A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications.

Melt extrusion-based additive manufacturing (ME-AM) is a promising technique to fabricate porous scaffolds for tissue engineering applications. However, most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate. Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct; however, there are limited strategies available to control the surface density. Here, we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k (PCL5k) containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios. Stable porous three-dimensional (3D) scaffolds were then fabricated using a high weight percentage (75 wt.%) of the low molecular weight PCL5k. As a proof-of-concept test, we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface, yielding a density of 201-561 pmol/cm2. Subsequently, a bone morphogenetic protein 2 (BMP-2)-derived peptide was grafted onto the films comprising different blend compositions, and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells (hMSCs) was assessed. After two weeks of culturing in a basic medium, cells expressed higher levels of BMP receptor II (BMPRII) on films with the conjugated peptide. In addition, we found that alkaline phosphatase activity was only significantly enhanced on films containing the highest peptide density (i.e., 561 pmol/cm2), indicating the importance of the surface density. Taken together, these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface. Moreover, we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of (modified) polymers. Furthermore, the use of alkyne-azide "click" chemistry enables spatial control over bioconjugation of many tissue-specific moieties, making this approach a versatile strategy for tissue engineering applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s42242-024-00286-2.

Hybrid microalgae-activated sludge system for carbon-efficient wastewater treatment.

Engineered microalgae-bacteria systems can play a key role in the realisation of energy-efficient carbon-neutral wastewater treatment technologies. An attempt was made to develop a hybrid microalgae-activated sludge (HMAS) system coupling carbon capture with domestic wastewater treatment. Photobioreactors internally illuminated with red light-emitting diodes (LEDs), and inoculated with mixed microbial culture, resulted in substantial savings in operational cost. System performance was evaluated at about 600 µmol/m2 s LED irradiance while treating synthetic municipal wastewater in a chemostat for about 2 months, containing about 250 mg/L soluble chemical oxygen demand (SCOD), 90 mg/L NH3-N and 10 mg/L orthophosphate. Carbon dioxide was supplied into the HMAS at 25 mL/min, 25% v/v. SCOD was efficiently removed from the wastewater (up to 70%) and bacterial oxygen requirement of >2 mg/L was met through microalgal photosynthesis. The system demonstrated its potential in achieving carbon-efficient wastewater treatment.

A method to produce a flexible and customized fuel models dataset.

Simulation of vegetation fires very often resorts to fire-behavior models that need fuel models as input. The lack of fuel models is a common problem for researchers and fire managers because its quality depends on the quality/availability of data. In this study we present a method that combines expert- and research-based knowledge with several sources of data (e.g. satellite and fieldwork) to produce customized fuel models maps. Fuel model classes are assigned to land cover types to produce a basemap, which is then updated using empirical and user-defined rules. This method produces a map of surface fuel models as detailed as possible. It is reproducible, and its flexibility relies on juxtaposing independent spatial datasets, depending on their quality or availability. This method is developed in a ModelBuilder/ArcGis toolbox named FUMOD that integrates ten sub-models. FUMOD has been used to map the Portuguese annual fuel models grids since 2019, supporting regional fire risk assessments and suppression decisions. Datasets, models and supplementary files are available in a repository (https://github.com/anasa30/PT_FuelModels). •FUMOD is a flexible toolbox with ten sub-models included that maps updated Portuguese fuel models.

Carbon dioxide-dependent signal transduction in mammalian systems.

