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1.
Sensors (Basel) ; 21(2)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33477828

RESUMO

GOAL: To develop and validate a field-based data collection and assessment method for human activity recognition in the mountains with variations in terrain and fatigue using a single accelerometer and a deep learning model. METHODS: The protocol generated an unsupervised labelled dataset of various long-term field-based activities including run, walk, stand, lay and obstacle climb. Activity was voluntary so transitions could not be determined a priori. Terrain variations included slope, crossing rivers, obstacles and surfaces including road, gravel, clay, mud, long grass and rough track. Fatigue levels were modulated between rested to physical exhaustion. The dataset was used to train a deep learning convolutional neural network (CNN) capable of being deployed on battery powered devices. The human activity recognition results were compared to a lab-based dataset with 1,098,204 samples and six features, uniform smooth surfaces, non-fatigued supervised participants and activity labelling defined by the protocol. RESULTS: The trail run dataset had 3,829,759 samples with five features. The repetitive activities and single instance activities required hyper parameter tuning to reach an overall accuracy 0.978 with a minimum class precision for the one-off activity (climbing gate) of 0.802. CONCLUSION: The experimental results showed that the CNN deep learning model performed well with terrain and fatigue variations compared to the lab equivalents (accuracy 97.8% vs. 97.7% for trail vs. lab). SIGNIFICANCE: To the authors knowledge this study demonstrated the first successful human activity recognition (HAR) in a mountain environment. A robust and repeatable protocol was developed to generate a validated trail running dataset when there were no observers present and activity types changed on a voluntary basis across variations in terrain surface and both cognitive and physical fatigue levels.


Assuntos
Atividades Humanas , Redes Neurais de Computação , Corrida , Análise de Dados , Humanos , Projetos Piloto , Caminhada
2.
Sensors (Basel) ; 21(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34450884

RESUMO

AIM: To determine whether an AI model and single sensor measuring acceleration and ECG could model cognitive and physical fatigue for a self-paced trail run. METHODS: A field-based protocol of continuous fatigue repeated hourly induced physical (~45 min) and cognitive (~10 min) fatigue on one healthy participant. The physical load was a 3.8 km, 200 m vertical gain, trail run, with acceleration and electrocardiogram (ECG) data collected using a single sensor. Cognitive load was a Multi Attribute Test Battery (MATB) and separate assessment battery included the Finger Tap Test (FTT), Stroop, Trail Making A and B, Spatial Memory, Paced Visual Serial Addition Test (PVSAT), and a vertical jump. A fatigue prediction model was implemented using a Convolutional Neural Network (CNN). RESULTS: When the fatigue test battery results were compared for sensitivity to the protocol load, FTT right hand (R2 0.71) and Jump Height (R2 0.78) were the most sensitive while the other tests were less sensitive (R2 values Stroop 0.49, Trail Making A 0.29, Trail Making B 0.05, PVSAT 0.03, spatial memory 0.003). The best prediction results were achieved with a rolling average of 200 predictions (102.4 s), during set activity types, mean absolute error for 'walk up' (MAE200 12.5%), and range of absolute error for 'run down' (RAE200 16.7%). CONCLUSIONS: We were able to measure cognitive and physical fatigue using a single wearable sensor during a practical field protocol, including contextual factors in conjunction with a neural network model. This research has practical application to fatigue research in the field.


