheter-related bacteremia (CRB) episodes diagnosed at acute care hospitals in Catalonia, Spain, during the COVID-19 pandemic in 2020 with those detected during 2007–2019. We compared the annual observed and predicted CRB rates by using the negative binomial regression model and calculated stratified annual root mean squared errors. A total of 10,030 episodes were diagnosed during 2007–2020. During 2020, the observed CRB incidence rate was 0.29/103 patient-days, whereas the predicted CRB rate was 0.14/103 patient-days. The root mean squared error was 0.153. Thus, a substantial increase in hospital-acquired CRB cases was observed during the COVID-19 pandemic in 2020 compared with the rate predicted from 2007–2019. The incidence rate was expected to increase by 1.07 (95% CI 1–1.15) for every 1,000 COVID-19–related hospital admissions. We recommend maintaining all CRB prevention efforts regardless of the coexistence of other challenges, such as the COVID-19 pandemic.

Abstract Background Post-traumatic stress disorder (PTSD) is a debilitating disorder defined by the onset of intrusive, avoidant, negative cognitive or affective, and/or hyperarousal symptoms after witnessing or experiencing a traumatic event. Previous voxel-based morphometry studies have provided insight into structural brain alterations associated with PTSD with notable heterogeneity across these studies. Furthermore, how structural alterations may be associated with brain function, as measured by task-free and task-based functional connectivity, remains to be elucidated. Methods Using emergent meta-analytic techniques, we sought to first identify a consensus of structural alterations in PTSD using the anatomical likelihood estimation (ALE) approach. Next, we generated functional profiles of identified convergent structural regions utilizing resting-state functional connectivity (rsFC) and meta-analytic co-activation modeling (MACM) methods. Finally, we performed functional decoding to examine mental functions associated with our ALE, rsFC, and MACM brain characterizations. Results We observed convergent structural alterations in a single region located in the medial prefrontal cortex. The resultant rsFC and MACM maps identified functional connectivity across a widespread, whole-brain network that included frontoparietal and limbic regions. Functional decoding revealed overlapping associations with attention, memory, and emotion processes. Conclusions Consensus-based functional connectivity was observed in regions of the default mode, salience, and central executive networks, which play a role in the tripartite model of psychopathology. Taken together, these findings have important implications for understanding the neurobiological mechanisms associated with PTSD.

Abstract Goat warble fly infestation (GWFI) is a subcutaneous myiasis caused by larvae of Przhevalskiana silenus, an insect belonging to the order Diptera. The diagnosis of GWFI is challenging in the early larval instars (L1 and L2) as they are occult under the skin and hair coat causing prolonged economic loss in form of meat and hide damage. This necessitates early diagnosis for disease control at herd level and its prophylactic management to prevent economic losses. Hypodermins, a class of serine proteases from Hypoderminae subfamily have been used as serodiagnostic antigens for the past four decades for diagnosis of warble fly myiasis. In this study,the immunodominant antigen Hypodermin C (HyC) from P. silenus has been recombinantly expressed in E. coli and immunogenic characterisation of expressed protein was done. The protein shows hallmark residues in conserved cysteine and catalytic triad typical of serine proteases along with similar profile of immunoreactivity towards Hypoderminae infestation. The present study reports an optimised indirect-ELISA based on recombinant HyC derived from P. silenus for early diagnosis of GWFI. The optimised indirect ELISA provides a sensitive and specific immunodiagnostic for mass surveillance of the GWFI with diagnostic specificity and sensitivity of 96% and 100%, respectively and not showing any cross reactivity against other important parasitic and bacterial diseases of goats. This study presents the first report of indirect ELISA based on recombinant Hypodermin C antigen derived from P. silenus for the serosurveillance of goat warble fly disease.

Abstract Background Age and comorbidity are the main determinants of COVID-19 outcome. Shorter leukocyte telomere length (TL), a hallmark of biological aging, has been associated with worse COVID-19 outcomes. We sought to determine TL in patients with severe COVID-19 requiring hospitalization to analyze whether clinical outcomes and post-COVID-19 manifestations are associated with shorter TL. Results We analyzed 251 patients with PCR-confirmed COVID-19, hospitalized in the first months of the pandemics. We determined TL in PBL at admission by quantitative-PCR (qPCR) analysis in patients. A healthy cohort from the same area with a similar age range (n = 169) was used to calculate TL Z-scores. After hospital discharge, 144 COVID-19 survivors were followed-up for persistent COVID-19 manifestations. A second TL determination was performed in a smaller group of 63 patients 1 year later and compared with baseline TL. Hospitalized COVID-19 patients had a decreased baseline age-adjusted TL Z-score compared to the reference group. No differences in Z-scores were observed in patients with different COVID-19 outcomes, classified as WHO ordinal scores. In 144 patients, followed for a median of 8 months, post-COVID manifestations were not associated to differences in TL. Persistence of lung radiographic abnormalities was associated with shorter baseline TL. In patients with a second TL determination, further telomere shortening (TS) was observed in 35% and telomere lengthening in 49%. Patients with further TS had suffered a more severe disease. Conclusion Shorter TL is associated with COVID-19 hospitalization but not with hospital clinical outcomes nor with persistent post-COVID-19 manifestations. Delayed resolution of radiographic lung abnormalities was also associated with shorter TL.

