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Abstract Anophthalmia, microphthalmia and coloboma (AMC) comprise a spectrum of developmental eye disorders, accounting for approximately 20% of childhood visual impairment. While non-coding regulatory sequences are increasingly recognised as contributing to disease burden, characterising their impact on gene function and phenotype remains challenging. Furthermore, little is known of the nature and extent of their contribution to AMC phenotypes. We report two families with variants in or near MAB21L2, a gene where genetic variants are known to cause AMC in humans and animal models. The first proband, presenting with microphthalmia and coloboma, has a likely pathogenic missense variant (c.338 G > C; p.[Trp113Ser]), segregating within the family. The second individual, presenting with microphthalmia, carries an ~ 113.5 kb homozygous deletion 19.38 kb upstream of MAB21L2. Modelling of the deletion results in transient small lens and coloboma as well as midbrain anomalies in zebrafish, and microphthalmia and coloboma in Xenopus tropicalis. Using conservation analysis, we identify 15 non-coding conserved elements (CEs) within the deleted region, while ChIP-seq data from mouse embryonic stem cells demonstrates that two of these (CE13 and 14) bind Otx2, a protein with an established role in eye development. Targeted disruption of CE14 in Xenopus tropicalis recapitulates an ocular coloboma phenotype, supporting its role in eye development. Together, our data provides insights into regulatory mechanisms underlying eye development and highlights the importance of non-coding sequences as a source of genetic diagnoses in AMC.

Introdução: As leucemias mieloides agudas são um tipo de neoplasia hematologica cronica guiadas, fundamentalmente, pela presença da translocação 9:22, o cromossomo philadelphia, que leva a um hiperestimulo proliferativo. Embora menos comum desde o advento dos inibidores de tirosinoquinase, o descontrole dessas celulas leva ao acumulo progressivo de mutações e surgimento de clones imaturos, levando a um fenomeno denominado crise blastica. Esse quadro se comporta, biológicamente, como uma leucemia aguda e é, quase sempre, de linhagem mielóide mas pode se apresentar de outras formas. Essa infideldade de linhagem e a possibilidade de pluriclonalidade traz, em alguns casos, desafios e considerações terapeuticas interessantes. Aqui apresentamos um caso modelo para debater esses processos. Relato de caso: Paciente do sexo feminino, 55 anos, hipertensa, encaminhada ao serviço de hematologia por quadro de petéquias, leucocitose e sintomas B. Na analise inicial demonstra uma leucemia com expressão fraca de CD33 e CD13 e parcial fraca de MPO, com cariotipo demonstrando 2 clones anomalos, um com a t(9;22)(q34;q11.2) isolada, compondo 18 das 20 metafases e outro com 47,idem,+der(22)t(9;22), menos prevalente, o cromossomo Philadelphia foi positivo na variante p210 sugerindo fortemente se tratar de uma crise blastica com marcadores de linhagem escaços. Inicialmente optado por inducao com protocolo mieloide de intensidade reduzida, baseado na consolidação 1 do protocolo ALPHA, com plano de manutencao com imatinibe monodroga, completou esse planejamento sem intercorrencia. Durante a manutencao, no entanto, iniciou progressao de citopenias e, em 30/05/24 suspenso Imatinibe sob suspeita de toxicidade da droga, com a solicitação de coleta de nova avaliação de medula ossea. Uma semana após, paciente procura serviço de emergência por febre, dor e abscesso em região mandibular direita. Iniciou tratamento para gengivite ulcerativa necrotizante aguda (GUNA). Exames evidenciaram aumento importante de blastos em sangue periférico, cuja imunofenotipagem agora demonstrava presença de marcadores linfóides, determinando um clone predominante linfoide B, com marcacao anomala CD13 e 33 fraca e o desaparecimento do clone co mutacoes adicionais inicialmente observado mas manutencao do clone com o cromossomo philadelfia isolado. Foi entao realizada cobertura antimircobiana e optado por inducao com HyperCVAD enquanto aguardavamos liberação de Dasatinibe. Durante a recuperacao medular apos quimioterapia apresentou protusao orbitaria e necrose de conchas nasais tendo sido realizado diagnostico de aspergilose em seios da fase. Nesse ponto, foi parada a quimioterapia e mantida em manutencao com dasatinibe, além de tratamento atntifungico que posteriormente foi ajustado para voriconazol, com resução subsequente da dose do inibidor de tirosinoquinase. Atualmente paciente segue bem, comregressao do quadro infeccioso, em RM3 e resposta hematologica completa, mantendo dasatinibe 40mg e voriconazol. Discussão: Embora rara, a crise blastica é ainda uma preocupação dentro do tratamento de pacientes com leucemia mieloide cronica. O entendimento da instabilidade cromossomica da doença nessa fase, potencial de pluriclonalidade e adequado entendimento da linhagem do clone blastico é fundamental para o tratamento. Conclusao: Esse caso nao apenas demonstra as diferentes faces da forma mais grave da leucemia mieloide cronica como tambem reflete o manejo infecioso e quimioterapico que sao parte do manejo dessa doença e as consideracoes necessarias quanto identificacao adequada do clone e ajustes terapeuticos para situacoes complexas.