Assuntos
Aprendizado Profundo , Fadiga/diagnóstico , Humanos , Redes Neurais de Computação , Caminhada
3.
Biotechnol Bioeng ; 116(9): 2223-2235, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31062870

RESUMO

Biomanufacturing exhibits inherent variability that can lead to variation in performance attributes and batch failure. To help ensure process consistency and product quality the development of predictive models and integrated control strategies is a promising approach. In this study, a feedback controller was developed to limit excessive lactate production, a widespread metabolic phenomenon that is negatively associated with culture performance and product quality. The controller was developed by applying machine learning strategies to historical process development data, resulting in a forecast model that could identify whether a run would result in lactate consumption or accumulation. In addition, this exercise identified a correlation between increased amino acid consumption and low observed lactate production leading to the mechanistic hypothesis that there is a deficiency in the link between glycolysis and the tricarboxylic acid cycle. Using the correlative process parameters to build mechanistic insight and applying this to predictive models of lactate concentration, a dynamic model predictive controller (MPC) for lactate was designed. This MPC was implemented experimentally on a process known to exhibit high lactate accumulation and successfully drove the cell cultures towards a lactate consuming state. In addition, an increase in specific titer productivity was observed when compared with non-MPC controlled reactors.


Assuntos
Ciclo do Ácido Cítrico , Glicólise , Ácido Láctico/metabolismo , Modelos Biológicos , Animais , Células CHO , Cricetinae , Cricetulus , Previsões
4.
Biotechnol Bioeng ; 114(6): 1264-1274, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28186329

RESUMO

Antibody disulfide bond reduction during monoclonal antibody (mAb) production is a phenomenon that has been attributed to the reducing enzymes from CHO cells acting on the mAb during the harvest process. However, the impact of antibody reduction on the downstream purification process has not been studied. During the production of an IgG2 mAb, antibody reduction was observed in the harvested cell culture fluid (HCCF), resulting in high fragment levels. In addition, aggregate levels increased during the low pH treatment step in the purification process. A correlation between the level of free thiol in the HCCF (as a result of antibody reduction) and aggregation during the low pH step was established, wherein higher levels of free thiol in the starting sample resulted in increased levels of aggregates during low pH treatment. The elevated levels of free thiol were not reduced over the course of purification, resulting in carry-over of high free thiol content into the formulated drug substance. When the drug substance with high free thiols was monitored for product degradation at room temperature and 2-8°C, faster rates of aggregation were observed compared to the drug substance generated from HCCF that was purified immediately after harvest. Further, when antibody reduction mitigations (e.g., chilling, aeration, and addition of cystine) were applied, HCCF could be held for an extended period of time while providing the same product quality/stability as material that had been purified immediately after harvest. Biotechnol. Bioeng. 2017;114: 1264-1274. © 2017 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/isolamento & purificação , Meios de Cultura/química , Dissulfetos/química , Contaminação de Medicamentos/prevenção & controle , Animais , Células CHO , Cricetulus , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Oxirredução
5.
J Med Internet Res ; 19(10): e325, 2017 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-29021126

RESUMO

BACKGROUND: Up to 18% of men experience depression and/or anxiety during the transition to parenthood. Interventions designed specifically to promote the mental health of men during the transition to parenthood are scarce. Internet-delivered interventions may be acceptable and far-reaching in enhancing mental health, parenting knowledge, and healthy behaviors in expectant or new fathers. OBJECTIVE: To guide the development of Healthydads.ca, a website designed to enhance mental health and healthy behaviors in expectant fathers, a needs assessment was conducted to identify fathers' perspectives of barriers to seeking help for emotional wellness, informational needs, and factors affecting the decision to visit such a website. METHODS: One hundred and seventy-four men whose partners were expecting, or had recently given birth, in 3 Canadian provinces (Quebec, Ontario, and Alberta) completed a Web-based survey inquiring about information needs related to psychosocial aspects of the transition to parenthood, lifestyle behaviors, parenting, and factors associated with the decision to visit a father-focused website. RESULTS: Most men (155/174, 89.1%) reported accessing the Internet to obtain information on pregnancy and spent an average of 6.2 hours online per month. Seeking information about parenting on the Internet was reported by 67.2% (117/174) of men, with a mean of 4.4 hours per month of online searching. Top barriers to seeking help to improve emotional wellness during the perinatal period were: no time to seek help/assistance (130/174, 74.7%), lack of resources available in the health care system (126/174, 72.4%), financial costs associated with services (118/174, 67.8%), and feeling that one should be able to do it alone (113/174, 64.9%). Information needs that were rated highly included: parenting/infant care (52.9-81.6%), supporting (121/174, 69.5%) and improving (124/174, 71.3%) relationship with their partner, work-family balance (120/174, 69.0%), improving sleep (100/174, 57.5%), and managing stress (98/174, 56.3%). Perceiving the website as personally relevant (151/174, 86.8%), credible (141/174, 81.0%), effective (140/145, 80.5%), and having an easy navigation structure (141/174, 81.0%) were identified as important factors related to a first website visit. Providing useful (134/174, 77.0%) and easy to understand (158/174, 90.8%) information, which was also free of charge (156/174, 89.7%), were considered important for deciding to prolong a website visit. Providing the possibility to post questions to a health professional (133/174, 76.4%), adding new content regularly (119/174, 68.4%), and personal motivation (111/174, 63.8%) were factors identified that would encourage a revisit. CONCLUSIONS: Our findings demonstrate that there is substantial interest among expectant and new fathers for using Internet-delivered strategies to prepare for the transition to parenthood and support their mental health. Specific user and website features were identified to optimize the use of father-focused websites.


