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Plant homeodomain leucine zipper IV (HD-Zip IV) transcription factors (TFs) contain an evolutionarily conserved steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain. While the START domain is required for TF activity, its presumed role as a lipid sensor is not clear. Here we used tandem affinity purification from Arabidopsis cell cultures to demonstrate that PROTODERMAL FACTOR2 (PDF2), a representative member that controls epidermal differentiation, recruits lysophosphatidylcholines (LysoPCs) in a START-dependent manner. Microscale thermophoresis assays confirmed that a missense mutation in a predicted ligand contact site reduces lysophospholipid binding. We additionally found that PDF2 acts as a transcriptional regulator of phospholipid- and phosphate (Pi) starvation-related genes and binds to a palindromic octamer with consensus to a Pi response element. Phospholipid homeostasis and elongation growth were altered in pdf2 mutants according to Pi availability. Cycloheximide chase experiments revealed a role for START in maintaining protein levels, and Pi starvation resulted in enhanced protein destabilization, suggesting a mechanism by which lipid binding controls TF activity. We propose that the START domain serves as a molecular sensor for membrane phospholipid status in the epidermis. Our data provide insights toward understanding how the lipid metabolome integrates Pi availability with gene expression.
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BACKGROUND: The incidence of obesity in African Americans (AAs) is higher than in non-AA in the USA. Previous studies using large national databases report that AA patients have worse outcomes than non-AA patients. OBJECTIVES: To assess perioperative outcomes among AA patients after MBS at a center of excellence (COE) that serves a large, diverse patient population. SETTING: University Hospital METHODS: A retrospective analysis was performed on patients undergoing MBS between 2010 and 2020 at our two accredited MBSAQIP (Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program) COEs where the AA population makes up over 35% of the population. Preoperative variables were compared using unpaired t-test or chi-squared test where appropriate. Thirty-day outcomes were compared following propensity score matching (exact algorithm) of demographics and comorbidities. RESULTS: Overall, 5742 patients (AA = 2058, 36%) had Roux-en-Y gastric bypass (AA = 1028, 26%) or sleeve gastrectomy (AA = 1030, 27%). AA patients were more often female (90.2% vs. 80.2%, p < 0.001) and had higher rates of hypertension (56.3% vs. 47.8%, p < 0.001), while non-AA patients had higher rates of hyperlipidemia (27.3% vs. 20.7%, p < 0.001) and obstructive sleep apnea (41.2% vs. 37.1%, p = 0.0024). Matched data showed that AA patients had higher rates of pulmonary embolism (PE) (0.3% vs. 0.1%, p = 0.020) and more emergency department visits (7.0% vs. 5.1%, p = 0.012) but no differences in mortality, readmission, reintervention, or reoperation rates. CONCLUSIONS: In a diverse area, AA patients who underwent MBS had similar perioperative outcomes compared to non-AA patients except that they experienced higher rates of PE. They also experienced higher rates of emergency department visits but had similar readmission rates.
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Cardiac output (QÌC) and leg blood flow (QÌLEG) can be measured simultaneously with high accuracy using transpulmonary and femoral vein thermodilution with a single-bolus injection. The invasive measure has offered important insight into leg hemodynamics and blood flow distribution during exercise. Despite being the natural modality of exercise in humans, there has been no direct measure of QÌLEG while running in humans. We sought to determine the feasibility of the thermodilution technique for measuring QÌLEG and conductance during high-intensity running, in an exploratory case study. A trained runner (30 years male) completed two maximal incremental tests on a cycle ergometer and motorized treadmill. QÌLEG and QÌC were determined using the single-bolus thermodilution technique. Arterial and venous blood were sampled throughout exercise, with continuous monitoring of metabolism, intra-arterial and venous pressure, and temperature. The participant reached a greater peak oxygen uptake (VÌO2peak) during running relative to cycling (74 vs. 68 mL/kg/min) with comparable QÌLEG (19.0 vs. 19.5 L/min) and QÌC (27.4 vs. 26.2 L/min). Leg vascular conductance was greater during high-intensity running relative to cycling (82 vs. 70 mL/min/mmHg @ ~80% VÌO2peak). The "beat phenomenon" was apparent in femoral flow while running, producing large gradients in conductance (62-90 mL/min/mmHg @ 70% VÌO2peak). In summary, we present the first direct measure of QÌLEG and conductance in a running human. Our findings corroborate several assumptions about QÌLEG during running compared with cycling. Importantly, we demonstrate that using thermodilution in running exercise can be completed effectively and safely.
