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Introduction: Avulsion fractures are common in skeletally immature athletes and occur more often in the proximal femur and in the iliac bone. An avulsion fracture of the lesser trochanter is a rare pathology, and it results from a sudden and violent muscle contraction of the iliopsoas muscle during sports practice. Radiography is important for the diagnosis and exclusion of other pathologies. In most cases, symptomatic treatment is recommended, and surgery is reserved for specific situations. Case report: We report a clinical case of an adolescent with groin and right thigh pain and impaired gait after kicking a ball during a football match. Discussion: The patient underwent a radiographic study, and an avulsion fracture of the lesser trochanter was diagnosed. He was successfully treated with a conservative approach and no sequelae were documented.

The aim of this study was to assess the effects of an intervention in the light of the Bobath concept on motor function, in children with cerebral palsy. This is a systematic literature review that includes nine studies published between 2014 and 2019, and those were researched in three distinct databases: B-On; PubMed; ScienceDirect. The nine studies contemplated are indicative of the positive effects of the Bobath concept on the motor function of children with cerebral palsy, as well as on visual attention, contributing to the improvement and increase in the quality of life and independence in the daily living activities of these children. We concluded that the Bobath concept should integrate the physical therapy intervention which aims to improve the motor function of children with cerebral palsy. However, it is necessary to mention the need to carry out more studies that focus not only on the concept of Bobath, but also on the effects produced in motor function in this specific population.

Serine tRNAs (tRNASer) are frequently overexpressed in tumors and associated with poor prognosis and increased risk of recurrence in breast cancer. Impairment of tRNA biogenesis and abundance also impacts proteome homeostasis, and activates protein quality control systems. Herein, we aimed at testing whether increasing tRNASer abundance could foster tumor establishment through activation of the UPR. In order to do so, firstly we confirmed that the expression of tRNA-Ser-AGA-2-1 [hereafter tRNASer(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNASer(AGA) in early stage tumorigenesis, we induced its upregulation in a non-tumoral bronchial cell line, BEAS-2B. Upregulation of this tRNA increased cellular proliferation and protein synthesis rate, driven by eIF2α dephosphorylation and ATF4 activation downstream of PERK signaling. Futhermore, tRNASer(AGA) enhanced transformation potential in vitro, and promoted the establishment of slow growing tumors with aggressive features in nude mice. Our work highlights the importance of studying tRNA deregulation on early stage tumorigenesis, as they may be potential malignancy and aggressiveness biomarkers.

O insucesso e o abandono escolar evidenciam-se como problemas sociais prioritários que não se devem apenas a fatores individuais ou familiares. O projeto PertenSer foi concebido como uma resposta educativa de base comunitária com o objetivo de oferecer aos jovens mais vulneráveis oportunidades de desenvolvimento de competências pessoais, sociais e profissionais, reforçando a sua motivação para a aprendizagem e a sua confiança e capacidade para construírem trajetos de vida. Participaram neste projeto 13 jovens dos 14 aos 18 anos, a frequentar o 8.º e o 9.º anos de escolaridade, enquadrados no Programa Integrado de Educação e Formação. A avaliação qualitativa do projeto considerou o envolvimento dos participantes nas ações implementadas e as mudanças no autoconceito e desenvolvimento pessoal e social, no envolvimento escolar e nas perspetivas de futuro. Os resultados destacam melhorias ao nível da autoconfiança e comportamento na escola, assim como na relação com os adultos e na capacidade de definir objetivos a curto e médio prazo. Destacam ainda a promoção da valorização e da motivação para a aprendizagem escolar, que contribuiu para a redução do abandono escolar e para a obtenção de maior sucesso. Como fatores de sucesso do projeto, realçam-se a abordagem comunitária envolvendo diferentes atores extraescolares e as relações de suporte estabelecidas com profissionais e professores.

Transitions between epithelial and mesenchymal cellular states (EMT/MET) contribute to cancer progression. We hypothesize that EMT followed by MET promotes cell population heterogeneity, favouring tumour growth. We developed an EMT model by on and off exposure of epithelial EpH4 cells (E-cells) to TGFβ1 that mimics phenotypic EMT (M-cells) and MET. We aimed at understanding whether phenotypic MET is accompanied by molecular and functional reversion back to epithelia by using RNA sequencing, immunofluorescence (IF), proliferation, wound healing, focus formation and mamosphere formation assays as well as cell xenografts in nude mice. Phenotypic reverted epithelial cells (RE-cells) obtained after MET induction presented epithelial morphologies and proliferation rates resembling E cells. However, the RE transcriptomic profile and IF staining of epithelial and mesenchymal markers revealed a uniquely heterogeneous mixture of cell subpopulations with a high self-renewal ability. RE cell heterogeneity was stably maintained for long periods after TGFβ1 removal both in vitro and in large tumours derived from the nude mice. Overall, we show that phenotypic reverted epithelial cells (RE cells) do not return to the molecular and functional epithelial state and present mesenchymal features related to aggressiveness and cellular heterogeneity that favour tumour growth in vivo. This work strengthens epithelial cell reprogramming and cellular heterogeneity fostered by inflammatory cues as a tumour growth-promoting factor in vivo.

