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Digital health and sustainable development goals have had strong impacts with the COVID-19 pandemic. In Brazil, the health crisis scenario required changes in social welfare programs and policies, based on recommendations from international agencies, such as the UN and WHO. This study aims to analyze the alignment of the arguments of Brazilian and international organizations for the adoption of digital health in Primary Health Care based on the COVID-19 pandemic. This is a qualitative documentary study of the rhetorical analysis type, based on Perelman and Obrechts-Tyteca's Theory of Argumentation. The search for documents was carried out by two independent researchers, between December 2021 and June 2022, through the websites of the World Health Organization, the Pan American Health Organization, the Brazilian Ministry of Health, and the Federal Councils of Medicine and Brazilian nursing, with the terms "digital health," "telehealth," "telemedicine," "e-health," "telehealth," "telenursing," "telemedicine," and "digital health." Twenty official documents were analyzed and identified in terms of context, authorship, authenticity, reliability, nature, and key concepts. The international and Brazilian arguments emphasize the applicability of Information and Communication Technologies (ICTs) in the health field. In logical arguments, based on the structure of reality, international agencies emphasize the overlap between health needs and the conditions for the applicability of ICTs. In Brazil, however, there was a need to regulate the digital practices of health professionals. In the international discourse, in the structuring of reality, there are illustrations of the relationship between the context of the health crisis caused by COVID-19 and the concrete conditions for the applicability of digital health; while in the Brazilian discourse, the need to strengthen an environment conducive to digital health is explicit. The Brazilian alignment in relation to the international premises is evident. Yet, there is a need, socially and economically sustainable, to strengthen the inclusion of digital health in PHC policy.
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Plant macrofossils from packrat (Neotoma spp.) middens provide direct evidence of past vegetation changes in arid regions of North America. Here we describe the newest version (version 5.0) of the U.S. Geological Survey (USGS) North American Packrat Midden Database. The database contains published and contributed data from 3,331 midden samples collected in southwest Canada, the western United States, and northern Mexico, with samples ranging in age from 48 ka to the present. The database includes original midden-sample macrofossil counts and relative-abundance data along with a standardized relative-abundance scheme that makes it easier to compare macrofossil data across midden-sample sites. In addition to the midden-sample data, this version of the midden database includes calibrated radiocarbon (14C) ages for the midden samples and plant functional type (PFT) assignments for the midden taxa. We also provide World Wildlife Fund ecoregion assignments and climate and bioclimate data for each midden-sample site location. The data are provided in tabular (.xlsx), comma-separated values (.csv), and relational database (.mdb) files.
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Clima , Fósseis , Plantas , México , América do Norte , SigmodontinaeRESUMO
This study aimed to evaluate Haloperidol's (Hal) effects on the behavioral, neurotrophic factors, and epigenetic parameters in an animal model of schizophrenia (SCZ) induced by ketamine (Ket). Injections of Ket or saline were administered intraperitoneal (once a day) between the 1st and 14th days of the experiment. Water or Hal was administered via gavage between the 8th and 14th experimental days. Thirty minutes after the last injection, the animals were subjected to behavioral analysis. The activity of DNA methyltransferase (DNMT), histone deacetylase (HDAC), and histone acetyltransferase and levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and glial-derived neurotrophic factor (GDNF) were evaluated in the frontal cortex, hippocampus, and striatum. Ket increased the covered distance and time spent in the central area of the open field, and Hal did not reverse these behavioral alterations. Significant increases in the DNMT and HDAC activities were detected in the frontal cortex and striatum from rats that received Ket, Hal, or a combination thereof. Besides, Hal per se increased the activity of DNMT and HDAC in the hippocampus of rats. Hal per se or the association of Ket plus Hal decreased BDNF, NGF, NT-3, and GDNF, depending on the brain region and treatment regimen. The administration of Hal can alter the levels of neurotrophic factors and the activity of epigenetic enzymes, which can be a factor in the development of effect collateral in SCZ patients. However, the precise mechanisms involved in these alterations are still unclear.
