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Objetivos: Determinar os limites referenciais do Tempo de Protrombina (TP) e do Tempo de Tromboplastina Parcialmente Ativada (TTPa), no grupo etário com idade até 18 anos. Além disso, comparar os valores de TP e TTPa de indivíduos saudáveis entre idades e dois grupos etários, os com idade até 18 anos e aqueles com idade superior a 18 anos. Materiais e métodos: Foram avaliados um total de 471 resultados de crianças saudáveis e não internadas provenientes do atendimento ambulatorial de um hospital universitário, sendo 238 resultados de TP e 233 de TTPa. Para a análise comparativa entre crianças/adolescentes e adultos, foram avaliados 2121 resultados de indivíduos adultos, sendo 1084 resultados de TP e 1037 de TTPa. A mediana de idade do grupo dos < 18 anos foi de 8 anos (variando de 1 a 17 anos) e 52 anos (variando de 18 a 89 anos) no grupo dos adultos. Sangue periférico foi coletado em tubo à vácuo BD Vacutainer® de citrato de sódio tamponado 0,105 mol/L (Becton Dickinson, Franklin Lakes, USA) na proporção de nove partes de sangue para uma parte de solução de Citrato, conforme recomendado pela CLSI (Clinical and Laboratory Standards Institute). As amostras foram imediatamente centrifugadas a 1500 g por 15 minutos. As determinações de TP e TTPa foram realizadas utilizando Neoplastine® CI Plus (Diagnóstica Stago S.A.S, Asnières sur Seine, França) e ATTP® (Diagnóstica Stago S.A.S, Asnières sur Seine, França) utilizando o equipamento STA Compact Max® (Diagnóstica Stago S.A.S, Asnières sur Seine, França). Resultados: Os valores medianos de TP e TTPa no grupo com idade até 18 anos foi 13,4 segundos (10,2 a 15,8 segundos) e 37,4 segundos (25,7 a 50,7 segundos), respectivamente. Houve diferença significativa entre os valores medianos de TP (p < 0,001) e TTPa (p < 0,001) de acordo com a idade (de 1 a 18 anos). Para o conjunto de dados analisados os limites inferior e superior com intervalo de confiança de 95% foram 11,90 segundos (11,40 a 12,10 segundos) e 15,30 segundos (14,80 a 15,70 segundos) para o TP e 30,12 segundos (26,40 a 31,10 segundos) e 47,33 segundos (45,50 a 49,60 segundos) para o TTPa naqueles com idade até 18 anos. Os valores foram significativamente maiores neste grupo com idade até 18 anos para o TP [13,4 segundos (10,2 a 15,8 segundos) versus 13,0 segundos (11,1 a 15,9 segundos), p < 0,001] e TTPa [37,4 segundos (25,7 a 50,7 segundos) versus 34,7 segundos (25,1 a 45,5 segundos), p < 0,001], em comparação com o grupo de indivíduos com idade superior a 18 anos. Conclusões: O conhecimento sobre as mudanças graduais, desde o nascimento até a fase adulta, que refletem a fisiologia do desenvolvimento da hemostasia, é importante para a correta realização e interpretação dos exames laboratoriais. As diferenças parecem ser mais pronunciadas entre as crianças com idade até 1 ano, adolescentes e adultos, sendo mais evidentes no período neonatal, destacando a importância de valores referenciais específicos para a idade. Deve-se considerar as dificuldades para a obtenção de múltiplas amostras para determinação dos valores de corte pediátricos, no entanto, há recomendação da International Society on Thrombosis and Haemostasis (ISTH) para que cada laboratório defina os intervalos de referência idade dependentes, baseando-se na sua própria condição técnica.

The advent of massive broad-band photometric surveys enabled photometric redshift estimates for unprecedented numbers of galaxies and quasars. These estimates can be improved using better algorithms or by obtaining complementary data such as narrow-band photometry, and broad-band photometry over an extended wavelength range. We investigate the impact of both approaches on photometric redshifts for quasars using data from Southern Photometric Local Universe Survey (S-PLUS) DR4, Galaxy Evolution Explorer (GALEX) DR6/7, and the unWISE catalog for the Wide-field Infrared Survey Explorer (WISE) in three machine learning methods: Random Forest, Flexible Conditional Density Estimation (FlexCoDE), and Bayesian Mixture Density Network (BMDN). Including narrow-band photometry improves the root-mean-square error by 11 per cent in comparison to a model trained with only broad-band photometry. Narrow-band information only provided an improvement of 3.8 per cent when GALEX and WISE colours were included. Thus, narrow bands play a more important role for objects that do not have GALEX or WISE counterparts, which respectively makes 92 per cent and 25 per cent of S-PLUS data considered here. Nevertheless, the inclusion of narrow-band information provided better estimates of the probability density functions obtained with FlexCoDE and BMDN. We publicly release a value-added catalogue of photometrically selected quasars with the photo- z predictions from all methods studied here. The catalogue provided with this work covers the S-PLUS DR4 area (∼3000 square degrees), containing 645 980, 244 912, 144 991 sources with the probability of being a quasar higher than, 80 per cent, 90 per cent, 95 per cent up to r < 21.3 and good photometry quality in the detection image. More quasar candidates can be retrieved from the S-PLUS data base by considering less restrictive selection criteria. [ABSTRACT FROM AUTHOR]

Abstract Lignin, a major plant cell wall component, has an important role in plant-defense mechanisms against pathogens and is a promising renewable carbon source to produce bio-based chemicals. However, our understanding of microbial metabolism is incomplete regarding certain lignin-related compounds like p-coumaryl and sinapyl alcohols. Here, we reveal peripheral pathways for the catabolism of the three main lignin precursors (p-coumaryl, coniferyl, and sinapyl alcohols) in the plant pathogen Xanthomonas citri. Our study demonstrates all the necessary enzymatic steps for funneling these monolignols into the tricarboxylic acid cycle, concurrently uncovering aryl aldehyde reductases that likely protect the pathogen from aldehydes toxicity. It also shows that lignin-related aromatic compounds activate transcriptional responses related to chemotaxis and flagellar-dependent motility, which might play an important role during plant infection. Together our findings provide foundational knowledge to support biotechnological advances for both plant diseases treatments and conversion of lignin-derived compounds into bio-based chemicals.

