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2.
J Appl Physiol (1985) ; 133(4): 867-875, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35952348

RESUMO

Repeat exposures to low oxygen (intermittent hypoxia, IH), like that observed in sleep apnea, elicit increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in men. Endothelin (ET) receptor antagonists can attenuate the sympathetic and BP response to IH in rodents; whether these data translate to humans are unclear. We hypothesized that ET-receptor antagonism would ameliorate any rise in MSNA and BP following acute IH in humans. Twelve healthy men (31 ± 1 yr) completed two visits (control, bosentan) separated by at least 1 wk. MSNA, BP, and baroreflex sensitivity (modified Oxford) were assessed during normoxic rest before and following 30 min of IH. The midpoint (T50) for each individual's baroreflex curve was calculated. Acute IH increased plasma ET-1 (P < 0.01), MSNA burst frequency (P = 0.03), and mean BP (P < 0.01). There was no effect of IH on baroreflex sensitivity (P = 0.46), although an increase in T50 was observed (P < 0.01). MSNA burst frequency was higher (P = 0.04) and mean BP (P < 0.01) was lower following bosentan treatment compared with control. There was no effect of bosentan on baroreflex sensitivity (P = 0.53), although a lower T50 was observed on the bosentan visit (P < 0.01). There was no effect of bosentan on increases in MSNA (P = 0.81) or mean BP (P = 0.12) following acute IH. Acute IH results in an increase in ET-1, MSNA, and BP in healthy young men. The effect of IH on MSNA and BP is not attenuated following ET-receptor inhibition. Present data suggest that acute IH does not increase MSNA or BP through activation of ET-receptors in healthy young men.NEW & NOTEWORTHY Repeat exposures to low oxygen (intermittent hypoxia, IH) elicit increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in men. Endothelin (ET) receptor antagonists can attenuate the sympathetic and BP response to IH in rodents; whether these data translate to humans were unclear. We show acute IH results in an increase in ET-1, MSNA, and BP in healthy young men; however, the effect of IH on MSNA and BP does not occur through activation of ET-receptors in healthy young men.


Assuntos
Barorreflexo , Sistema Nervoso Simpático , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Bosentana , Endotelina-1 , Endotelinas , Frequência Cardíaca/fisiologia , Hemodinâmica , Humanos , Hipóxia , Masculino , Músculo Esquelético , Oxigênio , Receptor de Endotelina A , Sistema Nervoso Simpático/fisiologia
3.
Front Neurol ; 13: 930303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016542

RESUMO

Although most neurophysiological studies of persons with cerebral palsy (CP) have been focused on supraspinal networks, recent evidence points toward the spinal cord as a central contributor to their motor impairments. However, it is unclear if alterations in the spinal pathways are also linked to deficits in the sensory processing observed clinically. This investigation aimed to begin to address this knowledge gap by evaluating the flexor carpi radialis (FCR) H-reflex in adults with CP and neurotypical (NT) controls while at rest and during an isometric wrist flexion task. The maximal H-wave (Hmax) and M-wave (Mmax) at rest were calculated and utilized to compute Hmax/Mmax ratios (H:M ratios). Secondarily, the facilitation of the H-wave was measured while producing an isometric, voluntary wrist flexion contraction (i.e., active condition). Finally, a wrist position sense test was used to quantify the level of joint position sense. These results revealed that the adults with CP had a lower H:M ratio compared with the NT controls while at rest. The adults with CP were also unable to facilitate their H-reflexes with voluntary contraction and had greater position sense errors compared with the controls. Further, these results showed that the adults with CP that had greater wrist position sense errors tended to have a lower H:M ratio at rest. Overall, these findings highlight that aberration in the spinal cord pathways of adults with CP might play a role in the sensory processing deficiencies observed in adults with CP.

