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AIMS: The Fick principle states that oxygen uptake (VÌO2) is cardiac output (Qc)*arterial-venous O2 content difference [ΔC(a-v)O2]. Blood flow distribution is hidden in Fick principle and its relevance during exercise in heart failure (HF) is undefined.To highlight the role of blood flow distribution, we evaluated peak-exercise VÌO2, Qc and ΔC(a-v)O2, before and after HF therapeutic interventions. METHODS: Symptoms-limited cardiopulmonary exercise tests with Qc measurement (inert-gas-rebreathing) was performed in 234 HF patients before and 6 months after successful exercise training, cardiac-resynchronization therapy or percutaneous-edge-to-edge mitral valve repair. RESULTS: Considering all tests (n=468) a direct correlation between peakVÌO2 and peakQc (R2=0.47) and workload (R2=0.70) were observed. Patients were grouped according to treatment efficacy in group 1 (peakVÌO2 increase >10%, n=93), group 2 (peakVÌO2 change between 0 and 10%, n=60) and group 3 (reduction in peakVÌO2, n=81). Post-treatment peakVÌO2 changes poorly correlated with peakQc and peakΔC(a-v)O2 changes. Differently, post-procedures peakQc vs. peakΔC(a-v)O2 changes showed a close negative correlation (R2=0.46), becoming stronger grouping patients according to peakVÌO2 improvement (R2=0.64, 0.79 and 0.58 in group 1, 2 and 3, respectively). In 76% of patients peakQc and ΔC(a-v)O2 changes diverged regardless of treatment. CONCLUSION: The bulk of these data suggests that blood flow distribution plays a pivotal role on peakVÌO2 determination regardless of HF treatment strategies. Accordingly, for assessing HF treatment efficacy on exercise performance the sole peakVÌO2 may be deceptive and the combination of VÌO2, Qc and ΔC(a-v)O2, must be considered.
This study aimed to understand how oxygen uptake during exercise is affected by heart failure therapeutic intervention. We evaluated 234 heart failure patients before and after treatments such as exercise training, cardiac resynchronization therapy, or mitral valve repair, finding that changes in oxygen uptake were poorly correlated with changes in cardiac output and oxygen content difference between arteries and veins. However, we observed a strong negative correlation between changes in cardiac output and oxygen content difference, especially in patients with significant improvement in oxygen uptake. This suggests that blood flow distribution is crucial for oxygen uptake during exercise, regardless of treatment. Therefore, relying solely on oxygen uptake may not accurately assess treatment effectiveness, and considering a combination of oxygen uptake, cardiac output, and oxygen content difference is important. Oxygen uptake during exercise was strongly related to cardiac output and workload.Changes in cardiac output and oxygen content difference were closely related after treatments, especially in patients with significant improvement in oxygen uptake.
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The etiopathology of Parkinson's disease has been associated with mitochondrial defects at genetic, laboratory, epidemiological, and clinical levels. These converging lines of evidence suggest that mitochondrial defects are systemic and causative factors in the pathophysiology of PD, rather than being mere correlates. Understanding mitochondrial biology in PD at a granular level is therefore crucial from both basic science and translational perspectives. In a recent study, we investigated mitochondrial alterations in fibroblasts obtained from PD patients assessing mitochondrial function in relation to clinical measures. Our findings demonstrated that the magnitude of mitochondrial alterations parallels disease severity. In this study, we extend these investigations to blood cells and dopamine neurons derived from induced pluripotent stem cells reprogrammed from PD patients. To overcome the inherent metabolic heterogeneity of blood cells, we focused our analyses on metabolically homogeneous, accessible, and expandable erythroblasts. Our results confirm the presence of mitochondrial anomalies in erythroblasts and induced dopamine neurons. Consistent with our previous findings in fibroblasts, we observed that mitochondrial alterations are reversible, as evidenced by enhanced mitochondrial respiration when PD erythroblasts were cultured in a galactose medium that restricts glycolysis. This observation indicates that suppression of mitochondrial respiration may constitute a protective, adaptive response in PD pathogenesis. Notably, this effect was not observed in induced dopamine neurons, suggesting their distinct bioenergetic behavior. In summary, we provide additional evidence for the involvement of mitochondria in the disease process by demonstrating mitochondrial abnormalities in additional cell types relevant to PD. These findings contribute to our understanding of PD pathophysiology and may have implications for the development of novel biomarkers and therapeutic strategies.