Abstract Background This study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR). Methods Six-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal–Wallis and Dunn. Results Echocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p

Abstract Robotic milking systems are successful innovations in the development of dairy cattle. The objective of this study was to analyse the milking characteristics and behavior of dairy cows of different calving orders in “milk first” robotic milking systems. The data were collected from a commercial herd located in the Midwest region of Minas Gerais (Brazil), which uses an automatic milking system (AMS TM, DeLaval). Were analysed 26,574 observations of 235 Holstein cows were available. Data were evaluated by multivariate analysis of variance and the Tukey test. - Tthe characteristics milk flow and milking efficiency were more favourable for multiparous cows (p

Developing metal-free electrodes for prototypes of bio-based devices is an essential step in producing non-toxic components for implantable devices and wearables. In particular, the advancement in self-powered devices is a hot topic for several applications due to the possibility of creating free-battery devices and sensors. In this paper, the modification of bacterial cellulose by the progressive incorporation of carbon black (a conductive filler) was explored as a prototype for bio-based electrodes for triboelectric nanogenerators. This process was controlled by the percolation pathways’ activation through the contact of carbon black grains with the bacterial cellulose membrane, which represents a critical step in the overall process of optimization in the power output performance, reaching an open circuit voltage value of 102.3 V, short circuit current of 2 μA, and power density of 4.89 μW/cm2.

Contamination of soil, water, and wastewater by pharmaceuticals, including antibiotics, is a global health problem. This work evaluated the use of a natural compound, curcumin (CUR), as a homogeneous photocatalyst, together with hydrogen peroxide (H2O2) as a benign oxidant, to promote the photodegradation of ciprofloxacin (CIP). Furthermore, we carried out theoretical calculations using density functional theory (DFT) to assess the chemical reactivity of ciprofloxacin. In addition, the intermolecular interaction patterns of two crystalline polymorphs of the antibiotic drug were analyzed through Hirshfeld surfaces. Finally, calculations using the TD-DFT formalism were carried out to understand the effects on the CIP molecule caused by the simultaneous presence of the CUR molecule and ultraviolet-visible light (UV-Vis). A photooxidative effect was observed in the presence of the CUR photocatalyst (CIP + CUR (1:0.5)), resulting in a degradation of CIP of up to 24.4%. However, increasing the concentration of the CUR photocatalyst (ciprofloxacin + curcumin (1:1)) decreased the photodegradation of CIP, which may be caused by competition between the CIP molecule and CUR for ROS generated in situ. Additionally, the calculation results showed that the electronic excitations caused by the associated CIP + CUR structures affect the CIP molecule, resulting in the effects observed experimentally. The results show that CUR, when applied as a photosensitizing catalyst, presents synergistic potential with H2O2 in the photocatalytic degradation of ciprofloxacin. This photocatalytic process can be applied to the environmental remediation of pharmaceutical micropollutants, a subject of ongoing studies.

Dimethyl fumarate (DMF, Tecfidera) is an oral drug utilized to treat relapsing-remitting multiple sclerosis (MS). DMF treatment reduces disease activity in MS. Gastrointestinal discomfort is a common adverse effect of the treatment with DMF. This study aimed to investigate the effect of DMF administration in the gut draining lymph nodes cells of C57BL6/J female mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We have demonstrated that the treatment with DMF (7.5 mg/kg) significantly reduces the severity of EAE. This reduction of the severity is accompanied by the increase of both proinflammatory and anti-inflammatory mechanisms at the beginning of the treatment. As the treatment progressed, we observed an increasing number of regulatory Foxp3 negative CD4 T cells (Tr1), and anti-inflammatory cytokines such as IL-27, as well as the reduction of PGE2 level in the mesenteric lymph nodes of mice with EAE. We provide evidence that DMF induces a gradual anti-inflammatory response in the gut draining lymph nodes, which might contribute to the reduction of both intestinal discomfort and the inflammatory response of EAE. These findings indicate that the gut is the first microenvironment of action of DMF, which may contribute to its effects of reducing disease severity in MS patients.

Introduction Despite the increased knowledge about the prevalence and consequences of eating disorders (ED), they continue to be underdiagnosed and undertreated. Being more common in women of childbearing age, the perinatal period may play a decisive role in the incidence and course of these pathologies. The Screen for Disordered Eating (SDE) was developed for the screen of ED in primary care. Objectives Our aim was to analyze the psychometric properties of the Portuguese Version of SDE in women during the perinatal period. Methods Participants were 346 women with a mean age of 31.68 of years old (± 4.061; range: 18-42). 160 were pregnant (second or third trimester) and 186 were in the post-partum (mean baby´s age=4.37 months (± 2.87; range: 1-12). They answered an online survey including the Portuguese version of the SDE and of the Eating Disorder Examination – Questionnaire (EDE-Q-7). Results Confirmatory Factor Analysis showed that the unidimensional model presented good fit indexes in pregnancy (), post-partum () and considering both – perinatal period (χ2/df=2.0335; RMSEA=.0547, p

Introduction The EDE-Q-7 Portuguese version presented good reliability and validity in Portuguese women fro the general population (Pereira et al. 2022). Objectives The aim of our study was to analyse the psychometric properties of the EDE-Q-7 in a sample of Portuguese women during the perinatal period. Methods Participants were 346 women with a mean age of 31.68 of years old (± 4.061; range: 18-42). 160 were pregnant (second or third trimester) and 186 were in the post-partum (mean baby´s age=4.37 months (± 2.87; range: 1-12). They answered an online survey including the Portuguese version of the EDE-Q-7 and of the Screen for Disordered Eating/SDE. Results Confirmatory factor analysis (CFA) presented adequate fit, in pregnancy (χ2/df=; RMSEA=, p0.90 for the total and approximately .70 for the three factors - Dietary restraint, Shape/weight overvaluation and Body dissatisfaction. All the items contributed to the internal consistency and presented high internal consistency. Pearson correlations between factors and total scores were significant, positive and high, as well as between the EDE-Q-7 measures and SDE (>.60 with the total; >.40 with the factors), in pregnancy, postpartum and considering both periods. Conclusions Presented sound psychometric properties across the perinatal period, the EDE-Q-7 and can be very useful to evaluate the presence and severity of eating disorders symptoms in women in pregnancy and post-partum. Disclosure of Interest None Declared

Introduction The perinatal period may intensify weight and body image concerns. Due to its specifics, the traditional body image scales are inaccurate in the perinatal period (Fuller-Tyszkiewicz et al. 2013). The Body Image Concerns During Pregnancy (Uçar et al. 2018) was developed to measures this cognitive-emotional variable in pregnancy. Objectives To analyze the psychometric properties of the Portuguese adapted (both for pregnancy and postpartum) version of the Body Image Concerns during the Perinatal Period (BICPP), namely its construct validity and the internal consistency. Methods A sample of 346 women recruited through social media and Family Health Units, assessed in the second trimester of pregnancy (mean gestational age=28.11±7.67 weeks) and after delivery (baby’s age 4.37±2.87 months), completed a survey including the Portuguese BICPP. The total sample was randomly divided into two sub-samples: sample A (n=173) was used to perform an exploratory factor analysis/EFA; sample B (n=173) to perform a confirmatory factor analysis/CFA. Results EFA resulted in four components. CFA revealed that the second-order model with four factors presented good fit indexes (X2/df=2.4141; CFI=.9195; GFI=.948; TLI=.9028; GFI=.8181; RMSEA=.0807). BICPP Cronbach alphas was α=.936; for F1 Concern about future weight and image, F2 Concern with the new body image, F3 Social avoidance and concern and F4 Concern with appearance were .922, .930, .809, .807, respectively. Conclusions This psychometric study provides evidence for the validity and reliability of the Portuguese version of BIC-Perinatal Period, which will be used in an ongoing research project on the relationship between eating, depressive and anxiety disorders in the perinatal period. Disclosure of Interest None Declared

