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1.
Alzheimers Dement ; 19(11): 5289-5295, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37157089

RESUMO

We propose an unbiased methodology to rank compounds for advancement into comprehensive preclinical testing for Alzheimer's disease (AD). Translation of compounds to the clinic in AD has been hampered by poor predictive validity of models, compounds with limited pharmaceutical properties, and studies that lack rigor. To overcome this, MODEL-AD's Preclinical Testing Core developed a standardized pipeline for assessing efficacy in AD mouse models. We hypothesize that rank-ordering compounds based upon pharmacokinetic, efficacy, and toxicity properties in preclinical models will enhance successful translation to the clinic. Previously compound selection was based solely on physiochemical properties, with arbitrary cutoff limits, making ranking challenging. Since no gold standard exists for systematic prioritization, validating a selection criteria has remained elusive. The STOP-AD framework evaluates the drug-like properties to rank compounds for in vivo studies, and uses an unbiased approach that overcomes the validation limitation by performing Monte-Carlo simulations. HIGHLIGHTS: Promising preclinical studies for AD drugs have not translated to clinical success. Systematic assessment of AD drug candidates may increase clinical translatability. We describe a well-defined framework for compound selection with clear selection metrics.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Modelos Animais de Doenças , Preparações Farmacêuticas
2.
Clin Pharmacol Ther ; 113(3): 565-574, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36408716

RESUMO

Precision dosing aims to tailor doses to individual patients with the goal of improving treatment efficacy and avoiding toxicity. Clinical decision support software (CDSS) plays a crucial role in mediating this process, translating knowledge derived from clinical trials and real-world data (RWD) into actionable insights for clinicians to use at the point of care. However, not all patient populations are proportionally represented in clinical trials and other data sources that inform CDSS tools, limiting the applicability of these tools for underrepresented populations. Here, we review some of the limitations of existing CDSS tools and discuss methods for overcoming these gaps. We discuss considerations for study design and modeling to create more inclusive CDSS, particularly with an eye toward better incorporation of biological indicators in place of race, ethnicity, or sex. We also review inclusive practices for collection of these demographic data, during both study design and in software user interface design. Because of the role CDSS plays in both recording routine clinical care data and disseminating knowledge derived from data, CDSS presents a promising opportunity to continuously improve precision dosing algorithms using RWD to better reflect the diversity of patient populations.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Humanos , Software , Algoritmos , Resultado do Tratamento , Atenção à Saúde
3.
Alcohol Clin Exp Res ; 46(11): 2025-2040, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36124871

RESUMO

BACKGROUND: Alcohol use is a major global healthcare burden that contributes to numerous adverse health outcomes, including liver disease. Many factors influence individual susceptibility to alcohol-associated diseases, including nutritional factors. The objective of the current study was to examine inter-relations among alcohol, dietary micronutrients and macronutrient consumption, and liver health by analyzing data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). METHODS: Based on self-reported alcohol consumption, NHANES respondents were assigned to one of four categories: never drinkers (lifetime abstainers), non-drinkers (past-year abstainers), moderate drinkers (1/2 drinks per day for females/males, respectively), and heavy drinkers (>1/>2 drinks per day for females/males, respectively, and/or frequent binge drinking). Survey-weighted regression analyses (adjusted for gender, age, race, education, and body mass index) were performed to examine associations between alcohol intake, dietary, and liver health characteristics. RESULTS: Individuals categorized as heavy drinkers were significantly younger, most often well-educated males with low incidences of diabetes and other comorbidities. They consumed the most overall calories and various micronutrients, indicating a diet that was not necessarily nutrient poor. Neither moderate nor heavy drinkers had liver steatosis or fibrosis as measured by liver elastography, although heavy drinkers had modestly elevated plasma biomarkers of liver injury, including ALT, AST, and GGT, compared with the other groups. CONCLUSIONS: Our findings suggest that the category of heavy drinkers in the 2017-2018 NHANES consisted of generally healthy individuals with high-energy intake and no evidence of liver steatosis or fibrosis. However, slightly increased plasma liver markers may indicate a risk of future progression to more advanced stages of liver disease over time in some individuals. Several limitations should be considered when interpreting these data, including the potential misclassification of drinking categories and the lack of standardized cutoff scores for fatty liver as assessed by elastography, among others.


