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Aerogel scaffolds are nanostructured materials with beneficial properties for tissue engineering applications. The tracing of the state of the aerogels after their implantation is challenging due to their variable biodegradation rate and the lack of suitable strategies capable of in vivo monitoring the scaffolds. Upconversion nanoparticles (UCNPs) have emerged as advanced tools for in vitro bioimaging because of their fluorescence properties. In this work, highly fluorescent UCNPs were loaded into aerogels to obtain theranostic implants for tissue engineering and bioimaging applications. 3D-printed alginate-hydroxyapatite aerogels labeled with UCNPs were manufactured by 3D-printing and supercritical CO2 drying to generate personalize-to-patient aerogels. The physicochemical performance of the resulting structures was evaluated by printing fidelity measurements, nitrogen adsorption-desorption analysis, and different microscopies (confocal, transmission and scanning electron microscopies). Stability of the aerogels in terms of physicochemical properties was also tested after 3 years of storage. Biocompatibility was evaluated in vitro by different cell and hemocompatibility assays, in ovo and in vivo by safety and bioimaging studies using different murine models. Cytokines profile, tissue index and histological evaluations of the main organs unveiled an in vivo downregulation of the inflammation after implantation of the scaffolds. UCNPs-decorated aerogels were first-time manufactured and long-term traceable by fluorescence-based bioimaging until 3 weeks post-implantation, thereby endorsing their suitability as tissue engineering and theranostic nanodevices (i.e. bifunctional implants).

Background and Aim: Feline chronic gingivostomatitis (FCGS) is a frequent chronic inflammatory condition in the oral cavity with an etiopathogenesis not completely identified. This study aimed to contribute to the knowledge of FCGS by identifying the presence of feline calicivirus (FCV) antigens and natural killer (NK) cells and comparing them. Materials and Methods: Forty biopsies from the oral mucosa of cats diagnosed with chronic gingivostomatitis were subjected to immunohistochemical techniques to evaluate cells with FCV antigens and NK cells positive for CD56. Results: NK cells were identified in all samples, with an average of 725.3 ± 409.1 cells. Regarding FCV, it was identified in 18 out of 30 samples (60%), with a different number of cells with virus in between the analyzed cases. In all cases, the number of cells infected with FCV was lower than the number of NK cells present in the same samples, but there was no statistical association between them. Conclusion: This preliminary study shows that NK cells are present in gingivostomatitis lesions not exclusively caused by FCV-stimulus, as only 60% of all cases were positive for this virus, but other antigens should be considered in the etiology of FCGS.

Desde, pelo menos, o início do século XIX que um conjunto de famílias com origem no Algarve central se dedica à extração, transformação industrial e comercialização de cortiça um pouco por todo o sul de Portugal. A cronologia identificada, bem como o âmbito geográfico alargado, fazem deste grupo social um elemento a ter em conta pela historiografia sempre que se analisar a génese e o desenvolvimento do negócio corticeiro em Portugal. Este artigo, baseado numa grande multiplicidade de fontes e bibliografia, vem demonstrar diacrónica e espacialmente o importante papel que esta comunidade desempenhou, para que no futuro também os corticeiros de Loulé, São Brás de Alportel e Faro tenham o devido destaque na História do setor corticeiro em Portugal, o que ainda não acontece.

Desde el siglo XVII, el regadío se apunta como una solución para asentar población en el Alentejo debido al aumento de la producción agrícola y la consecuente reforma agraria. Sin embargo, solo desde mediados del siglo XX se produjo un crecimiento de las zonas de regadío. Después de más de seis décadas, este trabajo estudia el impacto de la construcción de la presa de Maranhão, Avis, Alentejo cruzando los objetivos fijados con la respectiva evolución demográfica, económica y social. Del análisis de distintas series estadísticas se concluye que la mayoría de los objetivos no se alcanzaron. Avis es hoy un territorio despoblado, con bajos índices de desarrollo y una estructura agraria latifundista. Además, se ha producido una expansión de los monocultivos intensivos, poniendo en peligro la sostenibilidad medioambiental regional. Esta reflexión basada en el análisis histórico es fundamental en un momento en que se anuncia la construcción de nuevas presas.

