Múltiplas substituições em domínios biologicamente ativos da glicoproteína do vírus rábico podem estar relacionadas com o perfil patogênico

Pathogenic profile of a rabies virus isolated from an insectivorous bat Lasiurus ega was compared with a rabies fixed virus strain (CVS/32) in hamster and mouse. Incubation and clinical periods, clinical manifestation and death rates were compared. Challenge of hamsters with L. ega was performed using: 10 2,611-4,021 LD50 /0,05 mL;. For CVS were used 10 3,7- 4,7 LD50 /0,05 mL. Were tested intramuscular (IM), intradermal (ID), intranasal (IN), epidermal abrasion (EA) inoculation routes. Viral antigen in brains was confirmed by Direct Immunofluorescence Test. Mortality percentages observed with L. ega rabies virus isolate were the following in hamster: 3,5 % IM, 10,710% IN; in mice: 50.0% IM, 30.0% IN. Furious rabies was predominant. Mortality percentages observed with CVS/32 in hamster: 12.5% IM, 62.5% ID, 12.5% IN; in mice 100.0% IM, 70.0% ID, 10.0% IN. Paralytic rabies was found with this strain in both animal models. Epidermic abrasion was not a suitable challenge route. Incubation period was 5-7 days for CVS and 11-16 days for L. ega isolate, meanwhile clinical periods were comprehended between 47 days for both viruses. Several substitutions were detected at antigenic domains of glycoprotein: AI (position 231), AII (3442 and 198-200), domain of fusion dependent on low pH (102179), transmembrane domain (440461) and residue 242. These viruses showed contrasting biological behaviors that can be linked to those substitutions at antigenic domains previously described.O perfil patogênico de um vírus da raiva isolado de um morcego insetívoro Lasiurus ega foi comparado com o de vírus fixo de raiva (CVS/32) em hamster e camundongo, determinando os períodos de incubação e clínico, manifestação clínica e mortalidade. Os animais foram desafiados com 10 2,611-4,021 DL50 /0,05 mL do isolado de L. ega e 10 3,7- 4,7 LD50 /0,05 mL do CVS/32, usando as vias: intramuscular (IM), intradermica (ID), intranasal (IN) e abrasão epidermica (AE). A presença do antígeno viral foi confirmada pela prova de imunofluorescência direta. As porcentagens de mortalidade observadas com o isolado de L. ega foram as seguintes em hamster: 3,5% IM, 10,71% IN; em camundongo: 50.0% IM, 30.0% IN. A forma furiosa da doença foi predominante. As porcentagens de mortalidade observadas com o vírus CVS/32 em hamster foram as seguintes: 12.5% IM, 62.5% ID, 12.5% IN; em camundongo 100.0% IM, 70.0% ID, 10.0% IN. Com este vírus foi observada raiva paralitica. A via AE mostrou-se inadequada para induzir doença. O período de incubação foi de 57 dias para o CVS/32 e 11-16 dias para o isolado de L. ega, entre tanto os períodos clínicos oscilaram entre 47 dias para ambos os vírus. Varias substituições foram achadas em domínios antigênicos da glicoproteína: AI (posição 231), AII (34 42 e 198-200), domínio de fusão dependente de baixo pH (102179), domínio da transmembrana (440461) e resíduo 242. Esses vírus mostraram comportamentos biológicos distintos o que poderia estar ligados às substituições nos domínios antigênicos anteriormente descritos

Molecular epidemiology of livestock rabies viruses isolated in the northeastern Brazilian states of Paraíba and Pernambuco from 2003 - 2009

<p>Abstract</p> <p>Background</p> <p>Limited or no epidemiological information has been reported for rabies viruses (RABVs) isolated from livestock in the northeastern Brazilian states of Paraíba (PB) and Pernambuco (PE). The aim of this study was to clarify the molecular epidemiology of RABVs circulating in livestock, especially cattle, in these areas between 2003 and 2009.</p> <p>Findings</p> <p>Phylogenetic analysis based on 890 nt of the nucleoprotein (N) gene revealed that the 52 livestock-derived RABV isolates characterized here belonged to a single lineage. These isolates clustered with a vampire bat-related RABV lineage previously identified in other states in Brazil; within PB and PE, this lineage was divided between the previously characterized main lineage and a novel sub-lineage.</p> <p>Conclusions</p> <p>The occurrences of livestock rabies in PB and PE originated from vampire bat RABVs, and the causative RABV lineage has been circulating in this area of northeastern Brazil for at least 7 years. This distribution pattern may correlate to that of a vampire bat population isolated by geographic barriers.</p