BackgroundHypertension is characterized by upregulation of the renin–angiotensin system, increased blood–brain barrier (BBB) permeability, microglia activation within autonomic nuclei, and an intense sympathoexcitation. There is no information on the interplay of these events during the development of neurogenic hypertension. We sought to identify the interaction and time-course changes of Ang II availability, barrier dysfunction, microglia activation, and autonomic imbalance within autonomic areas during the development of neurogenic hypertension.MethodsSequential changes of hemodynamic/autonomic parameters, BBB permeability, microglia structure/density (IBA-1), and angiotensin II (Ang II) immunofluorescence were evaluated within the paraventricular hypothalamic nucleus, nucleus of the solitary tract, and rostral ventrolateral medulla of Wistar and spontaneously hypertensive rats (SHRs) aged 4 weeks, 5 weeks, 6 weeks, 8 weeks, and 12 weeks. The somatosensory cortex and hypoglossal nucleus were also analyzed as non-autonomic control areas.ResultsIncreased brain Ang II availability (4th–5th week) was the first observed change, followed by the incipient BBB leakage and increased microglia density (6th week). From the 5th–6th weeks on, BBB leakage, Ang II, and IBA-1 densities increased continuously, allowing a parallel increase in both Ang II-microglia colocalization and the transition of microglial cells from highly ramified in the basal surveillant condition (4th–5th week) to shorter process arbors, fewer endpoints, and enlarged soma in the disease-associate condition (6th week to the 12th week). Simultaneously with increased Ang II-microglia colocalization and microglia morphologic phenotypic changes, sympathetic activity and pressure variability increased, autonomic control deteriorated, and blood pressure increased. These responses were not specific for autonomic nuclei but also occurred at a lower magnitude in the somatosensory cortex and hypoglossal nucleus, indicating the predominance of hypertension-induced effects on autonomic areas. No changes were observed in age-matched controls where Ang II density did not change.ConclusionBrain Ang II density is the initial stimulus to drive coordinated changes in BBB permeability and microglial reactivity. Increased BBB dysfunction allows access of plasma Ang II and increases its local availability and the colocalization and activation of microglial cells. It is a potent stimulus to augments vasomotor sympathetic activity, autonomic imbalance, and pressure elevation during the establishment of hypertension.

