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Objective: To identify audiometric profiles of otosclerosis patients and present Computed Tomography (CT) findings with their otopathological correlates using human temporal bone specimens. Methods: We analyzed sequential patients diagnosed with otosclerosis at a university hospital. Each patient underwent hearing evaluations and CT scans. We assessed the type and severity of hearing loss and the presence and location of otosclerotic foci. Audiometric results and CT images were compared. Additionally, representative otopathological specimens from the Paparella Otopathology & Pathogenesis Laboratory were examined to understand the impact of otosclerotic foci on cochlear and inner ear structures. Results: The study included 40 patients (25 female, 15 male; mean age 50.9 years, range 24–72). Most patients were white (62.5%), with others being black (35%) or Asian (2.5%). Symptoms typically began at age 36.4 years, with an average disease duration of 14.3 years. Audiometric analysis of 71 ears (excluding 9 previously operated) showed mixed hearing loss in 64.78%, sensorineural loss in 23.94%, conductive loss in 2.81%, and normal hearing in 8.45%. Our data revealed a significantly higher prevalence of sensorineural hearing loss among patients with otosclerosis compared to previous reports. This disparity may be due to our higher diagnostic rate, as CT scans were used for patients with unexplained sensorineural hearing loss, and the longer disease course related to delayed specialist access caused by structural issues in the Brazilian health system. Relevant CT findings are presented and compared with similar otopathology specimens. Conclusions: Our study highlights a higher prevalence of mixed and sensorineural hearing loss in patients with otosclerosis than previously reported, suggesting that otosclerosis may be associated with more significant auditory impairment than commonly recognized. However, given the limitations of our retrospective design and the potential influence of co-morbidities, these findings should be interpreted with caution. Level of evidence: 2.

Introduction: The nose has great aesthetic and functional importance, with a high incidence of malignant lesions. There are several techniques for reconstructing the distal third of the nose, but there is no universal indication; will depend on the characteristics of the injury. Surgical options vary between skin grafts and local, regional, and microsurgical flaps. The objective is to present a series of cases of reconstruction of the distal third of the nose using different surgical techniques, discussing the peculiarities and the results obtained. Method: This is a retrospective study carried out at the Hospital do Servidor Público Estadual de São Paulo (HSPE), evaluating a series of eight patients diagnosed with non-melanoma skin cancer located in the distal third of the nose and who underwent reconstruction by the team of Plastic Surgery. Results: Satisfactory results were obtained for all patients undergoing distal nose reconstruction, using total skin graft techniques (n=1) and local flaps (n=7), such as the bilobed, nasolabial, and dorsal nose flap. nose, paramedian frontal, and nasolabial transposition. Conclusion: Reconstruction of defects in the distal third of the nose is challenging and involves great technical variability. A careful assessment of the patient and the injury must be carried out, risks and benefits assessed and the decision shared with the patient.

An extension of the linear H∞ filter, presented here as the extended H∞ particle filter (EH∞PF), is used in this work for attitude estimation, which presents a process and measurement model with nonlinear functions. The simulations implemented use orbit and attitude data from CBERS-4 (China–Brazil Earth Resources Satellite-4), making use of the robustness characteristics of the H∞ filter. The CBERS-4 is the fifth satellite of an advantageous international scientific interaction between Brazil and China for the development of remote sensing satellites used for strategic application in monitoring water resources and controlling deforestation in the Legal Amazon. In the extended H∞ particle filter (EH∞PF) the nature of the system, composed of dynamics and noises, seeks to degrade the state estimate. The EH∞PF deals with this by aiming for robustness, using a performance parameter in its cost function, in addition to presenting an advantageous feature of using a reduced number of particles for state estimation. The justification for the application of this method is because the non-Gaussian uncertainties that appear in the attitude sensors impair the estimation process and the EH∞PF minimizes in signal estimation the worst effects of disturbance signals without a priori knowledge of them, as shown in the results, in addition to presenting good precision within the prescribed requirements, with 100 particles representing a processing time 2.09 times less than the PF with 500 particles.

A organização empresarial é uma fonte inesgotável de conhecimento e suas transações podem refletir o talento humano, uma junção de conhecimento tácito e explicito. Entretanto, o emprego destes há muito de subjetividade e não ficam registros nem sobram resíduos de técnicas e estilos pessoais, que poderiam agregar valores à organização. Neste cenário, as organizações necessitam aprender a criar, reter e disseminar o conhecimento com vistas à perpetuação do negócio e algumas soluções da Tecnologia da Informação podem viabilizar tais processos. Este trabalho aborda os princípios da Gestão do Conhecimento no contexto das práticas administrativas e descreve a plataforma de colaboração IBM Lotus Notes, juntamente com o software DocNIX, usados para gerenciamento de documentos na Cocamar Cooperativa Agroindustrial.

Some plants popularly employed for the treatment of peptic ulcers have proved to be attractive sources of new drugs. Despite extensive research, the pharmacological and toxicological potentials of these plants are not fully understood. In this context, the aim of this work was to analyze the multielemental composition of the methanolic extracts of three of those plants, Alchornea glandulosa (AG), Davilla elliptica (DE) and Davilla nitida (DN), with the intention of contributing to the understanding of the mechanisms of action of these extracts. For this purpose, we used the analytical technique of total reflection X-ray fluorescence (TXRF) by synchrotron radiation at the Brazilian Synchrotron Light Source (LNLS/CNPEM). It was possible to determine the concentrations of the elements: P, S, Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, Rb and Br in all of the samples. Selenium (Se) was detected only in the DN extract. An inverse relationship between the concentrations of elements with proven effectiveness and the gastroprotective activity of extracts considering induction protocols with ethanol and non-steroidal anti-inflammatory drugs (NSAIDs) was obtained. This data suggests that the function of the extract is not only associated with providing the elements for restoring the gastric mucosa but that it also promotes the displacement of these elements from other parts of the mucosa to the damaged area. Correlations between the concentrations of the elements were also obtained. In the DE extract, which is the most effective extract for both induction protocols, the obtained correlations were above 70% among almost all of the elements, and no anticorrelations were found. For the other two extracts, in the less effective extract (AG) anticorrelations above 70% were predominantly found. Meanwhile, in the DN extract, a few high anticorrelations were found, which may explain its intermediate stage of effectiveness.