Carbon dioxide (CO2) is a fundamental physiological gas known to profoundly influence the behaviour and health of millions of species within the plant and animal kingdoms in particular. A recent Royal Society meeting on the topic of 'Carbon dioxide detection in biological systems' was extremely revealing in terms of the multitude of roles that different levels of CO2 play in influencing plants and animals alike. While outstanding research has been performed by leading researchers in the area of plant biology, neuronal sensing, cell signalling, gas transport, inflammation, lung function and clinical medicine, there is still much to be learned about CO2-dependent sensing and signalling. Notably, while several key signal transduction pathways and nodes of activity have been identified in plants and animals respectively, the precise wiring and sensitivity of these pathways to CO2 remains to be fully elucidated. In this article, we will give an overview of the literature relating to CO2-dependent signal transduction in mammalian systems. We will highlight the main signal transduction hubs through which CO2-dependent signalling is elicited with a view to better understanding the complex physiological response to CO2 in mammalian systems. The main topics of discussion in this article relate to how changes in CO2 influence cellular function through modulation of signal transduction networks influenced by pH, mitochondrial function, adenylate cyclase, calcium, transcriptional regulators, the adenosine monophosphate-activated protein kinase pathway and direct CO2-dependent protein modifications. While each of these topics will be discussed independently, there is evidence of significant cross-talk between these signal transduction pathways as they respond to changes in CO2. In considering these core hubs of CO2-dependent signal transduction, we hope to delineate common elements and identify areas in which future research could be best directed.

Synchrotron microtomography applied to the volumetric analysis of internal structures of Thoropa miliaris tadpoles.

Amphibians are models for studying applied ecological issues such as habitat loss, pollution, disease, and global climate change due to their sensitivity and vulnerability to changes in the environment. Developmental series of amphibians are informative about their biology, and X-ray based 3D reconstruction holds promise for quantifying morphological changes during growth-some with a direct impact on the possibility of an experimental investigation on several of the ecological topics listed above. However, 3D resolution and discrimination of their soft tissues have been difficult with traditional X-ray computed tomography, without time-consuming contrast staining. Tomographic data were initially performed (pre-processing and reconstruction) using the open-source software tool SYRMEP Tomo Project. Data processing and analysis of the reconstructed tomography volumes were conducted using the segmentation semi-automatic settings of the software Avizo Fire 8, which provide information about each investigated tissues, organs or bone elements. Hence, volumetric analyses were carried out to quantify the development of structures in different tadpole developmental stages. Our work shows that synchrotron X-ray microtomography using phase-contrast mode resolves the edges of the internal tissues (as well as overall tadpole morphology), facilitating the segmentation of the investigated tissues. Reconstruction algorithms and segmentation software played an important role in the qualitative and quantitative analysis of each target structure of the Thoropa miliaris tadpole at different stages of development, providing information on volume, shape and length. The use of the synchrotron X-ray microtomography setup of the SYRMEP beamline of Elettra Synchrotron, in phase-contrast mode, allows access to volumetric data for bone formation, eye development, nervous system and notochordal changes during the development (ontogeny) of tadpoles of a cycloramphid frog Thoropa miliaris. As key elements in the normal development of these and any other frog tadpole, the application of such a comparative ontogenetic study, may hold interest to researchers in experimental and environmental disciplines.

[Breath-holding spell or epileptic seizure? A description of three girls with epileptic seizures triggered by anoxia]. / ¿Espasmo del sollozo prolongado o crisis epiléptica?: descripción de tres niñas con crisis epilépticas desencadenadas por anoxia.

TITLE: ¿Espasmo del sollozo prolongado o crisis epiléptica?: descripción de tres niñas con crisis epilépticas desencadenadas por anoxia.

Culture Matters in Communicating the Global Response to COVID-19.

Current communication messages in the COVID-19 pandemic tend to focus more on individual risks than community risks resulting from existing inequities. Culture is central to an effective community-engaged public health communication to reduce collective risks. In this commentary, we discuss the importance of culture in unpacking messages that may be the same globally (physical/social distancing) yet different across cultures and communities (individualist versus collectivist). Structural inequity continues to fuel the disproportionate impact of COVID-19 on black and brown communities nationally and globally. PEN-3 offers a cultural framework for a community-engaged global communication response to COVID-19.

Cross-cutting view of current challenges in paediatric solid organ and haematopoietic stem cell transplantation in Europe: the European Reference Network TransplantChild.