Abstract Background The supracondylar fracture of the humerus is one of the most common fractures in pediatric age. Many classifications were proposed, with Gartland being the most widely used one and Lagrange and Rigault (L&R) the most used in French-speaking countries. Objectives The goal of this study was to compare the Wilkins-modified Gartland classification with the L&R classification in terms of reproducibility. Methods Three observers with similar training levels classified 35 fractures according to both classifications twice to evaluate both intra and interobserver variation. Results The mean intraobserver variation was 0.78 and 0.77 for Gartland and L&R classifications, respectively, and the mean interobserver variation was 0.55 and 0.62 for Gartland and L&R classifications, respectively. Conclusions Both classifications reveal adequate to usage in clinical and investigational practices, which is consistent with the literature.

Las fracturas por estrés afectan, con mayor frecuencia, a personas físicamente activas con hueso normal y son infrecuentes en los niños con placa de crecimiento abierta. Aun más infrecuentes son las fracturas por estrés del cuello femoral en la población pediátrica. Sin embargo, constituyen entidades muy importantes debido al riesgo de complicaciones graves, como la necrosis avascular. Se describe el caso de una niña de 7 años medicada con metilfenidato que sufrió una fractura por estrés del cuello del fémur atípica. La paciente consulta por dolor inguinal derecho sin limitaciones en las actividades cotidianas. La radiografía muestra una fractura por estrés del cuello del fémur, que se confirma con tomografía. Se instaura un tratamiento conservador, y la paciente está asintomática a las cuatro semanas. Este caso representa una alerta sobre esta infrecuente entidad en la que podrían presentarse errores diagnósticos. Investigaciones recientes también sugieren la posible participación de fármacos, como el metilfenidato, en la desmineralización ósea, que podría constituir un posible factor de riesgo de fractura. Abstract Stress fractures most commonly affect physically active individuals with normal bone, and they are rare in children with open growth plates. Even rarer are femoral neck stress fractures in pediatric age. Nevertheless, they constitute a very important entity due to the risk of severe complications, such as avascular necrosis. A seven-year-old girl, treated with methylphenidate, who suffered an atypical femoral neck stress fracture is presented. Patient complained of right inguinal pain without daily life activity limitations. The radiograph showed a stress femoral neck fracture, confirmed by CT imaging. Conservative treatment was instituted and the patient became asymptomatic after 4 weeks. This case report alerts the clinicians about this rare entity that might be misdiagnosed. Recent research also suggests a possible involvement of drugs, such as methylphenidate, in bone demineralization, which might constitute a possible risk factor for fractures.

As infeções do trato urinário associadas à cateterização são muito frequentes no contexto comunitário e hospitalar. Existem atualmente várias recomendações para sua prevenção, contudo, quando abordado o soluto a utilizar no meato urinário previamente à algaliação continuam a persistir dúvidas. Assim, este estudo procurou determinar a eficácia da limpeza do meato urinário com água ou soro fisiológico comparativamente à sua assepsia por meio de uma revisão sistemática com metanálise. Para isso foram seguidos os princípios propostos pelo Cochrane Handbook , a análise crítica realizada por dois investigadores e a análise estatística com recurso ao programa STATA 11.1. Podemos concluir que a limpeza ou desinfeção do meato urinário previamente à cateterização vesical não é estatisticamente significativa (OR=1,07, IC 95%=0,68-1,68, p=0,779), existindo alguma evidência de que a utilização de água/soro fisiológico reduz as taxas de ITU.