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Ketamina , Esquizofrenia , Humanos , Ratos , Animais , Haloperidol/farmacologia , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Ketamina/toxicidade , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Fator de Crescimento Neural/genética , Modelos Animais de Doenças , Epigênese GenéticaRESUMO
Safe and effective malaria transmission-blocking chemotherapeutics would allow a community-level approach to malaria control and eradication efforts by targeting the mosquito sexual stage of the parasite life cycle. However, only a single drug, primaquine, is currently approved for use in reducing transmission, and drug toxicity limits its widespread implementation. To address this limitation in antimalarial chemotherapeutics, we used a recently developed transgenic Plasmodium berghei line, Ookluc, to perform a series of high-throughput in vitro screens for compounds that inhibit parasite fertilization, the initial step of parasite development within the mosquito. Screens of antimalarial compounds, approved drug collections, and drug-like molecule libraries identified 185 compounds that inhibit parasite maturation to the zygote form. Seven compounds were further characterized to block gametocyte activation or to be cytotoxic to formed zygotes. These were further validated in mosquito membrane-feeding assays using Plasmodium falciparum and P. vivax. This work demonstrates that high-throughput screens using the Ookluc line can identify compounds that are active against the two most relevant human Plasmodium species and provides a list of compounds that can be explored for the development of new antimalarials to block transmission.
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Antimaláricos , Culicidae , Malária Falciparum , Malária Vivax , Malária , Animais , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Plasmodium berghei , Ensaios de Triagem em Larga Escala , Malária/prevenção & controle , Primaquina/uso terapêutico , Plasmodium falciparum , Malária Vivax/tratamento farmacológico , Malária Falciparum/tratamento farmacológicoRESUMO
Leukemia cells accumulate DNA damage, but altered DNA repair mechanisms protect them from apoptosis. We showed here that formaldehyde generated by serine/1-carbon cycle metabolism contributed to the accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells, especially in driver clones harboring oncogenic tyrosine kinases (OTKs: FLT3(internal tandem duplication [ITD]), JAK2(V617F), BCR-ABL1). To counteract this effect, OTKs enhanced the expression of DNA polymerase theta (POLθ) via ERK1/2 serine/threonine kinase-dependent inhibition of c-CBL E3 ligase-mediated ubiquitination of POLθ and its proteasomal degradation. Overexpression of POLθ in OTK-positive cells resulted in the efficient repair of DPC-containing DNA double-strand breaks by POLθ-mediated end-joining. The transforming activities of OTKs and other leukemia-inducing oncogenes, especially of those causing the inhibition of BRCA1/2-mediated homologous recombination with and without concomitant inhibition of DNA-PK-dependent nonhomologous end-joining, was abrogated in Polq-/- murine bone marrow cells. Genetic and pharmacological targeting of POLθ polymerase and helicase activities revealed that both activities are promising targets in leukemia cells. Moreover, OTK inhibitors or DPC-inducing drug etoposide enhanced the antileukemia effect of POLθ inhibitor in vitro and in vivo. In conclusion, we demonstrated that POLθ plays an essential role in protecting leukemia cells from metabolically induced toxic DNA lesions triggered by formaldehyde, and it can be targeted to achieve a therapeutic effect.
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Proteína BRCA1 , Dano ao DNA , Leucemia , Animais , Camundongos , Proteína BRCA2 , DNA/metabolismo , Leucemia/enzimologia , Leucemia/genética , DNA Polimerase tetaRESUMO
Plastic production began in the early 1900s and it has transformed our way of life. Despite the many advantages of plastics, a massive amount of plastic waste is generated each year, threatening the environment and human health. Because of their pervasiveness and potential for health consequences, small plastic residues produced by the breakdown of larger particles have recently received considerable attention. Plastic particles at the nanometer scale (nanoplastics) are more easily absorbed, ingested, or inhaled and translocated to other tissues and organs than larger particles. Nanoplastics can also be transferred through the food web and between generations, have an influence on cellular function and physiology, and increase infections and disease susceptibility. This review will focus on current research on the toxicity of nanoplastics to aquatic species, taking into account their interactive effects with complex environmental mixtures and multiple stressors. It intends to summarize the cellular and molecular effects of nanoplastics on aquatic species; discuss the carrier effect of nanoplastics in the presence of single or complex environmental pollutants, pathogens, and weathering/aging processes; and include environmental stressors, such as temperature, salinity, pH, organic matter, and food availability, as factors influencing nanoplastic toxicity. Microplastics studies were also included in the discussion when the data with NPs were limited. Finally, this review will address knowledge gaps and critical questions in plastics' ecotoxicity to contribute to future research in the field.