Investigaciones recientes han demostrado que la práctica continuada de actividad física (AF) aporta beneficios sobre el rendimiento académico en alumnado de diferentes etapas, siendo la etapa de preescolar la menos estudiada. El objetivo de este trabajo fue estudiar y sintetizar la relación existente entre la práctica de AF y la mejora de las funciones ejecutivas y el rendimiento académico en preescolar, dando una visión general del estado actual de la cuestión. Para ello, se realizó una revisión sistemática, centrada en la identificación de las características generales y la eficacia de los programas de intervención llevados a cabo en este contexto educativo. Para el desarrollo de la misma, se realizó una búsqueda de literatura científica en las bases de datos Web of Science (WOS), Scopus y Proquest. Se utilizaron simultáneamente como términos claves “physical activity”, “academic achievement” y “preschool”, y como operadores booleanos “and” y “or”, y se fijó una muestra válida para este estudio de un total de 18 artículos científicos para la síntesis cualitativa. Los resultados del estudio indican que existe una asociación positiva al integrar la AF en el aula y la mejora de las funciones ejecutivas y los resultados académicos, independientemente del contenido curricular trabajado y del tipo de AF que se utilice. Así, integrar la AF en el aula (como clases físicamente activas o descansos activos), puede ser una importante estrategia para mejorar la alfabetización temprana y el aprendizaje de los contenidos curriculares, al mismo tiempo que se consiguen niveles de AF cercanos a los recomendados diariamente.

Introducción: El tratamiento oncológico es cada vez más agresivo. El objetivo de este trabajo fue estimar las personas fallecidas por causa oncológica, reportar la frecuencia de uso de quimioterapia (QT) en los últimos 3 meses de vida, y describir las características clínicas-epidemiológicas de estos pacientes. Métodos: Se incluyó una muestra consecutiva de fallecidos durante el 2017, afiliados a prepaga del Hospital Italiano de Buenos Aires. Mediante revisión de historias clínicas, se los clasificó según la causa de muerte (oncológico u otra causa), validando diagnóstico y estadio de base, performance status (PS). Se reportan prevalencias con IC95% y se utilizó estadística descriptiva. Resultados: Fallecieron 2293 personas, 59% mujeres con mediana de 84 años. Hubo un total de 736 fallecidos por cáncer, representando el 32% (IC95% 30-34). Este último subgrupo presentó una mediana de 75 años, 54% eran mujeres y sólo una paciente tenía directivas anticipadas. En cuanto al lugar de fallecimiento, 80% ocurrió hospitalizado (65% sala general y 15% unidad cerrada). Los tumores más frecuentes fueron: pulmón, colorrectal-gástrico, hematológico, y mama. Un total de 390 pacientes recibieron QT al final de la vida (53%; IC95% 49-57), siendo 53% mujeres y con promedio de 68 años. En cuanto a la enfermedad oncológica de base: 81% tenían tumor sólido, 75% estadío avanzado, y mayoritariamente con mala/regular capacidad para realizar actividades cotidianas (25% PS3 y 32% PS4 respectivamente). Conclusión: Existe una frecuencia preocupante del uso de QT en el fin de vida y los fallecimientos siguen siendo principalmente intrahospitalarios.

Environmental pollutants are claimed to be major factors involved in the progressive decline of the fertility rate worldwide. Exposure to the heavy metal Cadmium (Cd) has been associated with reproductive toxicity due to its ionic mimicry. However, the possible direct accumulation of Cd in human sperm cells has been poorly investigated. In this study, we aimed to clarify the possible direct effect of Cd exposure on sperm function through the analysis of its cell accumulation. Semen samples from 30 male subjects residing in high environmental impact areas and adhering to the “Exposoma e Plurifocalità nella Prevenzione Oncologica” campaign for testis cancer prevention were compared with semen samples from 15 males residing in low exposure areas. Semen levels and cell Cd content were quantified by inductively coupled plasma (ICP) spectroscopy. Cell Cd distribution was assessed by scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS). The impact of Cd on sperm function was evaluated by the in vitro exposure to the heavy metal, whilst possible scavenging approaches/agents were assessed. In addition to higher values of semen Cd, exposed subjects showed a reduction in total motile sperm fraction compared to not-exposed controls (59.6% ± 13.6% vs. 66.3% ± 7.3%, p = 0.037). Semen Cd levels were also significantly correlated with SEM-EDS signals of Cd detected on the head and neck of sperm (respectively p = 0.738, p < 0.001 and ρ = 0.465, p < 0.001). A total of 2 h of in vitro exposure to 0.5 μM Cd was associated with a significant reduction of sperm progressive motility. Scavenging approaches with either hypo-osmotic swelling or 10 μM reduced glutathione were ineffective in blunting cell Cd and restoring motility. The reduction of exposure levels appears to be the main approach to reducing the reproductive issues associated with Cd.

