Interrelationship between muscle fitness in childhood and bone mineral density in adulthood: mediation analysis of muscle fitness in adulthood.

BACKGROUND: This study was aimed to examine the relationship between muscular fitness indicators in childhood and areal bone mineral density (aBMD) in adulthood and to verify whether the relationship is mediated by performance on muscular fitness indicators in adulthood. METHODS: A sample of 138 healthy adults (69 males; 22.3 years) were followed after a previous assessment at the age of 7-10 years. Stature, body mass and muscular fitness indicators (handgrip strength, standing long jump and sit-ups tests) were assessed in childhood and adulthood. Additionally, total body, upper limbs, lower limbs, right femoral neck and lumbar spine aBMD was assessed in adulthood using dual X-ray absorptiometry. Analysis included descriptive statistics; t-test or Mann-Whitney U-test for comparison between males and females, multiple linear regression for the prediction aBMD from muscular fitness indicators in childhood, mediation analysis of the respective muscular fitness indicators in adulthood and the relationship between muscular fitness indicators in childhood and aBMD. RESULTS: Males were stronger compared to females regarding muscular fitness indicators in childhood and adulthood, and presented higher mean values for aBMD in adulthood, except for lumbar spine (p < 0.05). Regression analysis revealed that some muscular fitness indicators in childhood showed significant positive relationship with bone health indicators in adulthood, such as: handgrip strength and total body aBMD (ß = 0.005; R2 = 0.35; p = 0.040) and upper limbs aBMD (ß = 0.005; R2 = 0.55; p = 0.019); and sit-ups test was a significant predictors of lumbar spine BMD (ß = 0.003; R2 = 0.06; p = 0.039). Mediation analysis pointed out the following: adulthood handgrip strength mediated relationships between childhood handgrip strength and total aBMD (indirect effect (IE) = 0.0025; 95%CI = 0.0005-0.0048), and upper limbs aBMD (IE = 0.0040; 95%CI = 0.0017-0.0069). CONCLUSIONS: Muscular fitness indicators in childhood showed significant relationship with bone health indicators in adulthood and the sit-ups test in childhood had direct effect on lumbar spine aBMD in adulthood. Adulthood handgrip strength mediated the relationship between childhood handgrip strength and total body and upper limb aBMD, pointing out that muscular fitness in childhood may be a aBMD determinant in adulthood, especially when higher muscle fitness performance is maintained in adulthood.

Dermatological manifestations of hematologic neoplasms. Part II: nonspecific skin lesions/paraneoplastic diseases

Abstract Cutaneous manifestations occur in the course of hematologic malignancies and precede, accompany or occur late in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, immunosuppression resulting from the hematologic disease itself or its treatment. The dermatologist must be aware of these conditions that may be helpful both in the diagnosis of the underlying disease and in reducing patient morbidity. This review (part II) addresses the paraneoplastic dermatological changes associated with systemic hematologic malignancies.

Molecular Determinants of Mouse Adaptation of Rat Hepacivirus.

The lack of robust immunocompetent animal models for hepatitis C virus (HCV) impedes vaccine development and studies of immune responses. Norway rat hepacivirus (NrHV) infection in rats shares HCV-defining characteristics, including hepatotropism, chronicity, immune responses, and aspects of liver pathology. To exploit genetic variants and research tools, we previously adapted NrHV to prolonged infection in laboratory mice. Through intrahepatic RNA inoculation of molecular clones of the identified variants, we here characterized four mutations in the envelope proteins responsible for mouse adaptation, including one disrupting a glycosylation site. These mutations led to high-titer viremia, similar to that observed in rats. In 4-week-old mice, infection was cleared after around 5 weeks compared to 2 to 3 weeks for nonadapted virus. In contrast, the mutations led to persistent but attenuated infection in rats, and they partially reverted, accompanied by an increase in viremia. Attenuated infection in rat but not mouse hepatoma cells demonstrated that the characterized mutations were indeed mouse adaptive rather than generally adaptive across species and that species determinants and not immune interactions were responsible for attenuation in rats. Unlike persistent NrHV infection in rats, acute resolving infection in mice was not associated with the development of neutralizing antibodies. Finally, infection of scavenger receptor B-I (SR-BI) knockout mice suggested that adaptation to mouse SR-BI was not a primary function of the identified mutations. Rather, the virus may have adapted to lower dependency on SR-BI, thereby potentially surpassing species-specific differences. In conclusion, we identified specific determinants of NrHV mouse adaptation, suggesting species-specific interactions during entry. IMPORTANCE A prophylactic vaccine is required to achieve the World Health Organization's objective for hepatitis C virus elimination as a serious public health threat. However, the lack of robust immunocompetent animal models supporting hepatitis C virus infection impedes vaccine development as well as studies of immune responses and viral evasion. Hepatitis C virus-related hepaciviruses were discovered in a number of animal species and provide useful surrogate infection models. Norway rat hepacivirus is of particular interest, as it enables studies in rats, an immunocompetent and widely used small laboratory animal model. Its adaptation to robust infection also in laboratory mice provides access to a broader set of mouse genetic lines and comprehensive research tools. The presented mouse-adapted infectious clones will be of utility for reverse genetic studies, and the Norway rat hepacivirus mouse model will facilitate studies of hepacivirus infection for in-depth characterization of virus-host interactions, immune responses, and liver pathology.