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BACKGROUND AND AIMS: Increasing demand for inpatient endoscopic services results in performing more non-emergent endoscopic cases after-hours, which poses risks to patient safety and negatively impacts patient and provider satisfaction. This study sought to quantify the existing state using quality improvement (QI) methodology, design targeted interventions, and determine their effectiveness. METHODS: We conducted an existing state evaluation through a process map, time-series study, and caseload analysis from 7/2017-12/2018. Using end-of-workday (EOW) as a proxy for patient/provider dissatisfaction and risk for patient safety events, we performed a prospective evaluation of a staged interdisciplinary multimodal intervention aimed to decrease the proportion of days with EOW after 7PM, decrease the proportion of cases begun after 5PM, and decrease EOW variability. The post-intervention period was 6/2019-2/2020. RESULTS: Based on existing state analyses, we implemented a series of targeted interventions: (1) provider workflow tips, (2) expedited transport for select patients, (3) pathway to reschedule appropriate cases to outpatient endoscopy, and (4) increased staffing for high caseload days through resource pooling. The proportion of days with EOW after 7PM decreased from 42.4% to 29.3% (caseload-adjusted odds ratio of 0.39, p< 0.001). Despite increased caseload, cases begun after 5PM decreased from 17.5% to 14.2% (OR 0.75, p = 0.009). EOW SD decreased from 2:20 hours to 1:36 hours. CONCLUSIONS: The multimodal intervention reduced days with EOW after 7PM and the proportion of cases begun after 5PM, despite increased caseload. This study shows how applying research methods to implement QI interventions successfully decreases late inpatient endoscopic cases.
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OBJECTIVE: The primary objectives of the study were to describe the association between cardiac manifestations and in-hospital mortality among children with hemolytic uremic syndrome. STUDY DESIGN: Using the Pediatric Health Information System database, this retrospective, multicenter, cohort study identified the first hemolytic uremic syndrome-related inpatient visit among children ≤18 years (years 2004-2018). The frequency of selected cardiac manifestations and mortality rates were calculated. Multivariate analysis identified the association of specific cardiac manifestations and the risk of in-hospital mortality. RESULTS: Among 3915 patients in the analysis, 238 (6.1%) had cardiac manifestations. A majority of patients (82.8%; n = 197) had 1 cardiac condition and 17.2% (n = 41) had ≥2 cardiac conditions. The most common cardiac conditions was pericardial disease (n = 102), followed by congestive heart failure (n = 46) and cardiomyopathy/myocarditis (n = 34). The percent mortality for patients with 0, 1, or ≥2 cardiac conditions was 2.1%, 17.3%, and 19.5%, respectively. Patients with any cardiac condition had an increased odds of mortality (OR, 9.74; P = .0001). In additional models, the presence of ≥2 cardiac conditions (OR, 9.90; P < .001), cardiac arrest (OR, 38.25; P < .001), or extracorporeal membrane oxygenation deployment (OR, 11.61; P < .001) were associated with increased risk of in-hospital mortality. CONCLUSIONS: This study identified differences in in-hospital mortality based on the type of cardiac manifestations, with increased risk observed for patients with multiple cardiac involvement, cardiac arrest, and extracorporeal membrane oxygenation deployments.
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Cardiopatias/epidemiologia , Síndrome Hemolítico-Urêmica/epidemiologia , Pré-Escolar , Estudos de Coortes , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Parada Cardíaca/epidemiologia , Mortalidade Hospitalar , Humanos , Lactente , Masculino , América do Norte/epidemiologia , Estudos RetrospectivosRESUMO
Diacylglycerol O-acyltransferase 1 deficiency is a recently discovered, rare congenital diarrheal disorder. We report 2 patients with newly described pathogenic mutations in diacylglycerol O-acyltransferase 1 with compound heterozygous inheritance and unusual phenotypes. This included a macrophage activation syndrome-like response seen in one patient, ameliorated with low dietary fat.