Anxiety disorders in dogs are ever-growing and represent an important concern in the veterinary behavior field. These disorders are often disregarded in veterinary clinical practice, negatively impacting the animal’s and owner’s quality of life. Moreover, these anxiety disorders can potentially result in the abandonment or euthanasia of dogs. Growing evidence shows that the gut microbiota is a central player in the gut-brain axis. A variety of microorganisms inhabit the intestines of dogs, which are essential in maintaining intestinal homeostasis. These microbes can impact mental health through several mechanisms, including metabolic, neural, endocrine, and immune-mediated pathways. The disruption of a balanced composition of resident commensal communities, or dysbiosis, is implicated in several pathological conditions, including mental disorders such as anxiety. Studies carried out in rodent models and humans demonstrate that the intestinal microbiota can influence mental health through these mechanisms, including anxiety disorders. Furthermore, novel therapeutic strategies using prebiotics and probiotics have been shown to ameliorate anxiety-related symptoms. However, regarding the canine veterinary behavior field, there is still a lack of insightful research on this topic. In this review, we explore the few but relevant studies performed on canine anxiety disorders. We agree that innovative bacterial therapeutical approaches for canine anxiety disorders will become a promising field of investigation and certainly pave the way for new approaches to these behavioral conditions.

Plastic pollution poses a significant environmental challenge, necessitating the investigation of bioplastics with reduced end-of-life impact. This study systematically characterizes four promising bioplastics—polybutylene adipate terephthalate (PBAT), polybutylene succinate (PBS), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and polylactic acid (PLA). Through a comprehensive analysis of their chemical, thermal, and mechanical properties, we elucidate their structural intricacies, processing behaviors, and potential morphologies. Employing an environmentally friendly process utilizing supercritical carbon dioxide, we successfully produced porous materials with microcellular structures. PBAT, PBS, and PLA exhibit closed-cell morphologies, while PHBV presents open cells, reflecting their distinct overall properties. Notably, PBAT foam demonstrated an average porous area of 1030.86 μm2, PBS showed an average porous area of 673 μm2, PHBV displayed open pores with an average area of 116.6 μm2, and PLA exhibited an average porous area of 620 μm2. Despite the intricacies involved in correlating morphology with material properties, the observed variations in pore area sizes align with the findings from chemical, thermal, and mechanical characterization. This alignment enhances our understanding of the morphological characteristics of each sample. Therefore, here, we report an advancement and comprehensive research in bioplastics, offering deeper insights into their properties and potential morphologies with an easy sustainable foaming process. The alignment of the process with sustainability principles, coupled with the unique features of each polymer, positions them as environmentally conscious and versatile materials for a range of applications.

The canonical G406R mutation that increases Ca 2+ influx through the CACNA1C-encoded Ca V 1.2 Ca 2+ channel underlies the multisystem disorder Timothy syndrome (TS), characterized by life-threatening arrhythmias. Severe episodic hypoglycemia is among the poorly characterized non-cardiac TS pathologies. While hypothesized from increased Ca 2+ influx in pancreatic beta cells and consequent hyperinsulinism, this hypoglycemia mechanism is undemonstrated because of limited clinical data and lack of animal models. We generated a Ca V 1.2 G406R knockin mouse model that recapitulates key TS features, including hypoglycemia. Unexpectedly, these mice do not show hyperactive beta cells or hyperinsulinism in the setting of normal intrinsic beta cell function, suggesting dysregulated glucose homeostasis. Patient data confirm the absence of hyperinsulinism. We discover multiple alternative contributors, including perturbed counterregulatory hormone responses with defects in glucagon secretion and abnormal hypothalamic control of glucose homeostasis. These data provide new insights into contributions of Ca V 1.2 channels and reveal integrated consequences of the mutant channels driving life-threatening events in TS., (© 2024. The Author(s).)

One of the most complex human physiological processes to study is pregnancy. Standard animal models, as well as two-dimensional models, lack the complexity and biological relevance required to accurately study such a physiological process. Recent studies have focused on the development of three-dimensional models based on microfluidic systems, designated as placental microphysiological systems (PMPSs). PMPS devices provide a model of the placental barrier through culturing relevant cell types in specific arrangements and media to mimic the in vivo environment of the maternal-fetal circulation. Here, recent developments of PMPS models for embryo uterine implantation, preeclampsia evaluation, and toxicological screening are presented. Studies that use bioprinting techniques are also discussed. Lastly, recent developments in endometrium microphysiological systems are reviewed. All these presented models showed their superiority compared to standard models in recapitulating the biological environment seen in vivo . However, several limitations regarding the types of cells and materials used for these systems were also widely reported. Despite the need for further improvements, PMPS models contribute to a better understanding of the biological mechanisms surrounding pregnancy and the respective pathologies.

Major depressive disorder (MDD) is a significant cause of disability in adults worldwide. However, the underlying causes and mechanisms of MDD are not fully understood, and many patients are refractory to available therapeutic options. Impaired control of brain mRNA translation underlies several neurodevelopmental and neurodegenerative conditions, including autism spectrum disorders and Alzheimer's disease (AD). Nonetheless, a potential role for mechanisms associated with impaired translational control in depressive-like behavior remains elusive. A key pathway controlling translation initiation relies on the phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α-P) which, in turn, blocks the guanine exchange factor activity of eIF2B, thereby reducing global translation rates. Here we report that the expression of EIF2B5 (which codes for eIF2Bε, the catalytic subunit of eIF2B) is reduced in postmortem MDD prefrontal cortex from two distinct human cohorts and in the frontal cortex of social isolation-induced depressive-like behavior model mice. Further, pharmacological treatment with anisomycin or with salubrinal, an inhibitor of the eIF2α phosphatase GADD34, induces depressive-like behavior in adult C57BL/6J mice. Salubrinal-induced depressive-like behavior is blocked by ISRIB, a compound that directly activates eIF2B regardless of the phosphorylation status of eIF2α, suggesting that increased eIF2α-P promotes depressive-like states. Taken together, our results suggest that impaired eIF2-associated translational control may participate in the pathophysiology of MDD, and underscore eIF2-eIF2B translational axis as a potential target for the development of novel approaches for MDD and related mood disorders., (© 2024. The Author(s).)