Carbon nanotubes (CNT) are promising electroconductive nano-scale materials for neuroregeneration. Herein, we report on a new electroconductive composite scaffold made of the polymer 1% oxidized polyvinyl alcohol (OxPVA) combined with functionalized water soluble multiwalled CNT (OxPVA + MWCNT-S) (diazotization reaction). Preliminarily, MWCNT-S were characterized to evaluate the reaction outcome, the degree of functionalization and the dispersibility in water. Thereafter, OxPVA + MWCNT-S nanocomposite membranes were fabricated and analyzed for physicochemical properties (Raman spectroscopy, thermal decomposition, calorimetric properties, electroconductivity), macroscopic appearance and ultrastructure, mechanical behavior, in vitro cytotoxicity and in vivo biocompatibility. In parallel, OxPVA + MWCNT-S membranes with a linear pattern were also developed and analyzed for interaction with SH-SY5Y cells. Compared to OxPVA, the presence of MWCNT-S (only 0.016 wt%) significantly increased polymer conductivity and imparted a certain porosity without altering mechanical behaviour, as corroborated by uniaxial tensile tests. Neither cytotoxicity nor local signs of inflammation were detected in vitro and after subcutaneous implantation (14 and 42 days), proving composite material biocompatibility. OxPVA + MWCNT-S nanocomposite revealed as promising for future electroconductive conduits free from toxic effects amenable to CNT agglomeration within the polymer. Ideally, nerve lesions with wide gaps, may be effectively supported by those “active” devices, overcoming limitations of the available ones. Despite preliminary data, the presence of a linear pattern confirmed to have a beneficial effect over the scaffold/cells interaction.

Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic component in which rare variants contribute significantly to risk. We performed whole genome and/or exome sequencing (WGS and WES) and SNP-array analysis to identify both rare sequence and copy number variants (SNVs and CNVs) in 435 individuals from 116 ASD families. We identified 37 rare potentially damaging de novo SNVs (pdSNVs) in the cases (n = 144). Interestingly, two of them (one stop-gain and one missense variant) occurred in the same gene, BRSK2. Moreover, the identification of 8 severe de novo pdSNVs in genes not previously implicated in ASD (AGPAT3, IRX5, MGAT5B, RAB8B, RAP1A, RASAL2, SLC9A1, YME1L1) highlighted promising candidates. Potentially damaging CNVs (pdCNVs) provided support to the involvement of inherited variants in PHF3, NEGR1, TIAM1 and HOMER1 in neurodevelopmental disorders (NDD), although mostly acting as susceptibility factors with incomplete penetrance. Interpretation of identified pdSNVs/pdCNVs according to the ACMG guidelines led to a molecular diagnosis in 19/144 cases, although this figure represents a lower limit and is expected to increase thanks to further clarification of the role of likely pathogenic variants in ASD/NDD candidate genes not yet established. In conclusion, our study highlights promising ASD candidate genes and contributes to characterize the allelic diversity, mode of inheritance and phenotypic impact of de novo and inherited risk variants in ASD/NDD genes.

Abstract Dermal tattoo biosensors are promising platforms for real‐time monitoring of biomarkers, with skin used as a diagnostic interface. Traditional tattoo sensors have utilized small molecules as biosensing elements. However, the rise of synthetic biology has enabled the potential employment of engineered bacteria as living analytical tools. Exploiting engineered bacterial sensors will allow for potentially more sensitive detection across a broad biomarker range, with advanced processing and sense/response functionalities using genetic circuits. Here, the interfacing of bacterial biosensors as living analytics in tattoos is shown. Engineered bacteria are encapsulated into micron‐scale hydrogel beads prepared through scalable microfluidics. These biosensors can sense both biochemical cues (model biomarkers) and biophysical cues (temperature changes, using RNA thermometers), with fluorescent readouts. By tattooing beads into skin models and confirming sensor activity post‐tattooing, our study establishes a foundation for integrating bacteria as living biosensing entities in tattoos.

PurposeTibial torsion disorders may lead to abnormal gait, frequently leading to a consultation with a pediatric orthopedic surgeon. The present study evaluated an alternative method for assessing tibial torsion on computerized tomography (CT) images that considers the tibial distal axis to be equivalent to the geometric axis of the tibiotalar joint.MethodsOne hundred CT scans were reviewed retrospectively, and four measurements were taken: proximal transtibial angle (PTTA), posterior margin tibial plateau angle (PMTPA), intermalleolar angle (IMA), and talar angle (TA). The tibial torsion angle was then calculated using these different angles.ResultsThe patient cohort comprised 38 girls and 62 boys, with a mean age of 12 ± 4.4 years. Median PTTA and PMTPA were −8.4° ± 14.7° and −8.8° ± 14.2°, respectively, with no statistically significant difference. Mean IMA and TA were 23° ± 16.2° and 17.2° ± 16.9°, respectively, with a statistically significant difference. Mean total measurement time per patient was 6'44", with means of 2'24" for PTTA, 36" for PMTPA, 2'14" for IMA, and 1'12" for TA.ConclusionTibial torsion values may differ significantly depending on the axis chosen to define tibial orientation. At the level of the proximal tibia, the choice of PTTA or PMTPA had little influence on the calculation of the tibial torsion angle. There was a significant difference of 5.8° when measuring the distal tibia. Measuring the PMTPA and TA is probably more suited for use in clinical practice because their tracing is simple and faster.

