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Mycobacterium leprae, the pathogen that causes human leprosy, has a unique affinity for infecting and persisting inside Schwann cells, the principal glia of the peripheral nervous system. Several studies have focused on this intricate host-pathogen interaction as an attempt to advance the current knowledge of the mechanisms governing nerve destruction and disease progression. However, during the chronic course of leprosy neuropathy, Schwann cells can respond to and internalize both live and dead M. leprae and bacilli-derived antigens, and this may result in divergent cellular pathobiological responses. This may also distinctly contribute to tissue degeneration, failure to repair, inflammatory reactions, and nerve fibrosis, hallmarks of the disease. Therefore, the present study systematically searched for published studies on M. leprae-Schwann cell interaction in vitro to summarize the findings and provide a focused discussion of Schwann cell dynamics following challenge with leprosy bacilli.

RESUMO: O objetivo deste estudo foi identificar a compreensão das pessoas com deficiência intelectual sobre o ambiente de trabalho. A pesquisa foi realizada na perspectiva da psicologia histórico-cultural, em uma metodologia qualitativa, com participação de quatro pessoas com deficiência intelectual, maiores de 18 anos, por meio de entrevistas semiestruturadas de perspectiva narrativa. Os resultados indicaram que o conceito complexo Inclusão no Mercado de Trabalho foi formado por sete temas iniciais (sentido do trabalho; relações interpessoais; facilidades no trabalho; dificuldades no trabalho; autopercepção – significado da deficiência intelectual; percepção do outro em relação à pessoa com deficiência intelectual; e perspectivas laborais), que, por sua vez, foram organizados em cinco temas complexos (sentido do trabalho, relações interpessoais, políticas públicas, barreiras atitudinais e perspectivas laborais). A análise da formação conceitual indica que as narrativas apresentaram diversas conotações sobre a inclusão no ambiente de trabalho, sendo um importante espaço de desenvolvimento humano. Concluiu-se que a implementação de estudos com vistas à compreensão da inclusão no mercado de trabalho torna-se relevante para a compreensão do desenvolvimento humano e para a implementação e o planejamento de políticas públicas de inclusão.

Abstract To gain insight on dystrophin (DMD) gene transcription dynamics and spatial localization, we assayed the DMD mRNA amount and defined its compartmentalization in myoblasts, myotubes, and skeletal muscle biopsies of Duchenne muscular dystrophy (DMD) patients. Using droplet digital PCR, Real-time PCR, and RNAscope in situ hybridization, we showed that the DMD transcript amount is extremely reduced in both DMD patients’ cells and muscle biopsies and that mutation-related differences occur. We also found that, compared to controls, DMD transcript is dramatically reduced in the cytoplasm, as up to 90% of it is localized in nuclei, preferentially at the perinuclear region. Using RNA/protein colocalization experiments, we showed that about 40% of nuclear DMD mRNA is localized in the nucleoli in both control and DMD myogenic cells. Our results clearly show that mutant DMD mRNA quantity is strongly reduced in the patients’ myogenic cells and muscle biopsies. Furthermore, mutant DMD mRNA compartmentalization is spatially unbalanced due to a shift in its localization towards the nuclei. This abnormal transcript repartition contributes to the poor abundance and availability of the dystrophin messenger in cytoplasm. This novel finding also has important repercussions for RNA-targeted therapies.

Abstract This paper examines the triadic dynamics of baby-teacher-book during shared reading in an Early Childhood Education School to explain how educational teaching practices can enhance initial reading experiences and development processes in Early Childhood. A ten-months-old baby and a teacher participated in this study and, as an instrument for data collection, reading situations were registered and later these sessions were weighted through use of microgenetic analysis. From the analysis of the data present in the detailed case, it was identified the emergence of qualitative indicators that favoured the involvement of the baby in the activity, the mediation and educational actions of the teacher and the use of the book were more frequent. The effective use of the object book with that baby has contributed to qualitative changes in the baby’s development and learning and emphasizes the incentive to share reading with other children.