Extant salamanders are used as modern analogs of early digit-bearing tetrapods due to general similarities in morphology and ecology, but the study species have been primarily terrestrial and relatively smaller when the earliest digit-bearing tetrapods were aquatic and an order of magnitude larger. Thus, we created a 3D computational model of underwater walking in extant Japanese giant salamanders (Andrias japonicus) using 3D photogrammetry and open-access graphics software (Blender) to broaden the range of testable hypotheses about the incipient stages of terrestrial locomotion. Our 3D model and software protocol represent the initial stages of an open-access pipeline that could serve as a "one-stop-shop" for studying locomotor function, from creating 3D models to analyzing the mechanics of locomotor gaits. While other pipelines generally require multiple software programs to accomplish the different steps in creating and analyzing computational models of locomotion, our protocol is built entirely within Blender and fully customizable with its Python scripting so users can devote more time to creating and analyzing models instead of navigating the learning curves of several software programs. The main value of our approach is that key kinematic variables (e.g. speed, stride length, and elbow flexion) can be easily altered on the 3D model, allowing scientists to test hypotheses about locomotor function and conduct manipulative experiments (e.g. lengthening bones) that are difficult to perform in vivo. The accurate 3D meshes (and animations) generated through photogrammetry also provide exciting opportunities to expand the abundance and diversity of 3D digital animals available for researchers, educators, artists, conservation biologists, etc. to maximize societal impacts., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Background: Mechanical ventilation in the intensive care unit (ICU) is a life-saving technique for patients with acute respiratory failure, but is also associated with a high incidence of complications in the injured lung. Currently, there is no widely used monitoring technique to guide the ventilator setting to facilitate a precision medicine approach or to provide a real-time alert for developing adverse pulmonary conditions. Conventional ultrasound has been used as a thoracic bedside technology, but the lack of signal penetration into lung tissue results in images that often contain more information in their artifacts than in the images themselves. Perhaps the greatest obstacle to using traditional ultrasound in the ICU is the need for highly skilled technicians to perform the data collection. In contrast, low-frequency ultrasound (50-500 kHz) has been shown to penetrate the lung, and can detect air trapping in patients with chronic obstructive pulmonary disease (COPD)., Purpose: Here, we present a method of collecting low-frequency ultrasound computed tomographic (USCT) data in vivo on a mechanically ventilated porcine model and computing tomographic reconstructions of airflow during tidal breathing and induced lung injuries. We evaluate the ability of the novel low-frequency USCT system to image regional changes in sound speed in the thorax due to changes in airflow during tidal breathing and induced lung injuries. This represents the first study of low-frequency tomographic ultrasound imaging in vivo and the first to produce tomographic images of ventilatory changes in vivo., Methods: USCT and computed tomography (CT) scan data were collected alternately on a mechanically ventilated Landrace pig weighing approximately 75 kg during tidal breathing, induced pneumothorax, atelectasis, and pleural effusion. The pneumothorax was induced by injecting air through a 5 mm thick intrathoracic tube inserted in the 8th posterior intercostal space. After removing the air, atelectasis was induced by ventilating the animal with a high concentration of oxygen and low tidal volumes. The pleural effusion was induced by injecting a saline solution through the tube. The USCT data were collected at 125 kHz using the USCT low-frequency ultrasound tomography (LUFT) system on a transducer belt placed around the animal's thorax. Tomographic reconstructions were computed from the USCT data using a regularized refraction-corrected Gauss-Newton-based time-of-flight reconstruction algorithm., Results: Cyclic changes in computed lung area during tidal breathing were demonstrated to agree with the respiratory rate on the mechanical ventilator. Reconstructed images computed at time steps during the procedure demonstrate regional changes consistent with what would be expected during the induced lung injury. No ground truth was available for images during the procedures since CT scans could only be taken before and after each established lung injury., Conclusions: In this work, we have demonstrated in the first in vivo study using a mechanically ventilated porcine animal model that low-frequency ultrasound tomography has the ability to image regional changes in sound speed in the thorax corresponding to changes in airflow during tidal breathing and induced lung injury. The results show promise for using low-frequency USCT as a bedside imaging technique in the future for patients with acute respiratory distress syndrome., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

The development of new treatments for ocular diseases often requires investigating eyes similar in size and structure to human eyes. Such studies are challenging because analyzing the histopathology of large, human-sized eyes can be technically difficult. In particular, obtaining high-quality frozen sections is almost impossible due to the formation of ice crystals in the vitreous, which causes crush artifacts during the procedures of section and post sectioning manipulations. Herein, we describe a new method that provides high-quality frozen sections for large eyes and demonstrate its usefulness in the eyes of rabbits, pigs, minipigs, monkeys, and humans. We observed that artifactual separation of the photoreceptors from the retinal pigment epithelium is minimized and photoreceptor morphology is preserved. This method can be highly beneficial for investigators seeking to translate new treatments for ocular disease into the clinic. RESEARCH HIGHLIGHTS: Histopathological analysis of large and human-sized eyes presents significant challenges, particularly in obtaining high-quality frozen sections. A multistep fixation followed by vitreous removal and replacement ensures better cryopreservation and embedding of large eyes, minimizing the morphological and structural retinal loss found in many studies. Our results demonstrate that a multistep fixation and cryopreservation method for large eyes in histopathology consistently minimizes the artifactual separation of photoreceptors from the retinal pigment epithelium, thereby preserving photoreceptor morphology and providing high-quality frozen sections. A new method providing high-quality sections is necessary and will be highly useful for investigators aiming to translate new treatments for ocular diseases into clinical applications., (© 2024 The Author(s). Microscopy Research and Technique published by Wiley Periodicals LLC.)

Background: European and North-American guidelines on management of H. pylori infection in children provide the option not to treat even if the infection is endoscopically confirmed. We used data from the EuroPedHp Registry to identify factors associated with therapy decisions., Methods: We included treatment-naïve patients reported between 2017 and 2020 from 30 centers in 17 European countries. Multivariable logistic regression identified factors including comorbidities within and outside the gastrointestinal (GI) tract influencing the decision for or against therapy., Results: Of 1165 patients (52% females, median age 12.8), 28% (321/1165) reported any alarm symptom, 26% (307/1165) comorbidities, and 16% (192/1165) did not receive eradication treatment. Therapy was initiated less often in children having any GI comorbidity (57%, n = 181), particularly in those with eosinophilic esophagitis (60%, n = 35), inflammatory bowel disease (54%, n = 28), and celiac disease (43%, n = 58), compared to those with non-GI (86%, n = 126) or no comorbidity (89%, n = 858), despite similar frequencies of alarm and non-alarm symptoms, ulcers, erosions, and nodular gastritis. Patients with GI and without comorbidities remained more likely untreated in high versus low H. pylori prevalence countries (p < 0.0001). In children without comorbidities, factors favoring therapy included older age, being overweight, having symptoms, erosions, antral nodularity, and available antibiotic susceptibility results., Conclusion: In this cohort, H. pylori-infected children with GI comorbidities compared to no comorbidity showed 75% reduced chance of receiving eradication therapy. We found no evidence supporting different management strategies in infected patients with GI comorbidities compared to all pediatric patients with endoscopically proven H. pylori infection., (© 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.)