Inositol phosphorylceramide (IPC), the major sphingolipid in the genus Leishmania but not found in mammals, is considered a potentially useful target for chemotherapy against leishmaniasis. Leishmania (Viannia) braziliensis is endemic in Latin America and causes American tegumentary leishmaniasis. We demonstrated that IPCs are localized internally in parasites, using a specific monoclonal antibody. Treatment with 5 μM myriocin (a serine palmitoyltransferase inhibitor) rendered promastigotes 8-fold less infective than controls in experimental hamster infection, as determined by number of parasites per inguinal lymph node after 8 weeks infection, suggesting the importance of parasite IPC or sphingolipid derivatives in parasite infectivity or survival in the host. IPC was isolated from promastigotes of three L. (V.) braziliensis strains and analyzed by positive- and negative-ion ESI-MS. The major IPC ions were characterized as eicosasphinganine and eicosasphingosine. Negative-ion ESI-MS revealed IPC ion species at m/z 778.6 (d20:1/14:0), 780.6 (d20:0/14:0), 796.6 (t20:0/14:0), 806.6 (d20:1/16:0), and 808.6 (d20:0/16:0). IPCs isolated from L. (V.) braziliensis and L. (L.) major showed significant differences in IPC ceramide composition. The major IPC ion from L. (L.) major, detected in negative-ion ESI-MS at m/z 780.6, was composed of ceramide d16:1/18:0. Our results suggest that sphingosine synthase (also known as serine palmitoyltransferase; SPT) in L. (V.) braziliensis is responsible for synthesis of a long-chain base of 20 carbons (d20), whereas SPT in L. (L.) major synthesizes a 16-carbon long-chain base (d16). A phylogenetic tree based on SPT proteins was constructed by analysis of sequence homologies in species of the Leishmania and Viannia subgenera. Results indicate that SPT gene position in L. (V.) braziliensis is completely separated from that of members of subgenus Leishmania, including L. (L.) major, L. (L.) infantum, and L. (L.) mexicana. Our findings clearly demonstrate sphingoid base differences between L. (V.) braziliensis and members of subgenus Leishmania, and are relevant to future development of more effective targeted anti-leishmaniasis drugs.

A otospongiose é uma osteodistrofia focal primária da cápsula ótica que acomete indivíduos geneticamente predispostos e promove perda auditiva progressiva. OBJETIVO: Verificar a aplicabilidade da avaliação audiométrica no tratamento medicamentoso da otospongiose. MATERIAL E MÉTODO: Estudo prospectivo, randomizado, controlado, duplo-cego, envolvendo 26 pacientes com diagnóstico clínico, audiométrico e tomográfico de otospongiose. Os pacientes elegíveis para o estudo foram alocados em três grupos (A, B e C) e receberam o tratamento com alendronato de sódio (B), fluoreto de sódio (C) e placebo (A) por 6 meses. Após este período, os mesmos realizaram nova avaliação audiométrica. RESULTADOS: Na análise das diferenças entre as vias aérea e óssea (gap), não houve diferença estatisticamente significante. Também não foram encontradas diferenças em relação ao limiar de reconhecimento da fala (SRT) e a discriminação vocal (IRF) entre os períodos pré e pós-tratamento. CONCLUSÃO: Após seis meses de tratamento medicamentoso, a avaliação audiométrica evidenciou manutenção dos limiares auditivos, sugerindo estabilização da atividade da lesão otospongiótica.Otospongiosis is a primary osteodystrophy of the otic capsule that affects genetically predisposed individuals and leads to a progressive hearing loss. AIM: To evaluate the applicability of audiometric evaluation during drug treatment for otospongiosis. MATERIALS AND METHODS: A prospective, randomized, controlled, double-blind study involving 26 patients with clinical, audiometric and CT scan image of otosclerosis. Patients eligible for the study were divided into three groups (A, B and C) and received treatment with alendronate sodium (B), sodium fluoride (C) and placebo (A) for 6 months. After this period they were submitted to new tests. RESULTS: There were not statistically significant differences between air and bone conduction (gap). We also found no differences in the speech recognition threshold (SRT) and speech discrimination (IRF) between before and after treatment. CONCLUSION: After six months of drug treatment the audiometric evaluation kept the same hearing thresholds, suggesting stabilization of the otospongiotic lesions.

OBJETIVO: avaliar os padrões dentofaciais de pacientes portadores de oclusão normal e más oclusões de Angle quanto a possíveis diferenças entre as grandezas estudadas, em relação ao sexo, dentro de cada grupo e entre os grupos. MÉTODOS: a amostra constou de 200 telerradiografias cefalométricas laterais obtidas de jovens brasileiros, de ambos os sexos, na faixa etária de 11 anos e 2 meses a 19 anos e 10 meses, apresentando dentição permanente. O material foi dividido, quanto ao tipo de oclusão, em cinco grupos: um de pacientes portadores de oclusão normal, e quatro de pacientes portadores de más oclusões de Angle, sendo cada grupo dividido igualmente quanto ao sexo. Foram avaliadas grandezas cefalométricas angulares e lineares. RESULTADOS: na grande maioria das grandezas, os sexos masculino e feminino não diferiram; entre os grupos, a posição da maxila não mostrou diferença significativa, o retrognatismo mandibular foi marcante nos grupos de Classe II divisões 1ª e 2ª e foram observados alguns desequilíbrios verticais com diferenças significativas; o padrão foi hipodivergente para os grupos de oclusão normal e Classe II, divisão 2ª, e neutro para os grupos de Classe I; Classe II, divisão 1ª; e Classe III; a compensação dentoalveolar foi evidente nos grupos de Classe III e de Classe II, divisão 2ª; o grupo de oclusão normal apresentou perfil mais convexo que os padrões americanos. CONCLUSÃO: foi possível configurar, de forma geral, algumas características da morfologia facial para alguns tipos de más oclusões. Entretanto, existe a necessidade de avaliar a face individualmente, pois algumas características permeiam entre os diferentes tipos de oclusão.OBJECTIVE: To determine the dentofacial patterns in patients presenting normal occlusion and Angle malocclusions, evaluating the possible differences in the studied measurements, considering the gender, the differences within each group and the differences among the groups. METHODS: The sample comprised 200 lateral cephamometric radiographs of young Brazilian subjects, from both genders, with average age between 11 years and 2 months and 19 years and 10 months. The sample was classified according to the type of occlusion into five groups: one group with subjects presenting normal malocclusions, and four groups with subjects presenting Angle malocclusions. Each group was equally divided according to the gender of subjects. Angular and linear measurements were evaluated in this study. RESULTS: For most measurements, males and females did not differ; among the groups, the position of the maxilla did not show a significant difference, mandibular retrognathia was notable in the groups with Class II division 1 and 2, with a few vertical imbalances with significant differences were observed; the pattern was hypodivergent for the groups with normal occlusion and Class II division 1; and neutral for Class I, Class II division 1 and Class III groups; dentoalveolar compensation was evident in Class III and Class II division 2 groups; the normal occlusion group had a more convex profile than American standards. CONCLUSION: It was possible to generally construct a few characteristics of facial morphology for some types of malocclusion. However, there is the need to individually evaluate each face, as some characteristics prevail among the different occlusion types.

We describe the effect of influenza-like illness (ILI) during the outbreak of pandemic (H1N1) 2009 on health care worker (HCW) absenteeism and compare the effectiveness and cost of 2 sick leave policies for HCWs with suspected influenza. We assessed initial 2-day sick leaves plus reassessment until the HCW was asymptomatic (2-day + reassessment policy), and initial 7-day sick leaves (7-day policy). Sick leaves peaked in August 2009: 3% of the workforce received leave for ILI. Costs during May–October reached R$798,051.87 (≈US $443,362). The 7-day policy led to a higher monthly rate of sick leave days per 100 HCWs than did the 2-day + reassessment policy (8.72 vs. 3.47 days/100 HCWs; p

The purpose of this paper was to analyze the modeling of an artificial satellite orbit, using signals of the GPS constellation and least squares algorithms as the method of estimation, with the aim of analyzing the performance of the orbit estimation process. One pursues to verify how differences of modeling can affect the final accuracy of orbit determination. To accomplish that, the following effects were considered: high degree and order for the geopotential coefficients; direct solar radiation pressure; and Sun-Moon attraction. The measurements were used to feed the batch least squares orbit determination process, in order to yield conclusive results about the orbit modeling issue. An application has been done, using GPS data of the TOPEX/Poseidon satellite, whose accurate ephemeris are available on the Internet. It is shown that from a poor but acceptable modeling up to all effects included, the accuracy can vary from 28 to 9m in the long-period analysis.