4.
Am J Physiol Regul Integr Comp Physiol ; 323(3): R351-R362, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35816718

RESUMO

We examined the effect of intermittent hypoxia (IH, a hallmark feature of sleep apnea) on adipose tissue lipolysis and the role of endothelin-1 (ET-1) in this response. We hypothesized that IH can increase ET-1 secretion and plasma free fatty acid (FFA) concentrations. We further hypothesized that inhibition of ET-1 receptor activation with bosentan could prevent any IH-mediated increase in FFA. To test this hypothesis, 16 healthy male participants (32 ± 5 yr, 26 ± 2 kg/m2) were exposed to 30 min of IH in the absence (control) and presence of bosentan (62.5 mg oral twice daily for 3 days prior). Arterial blood samples for ET-1, epinephrine, and FFA concentrations, as well as abdominal subcutaneous adipose tissue biopsies (to assess transcription of cellular receptors/proteins involved in lipolysis), were collected. Additional proof-of-concept studies were conducted in vitro using primary differentiated human white preadipocytes (HWPs). We show that IH increased circulating ET-1, epinephrine, and FFA (P < 0.05). Bosentan treatment reduced plasma epinephrine concentrations and blunted IH-mediated increases in FFA (P < 0.01). In adipose tissue, bosentan had no effect on cellular receptors and proteins involved in lipolysis (P > 0.05). ET-1 treatment did not directly induce lipolysis in differentiated HWP. In conclusion, IH increases plasma ET-1 and FFA concentrations. Inhibition of ET-1 receptors with bosentan attenuates the FFA increase in response to IH. Based on a lack of a direct effect of ET-1 in HWP, we speculate the effect of bosentan on circulating FFA in vivo may be secondary to its ability to reduce sympathoadrenal tone.


Assuntos
Bosentana , Endotelina-1 , Hipóxia , Adipócitos , Adulto , Bosentana/farmacologia , Células Cultivadas , Endotelina-1/metabolismo , Epinefrina , Humanos , Lipólise , Masculino
5.
Exp Physiol ; 107(8): 854-863, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35603981

RESUMO

NEW FINDINGS: What is the central question of this study? Do humans with high-affinity haemoglobin (HAH) demonstrate attenuated skeletal muscle deoxygenation during normoxic and hypoxic exercise? What is the main finding and its importance? Examination of near-infrared spectroscopy-derived muscle oxygenation profiles suggests that fractional oxygen extraction is blunted during hypoxic exercise in humans with HAH compared with control subjects. However, muscle tissue oxygen saturation levels were higher in humans with HAH during exercise in normoxia compared with control subjects. These alterations in fractional oxygen extraction in humans with HAH might influence blood flow regulation and exercise capacity during hypoxia. ABSTRACT: Recently, researchers in our laboratory have shown that humans with genetic mutations resulting in high-affinity haemoglobin (HAH) demonstrate better maintained aerobic capacity and peak power output during hypoxic exercise versus normoxic exercise in comparison to humans with normal-affinity haemoglobin. However, the influence of HAH on tissue oxygenation within exercising muscle during normoxia and hypoxia is unknown. Therefore, we examined near-infrared spectroscopy-derived oxygenation profiles of the vastus lateralis during graded cycling exercise in normoxia and hypoxia among humans with HAH (n = 5) and control subjects with normal-affinity haemoglobin (n = 12). The HAH group elicited a blunted increase of deoxygenated haemoglobin + myoglobin during hypoxic exercise compared with the control group (P = 0.03), suggesting reduced fractional oxygen extraction in the HAH group. In addition, the HAH group maintained a higher level of muscle tissue oxygen saturation during normoxic exercise (HAH, 75 ± 4% vs. controls, 65 ± 3%, P = 0.049) and there were no differences between groups in muscle tissue oxygen saturation during hypoxic exercise (HAH, 68 ± 3% vs. controls, 68 ± 2%, P = 0.943). Overall, our results suggest that humans with HAH might demonstrate divergent patterns of fractional oxygen extraction during hypoxic exercise and elevated muscle tissue oxygenation during normoxic exercise compared with control subjects.


