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Sex differences are widespread during neurodevelopment and play a role in neuropsychiatric conditions such as autism, which is more prevalent in males than females. In humans, males have been shown to have larger brain volumes than females with development of the hippocampus and amygdala showing prominent sex differences. Mechanistically, sex steroids and sex chromosomes drive these differences in brain development, which seem to peak during prenatal and pubertal stages. Animal models have played a crucial role in understanding sex differences, but the study of human sex differences requires an experimental model that can recapitulate complex genetic traits. To fill this gap, human induced pluripotent stem cell–derived brain organoids are now being used to study how complex genetic traits influence prenatal brain development. For example, brain organoids from individuals with autism and individuals with X chromosome–linked Rett syndrome and fragile X syndrome have revealed prenatal differences in cell proliferation, a measure of brain volume differences, and excitatory-inhibitory imbalances. Brain organoids have also revealed increased neurogenesis of excitatory neurons due to androgens. However, despite growing interest in using brain organoids, several key challenges remain that affect its validity as a model system. In this review, we discuss how sex steroids and the sex chromosomes each contribute to sex differences in brain development. Then, we examine the role of X chromosome inactivation as a factor that drives sex differences. Finally, we discuss the combined challenges of modeling X chromosome inactivation and limitations of brain organoids that need to be taken into consideration when studying sex differences.

Abstract Radiogenic isotopic compositions of arc magmas are a key tool for studying active margin evolution. They have two isotopic end-members: melts formed mostly from juvenile asthenosphere and melts sourced from evolved continental crust/continental lithospheric mantle. Cordilleran-margins are typically more isotopically juvenile near the trench, and conversely, increasingly evolved landward. However, this model has not been tested on the ~1,500 km long Mesozoic-Cenozoic arc of the Antarctic Peninsula. Here we show that while geochemical compositions remain largely constant, radiogenic isotopes become increasingly juvenile with time. Unlike other continental arcs, there is no association between isotopic composition and spatial distribution. This is attributed to: (i) slow subduction of young oceanic lithosphere, resulting in narrowing of the arc and reduced capacity to incorporate continental crust into melts, and (ii) the Cenozoic decrease in convergence rate, which reduced the friction in the slab-overriding plate interface, allowing the arc melts to increasingly source from young juvenile asthenosphere.

Abstract The amalgamation of Laurentia was initiated along the western margin of the Rae craton. However, the tectonic setting that generated magmatic rocks along this margin has long been debated, with the Thelon tectonic zone in the north having formed in an arc setting, and the Taltson magmatic zone in the south variably attributed to either continental arc or intracratonic magmatism. The magmatic rocks of the Great Slave Lake shear zone (GSLsz) lie between these two tectonic belts and, thus, may be critical to the interpretation of the evolution of the western Rae margin. To understand the origin of the rocks in the GSLsz, we have applied U‐Pb geochronology, trace‐element geochemistry, and O and Hf isotope analyses to zircons from a suite of samples that transect the La Loche River fault (LRf)—a major structure that bisects the GSLsz. Samples collected to the north of the LRf are Neoarchean in age, have mantle‐like δ18O (4.7–5.8‰) and chondritic to juvenile εHf values (0–4.5), whereas those to the south are exclusively Paleoproterozoic in age and have more elevated δ18O (6.3–7‰) and much more evolved εHf values (−12 to −6); these results indicate that the LRf marks a crustal‐scale suture between the Slave craton and the Taltson magmatic zone. Our isotopic data, together with other regional constraints from the area, are most consistent with the Taltson magmatic zone having formed in a continental arc setting emplaced into ca. 2.3 Ga juvenile basement crust.

O artigo apresenta em detalhe a gênese do Fundo Monteiro Lobato, no CEDAE/Unicamp, abrangendo desde o projeto inicial até o desenvolvimento do Acervo ao longo dos anos. Algumas seções são mais explicitadas, como cartas (algumas transcritas), fotografias, livros e presença na mídia. Destaca seu papel para o conhecimento mais completo das plateias e bastidores da história literária brasileira dos inícios do século XX, para além dos estereótipos correntes sobre o escritor.

Tiny contact transients prove very informative for dexterous, fine manipulation, both in virtual environments and teleoperation. Yet, it is challenging to obtain such quality of the rendering in compact and highly wearable haptic devices. To this aim we propose a novel miniature hydraulic actuator, aiming at low-noise rendering of tiny tactile signals, fully enclosed in a fingertip haptic device. Its novelty is in the use of ferrofluidic sealings, embedded within a miniature linear electromagnetic motor. The solution has two main advantages: it shows no static friction, due to the magnetohydrodynamic levitation effect of the ferrofluid, and a noiseless hydraulic reduction. Besides, the hydraulic actuator enables the use of a soft and compliant interface for transmission of signals to the fingerpad tissues. We evaluate here a prototype of the actuator implemented in a compact and soft haptic thimble: the low-noise rendering capabilities are evaluated in experiments at the bench and through perception study. Then, in a simplified teleoperation setup, we match one-to-one the pressure rendered by the device with a sensitive pneumatic pressure sensor mounted on a robotic fingertip. Results show that haptic feedback alone (no vision) is able to improve results over the visual condition in terms of maximum exerted pressure.