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Enfermedades Mitocondriales , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/metabolismo , Mitocondrias/metabolismo , Metabolismo Energético/fisiología , Fibroblastos/metabolismo , Enfermedades Mitocondriales/metabolismoRESUMEN
Cardiopulmonary exercise test (CPET) is a valuable diagnostic tool with a specific application in heart failure (HF) thanks to the strong prognostic value of its parameters. The most important value provided by CPET is the peak oxygen uptake (peak VO2), the maximum rate of oxygen consumption attainable during physical exertion. According to the Fick principle, VO2 equals cardiac output (Qc) times the arteriovenous content difference [C(a-v)O2], where Ca is the arterial oxygen and Cv is the mixed venous oxygen content, respectively; therefore, VO2 can be reduced both by impaired O2 delivery (reduced Qc) or extraction (reduced arteriovenous O2 content). However, standard CPET is not capable of discriminating between these different impairments, leading to the need for 'complex' CPET technologies. Among non-invasive methods for Qc measurement during CPET, inert gas rebreathing and thoracic impedance cardiography are the most used techniques, both validated in healthy subjects and patients with HF, at rest and during exercise. On the other hand, the non-invasive assessment of peripheral muscle perfusion is possible with the application of near-infrared spectroscopy, capable of measuring tissue oxygenation. Measuring Qc allows, by having haemoglobin values available, to discriminate how much any VO2 deficit depends on the muscle, anaemia or heart.
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Prueba de Esfuerzo , Insuficiencia Cardíaca , Humanos , Prueba de Esfuerzo/métodos , Gasto Cardíaco/fisiología , Consumo de Oxígeno/fisiología , Pronóstico , Insuficiencia Cardíaca/diagnóstico , OxígenoRESUMEN
Complex chromosomal rearrangements are rare events compatible with survival, consisting of an imbalance and/or position effect of one or more genes, that contribute to a range of clinical presentations. The investigation and diagnosis of these cases are often difficult. The interpretation of the pattern of pairing and segregation of these chromosomes during meiosis is important for the assessment of the risk and the type of imbalance in the offspring. Here, we investigated two unrelated pediatric carriers of complex rearrangements of chromosome 7. The first case was a 2-year-old girl with a severe phenotype. Conventional cytogenetics evidenced a duplication of part of the short arm of chromosome 7. By array-CGH analysis, we found a complex rearrangement with three discontinuous trisomy regions (7p22.1p21.3, 7p21.3, and 7p21.3p15.3). The second case was a newborn investigated for hypodevelopment and dimorphisms. The karyotype analysis promptly revealed a structurally altered chromosome 7. The array-CGH analysis identified an even more complex rearrangement consisting of a trisomic region at 7q11.23q22 and a tetrasomic region of 4.5 Mb spanning 7q21.3 to q22.1. The mother's karyotype examination revealed a complex rearrangement of chromosome 7: the 7q11.23q22 region was inserted in the short arm at 7p15.3. Finally, array-CGH analysis showed a trisomic region that corresponds to the tetrasomic region of the son. Our work proved that the integration of several technical solutions is often required to appropriately analyze complex chromosomal rearrangements in order to understand their implications and offer appropriate genetic counseling.
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INTRODUCTION: Psoriasis is a systemic immune-mediated disease primarily manifesting as skin redness and inflammation. Balneotherapy proved to be a successful non-pharmacological option to reduce the skin areas affected by the disease, but the specific mechanisms underlying this effect have not been elucidated yet. Here we test the hypothesis that the effect of thermal treatments on psoriatic lesions could be partially mediated by changes in the resident microbial population, i.e., the microbiome. METHODS: In this study, we enrolled patients with psoriasis and monitored changes in their skin and gut microbiome after a 12-bath balneotherapy course with a combination of 16S rRNA amplicon sequencing and metagenomics. Changes in the resident microbiome were then correlated with thermal therapy outcomes evaluated as changes in Psoriasis Area and Severity Index (PASI) and Body Surface Area index (BSA). RESULTS: The amplicon sequencing analysis of the skin microbiome showed that after thermal treatment the microbiome composition of affected areas improved to approach that typical of unaffected skin. We moreover identified some low-abundance bacterial biomarkers indicative of disease status and treatment efficacy, and we showed via metagenomic sequencing that thermal treatments and thermal water drinking affect the fecal microbiome to host more species associated with favorable metabolic health. CONCLUSIONS: Changes in lower-abundance microbial taxa presence and abundance could be the basis for the positive effect of thermal water treatment and drinking on the cutaneous and systemic symptomatology of psoriasis.
