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1.
Blood ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968143

RESUMO

Acute graft-vs-host disease (GVHD) grading systems that use only clinical symptoms at treatment initiation such as Minnesota risk identify standard and high risk categories but lack a low risk category suitable to minimize immunosuppressive strategies. We developed a new grading system that includes a low risk stratum based on clinical symptoms alone and determined whether the incorporation of biomarkers would improve the model's prognostic accuracy. We randomly divided 1863 patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) who were treated for GVHD into training and validation cohorts. Patients in the training cohort were divided into 14 groups based on similarity of clinical symptoms and similar NRM; we used a classification and regression tree (CART) algorithm to create three Manhattan risk groups that produced a significantly higher area under the receiver operating characteristic curve (AUC) for 6-month NRM than the Minnesota risk classification (0.69 vs. 0.64, P=0.009) in the validation cohort. We integrated serum GVHD biomarker scores with Manhattan risk using patients with available serum samples and again used a CART algorithm to establish three MAGIC composite scores that significantly improved prediction of NRM compared to Manhattan risk (AUC, 0.76 vs. 0.70, P=0.010). Each increase in MAGIC composite score also corresponded to a significant decrease in day 28 treatment response (80% vs. 63% vs. 30%, P<0.001). We conclude that the MAGIC composite score more accurately predicts response to therapy and long term outcomes than systems based on clinical symptoms alone and may help guide clinical decisions and trial design.

2.
J Strength Cond Res ; 38(5): 873-880, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38241480

RESUMO

ABSTRACT: Vehrs, PR, Reynolds, S, Allen, J, Barrett, R, Blazzard, C, Burbank, T, Hart, H, Kasper, N, Lacey, R, Lopez, D, and Fellingham, GW. Measurements of arterial occlusion pressure using hand-held devices. J Strength Cond Res 38(5): 873-880, 2024-Arterial occlusion pressure (AOP) of the brachial artery was measured simultaneously using Doppler ultrasound (US), a hand-held Doppler (HHDOP), and a pulse oximeter (PO) in the dominant (DOM) and nondominant (NDOM) arms of males ( n = 21) and females ( n = 23) using continuous (CONT) and incremental (INCR) cuff inflation protocols. A mixed-model analysis of variance revealed significant ( p < 0.05) overall main effects between AOP measured using a CONT (115.7 ± 10.9) or INCR (115.0 ± 11.5) cuff inflation protocol; between AOP measured using US (116.3 ± 11.2), HHDOP (115.4 ± 11.2), and PO (114.4 ± 11.2); and between males (120.7 ± 10.6) and females (110.5 ± 9.4). The small overall difference (1.81 ± 3.3) between US and PO measures of AOP was significant ( p < 0.05), but the differences between US and HHDOP and between HHDOP and PO measures of AOP were not significant. There were no overall differences in AOP between the DOM and NDOM arms. Trial-to-trial variance in US measurements of AOP was not significant when using either cuff inflation protocol but was significant when using HHDOP and PO and a CONT cuff inflation protocol. Bland-Altman plots revealed reasonable limits of agreement for both HHDOP and PO measures of AOP. The small differences in US, HHDOP, and PO measurements of AOP when using CONT or INCR cuff inflation protocols are of minimal practical importance. The choice of cuff inflation protocol is one of personal preference. Hand-held Doppler of PO can be used to assess AOP before using blood flow restriction during exercise.


Assuntos
Artéria Braquial , Ultrassonografia Doppler , Humanos , Masculino , Feminino , Artéria Braquial/fisiologia , Artéria Braquial/diagnóstico por imagem , Adulto , Adulto Jovem , Oximetria/instrumentação
3.
Sci Rep ; 13(1): 22255, 2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097707

RESUMO

Cisplatin (CP) induces acute kidney injury (AKI) whereby proximal tubules undergo regulated necrosis. Repair is almost complete after a single dose. We now demonstrate a role for Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (Apobec-1) that is prominently expressed at the interface between acute and chronic kidney injury (CKD), in the recovery from AKI. Apobec-1 knockout (KO) mice exhibited greater mortality than in wild type (WT) and more severe AKI in both CP- and unilateral ischemia reperfusion (IR) with nephrectomy. Specifically, plasma creatinine (pCr) 2.6 ± 0.70 mg/dL for KO, n = 10 and 0.16 ± 0.02 for WT, n = 6, p < 0.0001 in CP model and 1.34 ± 0.22 mg/dL vs 0.75 ± 0.06, n = 5, p < 0.05 in IR model. The kidneys of Apobec-1 KO mice showed increased necrosis, increased expression of KIM-1, NGAL, RIPK1, ASCL4 and increased lipid accumulation compared to WT kidneys (p < 0.01). Neutrophils and activated T cells were both increased, while macrophages were reduced in kidneys of Apobec-1 KO animals. Overexpression of Apobec-1 in mouse proximal tubule cells protected against CP-induced cytotoxicity. These findings suggest that Apobec-1 mediates critical pro-survival responses to renal injury and increasing Apobec-1 expression could be an effective strategy to mitigate AKI.


