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In order to bring the cost of this complex therapy down, scientists are looking at the possibility of allogenic (donor) therapy in lieu of autogenic therapy. Cellectis, a French biopharmaceutical company, has developed an allogenic CAR-T therapy, “UCAR-T” or universal CAR-T therapy. A pediatric patient with a refractory relapsed ALL was given UCAR-T in the UK after all previous treatment had failed in 2015. According to the CEO of Cellectis, at that time, the patient did not exhibit any adverse effects such as CRS and the UCAR-T-cells were still active after three months (Labiotech 2015) . With these results, in June of 2016, Cellectis announced the enrollment of their first pediatric patient in a Phase 1 clinical trial for acute B lymphoblastic leukemia (B-ALL) at the University College of London (UCL) (Cellectis 2016) .
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Die Teilnehmenden wurden im Erstgespräch, im ersten sowie im letzten Nachsorgegespräch mittels Fragebögen schriftlich befragt. Die Fragebögen wurden von den Betriebsärzt*innen zu den jeweiligen Messzeitpunkten ausgeteilt. Eine detaillierte Beschreibung der Erhebungsinstrumente findet sich in unserem Studienprotokoll der folgenden randomisierten kontrollierten Studie .
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If the user likes to restrict the value of a selected data element (i.e., set acute myocardial infarction to MHPTCD element), possible values can automatically be searched from the terminology server. PMSST knows in which coding system to look for the term by analyzing the value domain of the CDE definition automatically.
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Esses itens mostram que a maioria das populações está em desvantagem para acessar a carreira profissional. Porém, há outros fatores, como o pertencimento às minorias que têm acesso ainda mais limitado à educação superior. Isso ocorre principalmente em relação ao número reduzido de vagas reservadas às minorias. Um exemplo é da Universidad Nacional de Colombia , onde 2% dos estudantes são considerados indígenas, mas eles representam 3,43% da população do país.( 6 )Também, para admissão, há necessidade do preenchimento de documentação que comprove que o candidato pertence a um desses grupos minoritários. Contudo, essa documentação pode ser confusa, e o preenchimento e envio podem ser dificultados, já que requerem acesso a internet – serviço que é insuficiente nessas regiões.
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Within your Competing Interests Statement, please confirm that this commercial affiliation does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests) . If this adherence statement is not accurate and there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.
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Drs Mattsson, Schöll, Palmqvist, Insel, Strandberg, Hägerström, Ohlsson, Jögi and Smith report no conflicts of interest. Dr Hansson has served at advisory boards Eli Lilly, Roche Diagnostics and Fujirebio and received research support from GE Healthcare and Hoffmann La‐Roche. Dr Blennow has served at advisory boards or as a consultant for Alzheon, Eli Lilly, Fujirebio Europe, IBL International, Novartis and Roche Diagnostics. Dr Zetterberg has served at advisory boards for Roche Diagnostics, Pharmasum Therapeutics and Eli Lilly. Drs Zetterberg and Blennow are co‐founders of Brain Biomarker Solutions in Gothenburg AB, a GU Venture‐based platform company at the University of Gothenburg.
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Just over half (50.4, 95 % CI: 47.3–53.6) of surveyed refugee households reported had member(s) previously diagnosed with one of the five included NCDs (hypertension, cardiovascular disease, diabetes, chronic respiratory diseases, and arthritis), significantly lower than host community households (60.2, 95 % CI: 56.5–63.8; population comparison p <0.001).1 Among adult refugees, arthritis prevalence was the highest (7.9, 95 % CI: 6.8–9.0), followed by hypertension (7.4, 95 % CI: 6.6–8.3), chronic respiratory diseases (3.8, 95 % CI: 3.0–4.5), cardiovascular disease (3.3, 95 % CI: 2. 7–3.9), and diabetes (3.3, 95 % CI: 2.6–3. 9). As compared to refugees, host community prevalence rates were significantly different for all conditions except chronic respiratory diseases (p = 0.08). Hypertension was the most prevalent host community condition (10.7, 95 % CI: 9.3–12.0), followed by diabetes (6.3, 95 % CI: 4.2–7.4), arthritis (5.2, 95 CI: 4.3–6.2), cardiovascular disease (5.3, 95 % CI: 4.2–6.4), and chronic respiratory disease (2.6, 95 % CI: 1.9–3.3). Age-specific prevalence of surveyed NCDs is presented in Fig. 2. In younger adults age 18–39 years, arthritis (4.7, 95 % CI: 3.9–5.5) was most prevalent among refugees whereas chronic respiratory disease was most prevalent among host community members (2.0, 95 % CI: 1.1–2.8). Prevalence of all reported NCDs increased substantially after age 40 in both populations (Table 1 & Fig. 2). Hypertension was the most prevalent condition in the 40–59 and 60+ age categories both in the refugee and host community populations. Among children, NCDs were uncommon; chronic respiratory diseases were the most prevalent among children in the refugee (2.4, 95 % CI: 1.8–3.1) and host community populations (3.3, 95 % CI: 1.9–4.6).Table 1Age-specific chronic disease prevalenceHypertensionCardiovascular diseaseDiabetesChronic respiratory dis.Arthritis%(95 % CI)%(95 % CI)%(95 % CI)%(95 % CI)%(95 % CI)Households where any member(s) have condition Syrian refugees (n = 1376) 20.5 %(18.2–23.0)10.8 %(9.3–12.6)9.9 %(8.2–11.9)16.0 %(14.1–18.1)21.2 %(18.7–24.0) Host community (n = 686) 34.4 %(30.8–38.1)19.8 %(17.0–23.0)21.0 %(18.2–24.1)12.1 %(9.8–14.8)17.2 %(14.6–20.2) p-value<0.001<0.001<0.0010.0620.110Prevalence by age group 0–17 years Syrian refugees (n = 4371) 0.1 %(0.0–0.2)0.3 %(0.1–0.5)0.1 %(0.0–0.2)2.4 %(1.8–3.1)0.3 %(0.1–0.5) Host community (n = 1041) 0.5 %(−0.2–1.2)0.7 %(0.1–1.3)0.2 %(−0.2–0.7)3.3 %(1.9–4.6)0.6 %(−0.1–1.2) p-value0.2610.2040.7550.5260.352 18–39 years Syrian refugees (n = 2731) 1.9 %(1.4–2.4)0.8 %(0.5–1.1)0.8 %(0.4–1.2)3.2 %(2.5–3.85)4.7 %(3.9–5.5) Host community (n = 1180) 1.1 %(0.5–1.7)1.0 %(0.4–1.6)1.4 %(0.5–2.4)2.0 %(1.1–2.8)1.4 %(0.7–2.1) p-value0.2270.6740.1230.258<0.001 40–59 years Syrian refugees (n = 915) 17.6 %(15.1–20.1)9.2 %(7.3–11.1)8.1 %(6.1–10.1)4.4 %(3.0–5.7)14.4 %(11.8–17.0) Host community (n = 729) 15.0 %(12.5–17.5)5.6 %(3.9–7.4)9.2 %(7.1–11.3)3.0 %(1.7–4.3)8.5 %(6.5–10.5) p-value0.1370.0750.2530.1340.006 60+ years Syrian refugees (n = 240) 35.4 %(29.4–41.4)13.8 %(9.9–17.6)16.7 %(10.9–22.4)5.8 %(2.1–9.6)16.3 %(10.4–22.1) Host community (n = 337) 42.7 %(37.4–48.1)23.7 %(19.4–28.1)21.1 %(18.1–24.1)4.2 %(2.0–6.3)11.0 %(7.3–14.6) p-value0.0540.0010.1520.3860.140 Adult prevalence a Syrian refugees (n = 3886) 7.4 %(6.6–8.3)3.3 %(2.7–3.9)3.3 %(2.6–3.9)3.8 %(3.0–4.5)7.9 %(6.8–9.0) Host community (n = 2246) 10.7 %(9.3–12.0)5.3 %(4.2–6.4)6.3 %(4.2–7.4)2.6 %(1.9–3.3)5.2 %(4.3–6.2) p-value<0.001<0.001<0.0010.0800.028 a “Adult” defined as individual over 17 years old Fig. 2Age-specific prevalence of chronic health conditions by population. * population comparison p-value for age group <0.001 ** population comparison p-value for age group <0.05
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Moreover, the current study explores meaningful inferences concerning the influence of demographic variables on citizens’ readiness. In comparison with women, men are keener to follow COVID-19 preventive measures. The effect of educational level and age are un-balanced while including other factors. The use of social media has a positive influence on citizens’ readiness. It indicates that citizens who spent a long time in social media show positive readiness toward COVID-19 preventive measures. The finding is consistent with the literature . This suggests that a positive attitude and innovativeness play a vital role in shaping citizens’ willingness and readiness.
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Les personnes âgées vivent dans divers milieux résidentiels avec des niveaux de soutien variables. La crise sanitaire et sociale résultant de la COVID-19 a mis en lumière des problèmes existant depuis plusieurs années dans le système de prestation de soins pour les personnes âgées. Bien que la pandémie ait affecté les personnes âgées partout au Canada, quel que soit leur milieu de vie, les impacts les plus profonds se sont fait sentir dans les centres de soins de longue durée (SLD) 4. Au Canada, 80 % des décès dus à la COVID-19 se sont produits dans les centres de soins de longue durée, ce qui représente le plus fort pourcentage au niveau mondial parmi les pays ayant déclaré des cas de COVID-19 5 (Estabrooks, Flood, & Straus, 2020a; Estabrooks, Straus, et coll., 2020b). Toutefois, il n’y a que près de 7 % des personnes âgées au Canada qui vivent en centres de soins de longue durée 6, tandis que la plus grande partie de la population plus âgée vit dans la communauté et reçoit des services de soins à domicile ou communautaires, ou de l’aide de membres de leur famille pour fonctionner de façon relativement autonome 7. La quarantaine et la distanciation sociale ont fortement affecté la capacité de ces systèmes de soutien à fournir les soins et les ressources indispensables aux personnes âgées qui vivent de façon autonome. Plusieurs se sont retrouvées laissées à elles-mêmes, encore plus vulnérables et incapables de satisfaire à leurs besoins fondamentaux. En outre, de nombreuses personnes âgées sont atteintes de problèmes de santé pour lesquels elles nécessitent d’avoir accès à des services et à des traitements qui risquent d’être interrompus ou inaccessibles en temps de pandémie. Cette situation peut être exacerbée par des inégalités retrouvées dans le système médical, engendrant une perte de soins essentiels pour plusieurs personnes âgées.
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Figure S1. Rhizosphere microbiota richness and diversity. Figure S2. Abundance of carbon cycle-related genes in rhizosphere soil. Figure S3. Activities of carbon cycle-related enzymes in rhizosphere soil. Figure S4. Comparisons between WM- and WM-S-treated plants. Figure S5. Rarefaction curves of observed species. Table S1. Physiological parameters of Arabidopsis in three generations. Table S2. Significant enrichment of rhizosphere microorganisms in the third generation. Table S3. nriched rare microorganisms in Wt and pgr5 Arabidopsis. Table S4. Bulk soil properties measured after addition of WM and PM soil slurries. Table S5. Comparison of root exudates between Wt and pgr5 mutant Arabidopsis. Table S6. Sequences of the primer pairs used for qRT-PCR. (DOCX 348 kb)
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肺癌细胞侵入临近血管和淋巴管，很容易经过体循环到达远处器官形成转移。因脑的血供量约占全部体血循环的1/5，故发生转移癌细胞的机会较多。在肺癌脑转移的基础研究方面，近年来的研究报道较多。有研究表明在脑转移的肺癌患者中，CXCR4蛋白存在过表达，提示高表达CXCR4与肺癌脑转移相关。在以特异性脑转移肺癌细胞株PC14/B为研究对象的研究中发现，抑制该高表达的S100B蛋白后，细胞增殖和迁移功能明显降低，从而提示S100B蛋白的表达与脑转移的存在密切相关。microRNAs调控目标RNA的表达，在肺癌脑转移中也有相应研究，有研究[18, 19]认为microRNA-328、microRNA-378在肺癌脑转移中起着重要作用。亦有研究表明在SCLC患者血清中，高水平表达胎盘生长因子（placenta growth factor, PLGF）的患者更易于发生脑转移; 应用体外血脑屏障模型，进一步证实了PLGF可以使SCLC细胞透过血脑屏障，当抑制了PLGF的表达后，在模型中会抑制体外SCLC细胞发生脑转移的几率。巢蛋白（nestin）是一种中间丝类型的蛋白，对神经元分化有作用，是神经干细胞的特征性标志物。SKARDA等用免疫组化检测114例NSCLC标本，发现在发生脑转移的肺鳞癌中表达明显高于肺腺癌。
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(A–C) Association between (A) neighborhood poverty, (B) neighborhood PC7, (C) neighborhood social cohesion, and DNAm age acceleration measures for total sample (square), women (triangle), and men (circle). Models adjusted for race/ethnicity, education level, employment, smoking status, alcohol intake, and years residing in current neighborhood. Black symbols represent associations with Horvath age acceleration, dark gray represent Hannum age acceleration, and light gray represent PhenoAge acceleration.