Aims: To assess the comparative effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), 4-dipeptidyl peptidase inhibitors (DPP-4I), and metformin treatment during one year on metabolic syndrome (MetS) components and severity in MetS patients. Methods: Prospective study (n = 6165 adults) within the frame of PREDIMED-Plus trial. The major end-point was changes on MetS components and severity after one- year treatment of GLP-1RA, DPP-4I, and metformin. Anthropometric measurements (weight, height and waist circumference), body mass index (BM), and blood pressure were registered. Blood samples were collected after overnight fasting. Plasma glucose, glycosylated hemoglobin (HbA1c), plasma triglycerides and cholesterol were measured. Dietary intakes as well as physical activity were assessed through validated questionnaires. Results: MetS parameters improved through time. The treated groups improved glycaemia compared with untreated (glycaemia ∆ untreated: −1.7 mg/dL(± 13.5); ∆ metformin: − 2.5(± 23.9) mg/dL; ∆ DPP-4I: − 4.5(± 42.6); mg/dL ∆ GLP-1RA: − 4.3(± 50.9) mg/dL; and HbA1c: ∆ untreated: 0.0(± 0.3) %; ∆ metformin: − 0.1(± 0.7) %; ∆ DPP-4I: − 0.1(± 1.0) %; ∆ GLP-1RA: − 0.2(± 1.2) %. Participants decreased BMI and waist circumference. GLP-1RA and DPP-4I participants registered the lowest decrease in BMI (∆ untreated: −0.8(± 1.6) kg/m2; ∆ metformin: − 0.8(± 1.5) kg/m2; ∆ DPP-4I: − 0.6(± 1.3) kg/m2; ∆ GLP-1RA: − 0.5(± 1.2) kg/m2. and their waist circumference (∆ untreated: −2.8(± 5.2) cm; ∆ metformin: − 2.6(± 15.2) cm; ∆ DPP-4I: − 2.1(± 4.8) cm; ∆ GLP-1RA: − 2.4(± 4.1) cm. Conclusion: In patients with MetS and healthy lifestyle intervention, those treated with GLP-1RA and DPP-4I obtained better glycemic profile. Anthropometric improvements were modest.

Clinical trials have shown that lentiviral-mediated gene therapy can ameliorate bone marrow failure (BMF) in nonconditioned Fanconi anemia (FA) patients resulting from the proliferative advantage of corrected FA hematopoietic stem and progenitor cells (HSPC). However, it is not yet known if gene therapy can revert affected molecular pathways in diseased HSPC. Single-cell RNA sequencing was performed in chimeric populations of corrected and uncorrected HSPC co-existing in the BM of gene therapy-treated FA patients. Our study demonstrates that gene therapy reverts the transcriptional signature of FA HSPC, which then resemble the transcriptional program of healthy donor HSPC. This includes a down-regulated expression of TGF-β and p21, typically up-regulated in FA HSPC, and upregulation of DNA damage response and telomere maintenance pathways. Our results show for the first time the potential of gene therapy to rescue defects in the HSPC transcriptional program from patients with inherited diseases; in this case, in FA characterized by BMF and cancer predisposition.

The retinal pigment epithelium (RPE) is progressively degenerated during age-related macular degeneration (AMD), one of the leading causes of irreversible blindness, which clinical hallmark is the buildup of sub-RPE extracellular material. Clinical observations indicate that Zn dyshomeostasis can initiate detrimental intracellular events in the RPE. In this study, we used a primary human fetal RPE cell culture model producing sub-RPE deposits accumulation that recapitulates features of early AMD to study Zn homeostasis and metalloproteins changes. RPE cell derived samples were collected at 10, 21 and 59 days in culture and processed for RNA sequencing, elemental mass spectrometry and the abundance and cellular localization of specific proteins. RPE cells developed processes normal to RPE, including intercellular unions formation and expression of RPE proteins. Punctate deposition of apolipoprotein E, marker of sub-RPE material accumulation, was observed from 3 weeks with profusion after 2 months in culture. Zn cytoplasmic concentrations significantly decreased 0.2 times at 59 days, from 0.264 ± 0.119 ng·μg−1 at 10 days to 0.062 ± 0.043 ng·μg−1 at 59 days (p

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

Scotta is an underutilized whey by-product of ricotta making. In this study, we investigated the utilization of scotta in beer production. To understand the quality of regional scotta, samples from eight Sicilian ricotta makers were analyzed for pH, total protein, fat, lactose, titratable acidity, % salt, total plate count, lactic acid bacteria counts, and minerals. Overall, the samples had low amounts of residual protein and fat. The average lactose content was 4.81 g/100 mL ± 0.52 g, with a pH of 6.12 ± 0.17 and a salt content of 1.05% ± 0.24. The majority of lactic acid bacteria counts were below the limit of detection. The total plate counts were more variable, ranging between 102 to 103 CFU/mL, suggesting occasional post-processing contamination during handling. Scotta was then used to replace some of the water and sugar in the production of two beer styles: (i) a Gose, a salty and acidified German beer style, and (ii) a sweet milk stout. A trained panel used for sensory analysis found that these prototypes fit within the sensory profiles of commercial beers of these styles. This work highlights opportunities to upcycle dairy by-products into novel fermented beverages that would be appealing to consumers.

