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Purpose: This study investigates the communication behavior of public health organizations on Twitter during the COVID-19 vaccination campaign in Brazil. It contributes to the understanding of the organizational framing of health communication by showcasing several instances of framing devices that borrow from (Brazilian) internet culture. The investigation of this case extends the knowledge by providing a rich description of the organizational framing of health communication to combat misinformation in a politically charged environment. Design/methodology/approach: The authors collected a Twitter dataset of 77,527 tweets and analyzed a purposeful subsample of 536 tweets that contained information provided by Brazilian public health organizations about COVID-19 vaccination campaigns. The data analysis was carried out quantitatively and qualitatively by combining social media analytics techniques and frame analysis. Findings: The analysis showed that Brazilian health organizations used several framing devices that have been identified by previous literature such as hashtags, links, emojis or images. However, the analysis also unearthed hitherto unknown visual framing devices for misinformation prevention and debunking that borrow from internet culture such as "infographics," "pop culture references" and "internet-native symbolism." Research limitations/implications: First, the identification of framing devices relating to internet culture add to our understanding of the so far little addressed framing of misinformation combat messages. The case of Brazilian health organizations provides a novel perspective to knowledge by offering a notion of internet-native symbols (e.g. humor, memes) and popular culture references for misinformation combat, including misinformation prevention. Second, this study introduces a frontier of political contextualization to misinformation research that does not relate to the partisanship of the spreaders but that relates to the political dilemmas of public organizations with a commitment to provide accurate information to citizens. Practical implications: The findings inform decision-makers and public health organizations about framing devices that are tailored to internet-native audiences and can guide strategies to carry out information campaigns in misinformation-laden social media environments. Social implications: The findings of this case study expose the often-overlooked cultural peculiarities of framing information campaigns on social media. The report of this study from a country in the Global South helps to contrast several assumptions and strategies that are prevalent in (health) discourses in Western societies and scholarship. Originality/value: This study uncovers unconventional and barely addressed framing devices of health organizations operating in Brazil, which provides a novel perspective to the body of research on misinformation. It contributes to existing knowledge about frame analysis and broadens the understanding of frame devices borrowing from internet culture. It is a call for a frontier in misinformation research that deals with internet culture as part of organizational strategies for successful misinformation combat. [ABSTRACT FROM AUTHOR]

This paper analyzes how audiovisual contents produced to order by science communicators on YouTube can indicate and create discursive clashes on social media through the case observation of the science communicator and digital influencer Atila Imarino, considering the emergence of distinct intersectionalities concerning his position as a public figure. We understand that figures who invest in an intersection between the roles of researcher and digital influencer end up not only producing content related to their field of specialization, but also materials about the humanities, composing advertorials without clear distinctions. We’ve analyzed the video “The free market is a computer”, published on the YouTube channel Nerdologia, and the responses and comments generated on Twitter. We start from a qualitative multi-methodological perspective between platforms, combining textual analysis of YouTube videos to Analysis of the Construction of Meanings in Digital Networks (HENN, 2018 et al) and the categories of Intersection Roulette (CARRERA, 2020). As results, the status of “modest witness” (HARAWAY, 1997) and “moral entrepreneur (MIKOLSCI, 2021) materialized themselves in Attila’s positions and corroborate his social capital as an influencer and scientific disseminator. We understand that approaches that favor intersectionality and the problematization of the relationship between scientific production, subordinated identities and platformization are fundamental and bring more equity to combat scientific denial in digital media. [ABSTRACT FROM AUTHOR]

Background: COVID-19 vaccine hesitancy seems to be universal across countries and subgroups, and so are its determinants. We studied the willingness and factors associated with the decision to be vaccinated against COVID-19 in healthcare workers (HCW) in a Spanish tertiary hospital. Furthermore, we compared the percentage of willingness to vaccinate against COVID with actual vaccination rates among HCW in our hospital. Methods: From December 21, 2020 to January 4, 2021, before initiation of the COVID-19 HCW vaccination campaign at Germans Trias i Pujol University Hospital (HUGTiP), an anonymous self-administered questionnaire was administered to HCW. Univariate and multivariate logistic regression of the association of variables with the outcome "intention to receive the COVID-19 vaccine as soon as possible" was conducted. Vaccination rates were extracted from the hospital information systems. Results: Forty-four percent of HCW included in the study declared a willingness to be vaccinated against COVID-19 as soon as possible. This was associated with male sex [1.66 (95%CI 1.13–2.43); p = 0.009], older age [1.02 (95%CI 1.00–1.03); p = 0.014], belonging to the occupational groups "physician" or "other" [5.76 (95%CI 3.44–9.63) and 2.15 (95%CI 1.25–3.70); p<0.001], respectively, and reporting influenza vaccination during the last three seasons or at least one of the last three seasons [3.84 (95%CI 2.56–5.75) and 2.49 (95%CI 1.71–3.63); p<0.001]. One in ten hospital workers reported they were unwilling to receive COVID-19 vaccination. Actual COVID-19 vaccination uptake among HCW was higher (80.4%) than the percentage of willingness to vaccinate estimated from the questionnaire. Physicians not only had the highest vaccination rate, but also the highest correlation between the reported intention to vaccinate and the final decision to receive COVID-19 vaccination. Conclusions: COVID-19 vaccination uptake was higher than previously estimated according to the stated intentions of HCW. Doubts and fears must be addressed, particularly in persons less inclined to be vaccinated: females, younger people and those not vaccinated against influenza in recent seasons. The study of barriers and strategies aimed at promoting COVID-19 vaccination must be adapted in relation to occupational groups' attitudes, understanding their idiosyncrasies with respect to this and other vaccines. [ABSTRACT FROM AUTHOR]