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This similarity could either highlight their common genetic background since Cyprus is referred as a possible passage for the dispersal of olives westward of the Levant , or it could be a reintroduced genetic material from the central Mediterranean and possibly used as rootstocks . Since, oleiculture in Cyprus counts for millennia, both theories could be valid. In a more recent study by Chalak et al. , a distinction within the genotypes of Levant was evident. Syrian olive varieties diverged from all others, while most of the accessions from Cyprus and Lebanon (apart from individuals from the Bekaa region) were clustered into one gene pool. The centennial Lebanese trees of Bcheale were astonishingly affiliated to the Cypriot olive germplasm. Consequently, this pattern strongly indicates the ancient exchange of olive germplasm among Cyprus and Lebanon, given the long history of earlier trading transversely the Mediterranean . However, it cannot be uncritically ruled out, that the discrimination of olive accessions in two distinctive groups may be the result of the ongoing selection for olive usage (table/oil producing olives), as already demonstrated [11,32,38–41].
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慢性淋巴细胞白血病（CLL）是一种成熟B淋巴细胞克隆增殖性肿瘤，以淋巴细胞在外周血、骨髓、脾脏和淋巴结聚集为特征，其临床异质性较强。在众多预后因素中，细胞遗传学异常提供了重要的预后信息。随着CpG寡脱氧核苷酸（CpG-ODN）联合IL-2刺激方法的应用，染色体核型分析的成功率和异常率分别可达90％和80％。染色体易位在所有CLL中的发生率为19.8％～34.0％，涉及IGH基因的14q32易位是其中较为常见的类型，其伙伴基因多为BCL2/18q21、BCL3/19q13、MYC/8q24–。国内关于t(14;18)(q32;q21)在CLL中的报道罕见，本文报道我院收治的8例伴t(14;18)(q32;q21)的CLL患者，并对相关文献进行复习。
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Canine bone marrow derived OC were treated with rabbit anti-ferroportin 1 after 20 hours treatment of hepcidin (200, 400, 800 and 1200 nmol/L) to visualize the expression of FPN1 protein. Immunofluorescence showed the expression of FPN1 protein in OC treated MCSF and RANKL (Fig 5A). The intensity of fluorescence was reduced towards the 800 and 1200 nmol/L concentration of hepcidin (Fig 5B). Separate groups of OC were teared with different concentrations of PPS for overnight after treatment of 20 hours of 800 nmol/L hepcidin. However, heparin induced FPN1 internalization and degradation was inhibited with higher concentrations of PPS (5, 10, 20 and 40 μg/mL). Higher the fluorescence intensity was visualized toward the 40 μg/mL PPS (Fig 5C and 5D).
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在GWA研究的时代，预计最近GWA研究的趋势将持续。尽管已鉴定出了许多癌症的新型遗传变异，但鉴定有实际功能的遗传变异的工作仍待进行。由于鉴定罕见SNPs时统计学效能显著降低，因此有待增加样本数量来检测罕见变异。恰当的研究设计在决定GWA研究的成败中亦起关键作用。芯片需包含更多SNPs的罕见变异，并应采用严格的对照组来提高基因分型的准确性。也需发展整合分析CNVs和GWA的研究方法，包括GWA序列设计的创新和SNPs与常见拷贝数目多态性间连锁不平衡关系的使用。为了获得更有意义的荟萃分析结果，建议采用更具有一致性的实验设计和统计方法。我们在理解遗传变异在癌症治疗中的作用方面仍处于早期阶段。接下来的研究趋势是整合各种有用的DNA和RNA信息（编码与非编码转录）的生物组学技术和鉴定癌症诊断或治疗进展的遗传变异的数据库[58, 59]。
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Notre étude a été réalisée au Service des Maladies du Sang (SMAS) du Centre National Hospitalier Universitaire-Hubert Koutoukou Maga (CNHU-HKM) de Cotonou qui est l'hôpital de référence du Bénin. Clinique universitaire et unique service d'Hématologie Clinique du pays, le SMAS constitue le centre national de référence des pathologies hématologiques dont les hémoglobinopathies. Pour ces dernières, la prise en charge est globale et intègre les activités de prévention, de soins et de suivi. Les urgences drépanocytaires (médicale et chirurgicale) y sont directement admises et traitées avec une référence secondaire des cas chirurgicaux vers le service approprié. Il s'agit d'une étude rétrospective descriptive sur une période de 2 ans (Janvier 2014-Décembre 2015) et portant sur un recrutement exhaustif de tous les patients admis pour une urgence drépanocytaire et hospitalisés dans le service. Les critères d'inclusion étaient représentés par l'existence des urgences suivantes : les anémies aigues ; les infections graves (sepsis, ostéomyélites, méningites, pneumopathies,…) auxquels on peut rattacher le paludisme comme un facteur favorisant ; la crise vaso-occlusive osseuse (CVO); le syndrome thoracique aigu; le priapisme; les accidents vasculaires aigus (accident vasculaire cérébral, atteinte vestibulaire ou cochléaire, nécrose papillaire, infarctus viscéral, hémorragie ophtalmologique, thrombose veineuse) et les urgences aigues secondaires aux complications chroniques. Les critères de non inclusion étaient représentés par les hospitalisations pour complications drépanocytaires chroniques et ne relevant pas de l'urgence (ulcères cutanés, rétinopathie proliférante, néphropathie drépanocytaire, atteinte cardiaque). La grossesse représente une situation particulière où les patientes sont hospitalisées en obstétrique et font l'objet d'une prise en charge pluridisciplinaire. Notre échantillon était composé en majorité de drépanocytaires connus et faisant partie de la cohorte suivie dans notre service. Les moyens diagnostiques utilisés étaient cliniques (antécédents, examen physique), biologiques (hémogramme, bilans d'hémostase, électrophorèse quantitative de l'hémoglobine, bilans biochimique et microbiologique) et radiologiques (radiographie standard, échographie et scanner). Les avis spécialisés notamment ophtalmologique, oto-rhino-laryngologique, hépato-gastrologique, cardiologique et néphrologique étaient sollicités si besoin. L'évolution était jugée favorable devant l'amélioration de l'état général et la sortie du patient et défavorable en cas de décès. Les variables étudiées étaient les caractéristiques socio-démographiques (âge, sexe, profession); le motif de consultation; le type d'hémoglobinopathie (homozygotie SS, hétérozygotie composite SC ou S-β-thalassémie); le diagnostic retenu; le traitement reçu ; l'évolution et la durée d'hospitalisation. La collecte des données a été faite à partir des registres d'hospitalisation et des dossiers des patients à l'aide d'une fiche pré-testée. Les données ont été codées, enregistrées et analysées à partir des logiciels Excel et SPSS 20.0. Nous avons ressorti les pourcentages pour les variables quantitatives. Pour garantir la confidentialité des données, les fiches ont été conçues de façon à respecter l'anonymat des patients.
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Zur Ergänzung dieser Quellen wurde ein selektives Schneeballverfahren durchgeführt. Hierfür wurden solche Akteure ausgewählt, bei denen aufgrund ihrer Charakteristika von einer großen Wahrscheinlichkeit der Identifikation weiterer relevanter Akteure ausgegangen werden konnte. Zu diesen Charakteristika gehörten insbesondere zivilgesellschaftliche Netzwerke und institutionelle Arbeitsgemeinschaften. Durch ein Screening der Mitglieds‑, Partner- und/oder Förderorganisationen dieser Akteure auf ihren jeweiligen Homepages wurden weitere Akteure identifiziert.
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The locations of the injection sites were confirmed on histological criteria. Figure 2 shows the reconstruction of each injection site on surface views of the brain hemisphere. Each monkey received 2–4 distinct tracers injected in different PM areas. As the figure shows, the injection sites varied in size and location within each PM sub-area and, sometimes, encroached on an adjacent area (see also Table I). A particular protocol was conducted in Mks 1–3 in order to obtain large injection sites covering most of the injected PM sub-area. Examples of such large injection sites are shown on photomicrographs (Fig. 4), following injections of BDA, DY, FB and CB. The injections were performed in such a way (usually at 2 depths along each penetration) to form a cylinder covering all cortical layers, from the surface down to the limit between the grey and the white matter.
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另一个PD-1抑制剂Pembrolizumab在SCLC领域也崭露头角。KEYNOTE-028研究1b期通过22C3抗体筛选肿瘤细胞≥1%细胞膜性PD-L1阳性的经标准治疗失败的SCLC患者，给予Pembrolizumab单药治疗，研究筛选147例患者，PD-L1阳性42例，纳入24例患者，毒性方面：3级以上毒性的发生率为66.7%（16/24），常见的毒性包括关节痛（16.7%）、无力（16.7%）、皮疹（16.7%）、腹泻（12.5%）和疲乏（12.5%），关注的免疫相关的毒性发生率为12.5%（3/24），包括免疫性甲状腺炎，输注部位局部反应，细胞因子释放综合征和结肠炎，与之前Pembrolizumab治疗其他实体瘤的毒性一致；疗效方面：ORR为33.3%，PFS为1.9个月，OS为9.7个月，1年的生存率为37.7%。研究证实Pembrolizumab单药治疗PD-L1阳性经治SCLC具有良好的抗肿瘤活性。Pembro对比拓扑替康治疗复发耐药SCLC的Ⅱ期研究（NCT02963090）将进一步评价Pembro单药在SCLC二线及以上治疗的疗效和安全性。2017年ASCO上报告了pembro维持治疗经4-6周期铂类联合依托泊苷治疗后有效或疾病稳定的ED-SCLC患者的Ⅱ期研究，研究的主要终点为PFS。研究纳入45例患者，中位PFS为1.4个月，irPFS为4.7个月。中位OS为9.2个月，疾病控制率为42%；Pembro维持治疗常见的3级以上毒性包括：疲乏、恶心、呼吸困难、转氨酶升高，出现与药物相关严重不良反应为：房室传导阻滞（1例）和糖尿病Ⅰ型（1例），然而与之前CALGB 30504研究中观察组2.1个月和舒尼替尼维持治疗组3.7个月的PFS相比，Pembro维持治疗并没有延缓疾病进展风险，但是Pembro维持治疗的OS与CALGB 30504研究中舒尼替尼维持治疗组9.0个月的OS相当，明显优于观察组6.9个月的OS，Pembro维持治疗出现PFS与OS获益不一致的现象，考虑以下因素：其一，免疫靶向药物起效相对缓慢，但作用持久；其二，传统的RECIST评价标准不能准确评价免疫靶向药物的疗效，采用iRECIST进行评价Pembro维持治疗的iPFS为4.7个月，与对OS的影响一致；其三，部分SCLC患者能够从Pembro维持治疗中获益，在该研究中PD-L1表达与疗效的分析发现, 基质中PD-L1表达阳性的患者接受Pembro治疗有获益的趋势，但样本量有限，需要进一步研究。寻找更有效的生物标志物筛选适合进行免疫靶向维持治疗的患者，才能使SCLC真正获益。除了单药外，Pembro联合化疗一线（KEYNOTE-011, REACTION）、二线治疗（PembroPlus, MISP-MK3475）ED-SCLC，Pembro联合放化疗一线治疗SCLC（包括局限期和广泛期）（NCT02402920）以及Pembro联合PI3K抑制剂治疗复发耐药SCLC的研究（NCT02646748）正在进行，将为Pembro在SCLC的治疗中提供更多证据。
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The European diploma in emergency radiology subspeciality is delivered using a combination of self-directed learning, webinars, workshops, research & teaching, as well as on-the-job training.73 Electronic teaching files and internet-accessible case collections are also being used increasingly for radiology subspecialisation training in other European countries with limited access to complex equipment.25
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O ERICA adotou algumas estratégias visando estimular a participação dos alunos, tais como: elaboração de material explicativo sobre o estudo, confeccionado por renomado cartunista infantil de forma a atrair a atenção dos jovens – cartilha, cartaz e identidade visual da página do estudo; distribuição de kit-lanche para aqueles que fizeram jejum para coleta de sangue; e divulgação do estudo em página própria (www.erica.ufrj.br), com um canal de contato (fale conosco), e em mídia televisiva e impressa local no início da coleta em cada estado. Essas estratégias aumentaram o custo do estudo, mas são fundamentais para a redução da não-participação em estudos epidemiológicos. Da mesma forma, estratégias para alcançar os indivíduos não-participantes e obter deles algumas informações que possam caracterizá-los e ajudar a entender a resistência em participar são importantes e exigem um grande esforço logístico, de difícil implementação e alto custo em um grande estudo populacional 4 .