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Débito Cardíaco , Perna (Membro) , Consumo de Oxigênio , Fluxo Sanguíneo Regional , Corrida , Termodiluição , Humanos , Termodiluição/métodos , Débito Cardíaco/fisiologia , Corrida/fisiologia , Masculino , Perna (Membro)/irrigação sanguínea , Perna (Membro)/fisiologia , Adulto , Consumo de Oxigênio/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Teste de Esforço/métodosRESUMO
Harmful algal blooms (HABs) or higher levels of de facto water reuse (DFR) can increase the levels of certain contaminants at drinking water intakes. Therefore, the goal of this study was to use multi-class supervised machine learning (SML) classification with data collected from six online instruments measuring fourteen total water quality parameters to detect cyanobacteria (corresponding to approximately 950 cells/mL, 2900 cells/mL, and 8600 cells/mL) or DFR (0.5, 1 and 2 % of wastewater effluent) events in the raw water entering an intake. Among 56 screened models from the caret package in R, four (mda, LogitBoost, bagFDAGCV, and xgbTree) were selected for optimization. mda had the greatest testing set accuracy, 98.09 %, after optimization with 7 false alerts. Some of the most important water parameters for the different models were phycocyanin-like fluorescence, UVA254, and pH. SML could detect algae blending events (estimated <9000 cells/mL) due in part to the phycocyanin-like fluorescence sensor. UVA254 helped identify higher concentrations of DFR. These results show that multi-class SML classification could be used at drinking water intakes in conjunction with online instrumentation to detect and differentiate HABs and DFR events. This could be used to create alert systems for the water utilities at the intake, rather than the finished water, so any adjustment to the treatment process could be implemented.
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Cianobactérias , Água Potável , Monitoramento Ambiental , Aprendizado de Máquina , Água Potável/microbiologia , Monitoramento Ambiental/métodos , Proliferação Nociva de Algas , Qualidade da Água , Purificação da ÁguaRESUMO
As water treatment technology has improved, the amount of available process data has substantially increased, making real-time, data-driven fault detection a reality. One shortcoming of the fault detection literature is that methods are usually evaluated by comparing their performance on hand-picked, short-term case studies, which yields no insight into long-term performance. In this work, we first evaluate multiple statistical and machine learning approaches for detrending process data. Then, we evaluate the performance of a PCA-based fault detection approach, applied to the detrended data, to monitor influent water quality, filtrate quality, and membrane fouling of an ultrafiltration membrane system for indirect potable reuse. Based on two short case studies, the adaptive lasso detrending method is selected, and the performance of the multivariate approach is evaluated over more than a year. The method is tested for different sets of three critical tuning parameters, and we find that for long-term, autonomous monitoring to be successful, these parameters should be carefully evaluated. However, in comparison with industry standards of simpler, univariate monitoring or daily pressure decay tests, multivariate monitoring produces substantial benefits in long-term testing.