We report the case of a 50-year-old woman with systemic lupus erythematosus who had previously undergone pacemaker implantation. She developed recurrent pulmonary thromboembolism and was diagnosed with antiphospholipid syndrome. During investigation, pacemaker endocarditis was discovered, and the system was surgically explanted. Surprisingly, all microbiological studies, including culture of the extracted material and extensive serological analysis, were negative and she remained well with anticoagulation plus her usual immunosuppressant regimen.The data indicate that her pacemaker endocarditis could be an equivalent of the nonbacterial thrombotic endocarditis often described in native valves. Resumo: Descreve-se o caso de uma doente de 50 anos com lúpus eritematoso sistémico e história prévia de implantação de pacemaker. Esta desenvolveu tromboembolismo pulmonar recorrente, tendo-lhe sido diagnosticada síndrome antifosfolipídica. Durante a investigação foi descoberta uma endocardite de pacemaker, tendo sido sujeita a extracção cirúrgica do sistema. Inesperadamente, todos os exames microbiológicos, incluindo culturas do material removido, e extensa análise serológica, foram negativos, tendo a doente se mantido clinicamente estável com anticoagulação oral e o habitual regime imunossupressor.Os dados indicam que a esta endocardite de pacemaker poderá ser um equivalente da endocardite trombótica não bacteriana, habitualmente descrita em válvulas nativas. Keywords: Pacemaker, Endocarditis, Antiphospholipid syndrome, Palavras-chave: Pacemaker, Endocardite, Síndrome antifosfolipídica

Invasive pneumococcal disease predominantly affects younger children, elderly, and immunocompromised patients. Pneumococcal meningitis is a particularly important form of presentation, considering its high rate of morbimortality. We present the case of a previously healthy 12-year-old adolescent male who was hospitalized due to suspicion of osteoarticular infection in his left foot. A few hours later, he developed meningeal signs, exhibiting slight pleocytosis and Streptococcus pneumoniae isolates in both cerebrospinal fluid and blood. Imaging studies were inconclusive regarding the nature of the foot disorder. We considered the hypothesis of osteomyelitis of the navicular bone as the most likely, for which he completed six weeks of antibiotic therapy. There was a favorable clinical evolution, along with complete absence of osteoarticular or neurological sequelae. The relevance of this clinical case resides in the unusual presentation of invasive pneumococcal disease in this age group, as well as in the rare form of orthopedic involvement.

Background. Trichorhinophalangeal syndrome (TRPS) is an autosomal dominant skeletal dysplasia caused by defects involving the TRPS1 gene. Three types (TRPSs I, II, and III) have been described, exhibiting the common triad of hair, craniofacial, and skeletal abnormalities. TRPS II includes the additional characteristics of mental retardation and multiple exostoses. Case Report. We describe a sporadic case of TRPS type I in a child with two novel nonsense pathogenic mutations in the TRPS1 gene, both in heterozygosity—c.1198C>T (p. Gln400X) and c.2086C>T (p.Arg696X). None of these mutations were found in her parents. Clinical presentation included typical hair and facial features, as well as slight skeletal abnormalities. Discussion. There is a wide variability in clinical expression of TRPS I. Manifestations of the disease can be subtle, yet skeletal anomalies imply that TRPS I is more than an esthetic problem. Clinical and genetic diagnosis allows adequate followup and timely therapeutic procedures. When a single mutation was sufficient for the onset of the disease, our patient presented two different ones.

Introdução: O termo «crise hipertensiva» corresponde a uma variedade de situações clínicas que diferem entre si, pela gravidade dos valores da pressão arterial e pela necessidade de redução mais ou menos rápida dos mesmos. Esta entidade é arbitrariamente definida como qualquer elevação da pressão arterial diastólica acima de 120 mmHg e sintomas acompanhantes relacionados. Dependendo da existência de lesão de órgão-alvo aguda ou rapidamente progressiva, a «crise hipertensiva» pode manifestar-se como urgência ou emergência hipertensiva. Objectivos: Pretende-se apresentar uma breve revisão de conceitos básicos sobre o que é, e como diferenciar, uma verdadeira crise hipertensiva (urgência ou emergência hipertensiva) de uma «pseudocrise», qual a marcha diagnóstica desta patologia e qual a terapêutica mais adequada a implementar. Métodos: Revisão bibliográfica incluindo tratados de referência e artigos recentemente publicados na área de hipertensão arterial, nomeadamente referentes a urgências e emergências hipertensivas. Conclusão: As urgências hipertensivas e as emergências hipertensivas são igualmente denominadas «crises hipertensivas» e ambas se caracterizam por uma elevação súbita e sintomática da pressão arterial que pode ou não associar-se a uma lesão de órgão-alvo e/ou envolver risco de morte imediato ou potencial. O doente que se encontra numa situação de emergência hipertensiva, se considerado em estado grave e/ou agudo, deve ser internado numa unidade de cuidados intensivos, com monitorização da pressão arterial de forma contínua e cuidadosa, sendo necessária uma redução imediata da pressão arterial em minutos ou horas. A redução não necessita de atingir valores «normais» mas sim valores que possam afastar o risco de morte e impedir o agravamento ou deterioração de órgão-alvo. As urgências hipertensivas definem-se como elevações da pressão arterial sistólica e/ou diastólica sem evidência de lesão de órgão-alvo a curto prazo, sendo necessária uma redução gradual da pressão arterial em 24-48 horas para que ocorra a recuperação e a readaptação do doente.