Assuntos
Fígado Gorduroso , Micronutrientes , Masculino , Feminino , Humanos , Inquéritos Nutricionais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Biomarcadores , Fibrose
4.
Sci Rep ; 12(1): 1430, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-35082357

RESUMO

The effect of varying sinusoidal linear acceleration on perception of human motion was examined using 4 motion paradigms: off-vertical axis rotation, variable radius centrifugation, linear lateral translation, and rotation about an earth-horizontal axis. The motion profiles for each paradigm included 6 frequencies (0.01-0.6 Hz) and 5 tilt amplitudes (5°-20°). Subjects verbally reported the perceived angle of their whole-body tilt and the peak-to-peak translation of their head in space and used a joystick capable of recording 2-axis motion in the sagittal and transversal planes to indicate the phase between the perceived and actual motions. The amplitudes of perceived tilt and translation were expressed in terms of gain, i.e., the ratio of perceived tilt to equivalent tilt angle, and the ratio of perceived translation to equivalent linear displacement. Tilt perception gain decreased, whereas translation perception gain increased, with increasing frequency. During off-vertical axis rotation, the phase of tilt perception and of translation perception did not vary across stimulus frequencies. These motion paradigms elicited similar responses in roll tilt and interaural perception of translation, with differences likely due to the influence of naso-occipital linear accelerations and input to the semicircular canals that varied across motion paradigms.


Assuntos
Sensação Gravitacional/fisiologia , Movimentos da Cabeça/fisiologia , Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , Percepção de Movimento/fisiologia , Orientação Espacial/fisiologia , Aceleração , Adulto , Movimentos Oculares/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reflexo Vestíbulo-Ocular/fisiologia , Rotação , Canais Semicirculares/fisiologia
5.
J Laryngol Otol ; 136(12): 1203-1210, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35000639

RESUMO

BACKGROUND: Subjective tinnitus is a common symptom, and there is often an underlying otological cause. This study investigated the degree of tinnitus-related annoyance in patients with chronic otitis media and analysed whether associations with tinnitus severity exist. METHOD: The multinational collaborative Chronic Otitis Media Questionnaire-12 study collected prospective data on 478 adult patients suffering from chronic otitis media across 9 otology referral centres in 8 countries. Based on this dataset, we investigated tinnitus severity using participant responses to item 7 of a native version of the Chronic Otitis Media Questionnaire-12. RESULTS: With respect to tinnitus severity, 23.8 per cent, 17.4 per cent, 15.5 per cent, and 43.4 per cent of participants reported no, minor, moderate, and major inconvenience or greater, respectively. The absence of ear discharge, absence of cholesteatoma, and poorer disease-specific health-related quality-of-life were associated with increased tinnitus severity in patients with chronic otitis media, whereas age, hearing disability and geographical region showed no association. CONCLUSION: This analysis provided novel insight into potential risk factors for tinnitus in patients with chronic otitis media.


Assuntos
Otite Média , Zumbido , Humanos , Adulto , Zumbido/epidemiologia , Zumbido/etiologia , Estudos Prospectivos , Otite Média/complicações , Otite Média/epidemiologia , Inquéritos e Questionários , Doença Crônica , Fatores de Risco
6.
Nutrients ; 13(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34836309