Recently, glycosphingolipids have been attracting attention due to their role on biological systems as second messengers or modulators of signal transduction, affecting several events, which range from apoptosis to regulation of the cell cycle. In pathogenic fungi, glycolipids are expressed in two classes: neutral monohexosylceramides (glucosyl-or galactosylceramide) and acidic glycosylinositol phosphorylceramides (the latter class carries longer glycan chains). It is worth to mention that monohexosylceramides exhibit significant structural differences in their lipid moieties compared to their mammalian counterparts, whereas the glycosylinositol phosphorylceramides exhibit remarkable structural differences in their carbohydrate moieties in comparison to mammal glycosphingolipids counterpart. We observed that glycosylinositol phosphorylceramides are capable of promoting immune response in infected humans. In addition, inhibiting fungal glycosphingolipid biosynthetic pathways leads to an inhibition of colony formation, spore germination, cell cycle, dimorphism and hyphal growth. Other pathogens, such as trypanosomatids, also present unique glycolipids, which may have an important role for the parasite development and/or disease establishment. Regarding host-pathogen interaction, cell membrane rafts, which are enriched in sphingolipids and sterols, participate in parasite/fungal infection. In this review, it is discussed the different biological roles of (glyco) (sphingo)lipids of pathogenic/opportunistic fungi and trypanosomatids.Recentemente, glicoesfingolipídeos têm atraído atenção devido ao seu papel na biologia celular como segundo-mensageiro ou moduladores da transdução de sinal, afetando vários eventos, desde apoptose até a regulação do ciclo celular. Em fungos patogênicos, existem duas classes de glicolipídeos: monohexosil ceramidas neutras (glucosil-ou galactosilceramida) e glicosilinositol fosforilceramidas (os quais apresentam cadeias de carboidratos mais longas). É importante enfatizar que as monohexosil ceramidas exibem diferenças estruturais nas suas porções lipídicas quando comparadas às de mamíferos, enquanto que glicosilinositol fosforilceramidas exibem diferenças estruturais marcantes em suas porções carboidratos em comparação aos glicoesfingolipídeos de mamíferos. Observamos também que glicosilinositol fosforilceramidas são capazes de promover resposta imune em indíviduos infectados. Além do mais, inibição das vias biossintéticas de glicoesfingolipídeos de fungos acarreta a inibição da formação de colônias, germinação de esporos, ciclo celular, dimorfismo e crescimento de hifas. Outros patógenos, como os tripanosomatídeos, também apresentam glicolipídeos únicos, os quais apresentam um papel importante para o desenvolvimento do parasita e/ou para o estabelecimento da doença. Em relação à interação hospedeiro-patógeno, os "membrane rafts", estruturas da membrana plasmática enriquecidas em esfingolipídeos e esteróis, têm participação fundamental na infecção do parasita/fungo. Nesta revisão, discutimos os diferentes papéis biológicos dos (glico) (esfingo)lipídeos de fungos patogênicos/oportunistas e de tripanosomatídeos.

This study was designed to determine the gastroprotective effect of a Mangifera indica leaf decoction (AD), on different experimental models in rodents. The administration of AD up to a dose of 5 g/kg (p.o.) did not produce any signs or symptoms of toxicity in the treated animals, while significantly decreasing the severity of gastric damage induced by several gastroprotective models. Oral pre-treatment with AD (250, 500 or 1000 mg/kg) in mice and rats with gastric lesions induced by HCl/ethanol, absolute ethanol, non-steroidal anti-inflammatory drug (NSAID) or stress-induced gastric lesions resulted in a significant decrease of said lesions. Phytochemical analyses of AD composition demonstrated the presence of bioactive phenolic compounds that represent 57.3% of total phenolic content in this extract. Two main phenolic compounds were isolated, specifically mangiferin (C-glucopyranoside of 1,3,6,7-tetrahydroxyxanthone) and C-glucosyl-benzophenone (3-C-β-D-glucopyranosyl-4’,2,4,6-tetrahydroxybenzophenone). These findings indicate the potential gastroprotective properties of aqueous decoction from M. indica leaves.

A artrite reumatóide é uma doença sistêmica, de causa desconhecida e de natureza auto-imune. A característica clínica principal é a poliartrite crônica, em geral envolvendo pequenas e grandes articulações, com tendência a deformidades e incapacidades. A presença de nódulos subcutâneos pode ser parte da apresentação clínica e tem histopatologia típica. O comprometimento visceral pode incluir os pulmões, vasos, pericárdio etc. O envolvimento pulmonar pode se apresentar com derrame pleural, bronquiolite, vasculite pulmonar e mais raramente nódulos reumatóides. O desenvolvimento clássico é o dos envolvimentos viscerais após o aparecimento da artrite. Os nódulos reumatóides pulmonares têm baixa prevalência. Seu desenvolvimento precedendo a artrite acrescenta interesse ao assunto. Relata-se um caso de paciente do sexo feminino com nodulose reumatóide pulmonar que precedeu o envolvimento articular.Rheumatoid arthritis is a systemic disease of unknown cause and autoimune disease mechanisms. Its main clinical feature is a chronic polyarthritis involving large and small joints that may cause deformities and disabilities. Subcutaneous nodules can be part of the clinical presentation with a typical pathological appearance. Visceral involvement may include lungs, pericardium, and blood vessels. Pulmonary involvement is characterized by pleural effusions, vasculitis, bronchiolitis and pulmonary rheumatoid nodules. Usually, visceral manifestations appear after arthritis development. Pulmonary rheumatoid nodules are a rare feature. Its development preceding arthritis make this characteristic even more interesting. Our case report refers to a female patient with pulmonary rheumatoid nodules that has preceded the arthritis.

The non-linear estimators are certainly the most important algorithms applied to real problems, especially those involving the attitude estimation of spacecraft. The purpose of this paper was to use real data of sensors to analyze the behavior of Unscented Kalman Filter in attitude estimation problems when it is represented in different ways and compare it with the standard estimator for non-linear estimation problems. The robustness of the estimation was performed when this was subjected to imprecise initial conditions. The attitude parametrization was described in Euler angles, quaternion and quaternion incremental. The satellite China-Brazil Earth Resources Satellite and measurements provided by the Satellite Control Center of the Instituto Nacional de Pesquisas Espaciais were considered in the study. The results indicate that the behaviors for both estimators were equivalent for such parameterizations under the same conditions. However, comparing the Unscented Kalman Filter (UKF) with the standard filter for non-linear systems, Extended Kalman Filter (EKF), it was observed that, in the presence of inaccurate initial conditions, the Unscented Kalman Filter presented a fast convergence whereas Extended Kalman Filter had problems and only converged later on.