Psoriasis is an immune-mediated disease primarily manifesting as skin redness and inflammation that affects 23% of the world's population. No cure is currently available for this condition, and patients are offered pharmacological and non-pharmacological options to alleviate the discomfort. Previous studies and clinical practice have shown that thermal water treatment can be a non-pharmacological option to reduce the areas affected by the disease. However, the specific mechanisms causing this reduction have not been clarified yet. Given that neither the chemical nor the physical composition of thermal water can explain this beneficial effect, recent studies have suggested that it might be due to the effect of thermal water on the microbial communities living on the skin (i.e., the skin microbiome). In this work carried out at Terme di Comano, Northern Italy, we describe the effect of thermal water treatment on the skin microbiome of patients with psoriasis and we highlight the potentially beneficial effect of thermal water drinking on the microbial communities living in the gut, namely the gut microbiome. Specifically, we show that after balneotherapy the areas affected by psoriasis have a higher diversity of microbes usually present on healthy skin, potentially explaining the reduction in disease severity after treatment, and we describe how the gut microbiome of patients who drank thermal water changes to host more species linked with favorable metabolic health. These findings highlight that thermal water treatment and drinking could reduce both the skin and systemic symptomatology of psoriasis by affecting the skin and gut microbiome.
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Background: Hyperventilation and inadequate cardiac output (CO) increase are the main causes of exercise limitation in pulmonary hypertension (PH). Intrapulmonary blood flow partitioning between ventilated and unventilated lung zones is unknown. Thoracic impedance cardiography and inert gas rebreathing have been both validated in PH patients for non-invasive measurement of CO and pulmonary blood flow (PBF), respectively. This study sought to evaluate CO behaviour in PH patients during exercise and its partitioning between ventilated and unventilated lung areas, in parallel with ventilation partitioning between ventilated and unventilated lung zones. Methods: Eighteen PH patients (group 1 or 4) underwent a cardiopulmonary exercise test (CPET) with a three-step loaded workload protocol. The steps occurred at 0%, 20%, 40%, and 60% of peak workload reached during a preliminary maximum CPET. Ventilatory parameters, arterial blood gases, CO, PBF, and intrapulmonary shunt (calculated as the difference between CO and PBF) were obtained at each step, combining thoracic impedance cardiography and an inert gas rebreathing technique. Results: Dead space ventilation observed throughout the exercise was about 40% of total ventilation. A progressive increase of CO from 4.86 ± 1.24â L/min (rest) to 9.41 ± 2.63â L/min (last step), PBF from 3.81 ± 1.41â L/min to 7.21 ± 2.93â L/min, and intrapulmonary shunt from 1.05 ± 0.96â L/min to 2.21 ± 2.28â L/min was observed. Intrapulmonary shunt was approximately 20% of CO at each exercise step. Conclusions: Although the study population was small, the combined non-invasive CO measurement seems a promising tool for deepening our knowledge of lung exercise haemodynamics in PH patients. This technique could be applied in future studies to evaluate PH treatment influences on CO partitioning, since a secondary increase of intrapulmonary shunt is undesirable.