Robotic avatar technology has the potential to impact the future of human connectivity, transporting the sense of a human’s presence to a remote location anywhere and in real-time. In this regard, the recent ANA Avatar XPRIZE challenge fostered the development of the ultimate generation of non-autonomous robotic avatar designs. This paper is devoted to introducing our system proposal, allowing intuitive motion-based control and multi-modal feedback. The teleoperated robot endorses an anthropomorphic upper body with dual arms and dexterous hands for fine manipulation of even small objects, as well as an omnidirectional platform for improved and safe locomotion. Special focus is pointed at the crucial challenge of providing self-body perception to the operator, in particular regarding control of the arms and rendering of haptic sensations. To this end, we propose an upper-limb exoskeleton and a teleoperation architecture allowing retargeting of the operator’s skills and receiving tactile and kinesthetic force feedback with realistic and informative perception of the own’s arms. Lastly, the platform was validated during laboratory and challenge missions mimicking several social, cooperative, and cultural scenarios from which we report on the lesson learned and future improvements.

ABSTRACTThe Darıderesi mineralisation was recently discovered in the Balya district, which hosts Pb-Zn (Ag) deposits including Arı Mağara-Balya Main and Hastanetepe-Balya North. Darıderesi is a structurally controlled hydrothermal and associated replacement mineralisation hosted in the shale-mudstone and carbonaceous horizons within the Karakaya Complex. The mineralisation was formed in three main stages as pre-ore calc-silicate alteration, main ore, and supergene alteration. The substages of the sulphide-sulphosalt mineralisation can be summarised as: pyrite-arsenopyrite galena, sphalerite, ferrokesterite, chalcopyrite, fahlore group and geocronite-jordanite solid solution series members, xanthoconite, pyrargyrite and goldfieldite. Fluid inclusion studies indicate that both boiling and fluid mixing were the most effective processes causing the precipitation of sulphides and sulphosalts. Along its pathway, fluid–rock interaction coupled with decreasing temperature evolved the fluid to a lower sulphur and oxygen fugacity and nearly neutral to weakly alkali state which promoted the precipitation of base metal and the following silver-bearing sulphides and sulphosalts. The lead isotope composition of sulphides implies that lead was essentially derived from Oligo-Miocene magmatic rocks in the region with some interaction with basement rocks. The similarity of the lead and sulphur isotopic compositions between Darıderesi and Balya deposits suggests that they may relate to the same magmatic source.

Objetivo: conhecer a experiência de manejo familiar da criança à espera de um transplante de órgãos sólidos de acordo com o Modelo de estilos de manejo familiar. Método: foi realizado um estudo qualitativo que utilizou o modelo supracitado como referencial teórico. Foram aplicadas entrevistas, de forma remota, a nove familiares de crianças que aguardavam por um transplante de órgãos. Os dados foram analisados através do modelo híbrido de análise temática. Resultados: as famílias definem que essa fase oscila entre o medo do transplante, da rejeição do órgão e possibilidade de morte em fila de espera, e a esperança na melhora do quadro clínico. Considerações finais: identificar as necessidades da família que aguarda por um transplante possibilita ao profissional de saúde implementar intervenções.

A new concept for minimally invasive treatment involves abdominal laparoscopic surgery performed while the patient breathes independently without losing consciousness. Here we report the first series of laparoscopic partial nephrectomy (LPN) performed under neuroaxial anesthesia (NA). From May 2021 to September 2022 we prospectively enrolled selected patients with an organ-confined single renal mass to undergo LPN under NA. Anesthesia was administered using an epidural catheter placed at the level of T7, with additional anesthesia at the level of T10. The rationale was to avoid use of a tracheal tube and the side effects of general anesthesia. Ten patients were enrolled in the study. Targeted sedation was achieved in all cases. In one case, a switch to general anesthesia was needed because of patient anxiety. Food intake started at 12 h after surgery in 9/10 cases; mobilization started from 3 h after surgery. The length of hospital stay was 3 d in 4/10 cases and 4 d in 3/10 cases. This first experience worldwide of LPN performed under NA demonstrates the feasibility and safety of the procedure.

Weather disturbances pose a significant challenge when estimating the energy production of photovoltaic panel systems. Energy production and forecasting models have recently been used to improve energy estimations and maintenance tasks. However, these models often rely on environmental measurements from meteorological units far from the photovoltaic systems. To enhance the accuracy of the developed model, a measurement Internet of Things (IoT) prototype was developed in this study, which collects on-site voltage and current measurements from the panel, as well as the environmental factors of lighting, temperature, and humidity in the system’s proximity. The measurements were then subjected to correlation analysis, and various artificial neural networks (ANNs) were implemented to develop energy estimations and forecasting models. The most effective model utilizes lighting, temperature, and humidity. The model achieves a root mean squared error (RMSE) of 0.255326464. The ANN models are compared to an MLR model using the same data. Using previous power measurements and actual weather data, a non-autoregressive neural network (Non-AR-NN) model forecasts future output power values. The best Non-AR-NN model produces an RMSE of 0.1160, resulting in accurate predictions based on the IoT device.