Acidic glycosphingolipid components were extracted from the opportunistic mycopathogen Aspergillus fumigatus and identified as inositol phosphorylceramide and glycosylinositol phosphorylceramides (GIPCs). Using nuclear magnetic resonance sppectroscopy, mass spectrometry, and other techniques, the structures of six major components were elucidated as Ins-P-Cer (Af-0), Manp(α1→3)Manp(α1→2)Ins-P-Cer (Af-2), Manp(α1→2)Manp(α1→3)Manp(α1→2)Ins-P-Cer (Af-3a), Manp(α1→3)[Galf(β1→6)]Manp(α1→2)-Ins-P-Cer (Af-3b), Manp(α1→2)-Manp(α1→3)[Galf(β1→6)]Manp(α1→2)Ins-P-Cer (Af-4), and Manp(α1→3)Manp(α1→6)GlcpN(α1→2)Ins-P-Cer (Af-3c) (where Ins = myo-inositol and P = phosphodiester). A minor A. fumigatus GIPC was also identified as the N-acetylated version of Af-3c (Af-3c*), which suggests that formation of the GlcNα1→2Ins linkage may proceed by a two-step process, similar to the GlcNα1→6Ins linkage in glycosylphosphatidylinositol (GPI) anchors (transfer of GlcNAc, followed by enzymatic de-N-acetylation). The glycosylinositol of Af-3b, which bears a distinctive branching Galf(β1→6) residue, is identical to that of a GIPC isolated previously from the dimorphic mycopathogen Paracoccidioides brasiliensis (designated Pb-3), but components Af-3a and Af-4 have novel structures. Overlay immunostaining of A. fumigatus GIPCs separated on thin-layer chromatograms was used to assess their reactivity against sera from a patient with aspergillosis and against a murine monoclonal antibody (MEST-1) shown previously to react with the Galf(β1→6) residue in Pb-3. These results are discussed in relation to pathogenicity and potential approaches to the immunodiagnosis of A. fumigatus.

Os autores fizeram um estudo da coluna lombar de humanos, objetivando avaliar e determinar os diferentes tipos de fibras nervosas no disco intervertebral normal e no degenerado. Foram usadas dez colunas lombares de cadáveres com aproximadamente 48 a 72 horas de óbito. As peças foram submetidas a exames de radiografia simples e ressonância magnética. Após os exames, os discos foram classificados em normais e degenerados. Em seguida, foram dissecados, divididos em regiões anterior e posterior, incluídos em parafina e realizado estudo de imuno-histoquímica com a proteína S100. Com o auxílio de um programa de computador Image-Pro Plus (media cybernetics®), as fibras nervosas tiveram seu diâmetro medidos em micrômetros e classificadas em quatro tipos de fibras. Foram encontrados quatro tipos de fibras nervosas nas diferentes regiões discais. O número e o tipo de fibras variaram de acordo com a região e grau de degeneração do disco intervertebral. Concluíram que as fibras do tipo III são mais freqüentes na região anterior; as fibras dos tipos II e IV são mais freqüentes na região posterior, e as fibras do tipo I não apresentaram diferenças entre a região anterior e a posterior; além disso, o disco degenerado tem mais fibras nervosas que o disco normal.The authors conducted a study on human lumbar spine, aiming to assess and determine the different kinds of nervous fibers in normal and degenerated intervertebral discs. Ten cadaver’s lumbar spines with approximately 48 - 72 of death have been used. The pieces were submitted to simple X-ray and magnetic resonance tests. Subsequently to the tests, discs were divided into normal and degenerated. Then, they were dissected, divided into anterior and posterior according to the region, included in paraffin and an immunohistochemical study with S100 protein was performed. With the aid of Image-Pro Plus computer software (media cybernetics) ®, nervous fibers’ diameters were measured as micrometers and classified into four kinds of fibers. Four types of nervous fibers were found on different disc regions. The number and kind of fibers varied according to the region and degree of intervertebral disc degeneration. It was concluded that type-III fibers are more common at the anterior region; type-II and type-IV fibers are more common at the posterior region, and type-I fibers do not show any differences regarding anterior and posterior regions; in addition, a degenerated disc has a higher number of nervous fibers than a normal one.

Discute a questão do Acesso Livre ao conhecimento científico, abordando, de maneira sucinta, seus impactos na pesquisa. Discorre sobre algumas das principais questões relacionadas ao uso de tecnologias da informação na comunicação científica, com ênfase em questões recentes, como o auto-arquivamento de trabalhos científicos em repositórios (via verde) e os periódicos científicos eletrônicos de Acesso Livre (via dourada). Tais questões são focadas simultaneamente como uma reação dos pesquisadores ao modelo de negócios vigente nas editoras científicas comerciais e uma conscientização do grande aumento de impacto dos documentos disponibilizados em Acesso Livre. Acrescenta a essa discussão informação sobre as políticas institucionais necessárias à implementação plena do Acesso Livre. Trata das principais tecnologias que suportam o Acesso Livre, tais como sistemas de gestão de repositórios e de revistas científicas que obedecem às especificações OAI. Além disso, discute perspectivas futuras que deverão nortear as políticas, a tomada de decisões e as ações por parte das instituições acadêmicas e governamentais que garantam o Acesso Livre, particularmente nos países lusófonos.This paper discusses Open Access to scientific knowledge and its impacts on research. It overviews some of the major issues regarding the use of information technologies in scholarly communication activities, highlighting recent issues such as repository selfarchiving (green road) and Open Access journals (golden road). Such issues are focused both as a reaction of researchers to the current business models of commercial scholarly publishers and as an awareness of the increasingly impact of documents available inOpen Access. It adds to this discussion information about the necessary policies to fully implement Open Access. Authors describe the main technology facilities that support Open Access, such as OAI compliant Repositories and Journal Management systems. Moreover, future perspectives that should guide academic and governmentpolicies, decisions and actions that can assure Open Access, particularly in Portuguese Speaking Countries, are discussed.

Perfurações radiculares são aberturas artificiais que resultam na comunicação da cavidade pulpar com os tecidos periodontais, que podem ser causadas por iatrogênias, processo de reabsorção ou carie. O sucesso no tratamento vai depender do tamanho, local e tempo que houve a perfuração. Na atualidade o material mais utilizado para o selamento de perfurações tem sido o MTA (Agregado de Trióxido Mineral) por ser biocompativel e permitir a formação de cemento oferecendo condições para organização dos tecidos de suporte dentário. Relata-se nesse caso clinico a resolução de um caso de perfuração de um elemento dental no terço cervical acontecido a 12 anos atrás. O tratamento inicial foi a remoção da guta-percha que se encontrava no periodonto, selamento da perfuração com MTA e posterior obturação do conduto radicular.

Detergent-resistant membranes (DRMs) from Leishmania (Viannia) braziliensis promastigotes, insoluble in 1% Triton X-100 at 4°C, were fractionated by sucrose density gradient ultracentrifugation. They were composed of glycoinositolphospholipids (GIPLs), inositol phosphorylceramide (IPC), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and sterols. In contrast, 1% Triton X-100-soluble fraction was composed of PE, phosphatidylcholine, phosphatidylserine, PI, IPC, sterol, and lyso-PI. High-performance thin-layer chromatography (HPTLC) immunostaining using monoclonal antibody SST-1 showed that 85% of GIPLs are present in DRMs, and immunoelectron microscopic analysis showed that SST-1-reactive components are located in patches along the parasite surface. No difference in GIPL pattern was observed by HPTLC between Triton X-100-soluble versus -insoluble fractions at 4°C. Analysis of fatty acid composition in DRMs by GC-MS showed the presence of GIPLs containing an alkylacylglycerol, presenting mainly saturated acyl and alkyl chains. DRMs also contained sterol, IPC with saturated fatty acids, PI with at least one saturated acyl chain, and PE with predominantly oleic acid. Promastigotes treated with methyl-β-cyclodextrin to disrupt lipid microdomains showed significantly lower macrophage infectivity, suggesting a relationship between lipid microdomains and the infectivity of these parasites.