Ophthalmic rehabilitation refers to the multidisciplinary approach to restoring, maximizing, and preserving the visual function and quality of life for patients affected by ocular manifestations of cancer or its treatments. Besides its approach to low vision, ophthalmic rehabilitation also encompasses a series of reconstructive interventions to mitigate anatomic deficits that may interplay with visual impairment. A gamut of oncologic conditions may result in ocular disabilities, including primary intraocular tumours, secondary metastases, or adverse effects of systemic therapies such as chemotherapy, radiation, and surgery. Methods of ophthalmic rehabilitation are evolving constantly and involve the prescription of optical aids and adaptive technologies to enhance remaining vision, as well as supportive training and counselling to address psychosocial effects. Although studies in low vision have mostly covered aspects of rehabilitation in inherited and degenerative eye conditions, ophthalmic rehabilitation within the context of cancer carries specificities that have been poorly explored in the literature on ophthalmology and oncology. This review aims to build on the trends of low vision management, ocular oncology treatments, orbital reconstructive surgery, and visual therapy to revise the published rationale behind evaluating and managing patients facing debilitating ocular sequelae as the result of cancer., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

"Purple Drank", a soft drink containing promethazine (PMZ) and codeine (COD), has gained global popularity for its hallucinogenic effects. Consuming large amounts of this combination can lead to potentially fatal events. The binding of these drugs to plasma proteins can exacerbate the issue by increasing the risk of drug interactions, side effects, and/or toxicity. Herein, the binding affinity to human serum albumin (HSA) of PMZ and its primary metabolites [N-desmethyl promethazine (DMPMZ) and promethazine sulphoxide (PMZSO)], along with COD, was investigated by high-performance affinity chromatography (HPAC) though zonal approach. PMZ and its metabolites exhibited a notable binding affinity for HSA (%b values higher than 80%), while COD exhibited a %b value of 65%. To discern the specific sites of HSA to which these compounds were bound, displacement experiments were performed using warfarin and (S)-ibuprofen as probes for sites I and II, respectively, which revealed that all analytes were bound to both sites. Molecular docking studies corroborated the experimental results, reinforcing the insights gained from the empirical data. The in silico data also suggested that competition between PMZ and its metabolites with COD can occur in both sites of HSA, but mainly in site II. As the target compounds are chiral, the enantioselectivity for HSA binding was also explored, showing that the binding for these compounds was not enantioselective., (© 2024. The Author(s).)

Aims: Cardiovascular disease, primarily coronary artery disease (CAD), is the leading cause of mortality worldwide. Accurate diagnosis of CAD often requires pre-test probability (PTP) estimation, traditionally performed using scoring systems like the Diamond-Forrester (DF) and European Society of Cardiology (ESC) models. However, the applicability of such models in specific populations may vary. This study compares the performance of DF and PTP scores in the Brazilian context, using coronary computed tomography angiography (CCTA) as a reference standard., Methods and Results: PTP for obstructive CAD was calculated using DF and ESC scores in 409 symptomatic patients without known CAD who underwent CCTA between 2019 and 2022. Predicted PTP was compared with actual CAD prevalence. DF overestimated CAD prevalence across age and symptom categories, while ESC showed better alignment with actual prevalence., Conclusion: Our study confirms that the ESC PTP model is more appropriate than the DF model for determining PTP in the Brazilian population., Competing Interests: Conflict of interest: F.E.: Nothing to disclosure. R.L.: Nothing to disclosure. F.P.: Nothing to disclosure. R.G.: Nothing to disclosure. B.J.W.C. receives research support from TD Bank and Artrya. He is a consultant for and has an equity interest in Artrya., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Gamma cameras with cadmium-zinc telluride (CZT) detectors allowed the quantification of myocardial flow reserve (MBF), which can increase the accuracy of myocardial perfusion scintigraphy (MPS) to detect the cause of chest discomfort., Objective: To assess the clinical impact of MBF to detect the cause of chest discomfort., Methods: 171 patients with chest discomfort who underwent coronary angiography or coronary CT angiography also underwent MPS and MBF in a time interval of <30 days. The acquisitions of dynamic imaging of rest and stress were initiated simultaneously with the 99mTc injection sestamibi (10 and 30mCi, respectively), both lasting eleven minutes, followed by immediately acquiring perfusion images for 5 minutes. The stress was performed with dipyridamole. A global or per coronary territory MBF <2.0 was classified as abnormal., Results: The average age was 65.9±10 years (60% female). The anatomical evaluation showed that 115 (67.3%) patients had coronary obstruction significant, with 69 having abnormal MPs and 91 having abnormal MBF (60.0% vs 79.1%, p<0.01). Among patients without obstruction (56 - 32.7%), 7 had abnormal MPS, and 23 had reduced global MBF. Performing MBF identified the etiology of the chest discomfort in 114 patients while MPS identified it in 76 (66.7% vs 44.4%, p<0.001)., Conclusion: MBF is a quantifiable physiological measure that increases the clinical impact of MPS in detecting the cause of chest discomfort through greater accuracy for detecting obstructive CAD, and it also makes it possible to identify the presence of the microvascular disease.