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Adopting a functionalist analytic framework, the current study investigates children’s health as a necessary component for the functioning of the family institution and argues that children’s health is closely integrated in how parents interact with the children. Using a 2018 sample from the southern Jiangsu province of China, we employed a latent class analysis to categorize four types of a parent–child relationship: the loose, free, pressed, and concerted types. Multivariate logistic regressions showed that the concerted type, in which parents moderately regulate the behavior of the children, is associated with a better level of children’s health. The results suggest that children with good health render it possible for a family to develop a concerted parent–child relationship and function as an integrated unit. Such a finding calls for policymakers to consider that children’s health has consequences beyond medical and healthcare relevancy. Children’s health may further matter for a functioning family institution and, ultimately, a well-balanced and integrated society in which individuals find solidarity and cohesion among themselves.
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Haplotypes observed in homozygous individuals carrying the most frequent variants in this study defined by six polymorphic single nucleotide polymorphisms (SNPs) [p.Gln232= (rs1126758), p.Val245= (rs1042503), p.Leu385= (rs772897), c.168+19T>C (IVS2+19T>C; rs17842947), c.441+47C>T (IVS4+47C>T; rs1718301) e c.510‐54G>A (IVS5‐54G>A; rs2251905)]. (Individuals carrying the ancestral alleles are shown in unfilled circles, homozygosity for the derivate alleles is shown in red circles and heterozygosity is shown in half filled circles) (GenBank: NM_000277.3; ENSG00000171759; ENST00000553106.6)
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Para ingresar a la unidad, los pacientes debían tener una edad igual o mayor a 60 años y cumplir con uno o más de los siguientes criterios: múltiples comorbilidades (dos o más), condición funcional previa de dependencia grave o total, hospitalizaciones frecuentes (dos o más al mes), demencia previa o delirio al ingreso, presencia de dos o más síndromes geriátricos (por ejemplo, fragilidad, úlceras por presión o caídas), índice de masa corporal menor de 20 kg/m2, red de apoyo social insuficiente, proceder de instituciones geriátricas, o tener más de 80 años con enfermedad aguda.
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1983年Friedlander在宫颈癌的治疗中首次提出新辅助化疗(neo-adjuvant chemotherapy, NAC)的概念。理论上，新辅助治疗的优势包含：①降低肿瘤负荷使部分不可手术或难以进行根治性手术的患者获得根治性手术可能，相较于化疗、内分泌治疗等全身系统治疗，根治性手术切除是NSCLC现今获得治愈可能的最佳治疗方式，术前新辅助治疗的最主要目的是为更多患者争取根治性手术机会，进一步提高远期生存。因此新辅助治疗对于患者的选择主要集中在Ⅲa期，这部分患者有的肿瘤体积过大或侵及重要器官使手术难度增大，有的伴纵隔淋巴结转移，不推荐一线手术治疗。在进行新辅助治疗后可能使肿瘤体积缩小，降低手术风险，提高手术切除率，或使转移淋巴结转阴，达到降N分期的目的，现也有部分临床研究将患者群体扩展至Ib期-Ⅲa期甚至部分潜在可切除的Ⅲb期患者，以期使更多患者接受根治性手术治疗。②相较于辅助治疗，原发灶存在时可以更直观通过影像学评估疗效。③患者未经历手术创伤，对治疗耐受性好。④更早期开展全身治疗对抗潜在微转移灶，降低转移风险。⑤新辅助治疗后手术标本的病理缓解率可能成为术后生存的预测因子，指导复发高危人群及时进行辅助治疗。
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For being assigned to category B, a disease needs to comply with all criteria of the first set (1, 2.1–2.4), and according to the assessment, EHV‐1 complies with criteria 2.3 (more than 95% certainty) and 2.4 but not with 1 (1–5% certainty) and 2.2 (10–33% certainty). For being eligible for category B, a disease needs to comply additionally with one of the criteria of the second set (3, 4, 5a‐d), and EHV‐1 does not comply with criteria 3 (less than 1% certainty), 5a (10–33% certainty), 5c (5–10% certainty). The assessment was inconclusive on compliance with criteria 4 (33–66% certainty), 5b (10–66% certainty) and 5d (10–66% certainty). Overall, it was assessed with less than 5% certainty (extremely unlikely) that EHV‐1 may be assigned to category B according to criteria in Annex IV of the AHL for the purpose of categorisation as in Article 9.
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De huidige NDF-richtlijn adviseert drinkvoeding pas in te zetten wanneer iemand niet meer in staat is om met normale voedingsmiddelen in zijn voedingsbehoefte te voorzien.6 Een cruciale rol is weggelegd voor de diëtist om dit moment in te schatten en kwantitatief en kwalitatief te onderbouwen. Wanneer drinkvoeding werd ingezet, lieten de resultaten van de onderzochte groep patiënten kwantitatieve en kwalitatieve gezondheidsverbeteringen zien. Geïnterviewde patiënten gaven over het algemeen aan zich beter te voelen wanneer ze drinkvoeding namen.
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Pode-se, ainda, questionar a efetividade da atenção básica do município. Outros estudos mostram que a ampliação da Estratégia Saúde da Família não resultou em melhora no controle da SC (13, 32). É provável que os profissionais que realizam consultas de pré-natal na atenção básica não tenham conhecimento suficiente para o manejo adequado da sífilis na gestação (29-31).
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YN: conceptualization, methodology, software, formal analysis and investigation, writing—original draft preparation, and writing—review and editing. BH: software and investigation. HY: resources, formal analysis, and investigation. XLi: resources and investigation. BJ: conceptualization, methodology, and writing—review and editing. XLu: conceptualization, methodology, writing—original draft preparation, and writing—review and editing. All authors contributed to the article and approved the submitted version.
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Au-dessous d´une valeur proche de 7 g/dl au cours du 2e trimestre et de 9 g/dl au 3e trimestre, l´accroissement du débit cardiaque (objectivable par vélocimétrie) s´accompagne d´anomalies du rythme cardiaque fœtal (RCF) puis d´épanchements liquidiens réalisant une anasarque fœto-placentaire . Cette dernière est définie par une infiltration liquidienne anormale concernant au minimum deux séreuses (plèvre, péritoine, péricarde) associée à un œdème cutané généralisé . Ce tableau est d´abord réversible par transfusion (stade d´insuffisance cardiaque fonctionnelle), puis difficilement réversible après que l´état d´anoxie chronique a induit des lésions et des remaniements cellulaires profonds (stade d´anasarque lésionnel) . La résistance du fœtus à l´anémie semble plus importante au cours du début du 2e trimestre, durant lequel l´anasarque s´exprime chez des fœtus ayant des taux d´hémoglobine compris entre 2 g/dl et 6 g/dl. L´anémie peut se constituer très rapidement au cours des 8e et 9e mois et les signes d´anasarque peuvent être frustes avant la survenue du décès in utero . Le pronostic d´un fœtus en anasarque est sévère avec une évolution vers la Mort Fœtale In Utero (MFIU) et une mortalité périnatale importante .
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6,8-Di-O-Acetylmalyngamide 2 (1): Colorless oil; [α]D24 +4.8 (c 1.20, MeOH); IR (neat) 3302, 2929, 2856, 1731, 1651, 1539, 1445, 1373, 1232, 1132, 1096 cm−1; 1H NMR, 13C NMR and HMBC data, see Table 1; HRESIMS m/z 572.2989 [M + H]+ (calcd. for C29H47ClNO8 572.2985).
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文献更新。4项RCT比较了西妥昔单抗与化疗联合与单独化疗的疗效。在包括1 125例患者的Ⅲ期FLEX（艾比特思肺癌一线治疗）研究中，顺铂/长春瑞滨联合西妥昔单抗组患者的中位OS比顺铂/长春瑞滨组延长1.2个月（P=0.044 1），尽管两组间PFS相同。在另一项Ⅲ期试验的摘要中，西妥昔单抗联合化疗可使PFS显著延长，但生存期未见改善。FLEX试验的纳入标准为经IHC明确的EGFR蛋白表达阳性。不符合系统评价的1项Ⅱ期试验的相关研究发现，伴有EGFR扩增（通过荧光原位杂交明确）患者的PFS及中位OS均改善。这些结果尚未在前瞻性研究中得到证实。
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Antiviral responses are associated with TLR4, and viral RNA and DNA can interact with TLR4. Previous studies showed that TLR4 can interact with the lipoprotein (NS1) of Dengue virus and with NS5A of HCV . PEDV infection had no effect on TLR4 expression, but we further explored whether TLR4 regulated PEDV infection. We pretreated Vero cells with the TLR4 inhibitor TAK for 2 h and then infected the cells with PEDV (0.1 MOI) in the presence of various concentrations of TAK for 24 h. Vero cells and supernatants were collected for Western blotting, plaque formation assays, and qRT-PCR. Western blotting showed that TAK induced moderately decreased porcine epidemic diarrhea virus nucleocapsid (PEDV-N) protein expression in a dose-dependent manner, and about 73% PEDV-N protein decreased when treating with 10 μM concentration of TAK (Figure 2A), demonstrating the fact that TLR4 might regulate PEDV infection. Immunofluorescence assays (IFAs) confirmed that TAK reduced PEDV infection rate about 79% at 10 μM concentration (Figure 2B). In addition, TAK caused reductions in viral open reading frame (ORF3) mRNA levels at a concentration of 1 μM (Figure 2C). The plaque formation assay showed viral titer in the supernatant of cells was reduced by about 95% at 10 μM concentration (Figure 2D). These results suggested that TAK inhibited PEDV infection in a dose-dependent manner, and furthermore that TLR4 potentially regulated this infection. In addition, TAK reduced levels of proinflammatory cytokine mRNAs, namely, IL-1β (88%), IL-6 (93%), IL-8 (98%), and tumor necrosis factor- a (TNF-a) (97%) during PEDV infection (Figure 2E). However, TAK did not have cytotoxic effects in Vero cells at concentrations up to 10 μM after 24 h .
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There is a wide consensus about the central role of biodiversity loss as a key driver of emerging infectious diseases (see Everard et al., 2020; Kenyon, 2020; McNeely, 2021 and Olivero et al., 2017, among others). The growing interaction between humans and wildlife, due to the continuous reduction of intact natural habitats, is causing an increase of human diseases of animal origin, also known as zoonoses. According to Woolhouse (2002), the emergence of most pathogens is commonly associated with ecological change and three-quarters of emerging human pathogens are zoonotic.
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In humans, mutations within the NSUN2 gene have been linked to autosomal‐recessive intellectual disability (Khan et al., 2012). Genotyping of an affected consanguineous Pakistani family revealed a homozygosity‐by‐descent (HBD) locus within region 5p15.32, and a homozygous base substitution was mapped to exon 19 of NSUN2, resulting in a glycine to arginine change (G679R). Overall, all individuals showed significant delay in development and speech. Height and weight were below the 5% percentile but muscle tone was increased in all limbs. Although patients had smaller heads, computer tomography of the brain did not show any abnormalities. Expression of mutant NSUN2(G679R) protein in mouse brain prevented its localization to the nucleolus in Purkinje cells of the cerebellum (Khan et al., 2012). A different mutation in the NSUN2 gene affecting splicing of exons 5–7 was correlated with symptoms of the Dubowitz syndrome, characterized by small stature, intellectual disability, mild microcephaly and a distinct facial appearance. Aberrant splicing resulted in severe reduction of protein levels of the enzyme (Martinez et al., 2012). A recent report provides evidence that the decrease in brain size upon loss of Nsun2 in mice might derive from the inability to generate sufficient amounts of differentiated neurons during neurogenesis (Flores et al., 2017). Developing Nsun2 −/− mouse cerebral cortex exhibited a thicker layer and higher numbers of intermediate neuronal progenitors but a decrease in upper‐layer neurons. tRNAs within Nsun2 −/− brains were found to be hypomethylated and cleaved by angiogenin, which led to an accumulation of 5′ derived tRNA fragments. Indeed, injection of an angiogenin inhibitor into pregnant Nsun2+/− mice rescued the brain development phenotype of the progeny. It was further shown that Nsun2‐depleted human neuroepithelial stem cells exhibited migration defects. Thus, it was suggested that Nsun2‐dependent tRNA methylation is required for differentiation and migration of neural progenitor cells during brain development (Flores et al., 2017). Nsun2 has also been implicated in vascular endothelial inflammation and atherosclerosis. Dynamic methylation of the mRNA of intercellular adhesion molecule 1 (ICAM‐1), which is a critical factor for inflammatory and immune responses of the endothelium, upregulated expression of ICAM‐1 at the translational level. Elevated ICAM‐1 levels partly mediated TNF‐α or homocysteine induction of the endothelial inflammatory response, which in turn led to the adhesion of leukocytes to the endothelial cells (Luo, Feng, Xu, Wang, & Wang, 2016).