O acesso à informação científica tem sido um grande desafio para países em desenvolvimento como o Brasil. Com a crise dos periódicos, surgida em função dos altos custos na manutenção das assinaturas das revistas científicas, o acesso à informação científica ficou bastante limitado. Embora essa crise tenha começado em meados dos anos 80, ainda hoje não existe nenhuma solução definitiva. Com as tecnologias da informação e da comunicação, surge a iniciativa de arquivos abertos (Open Archvies Initiative), a qual define um modelo de interoperabilidade entre bibliotecas e repositórios digitais, possibilitando alternativas para a comunicação científica. Ao mesmo tempo, consolida-se o movimento em favor do acesso livre à informação científica em todo o mundo, pelos grandes editores ou publishers, por meio de propostas de ações que possam viabilizar essa iniciativa. Essas são as bases da proposta de um novo modelo para intensificar e consolidar o registro e a disseminação da produção científica brasileira, assim como do acesso à informação científica. Com as experiências obtidas na implantação da Biblioteca Digital Brasileira de Teses e Dissertações (BDTD), o Instituto Brasileiro de Informação em Ciência e Tecnologia (Ibict) detém, hoje, a competência técnica para consolidar e implantar essa proposta.Scientific information access has been a great challenge to undeveloped countries as Brazil. With the scientific journal crisis motivated by the high prices on the scholarly journals subscriptions, that access became very limited. Even that crisis had started in the middle 80's, until today there is not a definitive solution. With the information and communication technologies, rises, the Open Archives Initiative, which defines a model of interoperability for libraries and digital repositories, making possible new alternatives for scientific communication. At the same time, the open access to scientific information movement got stronger around the world, confronting the big editors and publishers, proposing actions to make possible the consolidation that initiative. Those are the bases proposed by the new model to intensified and consolidate the register and dissemination of the Brazilian scientific information content, as well as its access. With the experiences brought with the development of Brazilian Digital Library of Theses and dissertations (BDTD), the Brazilian Institute for Information on Science and Technology has today the technical ability to implement and consolidate that project.

Background: Rat trachea display a differential topographical distribution of connective tissue mast cells (CTMC) and mucosal mast cells (MMC) that may imply regional differences in the release of allergic mediators such as tumor necrosis factor-α (TNF-α) and eicosanoids.

Glycosphingolipids (GSLs) are ubiquitous membrane components and have key roles in biological systems, acting as second messengers or modulators of signal transduction by affecting several events, ranging from cell adhesion, cell growth, cell motility, regulation of apoptosis and cell cycle. Over the last 20 years our laboratory and other research groups determined the glycan and ceramide structures of more than 20 GSLs from several pathogenic/opportunistic fungi, using a combination of gas chromatography, mass spectrometry, nuclear magnetic resonance as well as other immunochemical and biochemical techniques. Fungal GSLs can be divided in two major classes: neutral GSLs, galactosyl- and glucosylceramide (GlcCer), and acidic GSLs, the glycosylinositol-phosphorylceramides (GIPCs). Glycosyl structures in fungal GIPCs exhibited significant structural diversity and distinct composition when compared to mammalian GSLs, e.g., the expression of inositol-mannose and inositol-glucosamine cores and the terminal residue of β-D-galactofuranose which are absent in mammalian cells. Studies performed by our group demonstrated that GIPC (Galfβ6[Manα3]Manα2InsPCer) elicited in patients with paracoccidioidomycosis an immune response with production of antibodies directed to the terminal residue of β-D-galactofuranose. Further studies also showed that inhibition of GlcCer biosynthetic pathways affects fungal colony formation, spore germination and hyphal growth, indicating that enzymes involved in GlcCer biosynthesis may represent promising targets for the therapy of fungal infections. Recently, it was shown that GlcCer and GIPCs are preferentially localized in membrane microdomains and monoclonal antibodies directed to these GSLs interfere in several fungal biological processes such as growth and morphological transition. This review focuses on glycan structures carried on sphingolipids of pathogenic/opportunistic fungi, and aspects of their biological significance are discussed.

As iniciativas idealizadas pelo movimento do Acesso Livre permitiram novas alternativas de alcance da informação científica aos pesquisadores radicados em qualquer parte do globo terrestre, que passaram a contar com ferramentas capazes de promover o registro e a disseminação da produção científica: os repositórios digitais e as revistas científicas de acesso livre. Existem mais de 2600 repositórios digitais em diversas partes do mundo, e o Brasil participou desde o início no desenvolvimento dessas iniciativas. Hoje, o país conta com 83 repositórios digitais e cerca de mil revistas científicas de acesso livre. A cada dois anos, um evento dedicado a esse tema, fruto de parceria firmada entre o Ministério da Ciência, Tecnologia e Inovação do Brasil e o Ministério da Ciência e Tecnologia de Portugal, se realiza, alternadamente, nesses dois países. Aqui serão brevemente apresentados os principais repositórios, usualmente mantidos por instituições de ensino superior e de pesquisa, organizações governamentais, agências de fomento ou organizações mundiais, bem como algumas das mais importantes iniciativas internacionais em prol do acesso livre. Serão evidenciadas também as diferenças preconizadas pelas bibliotecas universitárias brasileiras e a repentina desacelera­ ção dessas iniciativas no país. Concluindo, serão apresentadas algumas evidências, resultados e perspectivas futuras.

Major neutral glycosphingolipid components were extracted from Sporothrix schenckii, a dimorphic fungus exhibiting a hyphal saprophytic phase and a yeast parasitic phase responsible for chronic mycotic infections in mammalian hosts. These components, one from the mycelial form and two from the yeast form, were purified and their structures were elucidated by 1H nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization mass spectrometry (ESI-MS), and tandem ESI-MS/MS. All three were characterized as cerebrosides (monohexosylceramides) containing (4E, 8E)-9-methyl-4,8-sphingadienine as the long-chain base attached to N-2′-hydroxyoctadecanoate and N-2′-hydroxy-(E)-Δ3-octadecenoate as the fatty acyl components. However, while the mycelial form expressed only β-glucopyranosylceramide, the yeast form expressed both β-gluco- and β-galactopyranosylceramides in approximately equal amounts. In addition, while the glucosylceramides of both mycelial and yeast forms had similar proportions of saturated and (E)-Δ3 unsaturated 2-hydroxy fatty acid, the galactocerebroside of the yeast form had significantly higher levels of (E)-Δ3 unsaturation. The differences in cerebroside hexose structure represent a novel type of glycosphingolipid dimorphism not previously reported in fungi. Possible implications of these findings with respect to regulation of morphological transitions in S. schenckii and other dimorphic fungi are discussed.—Toledo, M. S., S. B. Levery, A. H. Straus, and H. K. Takahashi. Dimorphic expression of cerebrosides in the mycopathogen Sporothrix schenckii. J. Lipid Res. 2000. 41: 797–806.