Objective: The Ecological Momentary Assessment (EMA) concept was the basis for developing a smartphone application for the real-time report of awake bruxism (AB) activities. The aim of this study was to assess the effects of the EMA with a randomised controlled trial designed to compare the frequency of AB reported in two separate single observation points between a group of students monitored over time with an EMA smartphone application and a non-EMA monitored group., Methods: Sixty-four (N = 64) dental students (22.3 YO [±2.6]; 52F; 12 M) answered the Oral Behaviour Checklist (OBC-1) and were randomised into an EMA-group (EG) and control group (CG). EG were monitored with a smartphone application for AB report during seven consecutive days and completed three EMA monitoring periods (EMA-1, 2 and 3) at one-month intervals. After the third period (EMA-3), both EG and CG answered again the OBC (OBC-2). Descriptive statistics were performed to characterise the sample. Pearson's chi-squared test, Fixer Exact test and post hoc Z test with Bonferroni correction were performed. The study hypothesis was that EMA could influence the AB reported by the participants because it implies an increase in the awareness, self-recognition, and self-control of bruxism behaviours. The level of significance was set at p < .05., Result: The percentage of participants who changed the report of the activity of clenching their teeth while awake between OBC-1 and OBC-2 was significantly higher among participants in EG, when compared to CG (p = .027). For all other behaviours reported the within- and between-group differences from OBC-1 to OBC-2 were not significant. Clenching and bracing were the most frequently reported, whilst grinding was the less frequent behaviour., Conclusion: A smartphone-based EMA approach demonstrated be useful to monitor AB over time, increasing individual's awareness, particularly to bracing and clenching behaviours., (© 2024 The Authors. Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Background Aims: Parkinson's disease (PD) is the second most common neurodegenerative disorder. The etiology of the disease remains largely unknown, but evidence have suggested that the overexpression and aggregation of alpha-synuclein (α-syn) play key roles in the pathogenesis and progression of PD. Mesenchymal stromal cells (MSCs) have been earning attention in this field, mainly due to their paracrine capacity. The bioactive molecules secreted by MSCs, i.e. their secretome, have been associated with enhanced neuronal survival as well as a strong modulatory capacity of the microenvironments where the disease develops. The selection of the appropriate animal model is crucial in studies of efficacy assessment. Given the involvement of α-syn in the pathogenesis of PD, the evidence generated from the use of animal models that develop a pathologic phenotype due to the action of this protein is extremely valuable. Therefore, in this work, we established an animal model based on the viral vector-mediated overexpression of A53T α-syn and studied the impact of the secretome of bone marrow mesenchymal stromal cells MSC(M) as a therapeutic strategy., Methods: Adult male rats were subjected to α-syn over expression in the nigrostriatal pathway to model dopaminergic neurodegeneration. The impact of locally administered secretome treatment from MSC(M) was studied. Motor impairments were assessed throughout the study coupled with whole-region (striatum and substantia nigra) confocal microscopy evaluation of histopathological changes associated with dopaminergic neurodegeneration and glial cell reactivity., Results: Ten weeks after lesion induction, the animals received secretome injections in the substantia nigra pars compacta (SNpc) and striatum (STR). The secretome used was produced from bone marrow mesenchymal stromal cells MSC(M) expanded in a spinner flask (SP) system. Nine weeks later, animals that received the viral vector containing the gene for A53T α-syn and treated with vehicle (Neurobasal-A medium) presented dopaminergic cell loss in the SNpc and denervation in the STR. The treatment with secretome significantly reduced the levels of α-syn in the SNpc and protected the dopaminergic neurons (DAn) within the SNpc and STR., Conclusions: Our results are aligned with previous studies in both α-syn Caenorhabditis elegans models, as well as 6-OHDA rodent model, revealing that secretome exerted a neuroprotective effect. Moreover, these effects were associated with a modulation of microglial reactivity supporting an immunomodulatory role for the factors contained within the secretome. This further supports the development of new studies exploring the effects and the mechanism of action of secretome from MSC(M) against α-syn-induced neurotoxicity., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest, (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Importance: Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials., Objective: To analyze the association between pegcetacoplan and consensus GA SD-OCT end points., Design, Setting, and Participants: This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023., Interventions: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month., Main Outcomes and Measures: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal)., Results: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month., Conclusions and Relevance: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors., Trial Registration: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

This in vitro study aimed to verify the influence of chlorhexidine (CHX) (gel and solution) in association with different activation protocols on disinfection of root canals contaminated with Enterococcus faecalis. In total, 120 lower premolar roots were selected, contaminated and divided into 12 groups according to irrigation technique and substance. Samples were collected before and after each irrigation technique and analysed for colony-forming units (CFU). Three dentin discs were obtained for quantification of viable intratubular cells by using confocal laser scanning microscopy (CLSM). CFU results showed that sonic and ultrasonic were more effective than conventional irrigation. Ultrasonic activation was more effective than sonic for CHX gel (p < 0.05). CLSM showed that either activation was better than conventional in all groups and root canal thirds (p < 0.05). It was concluded that ultrasonic/sonic activation was more effective than conventional techniques and CHX enhanced intratubular dentin decontamination across all irrigation methods., (© 2024 Australian Society of Endodontology Inc.)

Purpose: This cohort study aimed to investigate the relationship between subjective (wellness and internal training load [ITL]) and objective (neuromuscular fatigue) monitoring markers and performance aspects (reception quality [RQ] and attack efficiency [AE]) in professional female volleyball players., Methods: The study was conducted over an 8-week period during the final mesocycle of the competitive phase. A total of 24 training sessions and 10 matches were included in the analysis. Subjective measures of wellness and ITL were assessed, and neuromuscular fatigue was evaluated using countermovement-jump (CMJ) height. RQ and AE were determined based on game statistics., Results: The study found a positive relationship between wellness and RQ, particularly affecting outside hitters and liberos. ITL showed a positive association with AE, primarily impacting outside hitters, opposite hitters, and middle blockers. Additionally, ITL demonstrated a negative correlation with RQ, mainly affecting outside hitters and liberos. CMJ performance was associated with AE, where a decrease in CMJ height was linked to reduced AE., Conclusions: The findings highlight the importance of considering players' wellness scores in training and match strategies for different positions. Careful management of training loads, considering both physical and technical demands, is crucial for optimizing performance outcomes. Monitoring neuromuscular fatigue, as indicated by CMJ performance, is particularly relevant for outside hitters, opposite hitters, and middle blockers involved in attack actions. Coaches, trainers, and sports practitioners can use these insights to develop position-specific training protocols and implement effective strategies for maintaining or improving performance metrics under various stressors.

A solar position sensor is an essential optoelectronic device used to monitor the sun's position in solar tracking systems. In closed-loop systems, this sensor is responsible for providing feedback signals to the control system, allowing motor adjustments to optimize the angle of incidence and minimize positioning errors. The accuracy required for solar tracking systems varies depending on the specific photovoltaic concentration. In the case of the concentrator photovoltaic (CPV), it is normally essential to track the sun with a position error of less than ±0.6°. To achieve such precision, a proposed sensor configuration composed of low-cost embedded electronics and multifiber optical cable is subjected to characterization through a series of measurements covering range, sensitivity, and resolution. These measurements are performed in controlled indoor environments as well as outdoor conditions. The results obtained exhibit a resolution of 2.6×10-3 degrees when the sensor is illuminated within its designated field of view of ±0.1°, particularly in external conditions. Considering the performance demonstrated by the proposed solar position sensor, coupled with its straightforward modeling and assembly compared to position sensors documented in the literature, it emerges as a promising candidate for integration into solar tracking systems.

Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4 + T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity., (© 2024. The Author(s).)

