RESUMO
Infectious diseases are caused by the invasion of pathogenic microorganisms such as fungi, bacteria, viruses, and parasites. After infection, disease progression relies on the complex interplay between the host immune response and the microorganism evasion strategies. The host's survival depends on its ability to mount an efficient protective anti-microbial response to accomplish pathogen clearance while simultaneously preventing tissue injury by keeping under control the excessive inflammatory process. The purinergic system has the dual function of regulating the immune response and triggering effector antimicrobial mechanisms. This review provides an overview of the current knowledge of the modulation of innate and adaptive immunity driven by the purinergic system during parasitic, bacterial and viral infections.
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Imunidade Inata , Parasitos , AnimaisRESUMO
Hypoxia leads to post-treatment metastasis and recurrences of cancer via the epithelial-mesenchymal transition (EMT). Radiotherapy itself may also contribute to the acquisition of EMT phenotypes. Despite extensive studies on the EMT driven by either hypoxia or radiation stimuli, the molecular mechanisms characterizing these EMT events remain unclear. Thus, we aimed to evaluate the differences in the molecular pathways between hypoxia-induced EMT (Hypo-EMT) and radiation-induced EMT (R-EMT). Further, we investigated the therapeutic effects of HIF-1α inhibitor (LW6) on Hypo-EMT and R-EMT cells. A549 cells, lung adenocarcinoma cell line, acquired enhanced wound-healing activity under both hypoxia and irradiation. Localization of E-cadherin was altered from the cell membrane to the cytoplasm in both hypoxia and irradiated conditions. Of note, the expression levels of vimentin, one of the major EMT markers, was enhanced in irradiated cells, while it decreased under hypoxia condition. Importantly, LW6 significantly blocked EMT-related malignant phenotypes in both Hypo-EMT cells and R-EMT cells with concomitant re-location of E-cadherin onto the cell membrane. Moreover, LW6 deflected stress responsive signalling, JNK, activated sustainably under hypoxic condition, and the blockage of JNK impaired EMT phenotypes. Together, this work demonstrated the molecular events underlying Hypo-EMT and R-EMT, and highlighted HIF-1α as a therapeutic target not only in Hypo- EMT, but also in R-EMT.
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Hipóxia Celular , Transição Epitelial-Mesenquimal , Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares , Células A549 , Antígenos CD , Caderinas , Transição Epitelial-Mesenquimal/efeitos da radiação , Humanos , Subunidade alfa do Fator 1 Induzível por HipóxiaRESUMO
BACKGROUND: Taxanes are the current first-line treatment for advanced cutaneous angiosarcoma (CAS) for patients who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. However, no effective second-line therapy for such patients has been established. METHODS: We designed a single-arm prospective observational study of eribulin mesylate (ERB) administered at a dose of 1·4 mg m-2 on days 1 and 8 in a 21-day cycle. Patients with advanced CAS who were previously treated with a taxane and were scheduled to begin ERB treatment were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were response rate (RR), progression-free survival (PFS) and toxicity assessment. RESULTS: We enrolled a total of 25 patients. The median OS and PFS were 8·6 months and 3·0 months, respectively. The best overall RR was 20% (five of 25). In total, 16 grade 3/4 severe adverse events (SAEs) occurred; however, all patients recovered. Patients who achieved partial response or stable disease as best response had longer OS than those with progressive disease (median OS not reached and 3·3 months, respectively; P < 0·001). Patients who did not experience SAEs showed longer OS than those who did (median OS 18·8 months and 7·5 months, respectively; P < 0·05). Patients with distant metastasis had shorter median OS than those with locoregional disease, but without statistically significant difference. CONCLUSIONS: ERB showed a promising RR and is a potential candidate for second-line treatment for patients with CAS, after treatment with taxanes. However, owing to the occurrence of SAEs in over half of the participants, caution should be exercised regarding ERB use in elderly patients. What is already known about this topic? Taxanes are the current first-line treatment for patients with advanced cutaneous angiosarcoma (CAS) who are considered difficult to treat with doxorubicin owing to advanced age or comorbidity. No effective therapy for taxane-resistant CAS has been established thus far. Eribulin suppresses microtubule polymerization and elicits an antitumour effect similar to that of taxanes. What does this study add? In our single-arm prospective observational study to evaluate the efficacy of eribulin for treating patients with advanced CAS who previously received taxanes, the median overall survival and progression-free survival were 8·6 and 3·0 months, respectively. Response rates at weeks 7, 13 and 25 were 20%, 17% and 14%, respectively. Although 16 grade 3/4 severe adverse events occurred, all patients recovered. Eribulin showed a promising response rate and is a potential candidate for second-line treatment in CAS after taxane treatment. Linked Comment: Smrke and Benson. Br J Dermatol 2020; 183:797-798.