Assuntos
Comportamentos Relacionados com a Saúde/fisiologia , Internet/estatística & dados numéricos , Adulto , Emoções , Feminino , Humanos , Masculino , Avaliação das Necessidades , Poder Familiar , Inquéritos e Questionários
6.
J Environ Manage ; 154: 208-15, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25728918

RESUMO

Over a 3-year period, the effect of differing N-application regimes on soil extractable-P concentration, soil phosphatase activity, and forage P uptake in a P-enriched grazed-pasture system was investigated. In the fall of each year, six 0.28-ha plots were overseeded with triticale ( × Triticosecale rimpaui Wittm.) and crimson clover (Trifolium incarnatum) into a tall fescue (Lolium arundinacea)/bermudagrass (Cynodon dactylon) sod and assigned to 1 of 3 N-fertilizer treatments (n = 2): 100% of N recommendation in a split application (100N), 50% in a single application (50N), and 0% of N recommendation (0N) for triticale. Cattle commenced grazing the following spring and grazed until May. In the summer, plots were overseeded with cowpea (Vigna unguiculata), fertilized at the same rates by reference to N recommendations for bermudagrass, and grazed by cattle until September. There were no effects of N fertilization on soil phosphatase activity, electrical conductivity, or concentrations of water-soluble P. Concentrations of extractable P decreased in plots receiving 50N, but increasing N fertilization to 100N resulted in no further reduction in extractable P. Forage biomass, foliar P concentrations, and forage P mass were not affected by N fertilization rates at the plant-community level, but responses were observed within individual forage species. Results are interpreted to mean that N fertilization at 50% of the agronomic recommendation for the grass component can increase forage P mass of specific forages and decrease soil extractable P, thus providing opportunity for decreasing P losses from grazed pasture.


Assuntos
Ração Animal/análise , Criação de Animais Domésticos , Fertilizantes , Solo/química , Animais , Bovinos , Cynodon/metabolismo , Grão Comestível/metabolismo , Feminino , Festuca/metabolismo , Masculino , Medicago/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Poaceae/metabolismo , Estações do Ano , Trifolium/metabolismo
7.
J Ark Med Soc ; 111(12): 258-60, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25966601

RESUMO

The definition of beauty has evolved as the trends valued by the top of society change. For centuries, fair skin was a requirement of the Western definition of beauty; however, a shift in the 1920s made tanned skin the new standard. In this article, smoking and tanning are presented as risky behaviors that are perpetuated through industry advertising and exploitation of the authority of health professionals. The article further explores the culture of complexion in Western society before and after the 1920s as well as the consequences of tanning and efforts to rewrite society's definition of beauty.