RESUMO

BACKGROUND: We aimed to establish an acute treatment protocol to increase serum vitamin D, evaluate the effectiveness of vitamin D3 supplementation, and reveal the potential mechanisms in COVID-19. METHODS: We retrospectively analyzed the data of 867 COVID-19 cases. Then, a prospective study was conducted, including 23 healthy individuals and 210 cases. A total of 163 cases had vitamin D supplementation, and 95 were followed for 14 days. Clinical outcomes, routine blood biomarkers, serum levels of vitamin D metabolism, and action mechanism-related parameters were evaluated. RESULTS: Our treatment protocol increased the serum 25OHD levels significantly to above 30 ng/mL within two weeks. COVID-19 cases (no comorbidities, no vitamin D treatment, 25OHD <30 ng/mL) had 1.9-fold increased risk of having hospitalization longer than 8 days compared with the cases with comorbidities and vitamin D treatment. Having vitamin D treatment decreased the mortality rate by 2.14 times. The correlation analysis of specific serum biomarkers with 25OHD indicated that the vitamin D action in COVID-19 might involve regulation of INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. CONCLUSIONS: Vitamin D treatment shortened hospital stay and decreased mortality in COVID-19 cases, even in the existence of comorbidities. Vitamin D supplementation is effective on various target parameters; therefore, it is essential for COVID-19 treatment.


Assuntos
Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Vitamina D/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/sangue , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/metabolismo , COVID-19/complicações , COVID-19/mortalidade , Suplementos Nutricionais , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interferon gama/sangue , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estudos Prospectivos , Estudos Retrospectivos , Vitamina D/sangue , Vitamina D/farmacologia , Vitaminas/administração & dosagem , Vitaminas/farmacologia , Catelicidinas
7.
J Laryngol Otol ; 135(11): 1010-1018, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34496986

RESUMO

OBJECTIVE: The primary goal of this study was to evaluate the association between olfactory dysfunction or taste impairment and disease severity and radiological findings in coronavirus disease-2019. The secondary goal was to assess the prevalence, severity and course of olfactory dysfunction or taste impairment in patients with coronavirus disease 2019. METHOD: This prospective observational cohort study evaluated patients hospitalised with coronavirus disease 2019 between April 1 and 1 May 2020. Olfactory dysfunction and taste impairment were evaluated by two questionnaires. Chest computed tomography findings and coronavirus disease-2019 severity were assessed. RESULTS: Among 133 patients, 23.3 per cent and 30.8 per cent experienced olfactory dysfunction and taste impairment, respectively, and 17.2 per cent experienced both. The mean age was 56.03 years, and 64.7 per cent were male and 35.3 per cent were female. No statistically significant association was found between olfactory dysfunction (p = 0.706) and taste impairment (p = 0.35) with either disease severity or chest computed tomography grading. CONCLUSION: Olfactory dysfunction or taste impairment does not have prognostic importance in patients with coronavirus disease 2019.


Assuntos
COVID-19/complicações , Transtornos do Olfato/epidemiologia , SARS-CoV-2 , Índice de Gravidade de Doença , Distúrbios do Paladar/epidemiologia , Adulto , Idoso , COVID-19/diagnóstico por imagem , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/virologia , Prevalência , Prognóstico , Estudos Prospectivos , Distúrbios do Paladar/virologia , Tomografia Computadorizada por Raios X
8.
Eur J Surg Oncol ; 47(10): 2506-2514, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34217580

RESUMO

PURPOSE: Factors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC). METHODS: Between 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 patients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24-172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14-5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16-5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89-5.01) were found to have an increased HR compared to others in 5-year DFS. However, no difference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44-3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63-5.79). CONCLUSION: ALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/patologia , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axila , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/radioterapia , Mastectomia Segmentar , Pessoa de Meia-Idade , Terapia Neoadjuvante , Micrometástase de Neoplasia , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Turquia , Adulto Jovem
9.
Hepatol Commun ; 5(6): 947-960, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34141982

