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1.
J Cardiothorac Surg ; 19(1): 320, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840211

RESUMO

BACKGROUND: Pre-operative coronary angiography and concomitant, planned coronary artery bypass are infrequently performed with type A aortic dissection repair. We present a case in which pre-operative coronary computed tomography angiography was appropriate, and subsequent dissection repair and concomitant coronary artery bypass were successfully performed. CASE PRESENTATION: The patient is a 58-year-old male with heart failure with preserved ejection fraction, renal insufficiency, hypertension, obesity, and smoking history, who presented with a three-to-four-day history of persistent back pain, worsening exertional dyspnea, and orthopnea, as well as a two-to-three month history of dyspnea, lower extremity edema, and intermittent angina. He was diagnosed with an acute type A aortic dissection and anti-impulse control was initiated. However, repair was delayed in order to allow apixaban to metabolize and decrease the risk of bleeding, as the patient was approximately six days post-dissection, without malperfusion, with a well-controlled blood pressure on anti-impulse therapy, and had received five days of anticoagulation. During this time, coronary computed tomography angiography was performed to assess the need for concomitant revascularization and showed coronary artery disease. Ascending aorta hemiarch replacement with aortic valve resuspension, two-vessel coronary artery bypass grafting, and left atrial appendage clipping were performed successfully. CONCLUSIONS: Pre-operative imaging can be considered in a select group of acute type A aortic dissections that present without malperfusion, and with well-controlled blood pressure on anti-impulse/negative inotropic therapy.


Assuntos
Dissecção Aórtica , Ponte de Artéria Coronária , Humanos , Masculino , Pessoa de Meia-Idade , Dissecção Aórtica/cirurgia , Dissecção Aórtica/complicações , Ponte de Artéria Coronária/métodos , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença Aguda , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/complicações
2.
World J Emerg Surg ; 19(1): 22, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851700

RESUMO

Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs.


Assuntos
Infecções Intra-Abdominais , Humanos , Infecções Intra-Abdominais/tratamento farmacológico , Fatores de Risco , Antibacterianos/uso terapêutico
3.
iScience ; 27(6): 109822, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38827409

RESUMO

The diffusion-driven Turing instability is a potential mechanism for spatial pattern formation in numerous biological and chemical systems. However, engineering these patterns and demonstrating that they are produced by this mechanism is challenging. To address this, we aim to solve the inverse problem in artificial and experimental Turing patterns. This task is challenging since patterns are often corrupted by noise and slight changes in initial conditions can lead to different patterns. We used both least squares to explore the problem and physics-informed neural networks to build a noise-robust method. We elucidate the functionality of our network in scenarios mimicking biological noise levels and showcase its application using an experimentally obtained chemical pattern. The findings reveal the significant promise of machine learning in steering the creation of synthetic patterns in bioengineering, thereby advancing our grasp of morphological intricacies within biological systems while acknowledging existing limitations.

4.
J Am Chem Soc ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837941

RESUMO

The absolute band edge positions and work function (Φ) are the key electronic properties of metal oxides that determine their performance in electronic devices and photocatalysis. However, experimental measurements of these properties often show notable variations, and the mechanisms underlying these discrepancies remain inadequately understood. In this work, we focus on ceria (CeO2), a material renowned for its outstanding oxygen storage capacity, and combine theoretical and experimental techniques to demonstrate environmental modifications of its ionization potential (IP) and Φ. Under O-deficient conditions, reduced ceria exhibits a decreased IP and Φ with significant sensitivity to defect distributions. In contrast, the IP and Φ are elevated in O-rich conditions due to the formation of surface peroxide species. Surface adsorbates and impurities can further augment these variabilities under realistic conditions. We rationalize the shifts in energy levels by separating the individual contributions from bulk and surface factors, using hybrid quantum mechanical/molecular mechanical (QM/MM) embedded-cluster and periodic density functional theory (DFT) calculations supported by interatomic-potential-based electrostatic analyses. Our results highlight the critical role of on-site electrostatic potentials in determining the absolute energy levels in metal oxides, implying a dynamic evolution of band edges under catalytic conditions.