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Neoplasias da Mama , Hemangiossarcoma , Idoso , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes , Furanos , Hemangiossarcoma/tratamento farmacológico , Humanos , Cetonas , Taxoides , Resultado do TratamentoRESUMO
BACKGROUND: Surgery is the gold standard for basal cell carcinomas (BCC). Current recommended surgical margins for BCCs are determined from studies in Caucasian populations. However, the appropriate surgical margins for BCCs in non-white races are unclear. OBJECTIVES: To investigate the accuracy of preoperative determination of clinical tumour borders and appropriate surgical margins in Japanese patients with BCC. METHODS: The maximum calculated differences in distance between the preoperatively determined surgical margins and the actual histologic tumour side margins were considered as 'accuracy gaps' of clinical tumour borders. Estimated side margin positivity rates (ESMPRs) with narrower (2 and 3 mm) surgical margins were calculated on the basis of the accuracy gaps. RESULTS: Overall, 1000 surgically excised BCCs from 980 Japanese patients were included. The most frequent histologic subtype was nodular BCC (67%). The median accuracy gap was 0.3 mm [interquartile range (IQR): -0.5 to +1 mm]. The ESMPRs with 2- and 3-mm surgical margins were 3.8% and 1.4%, respectively. Only the ESMPRs between the well-defined (n = 921) and poorly defined clinical tumour border groups (n = 79) showed statistical difference [2-mm margin: 3.1% vs. 11.7%, OR: 3.89, 95% confidential interval (CI): 1.41-10.71, P <0.01; 3-mm margin: 0.97% vs. 6.3%, OR: 6.58, 95% CI: 1.67-25.99, P <0.01]. No significant differences in ESMPRs were noted in other subgroups including risk classifications. CONCLUSIONS: The determined clinical tumour border accuracy gaps in this Japanese cohort were negligible. Dermatologic surgeons may use narrower surgical margins with acceptable margin positivity rates. The clarity of clinical tumour borders could be an appropriate guide for selection of different surgical margins in the Japanese cohort.
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Carcinoma Basocelular , Neoplasias Cutâneas , Carcinoma Basocelular/cirurgia , Humanos , Japão , Margens de Excisão , Estudos Retrospectivos , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND: Interaction between cancer cells and fibroblasts mediated by extracellular matrix metalloproteinase inducer (emmprin, CD147) is important in the invasion and proliferation of cancer cells. However, the exact mechanism of emmprin mediated stimulation of matrix metalloprotease-2 (MMP-2) production from fibroblasts has not been elucidated. Our previous studies using an inhibitory peptide against emmprin suggested the presence of a molecule on the cell membrane which forms a complex with emmprin. Here we show that CD73 expressed on fibroblasts interacts with emmprin and is a required factor for MMP-2 production in co-cultures of sarcoma cells with fibroblasts. METHODS: CD73 along with CD99 was identified by mass spectrometry analysis as an emmprin interacting molecule from a co-culture of cancer cells (epithelioid sarcoma cell line FU-EPS-1) and fibroblasts (immortalized fibroblasts cell line ST353i). MMP-2 production was measured by immunoblot and ELISA. The formation of complexes of CD73 with emmprin was confirmed by immunoprecipitation, and their co-localization in tumor cells and fibroblasts was shown by fluorescent immunostaining and proximity ligation assays. RESULTS: Stimulated MMP-2 production in co-culture of cancer cells and fibroblasts was completely suppressed by siRNA knockdown of CD73, but not by CD99 knockdown. MMP-2 production was not suppressed by CD73-specific enzyme inhibitor (APCP). However, MMP-2 production was decreased by CD73 neutralizing antibodies, suggesting that CD73-mediated suppression of MMP-2 production is non-enzymatic. In human epithelioid sarcoma tissues, emmprin was immunohistochemically detected to be mainly expressed in tumor cells, and CD73 was expressed in fibroblasts and tumor cells: emmprin and CD73 were co-localized predominantly on tumor cells. CONCLUSION: This study provides a novel insight into the role of CD73 in emmprin-mediated regulation of MMP-2 production.