Assuntos
Beleza , Cultura , Fumar/efeitos adversos , Valores Sociais , Curtume , Publicidade , Arkansas , Feminino , Humanos , Masculino , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Cutâneas/etiologia , Pigmentação da Pele
9.
Biotechnol Prog ; 40(2): e3410, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38013663

RESUMO

An important consideration for biopharmaceutical processes is the cost of goods (CoGs) of biotherapeutics manufacturing. CoGs can be reduced by dramatically increasing the productivity of the bioreactor process. In this study, we demonstrate that an intensified process which couples a perfused N-1 seed reactor and a fully automated high inoculation density (HID) N stage reactor substantially increases the bioreactor productivity as compared to a low inoculation density (LID) control fed-batch process. A panel of six CHOK1SV GS-KO® CHO cell lines expressing three different monoclonal antibodies was evaluated in this intensified process, achieving an average 85% titer increase and 132% space-time yield (STY) increase was demonstrated when comparing the 12-day HID process to a 15-day LID control process. These productivity increases were enabled by automated nutrient feeding in both the N-1 and N stage bioreactors using in-line process analytical technologies (PAT) and feedback control. The N-1 bioreactor utilized in-line capacitance to automatically feed the bioreactor based on a capacitance-specific perfusion rate (CapSPR). The N-stage bioreactor utilized in-line Raman spectroscopy to estimate real-time concentrations of glucose, phenylalanine, and methionine, which are held to target set points using automatic feed additions. These automated feeding methodologies were shown to be generalizable across six cell lines with diverse feed requirements. We show this new process can accommodate clonal diversity and reproducibly achieve substantial titer uplifts compared to traditional cell culture processes, thereby establishing a baseline technology platform upon which further increases bioreactor productivity and CoGs reduction can be achieved.


Assuntos
Anticorpos Monoclonais , Reatores Biológicos , Cricetinae , Animais , Cricetulus , Células CHO , Anticorpos Monoclonais/metabolismo , Perfusão , Técnicas de Cultura Celular por Lotes/métodos
10.
Anesthesiology ; 119(5): 1163-77, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24051388

RESUMO

BACKGROUND: Neurokinin-1 receptors (NK1-rs) located on superficial dorsal horn neurons are essential for integration of nociceptive input. Intrathecal injection of substance P-saporin (SP-SAP) leads to local loss of spinal NK1-r (+) neurons suggesting its potential as a therapeutic agent for chronic pain. The authors determined, in a canine model, effects of lumbar intrathecal SP-SAP. METHODS: Distribution of SP-SAP and Saporin was determined in plasma, lumbar cerebrospinal fluid, and tissue. Safety of intrathecal SP-SAP was determined in four groups (six dogs each) administered 0 (0.9% saline), 1.5, 15, or 150 µg SP-SAP through lumbar intrathecal catheters. Behavioral, physiologic, and biochemical variables were assessed. Spinal tissues were collected at 7 and approximately 90 days, or earlier if significant morbidity developed, and analyzed for NK1-r (+) neuron loss and histopathology. RESULTS: SP-SAP and Saporin were detectable in lumbar cerebrospinal fluid for up to 4 and 24 h, respectively. Animals receiving intrathecal saline, 1.5, or 15 µg of SP-SAP showed no persistent neurologic deficits. Three animals receiving 150 µg of SP-SAP developed pelvic limb paraparesis and were euthanized prematurely. Immunohistochemistry and in situ hybridization cell counts confirmed a significant reduction in NK1-r (+) in superficial dorsal horn neurons from lumbar spinal cord after intrathecal administration of 15 and 150 µg of SP-SAP. A significant loss of NK1-r neurons in the lumbar ventral horn occurred only with 150-µg SP-SAP. CONCLUSION: Intrathecal 15-µg SP-SAP reduced dorsal, but not ventral, NK1-r (+) neurons at the spinal level of delivery with minimal side effects, whereas 150-µg SP-SAP resulted in motor neuron toxicity.