Abstract Culturally dependent human social behaviours involving artificial light usage can potentially affect light pollution patterns and thereby impact the night‐time ecology in populated areas, although to date this has not been examined globally. By analysing continuous (monthly), highly resolved, spatially explicit data on global night lights (Visible and Infrared Imaging Radiometer Suite–Day/Night Band‐VIIRS‐DNB; 2014–2019) with circular statistical techniques, we evaluated whether macro‐cultural activities involving social aggregations and the use of artificial lights shape annual lighting patterns globally. Scheduled routines associated with cultural‐specific festivities appear to be important drivers of observed seasonal patterns in urban night‐time lights. For instance, the display of Christmas lights between Christmas and Epiphany Day celebrations (December–January) coincides with the annual peak in urban night‐time light intensity in Christian countries. Analogously, night celebrations during the Holy Month of Ramadam (from May to July) or the month‐long period of Karthika Masam (from October to November) fits with annual night light peaks in Muslim and Hindu countries. Annual peaks of urban light intensity in China and Vietnam also match with Chinese and Vietnamese (Tê't) New Year celebrations (January–February). In contrast, predominantly Buddhist countries, which do not have such prominent and prolonged celebrations involving artificial lights, show a relatively uniform distribution of night light peaks throughout the annual cycle. Social behaviour and sociocultural contexts help explain how people modify the global nightscape and contribute to light pollution globally. Understanding the cultural contexts responsible for peaks in artificial light usage is an important first step if humans are to mitigate any deleterious effects associated with global increases in night‐time light pollution. Read the free Plain Language Summary for this article on the Journal blog.

Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of global mortality. Despite clinical predictors (age, severity, comorbidities, etc.) being established, proteomics offers comprehensive biological profiling to obtain deeper insights into COPD pathophysiology and survival prognoses. This pilot study aimed to identify proteomic footprints that could be potentially useful in predicting mortality in stable COPD patients. Plasma samples from 40 patients were subjected to both blind (liquid chromatography–mass spectrometry) and hypothesis-driven (multiplex immunoassays) proteomic analyses supported by artificial intelligence (AI) before a 4-year clinical follow-up. Among the 34 patients whose survival status was confirmed (mean age 69 ± 9 years, 29.5% women, FEV1 42 ± 15.3% ref.), 32% were dead in the fourth year. The analysis identified 363 proteins/peptides, with 31 showing significant differences between the survivors and non-survivors. These proteins predominantly belonged to different aspects of the immune response (12 proteins), hemostasis (9), and proinflammatory cytokines (5). The predictive modeling achieved excellent accuracy for mortality (90%) but a weaker performance for days of survival (Q2 0.18), improving mildly with AI-mediated blind selection of proteins (accuracy of 95%, Q2 of 0.52). Further stratification by protein groups highlighted the predictive value for mortality of either hemostasis or pro-inflammatory markers alone (accuracies of 95 and 89%, respectively). Therefore, stable COPD patients’ proteomic footprints can effectively forecast 4-year mortality, emphasizing the role of inflammatory, immune, and cardiovascular events. Future applications may enhance the prognostic precision and guide preventive interventions.

Manipulation involves both fine tactile feedback, with dynamic transients perceived by fingerpad mechanoreceptors, and kinaesthetic force feedback, involving the whole hand musculoskeletal structure. In teleoperation experiments, these fundamental aspects are usually divided between different setups at the operator side: those making use of lightweight gloves and optical tracking systems, oriented toward tactile-only feedback, and those implementing exoskeletons or grounded manipulators as haptic devices delivering kinaesthetic force feedback. At the level of hand interfaces, exoskeletons providing kinaesthetic force feedback undergo a trade-off between maximum rendered forces and bandpass of the embedded actuators, making these systems unable to properly render tactile feedback. To overcome these limitations, here, we investigate a full upper limb exoskeleton, covering all the upper limb body segments from shoulder to finger phalanxes, coupled with linear voice coil actuators at the fingertips. These are developed to render wide-bandwidth tactile feedback together with the kinaesthetic force feedback provided by the hand exoskeleton. We investigate the system in a pick-and-place teleoperation task, under two different feedback conditions (visual-only and visuo-haptic). The performance based on measured interaction forces and the number of correct trials are evaluated and compared. The study demonstrates the overall feasibility and effectiveness of a complex full upper limb exoskeleton (seven limb-actuated DoFs plus five hand DoFs) capable of combined kinaesthetic and tactile haptic feedback. Quantitative results show significant performance improvements when haptic feedback is provided, in particular for the mean and peak exerted forces, and for the correct rate of the pick-and-place task.