Polysaccharides are described to inhibit aggregation between food polyphenols and salivary proteins (SP) and may hence lead to astringency modulation. In this work, the effect of two wine polysaccharides (arabinogalactan proteins-AGPs and rhamnogalacturonan II- RGII) on SP-polyphenol interaction was evaluated. In general, both polysaccharides were effective to inhibit or reduce SP-polyphenol interaction and aggregation. They can act by two different mechanisms (ternary or competitive) depending on the SP-tannin pair. In the case of salivary P-B peptide, AGPs and RGII seem to act by a ternary mechanism, in which they surround this complex, enhancing its solubility. Concerning acidic proline-rich proteins (aPRPs), it was possible to observe both mechanisms, depending on the tannin and the polysaccharide involved. Overall, this work point out for a specific property of wine polysaccharides important to modulate this and other beverages and food astringency perception. [ABSTRACT FROM AUTHOR]

T cells can use TCR on microvilli to interact with peptide-MHC (pMHC) complexes on antigen presenting cells. Here the authors characterise how T cells use microvilli to interrogate reconstituted membranes for pMHC complexes and how this is regulated by a balance between glycoproteins/glycocalyces that reduce detection, and the small adhesion protein CD2, which enhances detection.

The T-cell coreceptors CD4 and CD8 have well-characterized and essential roles in thymic development, but how they contribute to immune responses in the periphery is unclear. Coreceptors strengthen T-cell responses by many orders of magnitude – beyond a million-fold according to some estimates – but the mechanisms underlying these effects are still debated. T-cell receptor (TCR) triggering is initiated by the binding of the TCR to peptide-loaded major histocompatibility complex (pMHC) molecules on the surfaces of other cells. CD4 and CD8 are the only T-cell proteins that bind to the same pMHC ligand as the TCR, and can directly associate with the TCR-phosphorylating kinase Lck. At least three mechanisms have been proposed to explain how coreceptors so profoundly amplify TCR signaling: (1) the Lck recruitment model and (2) the pseudodimer model, both invoked to explain receptor triggering per se, and (3) two-step coreceptor recruitment to partially triggered TCRs leading to signal amplification. More recently it has been suggested that, in addition to initiating or augmenting TCR signaling, coreceptors effect antigen discrimination. But how can any of this be reconciled with TCR signaling occurring in the absence of CD4 or CD8, and with their interactions with pMHC being among the weakest specific protein-protein interactions ever described? Here, we review each theory of coreceptor function in light of the latest structural, biochemical, and functional data. We conclude that the oldest ideas are probably still the best, i.e., that their weak binding to MHC proteins and efficient association with Lck allow coreceptors to amplify weak incipient triggering of the TCR, without comprising TCR specificity.

Antibodies that block the immune checkpoint receptors PD1 and CTLA4 have revolutionized the treatment of melanoma and several other cancers, but in the process, a new class of drug side effect has emerged—immune related adverse events. The observation that therapeutic blockade of these inhibitory receptors is sufficient to break self-tolerance, highlights their crucial role in the physiological modulation of immune responses. Here, we discuss the rationale for targeting immune checkpoint receptors with agonistic agents in autoimmunity, to restore tolerance when it is lost. We review progress that has been made to date, using Fc-fusion proteins, monoclonal antibodies or other novel constructs to induce immunosuppressive signaling through these pathways. Finally, we explore potential mechanisms by which these receptors trigger and modulate immune cell function, and how understanding these processes might shape the design of more effective therapeutic agents in future.