Objective: The metalloprotease ADAM17 (also called TACE) plays fundamental roles in homeostasis by shedding key signaling molecules from the cell surface. Although its importance for the immune system and epithelial tissues is well-documented, little is known about the role of ADAM17 in metabolic homeostasis. The purpose of this study was to determine the impact of ADAM17 expression, specifically in adipose tissues, on metabolic homeostasis. Methods: We used histopathology, molecular, proteomic, transcriptomic, in vivo integrative physiological and ex vivo biochemical approaches to determine the impact of adipose tissue-specific deletion of ADAM17 upon adipocyte and whole organism metabolic physiology. Results: ADAM17adipoq-creΔ/Δ mice exhibited a hypermetabolic phenotype characterized by elevated energy consumption and increased levels of adipocyte thermogenic gene expression. On a high fat diet, these mice were more thermogenic, while exhibiting elevated expression levels of genes associated with lipid oxidation and lipolysis. This hypermetabolic phenotype protected mutant mice from obesogenic challenge, limiting weight gain, hepatosteatosis and insulin resistance. Activation of beta-adrenoceptors by the neurotransmitter norepinephrine, a key regulator of adipocyte physiology, triggered the shedding of ADAM17 substrates, and regulated ADAM17 expression at the mRNA and protein levels, hence identifying a functional connection between thermogenic licensing and the regulation of ADAM17. Proteomic studies identified Semaphorin 4B (SEMA4B), as a novel ADAM17-shed adipokine, whose expression is regulated by physiological thermogenic cues, that acts to inhibit adipocyte differentiation and dampen thermogenic responses in adipocytes. Transcriptomic data showed that cleaved SEMA4B acts in an autocrine manner in brown adipocytes to repress the expression of genes involved in adipogenesis, thermogenesis, and lipid uptake, storage and catabolism. Conclusions: Our findings identify a novel ADAM17-dependent axis, regulated by beta-adrenoceptors and mediated by the ADAM17-cleaved form of SEMA4B, that modulates energy balance in adipocytes by inhibiting adipocyte differentiation, thermogenesis and lipid catabolism.

This article analyses the relocation processes that the Portuguese cork industry underwent between the 1880s and 1980s. Beyond the historical-geographical aspects of the cork industry, its importance lies in the fact that it involves a paradigmatic case of a traditional industrial sector of vital importance for a developing country. Such was the case of Portugal in the late nineteenth century, where the change of location of the industry coincided with the country’s rise to become the world’s leading power in the cork industry. The article concludes that the factors that made certain regions more attractive for the development of the cork industry compared to others changed over the course of a few decades. There were two industrial relocations in a century as companies adapted to technical and organizational changes; this geographical reorganization was therefore due to a variety of factors and cannot be fully explained by just one theory of industrial location.

An individual diagnosed with dyslexia in childhood typically remains dyslexic throughout his/her life. However, the cognitive profile of adults with dyslexia has been less explored than that of children. This meta-analytic study is intended to clarify three questions: (1) To what extent, and in what manner, do adults with reading difficulties (dyslexia) differ from typical adult readers in measures of reading and writing competence and related cognitive skills?; (2) To what extent do speed measures pose a greater challenge than accuracy measures in an adult population that has already had years of print exposure?; and (3) To what extent does orthographic transparency modulate the reading profile of adults with dyslexia? A total of 178 studies comparing adults with dyslexia and matched controls were reviewed. The results showed that adults with dyslexia exhibited poor performance on almost all reading and writing tasks expressed by very large effect sizes (range 1.735 [less than or equal to] "d" [less than or equal to] 2.034), except for reading comprehension ("d" = 0.729). Deficits in reading- and writing-related variables are also present but with a lower expression (range 0.591 [less than or equal to] "d" [less than or equal to] 1.295). These difficulties are exacerbated for speed measures, especially for word and pseudoword reading, phonological awareness and orthographic knowledge. Orthographic transparency proved to be a significant moderator of dyslexic deficits in word and pseudoword reading, reading comprehension, spelling and phonological awareness, with the expression of the deficits being weaker on transparent--as opposed to intermediate and opaque--orthographies. Overall, the meta-analysis shows that reading and writing difficulties persist in adulthood and are more pronounced in speed measures. Moreover, symptoms are more severe for reading and writing than they are for measures tapping into the cognitive processes underlying reading skills. Orthographic transparency has a significant effect on the manifestation of dyslexia, with dyslexia symptoms being less marked on transparent orthographies. In addition, phonological awareness seems to be a minor problem in adulthood, especially for transparent orthographies.