Assuntos
Injúria Renal Aguda , Traumatismo por Reperfusão , Camundongos , Animais , Desaminase APOBEC-1/metabolismo , Cisplatino/efeitos adversos , Cisplatino/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Rim/metabolismo , Necrose/metabolismo , Camundongos Knockout , Traumatismo por Reperfusão/metabolismo , Camundongos Endogâmicos C57BL
4.
Prev Vet Med ; 221: 106055, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37918211

RESUMO

A farm level bio-economic model, for aquatic animal production, of the relationships between inputs (e.g. purchased animals), outputs (e.g. harvested animals) and gross margin (GM) was developed to assess ex-ante the economics of disease and animal health interventions. Feed costs were calculated from estimates of food conversion ratio (FCR), animals harvested and mortality. The model was applied to a typical grow-out rainbow trout (Oncorhynchus mykiss) farm on Lake Titicaca, Peru and a typical shrimp (Paenus vannamei) farm in the Mekong Delta, Vietnam. The model was used in two analyses. Firstly, an approach to assess the burden of disease developed by the Global Burden of Animal Diseases (GBADs) project was adopted. Output under conditions of 'ideal health' was estimated by reducing mortality to zero and removing health costs. GM in both systems increased by approximately 25% when production was kept constant (and stocking rates reduced) and more than doubled if production was allowed to rise (and initial stocking increased). The increase in GM under conditions of ideal compared with current production provided an estimate of the maximum possible benefit from improved health management. Secondly, break-even analysis was used to assess the economics of vaccination against infectious pancreatic necrosis (IPN) vaccine (rainbow trout - RBT) and probiotics (shrimp). If initial stocking was kept constant, and production allowed to rise, break-even points for the intervention (when GM was the same with and without the intervention) were achieved when mortality was reduced by 16% in RBT fry and juvenile and 28% in shrimp. If production was kept constant and benefit realised by reduced initial stocking, the break-even point was achieved for i) vaccination of RBT when mortality in fry and juveniles was reduced by 39%, and ii) probiotics in shrimp production when there was a 15% reduction in mortality (nursery and grow-out), 10% increase in shrimp weight at harvest and 10% improvement in FCR. The results demonstrate how relatively simple models, parameterised with basic farm production data, can assess the burden of disease and quantify ex-ante the potential benefit of interventions. In the absence of trial data, these analyses support decision-making by farmers. The models can be adapted for many aquaculture systems. Farm level results can be extrapolated to estimate disease burden, and benefits of interventions, at regional or national level and thus support informed decision-making and allocation of resources to health management.


Assuntos
Doenças dos Animais , Aquicultura , Animais , Custos e Análise de Custo , Aquicultura/métodos , Vacinação/veterinária , Modelos Econômicos
5.
medRxiv ; 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37398386

RESUMO

Arteriolar hyalinosis in kidneys is an independent predictor of cardiovascular disease, the main cause of mortality in chronic kidney disease (CKD). The underlying molecular mechanisms of protein accumulation in the subendothelial space are not well understood. Using single cell transcriptomic data and whole slide images from kidney biopsies of patients with CKD and acute kidney injury in the Kidney Precision Medicine Project, the molecular signals associated with arteriolar hyalinosis were evaluated. Co-expression network analysis of the endothelial genes yielded three gene set modules as significantly associated with arteriolar hyalinosis. Pathway analysis of these modules showed enrichment of transforming growth factor beta / bone morphogenetic protein (TGFß / BMP) and vascular endothelial growth factor (VEGF) signaling pathways in the endothelial cell signatures. Ligand-receptor analysis identified multiple integrins and cell adhesion receptors as over-expressed in arteriolar hyalinosis, suggesting a potential role of integrin-mediated TGFß signaling. Further analysis of arteriolar hyalinosis associated endothelial module genes identified focal segmental glomerular sclerosis as an enriched term. On validation in gene expression profiles from the Nephrotic Syndrome Study Network cohort, one of the three modules was significantly associated with the composite endpoint (> 40% reduction in estimated glomerular filtration rate (eGFR) or kidney failure) independent of age, sex, race, and baseline eGFR, suggesting poor prognosis with elevated expression of genes in this module. Thus, integration of structural and single cell molecular features yielded biologically relevant gene sets, signaling pathways and ligand-receptor interactions, underlying arteriolar hyalinosis and putative targets for therapeutic intervention.