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5'-Nucleotidase/metabolismo , Basigina/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Biomarcadores , Linhagem Celular Tumoral , Técnicas de Cocultura , Fibroblastos , Proteínas Ligadas por GPI/metabolismo , Humanos , Imuno-Histoquímica , Espectrometria de Massas , Modelos Biológicos , Proteômica/métodosRESUMO
BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.
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Aminopiridinas , Doenças dos Gânglios da Base/diagnóstico por imagem , Progressão da Doença , Tomografia por Emissão de Pósitrons , Quinolinas , Compostos Radiofarmacêuticos , Tauopatias/diagnóstico por imagem , Idoso , Aminopiridinas/farmacocinética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Quinolinas/farmacocinética , Compostos Radiofarmacêuticos/farmacocinéticaRESUMO
OBJECTIVES: Hyaluronan (HA), an important constituent of extracellular matrix in the skin, has many biological activities such as hydration that contributes to firmness and bounciness of the skin. We have reported that reduction in HA in the papillary dermis and over-expression of HYBID (HYaluronan Binding protein Involved in hyaluronan Depolymerization, alias KIAA1199 or CEMIP), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling in Japanese and Caucasian women. However, little or no information is available for substances which inhibit the HYBID-mediated HA degradation. METHODS: Inhibition of Sanguisorba officinalis root extract and ziyuglycoside I, one of the components of Sanguisorba officinalis root extract, to the HYBID-mediated HA degradation was assessed by size-exclusion chromatography of HA depolymerized by stable transfectants of HYBID in HEK293 cells (HYBID/HEK293 cells) or normal human skin fibroblasts (Detroit 551 cells and NHDF-Ad cells). The HYBID mRNA and protein expression was examined by quantitative real-time PCR and immunoblotting in the skin fibroblasts treated with Sanguisorba officinalis root extract, and size distribution of newly produced HA was evaluated by preparing metabolically radiolabelled HA. A double-blind, randomized and placebo-controlled study was carried out in the 21 healthy Japanese women, who were topically treated with the formulation containing Sanguisorba officinalis root extract or the placebo on each side of the face including crow's foot area. RESULTS: Sanguisorba officinalis root extract, but not ziyuglycoside I, abolished HYBID-mediated HA degradation by HYBID/HEK293 cells. Sanguisorba officinalis root extract also inhibited HYBID-mediated HA degradation in skin fibroblasts by down-regulating HYBID mRNA and protein expression. Although control untreated skin fibroblasts produced polydispersed HA, the cells treated with Sanguisorba officinalis root extract produced only high-molecular-weight HA. Treatment with Sanguisorba officinalis root extract-formulated lotion significantly improved skin elasticity, and reduced skin wrinkling scores at the outer eye corner compared with the placebo formulation. CONCLUSION: Sanguisorba officinalis root extract showed an anti-HYBID-mediated HA degradation activity and anti-wrinkle activity on human facial skin, which is accompanied by the improvement in elasticity. Our study provides the possibility of a new strategy to inhibit HYBID-mediated HA degradation for anti-wrinkle care.