This article analyses rice production in Portugal from its establishment in the late eighteenth century to the present. Today, not only are the Portuguese the main consumers of rice in Europe, but this cereal is the second most-produced by Portuguese agriculture. However, the historical analysis of rice production in Portugal is limited to specific eras and/or geographies. This research aims to contribute to filling several research gaps, providing a long-term view of a current problem, as the terms of public support for rice production have recently been discussed. Thus, based mainly on statistical sources, the conclusion is that rice, after a phase of slow growth, established itself from the 1930s onwards as one of the main crops of Portuguese agriculture. In fact, rice was the only cereal in Portugal that managed to keep up with the increase in productivity of the other European countries. To this end, in conjunction with favourable agroecological and market factors, public policies were decisive, such as seed selection and the introduction of more productive varieties, the elimination of public health problems and the construction of major agricultural hydraulic public works.

Coxiella burnetii causes Q fever, which is found worldwide and can be acute or chronic. This case report describes a 72-year-old man whose bilateral lower limb pain revealed a paravertebral abscess at L2–L3 due to Q fever spondylodiscitis. Surgical drainage of the abscess was performed and medical treatment is ongoing. Q fever is endemic in Portugal and transmitted by inhalation of aerosols containing spores from infected animals (cattle, goats and sheep) or by ingesting cottage cheese or unpasteurized milk. It has an incubation period of 2–3 weeks and 60% of patients are asymptomatic with only 2% needing hospitalization. Primary infection can manifest in any organ and most cases are self-limiting (self-limited febrile illness, atypical pneumonia or acute hepatitis). Less than 1% of cases evolve to chronic disease, presenting as osteomyelitis or endocarditis. Chronic disease poses a diagnostic challenge and spondylodiscitis has an insidious evolution. Diagnosis requires microbiological and clinical confirmation. Serological and polymerase chain reaction tests are used for diagnosis. Acute disease is usually treated with doxycycline for 3 weeks to avoid evolution to chronic disease. Chronic disease requires 18–24 months of doxycycline with hydroxychloroquine. Acute disease can recur so follow-up is essential as chronic Q fever can result in morbidity and mortality. In Portugal Q fever is a notifiable disease due to the epidemiological risk.

Reforçado pela ascensão do Constitucionalismo, o movimento associativo expandiu-se no século XIX nos mais variados campos de atuação. O progresso económico era um dos principais objetivos das associações Oitocentistas que, no contexto ibérico de sociedades essencialmente agrárias, apostaram na evolução da agricultura como motor do desenvolvimento. Neste artigo estuda-se, em perspetiva comparada, a ação do associativismo agrícola em duas das mais extensas regiões agrícolas de Espanha e Portugal, respetivamente Extremadura e Alentejo. Conclui-se que, embora aquém dos objetivos definidos, o associativismo agrícola na região espanhola não só foi mais precoce, como também mais ativo. No entanto, futuras investigações deverão ser conduzidas de forma a cimentar a ideia da existência de um associativismo agrícola espanhol mais dinâmico.

Climate change in the Mediterranean area is making summers warmer and dryer. Grapevine (Vitis vinifera L.) is mostly important for wine production in Mediterranean countries, and the variety Tempranillo is one of the most cultivated in Spain and Portugal. Drought decreases yield and quality and causes important economic losses. As full irrigation has negative effects on quality and water is scarce in this region, deficit irrigation is often applied. In this research, we studied the effects of two deficit irrigation treatments, Sustained Deficit Irrigation (SDI) and Regulated Deficit Irrigation (RDI), on the transcriptome of grape berries at full maturation, through RNAseq. The expression of differentially regulated genes (DEGs) was also monitored through RT-qPCR along berry development. Most transcripts were regulated by water stress, with a similar distribution of up- and down-regulated transcripts within functional categories (FC). Primary metabolism was the more severely affected FC under water stress, followed by signaling and transport. Almost all DEGs monitored were significantly up-regulated by severe water stress at veraison. The modulation of an auxin response repression factor, AUX22D, by water stress indicates a role of this gene in the response to drought. Further, the expression of WRKY40, a TF that regulates anthocyanin biosynthesis, may be responsible for changes in grape quality under severe water stress.

Antiseptics and disinfectants are extensively used for a variety of topical and hard-surface applications. A wide variety of biocides as active chemical agents is found in these products, including alcohols, phenols, iodine, and chlorine. Many of these active agents demonstrate broad-spectrum antimicrobial activity; however, the mode of action of these agents is not well-documented. This review is focused on several examples of ionic systems based on ionic surfactants and ionic liquids as well as nanomaterials and nanoparticles acting as antiseptics and disinfectants for surfaces. It is important to note that many of these biocides may be used singly or in combination in a variety of products, which vary considerably in activity against microorganisms. Antimicrobial activity can be influenced by several factors such as formulation effects, presence of an organic load, synergy, temperature, dilution, and test method. The most promissory compounds based on ionic systems and nanomaterials published in mainly the last decade is chronologically reported in this review.

