333 research outputs found

    Placas estabilizadoras: avaliação de sua eficácia no tratamento das disfunções temporomandibulares

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    A placa estabilizadora é o mais difundido método de tratamento das disfunções têmporo-mandibulares. A Ressonância Magnética (RM) é o exame mais indicado para a visualização dos componentes da Articulação têmporo-mandibular (ATM). Quarenta pacientes com sinais e sintomas de disfunções têmporo-mandibulares foram tratados com as placas estabilizadoras por um período médio de 12 meses, com controles periódicos quinzenais. Após a estabilização do quadro clínico foram realizados ajustes oclusais e a avaliação por meio da RM. Concluímos que os melhores resultados dessa modalidade de tratamento são relacionados à melhora total (70%) ou parcial (22,5%) da sintomatologia dolorosa e ao restabelecimento da função do complexo crânio-mandibular. A RM permitiu avaliar e concluir que as placas possibilitam condições para que o organismo possa criar meios resistentes às disfunções da articulação têmporo-mandibular por meio da eliminação de vários fatores etiológicos. E que após o tratamento, os pacientes podem conviver com os deslocamentos do disco, alguns com maior, outros com menor tolerância.Occlusal stabilization appliances or splints are the most widely employed method for treatment of temporomandibular disorders (TMD). Magnetic Resonance Imaging (MRI) is the most indicated imaging modality to evaluate the components of the temporomandibular joint (TMJ). Forty patients with signs and symptoms of temporomandibular disorders were treated with splints for a mean period of 12 months, comprising regular semimonthly follow-ups. After stabilization of the clinical status, occlusal adjustments and MRI evaluation were performed. It was concluded that the success of this kind of treatment are related to the total (70%) or partial improvement (22.5%) of painful symptomatology and to the functional reestablishment of the craniomandibular complex. The MRI allowed evaluation and also the conclusion that the splints provide conditions for the organism to develop means to resist to the temporomandibular disorders by means of elimination of several etiologic factors. Moreover, after treatment the patients are able to cope with disc displacements with larger or smaller tolerance

    RNA structure-wide discovery of functional interactions with multiplexed RNA motif library

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    RNA構造のライブラリ化を通じてRNA 構造ごとにおけるRNA-タンパク質相互作用を大規模に解析するシステム「FOREST」の開発 --RNAを標的とする創薬に道--. 京都大学プレスリリース. 2020-12-09.Biochemical assays and computational analyses have discovered RNA structures throughout various transcripts. However, the roles of these structures are mostly unknown. Here we develop folded RNA element profiling with structure library (FOREST), a multiplexed affinity assay system to identify functional interactions from transcriptome-wide RNA structure datasets. We generate an RNA structure library by extracting validated or predicted RNA motifs from gene-annotated RNA regions. The RNA structure library with an affinity enrichment assay allows for the comprehensive identification of target-binding RNA sequences and structures in a high-throughput manner. As a proof-of-concept, FOREST discovers multiple RNA-protein interaction networks with quantitative scores, including translational regulatory elements that function in living cells. Moreover, FOREST reveals different binding landscapes of RNA G-quadruplex (rG4) structures-binding proteins and discovers rG4 structures in the terminal loops of precursor microRNAs. Overall, FOREST serves as a versatile platform to investigate RNA structure-function relationships on a large scale

    Cost-Effectiveness Analysis of Canine Heartworm Preventive Products

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    Heartworm disease in domestic dogs is a preventable disease caused by infection with the parasite, Dirofilaria immitis, that can lead to severe pulmonary and cardiac disease. Prevention is through consistent use of FDA-approved heartworm preventive (HWP) products. Banfield® Pet Hospital (Banfield PH), the largest network of primary care small animal hospitals in the United States, carries 11 HWP products for dogs in its formulary. Preliminary research provide evidence that rates of “breakthrough” infections differ by the route of HWP product administration and that (previously) infected dogs that were treated to clear the infection are still at higher risk of cardiac disease later in life, emphasizing importance of prevention. A cost-effectiveness analysis was conducted to evaluate HWP product categories, based on their route of administration, and owner lifetime cost to prevent and/or treat heartworm infection with years-of-life gained (YLG) as the outcome. Comparing injectable extended release (6- or 12-month) products and monthly topical or oral products to receipt of no HWP product, the analysis revealed that expected owner costs and patient outcome did not differ greatly between the product categories with an estimated gain of 1.4 months of life if they received HWP products. The incremental cost-effectiveness analysis estimates that average dog owner cost of 7,500+perYLGregardlessofproductcategory.EvaluatingreasonablecostforHWPproductsforadiseasethatmaycost7,500+ per YLG regardless of product category. Evaluating reasonable cost for HWP products for a disease that may cost 3,000+ (out-of-pocket) to treat is difficult, as willingness-to-pay thresholds or accepted estimates for value of a pet’s life beyond fair market value have not been established. While no obvious indication that HWP product categories are more cost-effective, the analysis demonstrates the potential of this approach to compare individual products to inform decision-making for product selection and pricing in Banfield PH and the veterinary industry