The article analyzes The Scratchware Manifesto (2000), considering the development of indie games and the transformations in the production and creation of games in neoliberal capitalism. Therefore, we approach the textual genre manifesto as a sociocultural practice of transformation that presents limitations because of its Eurocentric nature, and the debate of The Scratchware Manifesto was held in dialogue with other manifestos, such as the Manifesto of the Communist Party (MARX; ENGELS, 2012) and Rise of the Videogame Zinesters (ANTROPY, 2012), among others. In addition, we point out some processes of creation, production and circulation of indie games, from their alignment or not with the market, as well as the labor precariousness. Finally, we indicate initiatives that are promoting alternative relationships of indie game creation, as well as other relationships with work in the video game industry. [ABSTRACT FROM AUTHOR]

Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles from 127 HR-NB patients: (1) Copy number aberration burden (%gains length +%losses length), (2) copy number load (CNL) (%gains length -%losses length) and (3) net genomic load (NGL) (%gains amount -%losses amount). Tumors were classified according to positive or negative CNL and NGL genomic subtypes. The impact of the genomic instability indexes on overall survival (OS) was assessed with Cox regression. We identified 38% of HR-NB patients with poor 5-year OS. A negative CNL genomic background was related to poor prognosis in patients ≥18 months showing tumors with homogeneous MYCN amplification (9.5% survival probability, P < 0.05) and patients with non- MYCN amplified NB (18.8% survival probability related to >2.4% CNL, P < 0.01). A positive CNL genomic background was associated with worse outcome in patients with heterogeneous MYCN amplification (22.5% survival probability, P < 0.05). We conclude that characterizing a tumor genomic background according to predominance of genome gained or lost contributes toward improved outcome prediction and brings greater insight into the tumor biology of HR-NB patients. [ABSTRACT FROM AUTHOR]

The multiplicity of functions, substrates, and molecular partners of the two KAT3 proteins defines a complex cat's cradle of relationships. • CBP and p300 (KAT3s) interact with dozens of TFs and acetylate hundreds of substrates. • KAT3s have both unique and overlapping functions during neural development. • The relative importance of KAT3s decreases along the neuronal differentiation process. • Scaffolding and KAT functions are both part of the same mechanism of transactivation. • Novel tools can address outstanding questions regarding the neuronal role of KAT3s. The paralogous transcriptional co-activators CBP and p300 (aka KAT3A and KAT3B, respectively) contain a characteristic and promiscuous lysine acetyltransferase (KAT) domain and multiple independent protein-binding domains that enable them to interact with hundreds of proteins, possibly promoting the acetylation of thousands of target lysine residues. Both proteins play critical roles during the development of the nervous system and may also regulate stimuli-driven transcription and plasticity in postmitotic neurons. The multiplicity of functions, substrates, and molecular partners, together with the redundancy and singularity of the two KAT3 paralogs, define a complex cat's cradle of relationships. In this review, we discuss the role of the KAT3 proteins in neurons and integrate recent information regarding their function and mode of action. [ABSTRACT FROM AUTHOR]

Purpose: Continuous improvement is a means of promoting and working through business excellence. However, due to the complexity of the implementation process, many companies fail. Some authors consider that this is partly due to the lack of studies which develop and validate theoretical constructs in order to push theory in the CI field. Therefore, this study aims at identifying and better understanding the factors that could act as enablers when implementing a CI initiative by designing and analyzing a new theoretical construct. Design/methodology/approach: After conducting a rigorous literature review and consulting a group of experts, Rasch Measurement Theory was used in order to validate the construct and rank the enablers. Findings: After validating the construct, a hierarchy of priority was obtained, being the following enablers the most important ones: establishing clear objectives, training, recognizing the achievements and learning from the CI process itself and motivation. Practical implications: Identifying the key enablers could help those companies that are about to start with the implementation process. Additionally obtaining a general classification could help managers to make good decisions and handle these enablers, fostering the most important ones. Originality/value: This paper provides additional evidence regarding the main enablers that an organization that decides to implement CI can foster. Additionally, as far as authors are concerned, this is the first paper that defines a theoretical construct concerning continuous improvement enablers. Going one-step further, this paper obtains a hierarchy of priority, identifying the main enablers according to managers' opinions. [ABSTRACT FROM AUTHOR]

During development, chromatin changes contribute to establishing and maintaining the distinct gene-expression profiles of each individual cell type in a multicellular organism. This feat is especially remarkable in the human brain considering the sheer number of distinct cell types that make up this organ. This epigenetic programing is sensitive to environmental influences such as the presence of toxicants, diet, temperature, maternal behavior and many other external factors that can lead to sustained differences in neuronal gene expression. Here, we review a number of studies that demonstrate the existence of these environmental fingerprints in the neuronal epigenome and discuss the current challenges and prospects of environmental neuroepigenetics research. [ABSTRACT FROM AUTHOR]

The objective of this review is to summarize the most relevant aspects of the attention to diners with specific diet in the catering sector. The characteristics of the final consumer usually determine both the variety of specific diets to be served and the operative of the service. There are two models of catering services that are differentiated from each other by the place where the foods are prepared and delivered: centralized production and on-site production. The specialized work of Dieticians and the implementation of technological solutions that entail the optimization and a better control of the process are usual in the catering sector. The management of specifics diets in catering sector is intrinsic to its activity. Despite the high professionalism of the sector in this area, it is necessary a constant adaptation to the new emerging needs, especially those related to allergies and food intolerances and the situations of dependence generated by the increase of the life expectancy of the population. [ABSTRACT FROM AUTHOR]