RESUMO

Alcohol-associated liver disease (ALD) is a spectrum of liver disorders ranging from steatosis to steatohepatitis, fibrosis, and cirrhosis. Alcohol-associated hepatitis (AH) is an acute and often severe form of ALD with substantial morbidity and mortality. The mechanisms and mediators of ALD progression and severity are not well understood, and effective therapeutic options are limited. Various bioactive lipid mediators have recently emerged as important factors in ALD pathogenesis. The current study aimed to examine alterations in linoleic acid (LA)-derived lipid metabolites in the plasma of individuals who are heavy drinkers and to evaluate associations between these molecules and markers of liver injury and systemic inflammation. Analysis of plasma LA-derived metabolites was performed on 66 individuals who were heavy drinkers and 29 socially drinking but otherwise healthy volunteers. Based on plasma alanine aminotransferase (ALT) levels, 15 patients had no liver injury (ALT ≤ 40 U/L), 33 patients had mild liver injury (ALT > 40 U/L), and 18 were diagnosed with moderate AH (mAH) (Model for End-Stage Liver Disease score <20). Lipoxygenase-derived LA metabolites (13-hydroxy-octadecadienoic acid [13-HODE] and 13-oxo-octadecadienoic acid) were markedly elevated only in patients with mAH. The cytochrome P450-derived LA epoxides 9,10-epoxy-octadecenoic acid (9,10-EpOME) and 12,13-EpOME were decreased in all patients regardless of the presence or absence of liver injury. LA-derived diols 9,10-dihydroxy-octadecenoic acid (9,10-DiHOME) and 12,13-DiHOME as well as the corresponding diol/epoxide ratio were elevated in the mAH group, specifically compared to patients with mild liver injury. We found that 13-HODE and 12,13-EpOME (elevated and decreased, respectively) in combination with elevated interleukin-1ß as independent predictors can effectively predict altered liver function as defined by elevated bilirubin levels. Conclusion: Specific changes in LA metabolites in individuals who are heavy drinkers can distinguish individuals with mAH from those with mild ALD.

10.
Folia Morphol (Warsz) ; 80(2): 297-301, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32488858

RESUMO

BACKGROUND: The Southern Karaman sheep, which is very fertile in terms of meat and milk production and is often preferred in livestock raising, is known as a domestic sheep breed. The Hasak sheep is a breed formed by the triple crossbreeding of the German Black-headed, Hampshire and Akkaraman breeds. Arterial feeding of the forelimb is provided by arteria axillaris, a continuation of arteria subclavia. In this study, it was aimed to examine the forelimb arteries in Southern Karaman and Hasak sheep breeds. MATERIALS AND METHODS: Totally, 8 Southern Karaman and 8 Hasak sheep were obtained from Konya Bahri Dagdas International Agricultural Institute. The sheep were anesthetised with xylazine and ketamine and extravasated by cutting the arteria carotis communis in the neck area of the sheep. The forelimbs of the sheep separated from the body were fixed in 10% formaldehyde solution and then dissections were made and the course and branching of the arteries were examined. RESULTS: It was determined that the arteria brachialis was divided into two main branches as distal arteria brachialis and proximal arteria subscapularis at the articulatio humeri level of the arteria axillary. Arteria mediana, which is a continuation of arteria brachialis, was also examined in different parts of antebrachium and ended by splitting into branches. CONCLUSIONS: According to the findings of the Southern Karaman and Hasak sheep breeds, it was determined that the forelimb arteries had some anatomical differences but were similar in structure to many sheep breeds.


Assuntos
Artéria Axilar , Artéria Braquial , Manguito Rotador , Animais , Artéria Axilar/anatomia & histologia , Artéria Braquial/anatomia & histologia , Cruzamento , Ovinos , Artéria Subclávia
11.
Curr Protoc Hum Genet ; 108(1): e105, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33085189

RESUMO

The AD Knowledge Portal (adknowledgeportal.org) is a public data repository that shares data and other resources generated by multiple collaborative research programs focused on aging, dementia, and Alzheimer's disease (AD). In this article, we highlight how to use the Portal to discover and download genomic variant and transcriptomic data from the same individuals. First, we show how to use the web interface to browse and search for data of interest using relevant file annotations. We demonstrate how to learn more about the context surrounding the data, including diagnostic criteria and methodological details about sample preparation and data analysis. We present two primary ways to download data-using a web interface, and using a programmatic method that provides access using the command line. Finally, we show how to merge separate sources of metadata into a comprehensive file that contains factors and covariates necessary in downstream analyses. © 2020 The Authors. Basic Protocol 1: Find and download files associated with a selected study Basic Protocol 2: Download files in bulk using the command line client Basic Protocol 3: Working with file annotations and metadata.