OBJECTIFS: l'acide hyaluronique (AH), un composant important de la matrice extracellulaire de la peau, assure de nombreuses activités biologiques, telles que l'hydratation qui contribue à la fermeté et l'élasticité de la peau. Nous avons rapporté que la réduction d'AH dans le derme papillaire et une surexpression de la protéine de liaison de l'AH impliquée dans la dépolymérisation de l'AH (HYBID, alias KIAA1199 ou CEMIP), une molécule clé de la dégradation de l'AH des fibroblastes cutanés, sont impliquées dans la formation des rides au niveau de la peau du visage chez les femmes d'origine japonaise et caucasienne. Cependant, peu ou aucune information n'est disponible concernant les substances qui inhibent la dégradation de l'AH provoquée par la protéine HYBID. MÉTHODES: l'inhibition de l'extrait de racine de la pimprenelle (Sanguisorba officinalis) et du ziyuglycoside I, l'un des composants de l'extrait de racine de Sanguisorba officinalis, sur la dégradation de l'AH provoquée par la protéine HYBID a été évaluée à l'aide d'une chromatographie par exclusion stérique de l'AH dépolymérisé par des transfectants stables de la protéine HYBID dans les cellules HEK293 (cellules HYBID/HEK293) ou les fibroblastes cutanés humains normaux (lignée cellulaire Detroit 551 et cellules des fibroblastes du derme humain chez l'adulte). L'expression de l'ARNm et de la protéine HYBID a été examinée par PCR quantitative en temps réel et par immuno-empreinte des fibroblastes cutanés traités avec de l'extrait de racine de Sanguisorba officinalis, et l'attribution des tailles des nouveaux échantillons produits de l'AH a été évaluée par préparation d'AH radiomarqué métaboliquement. Une étude en double aveugle, randomisée et contrôlée par placebo a été menée auprès des 21 femmes japonaises en bonne santé, qui ont été traitées localement avec la formulation élaborée à partir d'extraits de racine de Sanguisorba officinalis ou un placebo, sur chaque côté du visage, notamment sur la zone à pattes d'oie. RÉSULTATS: l'extrait de racine de Sanguisorba officinalis a permis d'arrêter la dégradation de l'AH provoquée par la protéine HYBID par les cellules HYBID/HEK293, mais ce n'était pas le cas du ziyuglycoside I. L'extrait de racine de Sanguisorba officinalis a également inhibé la dégradation de l'AH provoquée par la protéine HYBID des fibroblastes cutanés en diminuant l'expression de l'ARNm et des protéines HYBID. Bien que les fibroblastes cutanés témoins non traités aient produit de l'AH polydispersé, les cellules traitées aux extraits de racine de Sanguisorba officinalis ont produit uniquement de l'AH de haut poids moléculaire. Le traitement par lotion formulée à partir d'extraits de racine de Sanguisorba officinalis a amélioré de manière significative l'élasticité de la peau et réduit les scores de vieillissement du coin extérieur de la peau autour des yeux, par rapport à la formulation placebo. CONCLUSION: l'extrait de racine de Sanguisorba officinalis a démontré une action anti-dégradation de l'AH provoquée par la protéine HYBID et une activité antirides au niveau de la peau du visage humain, s'accompagnant d'une amélioration de l'élasticité. Notre étude fournit la possibilité d'une nouvelle stratégie pour inhiber la dégradation de l'AH provoquée par la protéine HYBID dans le cadre des soins antirides.