The shear fractures of the capitellum are rare fractures in the pediatric population. Their diagnosis is challenging because of the high cartilaginous component of the growing elbow, requiring a high level of clinical suspicion especially in the case of small osteochondral or chondral fragments. The literature on capitellar shear fractures is mainly represented by case reports, which provides a patchy view of the topic. For this reason, we aimed to draw a narrative review presenting the available management strategies and their outcomes, and present two cases treated in our institution.

The last few years have seen an increasing use of spherical metals powders to produce bulk parts through metal forming technologies like Additive Manufacturing and Metal Injection Molding. This, coupled with the wide availability of metal powders, leads to a critical issue: contamination across different systems in different process steps. Consequently, it is necessary to find a new, fast, and reliable analysis sensible to tiny traces of contamination. This work evaluates the applicability of Ultraviolet–Visible-Near InfraRed (UV–Vis-NIR) spectroscopy, a technique providing information on powders’ reflectance, for studying contaminated powders. This work focuses on assessing 3 binary systems obtained from the cross-contamination of 3 components (A92618, C10200 and S31603) in a low contamination range (from 0.5 vol% to vol. 6%) and in a high contamination range (25 vol% and vol.50%). After the UV–Vis-NIR analysis, multivariate analysis has been used to obtain quantitative results. Results show that, as the contamination level increases in the binary system, the shape of spectra changes and becomes progressively more similar to the contaminant one. The chemometric analysis allows the detection of the contaminant type and its concentration percentage in the contaminated powder.

ABSTRACT: Untargeted metabolomic profiling, by ambient mass spectrometry and chemometric tools, has made a dramatic impact on human disease detection. In a similar vein, this study attempted the translation of this clinical human disease experience to farmed poultry for precise veterinary diagnosis. As a proof of principle, in this diagnostic/prognostic study, direct analysis in real-time high resolution mass spectrometry (DART-HRMS) was used in an untargeted manner to analyze fresh tissues (abdominal fat, leg skin, liver, and leg muscle) of pigmented and non-pigmented broilers to investigate the causes of lack of pigmentation in an industrial poultry farm. Afterwards, statistical analysis was applied to the DART-HRMS data to retrieve the molecular features that codified for 2 broiler groups, that is, properly pigmented and non-pigmented broilers. Higher abundance of oxidized lipids, high abundance of oxidized bile derivatives, and lower levels of tocopherol isomers (Vitamin E) and retinol (Vitamin A) were captured in nonpigmented than in pigmented broilers. In addition, conventional rapid analyses were used: 1) color parameters of the tissues of pigmented and non-pigmented broilers were measured to rationalize the color differences in abdominal fat, leg skin and leg muscle, and 2) macronutrients were determined in broiler leg muscle, to capture a detailed picture of the pathology and exclude other possible causes. In this study, the DART-HRMS system performed well in retrieving valuable chemical information from broilers that explained the differences between the 2 groups of broilers in absorption of xanthophylls and the subsequent lack of proper broiler pigmentation in affected broilers. The results suggest this technology could be useful in providing near real-time feedback to aid in veterinary decision-making in poultry farming.