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Per- and polyfluoroalkyl substances (PFAS) enter surface waters from various sources such as wastewater treatment plants, fire-fighting sites, and PFAS-producing and PFAS-using industries. The Las Vegas Wash in Southern Nevada of the United States (U.S.) conveys wastewater effluent from the Las Vegas metropolitan area to Lake Mead, a drinking water source for millions of people in the U.S. Southwest. PFAS have previously been detected in the Las Vegas Wash, but PFAS sources were not identified. In this study, upstream wash tributaries, wastewater treatment effluents, and shallow groundwater wells were sampled in multiple campaigns during dry-weather conditions to investigate possible PFAS sources. Out of 19 PFAS, two short-chain PFAS-perfluoropentanoic acid (48 % of the total molar concentration) and perfluorohexanoic acid (32 %)-comprised the majority of PFAS loading measured in the Las Vegas Wash, followed by perfluorooctanoic acid (9 %). On a mass loading basis, the majority of total measured PFAS (approximately 90 %) and at least 48 % of each specific PFAS in the Las Vegas Wash likely entered via municipal wastewater effluents, of which the main source was likely residential wastewater. One of the drainage areas with a major civilian airport was identified as a potential source of relatively enriched perfluorosulfonic acids to a small wash tributary and shallow groundwater samples. Nonetheless, that tributary contributed at most 15 % of any specific PFAS to the mainstem of the Las Vegas Wash. Total PFAS concentrations were relatively low for the small tributary associated with an urban smaller airport and the lack of flow in the tributary channel immediately downgradient of an Air Force base indicates the smaller airport and base were unlikely significant PFAS sources to the Las Vegas Wash. Overall, this study demonstrated effective PFAS source investigation methodology and the importance of wastewater effluent as a PFAS environmental pathway.
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X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but it is difficult to implement due to the competing requirements of X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while addressing the limitations of conventional tomography tools. The instrument combines the electron beam of a scanning electron microscope (SEM) with the precise, broadband X-ray detection of a superconducting transition-edge sensor (TES) microcalorimeter. The electron beam generates a highly focused X-ray spot on a metal target held micrometers away from the sample of interest, while the TES spectrometer isolates target photons with a high signal-to-noise ratio. This combination of a focused X-ray spot, energy-resolved X-ray detection, and unique system geometry enables nanoscale, element-specific X-ray imaging in a compact footprint. The proof of concept for this approach to X-ray nanotomography is demonstrated by imaging 160 nm features in three dimensions in six layers of a Cu-SiO2 integrated circuit, and a path toward finer resolution and enhanced imaging capabilities is discussed.
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INTRODUCTION: This study aimed to explore the potential impact of incorporating blood flow restriction (BFR) training within a training block characterized by minimal high-intensity work on 2000-m rowing ergometer time trial (TT) performance in elite/world-class rowers. Physiological markers often associated with endurance performance (maximal aerobic capacity, VÌO 2max ; blood lactate thresholds and hemoglobin mass, Hb mass ) were measured to determine whether changes are related to an improvement in performance. METHODS: Using a quasi-experimental, observational study design (no control group), 2000-m TT performance, VÌO 2max , submaximal work rates eliciting blood lactate concentrations of ~2 and ~4 mmol·L -1 , and Hb mass were measured before and after 4 wk of noncompetitive season training, which included BFR rowing. BFR training consisted of 11 sessions of 2 × 10 min of BFR rowing at a workload equating to blood lactate concentrations of ~2 mmol·L -1 . Paired t -tests were used to compare pre-/postvalues, and Pearson correlation was used to examine whether physiological changes were associated with changes to TT performance. RESULTS: TT performance improved in both female (1.09% ± 1.2%, ~4.6 ± 5.2 s; P < 0.01) and male (1.17% ± 0.48%, ~4.5 ± 1.9 s; P < 0.001) athletes. VÌO 2max increased in female rowers only ( P < 0.01), but both sexes had an increase in work rates eliciting blood lactate concentrations of 2 mmol·L -1 (female: 184 ± 16 to 195 ± 15 W, P < 0.01; male: 288 ± 23 to 317 ± 26 W, P = 0.04) and 4 mmol·L -1 (female: 217 ± 13 to 227 ± 14 W, P = 0.02; male: 339 ± 43 to 364 ± 39 W, P < 0.01). No changes in Hb mass (both sexes, P = 0.8) were observed. Improvements in TT performance were not related to physiological changes (all correlations P ≥ 0.2). CONCLUSIONS: After 4 wk of training with BFR, the improvement in TT performance was greater than what is typical for this population. Physiological variables improved during this training block but did not explain improved TT performance.