Assuntos
Exercício Físico , Hemoglobinas , Músculo Esquelético , Consumo de Oxigênio , Oxigênio , Exercício Físico/fisiologia , Hemoglobinas/metabolismo , Humanos , Hipóxia , Músculo Esquelético/fisiologia , Oxigênio/metabolismo , Consumo de Oxigênio/fisiologia
6.
RSC Adv ; 12(6): 3721-3728, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35425363

RESUMO

Exceptionally coercive SmCo5 particles are produced through calcium vapor reduction of SmCo5O9 powders synthesized by flame spray pyrolysis. The resulting powders are composed of oblate hexagonal particles approximately 2 microns across with smooth surfaces. This microstructure yields record-breaking room temperature coercivity H c,i >80 kOe, or >60 kOe when combined with advanced manufacturing approaches such as electrophoretic deposition or molding with tetraglyme inks. These techniques enable straightforward low-loss fabrication of bulk parts. The high coercivity is extremely robust at elevated temperatures, exceeding 10 kOe even at 600 °C. The oxide precursor approach removes the need for strict environmental control during synthesis that is common to other nanoparticle-based routes and can readily be scaled to kilogram quantities of feedstock production. Magnet powders produced by calcium vapor reduction can thus function as the building blocks for traditional or advanced manufacturing techniques, while the high coercivity enables consistent performance across a wide range of temperatures.

7.
Sci Rep ; 12(1): 4807, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35314729

RESUMO

Previous animal models have illustrated that reduced cortical activity in the developing brain has cascading activity-dependent effects on the microstructural organization of the spinal cord. A limited number of studies have attempted to translate these findings to humans with cerebral palsy (CP). Essentially, the aberrations in sensorimotor cortical activity in those with CP could have an adverse effect on the spinal cord microstructure. To investigate this knowledge gap, we utilized magnetoencephalographic (MEG) brain imaging to quantify motor-related oscillatory activity in fourteen adults with CP and sixteen neurotypical (NT) controls. A subset of these participants also underwent cervical-thoracic spinal cord MRI. Our results showed that the strength of the peri-movement beta desynchronization and the post-movement beta rebound were each weaker in the adults with CP relative to the controls, and these weakened responses were associated with poorer task performance. Additionally, our results showed that the strength of the peri-movement beta response was associated with the total cross-sectional area of the spinal cord and the white matter cross-sectional area. Altogether these results suggest that the altered sensorimotor cortical activity seen in CP may result in activity-dependent plastic changes within the spinal cord microstructure, which could ultimately contribute to the sensorimotor deficits seen in this population.


Assuntos
Paralisia Cerebral , Córtex Sensório-Motor , Paralisia Cerebral/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Magnetoencefalografia , Córtex Sensório-Motor/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem
8.
Am Surg ; 88(1): 74-82, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33356437

RESUMO

BACKGROUND: Clostridium difficile infection (CDI) is now the most common cause of healthcare-associated infections, with increasing prevalence, severity, and mortality of nosocomial and community-acquired CDI which makes up approximately one third of all CDI. There are also increased rates of asymptomatic colonization particularly in high-risk patients. C difficile is a known collagenase-producing bacteria which may contribute to anastomotic leak (AL). METHODS: Machine learning-augmented multivariable regression and propensity score (PS)-modified analysis was performed in this nationally representative case-control study of CDI and anastomotic leak, mortality, and length of stay for colectomy patients using the ACS-NSQIP database. RESULTS: Among 46 735 colectomy patients meeting study criteria, mean age was 61.7 years (SD 14.38), 52.2% were woman, 72.5% were Caucasian, 1.5% developed CDI, 3.1% developed anastomotic leak, and 1.6% died. In machine learning (backward propagation neural network)-augmented multivariable regression, CDI significantly increases anastomotic leak (OR 2.39, 95% CI 1.70-3.36; P < .001), which is similar to the neural network results. Having CDI increased the independent likelihood of anastomotic leak by 3.8% to 6.8% overall, and in dose-dependent fashion with increasing ASA class to 4.3%, 5.7%, 7.6%, and 10.0%, respectively, for ASA class I to IV. In doubly robust augmented inverse probability weighted PS analysis, CDI significantly increases the likelihood of AL by 4.58% (95% CI 2.10-7.06; P < .001). CONCLUSIONS: This is the first known nationally representative study on CDI and AL, mortality, and length of stay among colectomy patients. Using advanced machine learning and PS analysis, we provide evidence that suggests CDI increases AL in a dose-dependent manner with increasing ASA Class.