6.
JAMA Intern Med ; 183(9): 955-962, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37486647

RESUMO

Importance: Social isolation is associated with adverse health outcomes, yet its implications for hospitalization and nursing home entry are not well understood. Objective: To evaluate whether higher levels of social isolation are associated with overnight hospitalization, skilled nursing facility stays, and nursing home placement among a nationally representative sample of community-dwelling older adults after adjusting for key health and social characteristics, including loneliness and depressive symptoms. Design, Setting, and Participants: This observational cohort study included 7 waves of longitudinal panel data from the Health and Retirement Study, with community-dwelling adults aged 65 years or older interviewed between March 1, 2006, and June 30, 2018 (11 517 respondents; 21 294 person-years). Data were analyzed from May 25, 2022, to May 4, 2023. Main Outcomes and Measures: Social isolation was measured with a multidomain 6-item scale (range, 0-6, in which a higher score indicates greater isolation). Multivariate logistic regressions were performed on survey-weighted data to produce national estimates for the odds of self-reported hospitalization, skilled nursing facility stays, and nursing home placement over time. Results: A total of 57% of this study's 11 517 participants were female, 43% were male, 8.4% were Black, 6.7% were Hispanic or Latino, 88.1% were White, 3.5% were other ("other" includes American Indian or Alaska Native, Asian or Pacific Islander, and other race, which has no further breakdown available because this variable was obtained directly from the Health and Retirement Study), and 58.2% were aged 65 to 74 years. Approximately 15% of community-dwelling older adults in the US experienced social isolation. Higher social isolation scores were significantly associated with increased odds of nursing home placement (odds ratio, 2.01; 95% CI, 1.21-3.32) and skilled nursing facility stays (odds ratio, 1.16; 95% CI, 1.06-1.28) during 2 years. With each point increase in an individual's social isolation score, the estimated probability of nursing home placement or a skilled nursing facility stay increased by 0.5 and 0.4 percentage points, respectively, during 2 years. Higher levels of social isolation were not associated with 2-year hospitalization rates. Conclusions and Relevance: This cohort study found that social isolation was a significant risk factor for nursing home use among older adults. Efforts to deter or delay nursing home entry should seek to enhance social contact at home or in community settings. The design and assessment of interventions that optimize the social connections of older adults have the potential to improve their health trajectories and outcomes.


Assuntos
Hospitalização , Vida Independente , Masculino , Humanos , Feminino , Idoso , Estudos de Coortes , Casas de Saúde , Isolamento Social
7.
Artigo em Inglês | MEDLINE | ID: mdl-36554797

RESUMO

Professional organizations advise prescribing intensity of aerobic exercise using heart rate reserve (%HRR) which is presumed to have a 1:1 relationship with either maximal oxygen uptake (%VO2max) or %VO2 reserve (%VO2R). Even though running and cycling are popular modes of training, these relationships have not been investigated in a group of males and females during both running and cycling. This study evaluated the %HRR-%VO2max and %HRR-%VO2R relationships in 41 college-aged males (n = 21) and females (n = 20) during treadmill running and cycling. Heart rate (HR) and VO2 data were collected at rest and during maximal exercise tests on a treadmill and cycle ergometer. The HR and VO2 data were analyzed using a Bayesian approach. Both the %HRR-%VO2max and %HRR-%VO2R relationships did not coincide with the line of identity in males and females in both treadmill running and cycling. %HRR was closer to %VO2max than to %VO2R. There were no significant differences in the intercepts of the %HRR-%VO2max and %HRR-%VO2R relationships between males and females during running or cycling, or between running and cycling in males or females. The credible intervals of the intercepts and slopes suggest interindividual variability in the HR-VO2 relationship that would yield significant error in the prescription of intensity of aerobic exercise for an individual.