Nowadays, there is considerable attention toward the use of food waste from food processing as possible sources of compounds with health properties, such as anticancer activity. An example is tomato processing, which is responsible for generating a remarkable amount of waste (leaves, peel, seeds). Therefore, our goal was to evaluate the potential anticancer property of tomato extracts, in particular “Datterino” tomato (DT) and “Piccadilly” tomato (PT), and to study their phytochemical composition. Liquid chromatography with tandem mass spectrometry (LC/MS-MS) results showed that these extracts are rich in alkaloids, flavonoids, fatty acids, lipids, and terpenes. Furthermore, their potential anticancer activity was evaluated in vitro by MTT assay. In particular, the percentage of cell viability was assessed in olfactory ensheathing cells (OECs), a particular glial cell type of the olfactory system, and in SH-SY5Y, a neuroblastoma cell line. All extracts (aqueous and ethanolic) did not lead to any significant change in the percentage of cell viability on OECs when compared with the control. Instead, in SH-SY5Y we observed a significant decrease in the percentage of cell viability, confirming their potential anticancer activity; this was more evident for the ethanolic extracts. In conclusion, tomato leaves extracts could be regarded as a valuable source of bioactive compounds, suitable for various applications in the food, nutraceutical, and pharmaceutical fields.

Tomato by-products represent a good source of phytochemical compounds with health properties, such as the steroidal glycoalkaloid α-tomatine (α-TM) and its aglycone tomatidine (TD). Both molecules have numerous beneficial properties, such as potential anticancer activity. Unfortunately, their therapeutic application is limited due to stability and bioavailability issues. Therefore, a valid strategy seems to be their encapsulation into Solid Lipid Nanoparticles (SLN). The nanoformulations containing α-TM (α-TM-SLN) and TD (TD-SLN) were prepared by solvent-diffusion technique and subsequently characterized in terms of technological parameters (particle size, polydispersity index, zeta potential, microscopy, and calorimetric studies). To assess the effect of α-TM and TD on the percentage of cellular viability in Olfactory Ensheathing Cells (OECs), a peculiar glial cell type of the olfactory system used as normal cells, and in SH-SY5Y, a neuroblastoma cancer cell line, an MTT test was performed. In addition, the effects of empty, α-TM-SLN, and TD-SLN were tested. Our results show that the treatment of OECs with blank-SLN, free α-TM (0.25 µg/mL), and TD (0.50 µg/mL) did not induce any significant change in the percentage of cell viability when compared with the control. In contrast, in SH-SY5Y-treated cells, a significant decrease in the percentage of cell viability when compared with the control was found. In particular, the effect appeared more evident when SH-SY5Y cells were exposed to α-TM-SLN and TD-SLN. No significant effect in blank-SLN-treated SH-SY5T cells was observed. Therefore, SLN is a promising approach for the delivery of α-TM and TD.

(1) Background: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is characterized by late-onset cerebellar ataxia, bilateral vestibulopathy, and sensory neuronopathy mostly due to biallelic RFC1 expansion. (2) Objectives: The aim of this case series is to describe vestibular, gait, and speech alterations in CANVAS via a systematic approach. (3) Methods: All patients (n = 5) underwent a standardized clinical–instrumental examination, including the perceptual and acoustic analysis of speech, instrumental gait, and balance analysis (posturographic data were acquired using a force plate [Kistler, Winterthur, Switzerland] while 3D gait analysis, inclusive of surface electromyography, was acquired using a motion capture system [SMART DX, BTS Bioengineering, Milan, Italy], a wireless electromyograph [FreeEMG, BTS Bioengineering, Milan, Italy]), and vestibular assessment with video-oculography. (4) Results: Five patients were included in the analysis: three females (patients A, B, C) and two males (patients D and E) with a mean age at evaluation of 62 years (SD ± 15.16, range 36–74). The mean age of symptoms’ onset was 55.6 years (SD ± 15.04, range 30–68), and patients were clinically and instrumentally evaluated with a mean disease duration of 6.4 years (SD ± 0.54, range 6–7). Video-Frenzel examination documented spontaneous downbeat nystagmus enhanced on bilateral gaze in all patients, except for one presenting with slight downbeat nystagmus in the supine position. All patients exhibited different degrees of symmetrically reduced VOR gain for allsix semicircular canals on the video-head impulse test and an unexpectedly normal (“false negative”) VOR suppression, consistent with combined cerebellar dysfunction and bilateral vestibular loss. Posturographic indices were outside their age-matched normative ranges in all patients, while 3D gait analysis highlighted a reduction in ankle dorsiflexion (limited forward rotation of the tibia over the stance foot during the stance phase of gait and fatigue of the dorsiflexor muscles) and variable out-of-phase activity of plantar flexors during the swing phase. Finally, perceptual-acoustic evaluation of speech showed ataxic dysarthria in three patients. Dysdiadochokinesis, rhythm instability, and irregularity were observed in the oral diadochokinesis task. (5) Conclusions: CANVAS is a recently discovered syndrome that is gaining more and more relevance within late-onset ataxias. In this paper, we aimed to contribute to a detailed description of its phenotype.