5.
J Strength Cond Res ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38838212

RESUMO

ABSTRACT: Lockie, RG, Orr, RM, Sanchez, KJ, Gonzales, SM, Viramontes, E, Kennedy, K, and Dawes, JJ. Relationships between physical ability test performance and fitness in recruits from a southeastern U.S. police department. J Strength Cond Res XX(X): 000-000, 2024-Police recruit occupational ability may be predicted by a physical ability test (PAT). This study determined relationships between a department-specific PAT and fitness test performance among police recruits. Retrospective analysis was conducted on recruit data (1,069 men and 404 women) from one department collected during 2005-2009 and 2016-2020. The following data were provided: grip strength; sit-and-reach; 60-second push-ups; 60-second sit-ups; 2.4-km run; and the PAT. The PAT involved exiting a vehicle and opening the trunk; running ∼201 m; completing an obstacle course; dragging a 68-kg dummy 31 m; completing an obstacle course and running ∼201 m; dry firing a weapon 6 times with each hand; and trunk item placement and vehicle reentry. Relationships between the PAT and fitness tests were measured by partial correlations and stepwise linear regression, both controlling for sex. The PAT was completed in a mean time of 4:16 ± 1:07 minutes:seconds. The PAT significantly (p < 0.001) related to all fitness tests. Moderate relationships were found for push-ups (r = -0.35), sit-ups (r = -0.41), and the 2.4-km run (r = -0.43). Small relationships were found with grip strength (r = -0.19) and the sit-and-reach (r = -0.17). The final regression model, which included sex and all fitness tests except the sit-and-reach, explained ∼53% of the variance. Sex and the 2.4-km run explained ∼47% of the variance. Aerobic fitness appeared to have the greatest impact on PAT performance, which may have related to the PAT design and duration. Tasks completed in succession, and the use of a relatively light dummy, may stress aerobic fitness and muscular endurance to a greater extent.

7.
Carbohydr Polym ; 339: 122264, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823928

RESUMO

Normal rice starch consists of amylopectin and amylose, whose relative amounts and chain-length distributions (CLDs) are major determinants of the digestibility and rheology of cooked rice, and are related to metabolic health and consumer preference. Here, the mechanism of how molecular structural features of pure amylopectin (waxy) starches affect starch properties was explored. Following debranching, chain-length distributions of seven waxy varieties were measured using size-exclusion chromatography, and parameterized using biosynthesis-based models, which involve breaking up the chain-length distribution into contributions from five enzyme sets covering overlapping ranges of chain length; structure-property correlations involving the fifth set were found to be statistically significant. Digestibility was measured in vitro, and parameters for the slower and longer digestion phase quantified using non-linear least-squares fitting. The coefficient for the significant correlation involving amylopectin fine structure for the fifth set was -0.903, while the amounts of amylopectin short and long chains were found to dominate breakdown viscosity (correlation coefficients 0.801 and - 0.911, respectively). This provides a methodology for finding or developing healthier starch in terms of lower digestion rate, while also having acceptable palatability. As rice breeders can to some extent control CLDs, this can help the development of waxy rices with improved properties.


Assuntos
Amilopectina , Amilose , Oryza , Oryza/química , Amilopectina/química , Viscosidade , Amilose/química , Amilose/análise , Amido/química , Digestão , Reologia
8.
Inorg Chem ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836624

RESUMO

We expand upon the synthetic utility of anionic rhenium complex Na[(BDI)ReCp] (1, BDI = N,N'-bis(2,6-diisopropylphenyl)-3,5-dimethyl-ß-diketiminate) to generate several rhenium-phosphorus complexes. Complex 1 reacts in a metathetical manner with chlorophosphines Ph2PCl, MeNHP-Cl, and OHP-Cl to generate XL-type phosphido complexes 2, 3, and 4, respectively (MeNHP-Cl = 2-chloro-1,3-dimethyl-1,3,2-diazaphospholidine; OHP-Cl = 2-chloro-1,3,2-dioxaphospholane). Crystallographic and computational investigations of phosphido triad 2, 3, and 4 reveal that increasing the electronegativity of the phosphorus substituent (C < N < O) results in a shortening and strengthening of the rhenium-phosphorus bond. Complex 1 reacts with iminophosphane Mes*NPCl (Mes* = 2,4,6-tritert-butylphenyl) to generate linear iminophosphanyl complex 5. In the presence of a suitable halide abstraction reagent, 1 reacts with the dichlorophosphine iPr2NPCl2 to afford cationic phosphinidene complex 6+. Complex 6+ may be reduced by one electron to form 6•, a rare example of a stable, paramagnetic phosphinidene complex. Spectroscopic and structural investigations, as well as computational analyses, are employed to elucidate the influence of the phosphorus substituent on the nature of the rhenium-phosphorus bond in 2 through 6. Furthermore, we examine several common analogies employed to understand metal phosphido, phosphinidene, and iminophosphanyl complexes.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38833135