Peritoneal protein loss (PPL) has been correlated with mortality, malnutrition and inflammation. More recently overhydration was brought to the equation. This study aims to review classic and recent factors associated with PPL. Prevalent and incident peritoneal dialysis (PD) patients were included. Dialysate and serum IL-6 was obtained during PET. Hydration and nutritional status were assessed by bio-impedance. Linear regression and Cox regression were performed. The 78 included patients presented median values of PPL 4.8 g/24 h, serum IL-6: 5.1 pg/mL, and IL-6 appearance rate 153.5 pg/min. Mean extracellular water excess (EWexc) was 0.88 ± 0.94 L, and lean body mass index (LBMI) 17.3 ± 2.4 kg/m2. After mean follow-up of 33.9 ± 29.3 months, 12 patients died. Linear univariable analysis showed positive associations between PPL and small solute transport, body composition (LBMI and EWexc), comorbidities and performing CAPD (vs. cycler). PPL correlated positively with dialysate appearance rate of IL-6, but not with serum IL-6. Linear multivariable analysis confirmed positive association between PPL and EWexc (p = 0.012; 95%CI: 4.162–31.854), LBMI (p = 0.008; 95%CI: 1.720–11.219) and performing CAPD (p = 0.023; 95%CI: 4.375–54.190). In survival analysis, no relationship was found between mortality and PPL. Multivariable Cox regression showed Charlson Comorbidity Index (HR: 1.896, 95%CI: 1.235–2.913), overhydration (HR: 10.034, 95%CI: 1.426–70.587) and lower PPL (HR: 0.576, 95%CI: 0.339–0.978) were predictors for mortality. Overhydration, was a strong predictor of PPL, overpowering variables previously reported as determinants of PPL, namely clinical correlates of endothelial dysfunction or local inflammation. PPL were not associated with malnutrition or higher mortality, emphasizing the importance of volume overload control in PD patients.

The D76N mutant of the β2m protein is a biologically motivated model system to study protein aggregation. There is strong experimental evidence, supported by molecular simulations, that D76N populates a highly dynamic conformation (which we originally named I2) that exposes aggregation-prone patches as a result of the detachment of the two terminal regions. Here, we use Molecular Dynamics simulations to study the stability of an ensemble of dimers of I2 generated via protein–protein docking. MM-PBSA calculations indicate that within the ensemble of investigated dimers the major contribution to interface stabilization at physiological pH comes from hydrophobic interactions between apolar residues. Our structural analysis also reveals that the interfacial region associated with the most stable binding modes are particularly rich in residues pertaining to both the N- and C-terminus, as well residues from the BC- and DE-loops. On the other hand, the less stable interfaces are stabilized by intermolecular interactions involving residues from the CD- and EF-loops. By focusing on the most stable binding modes, we used a simple geometric rule to propagate the corresponding dimer interfaces. We found that, in the absence of any kind of structural rearrangement occurring at an early stage of the oligomerization pathway, some interfaces drive a self-limited growth process, while others can be propagated indefinitely allowing the formation of long, polymerized chains. In particular, the interfacial region of the most stable binding mode reported here falls in the class of self-limited growth.

Studies addressing the recognition of emotions in blind or deaf participants have been carried out only with children and adolescents. Due to these age limits, such studies do not clarify the long-term effects of vision and hearing disabilities on emotion recognition in adults. We assessed the ability to recognize basic emotions in 15 deaf adults (aged 32.4 ± 8.1 yrs) and in 15 blind adults (48.3 ± 10.5 yrs). Auditory and visual stimuli expressing six basic emotional states were presented to participants ("Florida Affect Battery"). Participants also performed an empathy test. Deaf participants showed difficulties in emotion recognition tasks compared to the typical hearing participants; however, differences were only statistically reliable for Facial Emotion Discrimination and Naming tasks (specifically, naming expressions of fear). Deaf participants also revealed inferior levels of cognitive empathy. Concerning blind participants, their performance was lower than the controls' only when the task required the evaluation of emotional prosody while ignoring the semantic content of the sentence. Overall, although deaf and blind participants performed reasonably well on tasks requiring recognition of basic emotions, sensory loss may hinder their social perception skills when processing subtle emotions or when the extraction of simultaneous prosodic and semantic information is required.