Abstract Automated and non-invasive mammalian cell analysis is currently lagging behind due to a lack of methods suitable for a variety of cell lines and applications. Here, we report the development of a high throughput non-invasive method for tracking mammalian cell growth and performance based on plate reader measurements. We show the method to be suitable for both suspension and adhesion cell lines, and we demonstrate it can be adopted when cells are grown under different environmental conditions. We establish that the method is suitable to inform on effective drug treatments to be used depending on the cell line considered, and that it can support characterisation of engineered mammalian cells over time. This work provides the scientific community with an innovative approach to mammalian cell screening, also contributing to the current efforts towards high throughput and automated mammalian cell engineering.

Abstract Background Next-generation sequencing has had a significant impact on genetic disease diagnosis, but the interpretation of the vast amount of genomic data it generates can be challenging. To address this, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology have established guidelines for standardized variant interpretation. In this manuscript, we present the updated Hospital Israelita Albert Einstein Standards for Constitutional Sequence Variants Classification, incorporating modifications from leading genetics societies and the ClinGen initiative. Results First, we standardized the scientific publications, documents, and other reliable sources for this document to ensure an evidence-based approach. Next, we defined the databases that would provide variant information for the classification process, established the terminology for molecular findings, set standards for disease-gene associations, and determined the nomenclature for classification criteria. Subsequently, we defined the general rules for variant classification and the Bayesian statistical reasoning principles to enhance this process. We also defined bioinformatics standards for automated classification. Our workgroup adhered to gene-specific rules and workflows curated by the ClinGen Variant Curation Expert Panels whenever available. Additionally, a distinct set of specifications for criteria modulation was created for cancer genes, recognizing their unique characteristics. Conclusions The development of an internal consensus and standards for constitutional sequence variant classification, specifically adapted to the Brazilian population, further contributes to the continuous refinement of variant classification practices. The aim of these efforts from the workgroup is to enhance the reliability and uniformity of variant classification.

Gold nanoparticles have been extensively studied due to their unique optical and electronic properties which make them attractive for a wide range of applications in biomedicine, electronics, and catalysis. Over the past decade, atmospheric pressure plasma jets in contact with a liquid have emerged as a sustainable and environmentally friendly approach for synthesizing stable and precisely controlled dispersions. Within the context of plasma jet/liquid configurations, researchers have explored various power sources, ranging from kHz frequencies to nanopulse regimes. In this study, we investigated the effects of coupling two distinct power supplies: a high-voltage micropulse and a radio frequency (RF) generator. The variations within the plasma induced by this coupling were explored by optical and electrical measurements. Our findings indicated a transition from a bullet plasma propagation mechanism to a capacitive coupling mechanism upon the introduction of RF energy. The impact on the production of metal nanoparticles was also examined as a function of the radio frequency power and of two distinct process gases, namely helium and argon. The characterization of gold nanoparticles included UV-visible spectroscopy, dynamic light scattering, and scanning electron microscopy. The results showed that the size distribution depended on the type of process gas used and on the power supplies coupling. In particular, the incorporation of RF power alongside the micropulse led to a decrease in both average particle size and distribution width. The comparison of the different set up suggested that the current density can influence the particle size distribution, highlighting the potential advantages of the use of a dual-frequency atmospheric pressure plasma jet configuration.

Abstract Resource competition can be the cause of unintended coupling between co-expressed genetic constructs. Here we report the quantification of the resource load imposed by different mammalian genetic components and identify construct designs with increased performance and reduced resource footprint. We use these to generate improved synthetic circuits and optimise the co-expression of transfected cassettes, shedding light on how this can be useful for bioproduction and biotherapeutic applications. This work provides the scientific community with a framework to consider resource demand when designing mammalian constructs to achieve robust and optimised gene expression.

Objective: to evaluate the patient safety climate in Primary Health Care from the perspective of nurses working in the services. Method: a quantitative and cross-sectional study conducted with 148 nurses from a municipality in the state of São Paulo. The Brazilian version of the Primary Care Safety Questionnaire Survey and personal, professional, and organizational performance variables (intention to stay at work, job satisfaction, care quality, and frequency of incidents) were used. Parametric and non-parametric comparison tests and Spearman’s correlation coefficient were performed, considering a 5% significance level. Results: the safety climate was positive, varying from 4.52 to 5.33 and differing across districts for workload (p=0.0214) and leadership (p=0.0129). The safety climate professional variables and dimensions differed in relation to the frequency of incidents. Teamwork and safety and learning system were strongly correlated with job satisfaction and moderately with perceived care quality. Conclusion: teamwork and safety and learning system stood out for their positive correlations with job satisfaction and care quality. A positive safety climate favors the involvement of Primary Care nurses to develop improvement plans aligned with the National Patient Safety Program.