Effect of Demographics and Time to Sample Processing on the qPCR Detection of Pathogenic Leptospira spp. from Human Samples in the National Reference Laboratory for Leptospirosis, Brazil.

Leptospirosis diagnosis by MAT requires antibody levels that are typically present only after the first week of symptoms, many days after infection. To improve testing capacity and to develop a fast and reliable solution for the diagnosis of this disease in the first few days after clinical manifestations, the National Reference Laboratory for Leptospirosis/WHO Collaborating Center in Brazil implemented a duplex molecular method by qPCR for human samples for the detection of the gene lipL32, conserved in pathogenic Leptospira spp. In this paper, we describe the overall performance of this protocol in the first 3 months as a standard routine. Detection of pathogenic Leptospira spp. DNA was similar between blood, plasma, and tissue samples, with a limit of detection as low as one cell per sample, and among 391 samples from suspected cases, 174 (44.6%) were positive. The average RNASEP1 control gene detection cycle thresholds (Ct) were 28.4 and 29.8 for positive and negative samples, respectively. The median sample collection interval from the beginning of symptoms was 3 days for positive and 4 days for negative samples, respectively. Neither age, sex, nor the time intervals between sample collection and DNA extraction significantly influenced the results. Surprisingly, positivity was related to the time between DNA extraction and the qPCR reaction. These data support the use of this routine as a diagnostic approach to strengthen the molecular detection of leptospirosis and to develop new strategies.

Characterization of a TatA/TatB binding site on the TatC component of the Escherichia coli twin arginine translocase.

The twin arginine transport (Tat) pathway exports folded proteins across the cytoplasmic membranes of prokaryotes and the thylakoid membranes of chloroplasts. In Escherichia coli and other Gram-negative bacteria, the Tat machinery comprises TatA, TatB and TatC components. A Tat receptor complex, formed from all three proteins, binds Tat substrates, which triggers receptor organization and recruitment of further TatA molecules to form the active Tat translocon. The polytopic membrane protein TatC forms the core of the Tat receptor and harbours two binding sites for the sequence-related TatA and TatB proteins. A 'polar' cluster binding site, formed by TatC transmembrane helices (TMH) 5 and 6 is occupied by TatB in the resting receptor and exchanges for TatA during receptor activation. The second binding site, lying further along TMH6, is occupied by TatA in the resting state, but its functional relevance is unclear. Here we have probed the role of this second binding site through a programme of random and targeted mutagenesis. Characterization of three stably produced TatC variants, P221R, M222R and L225P, each of which is inactive for protein transport, demonstrated that the substitutions did not affect assembly of the Tat receptor. Moreover, the substitutions that we analysed did not abolish TatA or TatB binding to either binding site. Using targeted mutagenesis we introduced bulky substitutions into the TatA binding site. Molecular dynamics simulations and crosslinking analysis indicated that TatA binding at this site was substantially reduced by these amino acid changes, but TatC retained function. While it is not clear whether TatA binding at the TMH6 site is essential for Tat activity, the isolation of inactivating substitutions indicates that this region of the protein has a critical function.

Dermatological manifestations of hematologic neoplasms. Part I: secondary specific skin lesions

Abstract Cutaneous manifestations occur during the course of hematologic malignancies and precede, follow, or are late events in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, and immunosuppression resulting from the hematologic neoplasia itself or its treatment. The dermatologist must be aware of these conditions, which can help both in the diagnosis of the underlying disease and in the reduction of patient morbidity. This review (part I) addresses skin lesions associated with direct infiltration by systemic hematologic malignancies.