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There were 20 cases of complete response, 74 cases of partial response, 13 cases of stable disease, and six cases of progressive disease, Figure 1 . The 1-, 2-, 3-, and 5-year local control rate were 57.4%, 41.8%, 29.3%, and 15.2%, respectively. The median time to progression was 15 months [95% confidence interval (CI), 6.1-23.9 months], Table 2 . Univariate analysis showed that age, sex, previous surgery, radiotherapy, chemotherapy, and site of recurrence were not associated with local control (p = 0.311, 0.079, 0.582, 0.511, 0.697, and 0.738, respectively). The local control of patients with D90 > 90Gy was significantly better than that of patients with D90 ≤ 90Gy (p=0.000). The local control rate of the group with good performance (KPS score ≥ 80) was better than that of the group with poor performance (KPS score < 80) (p = 0.003), Table 3 and Figure 2 .
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По результатам проведенного исследования ЧНКБ в группах статистически не различалась (р=0,975), однако, возможно, полученные данные связаны с различной численностью выборок групп. Данные зарубежной литературы за 2019 г., посвященные проблеме влияния ИМТ на исходы лечения бесплодия методом ЭКО, противоречивы, но в последнее время появляется все больше сообщений о негативном влиянии ожирения: ухудшается восприимчивость яичников к стимуляции препаратами гонадотропинов, требуя более высоких доз лекарственных препаратов, повышается риск отмены программ лечения в связи со снижением или полным отсутствием овариального ответа, достаточным ростом фолликулов, снижается качество ооцитов и эмбрионов, частота имплантации, ЧНКБ, повышается частота остановки развития на ранних этапах эмбриогенеза, преждевременных родов, низкого веса детей при рождении по сравнению с женщинами с НМТ .
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Mit den nun vorliegenden Daten der PEACE-1-Studie hat sich dieses Konzept allerdings grundlegend verändert : Die Triplet-Therapie aus Abirateron + Docetaxel + ADT zeigte im Setting der High-volume-Metastasierung einen signifikanten Überlebensvorteil im Vergleich zur Doublet-Therapie aus Docetaxel + ADT mit einer HR von 0,72 sowie einer ebenso signifikant längerem PFS (HR 0,47). Übersetzt in absolute Zahlen bedeutet dies ein medianes OS von 5,1 vs. 3,5 Jahren sowie ein medianes PFS von 4,1 vs. 1,6 Jahren zugunsten der Triplet-Therapie. Erwähnenswert und wichtig in der Interpretation dieser Daten bleibt allerdings auch, dass einige mHSPC-Patienten in diesem Studiensetting zudem eine lokale Radiotherapie erhalten haben, was wohl mit Sicherheit einen Einfluss auf die Länge der oben genannten Endpunkte gehabt haben dürfte, allerdings keinen Unterschied in der Interpretation des grundsätzlichen Vorteils der Triplet- gegenüber der Doublet-Therapie darstellt. Aus diesen Daten dürfte beim High-volume-mHSPC die Triplet-Therapie die Doublet-Therapie aus ADT + Docetaxel obligat gemacht haben. Leider wurden bis zum heutigen Stand keine Daten bzgl. der Triplet-Therapie der ARASENS-Studie bestehend Darolutamid + Docetaxel + ADT im Setting der High-volume-Metastasierung veröffentlicht .
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Echocardiographic examinations using a VIVID 7 system (General Electric Medical Systems, Horten, Norway) were performed with patient’s lying in a left decubitus posture by two experienced cardiologists. The cardiologists were blind to patients’ clinical information. Images of two-dimensional (2D) and 2D-guided M-mode were obtained from the standard views. The Doppler ultrasound sample volume was placed at the tips of the mitral leaflets and aligned to the flow using an ultrasonic beam. LV inflow waveforms were obtained from apical 4-chamber views. To obtain tissue Doppler images, the sample volume was then placed at the lateral corner of the mitral annulus. The measurements on echocardiography included LA diameter, E, EDT, and Ea. The LV systolic function was assessed using the LVEF. The Devereux equation was applied for calculating the LV mass. The LVMI was defined as the LV mass divided by the body surface area. LVH was defined according to the 2007 European Society of Hypertension/European Society of Cardiology guidelines . All echocardiographic measurements were recorded and offline analyzed using EchoPAC software by another cardiologist.
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With this revision in mind, it is interesting to read the paper from Campos et al.12 in this issue of Arquivos Brasileiros de Cardiologia . In this study, the investigators evaluated patients referred for invasive coronary angiography presenting with angina and suspected of myocardial ischemia. Of the 1,292 patients undergoing coronary angiography, 247 had non-significant epicardial coronary artery disease, 101 patients met the inclusion criteria and were enrolled in the study. Subsequently, these patients with suspected CMD were stratified into two groups according to the diagnosis of Chagas disease, being 15 patients with Chagas and 86 with non-Chagas disease. The patients with Chagas disease showed a higher prevalence of regional wall motion abnormalities and lower left ventricular ejection fraction, when compared with those who had suspected CMD related to other cardiovascular risk factors. This study highlighted the importance of Chagas disease as a potential etiology for CMD, regardless of conventional risk factors for this disorder.
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The STING-dependent activation of type I IFNs as well as other pro-inflammatory cytokines generates cellular and tissue states that are adverse for virus replication (10). Additionally, transient and localized activation of STING can also lead to stimulation of antigen presenting cell (APC) phenotypes involving cytokine, effector, and costimulatory protein expression that promote antigen uptake and processing and lymph node trafficking, and ultimately facilitate establishment of adaptive immune responses. As such, STING-dependent processes are important for antibody and cytotoxic T cell-mediated activity against infecting microbes as well as tumor cells [reviewed in (11)]. Intriguingly, STING activation can be triggered pharmacologically by synthetic small molecules and engineered macromolecules (12). This represents a potentially formidable strategy for eliciting broad-spectrum antiviral activity (13), generating anti-tumor immunity (14), and enhancing vaccine immunogenicity (15). In light of this, numerous efforts are underway to discover novel and safe STING-based immunomodulators that can be utilized for potentiating desirable clinical outcomes. Unfortunately, significant STING polymorphism exists in the human population, which affects both the molecular responses induced by the protein's activation and the degree of sensitivity to stimulatory ligands (16). Consequently, this can greatly impact the efficacy and safety of molecular entities pursued for clinical purposes. Here we describe a novel small molecule that activates the IFN-I response by way of STING that is differentially active in naturally occurring variants of the protein. In primary human cells this compound is also capable of inducing innate activity that is consistent with facilitation of adaptive immunity and as such may represent a new STING-directed molecular entity with clinical applications.
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NAIC bestond uit een cisplatinegebaseerd regime (n = 73) of gemcitabine-carboplatin (n = 10). Patiënt- en tumorkarakteristieken – onder andere leeftijd, Charlson Comorbidity Index, ASA-score en nierfunctie – verschilden niet significant tussen de behandelgroepen. NAIC werd bij 11 patiënten (13%) vroegtijdig afgebroken vanwege progressie (n = 6) of toxiciteit (n = 5). ICI werd bij zes patiënten (25%) na twee cycli afgebroken vanwege toxiciteit (p = 0,205). Na NAIC ondergingen patiënten chirurgie (n = 50; 60%) of chemoradiatie (n = 26; 30%) en konden zeven patiënten (10%) geen consoliderende behandeling ondergaan vanwege progressie (n = 5) of toxiciteit (n = 2). Na ICI ondergingen alle patiënten chirurgie. Na chirurgie (n = 74) werd pCR door respectievelijk 11 (22%) NAIC- en 11 (48%) ICI-patiënten bereikt (n = 0,056). pCD werd door respectievelijk 17 (35%) NAIC- en 14 (58%) ICI-patiënten bereikt (p = 0,077). Patiënten die waren behandeld met NAIC kregen vaker progressie (43% vs. 8%; p = 0,001). Mediane (IQR) follow-up was 26 (20-32) maanden. In het gehele cohort (n = 107) was ICI geassocieerd met betere PFS (p = 0,003) en overleving (p = 0,003). Zie figuur 17.1.
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We observed a higher frequency of hypotensive episodes in patients receiving SLED, and this was countered by a tendency for more frequent vasopressor escalation to manage hypotension in patients receiving CRRT. We speculate that a possible reason for this difference relates to the fact that SLED is administered by hemodialysis nurses, who have considerably more experience managing hypotension during dialysis sessions and may be more tolerant of transient hypotensive episodes, whereas CRRT is administered by ICU nurses who are more accustomed to respond to altered hemodynamics with vasopressor titration.
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A multilevel analyses using a negative binominal model to account for overdispersion (Peeters et al., 2012) was performed to test classroom level influences of alcohol popularity norm on individual drinking behavior (Table 5). In negative binominal models, explained variance and intraclass correlations have a different meaning compared to traditional multilevel model as a consequence of accounting for overdispersion in the data. For that reason they were not calculated, but instead variances for each model were presented (cf. Wang et al., 2010). First, a random intercept model was evaluated, only including alcohol use. Second, individual level main effects of peer susceptibility (hypothesis 3) and impulsivity (hypothesis 5) on alcohol use were investigated and classroom level variables were added to the model, starting with a model including only educational track and grade (model 1). At the individual level, peer susceptibility did not predict relative change in alcohol use. In contrast, impulsivity significantly predicted an increase in alcohol use (b = 1.02, SE = 0.31). This indicates that adolescents who were more impulsive revealed a relative increase in their drinking behavior. Educational track significantly predicted classroom differences in alcohol use, with higher drinking levels in the vocational tracks (b = −0.33, SE = 0.09, AIC = 9867, BIC = 9950). Alcohol popularity norms were added to the model (model 2) to observe whether popularity norms predicted higher classroom levels of alcohol use at T3 (hypothesis 2; b = 1.73, SE = 0.56, AIC = 9856, BIC = 9944). The predictive effect of educational track on alcohol use remained significant after adding popularity norms to the model (b = −0.25, SE = 0.09), though reduced in magnitude and the residual variance decreased (σ2 = 0.95 versus σ2 = 0.69). To examine possible cross-level interactions (hypothesis 4 and 6), first random slopes for peer susceptibility (b = 0.15, SE = 0.55) and for impulsivity (b = 0.46, SE = 0.52) were added simultaneously to the model. Slope variance coefficients were non-significant. In line with suggestions by LaHuis & Ferguson (2009) cross-level interactions were tested anyway, as a lack of power could have hindered us from detecting significant slope variance. Even though the model including both cross-level interactions resulted in a slightly better model fit (AIC = 2989 BIC = 3076) compared with a model with only random slopes (AIC = 3060, BIC = 3142) both cross level interactions were non-significant. Consequently, results did not support a cross level interaction for peer susceptibility (b = −1.16, SE = 1.00) or impulsivity (b = 0.17, SE = 1.25) with alcohol popularity norms. As such, the association between impulsivity and peer susceptibility and alcohol use did not vary as a function of classroom popularity norms (Table 6).Table 5Individual and classroom level effects of impulsivity, peer susceptibility, alcohol popularity norms, and their interaction on adolescents’ alcohol use at T3bSE95% CIDeviance (AIC/BIC)Random Intercept1570/1586 Variance alcohol T33.76**0.94[1.34–6.18]Model 19867/9950 Variance alcohol T3 0.95**0.19[0.64–1.25] Alcohol T20.43**0.10[0.26–0.59] Sex0.510.31[0.04–1.01] Within-effect peer susceptibility0.140.25[−0.27–0.55] Within-effect impulsivity1.02**0.31[0.51–1.52] Education−0.33**0.09[−0.48–−0.18]Model 29856/9944 Variance alcohol T30.69**0.20[0.37–1.16] Alcohol T20.40**0.11[0.22–0.57] Sex0.450.31[−0.06–0.96] Within-effect peer susceptibility0.200.26[−0.23–0.63] Within-effect impulsivity0.99**0.31[0.48–1.51] Education−0.25**0.09[−0.41–−0.10] Popularity norms alcohol1.73**0.56[0.81–2.65]Model 1 = model with individual main effects and education; Model 2 = model with alcohol popularity norms added*p < 0.05; **p < 0.01Table 6Individual and classroom level effects of impulsivity, peer susceptibility, alcohol popularity norms, and their interaction on adolescents’ smoking behavior at T3BSE95% CIDeviance (AIC/BIC)Random intercept1746/1763 Variance smoking T3 3.76**0.94[2.13–5.39]Model 19980/10063 Variance smoking T32.39**0.51[1.55–3.24] Smoke T20.47**0.16[0.21–0.73] Sex0.94*0.09[0.28–1.60] Within effect peer susceptibility0.450.26[0.02–0.88] Within-effect impulsivity0.630.46[−0.13–1.39] Education−0.36**0.02[−0.55–−0.17]Model 29978/10066 Variance smoking T32.39**0.77[1.14–3.65] Smoke T20.44*0.18[0.14–0.75] Sex1.01*0.40[0.35–1.67] Within effect peer susceptibility0.420.26[−0.04–0.84] Within-effect impulsivity0.630.46[−0.13–1.39] Education−0.31*0.14[−0.54–−0.07] Popularity norms smoke1.96**0.87[0.29–3.17]Model 1 = model with individual main effects and education; Model 2 = model with alcohol popularity norms added*p < 0.05; **p < 0.01
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All the data were managed using GraphPad Prism 6.0 software and shown as the means ± SEM. The statistical significance was determined by an unpaired Student's t test for the comparison of two groups or one‐way analysis of variance (ANOVA) with Dunnett's test for multiple comparisons. Values of P < .05 were regarded as statistically significant.