The low prevalence of European paediatric transplanted patients and scarcity of resources and expertise led to the need for a multidisciplinary network able to improve the quality of life of paediatric patients and families requiring a solid organ or haematopoietic stem cell transplantation. The European Reference Network (ERN) TransplantChild is one of the 24 ERNs established in a European legal framework to improve the care of patients with rare diseases. ERN TransplantChild is the only ERN focused on both solid organ and haematopoietic stem cell paediatric transplantation, based on the understanding of paediatric transplantation as a complex and highly specialised process where specific complications appear regardless the organ involved, thus linking the skills and knowledge of different organ disciplines. Gathering European centres of expertise in paediatric transplantation will give access to a correct and timely diagnosis, share expertise and knowledge and collect a critical mass of patients and data that increases the speed and value of clinical research outcomes. Therefore, the ERN TransplantChild aims for a paediatric Pan-European, Pan-transplant approach.

A novel method for engineering autologous non-thrombogenic in situ tissue-engineered blood vessels for arteriovenous grafting.

The durability of prosthetic arteriovenous (AV) grafts for hemodialysis access is low, predominantly due to stenotic lesions in the venous outflow tract and infectious complications. Tissue engineered blood vessels (TEBVs) might offer a tailor-made autologous alternative for prosthetic grafts. We have designed a method in which TEBVs are grown in vivo, by utilizing the foreign body response to subcutaneously implanted polymeric rods in goats, resulting in the formation of an autologous fibrocellular tissue capsule (TC). One month after implantation, the polymeric rod is extracted, whereupon TCs (length 6 cm, diameter 6.8 mm) were grafted as arteriovenous conduit between the carotid artery and jugular vein of the same goats. At time of grafting, the TCs were shown to have sufficient mechanical strength in terms of bursting pressure (2382 ±â€¯129 mmHg), and suture retention strength (SRS: 1.97 ±â€¯0.49 N). The AV grafts were harvested at 1 or 2 months after grafting. In an ex vivo whole blood perfusion system, the lumen of the vascular grafts was shown to be less thrombogenic compared to the initial TCs and ePTFE grafts. At 8 weeks after grafting, the entire graft was covered with an endothelial layer and abundant elastin expression was present throughout the graft. Patency at 1 and 2 months was comparable with ePTFE AV-grafts. In conclusion, we demonstrate the remodeling capacity of cellularized in vivo engineered TEBVs, and their potential as autologous alternative for prosthetic vascular grafts.

Experimental sepsis induces sustained inflammation and acetylcholinesterase activity impairment in the hypothalamus.

Sepsis is one of the leading causes of mortality in intensive care units besides causing profound alterations in the brain. One of the structures notably affected during sepsis is the hypothalamus, resulting in important physiopathological consequences. Recently, we provided evidence that the presence of neuroinflammation, oxidative stress, and apoptosis in the hypothalamus of septic rats, is accompanied by impairment of arginine vasopressin (AVP) secretion. We had also demonstrated that sepsis survivor animals present attenuated AVP secretion after osmotic challenge, suggesting a persistent inflammation in the hypothalamus. However, the long-term course of inflammation in the hypothalamus remains unclear. Thus, we induced sepsis by cecal ligation and puncture (CLP) in Wistar rats and, five days after sepsis induction, the hypothalamus of each animal was collected for analysis. Nonmanipulated animals (naive) were used as controls. We found that CLP-induced morphological alterations in microglial cells are accompanied by an increase in Iba-1 immunoreactivity. Moreover, we observed enhanced expression of NF-κB and CREB transcription factors, which are well known to modulate the immune response. Additionally, we found that phosphorylation of GSK3α/ß (a kinase upstream to the CREB signaling pathway) was increased, as well as COX-2, iNOS, and IL-6 that are canonic inflammatory proteins. Thus, our results indicated the presence of sustained activation of resident glial cells that may result in neuroinflammation and cholinergic neurotransmission disruptions in the hypothalamus.

CARDIOVASCULAR RISK ASSESSMENT IN THE ADULT (AGED 40-79 YEARS) ROMANIAN POPULATION.