Abstract Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and z-score data obtained at Dual-Energy X-ray Absorptiometry (DXA) during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry DXA than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced z-score at DXA (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z-score (p

En el ámbito social y educativo, la perspectiva de género es uno de los elementos clave para conseguir la plena igualdad y una sociedad realmente democrática. Uno de los factores más importantes reside precisamente en las actitudes y la autoconciencia de la perspectiva de género por parte de los educadores y otros profesionales que trabajan en el campo de la educación. Con el fin de comprender cómo funciona el proceso de adquisición de la perspectiva de género de los futuros profesionales de la educación, este trabajo analiza en qué medida se incorpora la perspectiva de género en las asignaturas de los grados de Educación Social y Pedagogía de la Universitat de les Illes Balears. Se utiliza una metodología mixta, combinando, por un lado, el análisis documental y estadístico de las guías didácticas de las asignaturas de grado (64) y, por otro, el análisis cualitativo de grupos de discusión de estudiantes con el objetivo de captar su percepción. Los resultados indican que aún es necesario mejorar el uso del lenguaje inclusivo y no androcéntrico, así como la incorporación y transversalización de la perspectiva de género en la enseñanza de los estudios. En concreto, es necesario incluirlas en sus competencias, contenidos y evaluación, así como ampliar las referencias bibliográficas donde estén representadas las mujeres. El trabajo incluye algunas recomendaciones para mejorar la inclusión de la perspectiva docente en la práctica docente universitaria.

Abstract Background In Europe, Babesia infections in cats are sporadic and only partial knowledge is currently available since the number of described cases including both the clinical presentation and the molecular identification of the Babesia species involved is limited. In the present case report, the clinical signs, the epidemiological data and the molecular results suggest that this is the first reported fatal case of feline babesiosis caused by Babesia canis. Case presentation A six month old female European shorthair cat from north-western Spain died after being hospitalized for two days. This animal was pregnant and showed anorexia, lethargy, weakness, jaundice and fever with increased respiratory and heart rates. Haematological analysis revealed haemolytic regenerative anaemia, thrombocytopenia and leukocytosis. The presence of piroplasms was assessed using a PCR targeting the 18S rRNA gene of Babesia spp. and Theileria spp.; the sample resulted positive and B. canis was identified by DNA sequence analysis. The possible existence of co-infections with other vector-borne pathogens such as Anaplasma spp., Bartonella spp., Borrelia burgdorferi s.l., Cytauxzoon spp., Ehrlichia spp., Hepatozoon canis, Mycoplasma spp. or Rickettsia spp. was excluded by qPCR. Conclusions Our results together with previous reports on Babesia infections in cats from Europe suggest that feline babesiosis should be included in the differential diagnosis of animals with anaemia, thrombocytopenia, anorexia and lethargy, especially in young or immunocompromised animals from endemic areas for canine babesiosis.

Introduction: Choledocholithiasis is a disease in which the common bile duct is occupied by stones. Endoscopic retrograde cholangiopancreatography plays an important role in the treatment where the normal passage of bile is restored. Objective: To present a patient with COVID-19 and acute cholangitis due to multiple choledocholithiasis, who underwent endoscopic retrograde cholangiopancreatography. Clinical case: A 58-year-old woman, with a history of gallbladder stones, who was admitted in a state of septic shock due to possible acute cholangitis and mild respiratory symptoms, with a positive test for COVID-19. Choledocholithiasis was diagnosed by abdominal ultrasound and endoscopic retrograde cholangiopancreatography was performed, showing multiple stones in the common bile duct. Successful drainage of the main bile duct was achieved, without complications and favorable evolution. Conclusion: The treatment performed was a good option, in the clinical context, of a patient with COVID-19 and acute cholangitis due to common bile duct stones.

Introduction and Objectives: Patients with nonalcoholic fatty liver disease (NAFLD) are at increased cardiovascular risk, and there is a higher prevalence of this disease in patients with coronary heart disease (CHD). However, the evidence in favor of NAFLD as a risk factor for CHD is scarce. This study aimed to determine the prevalence of NAFLD in patients with CHD and to assess whether significant CHD is associated with NAFLD and liver fibrosis. Materials and Methods: Observational, analytical study in adult patients with coronary angiography for suspected coronary artery disease between July 2021-July 2022. The number of affected coronary vessels and the presence of significant CHD (stenosis >50%) were determined. In addition, FibroScan® was performed to evaluate steatosis and liver fibrosis up to 6 months after the coronary study, considering the presence of fibrosis at F>0. Descriptive statistics, Fisher's exact test and logistic regression models were reported for inferential analysis. Results: Ninety-seven patients were included, 73% male, age 63 ± 10 years (Table 1). 71% presented significant CHD, with 37% multivessel disease (2 or more). The prevalence of NAFLD was 38%, with no differences between those with and without CHD (43% vs. 36%, p=0.646). In turn, 16% of patients presented some degree of fibrosis, linearly associated with the number of vessels involved (OR=1.8, p=0.022), with an even higher risk in patients with two or more vessels involved (OR=3.5, p=0.027). Conclusions: There is a high prevalence of NAFLD in patients with CHD, with no differences between patients with significant stenosis vs not. Patients with multivessel disease have higher odd of presenting some degree of fibrosis. Although the presence of confounders should be evaluated in other studies, these data support the search for NAFLD and fibrosis in patients with CHD.