Assuntos
Ácido Hialurônico/metabolismo , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Sanguisorba/química , Saponinas/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Adulto , Sobrevivência Celular/efeitos dos fármacos , Método Duplo-Cego , Feminino , Fibroblastos/efeitos dos fármacos , Células HEK293 , Voluntários Saudáveis , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/química , Japão , Pessoa de Meia-Idade , Placebos , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Hyaluronan (HA) metabolism in skin fibroblasts is mediated by HYBID (hyaluronan binding protein involved in hyaluronan depolymerization, alias CEMIP and KIAA1199) and the HA synthases HAS1 and HAS2. However, photoageing-dependent changes in HA and their molecular mechanisms, and the relationship between HA metabolism and clinical symptoms in photoaged skin remain elusive. OBJECTIVES: We examined the amount, size and tissue distribution of HA and expression levels of HYBID, HAS1 and HAS2 in photoaged skin, and analysed their relationship with the degree of photoageing. METHODS: Photoageing-dependent changes of HA were investigated by studying skin biopsies isolated from photoprotected and photoexposed areas of the same donors, and the relationships between HA and photoageing symptoms such as skin wrinkling and sagging were examined. RESULTS: Skin biopsy specimens showed that the amount and size of HA are decreased in photoexposed skin compared with photoprotected skin, and this was accompanied by increased expression of HYBID and decreased expression of HAS1 and HAS2. Histologically, HA staining in the papillary dermis was decreased in photoexposed skin, showing reverse correlation with HYBID expression. HYBID expression in the photoexposed skin directly correlated with skin roughness and sagging parameters, and the reduced HA staining in the papillary dermis in the photoexposed skin positively correlated with these symptoms. CONCLUSIONS: These data demonstrate that imbalance between HYBID-mediated HA degradation and HAS-mediated HA synthesis may contribute to enhanced HA catabolism in photoaged skin, and suggest that HYBID-mediated HA reduction in the papillary dermis is related to skin wrinkling and sagging of photoaged skin.
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Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/metabolismo , Proteínas/metabolismo , Envelhecimento da Pele/fisiologia , Idoso , Feminino , Humanos , Hialuronoglucosaminidase , Pele/metabolismoRESUMO
BACKGROUND/PURPOSE: Previous studies have reported decreased dermal echogenicity and increased skin oxidative stress in overweight males. However, it is unknown whether these skin parameters of overweight and obese people are similar to those of individuals exhibiting a normal body weight following weight loss. The purpose of this study was to (1) compare the changes in the dermal structure parameters and levels of skin oxidative stress before and after weight loss in overweight and obese people in Japan and (2) to clarify how these aspects changed when body weight would be reduced to normal body weight. METHODS: Male volunteers with a body mass index of ≥25 kg/m2 were recruited. The dermal structure was visualized and dermal echogenicity and thickness were measured using ultrasound scanners. The mRNA expression level of heme oxygenase-1 in the hair follicles was quantitatively analyzed as a marker of skin oxidative stress. RESULTS: When overweight individuals in their 20s to 30s reduced their weight to normal, decreased dermal thickness in the abdominal region was observed in 50% of the subjects; however, no increase in dermal echogenicity was observed. A decrease in dermal thickness and an increase in dermal echogenicity in the thighs was observed in 83.3% of the subjects. No decrease in the level of dermal oxidative stress was observed. CONCLUSION: The dermal structure in the thighs of overweight young individuals can be improved to the level of the structure in those of normal body weight individuals following weight loss.
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Folículo Piloso/metabolismo , Heme Oxigenase-1/genética , Obesidade/metabolismo , Estresse Oxidativo/genética , RNA Mensageiro/metabolismo , Pele/diagnóstico por imagem , Redução de Peso , Abdome , Adulto , Povo Asiático , Humanos , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Tamanho do Órgão , Sobrepeso/diagnóstico por imagem , Sobrepeso/metabolismo , Pele/metabolismo , Ultrassonografia , Adulto JovemRESUMO