Assuntos
Consumo de Oxigênio , Corrida , Masculino , Humanos , Feminino , Adulto Jovem , Teorema de Bayes , Frequência Cardíaca/fisiologia , Consumo de Oxigênio/fisiologia , Exercício Físico/fisiologia , Corrida/fisiologia , Teste de Esforço , Nonoxinol
8.
PLoS One ; 17(12): e0278940, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36548357

RESUMO

BACKGROUND: Snakebite envenoming represents a tragically neglected tropical disease mostly affecting poor people living in remote areas of developing countries, primarily in sub-Saharan Africa. Anti-snake venom (ASV) is the only approved specific treatment for systemic envenoming from snakebite, but it remains largely unavailable in many parts of developing countries. There is paucity of data on snakebite management practice in Tanzania. This study aimed at assessing the community management practices of snakebite and availability of anti-snake venom in the public health facilities in Monduli District, Northern Tanzania. METHODS: A cross sectional study was carried out between May and June, 2018 involving 67 victims, 147 other household members, and 35 public health facilities. A structured questionnaire, respondent interview, and health facility report/document review were considered during data collection. Clean data were analyzed using SPSS version 20. RESULTS: Sixty-seven snakebite victims and 147 other household members were interviewed during a household survey. All snakebite cases reported to having visited a health facility after snakebite with the majority 55/67 (82.1%) reporting the use, prior attendance to medical care, of some form of local treatment such as tourniquets 13 (19.4%), local incision 11 (16.4%), and snakestone 7 (10.4%). None of the public health facilities in Monduli District attended a snakebite case and had never stocked anti-snake venom products. In this area, 45 snakebite cases were reported to be managed at Meserani snake park clinic where anti-snake venom products were available and provided for free in the period between January 2017 and December 2017. CONCLUSION: Majority of the snakebite cases at Meserani Juu relied on local methods for the management of snake bites of which most are of unknown efficacy and safety. Furthermore, none of the primary public health facilities in Monduli District stocked antivenom despite being a habitat for different kinds of venomous snakes. The government and local non-government organizations should collaborate so as to improve the anti-snake venom availability and the provision of snakebite preventive and management awareness programs, especially to the rural communities.


Assuntos
Mordeduras de Serpentes , Humanos , Mordeduras de Serpentes/tratamento farmacológico , Mordeduras de Serpentes/epidemiologia , Tanzânia/epidemiologia , Estudos Transversais , Antivenenos/uso terapêutico , Venenos de Serpentes
9.
Sci Rep ; 12(1): 18954, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347919

RESUMO

We present a framework based on non-equilibrium molecular dynamics (NEMD) to reproduce the phase transformation event of Aluminum under ramp compression loading. The simulated stress-density response, virtual x-ray diffraction patterns, and structure analysis are compared against the previously observed experimental laser-driven ramp compression in-situ x-ray diffraction data. The NEMD simulations show the solid-solid phase transitions are consistent to experimental observations with a close-packed face-centered cubic (fcc) (111), hexagonal close-packed (hcp) structure (002), and body-centered cubic bcc (110) planes remaining parallel. The atomic-level analysis of NEMD simulations identifiy the exact phase transformation pathway happening via Bain transformation while the previous in situ x-ray diffraction data did not provide sufficient information for deducing the exact phase transformation path.

10.
Clin J Am Soc Nephrol ; 17(9): 1284-1292, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35948365

RESUMO

BACKGROUND AND OBJECTIVES: Uromodulin, produced exclusively in the kidney's thick ascending limb, is a biomarker of kidney tubular health. However, the relationship between urine uromodulin and histologic changes in the kidney tubulointerstitium has not been characterized. In this study, we test the association of urine uromodulin with kidney histologic findings in humans and mice. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We investigated the independent association of urine uromodulin measured at the time of kidney biopsy with histologic features in 364 participants at two academic medical centers from 2015 to 2018 using multivariable linear regression models. This relationship was further examined by comparison of uromodulin staining in murine models of kidney fibrosis and repair. RESULTS: We found urine uromodulin to be correlated with serum creatinine (rho=-0.43; P<0.001), bicarbonate (0.20; P<0.001), and hemoglobin (0.11; P=0.03) at the time of biopsy but not with urine albumin (-0.07; P=0.34). Multivariable models controlling for prebiopsy GFR, serum creatinine at biopsy, and urine albumin showed higher uromodulin to be associated with lower severity of interstitial fibrosis/tubular atrophy and glomerulosclerosis (interstitial fibrosis/tubular atrophy: -3.5% [95% confidence intervals, -5.7% to -1.2%] and glomerulosclerosis: -3.3% [95% confidence intervals, -5.9% to -0.6%] per two-fold difference in uromodulin). However, when both interstitial fibrosis/tubular atrophy and glomerulosclerosis were included in multivariable analysis, only interstitial fibrosis/tubular atrophy was independently associated with uromodulin (interstitial fibrosis/tubular atrophy: -2.5% [95% confidence intervals, -4.6% to -0.4%] and glomerulosclerosis: -0.9% [95% confidence intervals, -3.4% to 1.5%] per two-fold difference in uromodulin). In mouse kidneys, uromodulin staining was found to be lower in the fibrotic model than in normal or repaired models. CONCLUSIONS: Higher urine uromodulin is independently associated with lower tubulointerstitial fibrosis in both human kidney biopsies and a mouse model of fibrosis. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_08_10_CJN04360422.mp3.