This study presents a meta-analytic review of serial rapid automatized naming (RAN) deficits in individuals with dyslexia relative to typical readers (based on 216 effect sizes comprising 8335 dyslexic readers, 14,083 age-matched controls, and 921 reading-matched controls). A random-effects model analysis indicated a large impairment in speeded RAN in individuals with dyslexia compared with age-matched controls (d = 1.19) but a similar performance when compared with reading-matched controls (d = 0.13). In addition, dyslexic readers presented a deficit in discrete-naming formats (d = 0.74), although the deficit in serial RAN was notably larger; hence, adding seriality is particularly detrimental for these readers. The deficit appears to span all stimulus types (alphanumeric and nonalphanumeric), indicating that processes beyond letter processing are responsible for the delays and are independent of set size. Poor RAN is a long-term and universal symptom of dyslexia, and the transparency of the writing system does not influence its severity.

In recent years, gold nanoparticles (AuNPs) have aroused the interest of many researchers due to their unique physicochemical and optical properties. AuNPs are being explored in a variety of biomedical fields, either in diagnostics or therapy, particularly for localized thermal ablation of cancer cells after light irradiation. Besides the promising therapeutic potential of AuNPs, their safety constitutes a highly important issue for any medicine or medical device. For this reason, in the present work, the production and characterization of physicochemical properties and morphology of AuNPs coated with two different materials (hyaluronic and oleic acids (HAOA) and bovine serum albumin (BSA)) were firstly performed. Based on the above importantly referred issue, the in vitro safety of developed AuNPs was evaluated in healthy keratinocytes, human melanoma, breast, pancreatic and glioblastoma cancer cells, as well as in a three-dimensional human skin model. Ex vivo and in vivo biosafety assays using, respectively, human red blood cells and Artemia salina were also carried out. HAOA-AuNPs were selected for in vivo acute toxicity and biodistribution studies in healthy Balb/c mice. Histopathological analysis showed no significant signs of toxicity for the tested formulations. Overall, several techniques were developed in order to characterize the AuNPs and evaluate their safety. All these results support their use for biomedical applications.

Presently, skin burns are considered one of the main public health problems and lack therapeutic options. In recent years, silver nanoparticles (AgNPs) have been widely studied, playing an increasingly important role in wound healing due to their antibacterial activity. This work is focused on the production and characterization of AgNPs loaded in a Pluronic® F127 hydrogel, as well as assessing its antimicrobial and wound-healing potential. Pluronic® F127 has been extensively explored for therapeutic applications mainly due to its appealing properties. The developed AgNPs had an average size of 48.04 ± 14.87 nm (when prepared by method C) and a negative surface charge. Macroscopically, the AgNPs solution presented a translucent yellow coloration with a characteristic absorption peak at 407 nm. Microscopically, the AgNPs presented a multiform morphology with small sizes (~50 nm). Skin permeation studies revealed that no AgNPs permeated the skin after 24 h. AgNPs further demonstrated antimicrobial activity against different bacterial species predominant in burns. A chemical burn model was developed to perform preliminary in vivo assays and the results showed that the performance of the developed AgNPs loaded in hydrogel, with smaller silver dose, was comparable with a commercial silver cream using higher doses. In conclusion, hydrogel-loaded AgNPs is potentially an important resource in the treatment of skin burns due to their proven efficacy by topical administration.

The valorisation of genetic variability through the identification suitable genotypes for traits such as yield and must quality is an effective strategy used for grapevine selection. Currently, climate change-driven heat waves and drought affect plant growth and wine quality, but little information is available on intravarietal variability regarding responses to stress. In the current work, the intravarietal genetic variability of the Portuguese variety Arinto was studied for yield, must quality, and tolerance to abiotic stress. An innovative approach using rapid, and nondestructive measurements of surface leaf temperature (SLT), Normalized Difference Vegetation Index (NDVI), Photochemical Reflectance Index (PRI), and chlorophyll content (SPAD), was used in an experimental population of 165 clones of Arinto installed according to a resolvable row-column design with 6 replicates. Also, yield and quality characteristics of the must were quantified. Linear mixed models were fitted to the data, and the empirical best linear unbiased predictors (EBLUPs) of genotypic effects for each trait were obtained as well as the coefficient of genotypic variation (CVG) and broad sense heritability. The results enabled the selection of a group of genotypes with increased tolerance to stress, which maintained the must quality of Arinto.