Chemotherapy is among the standard treatments for esophageal cancer. The docetaxel, 5-fluorouracil, and cisplatin (DCF) protocol yields a better response rate than 5-fluorouracil plus cisplatin. However, the incidence of side effects, such as febrile neutropenia and hematologic toxicity, is also significantly high with the DCF protocol. The granulocyte colony-stimulating factor and pegfilgrastim are prophylactically administered to prevent febrile neutropenia. This retrospective study evaluated the efficacy and safety of pegfilgrastim in patients receiving DCF therapy. Of the 65 patients who were administered DCF therapy in our hospital from 2011 through 2016, 21 received pegfilgrastim 24 hours or more after the end of chemotherapy. The protocol comprised 70 mg/m2 each of docetaxel and cisplatin on day 1 and 700 mg/m2 5-fluorouracil on days 1 to 5 via intravenous injection in a 3-week cycle. The primary endpoint was the rate of grade 3-4 neutropenia and febrile neutropenia. The mean patient age was 66.4 years. The incidence of grade 3 and 4 neutropenia was 14.2 % and 11.4 %, respectively, in the pegfilgrastim group and 31.9 % and 37.8 %, respectively, in the non-pegfilgrastim group. The incidence of febrile neutropenia in the pegfilgrastim group and non-pegfilgrastim group was 11.4 % and 40.3 %, respectively. Statistical analysis showed that the incidence of neutropenia and febrile neutropenia was significantly different (p<0.05) between the two groups. Pegfilgrastim prevents severe neutropenia and febrile neutropenia in patients with esophageal cancer who are treated according to the DCF protocol.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Filgrastim/farmacologia , Neutropenia/tratamento farmacológico , Polietilenoglicóis/farmacologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Neoplasias Esofágicas/sangue , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estudos RetrospectivosRESUMO
BACKGROUND/PURPOSE: Presently, skin-cleaning agents that claim to be removed by water or wiping alone are commercially available and have been used for the purpose of bed baths. However, there is a lack of knowledge on how water washing and wiping differently affect skin physiological functions or ceramide content. The aim of this study was to compare the effects of water washing and wiping on skin physiological functions and ceramide content. METHODS: Three kinds of the cleaning agents with different removal techniques (ie, water washing and wiping) were used in this study. Skin physiological functions (ie, transepidermal water loss, skin hydration, and skin pH) and skin ceramide content were measured before and after seven consecutive days of the application of each cleaning agent. RESULTS: No significant differences in skin physiological functions or ceramide content were observed between water washing and wiping. CONCLUSION: Cleaning agents that claim to be removed by water washing or wiping do not affect skin physiological functions or ceramide content by either removal method.
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Detergentes/farmacologia , Higiene , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Ceramidas/análise , Fármacos Dermatológicos/farmacologia , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Estado de Hidratação do Organismo/efeitos dos fármacos , Pele/química , Higiene da Pele , Água , Perda Insensível de Água/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND: Vertigo or dizziness is a common occurrence, but it remains a challenging symptom when encountered in the emergency department (ED). A diagnostic score for stroke with high accuracy is therefore required. METHODS: A single-center observational study (498 patients) was conducted. The predictor variables were derived from a multivariate logistic regression analysis with Akaike information criterion. The outcome was the occurrence of stroke. We evaluated the utility of a new diagnostic score (TriAGe+) and compared it with the ABCD2 score. RESULTS: The cohorts included 498 patients (147 with stroke [29.4%]). Eight variables were included: triggers, atrial fibrillation, male gender, blood pressure ≥140/90 mm Hg, brainstem or cerebellar dysfunction, focal weakness or speech impairment, dizziness, and no history of vertigo or dizziness or labyrinth or vestibular disease. We derived the TriAGe+ score from these variables. In the cohort, the prevalence of stroke increased significantly using the diagnostic score: 5.9% for a score of 0-4; 9.1% for 5-7; 24.7% for 8-9; and 57.3% for 10-17. At a cutoff value of 10 points, the sensitivity of the score was 77.5%, the specificity was 72.1%, and the positive likelihood ratio was 3.2. When the cutoff was defined as 5 points, the score obtained a high sensitivity (96.6%) with a good negative likelihood ratio (.15). The new score outperformed the ABCD2 score for the occurrence of stroke (C statistic, .818 versus .726; P < .001). CONCLUSIONS: The TriAGe+ score can identify the occurrence of stroke in patients with vertigo or dizziness presenting to the ED.