Oral melanomas are the most common oral malignancies in dogs and are characterized by an aggressive nature, invasiveness, and poor prognosis. With biological and genetic similarities to human oral melanomas, they serve as a valuable spontaneous comparative model. Primary cell cultures are widely used in human medicine and, more recently, in veterinary medicine to study tumorigenesis, cancer progression, and innovative therapeutic approaches. This study aims to establish two- and three-dimensional primary cell lines from oral canine melanomas using fine-needle aspiration as a minimally invasive sampling method. For this study, samples were collected from six dogs, represented by four primary oral melanomas and five lymph nodal metastases. The cells were digested to obtain single-cell suspensions, seeded in flasks, or processed with Matrigel® to form organoids. The cell cultures were characterized through flow cytometry using antibodies against Melan-A, PNL2, and Sox-10. This technique offers a minimally invasive means to obtain cell samples, particularly beneficial for patients that are ineligible for surgical procedures, and enables the establishment of in vitro models crucial for comparative studies in mucosal melanoma oncology. To the best of our knowledge, this is the first work establishing neoplastic primary cell cultures via fine-needle aspiration in dogs.

The D-enantiomer of lactic acid (D-lactate) is normally produced from bacterial fermentation in the gastrointestinal tract in mammals. In humans, increased D-lactate concentrations are related to gastrointestinal disease, including short bowel syndrome and malabsorptive syndrome. Similarly, increased D-lactate concentrations have been described in calves affected by diarrhea, in cats with gastrointestinal diseases, and in dogs with parvoviral enteritis. The purpose of the present study was to measure the serum D-lactate concentrations in dogs with inflammatory bowel disease (IBD). We retrospectively reviewed data from the database of the VTH of Perugia University, and dogs affected by IBD with serum samples stored at −80 °C were considered eligible for inclusion. A total of 18 dogs with IBD and 10 healthy dogs were included in the study. The dogs with IBD were divided into three subcategories based on the severity of the disease. Serum D-lactate concentrations (μM) were determined using a commercially available colorimetric assay kit (D-Lactate Colorimetric Assay Kit; Catalog #K667-100, BioVision Inc., Milpitas, CA, USA). Our results showed no significant difference (p > 0.05) in the serum concentrations of D-lactate between dogs with various degrees of IBD and healthy dogs. However, the wide variability of the D-lactate concentrations in dogs with IBD and evidence of increased serum D-lactate concentrations in dogs with confirmed dysbiosis encourage further studies on this topic to understand potential factors influencing the serum D-lactate concentrations in dogs affected by IBD.

Objective: Neuraxial anesthesia (NA) showed to reduce both morbidity and mortality in patients undergoing laparoscopic surgery. We aimed to investigate the use of NA in patients undergoing transperitoneal three-dimensional laparoscopic radical prostatectomy (t-3DLRP) and compare the intraoperative and postoperative outcomes with a control group of patients undergoing t-3DLRP under general anesthesia (GA). Methods: A prospective, double-center, double-surgeon study cohort of 84 consecutive patients undergoing t-3DLRP between June 2019 and June 2021 was analyzed. A study group of 42 patients undergoing t-3DLRP under NA was compared with a control group of 42 patients undergoing t-3DLRP under GA. Results: The two group were similar in all demographic, clinical, and pathological variables. Postoperative blood gas parameters were within physiologic limits in both groups. Muscle relaxation was adequate for surgery during both NA and GA. Median length of stay was 1 day shorter for NA group than GA group (5 days vs. 6 days, p=0.05). t-3DLRP under NA had a statistically lower rate of minor complications (4.8% vs. 19.0%, p=0.03) and less postoperative pain (median numeric rating scale 3 vs. 4, p=0.01) compared to GA. No major complications were observed in both groups. Significantly more patients were willing to undergo a similar intervention under NA than GA (p=0.04). Conclusion: t-3DLRP under NA is a feasible and safe procedure, with less postoperative pain and fewer minor complications than the same procedure under GA. NA allows the maintenance of muscle relaxation and respiratory excursions without interfering with surgery.