A cluster of eleven research and innovation projects, funded under the same call of the EU’s H2020 programme, are developing breakthrough and game-changing renewable energy technologies that will form the backbone of the energy system by 2030 and 2050 are, at present, at an early stage of development. These projects have joined forces at a collaborative workshop, entitled ‘Low-TRL Renewable Energy Technologies’, at the 10th Sustainable Places Conference (SP2022), to share their insights, present their projects’ progress and achievements to date, and expose their approach for exploitation and market uptake of their solutions.

Primary spinal infection (PSI) is a generic term covering a heterogeneous group of infections that can affect the vertebral body, intervertebral disks, the content of the medullary cavity, and adjacent paraspinal tissues. Patients’ characteristics can vary significantly, notably according to their age, and some of these characteristics undoubtedly play a primordial role in the occurrence of a PSI and in the type of offending pathogen. Before approaching the subject of laboratory diagnostics, it is essential to define the characteristics of the patient and their infection, which can then guide the physician toward specific diagnostic approaches. This review critically examined the roles and usefulness of traditional and modern laboratory diagnostics in supporting clinicians’ decision-making in cases of pediatric and adult primary spinal infection (PSI). It appears impossible to compare PSIs in children and adults, whether from an epidemiological, clinical, bacteriological, or biological perspective. The recipients are really too different, and the responsible germs are closely correlated to their age. Secondly, the interpretation of traditional laboratory blood tests appears to contribute little guidance for clinicians attempting to diagnose a PSI. Biopsy or needle aspiration for bacterial identification remains a controversial subject, as the success rates of these procedures for identifying causative organisms are relatively uncertain in pediatric populations.Using nucleic acid amplification assays (NAAAs) on biopsy samples has been demonstrated to be more sensitive than conventional cultures for diagnosing PSI. Recent advances in next-generation sequencing (NGS) are particularly interesting for establishing a microbiological diagnosis of a PSI when standard cultures and NAAAs have failed to detect the culprit. We can even imagine that plasma metagenomic NGS using plasma (known as “liquid biopsy”) is a diagnostic approach that can detect not only pathogens circulating in the bloodstream but also those causing focal infections, and thus eliminate the need for source sample collection using costly invasive surgical procedures.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.

Pediatric septic arthritis of the hip (SAH) in children is a severe pathology, requiring prompt diagnosis and treatment to avoid destructive sequelae of the joint. Its diagnosis can be challenging, however, due to its spectrum of manifestations and differential diagnosis. Last century, multiple research teams studied the curves of systemic inflammation markers to aid the differential diagnosis. Kocher showed that a history of fever >38.5 °C, non-weight bearing, an erythrocyte sedimentation rate >40 mm/h, and serum white blood cells >12,000/mm3 were highly suggestive of SAH, with a predicted probability of 99.6% when all these predictors manifested in pediatric patients. Caird validated these criteria, also adding a C-reactive protein >20 mg/L, reaching a 98% probability of SAH when these five criteria were present. The Kocher and the Caird criteria were then applied in multiple settings, but were never clearly validated. Moreover, they were studied and validated in the years when Kingella kingae was just emerging, and this was probably responsible for false-negative cases in multiple centers. For this reason, the Kocher and the Caird criteria are still at the center of a debate on the diagnostic tools for pediatric SAH. We provide a historical overview of the development of clinical and laboratory test algorithms for pediatric SAH. Further, new perspectives for future research on the prediction rules of pediatric SAH are here proposed.