Molecular epidemiological tracing of a cattle rabies outbreak lasting less than a month in Rio Grande do Sul in southern Brazil

Abstract\ud \ud Background\ud Vampire bat-transmitted cattle rabies cases are typically encountered in areas where the disease is endemic. However, over the period of a month in 2009, an outbreak of cattle rabies occurred and then ended spontaneously in a small area of the Rio Grande do Sul State in southern Brazil. To investigate the epidemiological characteristics of this rabies outbreak in Rio Grande do Sul, 26 nucleotide sequences of rabies virus (RABV) genomes that were collected in this area were analyzed phylogenetically.\ud \ud \ud Results\ud Nucleotide sequence identities of the nucleoprotein gene and G–L intergenic region of the 26 RABVs were greater than 99.6 %. Phylogenetic analysis showed that all RABVs clustered with the vampire bat-related cattle RABV strains and that the RABVs were mainly distributed in southern Brazil.\ud \ud \ud Conclusions\ud The findings of the present study suggested that a small population of rabid vampire bats carrying a single RABV strain produced a spatiotemporally restricted outbreak of cattle rabies in southern Brazil.This study was supported in part by a Grant-in-Aid for Scientific Research\ud (24580453) from the Japan Society for the Promotion of Science and the\ud Strategic Research Base Development Program, “International joint research\ud and training of young researchers for zoonosis control in a globalized world”,\ud and a matching fund subsidy from the Ministry of Education, Culture, Sports,\ud Science and Technology of Japan (S0991023 and S1491007)

日本人成人におけるパノラマX線写真上の下顎皮質骨と海綿骨構造との関係：コーンビームCTによる分析

Objectives The purpose of this study was to assess the association between the cortical shape of the mandible, as detected on panoramic radiographs, and trabecular bone structure, as assessed by cone-beam computed tomography (CBCT), in Japanese adults. Methods Panoramic radiographs and CBCT images of the mandibles of 50 subjects (18 men, 32 women), aged 45–86 years, were evaluated. An experienced oral and maxillofacial radiologist categorized the cortical shape of the mandible as detected on panoramic radiographs as normal, mildly to moderately eroded, and severely eroded cortices, respectively. All mandibles were scanned using CBCT. Four bone structure parameters of the basal portion of the mandible were calculated in three dimensions using an image-analysis system: total bone volume (mm3); cortical bone volume fraction (%); trabecular bone volume fraction (%); fractal dimension. One-way analysis of covariance with Bonferroni correction was employed to evaluate differences in the four bone parameters among the three cortical shape groups. Pearson’s correlation coefficient was calculated to examine correlations between age and cortical and trabecular bone volume fractions.Results Progression of cortical bone erosion was significantly associated with increased trabecular bone volume fraction (P\0.001) and increased fractal dimension(P = 0.01). Cortical bone volume fraction decreased significantly with age (P = 0.04). However, trabecular bone volume fraction tended to increase with age (P = 0.06). Conclusions The change in the trabecular bone structure of the mandible may differ from that of the general skeleton in Japanese adults.2013博士（歯学）松本歯科大

18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging evaluation of chorea

Chorea is thought to be caused by deactivation of the indirect pathway in the basal ganglia circuit. However, few imaging studies have evaluated the basal ganglia circuit in actual patients with chorea. We investigated the lesions and mechanisms underlying chorea using brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective case series included three patients with chorea caused by different diseases: hyperglycemic chorea, Huntington’s disease, and subarachnoid hemorrhage. All the patients showed dysfunction in the striatum detected by both MRI and FDG-PET. These neuroimaging findings confirm the theory that chorea is related to an impairment of the indirect pathway of basal ganglia circuit

Molecular and geographic analyses of vampire bat-transmitted cattle rabies in central Brazil