Background: We tested the hypothesis that, within the margin of 15% of risk difference, palonosetron is not inferior to ondansetron in reducing the incidence of postoperative nausea and vomiting (PONV) in laparoscopic cholecystectomy. Methods: We conducted a double-blind, non-inferiority, randomized, controlled trial of 212 patients aged 18 to 65 years undergoing laparoscopic cholecystectomy under general anesthesia in two secondary care hospitals. Patients were randomly assigned to receive either palonosetron (0.075.ßmg) or ondansetron (8.ßmg) intravenously at induction of anesthesia. Ondansetron (8.ßmg) was also administered 8 and 16.ßhours postoperatively. All anesthetic and surgical procedures were standardized. Patients were evaluated for 24.ßhours postoperatively for the occurrence of PONV. Results: A high incidence of PONV was observed at 2...6.ßhours postoperatively, with a rate of 36.8% (95% confidence interval [CI] 28.2...46.3) in the palonosetron group, as compared to 43.4% (95% CI 34.4...52.9) in the ondansetron group. The risk difference (95% CI) between palonosetron and ondansetron for PONV was 0 (-10.9 to 10.9) at 0...2.ßhours, -6.6 (-19.4 to 6.5) at 2...6.ßhours, -0.9 (-11.0 to 9.2) at 6...12.ßhours, and -2.8 (-9.6 to 3.6) at 12...24.ßhours. There was no statistically significant difference between the palonosetron and ondansetron groups in the use of rescue medication (dimenhydrinate). There were no adverse events associated with the medications under study. Conclusion: Palonosetron is not inferior to ondansetron in patients at risk of PONV undergoing laparoscopic cholecystectomy, providing a good option for PONV prophylaxis, as it can be administered in a single dose.

O trabalho avaliou a influência da variação de temperatura nas medidas de resistividade elétrica e na cinética de corrosão em estruturas de concreto armado sujeitos a cloretos. Os concretos foram caracterizados fisicamente e mecanicamente aos 28 e 90 dias. Após 204 dias, as amostras foram submetidas a ciclos de ida e volta de temperatura partindo dos 55°C até -5°C. Os resultados indicaram que a cinética de corrosão e a resistividade elétrica variaram com a alteração da temperatura. Em temperaturas mais elevadas, os traços contaminados com Cl- demonstraram uma alta probabilidade de corrosão e uma diminuição dos valores de resistividade elétrica. Porém, na temperatura negativa a probabilidade de corrosão foi insignificante e os valores de resistividade elétrica os mais elevados.

Glioblastoma (GBM) is the most commonly occurring type of primary tumor of the central nervous system (CNS) and is considered the worst type of glioma. Despite the current standard treatment for newly diagnosed GBM, which involves surgery followed by chemotherapy with temozolomide (TMZ) and radiation therapy, the average survival time for patients with GBM is only about 15 months. This is due to GBM’s tendency to recur, its high proliferative rates, its ability to evade apoptosis, and its ability to invade healthy tissue. Therefore, it is crucial to explore new treatment options for GBM. This study investigated the potential anticancer activities of a new series of synthetic chalcones, which are natural compounds found in the biosynthesis of flavonoids in plants. Primary cell culture of glioblastoma (GBM1) from surgical resection was used to evaluate the effects of synthetic chalcones on viability, cell death, reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), cell cycle, and invasion. One chalcone, Q1VA (at concentrations of 10, 50, and 100 μM for 24 h) induced cytotoxicity by increasing apoptosis levels and depolarizing the mitochondrial membrane, as evidenced by a TMRE assay. Further analysis using the molecular fluorescent probe H2DCFDA indicated that the increased levels of reactive oxygen species (ROS) might be linked to altered mitochondrial membrane potential and cell death. Furthermore, viable cells were observed to be delayed in the cell cycle, primarily in the M phase, and the invasion process was reduced. The findings of this study indicate that Q1VA is a potential adjuvant therapeutic agent for GBM due to its significant antitumor effects. If its safety and efficacy can be confirmed in animal models, Q1VA may be considered for clinical trials in humans. However, additional research is required to determine the optimal dosage, treatment schedule, and potential side effects of Q1VA.

Although Chronic Obstructive Pulmonary Disease (COPD) is highly prevalent, it is often underdiagnosed. One of the main characteristics of this heterogeneous disease is the presence of periods of acute clinical impairment (exacerbations). Obtaining blood biomarkers for either COPD as a chronic entity or its exacerbations (AECOPD) will be particularly useful for the clinical management of patients. However, most of the earlier studies have been characterized by potential biases derived from pre-existing hypotheses in one or more of their analysis steps: some studies have only targeted molecules already suggested by pre-existing knowledge, and others had initially carried out a blind search but later compared the detected biomarkers among well-predefined clinical groups. We hypothesized that a clinically blind cluster analysis on the results of a non-hypothesis-driven wide proteomic search would determine an unbiased grouping of patients, potentially reflecting their endotypes and/or clinical characteristics. To check this hypothesis, we included the plasma samples from 24 clinically stable COPD patients, 10 additional patients with AECOPD, and 10 healthy controls. The samples were analyzed through label-free liquid chromatography/tandem mass spectrometry. Subsequently, the Scikit-learn machine learning module and K-means were used for clustering the individuals based solely on their proteomic profiles. The obtained clusters were confronted with clinical groups only at the end of the entire procedure. Although our clusters were unable to differentiate stable COPD patients from healthy individuals, they segregated those patients with AECOPD from the patients in stable conditions (sensitivity 80%, specificity 79%, and global accuracy, 79.4%). Moreover, the proteins involved in the blind grouping process to identify AECOPD were associated with five biological processes: inflammation, humoral immune response, blood coagulation, modulation of lipid metabolism, and complement system pathways. Even though the present results merit an external validation, our results suggest that the present blinded approach may be useful to segregate AECOPD from stability in both the clinical setting and trials, favoring more personalized medicine and clinical research.