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Moreover, I understand that the targeting is relatively good when stable support grids are used and when relatively large fluorescent objects, such as lipid droplets (estimated 300-500 nm in diameter), are targeted. However, the size of the object to locate (when it is not diffraction-limited) will play a role in how frequently the targeting is successful: this issue should at least be discussed.
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Das systematische Cochrane-Review zeigte, dass Iloprost die Häufigkeit und Schwere von Raynaud-Attacken signifikant verringern kann. Hinsichtlich Prävention und schnellerer Abheilung digitaler Ulzera ergaben kleinere RCTs signifikante Ergebnisse, dagegen eine Metaanalyse nur einen Trend auf bessere Ergebnisse unter Iloprost.
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La bronchopneumopathie chronique obstructive (BPCO) est un problème majeur de santé publique. Elle représentera en 2020 la 3ème cause de décès dans le monde . C'est une maladie qu'on peut prévenir et traiter caractérisée par des symptômes respiratoires persistants et une limitation des débits aériens dues à des anomalies des voies aériennes et/ou des alvéoles souvent causées par une exposition significative à des particules ou gaz toxiques . L'exacerbation aiguë de BPCO (EABPCO) est définie comme une aggravation aiguë des symptômes respiratoires nécessitant un traitement supplémentaire [1, 3]. Elle est associée à une augmentation de la mortalité et de la morbidité, et peut avoir un impact péjoratif sur la qualité de vie des patients [3, 4]. Cependant, les EABPCO sont assez hétérogènes. Plusieurs études ont été conduites afin de mieux comprendre l'hétérogénéité des patients ayant une BPCO, et d'identifier les différents phénotypes. Plus particulièrement, différents biomarqueurs ont été étudiés et constituent une voie de recherche intéressante dans ce domaine. Certaines études suggèrent que l'éosinophilie sanguine ou dans les expectorations est associée à un phénotype particulier des patients BPCO. En effet, l'hyperéosinophilie des voies respiratoires connue caractéristique de l'asthme, est désormais un marqueur de l'inflammation dans la BPCO . Le pourcentage d'éosinophiles dans le sang périphérique est un biomarqueur simple et sensible pouvant refléter l'éosinophilie bronchique [8, 9]. Le dosage des éosinophiles dans le sang périphérique chez les patients BPCO est réalisé soit à l'état stable soit lors d'une EA. Bafadhel et al. ont classé les patients ayant une EABPCO en quatre groupes biologiques distincts. Le groupe avec une hyperéosinophilie constituait 28% de toutes les exacerbations . Le taux d'éosinophile sanguine (Eos) a été considéré comme un facteur prédictif indépendant de mortalité chez des patients BPCO en EA compliquée de pneumonie [10, 11]. Par ailleurs, une meilleure évolution sous corticothérapie systémique a été observée chez des patients BPCO éosinophiliques en EA dans d'autres études . L'objectif de ce travail est d'étudier l'hypothèse selon laquelle les éosinophiles dans le sang périphérique pourraient servir comme marqueur pronostique et phénotypique dans les EABPCO.
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The dry masses from leaves, leaf sheaths and roots from plants under each diel were measured at day 0 and from other set of plants at day 30. Values are mean ± SD where n = 27 for + 1 leaf length and width and plant height; and n = 3 for dry mass at day 0 and 30
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As infection and neuropathic arthropathy were least likely, we implanted a total shoulder prosthesis 4 months after symptom onset. At surgery, the articular cartilage was lost and the subchondral bone was eburnated (Fig. 8). There was a small amount of serobloody synovial fluid in the glenohumeral joint, which proved not to contain any crystals on microscopic examination. Histologically, the articular cartilage was lost, although there was a small area where degenerated cartilage was noted. In the subchondral zone, there was abundant new bone formation but no evidence of osteonecrosis (Fig. 9).Fig. 8Operative findings of case 2. The articular cartilage was lost, and the subchondral bone was eburnated both in the glenoid (a) [a small amount of serobloody synovial fluid was seen in the glenohumeral joint (b)] and in the humeral head (c) Fig. 9Microscopic findings of the humeral head in case 2. In some specimens, degenerated cartilage was noted (a) [hematoxylin and eosin (H&E) ×40]. There was abundant new bone formation surrounding preexisting trabeculae, which appeared near normal and did not suggest osteonecrosis (b) (H&E ×200)
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However, the fact that ATP level and mitochondrial function were not altered in resting GK muscle does not necessarily imply that oxidative capacity was preserved in working muscle, i.e., when energy demand may increase substantially. As compared to rest, muscle energy demand can actually increase by several orders of magnitude in exercising muscle in order to maintain ATP homeostasis . In the present study, we implemented an intense fatiguing protocol consisting in 6-min of repeated maximal isometric contractions to produce wide changes in metabolic and mechanical changes. Despite this, we did not measure any alteration of oxidative ATP production in contracting GK muscle. Moreover, the maximal oxidative capacity and the initial rate of post-electrostimulation PCr resynthesis–an in vivo index of mitochondrial function –did not differ between both groups thereby indicating that mitochondrial function was not altered in the GK model.
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Complementary mechanisms have been reported to protect C. jejuni from oxidative stress by scavenging free intracellular irons associated with ROS generation or by repairing cellular damages caused by ROS. The E. coli Dps (DNA binding protein from starved cells) is known to protect DNA by sequestrating free Fe2+ and by reducing the formation of ROS (Zhao et al., 2002). In C. jejuni, similarly, Dps captures free Fe2+ and confers resistance to H2O2 (Ishikawa et al., 2003). Upon activation by Fe2+ or H2O2, Dps binds to and protects DNA from damages from hydroxyl radicals (Huergo et al., 2013). Methionine sulphoxide reductases (MsrA and MsrB) reduces oxidized methionine (i.e., methionine sulphoxide [Met-SO]) to methionine and restores methionine function in protein synthesis (Ezraty et al., 2005). Mutations of msrA and msrB, especially an msrA/B double mutation, sensitize C. jejuni to peroxide and superoxide stress and nitrosative stress as well (Atack and Kelly, 2008). CmeG is a multidrug efflux pump that belongs to the major facilitator superfamily (MFS), playing a role in antimicrobial resistance in C. jejuni. Particularly, CmeG overexpression significantly increases C. jejuni resistance to fluoroquinolone antibiotics. In addition to the role in antibiotic resistance, interestingly, CmeG significantly affects C. jejuni susceptibility to H2O2 (Jeon et al., 2011).
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El objetivo de este artículo es presentar los hitos alcanzados durante el desarrollo de un Sistema de Cuentas de Salud, desde su inicio hasta la actualidad. Los períodos de desarrollo se describen de la siguiente forma: a) las bases, es decir, el fundamento económico común de las cuentas nacionales; b) las acciones iniciales realizadas por unos pocos países y organizaciones; c) la propuesta del primer Sistema de Cuentas de Salud como norma para la contabilidad del sistema de salud, y d) la consolidación con el Sistema de Cuentas de Salud del 2011 (conocido como el SHA 2011).
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Karnal bunt (KB) of wheat, caused by the fungus Tilletia indica Mitra [syn. Neovossia indica (Mitra) Mundkur], is one of the greatest challenges to the wheat grain industry. Yield loss is usually limited by this disease, but quality deterioration is a concern because 1–4% of kernel infection is sufficient to make wheat grain unpalatable and 5% of kernel infection causes a distinct deterioration in flour quality (Rush et al., 2005). Additionally, quarantine regulations restrict international movement of KB infected grains from endemic areas (Rush et al., 2005). Other than common wheat (Triticum aestivum L.), the disease also affects durum wheat (T. durum) and Triticale (x Triticosecale). The disease owes its name to Karnal district in India, where it was first reported in 1931, and since has become an important disease in north-western India (Mitra, 1931; Bonde et al., 1997). Apart from India, KB has been reported from Mexico (Duran, 1972), Pakistan (Munjal, 1975), Nepal (Singh et al., 1989), Brazil (Da Luz et al., 1993), the United States of America (APHIS, 1996), Iran (Torarbi et al., 1996), and the Republic of South Africa (Crous et al., 2001). More recently, it has been reported: CIMMYT-blog/tag/karnal-bunt (CIMMYT, 2011), that “Karnal bunt has long been present in Afghanistan, with favorable climatic conditions promoting occasional outbreaks. A recent survey by Agricultural Research Institute of Afghanistan (ARIA) indicated that several popular wheat varieties are susceptible to the disease (Singh, personal communication). It is particularly prevalent in the eastern region bordering Pakistan, which has emerged in recent years as an important seed-producing area within Afghanistan. Despite this, there is no public information regarding the history, disease incidence and the area affected of Karnal bunt in that country. The disease had its worst epiphytotics in North America in 1983, 1985 and 1986 in southern Sonora, Mexico (Lira, 1991).
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The management of CPPS is based on a bio-psychosocial model which includes an active patients’ involvement. Pharmacological and non-pharmacological interventions such as psychotherapy, physiotherapy, drugs and invasive treatments rarely works in isolation and often need to be considered together as a part of a personalized treatment strategy .
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Data were gathered on 1373 visited rabbitries; 1283 in Spain and 90 in Portugal. Farms in Spain are inscribed in the official database Registro General de Explotaciones Ganaderas (REGA). According to the Ministerio de Agricultura, Pesca y Alimentación , the number of farms varied greatly throughout the 26-year study. In a preliminary paper, we provided a detailed explanation of the farms registered in the REGA database and those visited between 2001 and 2017 (Figure 1, in ), and those visited in Portugal. On each visit, we asked producers about their rabbit breeds and lines, doe inventories, i.e., females bred once or more, generally at ≥4.5 months old. In Spain and Portugal, the majority of food-producing rabbits belong to breeding companies, with the exception of New Zealand White rabbits (we examined does on two farms for laboratory and two for meat). In addition, we visited two doe farms with Rex rabbits, three doe farms for pets, not included in the current study, and also farms with non-selected “colored” breeds/lines .
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El modelado geoespacial constituye una herramienta para la priorización y planificación de acciones y para dar soporte en la toma de decisiones en la salud pública, debido a que representan el riesgo sanitario desde los puntos de vista epidemiológico, espacial y temporal ante enfermedades reemergentes como el agente causal de los virus de influenza tipo A. Se vislumbra un escenario probabilístico de alarma, ya que más de la mitad del territorio mexicano se encontraría en algún nivel de riesgo de tener contacto con virus con alto grado de patogenicidad y una posible combinación con los de baja patogenicidad.