Assuntos
Envelhecimento , Doença de Alzheimer/terapia , Bases de Dados Genéticas/estatística & dados numéricos , Genômica/métodos , Armazenamento e Recuperação da Informação/métodos , Software , Doença de Alzheimer/diagnóstico , Genômica/estatística & dados numéricos , Humanos , Internet
12.
Folia Morphol (Warsz) ; 79(4): 742-747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32073138

RESUMO

BACKGROUND: The interdigital glands of sheep perform various functions including those pertaining to sexual behaviours. Morphological and histological structure of the gland demonstrates differences among species. The aim of this study is to examine the morphological and histological structure of Hasak and Hasmer sheep's interdigital glands and to determine the differences with other sheep breeds. MATERIALS AND METHODS: For this research, we selected 7 Hasak and 7 Hasmer female sheep. After scarification, the feet were obtained and used for anatomical and histological examinations. For the histological examination, the interdigital gland tissues were stained with Crossman modified triple, periodic acid Schiff (PAS) and Alcian blue (AB) staining. RESULTS: The morphometric analysis results, mean values of weight, body length, body diameter, flexura, ductus length, ductus diameter, were observed as 0.80 mm, 14.61 mm, 5.98 mm, 5.62 mm, 26.58 mm, and 3.25 mm, respectively in Hasak and 0.8 mm, 15.46 mm, 6.37 mm, 5.70 mm, 24.52 mm, and 3.52 mm in Hasmer sheep. The histochemical staining revealed that the apocrine secretion of this gland was PAS positive and AB negative. CONCLUSIONS: The weight, body length, body diameter, flexura, ductus length and ductus diameter in the forefoot's interdigital glands of both Hasak and Hasmer sheep were higher in a statistically significant manner than those of the hindfeet's glands.


Assuntos
Casco e Garras/patologia , Ovinos , Coloração e Rotulagem , Animais , Feminino
13.
Astrobiology ; 19(3): 300-320, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30840499

RESUMO

Biologic Analog Science Associated with Lava Terrains (BASALT) is a science-driven exploration program seeking to determine the best tools, techniques, training requirements, and execution strategies for conducting Mars-relevant field science under spaceflight mission conditions. BASALT encompasses Science, Science Operations, and Technology objectives. This article outlines the BASALT Science Operations background, strategic research questions, study design, and a portion of the results from the second field test. BASALT field tests are used to iteratively develop, integrate, test, evaluate, and refine new concepts of operations (ConOps) and capabilities that enable efficient and productive science. This article highlights the ConOps investigated during BASALT in light of future planetary extravehicular activity (EVA), which will focus on scientific exploration and discovery, and serves as an introduction to integrating exploration flexibility with operational rigor, the value of tactical and strategic science planning and execution, and capabilities that enable and enhance future science EVA operations.


Assuntos
Astronautas , Exobiologia/métodos , Atividade Extraespaçonave/fisiologia , Simulação de Ambiente Espacial , Eficiência , Havaí , Humanos , Marte , Aptidão Física , Projetos de Pesquisa
14.
Astrobiology ; 19(3): 284-299, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30840501

RESUMO

A major objective in the exploration of Mars is to test the hypothesis that the planet hosted life. Even in the absence of life, the mapping of habitable and uninhabitable environments is an essential task in developing a complete understanding of the geological and aqueous history of Mars and, as a consequence, understanding what factors caused Earth to take a different trajectory of biological potential. We carried out the aseptic collection of samples and comparison of the bacterial and archaeal communities associated with basaltic fumaroles and rocks of varying weathering states in Hawai'i to test four hypotheses concerning the diversity of life in these environments. Using high-throughput sequencing, we found that all these materials are inhabited by a low-diversity biota. Multivariate analyses of bacterial community data showed a clear separation between sites that have active fumaroles and other sites that comprised relict fumaroles, unaltered, and syn-emplacement basalts. Contrary to our hypothesis that high water flow environments, such as fumaroles with active mineral leaching, would be sites of high biological diversity, alpha diversity was lower in active fumaroles compared to relict or nonfumarolic sites, potentially due to high-temperature constraints on microbial diversity in fumarolic sites. A comparison of these data with communities inhabiting unaltered and weathered basaltic rocks in Idaho suggests that bacterial taxon composition of basaltic materials varies between sites, although the archaeal communities were similar in Hawai'i and Idaho. The taxa present in both sites suggest that most of them obtain organic carbon compounds from the atmosphere and from phototrophs and that some of them, including archaeal taxa, cycle fixed nitrogen. The low diversity shows that, on Earth, extreme basaltic terrains are environments on the edge of sustaining life with implications for the biological potential of similar environments on Mars and their exploration by robots and humans.