A series of azobenzene-containing peptidic boronate esters was prepared and the activity of the thermally adapted states (TAS), enriched in trans isomer, and the photostationary states (PSS), enriched in cis isomer, for each compound were evaluated against β5 and β1 proteasome subunits. Compounds with a sterically demanding phenyl-substituted azobenzene at P2 ( 4c ), and a less sterically demanding unsubstituted azobenzene at the N -terminus ( 5a ), showed the greatest difference in activity between the two states. In both cases, the more active trans -enriched TAS had activity comparable to bortezomib and delanzomib. Furthermore, cis -enriched 4c inhibited tumor growth in both breast and colorectal carcinoma cell lines. Significantly, the initial trans -enriched TAS of 4c was not cytotoxic against the non-malignant MCF-10A cells. [ABSTRACT FROM AUTHOR]

• Children adopt different roles in the process of collaboratively resolv a game. • Learning social skills is an important part of the socialisation process of children. • By understanding how children interact with the environment and persons within that environment, we can understand how the environment promotes children's learning and development. • In a group activity, each individual works differently according to his or her objectives, skills and knowledge about the task. • Tangible interfaces are suitable for addressing learning and fun collaborative tasks. Learning social skills is an important part of the socialisation process of children, which should occur at school, at home and in any place where children live. There are very few studies on social interaction and collaboration roles with 3–4 year old. In this paper, we aim to understand collaboration in young children to help them develop their social skills and improve their overall development. To get this, we have designed an observational experiment to monitor and characterise group activity and roles, mediated by technology and using data mining techniques. First, we have designed a game as a free-play situation where the conditions require interplay of three children with toys and among interaction among peers. Children interacts with game through tangible toys. The environment collects accurate data on children's actions automatically and non-intrusively. We also consider other data from direct observation by psychologists and educators. Then, we have organised a study for groups(triads) of 3 to 4-year-old children playing with this game. We analyse data from 81 children (51.9% boys and 48.1% girls) in groups of three randomly selected. The work proposes a set of actions in the game and from them a set of indicators, which are used as intermediate measures of observation to analyse the playing process. Social interaction is characterised in 5 levels: Coordination, Cooperation, Collaboration, Troubled and Unproductive; and five roles: Saboteur, Missing, Explorer, Actor, Collaborator and Director. We found that children interact socially, engage in play, help each other and mostly reach the level of collaboration. There are minority cases of non-cooperation (Troubled or Unproductive), with conflict situations or trial and error solving processes, which cause the task to last a long time before it is finally finished. We have also found that children can adopt different roles in the group. Occasionally, there are cases of children who act as conductors, organising the work while others follow. This work provides a contribution for teachers and educators in the preschool classroom, relating to social interaction. It tells us that young children can play in randomly organised groups, collaborate and take roles, help their peers and learn to do so in classroom games. It shows a learning situation that can serve as an example of how to conduct technology-mediated activities in the classroom to promote social interaction among children in an effective, engaging and motivating way. [ABSTRACT FROM AUTHOR]

Severe gastroenteritis caused by canine parvovirus type 2 (CPV2) is a serious life-threatening disease in puppies less than 4-months of age. The emergence of new variants has provoked some concern about the cross-protection elicited by licensed canine parvovirus modified-live type 2 (CPV2) and type 2b (CPV2b) vaccines against the most recent subtype CPV2c. A systematic review was carried out to assess the efficacy of commercial vaccines. We conducted a literature search of Pub Med/MEDLINE from January 1990 to May 2014. This was supplemented by hand-searching of related citations and searches in Google/Google Scholar. Controlled clinical trials in which vaccinated puppies were challenged with CPV2c virus were evaluated. Reporting of outcome measures and results for vaccine efficacy were critically appraised through a variety of clinical signs, serological tests, virus shedding and the ability to overcome maternally derived antibodies (MDA) titres. Six controlled clinical trials were included in the review. In most cases, the results of the selected studies reported benefits in terms of clinical signs, serological tests and virus shedding. However, MDA interference was not considered or evaluated in 5 of the selected trials. No accurate definitions of baseline healthy status and/or clinical outcomes were provided. Methods of randomization, allocation concealment and blinding were usually poorly reported. As a result of the limited number of included studies matching the inclusion criteria, the small sample sizes, short follow-up and the methodological limitations observed, it was not possible to reach a final conclusion regarding the cross-protection of licensed CPV2 and CPV2b vaccines against the subtype 2c in puppies. Further and specifically designed trials are required in order to elucidate whether cross-protection is acquired from licensed CPV vaccines. [ABSTRACT FROM AUTHOR]