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L'indice de masse corporelle (IMC): environ un patient sur deux était amaigri. Ce constat témoigne de l'altération de l'état général en rapport avec le stade d'évolution de l'infection VIH. Dans notre étude le surpoids était un facteur défavorable de l'IRA (P=0,047).
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Rheumatoid arthritis (RA) is a common chronic, systemic autoimmune disease, affecting an estimated 1-2% of the global population, being three times more frequent in women . Leading to synovitis, RA comes along with hypertrophy of the synovial tissue as pannus formation. Distinctively, these inflammatory, symmetric processes occur at peripheral joints, resulting in erosion of the articular cartilage and subchondral bone [2, 3].
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The studies involving human participants were reviewed and approved by Ethical Committee of the Department of Human Sciences of the University of Verona (protocol n. 118846/2020). The patients/participants provided their written informed consent to participate in this study.
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From the presented model the response surface plots were obtained (Figure 2). The surface plot in Figure 2 shows that in the whole range tested, intermediate values of SA are necessary to increase IY when intermediate to high values of CTS and CaCl2 are used (Figure 2a–c). Considering the complexation time, if intermediate values of SA are used (Figure 2d), as well as high values of CaCl2 (Figure 2e), high IY are reached independent of the CT chosen. However, high CTS is needed to achieve high values of IY and this condition is obtained with high CT.
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A inflamação dos vasos sanguíneos, de fato, contribui para o remodelamento vascular, aumento da resistência periférica e desordens circulatórias.7 , 15 , 16 Neste contexto, o remodelamento vascular é um processo crônico adaptativo, caracterizado por alterações na estrutura dos vasos sanguíneos, derivadas de citocinas pró-inflamatórias, além de interações entre fatores de crescimento, estímulos hemodinâmicos e espécies reativas de oxigênio. Compreende modificações no crescimento, morte e migração celular, e na síntese e degradação da matriz extracelular.17 - 19
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之后，我们对上一个Cox风险比例模型进行了进一步的调整，排除了人种、肿瘤位置、偏侧性和诊断年份这些与临床关系不是非常密切的变量，并根据年龄、性别、肿瘤大小、分化程度、组织学类型和治疗方式重新调整Cox风险比例模型（表 5）。在该模型中，与消融组相比，亚肺叶切除组治疗Ia期NSCLC患者的HR为0.605（P < 0.001），即亚肺叶切除术组的风险是消融组的0.605倍（95%CI: 0.477-0.766），可以认为两种治疗方式对Ia期NSCLC患者的生存时间产生不同的影响，消融组和亚肺叶切除组之间存在显著性差异。可以认为相比于消融术，亚肺叶切除术有更好的生存预后。
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The RNA quality assessment and gene expression microarray were performed in the Genome Research Centre of the University of Hong Kong. GeneChip Human Genome U133 Plus 2.0 Array (Affymetrix) was employed to examine global gene expression profiling. Agilent 2100 bioanalyzer (Agilent Technologies) was used to evaluate RNA quality. GeneSpring GX version 10.0 (Agilent Technologies) was employed to analyze microarray data. The microarry data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE79571. Microarray data of 31 NPC tissues were obtained from GSE12452 of GEO. Microarray data of HONE1, CNE1, CNE2 were obtained from GSE15047. Raw microarray data of C666-1 were obtained from GSE34573. All the microarray data were normalized and analyzed using Gene Expression Commons . Targets of ebv-miR-BART7 was predicted using Vir-Mir db . The minimum free energy (mfe) of the miRNA/mRNA duplex was calculated and a lower mfe indicated greater stability of the miRNA/mRNA duplex.
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Der zijn mensen die perfect Algemeen Nederlands kunnen ma (maar) da's (dat is) nie (niet) de normale […] iedereen probeert dan Algemeen Nederlands te spreken ma vo (voor) mij is da (dat) altijd een tussentaal en… […] ok misschien Martine Tanghe die op't journaal presenteert dat die Algemeen Nederlands spreekt daar kan ik mee z…. ma (maar) da (dat) vin (vind) ik nie (niet) dat da (dat) gesproken wordt in… in… in België op straat.
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In der Pharmakodynamik, die das Wirkprofil eines Medikaments am Zielort beschreibt, können additive bzw. synergistische und antagonistische Wechselwirkungen von Medikamenten unterschieden werden. Ein synergistischer Effekt ist oftmals erwünscht und findet in Form von Kombinationstherapien unter anderem in der Schmerztherapie nach WHO(World Health Organization)-Stufenschema, bei der Behandlung mit Antiinfektiva, in der Tumortherapie oder bei der Behandlung der Hypertonie Anwendung. Eine synergistische Wirkung kann jedoch auch unerwünschte Komplikationen hervorrufen. So besteht beispielsweise durch die gleichzeitige Gabe von Methotrexat und Sulfonamiden das erhöhte Risiko des Auftretens einer Panzytopenie infolge einer Knochenmarksuppression bedingt durch einen additiven Folsäureantagonismus .
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Data from IOP-inoculated pigs from the three studies were evaluated based on FMDV RNA dynamics in serum and OPF. Two distinct Generalized Additive Mixed Models (GAMMs) were fitted to the data. The levels of FMDV RNA in serum or OPF were the dependent variables, whereas time (hours) and an indicator variable for the challenge dose (low 10 PHID50 vs. high 100 PHID50) were the explanatory variables for each model. Individual animal identification was used as a random effect to account for repeated measurements on the same animal. If the groups did not differ significantly (significant differences were determined using p < 0.05 for between group comparisons), they were combined into a single category for further analysis.
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Health outcomes (e.g. life expectancy, quality of life, and patient satisfaction) have steadily improved worldwide over recent decades. This improvement is largely attributed to the use of conventional medicine (CM). However, there are many unfulfilled health expectations [1, 2] and issues with regard to maintaining wellness and treating several chronic, irreversible, and/or incurable diseases such as ischaemic heart disease and end-stage renal disease (ESRD) [1, 4, 5]. Many patients supplement their health care with complementary and alternative medicine. People use CAM for many reasons, including to cure illness , to counteract the adverse effects of CM , and/or to promote wellness and holistic care [8, 9]. Patients may also resort to CAM because CM is beyond their financial means . Studies in Trinidad and India reveal that a patient’s CAM use is largely based on perception rather than on science or logic [11, 12]. Patients’ expectations of CAM are less likely to be influenced by the limitations of CM than by the desire to be treated in a manner that is beyond the perceived scope of CM. The reported global prevalence of CAM use ranges widely from 9.8% to 76.0% . It is estimated that CAM is used by 38% of adults in the United States of America (USA) , 51.8% of adults in the United Kingdom (UK) , and 68.9% of adults in Australia . The annual expenditure on CAM in the UK is on the order of 1.47–1.6 billion pounds and that adults in the USA pay $34 billion out-of-pocket costs for CAM annually . The prevalence of CAM use in Trinidad and Tobago is unknown, but appears to be high.
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In this study, the T11-12 segment was injured for model establishment, and the injury level was above the conus medullaris (upper motor neuron injury). The bowel dysfunction in the SCI models generated here should mainly be manifested as extended colonic transit time, delayed transmission, and difficult bowel movement [4, 31]. In line with the theoretical expectations, the SCI rats showed reduced weight, dry stool, difficult bowel movement, prolonged defecation, reduced feces amounts, and intestinal transit disorder. Mosapride is a prokinetic therapeutic for dyspeptic symptoms of gastrointestinal disorders . Although mosapride treatment shortened defecation time in rats with SCI to some extent and increased feces amounts, its improvement of fecal pellet traits was not significant. Interestingly, AMT with different intensities showed more advantages than mosapride treatment in shortening defecation time, increasing feces amounts, and improving stool traits, and is worthy of clinical attention.
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La gobernanza incluyente también abarca la rendición de cuentas sobre las acciones y los resultados. En el marco de la recomendación de la Comisión de hacer de la equidad en la salud un indicador clave del desarrollo de la sociedad y de establecer mecanismos de rendición de cuentas, es fundamental que se generen y notifiquen datos desglosados. En consonancia con la primera función esencial de la salud pública —la vigilancia de la salud y el bienestar de la población (31)— y el primer indicador de impacto del actual Plan Estratégico de la OPS (32), “Reducción de las desigualdades en la salud dentro de los países”, es menester que las instituciones inviertan en la capacidad de no solo informar esporádicamente sobre las desigualdades en la salud sino de institucionalizar su seguimiento dentro del análisis de la situación de salud. De esta forma, subsanar las inequidades puede normalizarse como un parámetro del éxito. Además, deben emplearse datos para fundamentar medidas de política a fin de incrementar su impacto potencial. Necesitamos más investigación sobre los aspectos específicos de lo que funciona, así como hacer mejor uso de la información que ya tenemos. La transparencia también constituye la base de una gobernanza incluyente y eficaz. Es necesario poner la evidencia científica a disposición del público, y demostrar cómo se está utilizando esa evidencia sobre las inequidades en la formulación de políticas y en el seguimiento y, quizás aún más importante, señalar dónde están las brechas.
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Structural studies of RimK to date have been limited to RimKEC, which has been resolved as a tetramer. 12 , 13 At this stage, however, the structural biology of the Pseudomonas Rim system is largely unstudied. Here, we solve the structures of two Pseudomonas RimK proteins and use them to shed new light on the mechanism of protein function. A detailed comparison of these proteins allows us to identify key structural factors, such as the hitherto unknown location of glutamate binding, which help to explain the differences in enzyme activity and protein regulation seen for different RimK variants. Finally, we use the structural differences between these proteins to identify a potential RimB‐RimK interaction site, which is specific to Pseudomonas RimK and allows for the regulation of enzyme activity.
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Analysis of these miRNA degradomes and transcriptomes indicated that most genes with altered expression were enriched in GO terms related to the nucleus, regulation of transcription and DNA templates, and DNA binding (Fig. 6a). Genes related to photosynthesis in KEGG were also enriched (Fig. 6b). To detect negatively regulated miRNAs and their target genes, combined analysis of the expression of miRNAs, the degradome, and the transcriptome was performed. A total of 30 negatively regulated genes, which are targeted by six miRNAs (miR169i-p5, miR169l-5p, miR319b-p3, miR319b-p3-1, miR319b-p3-Pt, and miR8155), were identified (Supplementary Table S5). Among these 30 genes, the expression of only five (GRMZM2G069316, GRMZM2G057576, GRMZM2G120329, GRMZM2G142093, and GRMZM2G031169) changed significantly (P<0.05). Furthermore, the expression of two target genes GRMZM2G069316 (targeted by miR169i-p5) and GRMZM2G031169 (targeted by miR8155) changed more than 1.5-fold (|log2FC| > 0.58; P<0.05) (Supplementary Table S5). GRMZM2G069316 was related to only one GO term (GO:0005488//binding) (Fig. 7a). Thirteen DEGs were detected for GO:0005488, which included annotations for HEAT repeat family proteins, a lectin-like protein kinase, a mitochondrial carrier protein, and a U-box domain-containing protein component of ubiquitin ligase (Supplementary Table S11). GRMZM2G031169 was related to three GO terms (GO:0003824//catalytic activity; GO: 0044237//cellular metabolic process; and GO:0050662//coenzyme binding) (Fig. 7b). Fifty-one DEGs that were detected were related to GO:0003824, and were annotated as a 3-ketoacyl-CoA synthase, an alpha-amylase precursor, an AMP-binding domain-containing protein, a protein phosphatase 2C, a reticuline oxidase-like protein precursor, and UDP-glucuronate 4-epimerase (Supplementary Table S12). The same four DEGs were detected in each of GO:0003824, GO:0044237, and GO:0050662, which were annotated as a dehydrogenase/reductase SDR family member 12, a dehydrogenase, and UDP-glucuronate 4-epimerase, respectively (Supplementary Table S12).
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Cancer was responsible for about 10 million deaths in 2020, making it one of the biggest civilizational health problems, just behind the heart diseases . Among all cancers, breast cancer was the most common in terms of new cases of cancer last year and in general is the most prevalent cancer among women, alone accounting for 30% of female cancers . On the other hand, lung cancer was the most common cause of cancer death, being responsible for 1.80 million deaths in 2020. The next most common were cancers of the colon and rectum (935,000 deaths) and of the liver (830,000 deaths) . Although significant progress has been made to improve cancer treatment over the past decade, the field is still waiting for new breakthrough treatments.