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Técnicas de Apoio para a Decisão , Tontura/epidemiologia , Serviço Hospitalar de Emergência , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Triagem/métodos , Vertigem/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Prevalência , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de RiscoRESUMO
PURPOSE: We evaluated the efficacy and toxicity of accelerated hypofractionated radiotherapy (ahypof-rt) for central-type small lung tumours. METHODS: Between November 2006 and January 2015, 40 patients with central-type small lung tumours underwent ahypof-rt delivered using 10 MV X-rays and a coplanar 3-field technique. The number of fractions ranged from 24 to 28, with a fraction size of 2.5-3 Gy. A total dose of 69-75 Gy to the isocentre of the planning target volume was administered to each patient. Cumulative survival and local control rates were calculated using the Kaplan-Meier method. RESULTS: The 27 men and 13 women enrolled in the study had a median age of 79 years (range: 60-87 years). The tumour stage was T1a in 9 patients, T1b in 17 patients, and T2a in 14 patients, with a median size of 26.5 cm (range: 11-49 cm). The median follow-up period was 23 months. A complete response was achieved in 3 patients (7.5%), and a partial response, in 17 patients (42.5%). The overall 2-year and 3-year local control rates were 87.3% and 81.8% respectively; the 2-year and 3-year overall survival rates were 78.9% and 66.7% respectively. Grade 3 pneumonitis occurred in 3 patients; no other severe adverse events (≥grade 3) were observed in any patient. CONCLUSIONS: Accelerated hypofractionated radiotherapy using a fraction size of 2.5-3 Gy was highly safe and can be a more effective treatment option than conventional radiotherapy for patients with central-type small lung tumours.
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The aim of the present study was to examine the effect of an intensified training phase followed by a tapering phase on the salivary immunoglobulin A concentration and on the upper respiratory tract infection (URTI) symptoms in young male basketball players. The session rating of perceived exertion method was used to quantify the internal training load, and the Wisconsin Upper Respiratory Symptom Survey-21 questionnaire was used to assess URTI symptoms. The Yo-Yo IR1 test and saliva collection were carried out at the beginning of the study (T1), after the intensified phase (T2), and after tapering (T3). A higher internal training load was observed for the intensified phase compared with the tapering phase (t=19.10; p<0.001), and a significant decrease in salivary immunoglobulin A concentration was detected (F=7.48; p=0.004) at T3 compared to T1 (p=0.02) and T2 (p=0.05). However, there was no significant difference between phases for severity of URTI (χ2= 2.83; p=0.242). The Yo-Yo IR1 test performance increased from T2 and T3 compared to T1 (F=58.24; p<0.001). There was no significant effect of aerobic fitness level on salivary immunoglobulin A response (F=1.095; p=0.344). In summary, the present findings suggest that an intensified training load followed by a tapering period negatively affects the mucosal immune function with no significant change in severity of URTI in young basketball players.
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AIMS: Molecular epidemiological techniques, such as pulsed-field gel electrophoresis (PFGE), or multilocus sequence typing (MLST) have facilitated our understanding of the transmission routes of nosocomial infections by Pseudomonas aeruginosa. However, they are time consuming and technically demanding. To perform molecular epidemiological analysis in a standard microbiology laboratory, we aimed to develop a simpler and effective molecular epidemiological technique based on the open-reading frame (ORF) distribution patterns detected by PCR, which we call PCR-based ORF typing (POT). METHODS AND RESULTS: Ten ORFs from genomic islets, five ORFs from genomic islands, and the metallo-ß-lactamases (MBLs) blaIMP and blaVIM were selected by comparing the whole-genome sequences of different Ps. aeruginosa strains (PAO1, PA7, UCBPP-PA14 and LESB58). These 17 ORFs were detected, along with a Ps. aeruginosa marker, using 9-plex and 10-plex PCR systems. The genotypes in the POT were compared to those obtained by using PFGE and MLST. CONCLUSIONS: Using the POT method, molecular epidemiological analyses of Ps. aeruginosa can be completed in 4 h. SIGNIFICANCE AND IMPACT OF THE STUDY: Since this method is very easy to perform, even in standard clinical laboratories, it could be a valuable tool for monitoring daily infection control measures.