Since the last decade of the last century, it is known that many old grapevine varieties are descendants of other varieties through natural crossing. Portugal has an important program for the conservation of representative samples of intra-varietal variability of all autochthonous varieties, managed by the Portuguese Association for Grapevine Diversity (PORVID), which makes looking for genotypes with dubious identification an important activity from a perspective of its valorisation. This communication presents the results of the molecular analysis of 5,000 samples (accessions) from the PORVID’s collection, using nine microsatellite loci currently recommended by the International Organization of Vine and Wine (OIV) for genetic grapevine identification. The results obtained confirmed the molecular identity of 4,220 samples corresponding to 214 varieties present in the official list of Portuguese varieties. In 780 samples, 95 profiles with a plural number of accessions revealed not to be listed in the Vitis International Variety Catalogue (VIVC) database, corresponding to possible varieties either descendent from natural crossing from at least one known parental variety, or from undetermined origin. Furthermore, the need for a comprehensive strategy aimed at uncovering other hidden varieties is discussed to prevent their imminent loss, deepen understanding of their origin, and add economic value and sustainability to the vine and wine sector.

Effects of emotional valence have been observed in lexical decision tasks, suggesting that valence information modulates early word recognition. However, is still unclear the processing advantage of the different valence categories, and how these advantages might be modulated by word frequency and arousal. To clarify this question, a lexical decision task was designed using emotional words as stimuli. Emotional words were divided into three categories: 60 positive, 60 negative, and 60 neutral words. Word frequency was manipulated into low and high conditions and arousal was controlled among experimental conditions (word valence and frequency). In the first experiment, 54 participants performed the task with a maximum stimuli exposure time of 2000 ms. In a follow-up experiment, 42 participants performed the same task with two shorter fixed time exposures (150 ms and 300 ms). The results were similar between experiments: positive words were recognized faster and negative words were recognized slower than neutral ones. Furthermore, this valence effect was modulated by word frequency, affecting only words that take longer to be recognized (low-frequency words). However, the valence by frequency interaction was attenuated for high-arousal words when the pressure to respond was high (short exposure time - 150 ms). Overall, the results confirm that the emotional status of a word can affect word processing at early stages when automatic processes are taking place.

Based on a reading influenced by the professional experience of the author, this study aims to understand the reality experienced in the State of Tocantins with regard to music education, based on an analysis of its state education network, and the municipal education network of its state capital, in a study focused on two distinct axes: the evolution of the curriculum in the state network, between 2013 and 2017, and the reality experienced in the schools of the municipal network of Palmas, Tocantins, as far as music education is concerned. Seeking in this analysis to start from a national view of the curriculum guidelines in the area of music education, the research methodology used is of a qualitative nature, based on observation, document collection, discourse analysis, and the application of a questionnaire to music teachers working in the city of Palmas, Tocantins, during the second half of 2017. In the end, it is concluded that, persisting in the Brazilian reality a dispute between two distinct models of artistic education – one characterized by an integrative approach of different languages, and another by a more autonomous vision that provides curriculum spaces specific to each of these languages –, there is a tendency to regress, namely with the approval of the Common National Curriculum Base, to a more integrative vision of artistic languages, in the wake of the Artistic Education provided by LDB of 1971. It is also noted the state non-compliance with standards and programmatic guidelines for music education at national level.

Objective: Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energy dissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Here we evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in the pathophysiology of metabolic syndrome. Methods: We challenged WT versus iRhom2 KO mice to positive energy balance by chronic exposure to a high fat diet and then compared their metabolic phenotypes. We also carried out ex vivo assays with primary and immortalized mouse brown adipocytes to establish the autonomy of the effect of loss of iRhom2 on thermogenesis and respiration. Results: Deletion of iRhom2 protected mice from weight gain, dyslipidemia, adipose tissue inflammation, and hepatic steatosis and improved insulin sensitivity when challenged by a high fat diet. Crucially, the loss of iRhom2 promotes thermogenesis via BAT activation and beige adipocyte recruitment, enabling iRhom2 KO mice to dissipate excess energy more efficiently than WT animals. This effect on enhanced thermogenesis is cell-autonomous in brown adipocytes as iRhom2 KOs exhibit elevated UCP1 levels and increased mitochondrial proton leak. Conclusion: Our data suggest that iRhom2 is a negative regulator of thermogenesis and plays a role in the control of adipose tissue homeostasis during metabolic disease. Keywords: iRhom2, ADAM17/TACE, Obesity, Insulin resistance, NAFLD, BAT, Browning, Thermogenesis, UCP1