Atherosclerotic Cardiovascular Diseases are the leading cause of death worldwide. AIM: To estimate the prevalence of cardiovascular risk (CVR) categories in the adult population (aged 40-79 years) of Romania. DESIGN: The present study was part of the epidemiological, cross-sectional PREDATORR study (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania). SUBJECTS AND METHODS: Exclusion criteria: age <40/or>79 years old and diagnosis of ischemic vascular disease. The CVR was evaluated using charts developed by the World Health Organization/ International Society of Hypertension (WHO/ISH) available for Europe B (epidemiological sub-region where Romania was included). The CVR was divided into 5 categories: <10%, 10-20%, 20-30%, 30-40%, > 40%. RESULTS: A total of 1631 subjects (57.0±10.7 years, 45.1% males) were included in the present study.The age and sex-adjusted prevalence of CVR >40% was 2.9% (95%CI 2.8-3.1%), CVR 30-40% was 1.85% (95%CI 1.8-1.9%), CVR 20-30% was 5.8% (95%CI 5.6-6.0%) and 13.0% (95%CI 12.8-13.3%) of the adult Romanian population has a 10-20% CVR, these CVR categories being more frequent in male and older age. Diabetes, overweight/obesity and smoking were associated with high CVR categories. CONCLUSION: Romania is one of the countries with high CVR, requiring CVD prevention measures.

Dietary management of maternal phenylketonuria with glycomacropeptide and amino acids supplements: A case report.

BACKGROUND: In maternal PKU, protein substitute (PS) is provided by phenylalanine (PHE)-free l-amino acids (AA), but glycomacropeptide-based protein substitute (GMP) is an alternative consideration. OBJECTIVE: To describe the first Portuguese Maternal Phenylketonuria (MPKU) partially managed with GMP. CASE REPORT: A 31 year old MPKU female with classical PKU (mutations P281L/P281L), diagnosed by newborn screening, had a lifelong history of poor metabolic control. She has a history of partial bicornuate uterus and had a previous miscarriage in the first trimester. Pre-conception, her median blood PHE was 462 µmol/L but throughout pregnancy the median reduced to 258 µmol/L. GMP provided 30 g/day protein equivalent (46 mg/day PHE). Total protein equivalent from PS increased from 58 to 86 g/day during pregnancy but AA provided all additional protein equivalent intake. Both GMP and AA were well tolerated with no morning sickness. Normal morphologic evaluation and adequate fetal growth with cephalic biometry near the 5th percentile was determined. The infant was born at 39.3 weeks: weight 2570 g (3rd percentile), length 47.5 cm (10th percentile) and head circumference (HC) of 31.5 cm (1st percentile). In the neonatal period, the infant had craniofacial dimorphism with metopic suture prominence. Father also had bitemporal narrowing. By 12 months of age, the infant's weight (15th percentile), length (50th percentile) and HC (10th-50th percentile) were normal although bitemporal narrowing persisted. CONCLUSIONS: This is the first case reporting the use of GMP in MPKU. Its PHE content did not adversely affect metabolic control although it only provided part of the PS intake. Some intrauterine development delay occurred in the last trimester, although we consider that this is unlikely to be associated with MPKU syndrome or the use of GMP. More published data is essential to examine the impact of using GMP in MPKU on morning sickness severity and aversion, maternal weight gain, blood amino acid concentrations and variability of blood PHE concentrations.

Displasia cortical focal en paciente de 3 años con epilepsia parcial continua / Focal cortical dysplasia in a three years old patient with epilepsia partialis continua

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[Restless legs syndrome in patients diagnosed with attention deficit hyperactivity disorder]. / Sindrome de piernas inquietas en pacientes diagnosticados de trastorno por deficit de atencion/hiperactividad.