Carbon nanomaterials are promising adsorbents for dye removal from wastewater also due to their possible surface functionalization that, in principle, can increase the adsorption rate and provide regeneration. To investigate the real advantages of functionalization, we synthesized and characterized through IR, TGA, TEM, XPS and DLS measurements a multi-walled carbon nanotube (MWCNT) derivative bearing benzenesulfonate groups (MWCNT-S). The obtained material demonstrated to have good dispersibility in water and better capability to adsorb methylene blue (MB) compared to the pristine MWCNT adsorbent. Adsorption kinetic studies showed a very fast process, with a constant significantly higher with respect not only to that of the unfunctionalized MWCNT adsorbent but also to those of widely used activated carbons. Moreover, the adsorption capacity of MWCNT-S is more than doubled with respect to that of the insoluble pristine MWCNT adsorbent, thanks to the dispersibility of the derivatives, providing a larger available surface, and to the possible electrostatic interactions between the cationic MB and the anionic sulfonate groups. Additionally, the reversibility of ionic interactions disclosed the possibility to release the adsorbed cationic pollutant through competition with salts, not only regenerating the adsorbent, but also recovering the dye. Indeed, by treating the adsorbed material for 1 h with 1 M NaCl, a regeneration capacity of 75% was obtained, demonstrating the validity of this strategy.

El hecho de que la Diabetes Mellitus se ha convertido en un problema de salud y que es además una importante causa de muerte a nivel mundial, nos llevó ha investigar la mortalidad producida por esta patología en la Provincia de Córdoba durante el período 1986 /1995. Para dicho estudio se obtuvieron del Departamento de Estadística del Ministerio de Salud de la Provincia de Córdoba los registros de defunción por Diabetes Mel litus de toda la provincia (años 1986 - 1995). De un total de 6.718 fallecidos (3.300 varones y 3.418 mujeres), se determinaron las tasas brutas y especificas por sexo y grupo etarios, la evolución de las mismas y su relación con diversas variables tales como: nivel de instrucción, viviendas deficitarias y N.B.I.(Necesidades Básicas: Insatisfechas). Los resultados indicaron que la tasa de mortalidad se incrementó en el período estudiado, siendo la tasa media anual del mismo de 24,421/13000, no existiendo diferencia significativa entre ambos sexos (P= 0,76 > 0,05). Con relación a la edad, las tasas aumentaron al elevarse la misma, predominando las masculinas, en general desde los 45 aios en adelante a excepción de los años 1986, 1989 y 1995 donde son mayores las femeninas en el grupo de 75 y más aáos. Respecto a las demás variables consideradas, al compararlas con el desarrollo socio- económico de cada Departamento de la Pcia de Córdoba, nos permitirían inferir que la industrialización, la urbanización y la evolución social y económica de los mismos tienen una correlación positiva con la mortalidad por diabetes.

ABSTRACT Objective: To evaluate the perception of the patient safety climate in primary health care associated with professional categories, health centers, and previous experience of participation in the National Program for the Improvement of Access and Quality of Primary Care. Method: Cross-sectional study with 119 health professionals in a city in the interior of the state of São Paulo, between August 2019 and February 2020, using the Brazilian version of the Primary Care Safety Questionnaire. Results: The safety climate was favorable, with better evaluation for communication and leadership and worse evaluation for workload. There were differences among health centers regarding teamwork (p=0.0010), workload (p=0.0001) and total score (p=0.0185). Professionals with previous experience participating in the improvement program have a better perception of the climate. Conclusion: The perception of climate did not differ between professional categories but differed between health centers.

We must rethink and test assumptions about relationships among biological research, security, and society