Background Alopecia areata is a T-cell mediated autoimmune disease that occurs in humans and various other mammalian species. When the disease progresses to total alopecia it is defined as alopecia areata universalis (AAU), although this outcome has only been described in humans. Hypothesis/objectives To describe a case of canine alopecia areata universalis and its clinical outcome after 22 months of follow-up. Animal A 9-year-old intact male cross-breed hunting dog was presented with generalized and complete noninflammatory alopecia of 12-14 months duration. Methods Clinical examination; histopathological and immunohistochemical examination of skin biopsies. Results There was loss of all body hair including eyelashes and vibrissae. The histopathological and immunohistochemical findings supported a diagnosis of long-standing alopecia areata. Treatment with oral ciclosporin was associated with hair regrowth but muzzle hair, most eyelashes and whiskers were still lacking after 17 months of therapy. Conclusions and clinical importance To the best of the author's knowledge this is the first documented case of canine AAU. The clinical and histopathological features were consistent with a diagnosis of AAU as defined in humans. Treatment with oral ciclosporin resulted in near complete resolution of the alopecia, but after 5 months without treatment the alopecia did not relapse and spontaneous resolution cannot be ruled out. [ABSTRACT FROM AUTHOR]

Structuraland computational studies to explore the WAT1 bindingpocket in the structure-based design of inhibitors against the typeII dehydroquinase (DHQ2) enzyme are reported. The crystal structuresof DHQ2 from M. tuberculosisin complex with fourof the reported compounds are described. The electrostatic interactionobserved between the guanidinium group of the essential arginine andthe carboxylate group of one of the inhibitors in the reported crystalstructures supports the recently suggested role of this arginine asthe residue that triggers the release of the product from the activesite. The results of the structural and molecular dynamics simulationstudies revealed that the inhibitory potency is favored by promotinginteractions with WAT1 and the residues located within this pocketand, more importantly, by avoiding situations where the ligands occupythe WAT1 binding pocket. The new insights can be used to advantagein the structure-based design of inhibitors. [ABSTRACT FROM AUTHOR]

Shikimate kinase (SK) is an essential enzyme in several pathogenic bacteria and does not have any counterpart in human cells, thus making it an attractive target for the development of new antibiotics. The key interactions of the substrate and product binding and the enzyme movements that are essential for catalytic turnover of the Mycobacterium tuberculosis shikimate kinase enzyme (Mt-SK) have been investigated by structural and computational studies. Based on these studies several substrate analogs were designed and assayed. The crystal structure of Mt-SK in complex with ADP and one of the most potent inhibitors has been solved at 2.15 Å. These studies reveal that the fixation of the diaxial conformation of the C4 and C5 hydroxyl groups recognized by the enzyme or the replacement of the C3 hydroxyl group in the natural substrate by an amino group is a promising strategy for inhibition because it causes a dramatic reduction of the flexibility of the LID and shikimic acid binding domains. Molecular dynamics simulation studies showed that the product is expelled from the active site by three arginines (Arg117, Arg136, and Arg58). This finding represents a previously unknown key role of these conserved residues. These studies highlight the key role of the shikimic acid binding domain in the catalysis and provide guidance for future inhibitor designs. [ABSTRACT FROM AUTHOR]

The paralogous lysine acetyltransferases 3 (KAT3), CBP and P300, play critical roles during neurodevelopment, but their specific roles in neural precursors maintenance and differentiation remain obscure. In fact, it is still unclear whether these proteins are individually or jointly essential in processes such as proliferation of neural precursors, differentiation to specific neural cell types, or both. Here, we use subventricular zone-derived neurospheres as a potential ex vivo developmental model to analyze the proliferation and differentiation of neural stem cells (NSCs) lacking CBP, p300, or both proteins. The results showed that CBP and p300 are not individually essential for maintenance and proliferation of NSCs, although their combined ablation seriously compromised cell division. In turn, the absence of either of the two proteins compromised the differentiation of NSC into the neuronal and astrocytic lineages. Single-nucleus RNA sequencing analysis of neural cell cultures derived from CBP or p300 mutant neurospheres revealed divergent trajectories of neural differentiation upon CBP or p300 ablation, confirming unique functions and nonredundant roles in neural development. These findings contribute to a better understanding of the shared and individual roles of KAT3 proteins in neural differentiation and the etiology of neurodevelopmental disorders caused by their deficiency. [ABSTRACT FROM AUTHOR]

The Tcra enhancer (E&agr;) is essential for pre-TCR-mediated activation of germline transcription and V(D)J recombination. E&agr; is considered an archetypical enhanceosome that acts through the functional synergy and cooperative binding of multiple transcription factors. Based on dimethylsulfate genomic footprinting experiments, there has been a long-standing paradox regarding E&agr; activation in the absence of differences in enhancer occupancy. Our data provide the molecular mechanism of E&agr; activation and an explanation of this paradox. We found that germline transcriptional activation of Tcra is dependent on constant phospholipase C&ggr;, as well as calcineurin- and MAPK/ERK-mediated signaling, indicating that inducible transcription factors are crucially involved. NFAT, AP-1, and early growth response factor 1, together with CREB-binding protein/p300 coactivators, bind to E&agr; as part of an active enhanceosome assembled during pre-TCR signaling. We favor a scenario in which the binding of lymphoid-restricted and constitutive transcription factors to E&agr; prior to its activation forms a regulatory scaffold to recruit factors induced by pre-TCR signaling. Thus, the combinatorial assembly of tissue- and signal-specific transcription factors dictates the E&agr; function. This mechanism for enhancer activation may represent a general paradigm in tissue-restricted and stimulus-responsive gene regulation. [ABSTRACT FROM AUTHOR]