Introduction and Objectives: In chronic pathologies, such as cirrhosis, information is essential for disease acceptance, adherence to treatment and prevention of complications. This study aimed to determine whether written information in patients with cirrhosis has an effect on the level of knowledge and treatment adherence and to evaluate possible factors associated with disease-related knowledge in cirrhosis. Materials and Methods: Longitudinal, analytical study. Adult outpatients with cirrhosis were included in July-December 2021. Self-completed survey with demographic, clinical information, disease-related knowledge with ''Cirrhosis Knowledge Questionnaire'' (1 - 7 points) and treatment adherence with Morisky-Green-Levine scale (Low, Medium, High) were assessed. History of complications and hospitalizations in the last two years were obtained from clinical records. Patients were provided with an educational brochure and after four months, the disease-related knowledge and treatment adherence were re-evaluated. Comparative analysis was performed with T Student or ANOVA. Multiple linear regression models were assessed to identify possible associated factors (p < 0.05). Results: We included 104 patients, 53% men, the median age of 64 years, and 80% of them with middle or higher education. The most frequent etiologies of cirrhosis were alcohol (27%) and non-alcoholic steatohepatitis (26%). The median level of disease-related knowledge was 3 (RIC 2 - 5). Forty-three percent of the patients answered >50% of the answers correctly. Bivariate and multivariate analyses of the disease-related knowledge are described in Table 1. Disease-related knowledge levels increased after delivery of written information at the 4-month follow-up (3.21 vs. 3.96; p=0.0007), but treatment adherence did not. Conclusions: Less than half of the patients answered > 50% of disease-related knowledge correctly. Higher educational levels, history of hospitalization and complications due to cirrhosis were associated with a higher disease-related knowledge level score. The provision of written information is associated with an increase in disease-related knowledge levels in patients with cirrhosis.

Hemos leído con mucho interés el artículo “Ideación e intento suicida en pacientes con padecimientos psiquiátricos en un hospital de la Ciudad de México”, de Jiménez Genchi, en el que se concluye en la necesidad de la identificación temprana de los factores de riesgo que pueden incidir en incremento del comportamiento suicida.1

IntroductionPituitary metastases are very rare in cancer patients and often originate from lung or breast tumors. They usually occur in patients with known metastatic disease, but rarely may be the first presentation of the primary tumor.MethodsWe present the case of a 58 years-old-man who reported a three-month history of polyuria-polydipsia syndrome, generalized asthenia, panhypopituitarism and bitemporal hemianopsia. Brain-MRI showed a voluminous pituitary mass causing posterior sellar enlargement and compression of the surrounding structures including pituitary stalk, optic chiasm, and optic nerves.ResultsThe patient underwent neurosurgical removal of the mass. Histological examination revealed a poorly differentiated adenocarcinoma of uncertain origin. A total body CT scan showed a mass in the left kidney that was subsequently removed. Histological features were consistent with a clear cell carcinoma. However, endoscopic examination of the digestive tract revealed an ulcerating and infiltrating adenocarcinoma of the gastric cardia. Total body PET/CT scan with 18F-FDG confirmed an isolated area of accumulation in the gastric cardia, with no hyperaccumulation at other sites.ConclusionTo the best of our knowledge, there are no reports of pituitary metastases from gastric cardia adenocarcinoma. Our patient presented with symptoms of sellar involvement and without evidence of other body metastases. Therefore, sudden onset of diabetes insipidus and visual deterioration should lead to the suspicion of a rapidly growing pituitary mass, which may be the presenting manifestation of a primary extracranial adenocarcinoma. Histological investigation of the pituitary mass can guide the diagnostic workup, which must however be complete.

Many priority pollutants are concentrated in the environment due to human activity. Most are highly toxic to various organisms, including endocrine disruptors EDCs, aromatic polycyclic hydrocarbons PAHs, pesticides. While the effects of single and binary exposure have been widely explored, several pollutants can be simultaneously present at the same time in the environment, in in more or less polluted matrices. Effective pollution control requires the presence and sources of contamination to be identified. Previously we used Drosophila melanogaster to investigate metal pollution. Here, we re-used Drosophila to identify the biomarkers of pollution, and to determine if they can be used for specific types of pollution. Single and combined exposure of Bis(2-ethylhexyl) phthalate (DEHP), bisphenol A, nonylphenol, benzo(a)pyrene, and glyphosate was investigated. The impact of these pollutants on post-embryonic development and the expression pattern of 38 molecular targets were examined using qPCR. During single exposure, different profiles were observed at the molecular level. In complex mixtures, the expression profile resembled that of bisphenol A. In contrast, relatively specific gene expression profiles were obtained for the effects of each pollutant separately. While direct pollutant-gene profiling remains difficult in mixtures, molecular biology analyses enhance pollution monitoring, and should be incorporated in toxicological studies.

Prostate cancer is the most frequent malignant tumor in male. Despite its incidence increased in the last few years, the mortality is gradually decreasing, even in patients with metastatic prostate cancer (mPC). Unfortunately, prolongation of survival leads to the exhaustion of therapeutic chances. Therefore, patients with good performance status (PS) may remain out of further active treatments. We report the clinical case of a 71-year-old patient with symptomatic metastatic castration-resistant prostate cancer (mCRPC) and good PS who progressed after multiple treatments and started a hormonal therapy with megestrol acetate (MA). MA is a synthetic progestin used for treatment of mPC in 1990s since it was shown to have an antiandrogen activity. In our case, MA managed to overcome resistance to androgen receptor-targeted agents (ARTAs), getting a dramatic biochemical and radiological response and a rapid improvement of symptoms. Our clinical case shows that MA is an interesting therapeutic option especially in long-survivor patients with mCRPC and a long progression-free survival during ARTAs therapies.