Dermatological manifestations of hematologic neoplasms. Part II: nonspecific skin lesions/paraneoplastic diseases.

Cutaneous manifestations occur in the course of hematologic malignancies and precede, accompany or occur late in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, immunosuppression resulting from the hematologic disease itself or its treatment. The dermatologist must be aware of these conditions that may be helpful both in the diagnosis of the underlying disease and in reducing patient morbidity. This review (part II) addresses the paraneoplastic dermatological changes associated with systemic hematologic malignancies.

Front-of-package nutrition labeling as a driver for healthier food choices: Lessons learned and future perspectives.

This work aims to provide a comprehensive overview of the use of front-of-package nutritional labeling (FOPL), identify and characterize the major existing FOPL systems, examine the impact of FOPL systems on consumer behavior, and discuss future perspectives. The searched databases were PubMed, Scopus, and Web of Science, and papers in English, Portuguese, Spanish, and French were considered. The integrative review method was used, comprising 68 papers. The FOPL system from more than 47 countries from North America, South America, Africa, Europe, Australia, and Asia was included in this study. The two main ways to characterize FOPL are the level of interpretation and the type of information provided. Interpretive schemes (such as warning labels, multiple traffic lights, and Nutri-Score) appear to lead to better consumer understanding and support healthier food purchases. However, due to the differences among the results and the specificity of the contexts in which they are used, it is impossible to define one FOPL interpretation scheme superior to the others. Some potential factors that influence the effectiveness of FOPL on consumer attitudes have been identified, such as food taste, as a major intrinsic factor. Extrinsic factors, such as price, food category, cultural diversity, politics, and economics, were also relevant. The lack of availability of similar alternatives, lack of understanding of the importance of FOPL, and lower levels of income and education were also some cognitive and social aspects impairing FOPL effectiveness. Prospects for the United States, Europe, Brazil, Colombia, and Argentina were discussed.

Dermatological manifestations of hematologic neoplasms. Part I: secondary specific skin lesions.

Cutaneous manifestations occur during the course of hematologic malignancies and precede, follow, or are late events in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, and immunosuppression resulting from the hematologic neoplasia itself or its treatment. The dermatologist must be aware of these conditions, which can help both in the diagnosis of the underlying disease and in the reduction of patient morbidity. This review (part I) addresses skin lesions associated with direct infiltration by systemic hematologic malignancies.

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis: Clinicopathological study in a case series of 96 patients with analysis of 427 tumours.

BACKGROUND/OBJECTIVES: Low-dose X-ray radiotherapy to treat tinea capitis during childhood is a well-known risk factor for scalp basal cell carcinomas (BCCs). Post-radiotherapy BCCs are often multiple, and it has been suggested that they display more aggressive features. Our main objective was to study the clinicopathological aspects of post-radiotherapy BCCs to evaluate their biological behaviour and identify features that may differ from other BCCs. METHODS: We performed an observational, retrospective study assessing multiple clinical and pathological characteristics of patients with post-radiotherapy BCCs. RESULTS: We studied 96 patients with 427 post-radiotherapy scalp BCCs. Post-radiotherapy BCCs were often multiple (median of 4 lesions/patient, ranging from 1 to 54). Significant comorbidities included a high incidence of thyroid disease and meningiomas. Recurrences were observed in 23% of patients, but there may be confounding factors, such as referral bias, heterogenous treatment modalities and occurrence of new tumours due to field effect. We found a high incidence of infundibulocystic BCCs (in 14.6% of patients and corresponding to 5.4% of the total number of tumours), trichoblastomas (5.2%) and neurofibromas of the scalp (10%). CONCLUSIONS: This study is consistent with the occurrence of multiple lesions (sometimes numerous) and a relatively high tendency for recurrence in post-radiotherapy BCCs, as suggested by previous studies. We also found a high incidence of the infundibulocystic variant and a higher risk of follicular tumours and neurofibromas, which suggests that radiotherapy may influence the type of differentiation of BCCs and contribute to induce neoplasms of different cell lines.

fHER2, PR, ER, Ki-67 and Cytokeratin 5/6 Expression in Benign Feline Mammary Lesions.