Assuntos
Fístula Anastomótica/microbiologia , Clostridioides difficile , Infecções por Clostridium/complicações , Colectomia/efeitos adversos , Infecção Hospitalar/microbiologia , Aprendizado de Máquina , Fístula Anastomótica/mortalidade , Infecções Assintomáticas/epidemiologia , Infecções Assintomáticas/mortalidade , Estudos de Casos e Controles , Clostridioides difficile/enzimologia , Colectomia/mortalidade , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Infecção Hospitalar/complicações , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Análise de Regressão
9.
PLoS Med ; 18(12): e1003872, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34928960

RESUMO

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.


Assuntos
COVID-19/terapia , Ensaios de Uso Compassivo/métodos , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Sistemas de Distribuição no Hospital/organização & administração , Sistema de Registros , Reação Transfusional/complicações , Reação Transfusional/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Minorias Étnicas e Raciais , Feminino , Humanos , Imunização Passiva/efeitos adversos , Imunização Passiva/métodos , Pacientes Internados , Masculino , Área Carente de Assistência Médica , Pessoa de Meia-Idade , Pandemias , Segurança do Paciente , SARS-CoV-2 , Resultado do Tratamento , Estados Unidos
10.
Am J Physiol Regul Integr Comp Physiol ; 321(6): R903-R911, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34668438

RESUMO

Sex-related differences in respiratory modulation of sympathetic activity have been observed in rodent models of sleep apnea [intermittent hypoxia (IH)]. In light of sex disparities in the respiratory response to acute IH in humans as well as changes in respiratory modulation of muscle sympathetic nerve activity (MSNA) in clinical sleep apnea, we examined sex-related differences in respiratory modulation of MSNA following acute IH. We hypothesized that respiratory modulation of MSNA would be altered in both male and female participants after IH; however, the respiratory patterning of MSNA following IH would be sex specific. Heart rate, MSNA, and respiration were evaluated in healthy male (n = 21, 30 ± 5 yr) and female (n = 10, 28 ± 5 yr) participants during normoxic rest before and after 30 min of IH. Respiratory modulation of MSNA was assessed by fitting polynomials to cross-correlation histograms constructed between sympathetic spikes and respiration. MSNA was elevated after IH in male (20 ± 6 to 24 ± 8 bursts/min) and female (19 ± 8 to 22 ± 10 bursts/min) participants (P < 0.01). Both male and female participants exhibited respiratory modulation of MSNA (P < 0.01); however, the pattern differed by sex. After IH, modulation of MSNA within the breath was reduced in male participants (P = 0.03) but increased in female participants (P = 0.02). Both male and female adults exhibit changes in respiratory patterning of MSNA after acute IH; however, this pattern differs by sex. These data support sex disparities in respiratory modulation of MSNA and may have implications for conditions such as sleep apnea.


Assuntos
Hipóxia/fisiopatologia , Pulmão/inervação , Músculo Esquelético/inervação , Oxigênio/sangue , Mecânica Respiratória , Sistema Nervoso Simpático/fisiopatologia , Adaptação Fisiológica , Adulto , Biomarcadores/sangue , Feminino , Frequência Cardíaca , Humanos , Hipóxia/sangue , Masculino , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
11.
Front Microbiol ; 12: 696473, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413839