Desde el punto de vista comunicativo, los partidos conectivos se definen por su inclinación hacia modelos participativos donde los flujos conversacionales posean una estructura horizontal y bidireccional entre la élite de la formación y el activismo de base. Esto es posible gracias a que ceden parte de su organización a herramientas de la Web. Dentro de esta taxonomía se encuentra el partido español Unidas-Podemos como ejemplo de partido conectivo. En esta investigación se analiza la vertiente comunicativa externa, basada en el uso de redes sociales online, de los principales partidos políticos españoles durante el periodo de Estado de Alarma provocado por el COVID-19. Para ello, se observará la tasa de interacción y respuestas en Twitter de los representantes del Congreso de los Diputados. Los resultados muestran que los patrones comunicativos a nivel externo de Unidas-Podemos responden a criterios verticales, propios de los partidos convencionales. From a communicational point of view, connective parties are based on horizontal and bidirectional structure of conversational flows between the elite of the formation and the party activists. This is possible because they delegate part of their organization to digital and online platforms. In this paper we use the Spanish party Unidas-Podemos as a case of study of connective parties. Drawing upon the Twitter response and interaction rate between Spanish representatives and citizens, this research analyzes the external communicative aspect of the main Spanish political parties during the Lockdown caused by COVID-19. The results show that the external communication patterns of Unidas-Podemos respond to vertical criteria, typical of conventional parties.

Abstract Background To investigate the role of cell senescence in systemic sclerosis (SSc), we analyzed telomere shortening (TS) in SSc patients and the effect of targeting DNA damage in the bleomycin model of skin fibrosis. Results Telomere length (TL) in blood leukocytes of 174 SSc patients and 68 healthy controls was measured by Southern blot, and we found shorter age-standardized TL in SSc patients compared to healthy controls. TL was shorter in SSc patients with ILD compared to those without ILD and in anti-topoisomerase I positive compared to anti-centromere positive patients. To analyze the potential role of DNA damage in skin fibrosis, we evaluated the effects of the DNA protective GSE4 peptide in the bleomycin mouse model of scleroderma and the fibrotic response of cultured human dermal fibroblasts. Administration of GSE4-nanoparticles attenuated bleomycin-induced skin fibrosis as measured by Masson’s staining of collagen and reduced Acta2 and Ctgf mRNA expression, whereas transduction of dermal fibroblasts with a lentiviral GSE4 expression vector reduced COL1A1, ACTA2 and CTGF gene expression after stimulation with bleomycin or TGF-β, in parallel to a reduction of the phospho-histone H2A.X marker of DNA damage. Conclusions SSc is associated with TS, particularly in patients with lung disease or anti-topoisomerase I antibodies. Administration of GSE4 peptide attenuated experimental skin fibrosis and reduced fibroblast expression of profibrotic factors, supporting a role for oxidative DNA damage in scleroderma.

4-H academics responded to the COVID pandemic by rapidly adapting CDC and other resources for virtual delivery. A statewide epidemiology project was taught to 48 youth with the goal of minimizing fears and confusion, increasing prevention measures, leveraging current topics for education, and bolstering the social-emotional health of youth participants. Results indicated that youth enjoyed the project and adopted behaviors to reduce the spread of infectious diseases, such as increased mask-wearing.

Small vessel diseases (SVD) is an umbrella term including several entities affecting small arteries, arterioles, capillaries, and venules in the brain. One of the most relevant and prevalent SVDs is cerebral amyloid angiopathy (CAA), whose pathological hallmark is the deposition of amyloid fragments in the walls of small cortical and leptomeningeal vessels. CAA frequently coexists with Alzheimer’s Disease (AD), and both are associated with cerebrovascular events, cognitive impairment, and dementia. CAA and AD share pathophysiological, histopathological and neuroimaging issues. The venular involvement in both diseases has been neglected, although both animal models and human histopathological studies found a deposition of amyloid beta in cortical venules. This review aimed to summarize the available information about venular involvement in CAA, starting from the biological level with the putative pathomechanisms of cerebral damage, passing through the definition of the peculiar angioarchitecture of the human cortex with the functional organization and consequences of cortical arteriolar and venular occlusion, and ending to the hypothesized links between cortical venular involvement and the main neuroimaging markers of the disease.