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DNA/genética , Diacilglicerol O-Aciltransferase/genética , Diarreia/genética , Mutação , Biomarcadores/sangue , Análise Mutacional de DNA , Diacilglicerol O-Aciltransferase/sangue , Diarreia/sangue , Diarreia/enzimologia , Humanos , Recém-Nascido , MasculinoRESUMO
Abstract Introduction Our goal was to evaluate if traffic-light driven personalized care for COVID-19 was associated with improved survival in acute hospital settings. Methods Discharge outcomes were evaluated before and after prospective implementation of a real-time dashboard with feedback to ward-based clinicians. Thromboembolism categories were "medium-risk" (D-dimer >1000 ng/mL or CRP >200 mg/L); "high-risk" (D-dimer >3000 ng/mL or CRP >250 mg/L) or "suspected" (D-dimer >5000 ng/mL). Cytokine storm risk was categorized by ferritin. Results 939/1039 COVID-19 positive patients (median age 67 years, 563/939 (60%) male) completed hospital encounters to death or discharge by 21st May 2020. Thromboembolism flag criteria were reached by 568/939 (60.5%), including 238/275 (86.6%) of the patients who died, and 330/664 (49.7%) of the patients who survived to discharge, p < 0.0001. Cytokine storm flag criteria were reached by 212 (22.6%) of admissions, including 80/275 (29.1%) of the patients who died, and 132/664 (19.9%) of the patients who survived, p < 0.0001. The maximum thromboembolism flag discriminated completed encounter mortality (no flag: 37/371 [9.97%] died; medium-risk: 68/239 [28.5%]; high-risk: 105/205 [51.2%]; and suspected thromboembolism: 65/124 [52.4%], p < 0.0001). Flag criteria were reached by 535 consecutive COVID-19 positive patients whose hospital encounter completed before traffic-light introduction: 173/535 (32.3% [95% confidence intervals 28.0, 36.0]) died. For the 200 consecutive admissions after implementation of real-time traffic light flags, 46/200 (23.0% [95% confidence intervals 17.1, 28.9]) died, p = 0.013. Adjusted for age and sex, the probability of death was 0.33 (95% confidence intervals 0.30, 0.37) before traffic light implementation, 0.22 (0.17, 0.27) after implementation, p < 0.001. In subgroup analyses, older patients, males, and patients with hypertension (p ≤ 0.01), and/or diabetes (p = 0.05) derived the greatest benefit from admission under the traffic light system. Conclusion Personalized early interventions were associated with a 33% reduction in early mortality. We suggest benefit predominantly resulted from early triggers to review/enhance anticoagulation management, without exposing lower-risk patients to potential risks of full anticoagulation therapy.
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Idoso , Humanos , Masculino , Pneumonia Viral , Tromboembolia , Infecções por Coronavirus , Pandemias , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Citocinas , Infecções por Coronavirus/epidemiologia , Betacoronavirus , SARS-CoV-2 , COVID-19 , Pacientes InternadosRESUMO
INTRODUCTION: Our goal was to evaluate if traffic-light driven personalized care for COVID-19 was associated with improved survival in acute hospital settings. METHODS: Discharge outcomes were evaluated before and after prospective implementation of a real-time dashboard with feedback to ward-based clinicians. Thromboembolism categories were "medium-risk" (D-dimer >1000ng/mL or CRP >200mg/L); "high-risk" (D-dimer >3000ng/mL or CRP >250mg/L) or "suspected" (D-dimer >5000ng/mL). Cytokine storm risk was categorized by ferritin. RESULTS: 939/1039 COVID-19 positive patients (median age 67 years, 563/939 (60%) male) completed hospital encounters to death or discharge by 21st May 2020. Thromboembolism flag criteria were reached by 568/939 (60.5%), including 238/275 (86.6%) of the patients who died, and 330/664 (49.7%) of the patients who survived to discharge, p<0.0001. Cytokine storm flag criteria were reached by 212 (22.6%) of admissions, including 80/275 (29.1%) of the patients who died, and 132/664 (19.9%) of the patients who survived, p<0.0001. The maximum thromboembolism flag discriminated completed encounter mortality (no flag: 37/371 [9.97%] died; medium-risk: 68/239 [28.5%]; high-risk: 105/205 [51.2%]; and suspected thromboembolism: 65/124 [52.4%], p<0.0001). Flag criteria were reached by 535 consecutive COVID-19 positive patients whose hospital encounter completed before traffic-light introduction: 173/535 (32.3% [95% confidence intervals 28.0, 36.0]) died. For the 200 consecutive admissions after implementation of real-time traffic light flags, 46/200 (23.0% [95% confidence intervals 17.1, 28.9]) died, p=0.013. Adjusted for age and sex, the probability of death was 0.33 (95% confidence intervals 0.30, 0.37) before traffic light implementation, 0.22 (0.17, 0.27) after implementation, p<0.001. In subgroup analyses, older patients, males, and patients with hypertension (p≤0.01), and/or diabetes (p=0.05) derived the greatest benefit from admission under the traffic light system. CONCLUSION: Personalized early interventions were associated with a 33% reduction in early mortality. We suggest benefit predominantly resulted from early triggers to review/enhance anticoagulation management, without exposing lower-risk patients to potential risks of full anticoagulation therapy.