IntroductionPatients’ quality of life (QoL), facial nerve (FN), and cochlear nerve (CN) (if conserved) functions should be pursued as final outcomes of vestibular schwannoma (VS) surgery. In regard to FN function, different morphologic and neurophysiological factors have been related to postoperative outcomes. The aim of the current retrospective study was to investigate the impact of these factors on the short- and long-term FN function after VS resection. The combination of preoperative and intraoperative factors resulted in designing and validating a multiparametric score to predict short- and long-term FN function.MethodsA single-center retrospective analysis was performed for patients harboring non-syndromic VS who underwent surgical resection in the period 2015–2020. A minimum follow-up period of 12 months was considered among the inclusion criteria. Morphological tumor characteristics, intraoperative neurophysiological parameters, and postoperative clinical factors, namely, House–Brackmann (HB) scale, were retrieved in the study. A statistical analysis was conducted to investigate any relationships with FN outcome and to assess the reliability of the score.ResultsSeventy-two patients with solitary primary VS were treated in the period of the study. A total of 59.8% of patients showed an HB value < 3 in the immediate postoperative period (T1), reaching to 76.4% at the last follow-up evaluation. A multiparametric score, Facial Nerve Outcome Score (FNOS), was built. The totality of patients with FNOS grade A showed an HB value < 3 at 12 months, decreasing to 70% for those with FNOS grade B, whereas 100% of patients with FNOS grade C showed an HB value ≥ 3. The ordinal logistic regression showed three times increasing probability to see an HB value ≥ 3 at 3-month follow-up for each worsening point in FNOS score [Exp(B), 2,999; p < 0.001] that was even more probable [Exp(B), 5.486; p < 0.001] at 12 months.ConclusionThe FNOS score resulted to be a reliable score, showing high associations with FN function both at short- and long-term follow-up. Although multicenter studies would be able to increase its reproducibility, it could be used to predict the FN damage after surgery and the potential of restoring its function on the long-term period.

El siguiente texto se centra en comprender las características específicas del proceso de financiarización de la tierra en Uruguay, con foco en los capitales de gran escala. En función de un diseño cualitativo-cuantitativo que procesó diversas fuentes de información, se identificaron 37 capitales que abarcan un 11,6 % de la superficie productiva del país. Se identificaron 23 corporaciones privadas nacionales y extranjeras, siete fondos de inversión extranjeros y siete operadores de fideicomisos financieros. Estos capitales registran distintas modalidades de tenencia de la tierra (propietarios, arrendatarios y arrendadores), diverso origen del capital (estatal o privado), composición cerrada o abierta con acciones en bolsa y territorialización nacional o transnacional. El análisis evidenció el rol clave que juegan diversos instrumentos y actores financieros, los que en muchos casos invisibilizan a los acreedores y accionistas detrás de los grandes capitales que operan en el mercado de tierras.

Background: Despite the public health implications of language difficulties associated with social disadvantage, there is a dearth of effectiveness studies investigating the effects of targeted speech and language programmes in this area. Aims: To determine the effects of a targeted selective community-based child language intervention programme (Happy Talk), which simultaneously engaged with parents and early childhood educators, in the Republic of Ireland. Methods & Procedures: A mixed methods methodology was applied with quantitative outcome and qualitative process data collected. Effectiveness was examined using a quasi-experimental single blind study design comparing Happy Talk with 'usual care' across four preschools. Qualitative process data were also gathered to examine the acceptability and feasibility of the Happy Talk approach in practice, and to identify factors to improve the probability of successful wider implementation. Child language (PLS-5) and quality-of-life measures were administered pre- and immediately post- the 11-week intervention. Responsiveness was assessed as the parental outcome, and the oral language environment of preschools was measured using the Communication Supporting Classroom Observation Tool (CSCOT). Retrospective acceptability was analysed with reference to the theoretical framework of acceptability (v 2). Outcomes & Results: Pre-/post-expressive and composite language scores were collected for 58 children, and receptive scores for 54 children. Multiple linear regression revealed significant intervention effects for comprehension and total language with large and moderate effect sizes, respectively (0.60 and 0.46 SD). No significant effect was shown for parental responsiveness. No effects were found for the preschool environment or children's quality of life. Preschool staff deemed the programme to be an acceptable method of enhancing children's speech and language skills and rated the intervention positively. Conclusions & Implications: The Happy Talk pilot effectiveness trial shows that comprehension can be improved (with a large effect) in preschool children from areas of social disadvantage, following an 11-week intervention, in which parents and preschool staff are simultaneously engaged. The ecological validity of the programme, as well as feasibility and acceptability to staff, make it a suitable programme to be delivered at scale.