Assuntos
Antagonistas dos Receptores de Neurocinina-1 , Proteínas Inativadoras de Ribossomos Tipo 1/farmacologia , Medula Espinal/metabolismo , Substância P/análogos & derivados , Animais , Comportamento Animal/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cães , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Hibridização In Situ , Injeções Espinhais , Exame Neurológico , Síndromes Neurotóxicas/patologia , Oftalmoscopia , Fenótipo , Receptores da Neurocinina-1/metabolismo , Proteínas Inativadoras de Ribossomos Tipo 1/farmacocinética , Proteínas Inativadoras de Ribossomos Tipo 1/toxicidade , Saporinas , Medula Espinal/efeitos dos fármacos , Substância P/farmacocinética , Substância P/farmacologia , Substância P/toxicidade , Distribuição Tecidual
11.
Pediatr Dermatol ; 30(6): e246-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22299662

RESUMO

A 7-year-old boy presented with an annular verrucous plaque on the chin of 5 weeks duration. The lesion occurred after a bicycle accident and was unresponsive to antibiotics. Fungal culture grew Sporothrix schenckii. Sporotrichosis should be considered and fungal culture obtained whenever a nodule or plaque fails to respond to initial treatment.


Assuntos
Ciclismo , Queixo/lesões , Sporothrix/isolamento & purificação , Esporotricose/etiologia , Ferimentos e Lesões/microbiologia , Acidentes , Criança , Queixo/microbiologia , Humanos , Masculino , Esporotricose/patologia , Esporotricose/terapia
12.
Int J Hematol ; 117(5): 652-659, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36964840

RESUMO

Immune dysregulation is a hallmark of clinically active multiple myeloma (MM). Interactions between malignant clonal cells and immune cells within the bone marrow microenvironment are associated with the formation of a milieu favorable to tumor progression. IL-10, TGF-ß and other immunoregulatory pathways are upregulated, promoting angiogenesis, tumor cell survival and inhibition of the native immune response. Transcriptomic evaluation of the bone marrow microenvironment reveals polarization of the T cell repertoire towards exhaustion and predominance of accessory cells with immunosuppressive qualities. These changes facilitate the immune escape of tumor cells and functional deficiencies that manifest as an increased risk of infection and a reduction in response to vaccinations. Immunotherapy with Chimeric Antigen Receptor (CAR) T cells and other cellular-based approaches have transformed outcomes for patients with advanced MM. Characterization of the immune milieu and identification of biomarkers predictive of treatment response are essential to increasing durability and allowing for the incorporation of novel strategies such as cancer vaccines. This paper will review the current use of cancer vaccines and CAR T cell therapy in MM as well as potential opportunities to expand and improve the application of these platforms.


Assuntos
Vacinas Anticâncer , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/terapia , Vacinas Anticâncer/uso terapêutico , Imunoterapia , Medula Óssea , Imunoterapia Adotiva , Microambiente Tumoral
13.
J Sci Med Sport ; 26 Suppl 1: S40-S45, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36934030

RESUMO

Wearable sensors enable down range data collection of physiological and cognitive performance of the warfighter. However, autonomous teams may find the sensor data impractical to interpret and hence influence real-time decisions without the support of subject matter experts. Decision support tools can reduce the burden of interpreting physiological data in the field and incorporate a systems perspective where noisy field data can contain useful additional signals. We present a methodology of how artificial intelligence can be used for modeling human performance with decision-making to achieve actionable decision support. We provide a framework for systems design and advancing from the laboratory to real world environments. The result is a validated measure of down-range human performance with a low burden of operation.