Over the last decade, researchers have developed a variety of new analytical and clinical diagnostic devices. These devices are predominantly based on microfluidic technologies, where biological samples can be processed and manipulated for the collection and detection of important biomolecules. Polydimethylsiloxane (PDMS) is the most commonly used material in the fabrication of these microfluidic devices. However, it has a hydrophobic nature (contact angle with water of 110°), leading to poor wetting behavior and issues related to the mixing of fluids, difficulties in obtaining uniform coatings, and reduced efficiency in processes such as plasma separation and molecule detection (protein adsorption). This work aimed to consider the fabrication aspects of PDMS microfluidic devices for biological applications, such as surface modification methods. Therefore, we studied and characterized two methods for obtaining hydrophilic PDMS surfaces: surface modification by bulk mixture and the surface immersion method. To modify the PDMS surface properties, three different surfactants were used in both methods (Pluronic ® F127, polyethylene glycol (PEG), and polyethylene oxide (PEO)) at different percentages. Water contact angle (WCA) measurements were performed to evaluate the surface wettability. Additionally, capillary flow studies were performed with microchannel molds, which were produced using stereolithography combined with PDMS double casting and replica molding procedures. A PDMS microfluidic device for blood plasma separation was also fabricated by soft lithography with PDMS modified by PEO surfactant at 2.5% ( v / v ), which proved to be the best method for making the PDMS hydrophilic, as the WCA was lower than 50° for several days without compromising the PDMS's optical properties. Thus, this study indicates that PDMS surface modification shows great potential for enhancing blood plasma separation efficiency in microfluidic devices, as it facilitates fluid flow, reduces cell aggregations and the trapping of air bubbles, and achieves higher levels of sample purity.

Background: Three-dimensional (3D) imaging using computer simulations is an evolving technology. There is a lack of strong data on the use of this technology for oncoplastic (OP) and reconstructive surgery., Methods: A prospective, randomized, single-center trial including breast cancer patients undergoing OP or mastectomy with immediate breast reconstruction with implant (IBR) enrolled from November 2019 to October 2021 at the Hospital Nossa Senhora das Graças, Breast Unit in Curitiba, Brazil. Both patients undergoing OP and those in the IBR group were randomized to undergo 3D imaging and simulation of postoperative results (intervention group) or 3D imaging without simulation (control group). All patients were invited to complete a patient-reported outcome (BREAST-Q) expectations module and breast reconstruction or reduction/mastopexy module before and 6 months after surgery., Results: A total of 96 patients were enrolled. Sixty-nine patients (45 OP and 24 IBR) completed the pre- and postoperative questionnaires and were randomized for the simulation. Women in the OP group had higher expectations for breast appearance when clothed than those in the IBR implant group (93.4 ± 16.3 versus 82.9 ± 26.5; P = 0.03). The intervention group was more satisfied with information than the control group ( P = 0.021). Both patients who underwent OP and IBR believed that the 3D simulation helped them understand the surgical process (86.6% and 75%, respectively)., Conclusions: Preoperative 3D simulation significantly improved patient's satisfaction with information and did not decrease postoperative satisfaction with the outcomes. The incorporation of preoperative 3D simulation may be a valuable tool in breast reconstruction., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Suprachoroidal nonviral gene therapy with biodegradable poly(β-amino ester) nanoparticles (NPs) provides widespread expression in photoreceptors and retinal pigmented epithelial (RPE) cells and therapeutic benefits in rodents. Here, we show in a human-sized minipig eye that suprachoroidal injection of 50 μl of NPs containing 19.2 μg of GFP expression plasmid caused GFP expression in photoreceptors and RPE throughout the entire eye with no toxicity. Two weeks after injection of 50, 100, or 200 μl, there was considerable within-eye and between-eye variability in expression that was reduced 3 months after injection of 200 μl and markedly reduced after three suprachoroidal injections at different locations around the eye. Reduction of bacterial CpG sequences in the expression plasmid resulted in a trend toward higher expression. These data indicate that nonviral suprachoroidal gene therapy with optimized polymer, expression plasmid, and injection approach has potential for treating photoreceptors throughout the entire retina of a human-sized eye.

Background: Biogenic metallic and oxide metal nanoparticles have potential as alternatives for several current problems in agriculture, such as the control of caterpillars which cause huge losses in the production of important crops. In the present study, capped and uncapped silver, iron oxide and titanium dioxide nanoparticles were synthesized from the filtrate of Beauveria bassiana and evaluated in regard to physico-chemical characteristics, capping composition, cytotoxicity, genotoxicity and biological activity on Helicoverpa armigera and Spodoptera frugiperda caterpillars., Results: A difference in the physico-chemical parameters of the capped and uncapped nanoparticles was observed, with larger aggregation and lower stability of the uncapped. In regard to the study of the capping, the presence of functional groups of biomolecules as well as the activity of B. bassiana hydrolytic enzymes were observed. Cytotoxic effects on the tested cell lines were not observed and DNA damage levels increased with more intense effects of the uncapped nanoparticles. In regard to the biological activity against Noctuidae pests, the uncapped and capped iron oxide, and uncapped titanium dioxide nanoparticles occasioned higher mortality (76%, 60% and 51%, respectively) but no differences in LC 50 were recorded. Moreover, sublethal effects were reported on Helicoverpa armigera whereas Spodoptera frugiperda showed low susceptibility to the nanoparticles., Conclusion: The results demonstrate that biogenic metallic and oxide metal nanoparticles might show promising effects for the control of caterpillars which cause damage on important agricultural crops. Further investigations are necessary to understand the mechanisms of action and optimize the biological activity of these new nanomaterials. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Introduction: The inflammatory response after spinal cord injury (SCI) is an important contributor to secondary damage. Infiltrating macrophages can acquire a spectrum of activation states, however, the microenvironment at the SCI site favors macrophage polarization into a pro-inflammatory phenotype, which is one of the reasons why macrophage transplantation has failed., Methods: In this study, we investigated the therapeutic potential of the macrophage secretome for SCI recovery. We investigated the effect of the secretome in vitro using peripheral and CNS-derived neurons and human neural stem cells. Moreover, we perform a pre-clinical trial using a SCI compression mice model and analyzed the recovery of motor, sensory and autonomic functions. Instead of transplanting the cells, we injected the paracrine factors and extracellular vesicles that they secrete, avoiding the loss of the phenotype of the transplanted cells due to local environmental cues., Results: We demonstrated that different macrophage phenotypes have a distinct effect on neuronal growth and survival, namely, the alternative activation with IL-10 and TGF-β1 (M(IL-10+TGF-β1)) promotes significant axonal regeneration. We also observed that systemic injection of soluble factors and extracellular vesicles derived from M(IL-10+TGF-β1) macrophages promotes significant functional recovery after compressive SCI and leads to higher survival of spinal cord neurons. Additionally, the M(IL-10+TGF-β1) secretome supported the recovery of bladder function and decreased microglial activation, astrogliosis and fibrotic scar in the spinal cord. Proteomic analysis of the M(IL-10+TGF-β1)-derived secretome identified clusters of proteins involved in axon extension, dendritic spine maintenance, cell polarity establishment, and regulation of astrocytic activation., Discussion: Overall, our results demonstrated that macrophages-derived soluble factors and extracellular vesicles might be a promising therapy for SCI with possible clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision, (Copyright © 2024 Lentilhas-Graça, Santos, Afonso, Monteiro, Pinho, Mendes, Dias, Gomes, Lima, Fernandes, Fernandes-Amorim, Pereira, de Sousa, Cibrão, Fernandes, Serra, Rocha, Campos, Pinho, Monteiro, Manadas, Salgado, Almeida and Silva.)