Biomarkers are essential in the characterization of neoplastic lesions and aid not only in the classification of the nature of the lesions, but also in the understanding of their ontogeny, development and prognosis. In cats, while mammary carcinomas are increasingly being characterized, information on their benign lesions is still scarce. Indeed, a better characterization of benign lesions could have an important role in unravelling mammary oncogenesis, similar to that in human breast cancer. Thus, in this study, the expression of five markers was analyzed in 47 benign mammary lesions (hyperplasia, dysplasia and benign tumors) collected from 27 queens. Dysplastic and hyperplastic lesions were the most common (41/47, 81.7%). Most of the lesions were classified as ER positive (43/47, 91.5%), PR negative (30/47, 63.8%), fHER2 negative (29/47, 64.4%), CK 5/6 negative (36/47, 76.6%) and with a low Ki-67 index (37/47, 78.7%). Statistical analysis revealed a correlation between younger ages and ER positivity (p = 0.013) and between larger lesions and negative PR status (p = 0.038). These results reinforce the importance of evaluating the expression of the ER status, prevalent in benign lesions, as a putative precursor in cancer progression.

Immunolocalization of Notch Signaling in Mouse Preimplantation Embryos.

The Notch signaling pathway is an important determinant of cell diversity and identity in most developing embryonic tissues. The pathway components are expressed dynamically, and their function is critical for embryonic survival.This protocol addresses the immunolocalization of Notch pathway components by confocal microscopy.

Tying the successor's hands or following the neighbor? Diffusion of access to information in Brazilian municipalities / ¿Atar las manos del sucesor o seguir al vecino? Difusión del acceso a la información en municipios brasileños / Atar as mãos do sucessor ou seguir o vizinho? Difusão do acesso à informação nos municípios brasileiros

Abstract Why do political actors promote public transparency? Studies show that adherence to transparency can be both politically strategic, i.e., to tie the hands of the successor, and a result of observing the adoption of the policy made by other municipalities, i.e., to minimize the cost of information. We test both the political and the informational motivations to explain the adoption of transparency laws with a subnational analysis of the diffusion of LAI in Brazilian municipalities (2011-2019). Results show that both the informational and the political strategy motivations affect the probability of adopting the LAI. Socioeconomic factors are also important explanatory factors. However, an analysis of heterogeneous effects shows that the learning mechanism is relevant for reducing the impact of socioeconomic factors. This means that learning from neighboring municipalities minimizes the cost of information and the reliance on structural factors to promote transparency at the local level.

Resumen ¿Por qué los actores políticos promueven la transparencia pública? Los estudios muestran que la adhesión a la transparencia puede ser tanto políticamente estratégica, es decir, para atar las manos del sucesor, como resultado de la observación de la adopción de la política hecha por otros municipios, esto es, para minimizar el costo de la información. Probamos las motivaciones políticas e informativas para explicar la adopción de leyes de transparencia con un análisis subnacional de la difusión de la LAI en los municipios brasileños (2011-2019). Los resultados muestran que tanto las motivaciones de aprendizaje como las de estrategia política afectan la probabilidad de adopción de la LAI. Los factores socioeconómicos también son factores explicativos importantes. Sin embargo, un análisis de los efectos heterogéneos muestra que el mecanismo de aprendizaje es relevante para reducir el impacto de los factores socioeconómicos. Esto significa que aprender de los vecinos minimiza el costo de la información y la dependencia de factores estructurales para promover la transparencia a nivel local.

Resumo Por que os atores políticos promovem a transparência pública? Estudos mostram que a adesão à transparência pode ser tanto politicamente estratégica, ou seja, para atar as mãos do sucessor, quanto resultado da observação da adoção da política feita por outros municípios, isto é, para minimizar o custo da informação. Testamos as motivações políticas e informacionais para explicar a adoção de leis de transparência com uma análise subnacional da difusão da LAI nos municípios brasileiros (2011-2019). Os resultados mostram que tanto o aprendizado quanto as motivações da estratégia política afetam a probabilidade de adoção da LAI. Fatores socioeconômicos também são importantes fatores explicativos. No entanto, uma análise dos efeitos heterogêneos mostra que o mecanismo de aprendizagem é relevante para reduzir o impacto dos fatores socioeconômicos. Isso significa que aprender com os vizinhos minimiza o custo da informação e a dependência de fatores estruturais para promover a transparência em nível local.