Research on the predictors of reading comprehension has been largely focused on school-aged children and mainly in opaque orthographies, hindering the generalization of the results to adult populations and more transparent orthographies. In the present study, we aim to test two versions of the Simple View of Reading (SVR): the original model and an extended version, including reading fluency and vocabulary. Additional mediation models were analyzed to verify if other reading comprehension predictors (rapid automatized naming, phonological decoding, phonological awareness, morphological awareness, and working memory) have direct effects or if they are mediated through word reading and reading fluency. A sample of 67 typical adult Portuguese readers participated in this study. The SVR model accounted for 27% of the variance in reading comprehension, with oral language comprehension displaying a larger contribution than word reading. In the extended SVR model, reading fluency and vocabulary provided an additional and significant contribution of 7% to the explained variance. Moreover, vocabulary influenced reading comprehension directly and indirectly, via oral language comprehension. In the final mediation model, the total mediation hypothesis was rejected, and only morphological awareness showed a direct effect on reading comprehension. These results provide preliminary evidence that the SVR (with the possible addition of vocabulary) might be a reliable model to explain reading comprehension in adult typical readers in a semitransparent orthography. Furthermore, oral language comprehension and vocabulary were the best predictors in the study, suggesting that remediation programs addressing reading comprehension in adults should promote these abilities.

Nos últimos anos, seguindo uma tendência europeia com várias décadas, a historiografia portuguesa tem construído séries estatísticas de longa duração para diversos indicadores económicos e sociais. Ainda que a agricultura seja uma das atividades historicamente mais relevantes, esses indicadores continuam a faltar. Resultando de uma longa pesquisa que tem tentado colmatar algumas das lacunas identificadas, apresentam-se as primeiras séries de produção agrícola regional para Portugal Continental. A análise começa no século XIX, quando os serviços oficiais passaram a recolher sistematicamente alguns dados estatísticos. O artigo está focado no processo de produção destas fontes históricas, avaliando como as mudanças no enquadramento institucional e nos objetivos do Estado podem ter influenciado a qualidade dos dados existentes para cada região. Seguidamente, traça um roteiro dos fundos documentais guardados e disponíveis nos arquivos nacionais e distritais, facilitando o desenvolvimento de futuras investigações.

Head and neck cancer (HNC), also known as the cancer that can affect the structures between the dura mater and the pleura, is the 6th most common type of cancer. This heterogeneous group of malignancies is usually treated with a combination of surgery and radio- and chemotherapy, depending on if the disease is localized or at an advanced stage. However, most HNC patients are diagnosed at an advanced stage, resulting in the death of half of these patients. Thus, the prognosis of advanced or recurrent/metastatic HNC, especially HNC squamous cell carcinoma (HNSCC), is notably poorer than the prognosis of patients diagnosed with localized HNC. This review explores the epidemiology and etiologic factors of HNC, the histopathology of this heterogeneous cancer, and the diagnosis methods and treatment approaches currently available. Moreover, special interest is given to the novel therapies used to treat HNC subtypes with worse prognosis, exploring immunotherapies and targeted/multi-targeted drugs undergoing clinical trials, as well as light-based therapies (i.e., photodynamic and photothermal therapies).

Monte Carlo simulations are a powerful technique and are widely used in different fields. When applied to complex molecular systems with long chains, such as those in synthetic polymers and proteins, they have the advantage of providing a fast and computationally efficient way to sample equilibrium ensembles and calculate thermodynamic and structural properties under desired conditions. Conformational Monte Carlo techniques employ a move set to perform the transitions in the simulation Markov chain. While accepted conformations must preserve the sequential bonding of the protein chain model and excluded volume among its units, the moves themselves may take the chain across itself. We call this a break in linear topology preservation. In this manuscript, we show, using simple protein models, that there is no difference in equilibrium properties calculated with a move set that preserves linear topology and one that does not. However, for complex structures, such as those of deeply knotted proteins, the preservation of linear topology provides correct equilibrium results but only after long relaxation. In any case, to analyze folding pathways, knotting mechanisms and folding kinetics, the preservation of linear topology may be an unavoidable requirement.