Assuntos
Nefropatias , Rim , Humanos , Camundongos , Animais , Uromodulina/urina , Creatinina , Rim/patologia , Nefropatias/patologia , Fibrose , Biomarcadores , Atrofia/patologia , Albuminas
11.
Phys Rev Lett ; 129(1): 015701, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35841582

RESUMO

Triple bonding in the nitrogen molecule (N_{2}) is among the strongest chemical bonds with a dissociation enthalpy of 9.8 eV/molecule. Nitrogen is therefore an excellent test bed for theoretical and numerical methods aimed at understanding how bonding evolves under the influence of the extreme pressures and temperatures of the warm dense matter regime. Here, we report laser-driven shock experiments on fluid molecular nitrogen up to 800 GPa and 4.0 g/cm^{3}. Line-imaging velocimetry measurements and impedance matching method with a quartz reference yield shock equation of state data of initially precompressed nitrogen. Comparison with numerical simulations using path integral Monte Carlo and density functional theory molecular dynamics reveals clear signatures of chemical dissociation and the onset of L-shell ionization. Combining data along multiple shock Hugoniot curves starting from densities between 0.76 and 1.29 g/cm^{3}, our study documents how pressure and density affect these changes in chemical bonding and provides benchmarks for future theoretical developments in this regime, with applications for planetary interior modeling, high energy density science, and inertial confinement fusion research.

12.
Children (Basel) ; 9(5)2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35626921

RESUMO

This study evaluates the cross-sectional trends in body fat percentage (BF%) and body mass index (BMI) percentile rank, and the relationship between the two in 332 (177 boys, 155 girls) 12- to 17-year-old children. Body mass index (BMI) was calculated using measured height and body mass, and sex-specific BMI for age percentile rank was determined using CDC growth charts. Body fat percentage (BF%) was measured with DEXA. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated by normalizing the fat mass and fat-free mass for height. Compared to boys of the same age, girls had significantly higher BF% and FMI values and lower FFMI values. Compared to boys, at a given BMI percentile rank, females had a higher BF% and FMI, and a lower FFMI. In both boys and girls, there was an exponential increase in adiposity above the 70th percentile rank. BMI percentile rank is not an equivalent indicator of body fatness in boys and girls. Other measures of body composition can further inform the practitioner of a child's adiposity.

13.
Nat Commun ; 13(1): 2534, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534461

RESUMO

The properties of all materials at one atmosphere of pressure are controlled by the configurations of their valence electrons. At extreme pressures, neighboring atoms approach so close that core-electron orbitals overlap, and theory predicts the emergence of unusual quantum behavior. We ramp-compress monovalent elemental sodium, a prototypical metal at ambient conditions, to nearly 500 GPa (5 million atmospheres). The 7-fold increase of density brings the interatomic distance to 1.74 Å well within the initial 2.03 Å of the Na+ ionic diameter, and squeezes the valence electrons into the interstitial voids suggesting the formation of an electride phase. The laser-driven compression results in pressure-driven melting and recrystallization in a billionth of a second. In situ x-ray diffraction reveals a series of unexpected phase transitions upon recrystallization, and optical reflectivity measurements show a precipitous decrease throughout the liquid and solid phases, where the liquid is predicted to have electronic localization. These data reveal the presence of a rich, temperature-driven polymorphism where core electron overlap is thought to stabilize the formation of peculiar electride states.