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Infecções por Coronavirus , Pandemias , Pneumonia Viral , Tromboembolia , Idoso , Betacoronavirus , COVID-19 , Infecções por Coronavirus/epidemiologia , Citocinas , Humanos , Pacientes Internados , Masculino , Pneumonia Viral/epidemiologia , Estudos Prospectivos , SARS-CoV-2RESUMO
Chimeric antigen receptor T-cell (CAR-T) therapy yields durable responses in patients with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Cytokine release syndrome (CRS) is a CAR-T therapy-related adverse event. To date, clinical trials of different CAR-T products have not been aligned on CRS grading scales and management algorithms. We assessed concordance between the Penn, Lee, and American Society for Transplantation and Cellular Therapy (ASTCT) grading systems by retrospectively regrading CRS events in the JULIET (A Phase 2, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Adult Patients With Relapsed or Refractory DLBCL) trial. Four medical experts with experience treating patients with 3 different CAR-T products independently regraded individual patient-level CRS events from the phase 2, global, pivotal JULIET trial (#NCT02445248). As of 8 December 2017, a total of 111 patients with r/r DLBCL underwent infusion with tisagenlecleucel. Sixty-four patients had CRS events graded per the Penn scale; on retrospective review, 63 and 61 patients had CRS events regraded per the Lee and ASTCT criteria, respectively. The Lee scale yielded concordance for 39, lower grade for 20, and higher grade for 5 events compared with the Penn scale. The ASTCT criteria provided concordance for 37, lower grade for 23, and higher grade for 4 events compared with the Penn scale. Sixteen (14%) of 111 patients in the JULIET trial received tocilizumab, all for severe events (Penn grade 3/4 CRS). This study is the first to assess concordance between 3 CRS grading scales using the same patient data set and to compare tocilizumab use according to the Lee scale in the JULIET trial and the ZUMA-1 (Long-Term Safety and Activity of Axicabtagene Ciloleucel in Refractory Large B-Cell Lymphoma) trial. This analysis describes key differences between grading scales and may inform CRS management practices.
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Síndrome da Liberação de Citocina , Receptores de Antígenos Quiméricos , Adulto , Humanos , Receptores de Antígenos de Linfócitos T/genética , Estudos RetrospectivosRESUMO
BACKGROUND: Duration of viral shedding is a determinant of infectivity and transmissibility, but few data exist about oseltamivir's ability to alter viral shedding. METHODS: From January 2012 through October 2017, a randomized, double-blinded multicenter clinical trial was conducted in adults aged 18-64 years at 42 sites in Thailand, the United States, and Argentina. Participants with influenza A or B and without risk factors for complications of influenza were screened for the study. Eligible participants were randomized to receive oseltamivir 75 mg or placebo twice daily for 5 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at day 3. RESULTS: Of 716 adults screened for the study, 558 were randomized, and 501 were confirmed to have influenza. Forty-six participants in the pilot study were excluded, and 449 of the 455 participants in the population for the primary analysis had day 3 viral shedding results. Ninety-nine (45.0%) of 220 participants in the oseltamivir arm had virus detected at day 3 compared with 131 (57.2%) of 229 participants in the placebo arm (absolute difference of -12.2% [-21.4%, -3.0%], P =; .010). The median time to alleviation of symptoms was 79.0 hours for the oseltamivir arm and 84.0 hours for the placebo arm (P =; .34) in those with confirmed influenza infection. CONCLUSIONS: Oseltamivir decreased viral shedding in this low-risk population. However, in the population enrolled in this study, it did not significantly decrease the time to resolution of clinical symptoms. CLINICAL TRIALS REGISTRATION: NCT01314911.