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Desempenho Atlético , Ácido Láctico , Consumo de Oxigênio , Esportes Aquáticos , Humanos , Feminino , Masculino , Ácido Láctico/sangue , Esportes Aquáticos/fisiologia , Desempenho Atlético/fisiologia , Consumo de Oxigênio/fisiologia , Hemoglobinas/metabolismo , Hemoglobinas/análise , Adulto Jovem , Condicionamento Físico Humano/métodos , Condicionamento Físico Humano/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Resistência Física/fisiologia , AdultoRESUMO
PURPOSE: To characterize and compare female ice hockey players' peak skating speed and acceleration ability during linear sprints and gameplay. We also sought to quantify the time spent at various speeds and the frequency of accelerations at different thresholds during games. METHODS: Seventeen varsity-level female ice hockey players (20 [1.4] y, 68.9 [4.9] kg, 167.6 [4.7] cm) participated in an on-ice practice session (performing 3 × 40-m linear sprints) and 4 regular-season games while being monitored using a local positioning system. Speed and acceleration were recorded from the sprint and within-game monitoring. Time on ice spent in relative skating speed zones and the frequency of accelerations at different intensities were recorded. RESULTS: Players' greatest peak speeds (29.5 [1.3] vs 28.3 [1.1] km/h) and accelerations (4.39 [0.48] vs 3.34 [0.36] m/s2) reached during gameplay were higher than those reached in linear sprinting (both P < .01). Peak in-game values were moderately predicted by linear sprint values for speed (r = .69, P < .01) but not for acceleration (r < .01, P = .95). Players spent little time at near-peak linear sprint speeds (≥80% [22.7 km/h], â¼3% time on ice; ≥90% [25.5 km/h], <1% of time on ice) during gameplay. However, 26% to 35% of accelerations recorded during the 4 games were ≥90% of linear sprint acceleration. CONCLUSIONS: Although skating speed may be advantageous in specific game situations, our results suggest that players spend little time at near-maximal speeds while accelerating frequently during games. This warrants further investigation of direction changes, skating transitions, repeated sprints, and other determinant variables potentially related to on-ice success and the implementation of training strategies to improve repeated acceleration or qualities beyond maximal skating speed.
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Aceleração , Desempenho Atlético , Hóquei , Corrida , Humanos , Hóquei/fisiologia , Feminino , Desempenho Atlético/fisiologia , Adulto Jovem , Corrida/fisiologia , Sistemas de Informação Geográfica , Estudos de Tempo e Movimento , Fatores de TempoRESUMO
PURPOSE: The purpose of this study is to characterize both the efficacy of altered restriction pressures and consequences of optimized blood flow restriction (BFR) for altering the cardiovascular and fluid regulating response in humans. METHODS: This work comprised a series of related trials. Phase 1: during semi-recumbent cycling (5 min, 60 W) with BFR at 0%, 50%, 75%, 100%, and 125% of participants' lowest arterial occlusion pressure (LOP) echocardiographic images were collected alongside continuous heart rate (HR) and blood pressure (BP). In phase 2, 24 h fluid balance (intake-output) and fluid-regulating hormone responses were measured after a practical BFR exercise session (treadmill walking: 5·3 min, 1 min rest, 5 km·h -1 , 5% incline, 100% LOP). Phase 3 examined