Assuntos
Inteligência Artificial , Militares , Humanos
14.
NPJ Microgravity ; 9(1): 46, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344482

RESUMO

As NASA prepares for crewed lunar missions over the next several years, plans are also underway to journey farther into deep space. Deep space exploration will require a paradigm shift in astronaut medical support toward progressively earth-independent medical operations (EIMO). The Exploration Medical Capability (ExMC) element of NASA's Human Research Program (HRP) is investigating the feasibility and value of advanced capabilities to promote and enhance EIMO. Currently, astronauts rely on real-time communication with ground-based medical providers. However, as the distance from Earth increases, so do communication delays and disruptions. Moreover, resupply and evacuation will become increasingly complex, if not impossible, on deep space missions. In contrast to today's missions in low earth orbit (LEO), where most medical expertise and decision-making are ground-based, an exploration crew will need to autonomously detect, diagnose, treat, and prevent medical events. Due to the sheer amount of pre-mission training required to execute a human spaceflight mission, there is often little time to devote exclusively to medical training. One potential solution is to augment the long duration exploration crew's knowledge, skills, and abilities with a clinical decision support system (CDSS). An analysis of preliminary data indicates the potential benefits of a CDSS to mission outcomes when augmenting cognitive and procedural performance of an autonomous crew performing medical operations, and we provide an illustrative scenario of how such a CDSS might function.

15.
Drugs Aging ; 39(4): 271-284, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35344197

RESUMO

Patients with urothelial carcinoma tend to be older and frailer with a large number of chronic medical conditions. This is particularly pronounced in those with unresectable locally advanced and metastatic urothelial carcinoma. Prior to 2016, treatment options in advanced urothelial carcinoma were limited to chemotherapy, and as a result, a large number of patients were not receiving disease-directed management. Over the last 6 years, multiple alternative modalities including immune checkpoint inhibitors and targeted therapies have been introduced. They are being utilized clinically in older and frail patients, but there are limited studies investigating outcomes in these specific populations. Based upon current evidence, age does not impact the efficacy and tolerance of immune checkpoint inhibitors if patients are fit enough to receive therapy. In frailer patients, immune checkpoint inhibitors appear to be safe, but outcomes from largely retrospective studies demonstrate mixed data regarding their efficacy. Although there are indications from clinical trials that enfortumab vedotin, sacituzumab govitecan, and erdafitinib are also efficacious irrespective of age, there is still not enough evidence to draw definitive conclusions about their use in older and frail patients. Regardless, in all older patients with advanced urothelial carcinoma, it is critical to evaluate for frailty through geriatric screening tools and comprehensive assessments. Combining these evaluations with consideration of an individual patient's goals should be the foundation upon which therapeutic decisions are made in this population of patients.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Idoso Fragilizado , Humanos , Inibidores de Checkpoint Imunológico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológico
16.
Animals (Basel) ; 12(21)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36359053

RESUMO

In southeastern USA, the use of baleage has increased as an alternative technology to hay production, thereby allowing for a timelier harvest of the conserved forage. A series of studies were conducted to determine the nutritive value, fermentation parameters, and in situ disappearance of the cool-season annual forage mixtures that were ensiled with or without silage inoculant for up to 120 d. The forage mixtures were wheat (Triticum aestivum L.) + brassica hybrid (Brassica rapa L. × napus L.) (WB), wheat + crimson clover (Trifolium incarnatum L.) (WC), and annual ryegrass (Lolium multiflorum Lam.) + oat (Avena sativa L.) + crimson clover (ROC). The inoculant strategy affected the CP concentration (p < 0.05), with it increasing in WB and decreasing in ROC. Among the mixtures, the DM concentration decreased by up to 5%, and the NDF and ADF concentrations decreased by up to 10% during the ensiling period. The pH averaged 5.0, 5.0, and 5.5 for the WC, WB, and ROC mixtures, respectively. Based on our results, the baleage of the cool-season annual forage mixtures may provide a viable high-quality option to sustain animal growth and performance.