High-speed counter-current chromatography (HSCCC) is a major tool for the fast separation of natural products from plants. It was used for the preparative isolation of the flavonoid monoglucosides present in the aerial parts of the Davilla elliptica St. Hill. (Dilleniaceae). This species is used in Brazilian folk medicine for the treatment of gastric disorders. The optimum solvent system used was composed of a mixture of ethyl acetate-n-propanol-water (140:8:80, v/v/v) and led to a successful separation of quercetin-3-O-alpha-L-rhamnopyranoside and myricetin-3-O-alpha-L-rhamnopyranoside in approximately 3.0 hours with purity higher than 95%. Identification was performed by ¹H NMR, 13C NMR and HPLC-UV-DAD analyses.

http://dx.doi.org/10.5028/jatm.v5i4.252 The nonlinear unscented Kalman filter (UKF) is evaluated for the satellite orbit determination problem, using Global Positioning System (GPS) measurements. The assessment is based on the robustness of the filter. The main subjects for the evaluation are convergence speed and dynamical model complexity. Such assessment is based on comparing the UKF results with the extended Kalman filter (EKF) results for the solution of the same problem. Based on the analysis of such criteria, the advantages and drawbacks of the implementations are presented. In this orbit determination problem, the focus is to analyze UKF convergence behavior using different sampling rates for the GPS signals, where scattering of measurements will be taken into account. A second aim is to evaluate how the dynamical model complexity affects the performance of the estimators in such adverse situation. After solving the real-time satellite orbit determination problem using actual GPS measurements, through EKF and UKF algorithms, the results obtained are compared in computational terms such as complexity, convergence, and accuracy.

Novos paradigmas da comunicação científica: ampliando o debate

Professor Stevan Harnad*, filho de Hernád István e Hesslein István, húngaro, nasceu em Budapest, nasceu cientista na área cognitiva. Ele fez seus trabalhos de prégraduação na Universidade McGill e graduou-se pela Universidade de Princeton University. Atualmente, ele ocupa a cátedra de pesquisa em Ciência Cognitiva na Universidade de Quebec, em Montreal – Canadá (UQAM) e é professor de Ciências Cognitivas na Universidade de Southampton. Participa, como membro externo, da Academia de Ciência Húngara. Sua pesquisa está concentrada nas áreas de categorização, comunicação e cognição.

Discute a questão do Acesso Livre ao conhecimento científico, abordando, de maneira sucinta, seus impactos na pesquisa. Discorre sobre algumas das principais questões relacionadas ao uso de tecnologias da informação na comunicação científica, com ênfase em questões recentes, como o auto-arquivamento de trabalhos científicos em repositórios (via verde) e os periódicos científicos eletrônicos de Acesso Livre (via dourada). Tais questões são focadas simultaneamente como uma reação dos pesquisadores ao modelo de negócios vigente nas editoras científicas comerciais e uma conscientização do grande aumento de impacto dos documentos disponibilizados em Acesso Livre. Acrescenta a essa discussão informação sobre as políticas institucionais necessárias à implementação plena do Acesso Livre. Trata das principais tecnologias que suportam o Acesso Livre, tais como sistemas de gestão de repositórios e de revistas científicas que obedecem às especificações OAI. Além disso, discute perspectivas futuras que deverão nortear as políticas, a tomada de decisões e as ações por parte das instituições acadêmicas e governamentais que garantam o Acesso Livre, particularmente nos países lusófonos.

A comunicação científica tradicional enfrenta uma série de barreiras que dificultam não apenas a publicação dos resultados de pesquisas, como também o seu acesso por parte da comunidade científica. Entre essas dificuldades, destacam-se: 1) alta excessiva no custo das assinaturas de revistas científicas; 2) longo prazo para a efetiva publicação de determinado artigo; 3) os direitos autorais são entregues gratuitamente aos editores científicos, os únicos a ganhar em toda a cadeia da comunicação científica. A convergência tecnológica propiciou alternativas que podem derrubar parte dessas barreiras. Uma das alternativas que as tecnologias da informação e da comunicação propiciaram é o modelo de interoperabilidade denominado Arquivos Abertos (Open Archives). Em conseqüência, surge o movimento em prol do acesso livre à informação científica (Open Access). A experiência da conjugação dessa base tecnológica com o movimento do Acesso Livre à Informação Científica é o tema deste número especial da revista Encontros Bibli. As contribuições de especialistas brasileiros e estrangeiros para esta edição trazem um enfoque variado sobre este tema. Iniciamos com uma entrevista com Stevan Harnad, um dos principais líderes do movimento do Acesso Livre à Informação Científica. Nessa entrevista, Stevan comenta sobre o papel do modelo de interoperabilidade Open Archives no movimento Acesso Livre à Informação Científica, falando sobre o futuro desse movimento e as suas estratégias para implantar o acesso livre à informação científica em todo o planeta. O artigo “Comunicação científica: o papel da Open Archives Initiative no contexto do Acesso livre” aborda a questão do acesso livre, relacionando-a ao uso de tecnologias de auto-arquivamento e à publicação em periódicos eletrônicos que seguem a filosofia dos arquivos abertos como uma reação aos editores científicos comerciais. Apresenta as principais tecnologias de acesso livre e discorre sobre a necessidade do envolvimento de instituições acadêmicas e governos, principalmente no âmbito dos países lusófonos, na definição de políticas que suportem ações voltadas ao acesso livre. Sob o ponto de vista tecnológico, é desenvolvido o artigo “Padrões para bibliotecas digitais abertas e interoperáveis”. Seu autor apresenta os principais padrões, normas e protocolos de arquivos abertos e enfatiza a necessidade da adoção dos mesmos para que se possa obter a interoperabilidade entre sistemas de bibliotecas digitais funcionando em rede. No contexto da educação a distância, é apresentado o trabalho “Comunicação científica em arquivos abertos e educação a distância no Brasil”. Após mostrar o cenário das publicações sobre EAD em nível internacional e nacional, a autora analisa a publicação de EAD em arquivos abertos e recomenda o seu uso. No artigo “Provedores de dados, provedores de serviços e periódicos em Ciência da Informação, Biblioteconomia e áreas afins”, realiza-se um levantamento de tipos de repositórios e são analisados periódicos científicos on-line, mostrando que esta opção vem ocupando cada vez mais espaço na realidade do acesso livre. Seu objetivo é contribuir com a divulgação e uso destes provedores. São apresentados também dois artigos que mostram aplicações das tecnologias de arquivos abertos. O primeiro refere-se à área de comunicação, com o trabalho “Repositório institucional em comunicação: o projeto Reposcom implementado junto à Federação de Bibliotecas Digitais em Ciências da Comunicação”. O segundo enfoca as universidades católicas e se intitula “O acesso aberto à produção científica das universidades católicas: o caso da CVA-RICESU”. Em uma vertente mais reflexiva, encontra-se o texto “A produção científica disponível ao mundo: a tecnologia, a vontade e os acessos”. Nele, a autora trata do acesso à informação sob a luz da evolução da tecnologia relacionada ao tratamento da informação e a vontade de obter conhecimento. Tece considerações quanto às bibliotecas tradicionais e digitais, assim como trata das iniciativas de acesso livre no Brasil e no mundo. Desejamos boa leitura a todos!