INTRODUCTION: Restless legs syndrome (RLS) is a common neurological disease. RLS has been linked to various psychiatric disorders, especially with attention deficit hyperactivity disorder (ADHD). AIMS: The main objective was to describe the frequency of RLS in pediatric patients diagnosed with ADHD. Secondary objectives of the study were describe other sleep disorders in ADHD patients. PATIENTS AND METHODS: A multicentre prospective study was conducted in nine Spanish centers. We included children aged 6-18 years diagnosed with ADHD between January and June 2015. Data were collected by 13 researchers doctors through an interview with the parent/caregiver and with the child. To assess the degree of functioning of patients with ADHD we used the Children's Global Assessment Scale. The Sleep Disturbance Scale for Children was applied to screening sleep disorders in childhood. RESULTS: A sample of 73 patients was collected. Five patients (6.8%) met diagnostic criteria for RLS: four of them definitive and one probable. CONCLUSIONS: RLS is a frequent condition in adulthood but also in adolescence and childhood. ADHD patients have an increased risk of an RLS.

TITLE: Sindrome de piernas inquietas en pacientes diagnosticados de trastorno por deficit de atencion/hiperactividad.Introduccion. El sindrome de piernas inquietas (SPI) es una patologia neurologica comun. Se ha relacionado con diferentes trastornos psiquiatricos, especialmente con el trastorno por deficit de atencion/hiperactividad (TDAH). Objetivos. El objetivo principal fue describir la frecuencia del SPI en pacientes pediatricos diagnosticados de TDAH. Los objetivos secundarios del estudio fueron describir otros trastornos del sueño en pacientes con TDAH. Pacientes y metodos. Se realizo un estudio descriptivo prospectivo multicentrico en nueve centros españoles de niños de 6-18 años con diagnostico de TDAH entre enero y junio de 2015. Los datos fueron recogidos por 13 medicos investigadores mediante entrevista con el padre/cuidador y con el menor. Para valorar el grado de funcionamiento de los pacientes con TDAH se utilizo la Children's Global Assessment Scale. Se aplico la Sleep Disturbance Scale for Children de Bruni para el cribado del trastorno de sueño de la infancia. Resultados. Se recogio una muestra de 73 pacientes. Cinco pacientes (6,8%) cumplen criterios diagnosticos de SPI: cuatro de ellos definitivos y uno probable. Conclusiones. El SPI es una entidad frecuente en la edad adulta, pero tambien en la adolescencia y en la infancia. Los pacientes con TDAH tienen un riesgo aumentado de presentar de manera concomitante un SPI.

Absence of IFNγ promotes hippocampal plasticity and enhances cognitive performance.

Cognitive functioning can be differentially modulated by components of the immune system. Interferon-γ (IFNγ) is a pro-inflammatory cytokine whose production is altered in many conditions displaying some degree of cognitive deficits, although its role in cognitive functioning is still unclear. Here we show that the absence of IFNγ selectively enhances cognitive behaviours in tasks in which the hippocampus is implicated. Moreover, the absence of IFNγ leads to volumetric and cell density changes that are restricted to the dorsal part of the hippocampus. In the dorsal hippocampus, the absence of this pro-inflammatory cytokine leads to an increase in the numbers of newly born neurons in the subgranular zone of the dentate gyrus (DG), an adult neurogenic niche known to support learning and memory, and to an enlargement of the dendritic arborization of DG granule and cornu ammonis (CA)1 pyramidal neurons. Moreover, it also modestly impacts synaptic plasticity, by decreasing the paired-pulse facilitation in the Schaffer collateral to CA1 pyramidal cell synapses. Taken together, our results provide evidence that IFNγ is a negative regulator of hippocampal functioning, as its absence positively impacts on dorsal hippocampus structure, cell density, neuronal morphology and synaptic plasticity. Importantly, these neuroplastic changes are associated with improved performance in learning and memory tasks. Therefore, blockage of the IFNγ signalling may present as promising therapeutic targets for the treatment of inflammation-associated cognitive dysfunction.

Effects of regular exercise and dual tasking on spatial and temporal parameters of obstacle negotiation in elderly women.