The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.

Severe equine asthma is a chronic respiratory disease of adult horses, occurring when genetically susceptible individuals are exposed to environmental aeroallergens. This results in airway inflammation, mucus accumulation and bronchial constriction. Although several studies aimed at evaluating the genetic and immune pathways associated with the disease, the results reported are inconsistent. Furthermore, the complexity and heterogeneity of this disease bears great similarity to what is described for human asthma. Currently available studies identified two chromosome regions (ECA13 and ECA15) and several genes associated with the disease. The inflammatory response appears to be mediated by T helper cells (Th1, Th2, Th17) and neutrophilic inflammation significantly contributes to the persistence of airway inflammatory status. This review evaluates the reported findings pertaining to the genetical and immunological background of severe equine asthma and reflects on their implications in the pathophysiology of the disease whilst discussing further areas of research interest aiming at advancing treatment and prognosis of affected individuals.

Resurrecting Golgi proteins to grasp Golgi ribbon formation and self-association under stress.

The Golgi complex is an essential organelle of the eukaryotic exocytic pathway. A subfamily of Golgi matrix proteins, called GRASPs, is central in stress-induced unconventional secretion, Golgi dynamics during mitosis/apoptosis, and Golgi ribbon formation. The Golgi ribbon is vertebrate-specific and correlates with the appearance of two GRASP paralogues and two Golgins (GM130/Golgin45), which form specific GRASP-Golgin pairs. The molecular details of their appearance only in Metazoans are unknown. Moreover, despite new functionalities supported by GRASP paralogy, little is known about their structural and evolutionary differences. Here, we used ancestor sequence reconstruction and biophysical/biochemical approaches to assess the evolution of GRASPs structure/dynamics, fibrillation, and how they started anchoring their Golgin partners. Our data showed that a GRASP ancestor anchored Golgins before gorasp gene duplication in Metazoans. After gene duplication, variations within the GRASP binding pocket determined which paralogue would recruit which Golgin. These interactions are responsible for their specific Golgi location and Golgi ribbon appearance. We also suggest that GRASPs have a long-standing capacity to form supramolecular structures, affecting their participation in stress-induced processes.

[Sarcoid Granulomas Over Scars: Beyond Sarcoidosis]. / Granulomas Sarcóides Sobre Cicatriz: Além da Sarcoidose.

Sarcoid granulomas can be found in a wide range of diseases and differentiating sarcoidosis from a sarcoid-like reaction may be a challenge. We present a woman with erythematoviolaceous papulonodular lesions located on the ears where piercings were placed. A skin biopsy showing an infiltrate of sarcoid and focal tuberculoid granulomas did not exclude sarcoidosis. There was a slight increase in the level of angiotensin-converting enzyme. Systemic involvement due to sarcoidosis was excluded. Epicutaneous tests performed revealed a strong positive reaction to palladium and nickel, supporting the diagnosis of granulomatous contact dermatitis. There are only a few reports of granulomatous contact dermatitis to palladium with piercings as the source of sensitization. The formation of sarcoid granulomas can represent either a sarcoid-like reaction or a form of cutaneous sarcoidosis, and patch tests are essential in order to establish the diagnosis.

Os granulomas sarcóides podem ser encontrados num vasto leque de doenças, pelo que diferenciar a sarcoidose de uma reação tipo sarcóide constituiu um desafio. Apresentamos o caso de uma jovem com lesões papulonodulares eritematovioláceas localizadas nos pavilhões auriculares sobre os locais de aplicação de piercings. A biópsia cutânea mostrou um infiltrado constituído por granulomas sarcóides ou focalmente tuberculóides, não excluindo a hipótese de sarcoidose. O estudo complementar, apesar de uma discreta elevação da enzima conversora da angiotensina, excluiu envolvimento ocular ou pulmonar por sarcoidose. Perante a localização das lesões foram realizados testes epicutâneos que revelaram uma reação fortemente positiva ao paládio e ao níquel, apoiando o diagnóstico de dermatite de contacto granulomatosa. Estão descritos escassos casos de dermatite de contacto granulomatosa ao paládio tendo o metal dos piercings como fonte de sensibilização. A formação de granulomas sarcóides pode representar quer uma reação tipo sarcóide, quer uma forma de sarcoidose cutânea, e os testes epicutâneos adquirem um papel fundamental no diagnóstico correto.