A primeira descrição de dor severa no trajeto do nervo glossofaríngeo foi realizada por Weisenberg, em 1910¹, em um paciente com tumor do ângulo ponto cerebelar. Entretanto, coube a Harris, em 1926², nomear como nevralgia do nervo glossofaríngeo esse raro quadro clínico, caracterizado por paroxismos de dor intensa, unilaterais, na região posterior da língua, no palato mole, na garganta e na região lateral e posterior da faringe, irradiando para o ouvido. A dor pode ser desencadeada por deglutição, tosse, bocejo ou mastigação e normalmente dura de segundos a minutos. A associaç��o de nevralgia do glossofaríngeo e síncope é muito rara e se deve a breves períodos de bradicardia, assistolia ou hipotensão, sendo a primeira descrição dessa associação, com essa fisiopatologia, realizada por Riley e cols., em 1942³.The first description of severe pain in the distribution of the glossopharyngeal nerve is credited to Weisenberg, in 1910¹, in a patient with cerebellopontine angle tumor. However, it was Harris, in 1926², who coined the term glossopharyngeal neuralgia to describe this rare condition characterized by paroxysms of excruciating pain located laterally at the back of the tongue, soft palate, throat, and lateral and posterior pharynx, radiating to the ear. Swallowing, coughing, yawning or chewing may trigger pain, which usually lasts from seconds to minutes. The association between glossopharyngeal neuralgia and syncope is very rare, being identified by brief episodes of bradycardia, asystole, and hypotension. Such an association, with this same pathophysiology, was first described by Riley et al³ in 1942.

O presente trabalho propõe uma abordagem alternativa de tratamento e recuperação de informação, onde os sintagmas nominais desempenham o principal papel. Trata-se da construção de um protótipo, de sistema de recuperação de informação capaz de navegar uma estrutura em árvore de sintagmas nominais. Para exploração deste protótipo, foi utilizada uma amostragem de 15 artigos em língua portuguesa, de onde foram extraídos os sintagmas nominais. O processo de extração foi manual, simulando um processo automatizado.

Visando à integração do País na competição tecnológica internacional no presente contexto da modernização ensejado pelo Governo, o IBICT, em consonância com os objetivos da Instituição, promove a criação do Laboratório de Tecnologiada Informação do Departamento de Ensino e Pesquisa. O projeto, seus objetivos, mecanismos e infra-estruturas para sua implantação são descritose enfatizada sua função como um dos elementos-chave de entrosamento, divulgação e geração de competência em tecnologias de informação para sistemas de informação. Laboratory of InformationTechnology: project of infrastructure creation Abstract According to the Brazilian integration on the international technological competition at the present context of modemization arised by the Government, the present Director of the Brazilian Institute for information in Science and Technology (IBICT), according to the Institute aims, promotes the creation of the Laboratory of information Technology of the Department of Education and Research. The project of the Laboratory, the aims,mechanims and infrastructures for te implantationare out lined, as well as its function as akey-element of organization, dissemination and generation of competence on information technologies for information systems is emphasised.

Hypervitaminosis D is a rarely reported condition. In general it is only perceived when hypercalcemia is not resolved. The use of vitamin D has increased in recent years because of its benefits, but as a result, intoxication cases have occurred more frequently. This report describes a patient who presented worsening of renal function and hypercalcemia. After investigation, vitamin D intoxication was confirmed and it was due to an error in compounding.

Background: Familial dilated cardiomyopathy (DCM) causes heart failure and may lead to heart transplantation. DCM is typically a monogenic disorder with autosomal dominant inheritance. Currently disease-causing variants have been reported in over 60 genes that encode proteins in sarcomeres, nuclear lamina, desmosomes, cytoskeleton, and mitochondria. Over half of the patients undergoing comprehensive genetic testing are left without a molecular diagnosis even when patient selection follows strict DCM criteria., Methods and Results: This study was a retrospective review of patients referred for genetic testing at Blueprint Genetics due to suspected inherited DCM. Next generation sequencing panels included 23-316 genes associated with cardiomyopathies and other monogenic cardiac diseases. Variants were considered diagnostic if classified as pathogenic (P) or likely pathogenic (LP). Of the 2,088 patients 514 (24.6%) obtained a molecular diagnosis; 534 LP/P variants were observed across 45 genes, 2.7% (14/514) had two diagnostic variants in dominant genes. Nine copy number variants were identified: two multigene and seven intragenic. Diagnostic variants were observed most often in TTN (45.3%), DSP (6.7%), LMNA (6.7%), and MYH7 (5.2%). Clinical characteristics independently associated with molecular diagnosis were: a lower age at diagnosis, family history of DCM, paroxysmal atrial fibrillation, absence of left bundle branch block, and the presence of an implantable cardioverter-defibrillator., Conclusions: Panel testing provides good diagnostic yield in patients with clinically suspected DCM. Causative variants were identified in 45 genes. In minority, two diagnostic variants were observed in dominant genes. Our results support the use of genetic panels in clinical settings in DCM patients with suspected genetic etiology., Competing Interests: MC, JH, JT, JH, IS, LK, MM, VK, JD, MG, PS, T-PA, JP, SM and JK are full-time employees of Blueprint Genetics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Heliö, Cicerchia, Hathaway, Tommiska, Huusko, Saarinen, Koskinen, Muona, Kytölä, Djupsjöbacka, Gentile, Salmenperä, Alastalo, Steinberg, Heliö, Paananen, Myllykangas and Koskenvuo.)

Background: Primary tumors of the heart are a rare phenomenon. Lymphatic malformations are congenital anomalies of the lymphatic system that tend to grow progressively. Lymphatic malformations are typically found in the cervical and axillary regions and found on pediatric patients. We report a 40-year-old woman with giant epimyocardial lymphatic malformation., Case Presentation: A 40-year-old woman was assessed due to suspected traumatic cardiac tamponade. Computed tomography of the heart and cardiac magnetic resonance imaging were compatible with either a large pericardial hemangioma or angiosarcoma. The tumor infiltrated deeply into the myocardium and could only be partially resected. Histopathological diagnosis was a cardiac lymphatic malformation with micro- and macrocystic components. The patient has remained asymptomatic for fourteen years after the surgery. In the latest follow-up, her left ventricular function had remained normal and the maximum thickness of the residual tumor had regressed., Conclusions: Even when a complete removal of a cardiac lymphatic malformation is not possible, a debulking procedure can yield a good long-term result., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Pathogenic variants in DSP associate with cardiac and cutaneous manifestations including arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, curly or wavy hair, and palmoplantar keratoderma (PPK). Episodes of myocardial inflammation associated with DSP cardiomyopathy might be confused in clinical work with myocarditis of other etiologies such as viral. Cardiac magnetic resonance imaging (CMR) may help in differential diagnosis., Methods and Results: This study comprised 49 Finnish patients: 34 participants from families with suspected DSP cardiomyopathy (9 index patients and 25 family members) and 15 patients with myocarditis. All 34 participants underwent genetic testing and cardiac evaluation, and 29 of them also underwent CMR. Participants with the DSP variant, numbering 22, were dermatologically examined. The 15 patients with myocarditis underwent CMR and were evaluated during their hospitalization.A heterozygous truncating DSP c.6310delA p.(Thr2104Glnfs*12) variant was confirmed in 29 participants. Only participants with the DSP variant had pacemakers and life-threatening ventricular arrhythmias. Of the participants with the DSP variant, 24% fulfilled cardiomyopathy criteria, and the median age at diagnosis was 53. Upon CMR, myocardial edema was found to be more common in patients with myocarditis. Both groups had a substantial percentage of late gadolinium enhancement (LGE). A ring-like LGE and increased trabeculation were observed only in participants with the DSP variant. All the studied participants with the DSP variant had PPK and curly or wavy hair. Hyperkeratosis developed before the age of 20 in most patients., Conclusions: The DSP c.6310delA p.(Thr2104Glnfs*12) variant associates with curly hair, PPK, and arrhythmogenic cardiomyopathy with increased trabeculation. Cutaneous symptoms developing in childhood and adolescence might help recognize these patients at an earlier stage. CMR, together with dermatologic characteristics, may help in diagnosis., Competing Interests: JWK is a cofounder, previous shareholder, and current full-time employee of Blueprint Genetics, which offers genetic diagnostic services. KH-J is a clinical consultant for Blueprint Genetics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Heliö, Brandt, Vaara, Weckström, Harjama, Kandolin, Järviö, Hannula-Jouppi, Heliö, Holmström and Koskenvuo.)