Assuntos
Infecção Hospitalar/microbiologia , Epidemiologia Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Proteínas de Bactérias/genética , Infecção Hospitalar/epidemiologia , Ilhas Genômicas , Genótipo , Humanos , Dados de Sequência Molecular , Fases de Leitura Aberta , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/genética , beta-Lactamases/genéticaRESUMO
OBJECTIVE: A state of chronic inflammation, characterized by an increased level of tumour necrosis factor-alpha (TNF-α), is often found in the obese population. The negative effects of elevated TNF-α are not limited to systemic metabolism. It also reportedly affects skin integrity. Recently, the relationship between obesity and skin fragility was reported; however, there has been little insight into how the level of TNF-α in the skin in situ is related to the severity of obesity. In this study, we aimed to measure the level of TNF-α on the skin and to find the relationship between obesity and the level of TNF-α detected on the skin. METHODS: We used a novel, non-invasive method called quantitative skin blotting. Fifty-nine healthy (but some were classified as being overweight or obese) Japanese males were enrolled as subjects. The levels of TNF-α detected on the abdominal and thigh skin along with the body composition were measured, followed by a correlation analysis. RESULTS: Significant positive correlations were found between the levels of TNF-α detected on the skin and the severity of obesity such as body mass index (BMI), body fat weight and visceral fat rating. CONCLUSION: We found that high levels of TNF-α were detected on the skin of Japanese obese males, which implied the higher TNF-α in the skin. The elevation of skin TNF-α may be one factor related to skin fragility that is often found in obese individuals.
Assuntos
Western Blotting/métodos , Obesidade/metabolismo , Pele/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The purpose of this study was to investigate the effect of court size on physiological responses and physical performance of young elite basketball players. Twelve male basketball players (18.6 ± 0.5 years; 88.8 ± 14.5 kg; 192.6 ± 6.5 cm) from an under-19 team performed two small-sided games (matches) with different court areas (28x15 m and 28x9 m; 28x15 and 28x9 protocols). The number of players (3x3) was kept the same in each protocol. The players performed a repeated-sprint ability (RSA) test before and after each match. Blood lactate concentration was collected before (pre) and after (post) the matches, and the session rating of perceived exertion (session-RPE) was determined 30 minutes after the match. Best and mean time in the RSA test were not different between the 28x15 and the 28x9 match protocols (p > 0.05). A significant difference was observed for lactate concentration from pre- to post-match (p < 0.05) in both protocols (28x15 and 28x9); however, there was no significant interaction between protocols. A similar session-RPE mean score (28x15: 7.2 ± 1.4 and 28x9: 6.6 ± 1.4) was detected for both protocols (p > 0.05, ES=0.41). In summary, the results of the current study suggest that the different court areas induced similar responses. Although there was no significant difference in effort perception, players tended to perceive a greater effort in the larger court size.
RESUMO
A new measurement of the branching ratio R_{e/µ}=Γ(π^{+}âe^{+}ν+π^{+}âe^{+}νγ)/Γ(π^{+}âµ^{+}ν+π^{+}âµ^{+}νγ) resulted in R_{e/µ}^{exp}=[1.2344±0.0023(stat)±0.0019(syst)]×10^{-4}. This is in agreement with the standard model prediction and improves the test of electron-muon universality to the level of 0.1%.
RESUMO
The aim of the present study was to investigate the effect of different resistance-training regimens (S or P) on the expression of genes related to the MSTN signaling pathway in physically-active men. 29 male subjects with at least 2 years of experience in strength training were assigned to either a strength-training group (S; n=11) or a power-training group (P; n=11). The control group (C; n=7) was composed of healthy physically-active males. The S and the P groups performed high- and low-intensity squats, respectively, 3 times per week, for 8 weeks. Muscle biopsies from the vastus lateralis muscle were collected before and after the training period. No change was observed in MSTN, ACTIIB, GASP-1 and FOXO-3 A gene expression after the training period. A similar increase in the gene expression of the inhibitory proteins of the MSTN signaling pathway, FLST (S: 4.2 fold induction and P: 3.7 fold induction, p<0.01) and FL-3 (S: 5.6 fold induction and P: 5.6 fold induction, p<0.01), was detected after the training period. SMAD-7 gene expression was similarly augmented after both training protocols (S: 2.5 fold induction; P: 2.8 fold induction; p<0.05). In conclusion, the resistance-training regimens (S and P) activated the expression of inhibitors of the MSTN signaling pathway in a similar manner.