ABSTRACT Aeromonas spp. are emerging human pathogens causing intestinal and extra-intestinal infections. Since their relevance in Western Europe as gastrointestinal pathogens is not well established, we investigated Aeromonas spp. prevalence in diarrheal fecal samples in an Italian University Hospital and characterized the virulence mechanisms of the isolates. Aeromonas spp. isolated from diarrheic stools using standard culture methods were identified by molecular techniques. Antimicrobial resistance was assessed by the micro broth dilution. Toxins, flagella, and type III secretion system genes were evaluated by polymerase chain reaction. Biofilm was quantified by crystal-violet staining. Interaction with human intestinal epithelial cells (Caco-2) was assessed by quantifying adhesion, interleukin (IL)-8 secretion, and epithelial barrier integrity. Aeromonas spp. represented 20.6% of bacterial pathogens isolated from diarrheic feces, the second most common enteropathogen. A. cavieae constituted 75% of the identified species, showing a relatively low clustering value. About 52% of Aeromonas isolates showed resistance to amikacin, whereas only 7.5% showed multiple drug resistance. Four or more virulence genes were identified in 66.7% of A. cavieae isolates and 100% of A. dakensis. Aeromonas isolates (82.5%) showed moderate or important biofilm-producing ability. Adhesion to Caco-2 cells correlated to fla+ gene, whereas ascV+ and aexU+ strains significantly induced IL-8 release from Caco-2. Aeromonas aer+ strains caused ZO1 and occluding redistribution and a significative reduction in trans-epithelial resistance. Aeromonas spp. emerge as relevant human intestinal pathogens with a disparate arsenal of pathogenicity factors causing diarrhea through different mechanisms. IMPORTANCE In this work, we demonstrate the epidemiologic relevance of the Aeromonas genus as the cause of infective diarrhea in North East Italy, both in children and adult subjects, with the significative presence of highly pathogenic strains. Aeromonas strains possess a heterogeneous armamentarium of pathogenicity factors that allows the microbe to affect a wide range of human intestinal epithelial cell processes that justify the ability to induce diarrhea through different mechanisms and cause diseases of variable severity, as observed for other gastrointestinal pathogens. However, it remains to be determined whether specific genotype(s) are associated with clinical pictures of different severity to implement the diagnostic and therapeutic approaches for this relevant enteric pathogen.

BackgroundLimited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m2] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS.MethodsIn this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012-2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015-2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring.ResultsThe standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m2), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m2). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13-0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74).ConclusionIndividualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.

Peripheral neuropathy is the main cause of physical disability in leprosy patients. Importantly, the extension and pattern of peripheral damage has been linked to how the host cell will respond against Mycobacterium leprae (M. leprae) infection, in particular, how the pathogen will establish infection in Schwann cells. Interestingly, viable and dead M. leprae have been linked to neuropathology of leprosy by distinct mechanisms. While viable M. leprae promotes transcriptional modifications that allow the bacteria to survive through the use of the host cell's internal machinery and the subvert of host metabolites, components of the dead bacteria are associated with the generation of a harmful nerve microenvironment. Therefore, understanding the pathognomonic characteristics mediated by viable and dead M. leprae are essential for elucidating leprosy disease and its associated reactional episodes. Moreover, the impact of the viable and dead bacteria in Schwann cells is largely unknown and their gene signature profiling has, as yet, been poorly explored. In this study, we analyzed the early differences in the expression profile of genes involved in peripheral neuropathy, dedifferentiation and plasticity, neural regeneration, and inflammation in human Schwann cells challenged with viable and dead M. leprae. We substantiated our findings by analyzing this genetic profiling in human nerve biopsies of leprosy and non-leprosy patients, with accompanied histopathological analysis. We observed that viable and dead bacteria distinctly modulate Schwann cell genes, with emphasis to viable bacilli upregulating transcripts related to glial cell plasticity, dedifferentiation and anti-inflammatory profile, while dead bacteria affected genes involved in neuropathy and pro-inflammatory response. In addition, dead bacteria also upregulated genes associated with nerve support, which expression profile was similar to those obtained from leprosy nerve biopsies. These findings suggest that early exposure to viable and dead bacteria may provoke Schwann cells to behave differentially, with far-reaching implications for the ongoing neuropathy seen in leprosy patients, where a mixture of active and non-active bacteria are found in the nerve microenvironment.