The growing prevalence of bacterial and viral infections, highlighted by the recent COVID-19 pandemic, urgently calls for new antimicrobial strategies. To this end, we have synthesized and characterized a novel fatty acid epoxy-ester plasticizer for polymers, named GDE. GDE is not only sustainable and user-friendly but also demonstrates superior plasticizing properties, while its epoxy components improve the heat stability of PVC-based matrices. A key feature of GDE is its ability to confer antimicrobial properties to surfaces. Indeed, upon contact, this material can effectively kill enveloped viruses, such as herpes simplex virus type 1 (HSV-1) and the β-coronavirus prototype HCoV-OC43, but it is ineffective against nonenveloped viruses like human adenovirus (HAdV). Further analysis using transmission electron microscopy (TEM) on HSV-1 virions exposed to GDE showed significant structural damage, indicating that GDE can interfere with the viral envelope, potentially causing leakage. Moreover, GDE demonstrates antibacterial activity, albeit to a lesser extent, against notorious pathogens such as Staphylococcus aureus and Escherichia coli. Overall, this newly developed plasticizer shows significant potential as an antimicrobial agent suitable for use in both community and healthcare settings to curb the spread of infections caused by microorganisms contaminating physical surfaces.

The light weight and compliance of exosuits are valuable benefits not present rigid exoskeleton devices, yet these intriguing features make it challenging to properly model and simulate their interaction with the musculoskeletal system. Tendon-driven exosuits adopt an electrical motor combined with pulleys and cable transmission in the actuation stage. An important aspect of the design of these systems for the load transfer efficacy and comfort of the user is the anchor point positioning. In this paper, we propose a framework, whose first purpose is as a design methodology for the synthesis of an exosuit device, achieved by optimizing the anchor point location. The optimization procedure finds the best 3D position of the anchor points based on the interaction forces between the exosuit and the upper arm. The computation of the forces is based on the combination of a mathematical model of a wrist–elbow exosuit and a dynamic model of the upper arm. Its second purpose is the simulation of the kinematic and physiological effects of the interaction between the arm, the exosuit, and the complex upper limb musculoskeletal system. It offers insights into muscular and exoskeleton loading during operation. The presented experiments involve the development and validation of personalized musculoskeletal models, with kinematic, anthropometric, and electromyographic data measured in a load-lifting task. Simulation of the exosuit operation—coupled with the musculoskeletal model—showed the efficacy of the suit in assisting the wrist and elbow muscles and provided interesting highlights about the impact of the assistance on shoulder muscles. Finally, we provide a possible design of an elbow and wrist exosuit based on the optimized results.

Edible plant and fruit-derived nanovesicles (NVs) are membrane-enclosed particles with round-shape morphology and signaling functions, which resemble mammalian cell-derived extracellular vesicles. These NVs can transmit cross-kingdom signals as they contain bioactive molecules and exert biological effects on mammalian cells. Their properties and stability in the gastrointestinal tract suggest NVs as a promising nutraceutical tool. In this study, we have demonstrated for the first time the presence of NVs in olive vegetation water (OVW), a waste by-product generated during olive oil production. Biophysical characterization by scanning electron microscopy, cryo-transmission electron microscopy, and nanoparticle tracking analysis revealed the presence in OVW of NVs having size and morphology similar to that of vesicles isolated from edible plants. Integrated lipidomic, metabolomic, and proteomic analyses showed that OVW-NVs carry a set of lipids, metabolites and proteins which have recognized antioxidant and anti-inflammatory activities. The nature of biomolecules identified in OVW-NVs suggests that these vesicles could exert beneficial effects on mammalian cells and could be used in the nutraceutical and food industries. The successful isolation of OVW-NVs and the characterization of their features strengthen the idea that agricultural waste might represent a source of NVs having features similar to NVs isolated from edible plants/fruits.

Abstract Animal-borne tagging (bio-logging) generates large and complex datasets. In particular, accelerometer tags, which provide information on behaviour and energy expenditure of wild animals, produce high-resolution multi-dimensional data, and can be challenging to analyse. We tested the performance of commonly used artificial intelligence tools on datasets of increasing volume and dimensionality. By collecting bio-logging data across several sampling seasons, datasets are inherently characterized by inter-individual variability. Such information should be considered when predicting behaviour. We integrated both unsupervised and supervised machine learning approaches to predict behaviours in two penguin species. The classified behaviours obtained from the unsupervised approach Expectation Maximisation were used to train the supervised approach Random Forest. We assessed agreement between the approaches, the performance of Random Forest on unknown data and the implications for the calculation of energy expenditure. Consideration of behavioural variability resulted in high agreement (> 80%) in behavioural classifications and minimal differences in energy expenditure estimates. However, some outliers with

Abstract Background Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibrosis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symptoms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free-survival. Methods PA was assessed by accelerometer and physiological, clinical, psychological factors and health-related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow-up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established. Results Forty participants with IPF were included and 22 completed the follow-up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six-minute walked distance, lower quadriceps strength (QMVC), and a higher depression score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender-Age-Physiology) GAP III stage, having a BMI ≥ 25 kg/m2 and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression-free survival was evidenced in those subjects that decreased PA compared to those that maintained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9–78.8); p = 0.009]. Conclusion Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis.