17.
Growth Horm IGF Res ; 40: 20-27, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29679919

RESUMO

OBJECTIVE: Overweight/obesity is characterized by decreased growth hormone (GH) secretion whereas circulating IGF-I levels are less severely reduced. Yet, the activity of the circulating IGF-system appears to be normal in overweight/obese subjects, as estimated by the ability of serum to activate the IGF-I receptor in vitro (bioactive IGF). We hypothesized that preservation of bioactive IGF in overweight/obese women is regulated by an insulin-mediated suppression of IGF-binding protein-1 (IGFBP-1) and IGFBP-2, and by suppression of IGFBP-3, mediated by low GH. We additionally hypothesized that increases in bioactive IGF would drive changes in body composition with low-dose GH administration. DESIGN: Cross-sectional analysis and 3-month interim analysis of a 6-month randomized, placebo-controlled study of GH administration in 50 overweight/obese women without diabetes mellitus. Bioactive IGF (kinase receptor activation assay) and body composition (DXA) were measured. RESULTS: Prior to treatment, IGFBP-3 (r = -0.33, p = 0.02), but neither IGFBP-1 nor IGFBP-2, associated inversely with bioactive IGF. In multivariate analysis, lower IGFBP-3 correlated with lower peak stimulated GH (r = 0.45, p = 0.05) and higher insulin sensitivity (r = -0.74, p = 0.003). GH administration resulted in an increase in mean serum IGF-I concentrations (144 ±â€¯56 to 269 ±â€¯66 µg/L, p < 0.0001) and bioactive IGF (1.29 ±â€¯0.39 to 2.60 ±â€¯1.12 µg/L, p < 0.0001). The treatment-related increase in bioactive IGF, but not total IGF-I concentration, predicted an increase in lean mass (r = 0.31, p = 0.03) and decrease in total adipose tissue/BMI (r = -0.43, p = 0.003). CONCLUSIONS: Our data suggest that in overweight/obesity, insulin sensitivity and GH have opposing effects on IGF bioactivity through effects on IGFBP-3. Furthermore, increases in bioactive IGF, rather than IGF-I concentration, predicted GH administration-related body composition changes. CLINICAL TRIAL REGISTRATION NUMBER: NCT00131378.


Assuntos
Biomarcadores/sangue , Hormônio do Crescimento Humano/administração & dosagem , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Obesidade/sangue , Sobrepeso/sangue , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Prognóstico
18.
Biotechnol Prog ; 33(6): 1647-1661, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28786215

RESUMO

As the biopharmaceutical industry evolves to include more diverse protein formats and processes, more robust control of Critical Quality Attributes (CQAs) is needed to maintain processing flexibility without compromising quality. Active control of CQAs has been demonstrated using model predictive control techniques, which allow development of processes which are robust against disturbances associated with raw material variability and other potentially flexible operating conditions. Wide adoption of model predictive control in biopharmaceutical cell culture processes has been hampered, however, in part due to the large amount of data and expertise required to make a predictive model of controlled CQAs, a requirement for model predictive control. Here we developed a highly automated, perfusion apparatus to systematically and efficiently generate predictive models using application of system identification approaches. We successfully created a predictive model of %galactosylation using data obtained by manipulating galactose concentration in the perfusion apparatus in serialized step change experiments. We then demonstrated the use of the model in a model predictive controller in a simulated control scenario to successfully achieve a %galactosylation set point in a simulated fed-batch culture. The automated model identification approach demonstrated here can potentially be generalized to many CQAs, and could be a more efficient, faster, and highly automated alternative to batch experiments for developing predictive models in cell culture processes, and allow the wider adoption of model predictive control in biopharmaceutical processes. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:1647-1661, 2017.