Abstract Background Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m2] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS. Methods In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012–2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015–2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring. Results The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m2), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m2). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13–0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74). Conclusion Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.

Este estudo se propõe a analisar as interações triádicas estabelecidas na Educação Precoce, de maneira a compreender os processos semióticos do bebê pré-verbal e o papel educativo de professores nesse contexto. O referencial teórico adotado é a perspectiva pragmática do objeto, que coloca que, para a compreensão do desenvolvimento do pensamento do bebê que ainda não fala, é necessário se trazer à luz a materialidade e o uso cultural de objetos nas interações bebê-adulto-objeto. Nesse sentido, foi realizada uma pesquisa empírica qualitativa com um bebê do sexo feminino, com histórico de prematuridade de 12 meses de idade cronológica, atendido na Educação Precoce, e sua professora. Os dados foram levantados com a ajuda de videogravação de uma sessão de atendimento da professora a esse bebê, com o uso de três objetos específicos. Estes dados foram analisados microgeneticamente, de modo que puderam ser observados os mediadores semióticos e os usos dos objetos empregados pela professora e pelo bebê no compartilhamento dos significados culturais subjacentes a estes sistemas. Os resultados indicam que a Educação Precoce tem um papel importante na construção dos primeiros sistemas semióticos de bebês pré-verbais, e, portanto, no processo de construção do seu pensamento, visto que é um espaço de interações triádicas intencionais, planejadas e consistentes. As práticas educativas contribuem significativamente para o ingresso de bebês na cultura e no mundo de significados, onde o professor atua como parceiro e guia.

Three specimens of Ammonites have been newly found in the Calcari Grigi Fm. (Lower and Middle Liassic). At present the total amount of known Ammonite specimens in the western part of the Venetian Liassic Carbonate Platform is at least of six. The occurrence of Ammonites ln an unfavourable environment suggests a post—mortem transport from the adjacent Lombardian Basin.

In the Recoaro area (Northern Italy) a channelized breccia containing abundant metamorphic clasts of the crystalline basement is interbedded in the Iower part of the Dolomia Principale formation (Upper Triassic) The breccia is interpreted as a fluvial deposit, which momentarily interrupted the cyclic sedimentation of the Dolomia Principale. This event is connected with a local tectonic phase The instability rnay be related to a more important tectonic activity which involved a region located South of the Recoaro area.

A slab with the tetrapod footprints Rhynchosauroides cf. schochardti (R. von Lilienstern, 1939) is described from the Werfen Fm. of Recoaro area (Vicentinian Alps). The slab is coming from red siltitic facies of the "Monte Naro Breccias" (Upper Scythian — Lower Anisian ? sedimentary cicles).

Dinosaurs originated ~245 million years ago (mya) but did not diversify until some time in the Late Triassic. Here, Bernardi and colleagues synthesize palaeontological and dated stratigraphic evidence to show that dinosaur diversification followed the Carnian Pluvial Episode 234–232 mya.

Like the seasons of the year, all natural things happen in stages, going through adaptations when challenged, and Schwann cells are a great example of that. During maturation, these cells regulate several steps in peripheral nervous system development. The Spring of the cell means the rise and bloom through organized stages defined by time-dependent regulation of factors and microenvironmental influences. Once matured, the Summer of the cell begins: a high energy stage focused on maintaining adult homeostasis. The Schwann cell provides many neuron-glia communications resulting in the maintenance of synapses. In the peripheral nervous system, Schwann cells are pivotal after injuries, balancing degeneration and regeneration, similarly to when Autumn comes. Their ability to acquire a repair phenotype brings the potential to reconnect axons to targets and regain function. Finally, Schwann cells age, not only by growing old, but also by imposed environmental cues, like loss of function induced by pathologies. The Winter of the cell presents as reduced activity, especially regarding their role in repair; this reflects on the regenerative potential of older/less healthy individuals. This review gathers essential information about Schwann cells in different stages, summarizing important participation of this intriguing cell in many functions throughout its lifetime.