Assuntos
Biodiversidade , Exobiologia/métodos , Meio Ambiente Extraterreno/química , Microbiota , Erupções Vulcânicas , Archaea/genética , Archaea/isolamento & purificação , Bactérias/genética , Bactérias/isolamento & purificação , DNA Arqueal/genética , DNA Arqueal/isolamento & purificação , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Havaí , Idaho , Marte , Filogenia , Silicatos/química
15.
Astrobiology ; 19(3): 426-439, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30840509

RESUMO

Science-driven, human spaceflight missions of the future will rely on regular and interactive communication between Earth- and space-based teams during activity in which astronauts work directly on Mars or other planetary surfaces (extravehicular activity, EVA). The Biologic Analog Science Associated with Lava Terrains (BASALT) project conducted simulated human missions to Mars, complete with realistic one-way light time (OWLT) communication latency. We discuss the modes of communication used by the Mars- and Earth-based teams, including text, audio, video, and still imagery. Real-time communication between astronauts in the field (extravehicular, EV) and astronauts in a communication relay station (intravehicular, IV) was broadcast over OWLT, providing important contextual information to the Science Backroom Team (SBT) in Mission Control. Collaborative communication between the Earth- and Mars-based teams, however, requires active communication across latency via the Mission Log. We provide descriptive statistics of text communication between IV and SBT in a high-fidelity, scientifically driven analog for human space exploration. Over an EVA, the SBT sent an average of ∼23 text messages containing recommendations, requests, and answers to questions, while the science-focused IV crew member (IV2) sent an average of ∼38 text messages. Though patterns varied, communication between the IV and SBT teams tended to be highest during ∼50-150 min into the EVA, corresponding to the candidate sample search and presampling instrument survey phases, and then decreased dramatically after minute ∼200 during the sample collection phase. Generally, the IV2 and SBT used ∼4.6 min to craft a reply to a direct question or comment, regardless of message length or OWLT, offering a valuable glimpse into actual time-to-reply. We discuss IV2-SBT communication within the context of case examples from an EVA during which communication failures affected operations in the field. Finally, we offer recommendations for communication practices for use in future analogs and, perhaps, science-driven human spaceflight.


Assuntos
Comunicação , Exobiologia/organização & administração , Atividade Extraespaçonave , Marte , Comunicações Via Satélite , Astronautas , Planeta Terra , Exobiologia/tendências , Previsões , Humanos , Simulação de Ambiente Espacial , Fatores de Tempo
16.
Astrobiology ; 19(3): 245-259, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30840510

RESUMO

The articles associated with this Special Collection focus on the NASA BASALT (Biologic Analog Science Associated with Lava Terrains) Research Program, which aims at answering the question, "How do we support and enable scientific exploration during human Mars missions?" To answer this the BASALT team conducted scientific field studies under simulated Mars mission conditions to both broaden our understanding of the habitability potential of basalt-rich terrains on Mars and examine the effects of science on current Mars mission concepts of operations. This article provides an overview of the BASALT research project, from the science, to the operational concepts that were tested and developed, to the technical capabilities that supported all elements of the team's research. Further, this article introduces the 12 articles that are included in this Special Collection.