the magnitude and effect of blood volume distribution following BFR treadmill walking using a modified CO-rebreathe technique. RESULTS: Cardiac ejection fraction remained stable irrespective of cuff pressure and despite a reduction in end-diastolic volume (Δ of 11 ± 9 mL, P = 0.02). HR and BP were highest at 100% LOP (ΔHR = 18 ± 19 bpm, ΔSBP = 51 ± 30 mm Hg, ΔDBP = 33 ± 15 mm Hg, ΔRate Pressure Product = 76 ± 32 bpm·mm Hg·100 -1 ). BFR treadmill walking stimulated a greater release of fluid-regulating hormones than normal walking (Δrenin = BFR: 25.3 ± 24.2 vs CON: 9.1 ± 11.8 ng·L -1 ; Δcopeptin = BFR: 50.1 ± 97.9 vs. CON: 0.43 ± 0.8 pmol·L -1 ), but no difference in fluid retention was observed ( P = 0.2). Approximately 27% of total blood volume was confined to the legs during BFR, but the relative volume trapped in the legs was not related to fluid-regulating hormone release (renin r = -0.04, P = 0.9; copeptin r = 0.27, P = 0.3). CONCLUSIONS: BFR exercise elicits the largest cardiovascular effect using 100% LOP, with evidence of appreciable fluid regulating hormonal response during a typical BFR exercise session. The relative volume of blood sequestered in the limb does not appear to drive this response.
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Terapia de Restrição de Fluxo Sanguíneo , Treinamento Resistido , Humanos , Exercício Físico/fisiologia , Hemodinâmica/fisiologia , Pressão Sanguínea/fisiologia , Hormônios , Fluxo Sanguíneo Regional/fisiologia , Músculo Esquelético/fisiologia , Treinamento Resistido/métodosRESUMO
PURPOSE: The purpose of the study was to investigate whether carbohydrate utilization is altered during exercise in overreached endurance athletes and examine the utility of continuous glucose monitors (CGM) to detect overreaching status. METHODS: Eleven endurance athletes (M:8, F:3) completed a 5-week training block consisting of 1 week of reduced training (PRE), 3 weeks of high-intensity overload training (POST), and 1 week of recovery training (REC). Participants completed a Lamberts and Lambert Submaximal Cycling Test (LSCT) and 5 km time-trial at PRE, POST, and REC time points, 15 min following the ingestion of a 50 g glucose beverage with glucose recorded each minute via CGM. RESULTS: Performance in the 5 km time-trial was reduced at POST (∆-7 ± 10 W, p = 0.04, η p 2 = 0.35) and improved at REC (∆12 ± 9 W from PRE, p = 0.01, η p 2 = 0.66), with reductions in peak lactate (∆-3.0 ± 2.0 mmol/L, p = 0.001, η p 2 = 0.71), peak HR (∆-6 ± 3 bpm, p < 0.001, η p 2 = 0.86), and Hooper-Mackinnon well-being scores (∆10 ± 5 a.u., p < 0.001, η p 2 = 0.79), indicating athletes were functionally overreached. The respiratory exchange ratio was suppressed at POST relative to REC during the 60% (POST: 0.80 ± 0.05, REC: 0.87 ± 0.05, p < 0.001, η p 2 = 0.74), and 80% (POST: 0.93 ± 0.05, REC: 1.00 ± 0.05, p = 0.003, η p 2 = 0.68) of HR-matched submaximal stages of the LSCT. CGM glucose was reduced during HR-matched submaximal exercise in the LSCT at POST (p = 0.047, η p 2 = 0.36), but not the 5 km time-trial (p = 0.07, η p 2 = 0.28) in overreached athletes. CONCLUSION: This preliminary investigation demonstrates a reduction in CGM-derived glucose and carbohydrate oxidation during submaximal exercise in overreached athletes. The use of CGM during submaximal exercise following standardized nutrition could be employed as a monitoring tool to detect overreaching in endurance athletes.