After new studies were carried out in the Lopingian Val Gardena Sandstone of northern Italy, in the Recoaro area (Venetian Prealps, NE Italy), the following tetrapod ichnotaxa are identified: cf. Capitosauroides isp., cf. Merifontichnus isp., Pachypes isp., Paradoxichnium isp., and Rynchosauroides isp., probably corresponding to ?parareptile, captorhinid eureptile, pareiasaurid parareptile, archosauromorph neodiapsid, and lacertoid neodiapsid trackmakers, respectively. An undetermined track shows features consistent with possible therapsid producers. These are the first possible records of Merifontichnus and Capitosauroides in the Lopingian (late Permian) and one of the few records of Paradoxichnium worldwide. The paleoecology of the ichnoassociation highlights a relatively high diversity in the floodplain lithofacies, a monospecific association of Rhynchosauroides in distal floodplain/sabkha environments and the occurrence of Paradoxichnium isp. and cf. Capitosauroides only in the lagoon lithofacies, suggesting different habits of the trackmakers. The tetrapod ichnoassociation is characterized by eureptile and parareptile tracks, and differs from the classic Lopingian tetrapod ichnoassociation of the Dolomites mainly because of the absence of chirotheriid and small parareptile ichnotaxa. A comparison of the Italian tetrapod ichnoassociation with other Lopingian non-eolian ichnofaunas suggests a possible preference for marginal marine settings by the archosauromorph and therapsid trackmakers at low-latitudes of Pangaea.

After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD), an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs) after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18) treated with an exogenous calpain inhibitor (20 mM) administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P

Traumatic injury to the central nervous system (CNS) or the peripheral nervous system (PNS) triggers a cascade of events which culminate in a robust inflammatory reaction. The role played by inflammation in the course of degeneration and regeneration is not completely elucidated. While, in peripheral nerves, the inflammatory response is assumed to be essential for normal progression of Wallerian degeneration and regeneration, CNS trauma inflammation is often associated with poor recovery. In this review, we discuss key mechanisms that trigger the inflammatory reaction after nervous system trauma, emphasizing how inflammations in both CNS and PNS differ from each other, in terms of magnitude, cell types involved, and effector molecules. Knowledge of the precise mechanisms that elicit and maintain inflammation after CNS and PNS tissue trauma and their effect on axon degeneration and regeneration is crucial for the identification of possible pharmacological drugs that can positively affect the tissue regenerative capacity.

Absorption and distribution of polyunsaturated fatty acids was investigated in rats receiving lysophospholipids per os (30 mg kg-1). Lysophosphatidylcholine (lysoPC) increased [3H]arachidonate absorption and its incorporation into mucosal phosphatidylcholine. Transport of [3H]arachidonate by the phospholipid fraction of lymph lipoproteins and the level of [3H]arachidonate in plasma and liver lipids was also increased by lyso PC. Lysophosphatidylserine also increased [3H]arachidonate absorption but channeled the fatty acids into the aminophospholipid fraction of mucosal phospholipids, thus decreasing its efflux in lymph lipoproteins. As a consequence, lysophosphatidylserine caused [3H]arachidonate accumulation in mucosa. As similar results were obtained with [14C]linoleate, the data suggest that the addition of an appropriate lysophospholipid to the diet may direct absorption and distribution of polyunsaturated fatty acids.