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Enzyme activity of TPL and TPL fused with peptides. Relative activity of supernatants and precipitates from TPL and TPL fused with peptides at 20 °C (a). Enzyme activity of TPL and TPL fused with peptides at 10 °C, 20 °C, 30 °C, 40 °C, and 50 °C (b). Experiments were performed in triplicate, and error bars represent the standard deviation
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Primeiramente, o padrão da alimentação da população em 2017–2018 foi descrito distribuindo o total de calorias consumidas segundo os quatro grandes grupos da Nova e, internamente a esses grupos, segundo subgrupos selecionados. Foram apresentadas médias de consumo de energia e o percentual de participação no total de energia consumida para cada um desses grupos e subgrupos.
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Alternativpräparate zur Basisimmunsuppression können sog. Mammalian-target-of-rapamycin(mTOR)-Inhibitoren (Sirolimus, Everolimus) darstellen. Jedoch auch hier kann es zum Auftreten von Hyperlipidämie, Knochenmarksuppression, Wundheilungsstörungen, Muskel- und Gelenksschmerzen, oralen Aphthen sowie in seltenen Fällen zu einer Pneumonitis kommen.
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With respect to the use of anti-inflammatories clinically there are a few reports using systemic COX (Cyclooxygenase) inhibitors, such as Pioglitazone and Rofecoxib in the management of melanoma [43, 44]. Also Lejeune et al, (2006) reported a case study of a patient with a metastatic melanoma of the leg who experienced sustained regression of skin metastases upon continuous single treatment with the cyclooxygenase-2 inhibitor Rofecoxib.
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Les caractéristiques immuno-histochimiques sont similaires à celles des mélanomes cutanés. les marqueurs tumoraux utilisés pour affirmer le diagnostic, sont l'anticorps anti Melan A, anti protéine S100, et l'anticorps HMB45, ce dernier étant plus spécifique de la cellule mélanique.L'utilisation des deux anticorps est souhaitable. Plus récemment, d'autres anticorps plus sélectifs de la lignée mélanocytaire sont utilisés: le NK1 /C-3 et le NK1BETEB. Une fois le diagnostic d'un mélanome est porté, il reste à prouver sa nature primitive. Ceci implique la recherche d'un mélanome primitif cutané, ophtalmologique, ORL digestif ou d'antécédents d'exérèse antérieure d'une lésion cutanée pigmentaire. Les facteurs pronostics des mélanomes admis par l'AJCC révisé en 2009, notamment l'ulcération et le Breslow ne semblent pas utiles dans les mélanomes muqueux . Cependant, après une revue de 115 cas de mélanomes vaginaux, Reid et al ont retenu la taille comme seul facteur pronostic avec une valeur seuil de 3cm . La plupart des auteurs tels que Mordel et al, défendent l'utilisation du système de FIGO (International Federation Of Gynecologists And Obstetricians) pour le staging, vue que le mélanome cervical est souvent diagnostiqué à un stade tardif et a une présentation clinique et un mode d'extension tout à fait comparable au carcinome cervical.
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Our previous studies indicate that the inhibition of ANXA1 expression by siRNAs in C2C12 cells caused reduction in myogenic differentiation, whereas analysis on sorted quiescent and activated SCs of Tg:Pax7nGFP mice showed that ANXA1 is expressed in both quiescent and activated SCs cells. Interestingly, we have shown that ANXA1 expression is not restricted to dividing transit amplifying myoblasts that are generated from SCs after injury, but is present also in the quiescent SCs isolated directly from homeostatic tissue. Immunofluorescence approaches on sections of Tibialis Anterior muscle confirmed that ANXA1 is expressed in quiescent and activated SCs co-stained with Pax7 (a marker of SC quiescence) and suggested that the protein is mainly localized in the cells that migrate in the lumen of regenerating fibers.
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The effect of decreasing the CBH reaction period on release of glucose and cellobiose from cellulose. For clarity, a single representative experiment is shown for each reaction period in the figure. CBH activity period is given in the legend (ms) where 500 ms represents the base case value. CBH: cellobiohydrolase.
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(a)The electrostatic potential map of a longitudinal section drawing of res-RolR calculated with deletion of the resorcinol molecule showing the internal binding pocket between RolR and resorcinol. (b)The section around the resorcinol of the binding pocket fitting to a resorcinol molecule and two water molecules highlighted the water-mediated interactions between resorcinol and RolR. (c) The 2Fo-Fc (blue) and Fo-Fc (red) omit map around the bound resorcinol molecule, contoured at 1σ and 3σ respectively. (d) The recognition mode between RolR and resorcinol unique in a water molecules-mediated hydrogen bond network. The sidechains of residues involved in ligand recognition and water molecules are shown in ball-and-stick, with atoms O, N and C in red, blue and green, respectively.
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1869年，Ashworth首先报道了1例肿瘤患者外周血中存在癌细胞以来，肿瘤微转移的概念在实践中逐步得到认识并成为近年来肿瘤转移研究的热点。肺癌微转移是指播散并存活于淋巴道、血循环、骨髓及各组织器官中，采用常规检查方法，如组织病理学、影像学等难以发现的肺癌细胞团或结节，需要通过免疫学或分子生物学技术才能发现。在肿瘤微转移的分子诊断研究中，标记物的含义与肿瘤标记物(tumor markers)不完全相同。前者是指正常组织细胞以及相应的肿瘤细胞所特有的，即具有组织特异性(tissue specificity)；而后者是指肿瘤组织和细胞所特有的。这类分子标记应具备2个特点：①特异性强，仅在待测的组织和来源于该组织的肿瘤细胞中表达，其它组织不表达；②敏感性高，在骨髓、淋巴结和体液中能稳定地被检测到。2001年，周清华等报道应用RT-PCR的方法能检测到每毫升中存在10个肺癌细胞的微转移。在肺癌微转移的研究中，常用的分子标记可分为以下几类：(1)组织特异性蛋白质(tissue specific proteins, TSPs)：组织细胞内大量存在着的蛋白质是细胞生命活动的基础，蛋白质的功能各不相同。在肺癌微转移的分子诊断研究中，TSPs是应用较为普遍的标记物。组织特异性蛋白质包括以下3类：①细胞角蛋白家族(cytokeratins, CKs)：细胞角蛋白家族是检测肺癌微转移最常应用的组织特异性蛋白质。细胞角蛋白来源于上皮组织，是真核细胞的细胞骨架中间丝蛋白(intermediate filament protein)中最为复杂的一类。现在已知CK家族由分子量不等的20个成员组成，即CK1-CK20。CKs一般在上皮组织中成对表达，特异性强。CKs的阳性表达已经成为上皮细胞及其肿瘤细胞较为敏感和特异的标记。单层上皮中，所有的分泌上皮(腺上皮)均表达CK8和CK18，多数细胞还表达CK19。因此在肺癌研究中常常以CK8、CK18和CK19作为分子标记。Pantel等以CK18为分子标记，在139例无远处转移的NSCLC患者的骨髓中检测到83例患者的骨髓微转移。②组织多肽抗原(tissue polypeptideantigen, TPA)：TPA是一种不含糖脂的蛋白质，即单链多肽。它由4个亚单位构成，其结构与CKs有较高的同源性，是CK8、CK18和CK19片段的复合物。TPA在细胞周期的S和M期合成，当细胞处于增殖分化时浓度较高。多个小组的研究表明，TPA是肺癌患者疗效和预后的判断指标，连续检测TPA对监测肺癌的播散和肿瘤复发有较好的参考价值。③上皮特异性抗原(epithelial specificantigen, EPA)：EPA是上皮组织特异表达的蛋白质，位于细胞膜或胞浆中。目前，主要应用上皮特异性抗原癌胚抗原(CEA)和上皮膜抗原(EMA)诊断肺癌微转移。(2)组织特异性基因(tissue specific genes)：这一类基因与组织特异性蛋白质相类似，仅在上皮组织和上皮组织源的肿瘤组织中特异地表达。在最近的研究中，不少研究者以此类基因作为肺癌微转移诊断的分子标记。组织特异性基因应用于肿瘤微转移的标志物主要有以下几类：①肺泡表面蛋白mRNA：肺泡表面蛋白(surfactant proteins, SP)是肺泡表面活性物质中的主要蛋白质，由Ⅱ型肺泡细胞和Clora细胞合成分泌。在肺癌患者微转移的检测中，Betz等以SP mRNA作为标记物，检测13例M1期NSCLC患者的淋巴结中发现SP mRNA表达阳性率为84.6%(11/13)。在组织学检查阴性的淋巴结中，SP mRNA阳性检出率为55.5% (10/18)[65, 68]。②粘蛋白基因MUC1：粘蛋白(mucin)是一种细胞表面糖蛋白，主要存在于粘液中，由上皮组织的G细胞和某些粘膜下腺体分泌，是一类高分子量、多分散度的分子族，包括6个成员(mucin 1, 2, 3, 4, 5a, 5b)。已有报道证明，MUC1在正常肺组织以及绝大多数NSCLC细胞系或实体瘤中均有较高表达，但不表达于正常的淋巴结组织中。牛中喜等应用MUC1 mRNA作为分子标记，检测了119枚肺癌患者淋巴结中MUC1 mRNA表达，发现65枚存在MUC1 mRNA表达，阳性率为54.5%(65/119)；而病理方法仅检测出41枚淋巴结存在癌转移，阳性率为34.5%(41/119)。病理学检测阴性的78枚淋巴结中，经RT-PCR方法检测到24枚淋巴结存在MUC1 mRNA表达，阳性率为20.77%(24/78)。肺良性病变患者35枚淋巴结MUC1 mRNA表达均为阴性。③ CKs mRNA：CKs已经在蛋白质水平被证明是较敏感和特异的鉴别上皮组织和上皮源性肿瘤细胞的标记物之一。牛中喜等应用CK19 mRNA检测了119枚肺癌患者淋巴结中CK19 mRNA表达，66枚淋巴结存在CK19 mRNA表达，阳性率为55.5%(66/119)，病理学方法检测出41枚淋巴结存在癌转移，阳性率为34.5%(41/119)。病理学检测阴性的78枚淋巴结中，经RT-PCR方法检测到25枚淋巴结存在CK19 mRNA表达，阳性率为32.1%(25/78)。Krismann等研究表明以CK19 mRNA为标记物可以检测出肺癌患者周围循环中的CTCs，其阳性检出率可以达到50%(25/50)。(3)癌基因和抑癌基因：现有的研究表明，癌基因/抑癌基因的缺失、突变及过量表达是最为特异的肿瘤标志物之一。但是缺乏稳定的表达是难以以此作为肿瘤微转移分子诊断标记物的主要原因。
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For each \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$m\in \{1,\ldots ,\bar{m}-1\}$$\end{document}m∈{1,…,m¯-1} (if nonempty) the translated maps \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$u_i^m(s,\theta ):=u_i(s+s_i^m,\theta )$$\end{document}uim(s,θ):=ui(s+sim,θ) converge to a nontrival bubble branch in the sense of Definition 1.8.
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Technology enhanced learning (TEL) kann im Kontext einer hybriden Lernumgebung den Bedarf an Präsenzunterricht reduzieren und ermöglicht die Fortführung akademischer Lehre unter Pandemiebedingungen.Der Transfer von existierenden, curricularen Lerninhalten in eine virtuelle Lernumgebung erfordert fundierte Kenntnisse in moderner Medizindidaktik.Die Akzeptanz von TEL unter Studierenden ist hoch.Selbstbestimmtes Lernen wird von den Studierenden als besonderer Vorteil gewertet.Klinischer Unterricht am Patienten oder im Simulationszentrum bleibt unverzichtbar.
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In 2004, Flammeovirga sp. strain MY04 was isolated from coastal sediment in eastern China. The bacterium showed a curved rod shape, grew well at 30°C and pH 7, and exhibited a significant color change (deep red-orange in the exponential growth phase and a white color in the later stage). Our previous work indicated that strain MY04 was a polysaccharide-degrading bacterium that could grow well on a variety of polysaccharide carbon source-limited media, such as agar, xylan, mannan, cellulose, and carrageenan (7). The complete genome sequence of Flammeovirga sp. MY04 was determined and assembled using Illumina HiSeq and Pacific Biosciences sequencing technologies (RefSeq Assembly Acceptance GCF_001682195.2). The complete genome size of the strain was 7,327,614 bp, encoding 5,618 genes that included 5,495 protein-coding genes, 24 rRNA genes, and 86 tRNA genes (Table 1). The genes for MY04 were distributed across three circular replicons named chromosome I (5.06 Mbp, 4,066 genes), chromosome II (2.19 Mbp, 1,481 genes), and plasmid (0.08 Mbp, 71 genes) (Fig. 1A). We found that the smaller replicon II of MY04 (i) encoded rRNA, while the rRNA (rrn) operon that encoded rRNA (16S, 23S, and 5S rRNA) was a marker that defines the replicon as a “chromosome” (20), and (ii) their sizes were between 1.41 Mb and 2.21 Mb, which was much larger than the average size of the plasmid (78.9 kb) and the average size of the megaplasmid (772 kb) (1), and (iii) the difference in GC content between chromosome II and chromosome I was no more than 1% (for example, 34% to 33.5% < 1%) (1). Taken together, we defined the replicon as chromosome II rather than a plasmid or megaplasmid.