RESUMO

The efficient delivery of electrochemically in situ produced H2 can be a key advantage of microbial electrosynthesis over traditional gas fermentation. However, the technical details of how to supply large amounts of electric current per volume in a biocompatible manner remain unresolved. Here, we explored for the first time the flexibility of complex 3D-printed custom electrodes to fine tune H2 delivery during microbial electrosynthesis. Using a model system for H2-mediated electromethanogenesis comprised of 3D fabricated carbon aerogel cathodes plated with nickel-molybdenum and Methanococcus maripaludis, we showed that novel 3D-printed cathodes facilitated sustained and efficient electromethanogenesis from electricity and CO2 at an unprecedented volumetric production rate of 2.2 L CH4 /L catholyte /day and at a coulombic efficiency of 99%. Importantly, our experiments revealed that the efficiency of this process strongly depends on the current density. At identical total current supplied, larger surface area cathodes enabled higher methane production and minimized escape of H2. Specifically, low current density (<1 mA/cm2) enabled by high surface area cathodes was found to be critical for fast start-up times of the microbial culture, stable steady state performance, and high coulombic efficiencies. Our data demonstrate that 3D-printing of electrodes presents a promising design tool to mitigate effects of bubble formation and local pH gradients within the boundary layer and, thus, resolve key critical limitations for in situ electron delivery in microbial electrosynthesis.

12.
Proc Natl Acad Sci U S A ; 118(32)2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34362842

RESUMO

Electrochemical reactors utilizing flow-through electrodes (FTEs) provide an attractive path toward the efficient utilization of electrical energy, but their commercial viability and ultimate adoption hinge on attaining high currents to drive productivity and cost competitiveness. Conventional FTEs composed of random, porous media provide limited opportunity for architectural control and engineering of microscale transport. Alternatively, the design freedom engendered by additively manufacturing FTEs yields additional opportunities to further drive performance via flow engineering. Through experiment and validated continuum computation we analyze the mass transfer in three-dimensional (3D)-printed porous FTEs with periodic lattice structures and show that, in contrast to conventional electrodes, the mesoscopic length scales in 3D-printed electrodes lead to an increase in the mass correlation exponent as inertial flow effects dominate. The inertially enhanced mass transport yields mass transfer coefficients that exceed previously reported 3D-printed FTEs by 10 to 100 times, bringing 3D-printed FTE performance on par with conventional materials.

13.
Nat Commun ; 12(1): 4864, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381030

RESUMO

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.


Assuntos
COVID-19/terapia , Plasma/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos , Variação Antigênica , Doadores de Sangue , COVID-19/mortalidade , Feminino , Humanos , Imunização Passiva/mortalidade , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
14.
Nature ; 595(7865): 58-65, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34194019

RESUMO

The natural world provides many examples of multiphase transport and reaction processes that have been optimized by evolution. These phenomena take place at multiple length and time scales and typically include gas-liquid-solid interfaces and capillary phenomena in porous media1,2. Many biological and living systems have evolved to optimize fluidic transport. However, living things are exceptionally complex and very difficult to replicate3-5, and human-made microfluidic devices (which are typically planar and enclosed) are highly limited for multiphase process engineering6-8. Here we introduce the concept of cellular fluidics: a platform of unit-cell-based, three-dimensional structures-enabled by emerging 3D printing methods9,10-for the deterministic control of multiphase flow, transport and reaction processes. We show that flow in these structures can be 'programmed' through architected design of cell type, size and relative density. We demonstrate gas-liquid transport processes such as transpiration and absorption, using evaporative cooling and CO2 capture as examples. We design and demonstrate preferential liquid and gas transport pathways in three-dimensional cellular fluidic devices with capillary-driven and actively pumped liquid flow, and present examples of selective metallization of pre-programmed patterns. Our results show that the design and fabrication of architected cellular materials, coupled with analytical and numerical predictions of steady-state and dynamic behaviour of multiphase interfaces, provide deterministic control of fluidic transport in three dimensions. Cellular fluidics may transform the design space for spatial and temporal control of multiphase transport and reaction processes.


Assuntos
Células/metabolismo , Microfluídica/instrumentação , Microfluídica/métodos , Absorção Fisico-Química , Dióxido de Carbono/metabolismo , Gases/metabolismo , Nutrientes/metabolismo , Oxigênio/metabolismo , Transpiração Vegetal , Gravação de Videodisco , Água/metabolismo
15.
Front Med (Lausanne) ; 8: 684151, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34164419

RESUMO

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan-Meier survival plots. Qualitative inspection of all available Kaplan-Meier survival data and an aggregate Kaplan-Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks.