RESUMO

PURPOSE OF REVIEW: Management of meniscal injuries in the elite athlete is a difficult problem secondary to the high demands of athletic competition, the need for a timely return to sport, and the desire to maximize performance over time. The purpose of this review is to provide an up-to-date summary on the current literature and trends regarding the management of meniscus injuries with a special consideration for elite athletes. RECENT FINDINGS: Historically, partial meniscectomy has been the primary treatment option for meniscus injuries. However, in recent years there has been an increased emphasis on meniscus preservation due to the increased risk of cartilage degeneration over time. Moreover, while partial meniscectomy still provides a quicker return to sport (RTS), recent literature has demonstrated similar rates of RTS and return to pre-injury levels between partial meniscectomy and meniscus repair. In the setting of symptomatic meniscal deficiency, meniscus allograft transplantation has become an increasingly utilized salvage procedure with promising yet variable outcomes on the ability to withstand elite competition. Currently, there is no uniform approach to treating meniscal injuries in elite athletes. Therefore, an individualized approach is required with consideration of the meniscus tear type, location, concomitant injuries, athlete expectations, rehabilitation timeline, and desire to prevent or delay knee osteoarthritis. In athletes with anatomically repairable tears, meniscus repair should be performed given the ability to restore native anatomy, provide high rates of RTS, and mitigate long-term chondral damage. However, partial meniscectomy can be indicated for unrepairable tears.

10.
PLoS One ; 19(6): e0303756, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38829903

RESUMO

The rapid spread of highly pathogenic avian influenza (HPAI) A (H5N1) viruses in Southeast Asia in 2004 prompted the New Zealand Ministry for Primary Industries to expand its avian influenza surveillance in wild birds. A total of 18,693 birds were sampled between 2004 and 2020, including migratory shorebirds (in 2004-2009), other coastal species (in 2009-2010), and resident waterfowl (in 2004-2020). No avian influenza viruses (AIVs) were isolated from cloacal or oropharyngeal samples from migratory shorebirds or resident coastal species. Two samples from red knots (Calidris canutus) tested positive by influenza A RT-qPCR, but virus could not be isolated and no further characterization could be undertaken. In contrast, 6179 samples from 15,740 mallards (Anas platyrhynchos) tested positive by influenza A RT-qPCR. Of these, 344 were positive for H5 and 51 for H7. All H5 and H7 viruses detected were of low pathogenicity confirmed by a lack of multiple basic amino acids at the hemagglutinin (HA) cleavage site. Twenty H5 viruses (six different neuraminidase [NA] subtypes) and 10 H7 viruses (two different NA subtypes) were propagated and characterized genetically. From H5- or H7-negative samples that tested positive by influenza A RT-qPCR, 326 AIVs were isolated, representing 41 HA/NA combinations. The most frequently isolated subtypes were H4N6, H3N8, H3N2, and H10N3. Multivariable logistic regression analysis of the relations between the location and year of sampling, and presence of AIV in individual waterfowl showed that the AIV risk at a given location varied from year to year. The H5 and H7 isolates both formed monophyletic HA groups. The H5 viruses were most closely related to North American lineages, whereas the H7 viruses formed a sister cluster relationship with wild bird viruses of the Eurasian and Australian lineages. Bayesian analysis indicates that the H5 and H7 viruses have circulated in resident mallards in New Zealand for some time. Correspondingly, we found limited evidence of influenza viruses in the major migratory bird populations visiting New Zealand. Findings suggest a low probability of introduction of HPAI viruses via long-distance bird migration and a unique epidemiology of AIV in New Zealand.