    Modification of a loop sequence between α-helices 6 and 7 of virus capsid (CA) protein in a human immunodeficiency virus type 1 (HIV-1) derivative that has simian immunodeficiency virus (SIVmac239) vif and CA α-helices 4 and 5 loop improves replication in cynomolgus monkey cells

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    <p>Abstract</p> <p>Background</p> <p>Human immunodeficiency virus type 1 (HIV-1) productively infects only humans and chimpanzees but not cynomolgus or rhesus monkeys while simian immunodeficiency virus isolated from macaque (SIVmac) readily establishes infection in those monkeys. Several HIV-1 and SIVmac chimeric viruses have been constructed in order to develop an animal model for HIV-1 infection. Construction of an HIV-1 derivative which contains sequences of a SIVmac239 loop between α-helices 4 and 5 (L4/5) of capsid protein (CA) and the entire SIVmac239 <it>vif </it>gene was previously reported. Although this chimeric virus could grow in cynomolgus monkey cells, it did so much more slowly than did SIVmac. It was also reported that intrinsic TRIM5α restricts the post-entry step of HIV-1 replication in rhesus and cynomolgus monkey cells, and we previously demonstrated that a single amino acid in a loop between α-helices 6 and 7 (L6/7) of HIV type 2 (HIV-2) CA determines the susceptibility of HIV-2 to cynomolgus monkey TRIM5α.</p> <p>Results</p> <p>In the study presented here, we replaced L6/7 of HIV-1 CA in addition to L4/5 and <it>vif </it>with the corresponding segments of SIVmac. The resultant HIV-1 derivatives showed enhanced replication capability in established T cell lines as well as in CD8+ cell-depleted primary peripheral blood mononuclear cells from cynomolgus monkey. Compared with the wild type HIV-1 particles, the viral particles produced from a chimeric HIV-1 genome with those two SIVmac loops were less able to saturate the intrinsic restriction in rhesus monkey cells.</p> <p>Conclusion</p> <p>We have succeeded in making the replication of simian-tropic HIV-1 in cynomolgus monkey cells more efficient by introducing into HIV-1 the L6/7 CA loop from SIVmac. It would be of interest to determine whether HIV-1 derivatives with SIVmac CA L4/5 and L6/7 can establish infection of cynomolgus monkeys <it>in vivo</it>.</p

    The comparison of endothelial function between conduit artery and microvasculature in patients with coronary artery disease

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    Background: Flow-mediated dilation (FMD) and reactive hyperemia-peripheral arterial tonometry (RH-PAT) are both established modalities to assess vascular endothelial function. However, clinical significance of FMD and RH-PAT may be different because these methods measure vascular function in different vessels (conduit arteries and resistance vessels). Methods: To elucidate differences in the clinical significance of FMD and RH-PAT, a simultaneous determination of FMD was performed and reactive hyperemia index (RHI) measured by RH-PAT in 131 consecutive patients who underwent coronary angiography for suspicion of coronary artery disease (CAD). Results: There was no significant correlation between FMD and RHI in patients overall. When patients were divided into four groups: FMD ≥ 6%/RHI ≥ 1.67 group, FMD ≥ 6%/RHI &lt; 1.67 group, FMD &lt; 6%/RHI ≥ 1.67 group and FMD &lt; 6%/RHI &lt; 1.67 group, the highest incidence of multivessel CAD was seen in the FMD &lt; 6%/RHI &lt; 1.67 group (52%). Multiple logistic regression analysis showed that a prevalence of both FMD &lt; 6% and RHI &lt; 1.67 was an independent predictor of multivessel CAD (odds ratio: 4.160, 95% confidence interval: 1.505–11.500, p = 0.006). RHI was negatively correlated with the baseline vessel diameter (R = –0.268, p = 0.0065) and maximum vessel diameter (R = –0.266, p = 0.0069) in patients with FMD &lt; 6%, whereas these correlations were absent in patients with FMD ≥ 6%. Conclusions: Present results suggest that noninvasive assessment of vascular endothelial functions provide pathophysiological information on both conduit arteries and resistance vessels in patients with CAD