V(D)J recombination is the assembly of gene segments at the antigen receptor loci to generate antigen receptor diversity in T and B lymphocytes. This process is regulated, according to defined developmental programs, by the action of a single specific recombinase complex formed by the recombination antigen gene (RAG-1/2) proteins that are expressed in immature lymphocytes. V(D)J recombination is strictly controlled by RAG-1/2 accessibility to specific recombination signal sequences in chromatin at several levels: cellular lineage, temporal regulation, gene segment order, and allelic exclusion. DNA cleavage by RAG-1/2 is regulated by the chromatin structure, transcriptional elongation, and three-dimensional architecture and position of the antigen receptor loci in the nucleus. Cis-elements specifically direct transcription and V(D)J recombination at these loci through interactions with transacting factors that form molecular machines that mediate a sequence of structural events. These events open chromatin to activate transcriptional elongation and to permit the access of RAG-1/2 to their recombination signal sequences to drive the juxtaposition of the V, D, and J segments and the recombination reaction itself. This chapter summarizes the advances in this area and the important role of the structure and position of antigen receptor loci within the nucleus to control this process. [ABSTRACT FROM AUTHOR]

What are the biomechanical implications in the dynamics and evolution of a growing solid tumor? Although the analysis of some of the biochemical aspects related to the signaling pathways involved in the spread of tumors has advanced notably in recent times, their feedback with the mechanical aspects is a crucial challenge for a global understanding of the problem. The aim of this paper is to try to illustrate the role and the interaction between some evolutionary processes (growth, pressure, homeostasis, elasticity, or dispersion by flux-saturated and porous media) that lead to collective cell dynamics and defines a propagation front that is in agreement with the experimental data. The treatment of these topics is approached mainly from the point of view of the modeling and the numerical approach of the resulting system of partial differential equations, which can be placed in the context of the Hele-Shaw-type models. This study proves that local growth terms related to homeostatic pressure give rise to retrograde diffusion phenomena, which compete against migration through flux-saturated dispersion terms. [ABSTRACT FROM AUTHOR]

There is a high prevalence for rhinitis with an increasing trend. However, there is a lack of specific quality of life pediatric questionnaires for sinonasal symptoms. The Sinus and Nasal Quality of Life Survey (SN-5) is the only validated instrument specifically designed with this objective. In this work we have translated and validated the Spanish version of the SN5 questionnaire. The SN5 was translated according to the World Health Organization recommendation for the translation and adaptation of instruments. The final version of the Sp-SN5 was administered twice (day 0 and day 7) to 137 participants with and without sinonasal symptoms. Reliability was measured with Cronbach α, temporal stability was measured with intraclass correlation coefficient. External validity was assessed with a ROC curve comparing a cohort of cases (children going to turbinate radiofrequency ablation) and controls (asymptomatic children). A Spearman correlation between the total result of the Sp-SN-5 questionnaire and the QOL score showed a strong negative correlation in the general sample and all the age subgroups. Internal consistency measured with Cronbach α was 0.87 for 5 items and was still over 0.83 after removing each item of the test. The intraclass correlation coefficient (ICC) for test-retest measurements was 0.94. The receiver operating characteristic (ROC) curve for all the included participants showed a very high area under the curve (0.998). The Sp–SN–5 questionnaire was successfully translated and cross-culturally adapted into Spanish, and the translated version exhibited adequate properties. The survey was effective in assessing the quality of life of pediatric patients with sinonasal complaints and can be used for this purpose both in a clinical setting and in future research. [ABSTRACT FROM AUTHOR]

Background: Probiotics are widely used in dogs but can be associated with alterations in some serum biochemistry test results. Objective: To assess the effect of Enterococcus faecium SF68 administration for 14 days on serum alanine transferase (ALT) and alkaline phosphatase (ALP) activity and total cholesterol and triglyceride concentrations in healthy dogs. Animals: Thirty‐six healthy privately owned neutered dogs were randomly allocated, stratified by sex, to control or probiotic groups. Dogs were clinically healthy, with normal physical examination findings, blood, urine, and fecal analyses and ultrasonographic examinations. Method: In this blinded, controlled study E. faecium SF68 was administered to the probiotic group for 14 days. Blood samples were taken from all dogs at days 0, 14, and 28. Serum ALT and ALP activity and total cholesterol and triglyceride concentrations were determined on these 3 days. Results: The probiotic induced no significant changes in mean ALT and ALP activity. Mean cholesterol concentration did not change during probiotic administration but a significant decrease was seen on day 28 (P < .01). Mean triglyceride concentration increased progressively, becoming significant at day 28 (P < .05), with 1 dog developing hypertriglyceridemia. Conclusions and Clinical Importance: E. faecium SF68 would not create confusion when monitoring dogs with hepatobiliary disease because ALT and ALP activity did not change significantly. A significant decrease in cholesterol and significant increase in triglyceride concentrations were seen at day 28 but were not clinically relevant, with 1 dog showing hypertriglyceridemia. A longer trial is warranted to assess if the probiotic effects could be clinically relevant and to assess its potential use in hypertriglyceridemic dogs. [ABSTRACT FROM AUTHOR]