Assuntos
Animais Selvagens , Aves , Influenza Aviária , Filogenia , Animais , Nova Zelândia/epidemiologia , Influenza Aviária/virologia , Influenza Aviária/epidemiologia , Animais Selvagens/virologia , Aves/virologia , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza A/classificação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Genoma Viral , Patos/virologia
11.
3D Print Addit Manuf ; 11(2): 485-495, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38689910

RESUMO

Multimaterial additive manufacturing is expanding the design space realizable with 3D printing, yet is largely constrained to sequential deposition of each individual material. The ability to coextrude two materials and change the ratio of materials while printing would enable custom-tailored polymer composites. Here, the evolution of a dynamic material coextrusion process for additive manufacturing capable of printing any ratio between and including two neat input materials is described across 3 hot-end generations and 14 implemented design iterations. The designs evolved with increased understanding of manufacturing constraints associated with the additive manufacturing of metal components with internal flow bore diameters on the order of 2 mm and typical bore length around 50 mm. The second generation overcame this issue by partitioning the design into two pieces to locate the flow channel geometry at the interface between the components so that the details could be easily printed on the components' external surfaces. The third concept generation then focused on minimizing flow channel volume to reduce the average length when transitioning between materials by 92%. The third-generation design was also used to investigate the improvements in dimensional stability during annealing of acrylonitrile butadiene styrene (ABS) made possible by coextruding ABS with a polycarbonate (PC) core. The standard deviation of part shrinkage after annealing was 7.08% for the neat ABS but reduced to 0.24% for the coextruded ABS/PC components.

12.
J Hum Kinet ; 91(Spec Issue): 19-31, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38689579

RESUMO

This study investigated the effects of a six-week strength training intervention on the physical fitness of female high school athletes, with a focus on training frequency. Twenty-three female high school basketball athletes were recruited and split into two groups: one group participated in strength training once per week (S1), while the other participated in two training sessions per week (S2). The groups were not random as training sessions were voluntary, and some participants were only able to train once per week. Participants were tested before and after the intervention, and the data included: age, body height, body mass, body fat percentage, grip strength, leg/back dynamometer (LBD) strength, a seated medicine ball throw (MBT), a vertical jump (VJ), 505 tests from each foot, 0-5, 0-10, and 0-20 sprint times, and multistage fitness test shuttles. Data were analyzed by a two (time) x two (group) repeated measures analysis of variance (ANOVA; p < 0.05). When significant F ratios were detected in any ANOVA calculations, post hoc pairwise comparisons were conducted using the Bonferroni adjustment procedure. There were significant main effects for time that indicated the following: increased body height, body mass, grip strength, LBD strength, MBT distance, and VJ height, faster 505 times, and slower 0-5 and 0-10 m sprint times (p ≤ 0.021). There were no significant time by group ANOVAs or between-group main effects. These performance changes occurred irrespective of training frequency. High school girls who participate in at least one strength training session per week can improve their strength (grip, LBD), power (MBT, VJ), and change-of-direction speed (505).

13.
Eur J Appl Physiol ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695912

RESUMO

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

15.
Carbohydr Polym ; 337: 122190, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710564

RESUMO

Starch structure is often characterized by the chain-length distribution (CLD) of the linear molecules formed by breaking each branch-point. More information can be obtained by expanding into a second dimension: in the present case, the total undebranched-molecule size. This enables answers to questions unobtainable by considering only one variable. The questions considered here are: (i) are the events independent which control total size and CLD, and (ii) do ultra-long amylopectin (AP) chains exist (these chains cannot be distinguished from amylose chains using simple size separation). This was applied here to characterize the structures of one normal (RS01) wheat and two high-amylose (AM) mutant wheats (an SBEIIa knockout and an SBEIIa and SBEIIb knockout). Absolute ethanol was used to precipitate collected fractions, then size-exclusion chromatography for total molecular size and for the size of branches. The SBEIIa and SBEIIb mutations significantly increased AM and IC contents and chain length. The 2D plots indicated the presence of small but significant amounts of long-chain amylopectin, and the asymmetry of these plots shows that the corresponding mechanisms share some causal effects. These results could be used to develop plants producing improved starches, because different ranges of the chain-length distribution contribute independently to functional properties.