This study investigates the implicit sequence learning abilities of dyslexic children using an artificial grammar learning task with an extended exposure period. Twenty children with developmental dyslexia participated in the study and were matched with two control groups--one matched for age and other for reading skills. During 3 days, all participants performed an acquisition task, where they were exposed to colored geometrical forms sequences with an underlying grammatical structure. On the last day, after the acquisition task, participants were tested in a grammaticality classification task. Implicit sequence learning was present in dyslexic children, as well as in both control groups, and no differences between groups were observed. These results suggest that implicit learning deficits per se cannot explain the characteristic reading difficulties of the dyslexics.

Natural products, especially those derived from seaweeds, are starting to be seen as effective against various diseases, such as cardiovascular diseases (CVDs). This study aimed to design a novel oral formulation of bovine albumin serum nanoparticles (BSA NPs) loaded with an extract of Eisenia bicyclis and to validate its beneficial health effects, particularly targeting hypercholesterolemia and CVD prevention. Small and well-defined BSA NPs loaded with Eisenia bicyclis extract were successfully prepared exhibiting high encapsulation efficiency. Antioxidant activity and cholesterol biosynthesis enzyme 3-hydroxy-3 methylutaryl coenzyme A reductase (HMGR) inhibition, as well as reduction of cholesterol permeation in intestinal lining model cells, were assessed for the extract both in free and nanoformulated forms. The nanoformulation was more efficient than the free extract, particularly in terms of HMGR inhibition and cholesterol permeation reduction. In vitro cytotoxicity and in vivo assays in Wistar rats were performed to evaluate its safety and overall effects on metabolism. The results demonstrated that the Eisenia bicyclis extract and BSA NPs were not cytotoxic against human intestinal Caco-2 and liver HepG2 cells and were also safe after oral administration in the rat model. In addition, an innovative approach was adopted to compare the metabolomic profile of the serum from the animals involved in the in vivo assay, which showed the extract and nanoformulation’s impact on CVD-associated key metabolites. Altogether, these preliminary results revealed that the seaweed extract and the nanoformulation may constitute an alternative natural dosage form which is safe and simple to produce, capable of reducing cholesterol levels, and consequently helpful in preventing hypercholesterolemia, the main risk factor of CVDs.

Analysis of canine and feline tumor malignancy data can help clinicians identify high-risk patients and make more accurate decisions. Based on a sample of 16,272 cancer records, including 3266 cats and 13,006 dogs, collected from January 2019 to December 2021 in the Vet-OncoNet Network database, this study aimed to compare the tumor malignancy profile between cats and dogs, considering animal-related factors (sex, age, and breed), topography, and geographic location using a mixed-effects logistic regression model. Cats had a higher proportion of malignant tumors (78.7%) than dogs (46.2%), and the malignancy profile was very different regarding tumors’ topographies. The mean age of malignant tumors occurred eight months later than benign ones (9.1, SD = 3.4; 9.8, SD = 3.2), in general. Species (OR = 3.96, 95%CI 3.57: 4.39) and topography (MOR = 4.10) were the two most important determinants of malignancy risk. Female dogs had a higher risk than male dogs (OR = 1.19, 95%CI 1.08: 1.31), which does not appear to be the case in cats (OR = 0.98, 95%CI 0.77: 1.23). Breed contributed significantly to differences in malignancy risk in dogs (MOR = 1.56), particularly in pit bulls and boxers. District of residence was not so relevant in predicting malignancy risk (MOR = 1.14). In both species, the risk of malignancy increased by approximately 20% every three years. It could be hypothesized that species differences in genetic structure may contribute to tumor malignancy.

Aerogels are materials with unique properties, among which are low density and thermal conductivity. They are also known for their exquisite biocompatibility and biodegradability. All these features make them attractive for biomedical applications, such as their potential use in photothermal therapy (PTT). This technique is, yet, still associated with undesirable effects on surrounding tissues which emphasizes the need to minimize the exposure of healthy regions. One way to do so relies on the use of materials able to block the radiation and the heat generated. Aerogels might be potentially useful for this purpose by acting as insulators. Silica- and pectin-based aerogels are reported as the best inorganic and organic thermal insulators, respectively; thus, the aim of this work relies on assessing the possibility of using these materials as light and thermal insulators and delimiters for PTT. Silica- and pectin-based aerogels were prepared and fully characterized. The thermal protection efficacy of the aerogels when irradiated with a near-infrared laser was assessed using phantoms and ex vivo grafts. Lastly, safety was assessed in human volunteers. Both types presented good textural properties and safe profiles. Moreover, thermal activation unveils the better performance of silica-based aerogels, confirming the potential of this material for PTT.

The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2][C1SO3]2 and [HCQH2][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2][SO4]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2][GlcCOO]2. Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra- and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.