Assuntos
Anticorpos Monoclonais/biossíntese , Técnicas de Cultura Celular por Lotes/normas , Biofarmácia/normas , Reatores Biológicos/normas , Animais , Anticorpos Monoclonais/química , Técnicas de Cultura Celular por Lotes/métodos , Biofarmácia/métodos , Células CHO , Cricetinae , Cricetulus , Humanos , Controle de Qualidade
19.
Growth Horm IGF Res ; 26: 17-23, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26774401

RESUMO

OBJECTIVE: Although growth hormone (GH) replacement is prescribed for patients with hypopituitarism due to many etiologies, it is not routinely prescribed for patients with GH deficiency (GHD) after cure of acromegaly (acroGHD). This study was designed to investigate the effect of GH replacement on cardiac parameters in acroGHD. DESIGN: We prospectively evaluated for 12months 23 patients with acroGHD: 15 subjects on GH replacement and eight subjects not on GH replacement. Main outcome measures included LV mass corrected for body surface area (LVM/BSA) and measures of diastolic dysfunction (E/A ratio and deceleration time), as assessed by echocardiography. RESULTS: After 12months of follow-up, there were no differences between the GH-treated group and the untreated group in LVM/BSA (GH: 74.4±22.5g/m(2) vs untreated: 72.9±21.3g/m(2), p=0.89), E/A ratio (GH: 1.21±0.39 vs untreated: 1.08±0.39, p=0.50) or deceleration time (GH: 224.5±60.1ms vs untreated: 260±79.8ms, p=0.32). The overall degree of diastolic function was similar between the groups with 42.9% of untreated subjects and 50% of GH-treated subjects (p=0.76) classified as having normal diastolic function at follow-up. CONCLUSIONS: There were no significant differences in LVM/BSA or parameters of diastolic function in patients with a history of acromegaly treated for GHD as compared to those who were untreated. These data are reassuring with respect to cardiovascular safety with GH use after treatment for acromegaly, although further longer term study is necessary to evaluate the safety and efficacy of GH treatment in this population.


Assuntos
Acromegalia/tratamento farmacológico , Diástole/efeitos dos fármacos , Terapia de Reposição Hormonal , Hormônio do Crescimento Humano/uso terapêutico , Hipopituitarismo/tratamento farmacológico , Acromegalia/complicações , Adulto , Idoso , Feminino , Seguimentos , Terapia de Reposição Hormonal/efeitos adversos , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Humanos , Hipopituitarismo/complicações , Masculino , Pessoa de Meia-Idade
20.
PLoS One ; 10(6): e0131109, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26098900

RESUMO

Modified handling is often claimed to reduce (sub-)lethal impacts among organisms caught-and-released in fisheries. Improving welfare of discarded fish warrants investigation, when their survival is of both economic and ecological importance. In this study, juvenile yellowfin bream (Acanthopagrus australis) were trawled in an Australian penaeid fishery and then discarded after on-board sorting in either dry or water-filled (modified) trays and with delays in starting sorting of either 2 or 15 mins. Blood plasma cortisol, glucose and potassium were sampled immediately from some yellowfin bream, while others were placed into cages (with controls) and sampled after five days. Irrespective of their on-board handling, all trawled fish incurred a relatively high acute stress response (i.e. an increase in Mean ± SE cortisol from a baseline of <4 to 122.0 ± 14.9 ng/mL) that was mostly attributed to the trawling process, and exacerbated by variation in key parameters (low salinity, changes in water temperature and the presence of jellyfish Catostylus mosaicus in catches). When C. mosaicus was present, the potassium concentrations of fish sampled immediately after sorting were significantly elevated, possibly due to nematocyst contact and subsequent inhibition of ion pumps or cytolysis. Stress also increased during handling in response to warmer air temperatures and longer exposure. While most fish had substantially recovered by 120 hours after discarding, deploying selective trawls (to reduce jellyfish) for short periods and then quickly sorting catches in water would benefit discard welfare.


Assuntos
Bem-Estar do Animal , Pesqueiros , Perciformes/fisiologia , Estresse Fisiológico , Animais , Austrália , Glicemia/metabolismo , Hidrocortisona/sangue , Perciformes/sangue , Perciformes/parasitologia , Potássio/sangue , Salinidade , Cifozoários/patogenicidade , Água do Mar/química , Temperatura
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