    Juvenile Bow Hunter’s Stroke without Hemodynamic Changes

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    Bow hunter’s stroke (BHS) is a cerebrovascular disease caused by occlusion of the vertebral artery (VA) on head rotation. BHS is generally associated with hemodynamic changes, often leading to vertebrobasilar insufficiency symptoms, such as vertigo and faintness. Although artery-to-artery embolism has also been proposed as an underlying mechanism, it remains controversial. This report documents a case of BHS without hemodynamic changes. We describe a 26-year-old male patient who had VA occlusion on head rotation and repetitive infarction of thalami. He had an anomalous bypass of the VA and therefore no symptomatic hemodynamic changes. Thus, non-hemodynamic BHS should be considered in juvenile patients with vertebrobasilar stroke

    Effects of sex and joint action on voluntary activation

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    The current study tested the hypothesis that voluntary activation during maximal voluntary contraction (MVC) conditionally depends on sex and joint action. Twenty-eight healthy adults (14 of each sex) performed knee extensor MVC and plantar flexor MVC at extended and flexed knee positions. Voluntary activation during MVC was assessed using a twitch interpolation technique. The voluntary activation during plantar flexor MVC at the extended knee position was significantly lower (P = 0.020, 95% confidence interval 1.4 to 14.6, Cohen’s d for between-subject design = 0.94) in women (88.3% ± 10.0%) than in men (96.2% ± 6.6%). In contrast, no significant sex differences were shown in the voluntary activation during knee extensor MVC (93.7% ± 5.9% (women) vs. 95.0%  ± 3.9% (men)) and during plantar flexor MVC at the flexed knee position (90.4% ± 12.2% (women) vs. 96.8% ± 5.6% (men)). The voluntary activation during knee extensor MVC was significantly higher (P = 0.001, 95% confidence interval 2.1 to 8.8, Cohen’s d for within-subject design = 0.69) than that during plantar flexor MVC at the extended knee position in women, whereas the corresponding difference was not observed in men. The results revealed that the existence of sex difference in the voluntary activation during MVC depends on joint action and joint angle

    Geographical, genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis)

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    The antiretroviral factor tripartite motif protein 5 (TRIM5) gene-derived isoform (TRIMCyp) has been found in at least three species of Old World monkey: rhesus (Macaca mulatta), pig-tailed (Macaca nemestrina) and cynomolgus (Macaca fascicularis) macaques. Although the frequency of TRIMCyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of TRIMCyp in cynomolgus macaques remain to be definitively elucidated. Here, the geographical and genetic diversity of TRIM5α/TRIMCyp in cynomolgus macaques was studied in comparison with their anti-lentiviral activity. It was found that the frequency of TRIMCyp in a population in the Philippines was significantly higher than those in Indonesian and Malaysian populations. Major and minor haplotypes of cynomolgus macaque TRIMCyp with single nucleotide polymorphisms in the cyclophilin A domain were also found. The functional significance of the polymorphism in TRIMCyp was examined, and it was demonstrated that the major haplotype of TRIMCyp suppressed human immunodeficiency virus type 1 (HIV-1) but not HIV-2, whilst the minor haplotype of TRIMCyp suppressed HIV-2 but not HIV-1. The major haplotype of TRIMCyp did not restrict a monkey-tropic HIV-1 clone, NL-DT5R, which contains a capsid with the simian immunodeficiency virus-derived loop between α-helices 4 and 5 and the entire vif gene. These results indicate that polymorphisms of TRIMCyp affect its anti-lentiviral activity. Overall, the results of this study will help our understanding of the genetic background of cynomolgus macaque TRIMCyp, as well as the host factors composing species barriers of primate lentiviruses

    Effects of 3 Years of Treatment with a Selective Estrogen Receptor Modulator for Postmenopausal Osteoporosis on Markers of Bone Turnover and Bone Mineral Density

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    Aim: The aim of the present study was to assess the changes in bone mineral density and bone turnover markers in long-term SERM. Methods: The study was performed on 25 female outpatients with primary osteoporosis treated at the Osteoporosis Department of Showa University School of Medicine. All patients had been on raloxifene (60mg/day) for ≥ 3 years. The mean patient age was 67.1 years and the women were, on average, 18.4 years postmenopausal. Levels of bone turnover markers (urinary naltrexone [NTX] and bone-specific alkaline phosphatase [BAP]) and bone mineral density (BMD; front lumbar vertebrae, three proximal femur sites, and two distal radius sites) were determined before and then annually after starting raloxifene for a period of 3 years. Results: Over the 3-year treatment period, significant decreases were seen in both urinary NTX and BAP levels. Although BMD of the lumbar vertebrae and distal radius was increased over the 3 years after initiation of raloxifene treatment, the difference failed to reach statistical significance. The BMD of the femoral neck decreased, whereas that of the femoral trochanter and femoral intertrochanter area increased. Conclusions: The selective estrogen receptor modulator raloxifene is suitable for the treatment of osteoporosis in postmenopausal patients because it reduces bone turnover while maintaining adequate bone density
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