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Antivirais , Influenza Humana , Adolescente , Adulto , Antivirais/uso terapêutico , Argentina/epidemiologia , Método Duplo-Cego , Humanos , Influenza Humana/tratamento farmacológico , Pessoa de Meia-Idade , Oseltamivir/uso terapêutico , Projetos Piloto , Tailândia , Resultado do Tratamento , Adulto JovemRESUMO
The timing and extent of international crossings by billfishes, tunas, and sharks in the Cuba-Mexico-United States (U.S.) triangle was investigated using electronic tagging data from eight species that resulted in >22,000 tracking days. Transnational movements of these highly mobile marine predators were pronounced with varying levels of bi- or tri-national population connectivity displayed by each species. Billfishes and tunas moved throughout the Gulf of Mexico and all species investigated (blue marlin, white marlin, Atlantic bluefin tuna, yellowfin tuna) frequently crossed international boundaries and entered the territorial waters of Cuba and/or Mexico. Certain sharks (tiger shark, scalloped hammerhead) displayed prolonged periods of residency in U.S. waters with more limited displacements, while whale sharks and to a lesser degree shortfin mako moved through multiple jurisdictions. The spatial extent of associated movements was generally associated with their differential use of coastal and open ocean pelagic ecosystems. Species with the majority of daily positions in oceanic waters off the continental shelf showed the greatest tendency for transnational movements and typically traveled farther from initial tagging locations. Several species converged on a common seasonal movement pattern between territorial waters of the U.S. (summer) and Mexico (winter).
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Migração Animal/fisiologia , Ecossistema , Perciformes/fisiologia , Dinâmica Populacional , Tubarões/fisiologia , Atum/fisiologia , Animais , Cuba , México , Oceanos e Mares , Estados UnidosRESUMO
Malaria remains an important parasitic disease with a large morbidity and mortality burden. Plasmodium transmission-blocking (TB) compounds are essential for achieving malaria elimination efforts. Recent efforts to develop high-throughput screening (HTS) methods to identify compounds that inhibit or kill gametocytes, the Plasmodium sexual stage infectious to mosquitoes, have yielded insight into new TB compounds. However, the activities of these compounds against gametes, formed in the first minutes of mosquito infection, are typically not assessed, unless screened in a standard membrane feeding assay, a labor-intensive assay. We demonstrate here the generation of a Plasmodium model for drug screens against gametes and fertilization. The new P. berghei line, named Ookluc, was genetically and pharmacologically validated and scalable for HTS. Screening the Pathogen Box from the Medicines for Malaria Venture using the new model identified promising TB compounds. The use of Ookluc in different libraries of compounds may aid in the identification of transmission-blocking drugs not assessed in screens against asexual stages or gametocytes.
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Antimaláricos/farmacologia , Malária/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Animais , Culicidae/parasitologia , Luciferases/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagemRESUMO
Defects in the crystalline structure of quartz facilitate the connection with the alkali hydroxides, since under a high alkalinity condition (e.g., in concrete), the Si-O bonds of quartz are easily broken. This study set out to investigate the influence of the deformation structures of quartz on its susceptibility to the alkaliâ»silica reaction. A granite, a protomylonite, and a mylonite were selected for this study. Using optical microscopy, the quartz grains contained in these rocks were quantified and their texture characterized. The quartz samples extracted from the rocks were analyzed by magnetic nuclear resonance, to evaluate their potential for dissolving silica as well as changes in their atomic scale before and after the reaction with alkali hydroxides. These analyses were compared with the results of the accelerated mortar bar test. The study showed that the quartz with intense undulatory extinction and deformation bands denotes the most favorable condition to the development of the alkaliâ»silica reaction. However, on an atomic scale, the slightly deformed grains were highly prone to react. Thus, in a high alkalinity condition, over a long period of time, any quartz tends to develop the alkaliâ»silica reaction, regardless of the deformation degree of the grain.