15.
Science ; 375(6577): 202-205, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35025665

RESUMO

The discovery of more than 4500 extrasolar planets has created a need for modeling their interior structure and dynamics. Given the prominence of iron in planetary interiors, we require accurate and precise physical properties at extreme pressure and temperature. A first-order property of iron is its melting point, which is still debated for the conditions of Earth's interior. We used high-energy lasers at the National Ignition Facility and in situ x-ray diffraction to determine the melting point of iron up to 1000 gigapascals, three times the pressure of Earth's inner core. We used this melting curve to determine the length of dynamo action during core solidification to the hexagonal close-packed (hcp) structure. We find that terrestrial exoplanets with four to six times Earth's mass have the longest dynamos, which provide important shielding against cosmic radiation.

16.
Catheter Cardiovasc Interv ; 99(3): 844-852, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34766734

RESUMO

AIMS: We evaluated the occurrence and physiology of respiration-related beat-to-beat variations in resting Pd/Pa and FFR during intravenous adenosine administration, and its impact on clinical decision-making. METHODS AND RESULTS: Coronary pressure tracings in rest and at plateau hyperemia were analyzed in a total of 39 stenosis from 37 patients, and respiratory rate was calculated with ECG-derived respiration (EDR) in 26 stenoses from 26 patients. Beat-to-beat variations in FFR occurred in a cyclical fashion and were strongly correlated with respiratory rate (R2  = 0.757, p < 0.001). There was no correlation between respiratory rate and variations in resting Pd/Pa. When single-beat averages were used to calculate FFR, mean ΔFFR was 0.04 ± 0.02. With averaging of FFR over three or five cardiac cycles, mean ΔFFR decreased to 0.02 ± 0.02, and 0.01 ± 0.01, respectively. Using a FFR ≤ 0.80 threshold, stenosis classification changed in 20.5% (8/39), 12.8% (5/39) and 5.1% (2/39) for single-beat, three-beat and five-beat averaged FFR. The impact of respiration was more pronounced in patients with pulmonary disease (ΔFFR 0.05 ± 0.02 vs 0.03 ± 0.02, p = 0.021). CONCLUSION: Beat-to-beat variations in FFR during plateau hyperemia related to respiration are common, of clinically relevant magnitude, and frequently lead FFR to cross treatment thresholds. A five-beat averaged FFR, overcomes clinically relevant impact of FFR variation.


Assuntos
Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Hiperemia , Adenosina , Cateterismo Cardíaco/métodos , Angiografia Coronária , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/terapia , Vasos Coronários , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Valor Preditivo dos Testes , Respiração , Índice de Gravidade de Doença , Resultado do Tratamento , Vasodilatadores
17.
Transplant Direct ; 7(7): e716, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34476295

RESUMO

BACKGROUND: Delayed graft function (DGF) affects over 25% of deceased donor kidney transplants (DDKTs) and is associated with increased cost, worsened graft outcomes, and mortality. While approaches to preventing DGF have focused on minimizing cold ischemia, donor factors such as acute tubular injury can influence risk. There are currently no pharmacologic therapies to modify DGF risk or promote repair, in part due to our incomplete understanding of the biology of preimplantation tubular injury. METHODS: We collected intraoperative, preimplantation kidney biopsies from 11 high-risk deceased donors and 10 living donors and followed transplant recipients for graft function. We performed quantitative high-dimensional histopathologic analysis using imaging mass cytometry to determine the cellular signatures that distinguished deceased and living donor biopsies as well as deceased donor biopsies which either did or did not progress to DGF. RESULTS: We noted decreased tubular cells (P < 0.0001) and increased macrophage infiltration (P = 0.0037) in high-risk DDKT compared with living donor biopsies. For those high-risk DDKTs that developed postimplant DGF (n = 6), quantitative imaging mass cytometry analysis showed a trend toward reduced tubular cells (P = 0.02) and increased stromal cells (P = 0.04) versus those that did not (n = 5). Notably, these differences were not identified by conventional histopathologic evaluation. CONCLUSIONS: The current study identifies donor tubular cell loss as a precursor of DGF pathogenesis and highlights an area for further investigation and potential therapeutic intervention.