<p>Abstract</p> <p>Background</p> <p>Vampire bats are important rabies virus vectors, causing critical problems in both the livestock industry and public health sector in Latin America. In order to assess the epidemiological characteristics of vampire bat-transmitted rabies, the authors conducted phylogenetic and geographical analyses using sequence data of a large number of cattle rabies isolates collected from a wide geographical area in Brazil.</p> <p>Methods</p> <p>Partial nucleoprotein genes of rabies viruses isolated from 666 cattle and 18 vampire bats between 1987 and 2006 were sequenced and used for phylogenetic analysis. The genetic variants were plotted on topographical maps of Brazil.</p> <p>Results</p> <p>In this study, 593 samples consisting of 24 genetic variants were analyzed. Regional localization of variants was observed, with the distribution of several variants found to be delimited by mountain ranges which served as geographic boundaries. The geographical distributions of vampire-bat and cattle isolates that were classified as the identical phylogenetic group were found to overlap with high certainty. Most of the samples analyzed in this study were isolated from adjacent areas linked by rivers.</p> <p>Conclusion</p> <p>This study revealed the existence of several dozen regional variants associated with vampire bats in Brazil, with the distribution patterns of these variants found to be affected by mountain ranges and rivers. These results suggest that epidemiological characteristics of vampire bat-related rabies appear to be associated with the topographical and geographical characteristics of areas where cattle are maintained, and the factors affecting vampire bat ecology.</p

One-year morbidity and mortality in patients treated with standard-dose and low-dose apixaban after acute large vessel occlusion stroke

The version of record of this article, first published in Journal of Thrombosis and Thrombolysis, is available online at Publisher’s website: https://doi.org/10.1007/s11239-024-02954-7.Although low-dose direct oral anticoagulants (DOACs) are recommended for patients at high risk of bleeding complications, it remains unclear whether the dose reduction in real-world setting is also appropriate in patients after large-vessel occlusion (LVO) stroke. This study hypothesized that patients with atrial fibrillation (AF) and LVO receiving low-dose DOACs have an increased risk of ischemic and hemorrhagic events. The study aimed to assess 1 year morbidity and mortality in patients treated with standard-dose and low-dose apixaban after LVO stroke. A post hoc analysis was performed using the acute LVO registry data, which enrolled patients with AF and LVO who received apixaban within 14 days of stroke onset. The incidences of ischemic events (ischemic stroke, acute coronary syndrome, acute myocardial infarction, and systemic embolism), major bleeding events, and death from any cause were compared between patients receiving standard- and low-dose apixaban. Of 643 patients diagnosed with LVO, 307 (47.7%) received low-dose apixaban. After adjustment for clinically relevant variables, no significant differences were observed in the incidence of ischemic events (adjusted hazard ratio [aHR]: 2.12, 95% confidence interval [CI] 0.75–6.02), major bleeding events (aHR: 1.17, 95% CI 0.50–2.73), and death from any cause (aHR: 1.95, 95% CI 0.78–4.89) between patients receiving standard- and low-dose apixaban. No significant differences were observed in the incidence of ischemic events, major bleeding events, or death from any cause between patients with AF and LVO receiving standard- and low-dose apixaban

Osteocrin ameliorates adriamycin nephropathy via p38 mitogen-activated protein kinase inhibition

Natriuretic peptides exert multiple effects by binding to natriuretic peptide receptors (NPRs). Osteocrin (OSTN) binds with high affinity to NPR-C, a clearance receptor for natriuretic peptides, and inhibits degradation of natriuretic peptides and consequently enhances guanylyl cyclase-A (GC-A/NPR1) signaling. However, the roles of OSTN in the kidney have not been well clarified. Adriamycin (ADR) nephropathy in wild-type mice showed albuminuria, glomerular basement membrane changes, increased podocyte injuries, infiltration of macrophages, and p38 mitogen-activated protein kinase (MAPK) activation. All these phenotypes were improved in OSTN- transgenic (Tg) mice and NPR3 knockout (KO) mice, with no further improvement in OSTN-Tg/NPR3 KO double mutant mice, indicating that OSTN works through NPR3. On the contrary, OSTN KO mice increased urinary albumin levels, and pharmacological blockade of p38 MAPK in OSTN KO mice ameliorated ADR nephropathy. In vitro, combination treatment with ANP and OSTN, or FR167653, p38 MAPK inhibitor, reduced Ccl2 and Des mRNA expression in murine podocytes (MPC5). OSTN increased intracellular cyclic guanosine monophosphate (cGMP) in MPC5 through GC-A. We have elucidated that circulating OSTN improves ADR nephropathy by enhancing GC-A signaling and consequently suppressing p38 MAPK activation. These results suggest that OSTN could be a promising therapeutic agent for podocyte injury