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AIMS: To determine the diagnostic accuracy of semi-automatic quantitative metrics compared to expert reading for interpretation of computed tomography perfusion (CTP) imaging. METHODS: The CORE320 multicenter diagnostic accuracy clinical study enrolled patients between 45 and 85 years of age who were clinically referred for invasive coronary angiography (ICA). Computed tomography angiography (CTA), CTP, single photon emission computed tomography (SPECT), and ICA images were interpreted manually in blinded core laboratories by two experienced readers. Additionally, eight quantitative CTP metrics as continuous values were computed semi-automatically from myocardial and blood attenuation and were combined using logistic regression to derive a final quantitative CTP metric score. For the reference standard, hemodynamically significant coronary artery disease (CAD) was defined as a quantitative ICA stenosis of 50% or greater and a corresponding perfusion defect by SPECT. Diagnostic accuracy was determined by area under the receiver operating characteristic curve (AUC). RESULTS: Of the total 377 included patients, 66% were male, median age was 62 (IQR: 56, 68) years, and 27% had prior myocardial infarction. In patient based analysis, the AUC (95% CI) for combined CTA-CTP expert reading and combined CTA-CTP semi-automatic quantitative metrics was 0.87(0.84-0.91) and 0.86 (0.83-0.9), respectively. In vessel based analyses the AUC's were 0.85 (0.82-0.88) and 0.84 (0.81-0.87), respectively. No significant difference in AUC was found between combined CTA-CTP expert reading and CTA-CTP semi-automatic quantitative metrics in patient based or vessel based analyses(pâ¯>â¯0.05 for all). CONCLUSION: Combined CTA-CTP semi-automatic quantitative metrics is as accurate as CTA-CTP expert reading to detect hemodynamically significant CAD.
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Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária , Vasos Coronários/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Imagem de Perfusão do Miocárdio/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Ásia , Automação , Angiografia por Tomografia Computadorizada/normas , Angiografia Coronária/normas , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Europa (Continente) , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/normas , Imagem de Perfusão do Miocárdio/normas , América do Norte , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Interpretação de Imagem Radiográfica Assistida por Computador/normas , Padrões de Referência , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , América do Sul , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND: Influenza continues to have a substantial socioeconomic and health impact despite a long established vaccination programme and approved antivirals. Preclinical data suggest that combining antivirals might be more effective than administering oseltamivir alone in the treatment of influenza. METHODS: We did a randomised, double-blind, multicentre phase 2 trial of a combination of oseltamivir, amantadine, and ribavirin versus oseltamivir monotherapy with matching placebo for the treatment of influenza in 50 sites, consisting of academic medical centre clinics, emergency rooms, and private physician offices in the USA, Thailand, Mexico, Argentina, and Australia. Participants who were aged at least 18 years with influenza and were at increased risk of complications were randomly assigned (1:1) by an online computer-generated randomisation system to receive either oseltamivir (75 mg), amantadine (100 mg), and ribavirin (600 mg) combination therapy or oseltamivir monotherapy twice daily for 5 days, given orally, and participants were followed up for 28 days. Blinded treatment kits were used to achieve masking of patients and staff. The primary endpoint was the percentage of participants with virus detectable by PCR in nasopharyngeal swab at day 3, and was assessed in participants who were randomised, had influenza infection confirmed by the central laboratory on a baseline nasopharyngeal sample, and had received at least one dose of study drug. Safety assessment was done in all patients in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01227967. FINDINGS: Between March 1, 2011, and April 29, 2016, 633 participants were randomly assigned to receive combination antiviral therapy (n=316) or monotherapy (n=317). Seven participants were excluded from analysis: three were not properly randomised, three withdrew from the study, and one was lost to follow-up. The primary analysis included 394 participants, excluding 47 in the pilot phase, 172 without confirmed influenza, and 13 without an endpoint sample. 80 (40·0%) of 200 participants in the combination group had detectable virus at day 3 compared with 97 (50·0%) of 194 (mean difference 10·0, 95% CI 0·2-19·8, p=0·046) in the monotherapy group. The most common adverse events were gastrointestinal-related disorders, primarily nausea (65 [12%] of 556 reported adverse events in the combination group vs 63 [11%] of 585 reported adverse events in the monotherapy group), diarrhoea (56 [10%] of 556 vs 64 [11%] of 585), and vomiting (39 [7%] of 556 vs 23 [4%] of 585). There was no benefit in multiple clinical secondary endpoints, such as median duration of symptoms (4·5 days in the combination group vs 4·0 days in the monotherapy group; p=0·21). One death occurred in the study in an elderly participant in the monotherapy group who died of cardiovascular failure 13 days after randomisation, judged by the site investigator as not related to study intervention. INTERPRETATION: Although combination treatment showed a significant decrease in viral shedding at day 3 relative to monotherapy, this difference was not associated with improved clinical benefit. More work is needed to understand why there was no clinical benefit when a difference in virological outcome was identified. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.