18.
Rev Sci Tech ; 40(2): 567-584, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34542092

RESUMO

Investments in animal health and Veterinary Services can have a measurable impact on the health of people and the environment. These investments require a baseline metric that describes the burden of animal health and welfare in order to justify and prioritise resource allocation and from which to measure the impact of interventions. This paper is part of a process of scientific enquiry in which problems are identified and solutions sought in an inclusive way. It poses the broad question: what should a system to measure the animal disease burden on society look like and what value would it add? Moreover, it aims to do this in such a way as to be accessible by a wide audience, who are encouraged to engage in this debate. Given that farmed animals, including those raised by poor smallholders, are an economic entity, this system should be based on economic principles. These poor farmers are negatively impacted by disparities in animal health technology, which can be addressed through a mixture of supply-led and demand-driven interventions, reinforcing the relevance of targeted financial support from government and non-governmental organisations. The Global Burden of Animal Diseases (GBADs) Programme will glean existing data to measure animal health losses within carefully characterised production systems. Consistent and transparent attribution of animal health losses will enable meaningful comparisons of the animal disease burden to be made between diseases, production systems and countries, and will show how it is apportioned by people's socio-economic status and gender. The GBADs Programme will produce a cloud-based knowledge engine and data portal, through which users will access burden metrics and associated visualisations, support for decisionmaking in the form of future animal health scenarios, and the outputs of wider economic modelling. The vision of GBADs, strengthening the food system for the benefit of society and the environment, is an example of One Health thinking in action.


Les investissements réalisés en santé animale et dans les Services vétérinaires ont un impact mesurable sur la santé des personnes et de l'environnement. Le système de mesure appliqué à ces investissements doit reposer sur un référentiel de base décrivant l'impact de la santé et du bien-être animal de manière à justifier et classer par priorités les ressources allouées et à mesurer les effets des interventions. Les auteurs présentent une étude conduite dans le cadre d'une enquête scientifique destinée à identifier les problèmes et à rechercher des solutions de manière inclusive. L'étude pose la question de savoir à quoi devrait ressembler un système conçu pour mesurer l'impact sur la société des maladies animales, et quelle serait sa valeur ajoutée. En outre, l'étude est conduite de manière à être accessible à une large audience afin d'encourager cette dernière à participer aux discussions. Étant donné que les animaux d'élevage constituent une entité économique, y compris les animaux appartenant à des éleveurs pauvres, le système de mesure doit reposer sur des principes économiques. Les exploitants pratiquant une agriculture de subsistance subissent les effets négatifs des disparités entre les différentes technologies applicables à la santé animale, disparités auxquelles il est possible de remédier par le biais d'interventions associant des mesures dictées par l'offre et par la demande et en renforçant l'efficacité du soutien financier ciblé apporté par les organisations gouvernementales et non gouvernementales. Le Programme « L'impact mondial des maladies animales ¼ (GBADs) aura pour tâche de glaner les données existantes afin de mesurer les pertes associées à la santé animale au sein de systèmes de production qui auront été soigneusement caractérisés au préalable. Grâce à l'élucidation cohérente et transparente des pertes imputables à chaque problème de santé animale, des comparaisons pertinentes pourront être effectuées concernant l'impact des maladies animales par maladies, par systèmes de production et par pays, et la répartition de cet impact dans les populations concernées suivant le statut socio-économique et le genre des intéressés sera mieux comprise. Le Programme GBADs entend créer un moteur de recherche et un portail de données qui seront disponibles sur le Cloud et donneront aux utilisateurs l'accès à des outils de mesure de l'impact des maladies et à d'autres informations présentées sous forme graphique, ainsi qu'à des outils d'aide à la décision sous forme de scénarios prospectifs sur la santé animale et aux résultats d'études plus larges de modélisation économique. La vision du GBADs, renforcer le système de production de denrées alimentaires au profit de la société et de l'environnement, est un exemple de mise en oeuvre du concept Une seule santé.