Simple Summary: The temporomandibular joint (TMJ) of dogs is a bilateral joint mainly used for chewing, and subsequently, an area where pathologies are frequently seen. Computed tomography (CT) represents a very important imaging modality used to diagnose TMJ diseases in dogs. A three-dimensional representation of CT images created by a volume rendering method (3DVR) could improve our understanding of the alterations in this joint. In this study, we assessed 3DVR as an ancillary method for the description and diagnosis of TMJ pathologies in dogs. Based on computed tomography (CT) images, volume rendering was used to obtain a three-dimensional representation of data (3DVR). The aims of this study included: describing the bone anatomy of the temporomandibular joint (TMJ) of dogs; comparing the TMJs of each dog by skull type and age; comparing 3DVR images with three-standard-plane CTs; assessing soft tissues adjacent to the TMJ and assessing pathological cases. Multidetector computed tomography scans of bilateral TMJs of 410 dogs were observed. From a ventral view, slight displacements in the positions of the skulls were seen, whereas from a caudal view, differences in amplitude of the articular space were observed. Dolichocephalic and mesaticephalic dogs showed more similar TMJ features than brachycephalic dogs. The shape of the TMJ bones were irregular in dogs under 1 year old. The 3DVR images related to the three-standard-plane CT improved the overall comprehension of the changes in the articular space amplitude and condylar process morphology. The fovea pterygoidea, mandibular fossa and retroarticular process were perfectly shown. A better spatial situation of adjacent soft tissues was obtained. The 3DVR represents an ancillary method to the standard-plane CT that could help in the understanding of the anatomy and diagnoses of different pathologies of the TMJ in dogs. [ABSTRACT FROM AUTHOR]

Objective: Adenoid hypertrophy may coexist, and often does, with rhinitis. Therefore, in some cases, adenoidectomy alone, despite the fact that it reduces nasal resistance, may be insufficient to restore nasal breathing. Juliusson et al. suggested using rhinomanometry with and without nasal decongestant as a method for selecting patients for adenoidectomy. In this study, we aim to assess whether the decongestant test, when using normative data, is useful to select children for adenoidectomy. Methods: Children between 4 and 15 years old undergoing adenoidectomy were selected from two tertiary referral university hospitals. Participants underwent anterior active rhinomanometry with and without nasal decongestant before and after surgery. Parents fill in the sinus and nasal quality-of-life survey (SN5). Results: 47 participants were included, and mean age 6.5 ± 2.15. 2 cohorts were defined according to the result of the nasal decongestant test (> 40% improvement in nasal resistance or not). There is a statistically significant difference between groups, with a higher improvement in nasal resistance and airflow after adenoidectomy in the group with less than 40% improvement in nasal resistance. Conclusions: In conclusion, this study supports the use of the decongestant test with rhinomanometry to select children for adenoidectomy; especially as it has proven to be a simple technique, harmless, fast, and easily performed on collaborative children. [ABSTRACT FROM AUTHOR]

Environmental factors and life experiences impinge on brain circuits triggering adaptive changes. Epigenetic regulators contribute to this neuroadaptation by enhancing or suppressing specific gene programs. The paralogous transcriptional coactivators and lysine acetyltransferases CREB binding protein (CBP) and p300 are involved in brain plasticity and stimulus-dependent transcription, but their specific roles in neuroadaptation are not fully understood. Here we investigated the impact of eliminating either CBP or p300 in excitatory neurons of the adult forebrain of mice from both sexes using inducible and cell type-restricted knock-out strains. The elimination of CBP, but not p300, reduced the expression and chromatin acetylation of plasticity genes, dampened activity-driven transcription, and caused memory deficits. The defects became more prominent in elderly mice and in paradigms that involved enduring changes in transcription, such as kindling and environmental enrichment, in which CBP loss interfered with the establishment of activity-induced transcriptional and epigenetic changes in response to stimulus or experience. These findings further strengthen the link between CBP deficiency in excitatory neurons and etiopathology in the nervous system. [ABSTRACT FROM AUTHOR]

Objective--To compare the adrenocortical response of healthy dogs to a commonly used dose of a nonadsorbed tetracosactide product (tetracosactide) with responses to 2 doses of a depot formulation of tetracosactide (depot tetracosactide). Animals--14 dogs. Procedures--Dogs were randomly assigned to receive tetracosactide (5 mg/kg, IV) or depot tetracosactide (250 µg, IM, or 5 µg/kg, IM). Dogs received each treatment once with a 2-week interval between treatments. Blood samples were assayed for cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, and estradiol concentrations. Results--Serum cortisol concentrations were significantly higher than the preadministration (baseline) concentrations for all treatments 60 minutes after administration of ACTH. Peak cortisol concentration was detected 180 minutes after IM administration of 250 µg of the depot tetracosactide. Serum concentrations of progesterone, 17-hydroxyprogesterone, and androstenedione did not differ significantly from baseline concentrations after stimulation with the 5 µg/kg dose of depot tetracosactide. Adrenal gland progesterone response was significantly higher than baseline concentrations at 60 minutes after administration of the 250-µg dose of depot tetracosactide, and the 17-hydroxyprogesterone and androstenedione responses were significantly higher than baseline concentrations at 120 minutes. Compared with the response to tetracosactide, adrenocortical response was higher and more sustained following administration of the depot tetracosactide, except for androstenedione concentration, which had a nonsignificant response. Conclusions and Clinical Relevance--Except for androstenedione concentrations, a high dose of the depot tetracosactide (250 µg, IM) induced an adrenocortical response similar to that after administration of tetracosactide. Thus, depot tetracosactide may represent an alternative to the nonadsorbed tetracosactide product. [ABSTRACT FROM AUTHOR]