This review attempts to provide a comprehensive assessment of recent methodologies, structures, and devices for pool boiling heat transfer enhancement. Several enhancement approaches relating to the underlying fluid route and the capability to eliminate incipient boiling hysteresis, augment the nucleate boiling heat transfer coefficient, and improve the critical heat flux are assessed. Hence, this study addresses the most relevant issues related to active and passive enhancement techniques and compound enhancement schemes. Passive heat transfer enhancement techniques encompass multiscale surface modification of the heating surface, such as modification with nanoparticles, tunnels, grooves, porous coatings, and enhanced nanostructured surfaces. Also, there are already studies on the employment of a wide range of passive enhancement techniques, like displaced enhancement, swirl flow aids, and bi-thermally conductive surfaces. Moreover, the combined usage of two or more enhancement techniques, commonly known as compound enhancement approaches, is also addressed in this survey. Additionally, the present work highlights the existing scarcity of sufficiently large available databases for a given enhancement methodology regarding the influencing factors derived from the implementation of innovative thermal management systems for temperature-sensitive electronic and power devices, for instance, material, morphology, relative positioning and orientation of the boiling surface, and nucleate boiling heat transfer enhancement pattern and scale. Such scarcity means the available findings are not totally accurate and suitable for the design and implementation of new thermal management systems. The analysis of more than 100 studies in this field shows that all such improvement methodologies aim to enhance the nucleate boiling heat transfer parameters of the critical heat flux and nucleate heat transfer coefficient in pool boiling scenarios. Finally, diverse challenges and prospects for further studies are also pointed out, aimed at developing important in-depth knowledge of the underlying enhancement mechanisms of such techniques.

Nanomaterials' application in cancer therapy has been driven by their ability to encapsulate chemotherapeutic drugs as well as to reach the tumor site. Nevertheless, nanomedicines' translation has been limited due to their lack of specificity towards cancer cells. Although the nanomaterials' surface can be coated with targeting ligands, such has been mostly achieved through non-covalent functionalization strategies that are prone to premature detachment. Notwithstanding, cancer cells often establish resistance mechanisms that impair the effect of the loaded drugs. This bottleneck may be addressed by using near-infrared (NIR)-light responsive nanomaterials. The NIR-light triggered hyperthermic effect generated by these nanomaterials can cause irreversible damage to cancer cells or sensitize them to chemotherapeutics' action. Herein, a novel covalently functionalized targeted NIR-absorbing nanomaterial for cancer chemo-photothermal therapy was developed. For such, dopamine-reduced graphene oxide nanomaterials were covalently bonded with hyaluronic acid, and then loaded with doxorubicin (DOX/HA-DOPA-rGO). The produced nanomaterials showed suitable physicochemical properties, high encapsulation efficiency, and photothermal capacity. The in vitro studies revealed that the nanomaterials are cytocompatible and that display an improved uptake by the CD44-overexpressing breast cancer cells. Importantly, the combination of DOX/HA-DOPA-rGO with NIR light reduced breast cancer cells' viability to just 23 %, showcasing their potential chemo-photothermal therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by the expansion of a noncoding triplet repeat., Methods: A cross-sectional study was performed to characterize pediatric patients with DM1 followed in a tertiary hospital over the last 29 years, comparing the congenital and the childhood/juvenile-onset forms., Results: Thirty-seven patients (59.5 % male) were included, with a median age at the latest assessment of 16.8 years and a median follow-up of 7.7 years. Eleven patients were lost to follow-up, and two died. Twenty-five had congenital DM1 (CDM1), and this form had significantly higher triplet repeat length, history of polyhydramnios, lower median age at diagnosis, and first and last assessment. Common symptoms included distal skeletal muscle weakness (75.7 %) and facial involvement (94.6 %), along with dysphonia/dysarthria (73.0 %) and myotonia (73.0 %). Delayed independent ambulation frequency was significantly higher for CDM1 cases. Skeletal deformities affected 54.1 %, with talipes equinovarus and scoliosis occurring exclusively in CDM1 patients. Cognitive deficit was present in 75.7 % of cases. Polysomnograms revealed seven cases of obstructive sleep apnea and two of hypoventilation. Noninvasive ventilation was used in nine cases, and three had recurrent respiratory infections. The cardiovascular system was affected in 21.6 % of cases. Gastrointestinal issues included constipation (24.3 %), feeding difficulties (16.2 %), and cholelithiasis (5.4 %). Cataracts, epilepsy, and diabetes mellitus were reported in two cases each., Conclusion: Our study highlights the diverse spectrum of severity and multiorgan involvement of DM1 in pediatric patients. It underscores the importance of establishing a pediatric-specific standard of care to enhance health outcomes through comprehensive multidisciplinary management., Competing Interests: Declaration of competing interest The authors declare no conflict of interest relevant to this study., (© 2023 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

The therapeutic approach to inflammatory bowel disease (IBD) is complex, often involving multiple pharmacologic classes. We aimed to evaluate the prevalence of drug-related adverse reactions (ARs) associated with therapies used in pediatric IBD. We conducted a retrospective study of pediatric patients with IBD followed in a tertiary hospital from 2010 to 2022. Ninety-nine patients were included (62.6% were male), with a median age at diagnosis of 13 years (interquartile range [IQR] 11-15 years). The majority had Crohn's disease (69.7%), followed by ulcerative colitis (21.2%) and unclassified IBD (9.1%). The most prescribed therapies were: immunomodulators (n = 75, 75.8%), exclusive enteral nutrition (n = 61, 61.6%), and biologics (n = 58, 58.6%). During a median follow-up time of 31 months (IQR 11-51 months), the incidence of ARs was 16.2% (16 ARs occurred in 14 patients). The main drug involved was azathioprine (12/16) and the most frequent AR was hepatitis (5/16). Drug discontinuation was necessary in all but 1 case. Of the ARs recorded, 75% were mild to moderate and 81.3% did not require specific treatment; all patients had clinical and/or analytical normalization. There was a positive association between the cumulative number of prescribed drugs and the occurrence of ARs (P = .044). The incidence of ARs was similar to the rates reported in the few existing previous studies. The majority of ARs were mild, but implied the discontinuation of therapy or dose reduction, with a possible impact on disease control., (© 2023, The American College of Clinical Pharmacology.)