Assuntos
Amantadina/uso terapêutico , Influenza Humana/tratamento farmacológico , Oseltamivir/administração & dosagem , Oseltamivir/uso terapêutico , Ribavirina/uso terapêutico , Amantadina/administração & dosagem , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Argentina/epidemiologia , Austrália/epidemiologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Influenza Humana/epidemiologia , Masculino , México/epidemiologia , Ribavirina/administração & dosagem , Tailândia/epidemiologia , Estados Unidos/epidemiologiaRESUMO
The production of echolocation calls in bats along with forces produced by contraction of thoracic musculature used in flight presumably puts relatively high mechanical loads on the lower respiratory tract (LRT). Thus, there are likely adaptations to prevent collapse or distortion of the bronchial tree and trachea during flight in echolocating bats. By clearing and staining (Alcian blue and Alizarin red) LRTs removed from nonvolant neonates, semivolant juveniles, volant subadults, and adult Jamaican fruit bats (Artibeus jamaicensis), I found that calcification of the tracheal, primary bronchial, and secondary bronchial (lobar) cartilage rings occurs over the span of about 3 days and coincides with later developmental stages of flight and the increased production of echolocation calls. Tracheal rings that are immediately adjacent to the larynx calcified first, followed by more caudal tracheal rings and then the rings of the primary and secondary bronchi. I suggest that calcification of LRT cartilage rings in echolocating bats provides increased rigidity to counter the thoracic compressions incurred during flight. Calcification of the LRT rings is an adaptation to support the emission of laryngeally produced echolocation calls during flight in bats.
Assuntos
Brônquios/crescimento & desenvolvimento , Calcificação Fisiológica , Ecolocação , Voo Animal , Traqueia/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Brônquios/anatomia & histologia , Calcificação Fisiológica/fisiologia , Quirópteros , Ecolocação/fisiologia , Feminino , Voo Animal/fisiologia , Masculino , Traqueia/anatomia & histologiaRESUMO
Soil organic matter (SOM) is critical for maintaining soil fertility and long-term agricultural sustainability. The molecular composition of SOM is likely altered due to global climate and land-use change; but rarely are these two aspects studied in tandem. Here we used molecular-level techniques to examine SOM composition along a bi-continental (from North to South America) mean annual temperature (MAT) gradient from seven native grassland/forest and cultivated/pasture sites. Biomarker methods included solvent extraction, base hydrolysis and cupric (II) oxide oxidation for the analysis of free lipids of plant and microbial origin, ester-bound lipids from cutin and suberin, and lignin-derived phenols, respectively. Solid-state 13C nuclear magnetic resonance (NMR) was used to examine the overall composition of SOM. Soil cultivation was found to increase the amount of microbial-derived compounds at warmer temperatures (up to 17% increase). The cultivated soils were characterized by much lower contributions of plant-derived SOM components compared to the native soils (up to 64% lower at the coldest site). In addition, cultivation caused an increase in lignin and cutin degradation (up to 68 and 15% increase, respectively), and an increase in the amount of suberin-derived inputs (up to 54% increase). Clear differences in the molecular composition of SOM due to soil cultivation were observed in soils of varying mineral composition and were attributed to disturbance, different vegetation inputs, soil aggregate destruction and MAT. A high organic allophanic tropical soil was characterized by its protection of carbohydrates and nitrogen-containing compounds. The conversion of native to cultivated land shows significant shifts in the degradation stage of SOM. In particular, cutin-derived compounds which are believed to be part of the stable SOM pool may undergo enhanced degradation with long-term cultivation and disruption of soil aggregates. On a per year basis, the total amount of cutin decreased only at the two forest sites that were converted to pasture, likely due to cutin degradation or to changes in vegetation and litter quality associated with land-use change. Overall, our study highlights that the implementation of different agricultural management practices enhances the degradation of recalcitrant SOM compounds that may become a source of atmospheric CO2 with increasing land-use and climate change.