Las inversiones en sanidad animal y en los Servicios Veterinarios pueden tener un efecto mensurable en la salud de las personas y el medio ambiente. Para efectuar estas inversiones se precisan parámetros que describan y cuantifiquen la situación de partida y el impacto de los problemas de sanidad y bienestar animales, a fin de poder, a partir de ahí, justificar y jerarquizar la asignación de recursos y medir los efectos de las intervenciones. Este artículo, inscrito en un proceso de indagación científica encaminado a detectar problemas y buscar soluciones de forma incluyente, plantea la cuestión general de cómo debería ser y qué valor añadido aportaría un sistema destinado a medir el impacto que imponen a la sociedad las enfermedades animales. Los autores, además, tratan de exponer la cuestión de manera que sea accesible a un público amplio, al que se alienta a participar en este debate. Dado que los animales de granja (incluidos los de pequeñas explotaciones) constituyen una entidad económica, tal sistema debería estar basado en principios económicos. Los productores que trabajan en régimen de subsistencia se ven negativamente afectados por las disparidades existentes en materia de tecnología zoosanitaria, disparidad que cabe corregir con una combinación de intervenciones marcadas por la oferta y otras marcadas por la demanda, dirigiendo así más selectivamente el apoyo económico de entidades gubernamentales y organizaciones no gubernamentales. El programa GBADs (El impacto global de las enfermedades animales) servirá para compilar datos ya existentes con el fin de medir las pérdidas zoosanitarias dentro de sistemas productivos cuidadosamente caracterizados. La atribución coherente y transparente de estas pérdidas zoosanitarias permitirá efectuar comparaciones significativas del impacto que representan las enfermedades animales en el caso de diferentes dolencias, sistemas productivos o países y pondrá de relieve cómo se distribuye este impacto en función del género y la condición socioeconómica de las personas. Por medio del programa GBADs se creará un motor de conocimiento y portal de datos ubicado en la nube que permita al usuario acceder a mediciones del impacto de enfermedades y representaciones gráficas conexas, a herramientas de apoyo a la adopción de decisiones, en forma de hipotéticas situaciones zoosanitarias futuras, y a los resultados de modelizaciones económicas más generales. La aspiración del programa GBADs ­ reforzar el sistema alimentario en beneficio de la sociedad y el medio ambiente ­ constituye un ejemplo de aplicación en la práctica del pensamiento en clave de Una sola salud.


Assuntos
Doenças dos Animais , Saúde Única , Doenças dos Animais/epidemiologia , Animais , Aquicultura , Gado
19.
Medicina (Kaunas) ; 57(9)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34577785

RESUMO

Background and Objectives: Blood flow restriction during low-load exercise stimulates similar muscle adaptations to those normally observed with higher loads. Differences in the arterial occlusion pressure (AOP) between limbs and between sexes are unclear. We compared the AOP of the superficial femoral artery in the dominant and non-dominant legs, and the relationship between blood flow and occlusion pressure in 35 (16 males, 19 females) young adults. Materials and Methods: Using ultrasound, we measured the AOP of the superficial femoral artery in both legs. Blood flow at occlusion pressures ranging from 0% to 100% of the AOP was measured in the dominant leg. Results: There was a significant difference in the AOP between males and females in the dominant (230 ± 41 vs. 191 ± 27 mmHg; p = 0.002) and non-dominant (209 ± 37 vs. 178 ± 21 mmHg; p = 0.004) legs, and between the dominant and non-dominant legs in males (230 ± 41 vs. 209 ± 37 mmHg; p = 0.009) but not females (191 ± 27 vs. 178 ± 21 mmHg; p = 0.053), respectively. Leg circumference was the most influential independent predictor of the AOP. There was a linear relationship between blood flow (expressed as a percentage of unoccluded blood flow) and occlusion pressure (expressed as a percentage of AOP). Conclusions: Arterial occlusion pressure is not always greater in the dominant leg or the larger leg. Practitioners should measure AOP in both limbs to determine if occlusion pressures used during exercise should be limb specific. Occlusion pressures used during blood flow restriction exercise should be chosen carefully.


Assuntos
Artéria Femoral , Perna (Membro) , Pressão Sanguínea , Exercício Físico , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Perna (Membro)/diagnóstico por imagem , Masculino , Músculo Esquelético , Fluxo Sanguíneo Regional , Adulto Jovem
20.
Rev Sci Instrum ; 92(6): 063514, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243556

RESUMO

Time-resolved radiography can be used to obtain absolute shock Hugoniot states by simultaneously measuring at least two mechanical parameters of the shock, and this technique is particularly suitable for one-dimensional converging shocks where a single experiment probes a range of pressures as the converging shock strengthens. However, at sufficiently high pressures, the shocked material becomes hot enough that the x-ray opacity falls significantly. If the system includes a Lagrangian marker such that the mass within the marker is known, this additional information can be used to constrain the opacity as well as the Hugoniot state. In the limit that the opacity changes only on shock heating, and not significantly on subsequent isentropic compression, the opacity of the shocked material can be determined uniquely. More generally, it is necessary to assume the form of the variation of opacity with isentropic compression or to introduce multiple marker layers. Alternatively, assuming either the equation of state or the opacity, the presence of a marker layer in such experiments enables the non-assumed property to be deduced more accurately than from the radiographic density reconstruction alone. An example analysis is shown for measurements of a converging shock wave in polystyrene at the National Ignition Facility.

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