Assuntos
Amilopectina , Amilose , Sintase do Amido , Triticum , Triticum/metabolismo , Triticum/química , Triticum/genética , Amilopectina/química , Amilopectina/biossíntese , Amilose/química , Amilose/biossíntese , Sintase do Amido/genética , Sintase do Amido/metabolismo , Sintase do Amido/química , Amido/química , Amido/biossíntese , Amido/metabolismo , Mutação , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
16.
Cogn Res Princ Implic ; 9(1): 29, 2024 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735013

RESUMO

Auditory stimuli that are relevant to a listener have the potential to capture focal attention even when unattended, the listener's own name being a particularly effective stimulus. We report two experiments to test the attention-capturing potential of the listener's own name in normal speech and time-compressed speech. In Experiment 1, 39 participants were tested with a visual word categorization task with uncompressed spoken names as background auditory distractors. Participants' word categorization performance was slower when hearing their own name rather than other names, and in a final test, they were faster at detecting their own name than other names. Experiment 2 used the same task paradigm, but the auditory distractors were time-compressed names. Three compression levels were tested with 25 participants in each condition. Participants' word categorization performance was again slower when hearing their own name than when hearing other names; the slowing was strongest with slight compression and weakest with intense compression. Personally relevant time-compressed speech has the potential to capture attention, but the degree of capture depends on the level of compression. Attention capture by time-compressed speech has practical significance and provides partial evidence for the duplex-mechanism account of auditory distraction.


Assuntos
Atenção , Nomes , Percepção da Fala , Humanos , Atenção/fisiologia , Feminino , Masculino , Percepção da Fala/fisiologia , Adulto , Adulto Jovem , Fala/fisiologia , Tempo de Reação/fisiologia , Estimulação Acústica
17.
PLoS One ; 19(5): e0300862, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38739614

RESUMO

Influenza A viruses of the H2 subtype represent a zoonotic and pandemic threat to humans due to a lack of widespread specific immunity. Although A(H2) viruses that circulate in wild bird reservoirs are distinct from the 1957 pandemic A(H2N2) viruses, there is concern that they could impact animal and public health. There is limited information on AIVs in Latin America, and next to nothing about H2 subtypes in Brazil. In the present study, we report the occurrence and genomic sequences of two influenza A viruses isolated from wild-caught white-rumped sandpipers (Calidris fuscicollis). One virus, identified as A(H2N1), was isolated from a bird captured in Restinga de Jurubatiba National Park (PNRJ, Rio de Janeiro), while the other, identified as A(H2N2), was isolated from a bird captured in Lagoa do Peixe National Park (PNLP, Rio Grande do Sul). DNA sequencing and phylogenetic analysis of the obtained sequences revealed that each virus belonged to distinct subtypes. Furthermore, the phylogenetic analysis indicated that the genomic sequence of the A(H2N1) virus isolated from PNRJ was most closely related to other A(H2N1) viruses isolated from North American birds. On the other hand, the A(H2N2) virus genome recovered from the PNLP-captured bird exhibited a more diverse origin, with some sequences closely related to viruses from Iceland and North America, and others showing similarity to virus sequences recovered from birds in South America. Viral genes of diverse origins were identified in one of the viruses, indicating local reassortment. This suggests that the extreme South of Brazil may serve as an environment conducive to reassortment between avian influenza virus lineages from North and South America, potentially contributing to an increase in overall viral diversity.