Summary: Background: Prostatic artery embolisation (PAE) is a minimally invasive treatment of symptomatic benign prostatic hyperplasia (BPH). Our aim was to compare patient's symptoms improvement after PAE and medical treatment. Methods: A randomised, open-label, superiority trial was set in 10 French hospitals. Patients with bothersome lower urinary tract symptoms (LUTS) defined by International Prostatic Symptom Score (IPSS) > 11 and quality of life (QoL) > 3, and BPH ≥50 ml resistant to alpha-blocker monotherapy were randomly assigned (1:1) to PAE or Combined Therapy ([CT], oral dutasteride 0.5 mg/tamsulosin hydrochloride 0.4 mg per day). Randomisation was stratified by centre, IPSS and prostate volume with a minimisation procedure. The primary outcome was the 9-month IPSS change. Primary and safety analysis were done according to the intention-to-treat (ITT) principle among patients with an evaluable primary outcome. ClinicalTrials.gov Identifier: NCT02869971. Findings: Ninety patients were randomised from September 2016 to February 2020, and 44 and 43 patients assessed for primary endpoint in PAE and CT groups, respectively. The 9-month change of IPSS was −10.0 (95% confidence interval [CI]: −11.8 to −8.3) and −5.7 (95% CI: −7.5 to −3.8) in the PAE and CT groups, respectively. This reduction was significantly greater in the PAE group than in the CT group (−4.4 [95% CI: −6.9 to −1.9], p = 0.0008). The IIEF-15 score change was 8.2 (95% CI: 2.9–13.5) and −2.8 (95% CI: −8.4 to 2.8) in the PAE and CT groups, respectively. No treatment-related AE or hospitalisation was noticed. After 9 months, 5 and 18 patients had invasive prostate re-treatment in the PAE and CT group, respectively. Interpretation: In patients with BPH ≥50 ml and bothersome LUTS resistant to alpha-blocker monotherapy, PAE provides more urinary and sexual symptoms benefit than CT up to 24 months. Funding: French Ministry of Health and a complementary grant from Merit Medical.

In Brazil, it is necessary to assess the different levels of health care in diabetes mellitus (DM) in order to integrate them. In this retrospective cohort study, we analyzed 1,122 medical records of patients with DM from specialized services with interdisciplinary health teams (IHT) in the city of Ourinhos, São Paulo state, Brazil, to assess the impact of secondary care on glycemic control in patients with DM in those places and to compare baseline and follow-up DM care indicators concerning clinical evaluation and drug treatment regimens in the aforementioned health services. The study covered consultations carried out from September/2013 to September/2017. Data were collected from initial and final appointments in medical records and revealed an increase of 31.21% in insulin introduction and of 73.53% in regimens with three or more non-insulin antidiabetic (NIA) medications. Among the 570 patients with at least two glycated hemoglobin (A1C) measurements in the aforementioned review, 146 did not require any therapeutic adjustment between initial and final appointments, 123 required a subtle adjustment, 95, a moderate adjustment, and 206, an intense adjustment. There was a noticeably higher A1C reduction between initial and final appointments when patients who required an intense drug adjustment were compared to those who did not need any different NIA drug (p-value < 0.0001). In addition to optimizing drug treatment, essential exams in DM were performed with higher frequency, with an increase of 63% in ophthalmology evaluation performed during secondary care approach and 60.65% more individuals being screened for diabetic chronic kidney disease. IHT secondary care considered in this study, therefore, not only improved glycemic control of patients with DM, especially by optimization of NIA regimens and timely prescription of insulin, but also increased the screening for microvascular complications.

Resumo Objetivo Adaptar e validar a The Humpty Dumpty Falls Scale para a cultura brasileira. Métodos Estudo metodológico, que seguiu, para a adaptação transcultural, os estágios de tradução, síntese, retrotradução, avaliação por especialistas, pré-teste e avaliação pela autora do instrumento original. Foram selecionadas 103 crianças/adolescentes internados em um hospital público do interior do estado de São Paulo. Foram utilizados ficha de caracterização, The Humpty Dumpty Falls Scale e o Instrumento de Classificação de Pacientes Pediátricos, o qual foi utilizado para avaliar a validade de construto, com o coeficiente de correlação de Spearman. A confiabilidade interobservador foi avaliada pelo Coeficiente de Correlação Intraclasse e pelo coeficiente Kappa. Resultados O comitê de 12 especialistas avaliou as equivalências, a clareza e a relevância dos itens e, após três rodadas, foi alcançado o percentual de 100% de concordância. As reformulações tornaram os itens mais compreensíveis e, após avaliação da autora, foi obtida a versão final do instrumento. Correlações positivas e significantes foram encontradas entre a Escala Humpty Dumpty e os domínios Paciente (r=0,5184; p