This paper aims to analyse the ductility of existing buildings to evaluate its influence in their seismic performance. This has been achieved through the retrospective analysis of an existing building in accordance with current seismic codes. This study has revealed the lack of guidance in the NCSE02 and the EC8 regarding the assessment of the ductility of existing buildings. This manuscript proposes a methodology to assess the ductility of Spanish existing buildings. For this purpose, this paper has implemented the American code procedure combined with the EC8 and the Spanish seismic code (NCSE02) requirements. A two-storey RC frame school located in the Spanish region of Huelva has been selected as a case study. Different versions of this school have been compared: as built, designed according to current best practice, EC8 provisions and NCSE02 provisions. To do so, different constructive features have been varied according to each of the ductility class requirements: geometrical properties and the reinforcement ratio of the structural elements. Nonlinear static analyses have been carried out to obtain the displacement ductility factor (μ) and the behaviour factor (q) of each model. Construction costs and the expected damage index have been determined and compared. Results have shown that the best performance, regarding the ductility and the costs, has been obtained with the models designed with deep beams. Conversely, models with wide beams, and where only the reinforcement ratios have been varied, have merely shown a slight enhancement of the resistant and ductile capacity. It has been concluded that the ductility affects the shear capacity, the seismic performance and the expected damage of RC buildings. [ABSTRACT FROM AUTHOR]

Background: Increased tissue stiffness is a common feature of malignant solid tumors, often associated with metastasis and poor patient outcomes. Vitronectin, as an extracellular matrix anchorage glycoprotein related to a stiff matrix, is present in a particularly increased quantity and specific distribution in high-risk neuroblastoma. Furthermore, as cells can sense and transform the proprieties of the extracellular matrix into chemical signals through mechanotransduction, genotypic changes related to stiffness are possible. Methods: We applied high density SNPa and NGS techniques to in vivo and in vitro models (orthotropic xenograft vitronectin knock-out mice and 3D bioprinted hydrogels with different stiffness) using two representative neuroblastoma cell lines (the MYCN-amplified SK-N-BE(2) and the ALK-mutated SH-SY5Y), to discern how tumor genomics patterns and clonal heterogeneity of the two cell lines are affected. Results: We describe a remarkable subclonal selection of genomic aberrations in SK-N-BE(2) cells grown in knock-out vitronectin xenograft mice that also emerged when cultured for long times in stiff hydrogels. In particular, we detected an enlarged subclonal cell population with chromosome 9 aberrations in both models. Similar abnormalities were found in human high-risk neuroblastoma with MYCN amplification. The genomics of the SH-SY5Y cell line remained stable when cultured in both models. Conclusions: Focus on heterogeneous intratumor segmental chromosome aberrations and mutations, as a mirror image of tumor microenvironment, is a vital area of future research. [ABSTRACT FROM AUTHOR]

Previous research has indicated that many European buildings are vulnerable to moderate-magnitude earthquakes. For example, during the L´Aquila (Italia, Mw 6.3, 2009) and Lorca (Spain, Mw 5.9, 2011) earthquakes, many old buildings were severely damaged and some of them collapsed. In specific, significant damage has been found in several school buildings after past earthquakes in Europe. This is due to the fact that many of them were constructed prior to the current seismic codes, thus considering only gravitational loads and with no seismic design whatsoever. Primary schools are even more vulnerable than other typologies because of their low adult/child ratio. The seismic activity of the Iberian Peninsula is low-moderate. However, the Algarve and Huelva regions, which are situated in the south-west, are influenced by large faults which have caused major earthquakes of long-return periods. The European project PERSISTAH (Projetos de Escolas Resilientes aos SISmos no Território do Algarve e de Huelva, in Portuguese) aims to cooperatively evaluate the seismic vulnerability of primary schools in the Algarve (Portugal) and Huelva (Spain) regions. The present work is framed under this project. The objective of this paper is to determine the most effective retrofitting scheme for a typical primary school building in this area, considering structural, architectural and constructive parameters. The scheme could be applied to several buildings of the same typology, decreasing costs and time. An existing reinforced concrete frame building has been selected for the study. This is one of the most commonly used typologies for primary schools in this area. A nonlinear static analysis has been carried out in order to study its seismic behaviour. The performance point of the building has been obtained through the capacity-demand spectrum method. The preliminary results have confirmed the poor seismic behaviour of this building. Specifically, soft-story behaviour has been identified in the ground floor and short columns have been observed in the upper floors. Therefore, specific seismic retrofitting solutions have been proposed and evaluated in order to identify the one that is the most efficient. The combination of reinforcements has been done considering the structural and architectural impact and constructive parameters. The calculations have shown that steel X-bracings are the best solution for preventing the formation of a soft-storey in the ground floor. Unfortunately, this scheme increases the deformation in the upper floor columns. The best solution for the upper floors' short columns has been the use of steel jackets. The results have also shown that this combination produces an important reduction of the expected general damage level. The resulting retrofitting scheme can be extrapolated to other buildings with a similar typology. [ABSTRACT FROM AUTHOR]

The effect of stacking on the near-infrared photoluminescence (NIR-PL) of InGaSb/GaSb quantum wells (QWs) which were inadvertently formed during an attempt to fabricate stacked InSb/GaSb quantum dots (QDs) using atmospheric pressure Metalorganic Vapor Phase Epitaxy (MOVPE) are investigated in this work. The morphology of uncapped dots was studied by means of scanning probe microscopy (SPM) which shows a significant deviation in the shape and density of dots grown directly on the buffer compared to those that terminated an “embedded-dot” sample. Cross-sectional scanning transmission electron microscopy (STEM) and transmission electron microscopy (TEM) of the capped structures clearly revealed the formation of QWs in the capped structures. An increase in the number of InSb QD-layers, which metamorphosed into QWs, was observed to cause an increase in the luminescence spectral line width and a long-wavelength shift of the QW PL lines, together with an enhancement in the strength of PL emission. Variations in layer thicknesses and alloy composition introduced as a result of inter-diffusion of Ga and In which is enhanced by the prolonged annealing time of the QDs (during spacer/cap layer deposition) and In adatom migration is suggested to alter the morphology of the capped dots and induce a change in PL peak positions and the spectral linewidth of the NIR low energy lines. [ABSTRACT FROM AUTHOR]

Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma. [ABSTRACT FROM AUTHOR]

Abstract: Botulinum neurotoxin A (BoNT/A) is the most potent toxin known. Unfortunately, it is also a potential bioweapon in terrorism, which is without an approved therapeutic treatment once cellular intoxication takes place. Previously, we reported how hydroxamic acid prodrug carbamates increased cellular uptake, which translated to successful inhibition of this neurotoxin. Building upon this research, we detail BoNT/A protease molecular modeling studies accompanied by the construction of small library of hydroxamic acids based on 2,4-dichlorocinnamic hydroxamic acid scaffold and their carbamate prodrug derivatization along with the evaluation of these molecules in both enzymatic and cellular models. [Copyright &y& Elsevier]

Background Insect bite hypersensitivity ( IBH) is a common cause of pruritus in horses, but there are few controlled studies on the efficacy of allergen-specific immunotherapy ( ASIT). Atopic dermatitis and IBH can present with overlapping clinical signs; multiple insect and environmental allergens could be indicated in these horses to achieve effective hyposensitization. Although the success of ASIT using Culicoides spp. whole-body extracts is controversial, there are no controlled studies published that clearly show benefit from this form of therapy. Hypothesis/Objectives The objective was to evaluate the efficacy of ASIT in horses with IBH using commercially available extracts and tests. Animals Twenty horses with seasonal pruritus and positive intradermal reactions to a whole Culicoides extract. Methods An enzyme-linked immunosorbent assay test (Allercept®) was used to detect concurrent allergen-specific Ig E for other insects and environmental allergens. The ASIT was formulated by adding the relevant serologically positive allergens to the Culicoides extract. After randomization, 10 horses received ASIT and the rest a placebo solution. Clinical response was assessed every 4 months during 1 year using a clinical scoring system based on the severity of four clinical signs at 10 different body regions. Horses were not stabled and, to minimize dropouts, an insect repellent was used weekly in both groups. Results Differences in clinical scores between groups were nonsignificant at any re-evaluation, while both groups improved to a similar extent, probably due to the insecticide treatment. Conclusions and clinical importance Using commercially available extracts and tests, we could not demonstrate a beneficial effect of 1 year multiple ASIT in nonstabled horses with IBH. [ABSTRACT FROM AUTHOR]

The most important aetiological agent of opportunistic mycoses worldwide is Candida spp. These yeasts can cause severe infections in the host, which may be fatal. Isolates of Candida albicans occur with greater frequency and variable resistance patterns. Photodynamic therapy (PDT) has been recognised as an alternative treatment to kill pathogenic microorganisms. PDT utilises a photosensitizer, which is activated at a specific wavelength and oxygen concentration. Their reaction yields reactive oxygen species that kill the infectious microorganism. A systematic review of new applications of PDT in the management of candidiasis was performed. Of the 222 studies selected for in-depth screening, 84 were included in this study. All the studies reported the antifungal effectiveness, toxicity and dosimetry of treatment with antimicrobial PDT (aPDT) with different photosensitizers against Candida spp. The manuscripts that are discussed reveal the breadth of the new applications of aPDT against Candida spp., which are resistant to common antifungals. aPDT has superior performance compared to conventional antifungal therapies. With further studies, aPDT should prove valuable in daily clinical practice. [ABSTRACT FROM AUTHOR]

adenoidectomy is one of the most common surgical procedure in pediatric otolaryngology practice. Clinical guidelines (such as the Spanish or American) suggest adenoidectomy when the enlargement of the adenoids is associated with nasal obstruction. Nasal endoscopy and cephalograms are adequate methods to estimate the size of the adenoids. However, they do not measure nasal patency. This systematic review is designed with the objective of exploring the relationship between adenoid size and nasal ventilation through rhinomanometry. 3 authors members of the YO-IFOS rhinology study group independently analyzed the data sources (Pubmed, the Cochrane Library, EMBASE, SciELO) for papers assessing both nasal resistance and/or nasal airflow in rhinomanometry and adenoid size by any method (endoscopy, cephalogram, direct examination). A total of 10 studies with a total population of 969 participants met the inclusion criteria. 5 authors explored the size of the adenoids through endoscopy. 4 authors explored the adenoids through lateral cephalograms. Finally, a further 2 authors explored adenoid size studying the resected tissue. Five studies explored the correlation between adenoid size and nasal resistance in rhinomanometry, which ranged from 0.20 to 0.84. Finally, 5 studies used nasal decongestant. It was found higher sensitivity and specificity, a higher area under the curve for the receiver operating characteristic curve, and higher correlation with adenoid size for rhinomanometry under nasal decongestion. Up to now, there is no ideal diagnostic method for adenoid hypertrophy. Therefore, it seems prudent to use a combination of all currently available tools, as they provide complementary, rather than supplementary information. Available evidence suggests that rhinomanometry combined with nasal decongestant could help to elucidate the existence of nasal obstruction in intermediate cases of adenoid hypertrophy, as well as throw light on other possible causes for nasal obstruction, mainly turbinate hypertrophy. [ABSTRACT FROM AUTHOR]