The ammonoid fauna of the Prati di Stuores/Stuores Wiesen section (Dolomites, north-eastern Italy) was studied in detail. This section was proposed as stratotype for the Carnian GSSP, with the first appearance of Daxatina cf. canadensis as primary marker, based on preliminary data. The validity of this proposal is confirmed by the present study, which integrates collections from the Prati di Stuores/Stuores Wiesen section and from others, particularly Bec de Roces (Passo Campolongo) and Antersass (Badia Valley). Ammonoids collected in these localities belong to three biostratigraphic units: regoledanus, canadensis and aon subzones. These subzones constitute, in the Southern Alps, the Ladinian/Carnian boundary interval. Regoledanus Subzone: the north American species Zestoceras enode is most probably documented in this biostratigraphic interval. Canadensis Subzone: the base is marked by the first appearance of Daxatina canadensis, and at least, another north American species, Daxatina laubei, seems to be present. Two species of Zestoceras were found: Z. barwicki e Z. lorigae sp.n. Two species of Trachyceras, distinct from T. aon, are represented in the canadensis Subzone: T. muensteri and T. bipunctatum. These species predate the first appearance of Trachyceras, justifying the canadensis Subzone to be included in the Carnian also on the basis of nomenclatural stability. Other significant taxa of this subzone are Rossiceras? armatum and Sirenotrachyceras thusneldae. Aon Subzone: the ammonoid fauna of this subzone is extensively treated in existing literature and thus not further discussed. Taxonomical notes and stratigraphic consequences: the new subfamily Anolcitinae (family Trachyceratidae) is erected. At present, Frankites regoledanus, F. apertus and F. sp. A have been recognized in the Southern Alps. The lectotype of Ammonites (Trachyceras ?) Regoledanus was defined. The latter species is exclusive of the regoledanus Subzone, whereas the distribution of the two other species encompasses the defined GSSP. The shell morphology of F. apertus and the north American species F. sutherlandi is identical. The suture line is also comparable, hence the two species are considered synonyms. This synonymy is relevant for long-distance correlations. The lectotypes of Trachyceras ruturanum and T. laricum were also defined.

A refined ammonoid biostratigraphy is reported for a critical interrval of the Bagolino section (Giudicarie Area, Northern Iraly), a candidate for the Anisian/Ladinian stage boundary. The Avisianum Subzone has been documented, and its boundary with the Crassus Subzone has been redefined, on the basis of new findings of Reitziites reitzi, Aplococeras aff. smithi, Aplococeras avisianum, Halilucites rusticus, Parasturia sp. and other significant ammonoids. Six potential criteria for the definition of the Anisian/Ladinian boundary can now be considered in this single stratigraphic section, so that the FO of Eoprotrachyceras curionii is no longer the unescapable choice at Bagolino. Despite several drawbacks, including the absence of palynomorphs and daonellid bivalves, the thermal history preventing the recovery of magnetic and isotopic signals, and a lower sedimentation rate with respect to many other sections of the Southern Alps, the Bagolino section is here accepted as stratotype for the Anisian/Ladinian boundary, but further paleontological and sedimentological studies should be considered.

The Prati di Stuores/Stuores Wiesen section (Dolomites, Italy) is proposed as a candidate Global Stratotype Section and Point for the base of the Carnian Stage. In addition to being a famous, richly fossiliferous locality, it includes the type-section of the Cordevolian substage. The section is located near Pralongià, along the southern slope of the crest separating the Badia/Abtei and Cordevole valleys. Below the levels with Trachyceras aon, the section contains a rich ammonoid fauna that chacterizes the lower part of the Regoledanus Subzone and subsequently records the first appearances of the mid-high latitude genus Daxatina (Daxatina sp., D. cf. canadensis) and of traditional Trachyceras with species different from T. aon. Moreover, the Daxatina cf. canadensis Subzone is recognised above the Regoledanus Subzone. Very rare conodonts of the Budurovignatus group and species of Gladigondolella from the diebeli Assemblage Zone occur. Gondolella polygnatyformis, already known from the Aon Subzone, is absent. Palynomorphs, foraminifers, gastropods, bivalves, brachiopods, microcrinoids and holothurian sclerites were studied. Variations in frequency and taxonomic diversity of these faunas suggest anaerobic-disaerobic bottom conditions for the lower-middle part of the section (0-105 m), followed by a more stable oxygen content in the upper portion. Magnetostratigraphy showed four intervals with normal polarity and three intervals with reversed polarity. The Daxatina cf. canadensis Subzone falls close to the normal polarity interval S2n. The present study proposes the FAD of the cosmopolitan genus Daxatina as a marker of the base of the Carnian Stage, placing it at a lower stratigraphic level than previously indicated in the Stuores area. The Prati di Stuores section is proposed as GSSP of the Ladinian-Carnian boundary.

A redução dos gastos com insumos através da determinação do fornecedor/matéria-prima de mais baixo custo.