Assuntos
Exobiologia/métodos , Meio Ambiente Extraterreno/química , Marte , Voo Espacial , Simulação de Ambiente Espacial , Astronautas , Humanos , Silicatos/química
17.
RSC Adv ; 9(62): 36005-36010, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-35540590

RESUMO

Carbendazim, is a broad-spectrum fungicide and also a promising experimental antitumor drug as reproduction and developmental toxicant, which is currently under phase II preclinical trials. In this study, an approach based on controlled and targeted release with aptamers and mesoporous silica nanoparticles was investigated to improve the antitumor activity of carbendazim. To this end, we synthesized aptamer conjugated silica nanoparticles for testing cytotoxicity properties in vitro with human cervical adenocarcinoma (HeLa) cultured cells. Nucleolin (AS1411) binding aptamers were used to entrap carbendazim molecules inside nanopores of MCM-41 type silica nanoparticles to obtain a stimuli-dependent release system. The effect of carbendazim loaded aptamer silica complex was tested and compared to free carbendazim treatment on HeLa cells, demonstrating 3.3 fold increase of toxicity on targeted cells with our delivery system. In addition, cytotoxicity of the complex was determined to be mostly due to increased apoptosis and to a less extend necrosis related pathways.

18.
Turk Gogus Kalp Damar Cerrahisi Derg ; 27(2): 251-253, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32082864

RESUMO

Video-assisted thoracoscopic surgery is becoming more popular in thoracic surgery practice. Use of endostaplers is mandatory for anatomical video-assisted thoracoscopic surgery resections. In this article, we present an unusual complication related to use of endostapler, which, to our knowledge, may be the first reported in the literature.

19.
Wideochir Inne Tech Maloinwazyjne ; 13(3): 388-393, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30302153

RESUMO

INTRODUCTION: Video-assisted mediastinal lymphadenectomy (VAMLA) is a valuable tool for invasive staging of the mediastinum. Unilateral vocal cord paralysis (UVCP) may occur in patients following VAMLA and may result in secretion retention within the lungs, atelectasis and associated infectious situations such as pneumonia. Minimally invasive injection laryngoplasty (ILP) is the treatment of choice in UVCP. AIM: To evaluate the efficacy and success of acute minimally invasive injection laryngoplasty for patients with UVCP following VAMLA. MATERIAL AND METHODS: Patients with the symptom of dysphonia following VAMLA were reviewed. All of the patients had UVCP according to the video laryngoscopy examination and had symptoms of aspiration and ineffective coughing. The Voice Handicap Index (VHI) questionnaire and maximum phonation time (MPT) were measured. Minimally invasive ILP was performed under general anesthesia with 1 cm of hyaluronic acid. RESULTS: There were 525 consecutive non-small cell lung cancer (NSCLC) patients who underwent VAMLA. Five (0.95%) of the patients had UVCP and were suffering from aspiration during oral intake and ineffective coughing reflex. Maximum phonation time (MFT) was measured before and after ILP, and the results were 7.1 ±1.6 and 11.1 ±2.3 s, respectively (p < 001). The Voice Handicap Index-10 (VHI-10) score was 30.4 ±4.7 and 13.4 ±3.5 (p < 0.01), respectively. Patients underwent surgical lung resection. There was no morbidity or mortality. CONCLUSIONS: Unilateral vocal cord paralysis may occur as a complication of VAMLA. ILP may be an active tool for treating UVCP before anatomical lung resection to avoid potential morbidities. Successful management of this complication with multidisciplinary team work may encourage the use of VAMLA more frequently.

20.
NPJ Microgravity ; 4: 17, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30211311

RESUMO

Long duration space flight is known to induce severe modifications in the sensorimotor and musculoskeletal systems. While in-flight strategies including physical fitness have been used to prevent the loss of bone and muscle mass using appropriate rehabilitative countermeasures, less attention has been put forth in the design of technologies that can quickly and effectively assess sensorimotor function during missions in space. The aims of the present study were therefore (1) to develop a Portable Sensorimotor Assessment Platform (PSAP) to enable a crewmember to independently and quickly assess his/her sensorimotor function during the NASA's Extreme Environment Mission Operations (NEEMO) and (2) to investigate changes in performance of static posture, tandem gait, and lower limb ataxia due to exposure in an extreme environment. Our data reveal that measuring the degree of upper body balance and gait regularity during tandem walking using PSAP provided a sensitive and objective quantification of body movement abnormalities due to changes in sensorimotor performance over the duration of mission exposure.

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