Von Willebrand Factor Antigen Levels Predict Poor Outcomes in Patients With Stroke and Cancer: Findings From the Multicenter, Prospective, Observational SCAN Study

Kawano T., Gon Y., Sakaguchi M., et al. Von Willebrand Factor Antigen Levels Predict Poor Outcomes in Patients With Stroke and Cancer: Findings From the Multicenter, Prospective, Observational SCAN Study. Journal of the American Heart Association 13, e032284 (2024); https://doi.org/10.1161/JAHA.123.032284.BACKGROUND: Patients with acute ischemic stroke and active cancer have more severe neurological symptoms, elevated risks of stroke recurrence, and death compared with the general population. We examined whether von Willebrand factor (vWF) antigen levels at stroke onset were associated with the poor outcomes of patients with stroke and cancer. METHODS AND RESULTS: Using data from 90 patients with acute ischemic stroke and active cancer who were registered in the SCAN (Ischemic Stroke in Patients With Cancer and Neoplasia) study, a prospective multicenter, observational study in Japan, we divided patients into 2 groups according to their median vWF antigen levels (high, n=46; or low, n=44). The high-vWF group had a significantly higher initial National Institutes of Health Stroke Scale score (median, 7 [interquartile range, 3-11.25] versus 3 [interquartile range, 1-8.5]; P<0.05) and a significantly higher incidence of cryptogenic stroke (32 [70%] versus 16 [36%]; P<0.01) and venous thromboembolism (7 [15%] versus 0 [0%]; P<0.01), as well as multiple lesions (28 [62%] versus 12 [27%]; P<0.001), than the low-vWF group. We observed no significant difference in the rate of stroke recurrence within 1 year between the groups. However, increased vWF levels were an independent predictor of death within 1 year of stroke onset, after adjusting for potential confounders (odds ratio, 6.77 [95% CI, 1.49-30.78]; P<0.05). CONCLUSIONS: Elevated vWF antigen levels were associated with adverse outcomes in patients with cancer-associated stroke and may represent a useful biomarker to guide future therapeutic interventions

Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study

BACKGROUND: Limited data exist on the prognostic factors for patients with ischemic stroke and active cancer. METHODS AND RESULTS: We conducted a prospective, multicenter, observational study in Japan, including patients with acute ischemic stroke and active cancer, to investigate the prognostic factors. We followed up the patients for 1 year after stroke onset. The patients were divided into 2 groups according to cryptogenic stroke and known causes (small-vessel occlusion, large-artery atherosclerosis, cardioembolism, and other determined cause), and survival was compared. The hazard ratios (HRs) and 95% CIs for mortality were calculated using Cox regression models. We identified 135 eligible patients (39% women; median age, 75 years). Of these patients, 51% had distant metastasis. A total of 65 (48%) and 70 (52%) patients had cryptogenic stroke and known causes, respectively. Patients with cryptogenic stroke had significantly shorter survival than those with known causes (HR [95% CI], 3.11 [1.82–5.32]). The multivariable Cox regression analysis revealed that distant metastasis, plasma D-dimer levels, venous thromboembolism (either deep venous thrombosis or pulmonary embolism) complications at stroke onset were independent predictors of mortality after adjusting for potential confounders. Cryptogenic stroke was associated with prognosis in univariable analysis but was not significant in multivariable analysis. The plasma D-dimer levels stratified the prognosis of patients with ischemic stroke and active cancer. CONCLUSIONS: The prognosis of patients with acute ischemic stroke and active cancer varied considerably depending on stroke mechanism, distant metastasis, and coagulation abnormalities. The present study confirmed that coagulation abnormalities were crucial in determining the prognosis of such patients.Gon Y., Sakaguchi M., Yamagami H., et al. Predictors of Survival in Patients With Ischemic Stroke and Active Cancer: A Prospective, Multicenter, Observational Study. Journal of the American Heart Association 12, e029618 (2023); https://doi.org/10.1161/JAHA.123.029618