The aim of this study is to analyse problems related to thermal mapping obtained from thermal data acquired from unmanned aerial systems (UAS) equipped with thermal cameras. We focused on an accurate analysis of uncertainties introduced by the PIX4D Mapper software version 4.4.12 used to obtain the surface temperature maps of thermal images acquired using the UAS. To achieve this aim, we used artificial thermal references during the surveys, as well as natural hot targets, i.e., thermal anomalies in the Pisciarelli hydrothermal system in Campi Flegrei caldera (CFc). Artificial thermal targets, expressly created and designed for this goal, are a prototype here called “developed thermal target” (DTT) created by the drone laboratory at Istituto Nazionale di Geofisica e Vulcanologia—Osservatorio Vesuviano (INGV-OV). We show the results obtained through three surveys, and during the last two, thermal targets were positioned on land at different flight heights of the UAS. Different heights were also necessary to test the spatial resolution of the DTT with the used thermal camera as well as possible temperature differences between the raw images acquired via UAS with the thermal mapping obtained from the PIX4D Mapper software. In this work, we estimate the uncertainty that may be introduced by the mosaic procedure, and furthermore we find an attenuation of the measured temperatures introduced by the different distances between the thermal anomaly and sensor. These results appear to be of great importance for the subsequent calibration phase of the thermal maps, especially in cases where these methodologies are applied for the purposes of monitoring volcanic/geothermal areas.

Book Review: Virtual reality in curriculum and pedagogy: Evidence from secondary classrooms. Ed. SheilaJagannathan.

Introducción: la cultura de paz tiene un enfoque integral para prevenir la violencia y los conflictos, que se ha ampliado a los lugares de trabajo, vinculando a las normas escritas y no escritas que deben ser seguidas para su adecuado funcionamiento. Método: la metodología de investigación que se utiliza en este artículo es la investigación documental que, como cualquier metodología de investigación científica, sigue un proceso sistemático para describir el papel que tiene la tecnología para fomentar la cultura de paz y el clima laboral en las organizaciones. Resultados: el gobierno corporativo se encarga de generar una cultura de paz, al igual que un clima laboral en las organizaciones, con el apoyo de los colaboradores motivados que trabajan con mayor compromiso y productividad, pero con la visión estratégica de la alta gerencia. Las organizaciones utilizan la tecnología para promover la productividad, automatización e innovación en los procesos, incluso desarrollar nuevas destrezas y habilidades, favorecer el diálogo, entre otros. En los últimos años, la tecnología ha revolucionado la humanidad y, también, alimenta el estrés, agotamiento e incluso la falta de compromiso de los trabajadores al utilizar técnicas intrusivas de supervisión. Conclusiones: considering that the coexistence of human beings is complex, the work environment and the culture of peace are key elements in the healthy life and growth of organizations, which improve the well-being, resilience and level of commitment of workers.

An ectopic thyroid is a form of thyroid dysgenesis in which the entire thyroid gland or parts of it may be located in another part of the body than the usual place. The most frequent location is the base of the tongue. Although most cases are asymptomatic, symptoms related to tumor size and its relationship with surrounding tissues, hormonal dysfunction, and seldom malignancy may also occur. Here, we describe the case of an asymptomatic woman who was thyroidectomized 19 years previously for a toxic goiter and treated with conventional L-thyroxine therapy, until we enacted a progressive reduction of dosage of the replacement therapy. Incidentally, because of occasional abdomen discomfort, she was hospitalized in our Division of Endocrinology as there was ultrasound evidence of a large mass in the liver dislocating and imprinting the choledochal duct in the pre-pancreatic site, the gallbladder, and the cystic duct, which could not be dissociated from the contiguous hepatic parenchyma and was in very close proximity to the second duodenal portion and the head of the pancreas. Imaging techniques, such as TC, MR, TC/PET, and 131I scintigraphy, confirmed the large lesion with a diameter on the axial plane of about 8 × 5.5 cm and a cranio-caudal extension of about 6 cm. The impossibility of surgical debulking and/or radiometabolic 131I therapy, in the absence of compression symptoms, led to the multidisciplinary decision of a clinical and instrumental follow-up of this rare lesion.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) represents the most frequent form of CAH and of 46, XX disorder of sex development in female newborns. In the majority of cases, particularly in developed countries, female patients suffering from the classic forms of CAH reach the diagnosis at birth or in the early childhood, allowing a prompt treatment with a correct gender assignment. The current manuscript describes an unusual case of an Italian 46-year-old woman, homeborn in the 60s, receiving an extraordinarily late diagnosis of simple virilising classic form of CAH due to 21-OHD, determining a relevant impairment of both physical and psychosexual development. The patient presented primary amenorrhea, height under target, overweight with visceral adiposity, hypercholesterolemia and insulin resistance, hirsutism with a typical male-pattern hair growth, external genital ambiguity, and a severe impairment in the entire series of psychological dimensions, particularly severe depressive symptoms, together with gender dysphoria relative to the female gender assigned at birth, cross-gender behaviours, and body image discomfort, which were associated with homosexual orientation, and sexual dysfunction. Following diagnosis and glucocorticoid (GC) replacement therapy, the hyperandrogenism control and familial and socio-cultural factors changes, particularly, living alone and the interruption of social isolation, were accompanied by menarche appearance, improvement in hirsutism and metabolic profile, and a resolution in all psychological dimensions, depressive symptoms, and gender dysphoria. The patient began to perceive homosexual orientation without discomfort, and ameliorating sexual function. Few cases of female patients with CAH due to 21-OHD receiving an extremely delayed diagnosis have been published. However, to the best of our knowledge, this is the first case including a complete psychosexual assessment at diagnosis with a detailed re-evaluation after 5 years of disease treatment.