Background: Familial dilated cardiomyopathy (DCM) is a monogenic disorder typically inherited in an autosomal dominant pattern. We have identified two Finnish families with familial cardiomyopathy that is not explained by a variant in any previously known cardiomyopathy gene. We describe the cardiac phenotype related to homozygous truncating GCOM1 variants. Methods and Results: This study included two probands and their relatives. All the participants are of Finnish ethnicity. Whole-exome sequencing was used to test the probands; bi-directional Sanger sequencing was used to identify the GCOM1 variants in probands' family members. Clinical evaluation was performed, medical records and death certificates were obtained. Immunohistochemical analysis of myocardial samples was conducted. A homozygous GCOM1 variant was identified altogether in six individuals, all considered to be affected. None of the nine heterozygous family members fulfilled any cardiomyopathy criteria. Heart failure was the leading clinical feature, and the patients may have had a tendency for atrial arrhythmias. Conclusions: This study demonstrates the significance of GCOM1 variants as a cause of human cardiomyopathy and highlights the importance of searching for new candidate genes when targeted gene panels do not yield a positive outcome., Competing Interests: Authors IS, SA, HJ, JT, MT, JH, PS, MMU, JS, PS, MG, JP, SM, T-PA, and JK were employed by the company Blueprint Genetics, A Quest Diagnostics Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Heliö, Mäyränpää, Saarinen, Ahonen, Junnila, Tommiska, Weckström, Holmström, Toivonen, Nikus, Hathaway, Siivonen, Muona, Sistonen, Salmenperä, Gentile, Paananen, Myllykangas, Alastalo, Heliö and Koskenvuo.)

Background: Genetic testing in hypertrophic cardiomyopathy (HCM) is a published guideline-based recommendation. The diagnostic yield of genetic testing and corresponding HCM-associated genes have been largely documented by single center studies and carefully selected patient cohorts. Our goal was to evaluate the diagnostic yield of genetic testing in a heterogeneous cohort of patients with a clinical suspicion of HCM, referred for genetic testing from multiple centers around the world., Methods: A retrospective review of patients with a suspected clinical diagnosis of HCM referred for genetic testing at Blueprint Genetics was undertaken. The analysis included syndromic, myopathic and metabolic etiologies. Genetic test results and variant classifications were extracted from the database. Variants classified as pathogenic (P) or likely pathogenic (LP) were considered diagnostic., Results: A total of 1376 samples were analyzed. Three hundred and sixty-nine tests were diagnostic (26.8%); 373 P or LP variants were identified. Only one copy number variant was identified. The majority of diagnostic variants involved genes encoding the sarcomere (85.0%) followed by 4.3% of diagnostic variants identified in the RASopathy genes. Two percent of diagnostic variants were in genes associated with a cardiomyopathy other than HCM or an inherited arrhythmia. Clinical variables that increased the likelihood of identifying a diagnostic variant included: an earlier age at diagnosis (p < 0.0001), a higher maximum wall thickness (MWT) (p < 0.0001), a positive family history (p < 0.0001), the absence of hypertension (p = 0.0002), and the presence of an implantable cardioverter-defibrillator (ICD) (p = 0.0004)., Conclusion: The diagnostic yield of genetic testing in this heterogeneous cohort of patients with a clinical suspicion of HCM is lower than what has been reported in well-characterized patient cohorts. We report the highest yield of diagnostic variants in the RASopathy genes identified in a laboratory cohort of HCM patients to date. The spectrum of genes implicated in this unselected cohort highlights the importance of pre-and post-test counseling when offering genetic testing to the broad HCM population.

Background: Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM., Methods and Results: We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, p<0.0001). Based on the frequency of NRAP PTVs in the gnomAD reference population, and predicting full penetrance, biallelic NRAP variants could explain 0.25%-2.46% of all DCM cases., Conclusion: Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing., Competing Interests: Drs. Koskenvuo, Saarinen, Ahonen, Tommiska, Seppälä, Tuupanen, Kangas-Kontio, Schleit, Hathaway, Kytölä, Muona, Sistonen, Salmenperä, Gentile, Paananen, Myllykangas, Alastalo are full-time employees of Blueprint Genetics, a Quest Diagnostics Company, which offers genetic diagnostics for cardiomyopathies. The funder provided support in the form of salaries for authors [JWK, IS, SA, JT, ST, TKK, JS, JH, VK, MM, JS, PS, MG, JP, SM, TPA], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Dilated cardiomyopathy (DCM) is a condition characterized by dilatation and systolic dysfunction of the left ventricle in the absence of severe coronary artery disease or abnormal loading conditions. Mutations in the titin (TTN) and lamin A/C (LMNA) genes are the two most significant contributors in familial DCM. Previously mutations in the desmoplakin (DSP) gene have been associated with arrhythmogenic right ventricular cardiomyopathy (ARVC) and more recently with DCM., Methods: We describe the cardiac phenotype related to a DSP mutation which was identified in ten unrelated Finnish index patients using next-generation sequencing. Sanger sequencing was used to verify the presence of this DSP variant in the probands' relatives. Medical records were obtained, and clinical evaluation was performed., Results: We identified DSP c.6310delA, p.(Thr2104Glnfs*12) variant in 17 individuals of which 11 (65%) fulfilled the DCM diagnostic criteria. This pathogenic variant presented with left ventricular dilatation, dysfunction and major ventricular arrhythmias. Two patients showed late gadolinium enhancement (LGE) and myocardial edema on cardiac magnetic resonance imaging (MRI) that may suggest inflammatory process at myocardium., Conclusions: The patients diagnosed with DCM showed an arrhythmogenic phenotype as well as SCD at young age supporting the recently proposed concept of arrhythmogenic cardiomyopathy. This study also demonstrates relatively low penetrance of truncating DSP variant in the probands' family members by the age of 40. Further studies are needed to elucidate the possible relations between myocardial inflammation and pathogenic DSP variants.