The first step of the adaptive immune response involves the interaction of T cells that express T-cell receptors (TCRs) with peptide-loaded major histocompatibility complexes expressed by antigen-presenting cells (APCs). Exactly how this leads to activation of the TCR and to downstream signaling is uncertain, however. Recent findings suggest that one of the key events is the exclusion of the large receptor-type tyrosine phosphatase CD45, from close contacts formed at sites of T-cell/APC interaction. If this is true, a full understanding of how close contact formation leads to signaling would require insights into the structures of, and interactions between, large membrane proteins like CD45 and other proteins forming the glycocalyx, such as CD43. Structural insights into the overall dimensions of these proteins using crystallographic methods are hard to obtain, and their conformations on the cell surface are also unknown. Several imaging-based optical microscopy techniques have however been developed for analyzing protein dimensions and orientation on model cell surfaces with nanometer precision. Here we review some of these methods with a focus on the use of hydrodynamic trapping, which relies on liquid flow from a micropipette to move and trap membrane-associated fluorescently labeled molecules. Important insights that have been obtained include (i) how protein flexibility and coverage might affect the effective heights of these molecules, (ii) the height of proteins on the membrane as a key parameter determining how they will distribute in cell-cell contacts, and (iii) how repulsive interactions between the extracellular parts of the proteins influences protein aggregation and distribution.

The immune system serves as a crucial line of defense from infection and cancer, while also contributing to tissue homeostasis. Communication between immune cells is mediated by small soluble factors called cytokines, and also by direct cellular interactions. Cell-cell interactions are particularly important for T cell activation. T cells direct the adaptive immune response and therefore need to distinguish between self and foreign antigens. Even though decades have passed since the discovery of T cells, exactly why and how they are able to recognize and discriminate between antigens is still not fully understood. Early imaging of T cells was very successful in capturing the early stages of conjugate formation of T cells with antigen-presenting cells upon recognition of peptide-loaded major histocompatibility complexes by the T cell receptor (TCR). These studies lead to the discovery of a “supramolecular activation cluster” now known as the immunological synapse, followed by the identification of microclusters of TCRs formed upon receptor triggering, that eventually coalesce at the center of the synapse. New developments in light microscopy have since allowed attention to turn to the very earliest stages of T cell activation, and to resting cells, at high resolution. This includes single-molecule localization microscopy, which has been applied to the question of whether TCRs are pre-clustered on resting T cells, and lattice light-sheet microscopy that has enabled imaging of whole cells interacting with antigen-presenting cells. The utilization of lattice light-sheet microscopy has yielded important insights into structures called microvilli, which are small membrane protrusions on T cells that seem likely to have a large impact on T cell recognition and activation. Here we consider how imaging has shaped our thinking about T cell activation. We summarize recent findings obtained by applying more advanced microscopy techniques and discuss some of the limitations of these methods.

The scavenger receptor cysteine-rich (SRCR) family comprises a group of membrane-attached or secreted proteins that contain one or more modules/domains structurally similar to the membrane distal domain of type I macrophage scavenger receptor. Although no all-inclusive biological function has been ascribed to the SRCR family, some of these receptors have been shown to recognize pathogen-associated molecular patterns (PAMP) of bacteria, fungi or other microbes. SSc5D is a recently described soluble SRCR receptor produced by monocytes/macrophages and T lymphocytes, consisting of an N-terminal portion which contains five SRCR modules, and a large C-terminal mucin-like domain. Towards establishing a global common role for SRCR domains, we interrogated whether the set of five SRCR domains of SSc5D displayed pattern recognition receptor (PRR) properties. For that purpose, we have expressed in a mammalian expression system the N-terminal SRCR-containing moiety of SSC5D (N-SSc5D), thus excluding the mucin-like domain likely by nature to bind microorganisms, and tested the capacity of the SRCR functional groups to physically interact with bacteria. Using conventional protein-bacteria binding assays, we showed that N-SSc5D had a superior capacity to bind to E. coli strains RS218 and IHE3034 compared with that of the extracellular domains of the SRCR proteins CD5 and CD6 (sCD5 and sCD6, respectively), and similar E. coli-binding properties as Spα, a proven PRR of the SRCR family. We have further designed a more sensitive, real-time and label-free surface plasmon resonance (SPR)-based assay, and examined the capacity of N-SSc5D, Spα, sCD5 and sCD6 to bind to different bacteria. We demonstrated that the N-SSc5D compares with Spα in the capacity to bind to E. coli and L. monocytogenes, and further that it can distinguish between pathogenic E. coli RS218 and IHE3034 strains and the non-pathogenic laboratory E. coli strain BL21(DE3). Our work thus advocates the utility of SPR-based assays as sensitive tools for the rapid screening of interactions between immune-related receptors and PAMP-bearing microbes. The analysis of our results suggest that SRCR domains of different members of the family have a differential capacity to interact with bacteria, and further that the same receptor can discriminate between different bacteria strains and species.