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Exercício Físico , Resistência Física , Humanos , Glicemia , Glucose , AtletasRESUMO
OBJECTIVES: To analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). METHODS: For the present study, the following variables were selected for harmonization and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD. RESULTS: The results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. CONCLUSIONS: For the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.
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Poluentes Atmosféricos , Poluição do Ar , Síndrome de Sjogren , Xerostomia , Humanos , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Material Particulado/efeitos adversos , Material Particulado/análise , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/etiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análiseRESUMO
OBJECTIVES: To analyse how the key components at the time of diagnosis of the Sjögren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. METHODS: For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. RESULTS: After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. CONCLUSIONS: Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjögren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.
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Síndromes do Olho Seco , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/complicações , FenótipoRESUMO
Females generally have smaller blood pressure (BP) responses to isolated muscle mechanoreflex and metaboreflex activation compared with males, which may explain sex differences in BP responses to voluntary exercise. The mechanoreflex may be sensitized during exercise, but whether mechanoreflex-metaboreflex interactions differ by sex or variations in sex hormones remains unknown. Thirty-one young healthy subjects (females, n = 16) performed unilateral passive cycling (mechanoreflex), active cycling (40% peak Watts), postexercise circulatory occlusion (PECO; metaboreflex), and passive cycling combined with PECO (combined mechanoreflex and metaboreflex activation). Beat-to-beat BP, heart rate, inactive leg vascular conductance, and active leg muscle oxygenation were measured. Ten females underwent exploratory testing during low- and high-hormone phases of their self-reported menstrual cycle or oral contraceptive use. Systolic BP and heart rate responses did not differ between sexes during active cycling [Δ30 ± 9 vs. 29 ± 11 mmHg (males vs. females), P = 0.9; Δ33 ± 8 vs. 35 ± 6 beats/min, P = 0.4] or passive cycling with PECO (Δ26 ± 11 vs. 21 ± 10 mmHg, P = 0.3; Δ14 ± 7 vs. 18 ± 15 beats/min, P = 0.3). Passive cycling with PECO revealed additive, not synergistic, effects for systolic BP [males: Δ23 ± 14 vs. 26 ± 11 mmHg (sum of isolated passive cycling and PECO vs. combined activation); females: Δ26 ± 11 vs. 21 ± 12 mmHg, interaction P = 0.05]. Results were consistent in subset analyses with sex differences in active cycling BP (P > 0.1) and exploratory analyses of hormone phase (P > 0.4). Despite a lack of statistical equivalence, no differences in cardiovascular responses were found during combined mechanoreflex-metaboreflex activation between sexes or hormone levels. These results provide preliminary data regarding the involvement of muscle mechanoreflex-metaboreflex interactions in mediating sex differences in voluntary exercise BP responses.NEW & NOTEWORTHY The muscle mechanoreflex may be sensitized by metabolites during exercise. We show that cardiovascular responses to combined mechanoreflex (passive cycling) and metaboreflex (postexercise circulatory occlusion) activation are primarily additive and do not differ between males and females, or across variations in sex hormones in females. Our findings provide new insight into the contributions of muscle mechanoreflex-metaboreflex interactions as a cause for prior reports that females have smaller blood pressure responses to voluntary exercise.
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Sistema Cardiovascular , Humanos , Feminino , Adulto , Masculino , Músculo Esquelético/fisiologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca , Hormônios , Hormônios Esteroides Gonadais/metabolismo , Reflexo/fisiologia , Força da MãoAssuntos
Eritropoetina , Cetose , Humanos , Cetonas , Corpos Cetônicos , Suplementos Nutricionais , Eritropoetina/farmacologiaRESUMO
Biallelic hypomorphic variants in PRORP have been recently described as causing the autosomal recessive disorder combined oxidative phosphorylation deficiency type 54 (COXPD54). COXPD54 encompasses a phenotypic spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy. Here, we report three additional families with homozygous missense PRORP variants with pleiotropic phenotypes. Each missense variant altered a highly conserved residue within the metallonuclease domain. In vitro mitochondrial tRNA processing assays with recombinant TRMT10C, SDR5C1 and PRORP indicated two COXPD54-associated PRORP variants, c.1159A>G (p.Thr387Ala) and c.1241C>T (p.Ala414Val), decreased pre-tRNAIle cleavage, consistent with both variants impacting tRNA processing. No significant decrease in tRNA processing was observed with PRORP c.1093T>C (p.Tyr365His), which was identified in an individual with leukodystrophy. These data provide independent evidence that PRORP variants are associated with COXPD54 and that the assessment of 5' leader mitochondrial tRNA processing is a valuable assay for the functional analysis and clinical interpretation of novel PRORP variants.