This study investigated the effects of regular exercise and dual tasking on bilateral spatial and temporal parameters of obstacle negotiation in elderly women. Sedentary (n=12) and physically active (n=12) elderly women volunteered to participate in this study. Gait kinematics were recorded during obstacle crossing when performing a dual task and when not performing a dual task. Physically active participants crossed obstacles more safely, in terms of clearance or distance to or over the obstacle, both with and without dual tasking, and usually for both lead and trail legs. Performing the dual task increased toe distance, and decreased heel distance and gait speed in the active participants, and increased toe clearance and heel distance, and decreased gait speed in the sedentary participants. Differences between preferred and non-preferred leg were accentuated for toe clearance in the lead limb. These results suggest that specialized exercises may not be needed for improvement in obstacle avoidance skills in the elderly, and participation in multi-activities, including aerobic exercises, may be sufficient.

Metabolic and feeding behavior alterations provoked by prenatal exposure to aspartame.

The use of artificial sweeteners has increased together with the epidemic growth of obesity. In addition to their widespread use in sodas, artificial sweeteners are added to nearly 6000 other products sold in the US, including baby foods, frozen dinners and even yogurts. It has been suggested that the use of nonnutritive sweeteners can lead to body weight gain and an altered metabolic profile. However, very few studies have evaluated the effects of maternal consumption of artificial non-caloric sweeteners on body weight, feeding behavior or the metabolism of offspring in adult life. In this study, we found that animals exposed to aspartame during the prenatal period presented a higher consumption of sweet foods during adulthood and a greater susceptibility to alterations in metabolic parameters, such as increased glucose, LDL and triglycerides. These effects were observed in both males and females, although they were more pronounced in males. Despite the preliminary nature of this study, and the need for further confirmation of these effects, our data suggest that the consumption of sweeteners during gestation may have deleterious long-term effects and should be used with caution.

Differential impact of chronic stress along the hippocampal dorsal-ventral axis.

Stress impacts differently in distinct brain regions. However, so far few studies have focused on the differential responses triggered by stressful stimuli on the intrinsic functional heterogeneity of the hippocampal axis. In this study, we assessed the functional and structural alterations caused by exposure to a chronic unpredictable stress (CUS) paradigm on the dorsal-ventral axis of the hippocampus. The morphological analysis demonstrated that CUS had opposite outcomes in the structure of the dorsal (DH) and ventral hippocampus (VH): whereas in the DH, stress triggered a volumetric reduction as a result of atrophy of CA3 and CA1 apical dendrites, in the VH there was an increase in hippocampal volume concurrent with the increase of CA3 apical dendrites. In parallel, electrophysiological data revealed that stress led to a decrease in VH LTD. In summary, the present work showed that stress impacts differently on the structure and function of the DH and VH which contributes to better understand the overall spectrum of the central effects of stress.

Associating high intensity and modulated frequency of TENS delays analgesic tolerance in rats.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a non-invasive analgesic resource extensively used in painful conditions. However, preclinical studies suggest that the prolonged use of TENS results in the development of tolerance to its analgesic effect. The present study investigated the analgesic effect and development of tolerance to TENS with four different stimulation protocols. METHODS: Male Wistar rats induced with joint inflammation were divided into four groups: sensory intensity, low motor intensity, high motor intensity and sham groups. TENS was applied daily for 20 min with alternating frequency between 4 and 100 Hz until tolerance development was evidenced. Mechanical hyperalgesia was measured before and after each TENS daily application. RESULTS: After TENS, tolerance was evidenced There was a significant reduction in the mechanical withdrawal threshold in all groups 24 h after induction of inflammation (p < 0.01). We observed a loss of analgesic efficacy of TENS around the 12th, 19th and 19th days in the groups treated with sensory intensity, low motor intensity and high motor intensity, respectively (p < 0.02) when analysed using paired measurements and compared with the control. CONCLUSIONS: The association between frequency variation and intensity at motor level promotes a delay in the development of analgesic tolerance to TENS, optimizing and extending its therapeutic effectiveness.