Assuntos
Charadriiformes , Vírus da Influenza A , Influenza Aviária , Filogenia , Vírus Reordenados , Animais , Brasil , Influenza Aviária/virologia , Influenza Aviária/epidemiologia , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Charadriiformes/virologia , Genoma Viral , Aves/virologia
18.
Anesthesiology ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38739769

RESUMO

General anesthetics adversely alters the distribution of infused fluid between the plasma compartment and the extravascular space. This maldistribution occurs largely from the effects of anesthetic agents on lymphatic pumping, which can be demonstrated by macroscopic fluid kinetics studies in awake versus anesthetized patients. The magnitude of this effect can be appreciated as follows: a 30% reduction in lymph flow may result in a fivefold increase of fluid-induced volume expansion of the interstitial space relative to plasma volume. Anesthesia-induced lymphatic dysfunction is a key factor why anesthetized patients require greater than expected fluid administration than can be accounted for by blood loss, urine output, and insensible losses. Anesthesia also blunts the transvascular refill response to bleeding, an important compensatory mechanism during hemorrhagic hypovolemia, in part through lymphatic inhibition. Last, this study addresses how catecholamines and hypertonic and hyperoncotic fluids may mobilize interstitial fluid to mitigate anesthesia-induced lymphatic dysfunction.

19.
J Cyst Fibros ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38749892

RESUMO

BACKGROUND: The forskolin-induced swelling (FIS) assay measures CFTR function on patient-derived intestinal organoids (PDIOs) and may guide treatment selection for individuals with Cystic Fibrosis (CF). The aim of this study is to demonstrate the repeatability and reproducibility of the FIS assay following a detailed Standard Operating Procedure (SOP), thus advancing the validation of the assay for precision medicine (theranostic) applications. METHODS: Over a 2-year period, FIS responses to CFTR modulators were measured in four European labs. PDIOs from six subjects with CF carrying different CFTR genotypes were used to assess the repeatability and reproducibility across the dynamic range of the assay. RESULTS: Technical, intra-assay repeatability was high (Lin's concordance correlation coefficient (CCC) 0.95-0.98). Experimental, within-subject repeatability was also high within each lab (CCCs all >0.9). Longer-term repeatability (>1 year) showed more variability (CCCs from 0.67 to 0.95). The reproducibility between labs was also high (CCC ranging from 0.92 to 0.97). Exploratory analysis also found that between-lab percentage of agreement of dichotomized CFTR modulator outcomes for predefined FIS thresholds ranged between 78 and 100 %. CONCLUSIONS: The observed repeatability and reproducibility of the FIS assay within and across different labs is high and support the use of FIS as biomarker of CFTR function in the presence or absence of CFTR modulators.

20.
Artigo em Inglês | MEDLINE | ID: mdl-38752959

RESUMO

BACKGROUND: Ventricular tachycardia (VT)/ventricular fibrillation (VF) rearrest after successful resuscitation is common, and survival is poor. A mechanism of VT/VF, as demonstrated in ex vivo studies, is when repolarization alternans becomes spatially discordant (DIS ALT), which can be enhanced by impaired gap junctions (GJs). However, in vivo spontaneous DIS ALT-induced VT/VF has never been demonstrated, and the effects of GJ on DIS ALT and VT/VF rearrest are unknown. OBJECTIVES: This study aimed to determine whether spontaneous VT/VF rearrest induced by DIS ALT occurs in vivo, and if it can be suppressed by preserving Cx43-mediated GJ coupling and/or connectivity. METHODS: We used an in vivo porcine model of resuscitation from ischemia-induced cardiac arrest combined with ex vivo optical mapping in porcine left ventricular wedge preparations. RESULTS: In vivo, DIS ALT frequently preceded VT/VF and paralleled its incidence at normal (37°C, n = 9) and mild hypothermia (33°C, n = 8) temperatures. Maintaining GJs in vivo with rotigaptide (n = 10) reduced DIS ALT and VT/VF incidence, especially during mild hypothermia, by 90% and 60%, respectively (P < 0.001; P < 0.013). Ex vivo, both rotigaptide (n = 5) and αCT11 (n = 7), a Cx43 mimetic peptide that promotes GJ connectivity, significantly reduced DIS ALT by 60% and 100%, respectively (P < 0.05; P < 0.005), and this reduction was associated with reduced intrinsic heterogeneities of action potential duration rather than changes in conduction velocity restitution. CONCLUSIONS: These results provide the strongest in vivo evidence to date suggesting a causal relationship between spontaneous DIS ALT and VT/VF in a clinically realistic scenario. Furthermore, our results suggest that preserving GJs during resuscitation can suppress VT/VF rearrest.

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