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It was proposed that ICP-associated fetal arrhythmia and intrauterine death may result from raised tauro-conjugated bile acids6, and previous work has focussed on the arrhythmogenic effects of TCA on cardiomyocytes and myofibroblasts15,16. However, TCA is not the only bile acid to be elevated in maternal and fetal serum, and the impact of other bile acids on fetal arrhythmias has not been established.
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250 µg recombinant hCG (r-hCG) (Ovitrelle, Merck Serono, Italy) was administered when at least three follicles had reached a diameter of 18 mm. Transvaginal-guided oocyte retrieval was done under general anesthesia 36 hours after the hCG injection. The morphological grading of the oocytes was done according to oocyte-cumulus complex, and embryo transfer was done between the 2nd to 5th days.
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然而，对于早期（Ⅰ期）肺癌的SPN患者的手术方案的仍存有争议。肺叶切除、亚肺叶切除（包括解剖性肺段切除及非解剖性肺楔形切除）在早期肺癌术式选择的地位备受关注。2012年，Stefani等回顾性分析了将82例楔形切除及124例肺叶切除的T1N0的NSCLC患者，发现术后并发症、死亡率无明显差异，但两者的局部复发率、5年生存率、5年无疾病生存率存在明显差异，分别是（22%, 8%）、（74%, 85%）、（62%, 77%）。Wolf等也认为在能耐受肺叶切除的患者中，肺叶切除仍应作为首选，而亚肺叶切除在年老或肺功能差的患者中值得考虑。同样，一项population-based研究支持了这一点，在14, 473例Ⅰ期NSCLC患者中，肺叶切除总生存率及肿瘤相关生存率均明显高于解剖性肺段切除，提出肺叶切除仍应作为Ⅰ期NSCLC标准术式且不考虑肿瘤大小。然而，有学者综合分析1988年-2008年（分三个阶段，三阶段手术方式的选择不一）≤2 cm的Ⅰa期NSCLC的手术方式与术后生存率的关系变化，提出肺叶切除是否作为≤2 cm的Ⅰa期NSCLC的标准术式应进行重新评估，他们发现在近些年来的Ⅰa期NSCLC病例中，肺段切除及肺楔形切除后患者的总生存率与肺叶切除相当；2012年，Zhong等比较了≤2 cm的Ⅰa期肿瘤患者中行胸腔镜下段切除和叶切除两种手术方式，发现术后并发症、术后局部复发率、5年生存率及无疾病生存率均未见明显差异。而Fan的一篇meta分析显示，Ⅰ期NSCLC患者行肺叶切除的总生存率和肿瘤相关生存率明显高于亚肺叶切除（P=0.000, 6），而 < 2 cm的Ⅰa期患者，总生存率没有差异（P=0.58）。而同肺段切除相比，肺叶切除的总生存率（P=0.45）和肿瘤相关生存率（P=0.97）在Ⅰ期NSCLC中没有明显差异。换言之，亚肺叶切除的术式范围应为解剖性段切除，而不是非解剖性楔形切除。目前，两项比较局部切除和肺叶切除的随机研究正在日本、美国进行，期待能为早期肺癌手术方式选择提供一定的依据。
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Zur ganzheitlichen Behandlungganzheitlichen Behandlung des Patienten sollten auch Spezialisten anderer Fachgebiete einbezogen werden. Dies ermöglicht eine raschere Versorgung und eine frühere Rehabilitation und verbessert beim geriatrischen Patienten nicht nur die funktionellen klinischen Ergebnisse, sondern senkt auch die längerfristige Mortalität erheblich [4, 5]. In Tab. 1 findet sich eine stichwortartige Zusammenfassung der relevanten Aspekte, die im Behandlungsteam vor Beginn der Behandlung diskutiert und geplant werden sollen.FragestellungWichtige GesichtspunkteFragen bei der Indikationsstellung im AlterErwartungen/Wünsche des Patienten, physische Belastung, Lebensqualität, Komorbiditäten, alternative Therapie, Rückzugsoptionen, Interdisziplinarität, EthikratOperationsvorbereitungDetaillierte, interdisziplinäre Planung, spezifische Gefäßdiagnostik u. a. Duplexsonographie, Angiographie (CT-/MR-Angiographie, konventionell, interventionell), Phlebographie, Notwendigkeit eines AV-Loop/Bypasses prüfen, Anwendung von zuverlässigen Standardtechniken („workhorse flaps“), Patientenverfügung/VorsorgevollmachtKomorbiditäten und perioperatives ManagementRelevanz kardiologischer, nephrologischer, pneumologischer, hämostaseologischer Komorbiditäten, Kooperation mit der Geriatrie etablieren, Anwendung von „frailty assessments“, Möglichkeit der Prehabilitation, Minimierung der anästhesiologischen Belastung, der Anzahl notwendiger Operationen sowie der Operationszeit, Vermeidung eines LehreingriffsBesonderheiten postoperative PhaseLeitlinien/Konsensus bezüglich Perfusionsmonitoring, Schmerztherapie, Gerinnungsmanagement, intensivierter Dekubitusprophylaxe, rascher Mobilisierung, Fortbildung der Ärzte/des Pflegepersonal bezüglich Versorgung alter Patienten, Delirprophylaxe/-therapieAV arteriovenös
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Badacze zajmujący się PKU wielokrotnie wykorzystywali model bliźniąt [17, 18, 19]. Wykazywano zmienność obrazu klinicznego choroby u osobników z tymi samymi mutacjami PAH porównując rodzeństwa, w tym zarówno bliźnięta dwujajowe , jak i jednojajowe [17, 21]. W 1995r. Verkerk i van der Meer z uniwersyteckiego szpitala w Maastricht przedstawili, interesujący a niejasny co do pierwotnej przyczyny, przypadek noworodka płci męskiej z wysokim stężeniem Phe w 7 dniu życia i jego siostry bliźniaczki z prawidłowym wynikiem badania przesiewowego, u której do wczesnego rozpoznania PKU doszło dzięki bezwarunkowej dociekliwości klinicystów. W opisie 18 chorych na PKU z Rumunii 22% stanowiły bliźnięta jednojajowe . Niekiedy jedno z bliźniąt, chore na PKU, swoimi potrzebami odnośnie terapii, przerasta wydolność rodziny i staje się przyczynkiem dla interwencji instytucji strzegących praw dziecka, która przypuszczalnie w przypadku niewystąpienia choroby nie byłaby konieczna .
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Plusieurs locataires ont souhaité voir le Programme être prolongé jusqu’à la fin de la pandémie, voire même d’envisager les appels sur une base régulière. Ce sont surtout les familles immigrantes, sans famille élargie à proximité, qui ont le plus largement apprécié le Programme.
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В связи с большим потенциалом антоцианов в качестве компонентов функционального питания сегодня становятся востребованными знания об их генетическом контроле, которые находят свое применение в селекционных программах, направленных на создание новых сортов культурных растений с повышенным содержанием этих ценных для здоровья человека соединений.
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Adressaten der Befragung waren niedergelassene und klinisch tätige HNO-Ärzte. Zur Weiterleitung der Fragebögen an niedergelassene HNO-Ärzte nahmen wir Kontakt zum Deutschen HNO-Berufsverband (Organisationsgrad ≥ 90 % der niedergelassenen Ärzte) auf, zur Weiterleitung an die in 160 HNO-Hauptabteilungen und 35 Universitätsklinika klinisch tätigen HNO-Ärzte kontaktierten wir die Deutsche Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie.
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TKI的肝脏毒性作用除了与细胞应激、免疫反应相关外，近年来也认为与药物代谢酶细胞色素P450 (cytochromep 450, CYP450)的基因多态性有关。CYP2D6是CYP酶家族重要成员之一，编码CYP2D6的基因位于第22号染色体，有9个外显子，8个内含子，共编码497种氨基酸。目前发现CYP2D6约有80个突变位点，基因突变可导致酶活性和数量的不同，引起药物代谢个体的差异，最后引起药物疗效或毒副作用的差异。按基因突变体产物的功能可分为功能基因、功能缺陷基因和无功能基因。携带等位基因CYP2D6*5因大段基因缺失，导致整个CYP2D6功能的缺失，使酶没有活性，称无功能等位基因。含有CYP2D6*10的纯合子或杂合子，编码的蛋白质结构不稳定，使酶活性明显下降，称功能缺陷等位基因。文献报道17例曾经服用Geftinib后发生肝脏毒性的肺癌患者，携带等位基因CYP2D6*5或*10者可以成功地转换到Erlotinib治疗(P=0.024)，但没有含这两个等位基因的患者则不能，提示那些曾经因Geftinib所致肝脏毒性且CYP2D6活性较弱的患者可以安全地使用Erlotinib。应用CYP3A4抑制剂后，7例携带CYP2D6*5或*10的患者再次使用Gefitinib仍引起肝脏毒性，而3例有正常等位基因的患者则不会发生肝脏毒性。提示CYP3A4被抑制后，CYP2D6酶功能的缺陷可能是Gefitnib引起肝脏毒性的主要原因。
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The maternal FN1 transcript isoform, expressed in oocytes and gradually degrading in 2-cell embryos, was identical to the embryonic FN1 transcript isoform expressed from the morula stage onwards. Sequencing followed by the comparison of this splice variant (EIIIB-/EIIIA+/IIICS+) with the in silico predicted bovine FN1 transcript variants in the NCBI Entrez Gene database revealed that it constitutes a new FN1 splice isoform (Genbank Accession Number: FJ513187) supporting our hypothesis that FN1 exerts a specific function during compaction and early blastocyst formation.
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Contudo, foram obtidas informações de grande valor para população idosa estudada, a qual está à margem dos grandes centros urbanos do Brasil, localizada em uma região com características peculiares quanto aos aspectos sociodemográficos, culturais e econômicos e que apresenta escassos estudos de seguimento para subpopulações vulneráveis. Dessa forma, a identificação dos efeitos independentes que o sono e os sintomas depressivos produzem sobre a taxa de mortalidade de idosos são de considerável importância nas políticas na saúde da pessoa idosa, principalmente para o planejamento público e clínico. Essas informações servirão para alicerçar as tomadas de decisão na organização do cuidado da pessoa idosa, sobretudo para mitigar os predisponentes de vulnerabilidade de sua capacidade funcional e sobrevida.
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Различия отражательных характеристик в определен- ных зонах спектра послужили основой для применения вегетационных индексов для обнаружения и диагностики корневой гнили на посевах и распознавания особенностей здоровых и пораженных заболеванием всходов пшеницы. В результате анализа различных вегетационных индексов, ранее используемых при диагностике и мониторинге развития других заболеваний пшеницы (Дубровская и др., 2018), а также на основе анализа спектральных характеристик, полученных при лабораторном эксперименте, было выбрано 13 вегетационных индексов для идентификации корневой гнили (В. sorokiniana) (табл. 1). Детальное описание индексов приведено в работе (Дубровская и др., 2018).
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Assim, o tratamento endovascular de AAVR com técnicas endovasculares parece ser boa alternativa ao tratamento aberto. No caso apresentado, a utilização de stent com molas para tratamento de ambos aneurismas se mostrou efetiva no tratamento e na evolução a curto prazo. Todas as técnicas apresentam suas particularidades, com vantagens e desvantagens, e a indicação da técnica utilizada deve ser individualizada. A utilização de novas técnicas e materiais derivados da neurointervenção parece ser uma alternativa promissora para aneurismas complexos com colos largos e ramos eferentes, porém mais estudos multicêntricos prospectivos e randomizados são necessários. Em conclusão, o tratamento endovascular de aneurismas de artéria esplênica e renal no mesmo tempo operatório é exequível e demonstrou segurança e efetividade no caso relatado.
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