While differences in foraging and reproductive success are well studied between seabird colonies, they are less understood at a smaller subcolony scale. Working with little penguins (Eudyptula minor) at Phillip Island, Australia, we used an automated penguin monitoring system and performed regular nest checks at two subcolonies situated 2 km apart during the 2015/2016 breeding seasons. We examined whether foraging and reproductive success differed between subcolonies. We used satellite data to examine how sea surface temperature, as environmental pressure, in the foraging regions from each subcolony influenced their foraging performance. In the pre-laying and incubation breeding stages, the birds from one subcolony had a lower foraging success than birds from the other. However, this pattern was reversed between the subcolonies in the guard and post-guard stages. Breeding success data from the two subcolonies from 2004–2018 showed that reproductive success and mean egg-laying had a negative relationship with sea surface temperature. We highlighted that variation in foraging and reproductive success can arise in subcolonies, likely due to different responses to environmental conditions and prey availability. Differences at the subcolony level can help refine, develop and improve appropriate species management plans for conserving a range of colonial central place seabirds.

A Clorose Variegada dos Citros ou CVC, doença também conhecida no Brasil por “amarelinho”, está sendo uma das principais preocupações dos citricultores. Esta doença, causada pela bactéria Xylella fastidiosa, foi constatada no Estado de São Paulo em 1987 e rapidamente difundiu-se em pomares de laranjeiras dos Estados de Minas Gerais, Rio de Janeiro, Paraná, Rio Grande do Sul, Goiás e Distrito Federal (1). Em 1995, esta doença foi verificada em laranjeiras ‘Valência’ e ‘Caipira’, de pomares comerciais e domésticos situados nas regiões Oeste e Extremo Oeste do Estado de Santa Catarina (2).

As lesmas são moluscos pertencentes à família Veronicellidae. Nas Américas, já foram constatadas 43 espécies desses animais e outras ainda necessitam de estudos mais detalhados para serem classificadas. Alimentam-se de grande variedade de vegetais e podem causar danos em lavouras de feijão, milho, soja e mandioca, além de atacar plantas frutíferas, jardins, hortas caseiras e comerciais.

IntroductionExtracellular vesicles (EVs) are nanometric-membrane-bound sub-cellular structures, which can be recovered from milk. Milk EVs have drawn increasing interest due to their potential biomedical applications, therefore it is important to investigate their impact on key immune cells, such as macrophages.MethodsIn this work, the immunomodulatory effects of goat milk EVs on untreated (moMФ) and classically activated (moM1) porcine monocyte-derived macrophages were investigated using flow cytometry, ELISA, and gene expression assays.ResultsThese particles were efficiently internalized by macrophages and high doses (60 mg protein weight) triggered the upregulation of MHC I and MHC II DR on moMФ, but not on moM1. In moMФ, exposure to low doses (0.6 mg) of mEVs enhanced the gene expression of IL10, EBI3, and IFNB, whereas high doses up-regulated several pro-inflammatory cytokines. These nanosized structures slightly modulated cytokine gene expression on moM1. Accordingly, the cytokine (protein) contents in culture supernatants of moMФ were mildly affected by exposure to low doses of mEVs, whereas high doses promoted the increased release of TNF, IL-8, IL-1a, IL-1b, IL-1Ra, IL-6, IL-10, and IL-12. The cytokines content in moM1 supernatants was not critically affected.DiscussionOverall, our data support a clinical application of these molecules: they polarized macrophages toward an M1-like phenotype, but this activation seemed to be controlled, to prevent potentially pathological over-reaction to stressors.

This work presents the design of the Rehab-Exos, a novel upper limb exoskeleton designed for rehabilitation purposes. It is equipped with high-reduction-ratio actuators and compact elastic joints to obtain torque sensors based on strain gauges. In this study, we address the torque sensor performances and the design aspects that could cause unwanted non-axial moment load crosstalk. Moreover, a new full-state feedback torque controller is designed by modeling the multi-DOF, non-linear system dynamics and providing compensation for non-linear effects such as friction and gravity. To assess the proposed upper limb exoskeleton in terms of both control system performances and mechanical structure validation, the full-state feedback controller was compared with two other benchmark-state feedback controllers in both a transparency test—ten subjects, two reference speeds—and a haptic rendering evaluation. Both of the experiments were representative of the intended purpose of the device, i.e., physical interaction with patients affected by limited motion skills. In all experimental conditions, our proposed joint torque controller achieved higher performances, providing transparency to the joints and asserting the feasibility of the exoskeleton for assistive applications.