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Perda Auditiva Neurossensorial , Doenças Mitocondriais , Ribonuclease P , Feminino , Humanos , Genótipo , Perda Auditiva Neurossensorial/genética , Homozigoto , Doenças Mitocondriais/genética , RNA de Transferência , Ribonuclease P/genéticaRESUMO
FARS2 encodes the mitochondrial phenylalanyl-tRNA synthetase (mtPheRS), which is essential for charging mitochondrial (mt-) tRNAPhe with phenylalanine for use in intramitochondrial translation. Many biallelic, pathogenic FARS2 variants have been described previously, which are mostly associated with two distinct clinical phenotypes; an early onset epileptic mitochondrial encephalomyopathy or a later onset spastic paraplegia. In this study, we report on a patient who presented at 3 weeks of age with tachypnoea and poor feeding, which progressed to severe metabolic decompensation with lactic acidosis and seizure activity followed by death at 9 weeks of age. Rapid trio whole exome sequencing identified compound heterozygous FARS2 variants including a pathogenic exon 2 deletion on one allele and a rare missense variant (c.593G > T, p.(Arg198Leu)) on the other allele, necessitating further work to aid variant classification. Assessment of patient fibroblasts demonstrated severely decreased steady-state levels of mtPheRS, but no obvious defect in any components of the oxidative phosphorylation system. To investigate the potential pathogenicity of the missense variant, we determined its high-resolution crystal structure, demonstrating a local structural destabilization in the catalytic domain. Moreover, the R198L mutation reduced the thermal stability and impaired the enzymatic activity of mtPheRS due to a lower binding affinity for tRNAPhe and a slower turnover rate. Together these data confirm the pathogenicity of this FARS2 variant in causing early-onset mitochondrial epilepsy.
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Epilepsia , Doenças Mitocondriais , Fenilalanina-tRNA Ligase , Humanos , Lactente , Recém-Nascido , Epilepsia/patologia , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Mutação , Fenilalanina-tRNA Ligase/genética , Fenilalanina-tRNA Ligase/química , RNA de Transferência/genética , RNA de Transferência de Fenilalanina/metabolismoRESUMO
BACKGROUND: Manufacturing methods for dimethyl sulfoxide (DMSO)-cryopreserved platelets (CPPs) are manual and labor intensive. Thawing and prepare-for-transfusion steps are in an open system that requires transfusion within 4 h. A fill-and-finish system (CUE) can automate the manufacturing process. A newly configured bag system allows freezing, thawing, and use of resuspension solutions while maintaining the functionally closed system, and extending the post-thaw shelf life beyond 4 h. Our objective is to evaluate the feasibility of the CUE system and the functionally closed bag system. STUDY DESIGN AND METHODS: DMSO was volumetrically added to double-dose apheresis platelets, concentrated, and delivered to a 50- or 500-mL ethylene-vinyl acetate (EVA) bag by the CUE (n = 12). The functionally closed bag system contained 25 mL platelet additive solution 3 (PAS-3) in a 50-mL EVA bag. Control CPP (n = 2) were manually prepared. PAS-3 and CPP were thawed together. CPP were stored up to 98 h (20-24°C) and tested using a standard assay panel. RESULTS: CUE prepared CPP met the design targets: volume, platelet content, and DMSO concentration. CUE CPP P-selectin was high. CD42b, phosphatidylserine (PS) expression, and live cell percentage were favorable compared to controls and favorably maintained over storage. The thrombin generation potency was slightly reduced compared to controls. The 50 mL EVA bag maintained pH for up to 30 h, and the 500 mL EVA bag beyond 76 h. DISCUSSION: The CUE system presents a technically feasible method to prepare CPP. A functionally closed bag system with resuspension solution was successful and can extend the post-thaw storage time of CPP.