16.
J Am Heart Assoc ; 10(13): e022203, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34184555
17.
Transfusion ; 61(8): 2503-2511, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34036587

RESUMO

In the absence of effective countermeasures, human convalescent plasma has been widely used to treat severe acute respiratory syndrome coronavirus 2, the causative agent of novel coronavirus disease 19 (COVID-19), including among patients with innate or acquired immunosuppression. However, the association between COVID-19-associated mortality in patients with immunosuppression and therapeutic use of convalescent plasma is unknown. We review 75 reports, including one large matched-control registry study of 143 COVID-19 patients with hematological malignancies, and 51 case reports and 23 case series representing 238 COVID-19 patients with immunosuppression. We review clinical features and treatment protocols of COVID-19 patients with immunosuppression after treatment with human convalescent plasma. We also discuss the time course and clinical features of recovery. The available data from case reports and case series provide evidence suggesting a mortality benefit and rapid clinical improvement in patients with several forms of immunosuppression following COVID-19 convalescent plasma transfusion. The utility of convalescent plasma or other forms of antibody therapy in immune-deficient and immune-suppressed patients with COVID-19 warrants further investigation.


Assuntos
COVID-19/complicações , COVID-19/terapia , Tolerância Imunológica , COVID-19/imunologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Humanos , Imunização Passiva/métodos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/imunologia , Transplante de Órgãos/efeitos adversos , Resultado do Tratamento
19.
Mayo Clin Proc ; 96(5): 1262-1275, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33958057

RESUMO

To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials, 20 matched control studies, 2 dose-response studies, and 96 case reports or case series. Studies published between January 1, 2020, and January 16, 2021, were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of randomized clinical trials and matched control data demonstrated that patients with COVID-19 transfused with convalescent plasma exhibited a lower mortality rate compared with patients receiving standard treatments. Additional analyses showed that early transfusion (within 3 days of hospital admission) of higher titer plasma is associated with lower patient mortality. These data provide evidence favoring the efficacy of human convalescent plasma as a therapeutic agent in hospitalized patients with COVID-19.


Assuntos
COVID-19/terapia , COVID-19/mortalidade , Humanos , Imunização Passiva/métodos , Mortalidade , SARS-CoV-2/imunologia , Tempo para o Tratamento
20.
ACS Appl Mater Interfaces ; 13(17): 20260-20268, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33886258

RESUMO

Three-dimensional (3D) printed, hierarchically porous nickel molybdenum (NiMo) electrocatalysts were synthesized and evaluated in a flow-through configuration for the hydrogen evolution reaction (HER) in 1.0 M KOH(aq) in a simple electrochemical H-cell. 3D NiMo electrodes possess hierarchically porous structures because of the resol-based aerogel precursor, which generates superporous carbon aerogel as a catalyst support. Relative to a traditional planar electrode configuration, the flow-through configuration allowed efficient removal of the hydrogen bubbles from the catalyst surface, especially at high operating current densities, and significantly decreased the overpotentials required for HER. An analytical model that accounted for the electrokinetics of HER as well as the mass transport with or without the flow-through configuration was developed to quantitatively evaluate voltage losses associated with kinetic overpotentials and ohmic resistance due to bubble formation in the porous electrodes. The chemical composition, electrochemical surface area (ECSA), and roughness factor (RF) were also systematically studied to assess the electrocatalytic performance of the 3D printed, hierarchically porous NiMo electrodes. An ECSA of 25163 cm2 was obtained with the highly porous structures, and an average overpotential of 45 mV at 10 mA cm-2 was achieved over 24 h by using the flow-through configuration. The flow-through configuration evaluated in the simple H-cell achieved high electrochemical accessible surface areas for electrochemical reactions and provided useful information for adaption of the porous electrodes in flow cells.

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