Assuntos
Plaquetas , Dimetil Sulfóxido , Humanos , Dimetil Sulfóxido/farmacologia , Estudos de Viabilidade , Plaquetas/metabolismo , Criopreservação/métodos , Transfusão de Plaquetas , Preservação de Sangue/métodosRESUMO
BACKGROUND: Compared to vertebral body fusion, artificial discs are thought to lessen the risks of adjacent segment disease and the need for additional surgery by maintaining spinal mobility as they mimic the intervertebral disc structure. No studies have compared the rates of postoperative complications and the requirement for secondary surgery at adjacent segments among patients who have undergone anterior lumbar interbody fusions (ALIF) versus those undergoing lumbar arthroplasty. METHODS: An all-payer claims database identified 11,367 individuals who underwent single-level ALIF and lumbar arthroplasty for degenerative disc disease (DDD) between January 2010 and October 2020. Rates of complications following surgery, the need for additional lumbar surgeries, length of stay (LOS), and postoperative opioid utilization were assessed in matched cohorts based on logistic regression models. Kaplan-Meyer plots were created to model the probability of additional surgery. RESULTS: Following 1:1 exact matching, 846 records of patients who had undergone ALIF or lumbar arthroplasty were analyzed. All-cause readmission within 30-30 days following surgery was significantly higher in patients undergoing ALIF versus arthroplasty (2.6% vs. 0.71%, p = 0.02). LOS was significantly lower among the patients who had undergone ALIF (1.043 ± 0.21 vs. 2.17 ± 1.7, p < .001). CONCLUSIONS: ALIF and lumbar arthroplasty procedures are equally safe and effective in treating DDD. Our findings do not support that single-level fusions may biomechanically necessitate revisional surgeries.
Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Disco Intervertebral , Fusão Vertebral , Humanos , Degeneração do Disco Intervertebral/complicações , Disco Intervertebral/cirurgia , Região Lombossacral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Artroplastia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The use of Gastrografin (GG) in the management of adhesive small bowel obstruction (SBO) has been shown to decrease the length of stay and operative intervention. METHODS: This retrospective cohort study examined patients with an SBO diagnosis prior to implementation (PRE, January 2017-January 2019) and following implementation (POST, January 2019-May 2021) of a GG challenge order set made available across 9 hospitals within a health care system. Primary outcomes were utilization of the order set across facilities and over time. Secondary outcomes included time to surgery for operative patients, rate of surgery, nonoperative length of stay, and 30-day readmission. Standard descriptive, univariate, and multivariable regression analyses were performed. RESULTS: PRE cohort had 1746 patients and POST had 1889. The utilization of GG increased from 14% to 49.5% following implementation. Significant variability existed within the hospital system with utilization at each individual hospital from 11.5% to 60%. There was an increase in surgical intervention (13.9% vs 16.4%, P = .04) and decrease in nonoperative LOS (65.6 vs 59.9 hours, P < .001) following implementation. For POST patients, multivariable linear regression showed significant reduction in nonoperative length of stay (-23.1 hours, P < .001) but no significant difference in time to surgery (-19.6 hours, P = .08). DISCUSSION: The availability of a standardized order set for SBO can result in increased Gastrografin administration across hospital settings. The implementation of a Gastrografin order set was associated with decreased length of stay in nonoperative patients.