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Background: A recent genome-wide association study identified the SLC17A4 locus associated with circulating free thyroxine (T4) concentrations. Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. However, apart from the cellular uptake of T3 and T4, transporter characteristics are currently unknown. In this study, we delineated basic transporter characteristics of this novel thyroid hormone (TH) transporter. Methods: We performed a broad range of well-established TH transport studies in COS-1 cells transiently overexpressing SLC17A4. We studied cellular TH uptake in various incubation buffers, TH efflux, and the inhibitory effects of different TH metabolites and known inhibitors of other TH transporters on SLC17A4-mediated TH transport. Finally, we determined the effect of tunicamycin, a pharmacological inhibitor of N-linked glycosylation, and targeted mutations in Asn residues on SLC17A4 function. Results: SLC17A4 induced the cellular uptake of T3 and T4 by â¼4 times, and of reverse (r)T3 by 1.5 times over control cells. The uptake of T4 by SLC17A4 was Na+ and Cl- independent, stimulated by low extracellular pH, and reduced by various iodothyronines and metabolites thereof, particularly those that contain at least three iodine moieties irrespective of the presence of modification at the alanine side chain. None of the classical TH transporter inhibitors studied attenuated SLC17A4-mediated TH transport. SLC17A4 also facilitates the efflux of T3 and T4, and to a lesser extent of 3,3'-diiodothyronine (T2). Immunoblot studies on lysates of transfected cells cultured in absence or presence of tunicamycin indicated that SLC17A4 is subject to N-linked glycosylation. Complementary mutational studies identified Asn66, Asn75, and Asn90, which are located in extracellular loop 1, as primary targets. Conclusions: Our studies show that SLC17A4 facilitates the transport of T3 and T4, and less efficiently rT3 and 3,3'-T2. Further studies should reveal the physiological role of SLC17A4 in TH regulation.
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Estudio de Asociación del Genoma Completo , Tiroxina , Humanos , Proteínas de Transporte de Membrana , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo I , Hormonas Tiroideas/metabolismo , Tiroxina/metabolismo , Triyodotironina/metabolismo , TunicamicinaRESUMEN
AIMS: Changes in peak exercise oxygen uptake (VO2 ) and cardiac output (CO) 6 months after successful percutaneous edge-to-edge mitral valve repair (pMVR) in severe primary (PMR) and functional mitral regurgitation (FMR) patients are unknown. The aim of the study was to assess the efficacy of pMVR at rest by echocardiography, VO2 and CO (inert gas rebreathing) measurement and during cardiopulmonary exercise test with CO measurement. METHODS AND RESULTS: We evaluated 145 and 115 patients at rest and 98 and 66 during exercise before and after pMVR, respectively. After successful pMVR, significant reductions in MR and NYHA class were observed in FMR and PMR patients. Cardiac ultrasound showed reverse remodelling (left ventricular end-diastolic volume from 158 ± 63 mL to 147 ± 64, P < 0.001; ejection fraction from 51 ± 15 to 48 ± 14, P < 0.001; pulmonary artery systolic pressure (PASP) from 43 ± 13 to 38 ± 8 mmHg, P < 0.001) in the entire population. These changes were significant in PMR (n = 62) and a trend in FMR (n = 53), except for PASP, which decreased in both groups. At rest, CO and stroke volume (SV) increased in FMR with a concomitant reduction in arteriovenous O2 content difference [ΔC(a-v)O2 ]. Peak exercise, CO and SV increased significantly in both groups (CO from 5.5 ± 1.4 L/min to 6.3 ± 1.5 and from 6.2 ± 2.4 to 6.7 ± 2.0, SV from 57 ± 19 mL to 66 ± 20 and from 62 ± 20 to 69 ± 20, in FMR and PMR, respectively), whereas peak VO2 was unchanged and ΔC(a-v)O2 decreased. CONCLUSIONS: These data confirm pMVR-induced clinical improvement and reverse ventricular remodelling at a 6-month analysis and show, in spite of an increase in CO, an unchanged exercise performance, which is achieved through a 'more physiological' blood flow distribution and O2 extraction behaviour. Direct rest and exercise CO should be measured to assess pMVR efficacy.
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Insuficiencia de la Válvula Mitral , Válvula Mitral , Gasto Cardíaco , Humanos , Insuficiencia de la Válvula Mitral/complicaciones , Insuficiencia de la Válvula Mitral/diagnóstico , Insuficiencia de la Válvula Mitral/cirugía , Oxígeno , Volumen SistólicoRESUMEN
It has been shown that protein low-sequence complexity domains (LCDs) induce liquid-liquid phase separation (LLPS), which is responsible for the formation of membrane-less organelles including P-granules, stress granules and Cajal bodies. Proteins harbouring LCDs are widely represented among RNA binding proteins often mutated in ALS. Indeed, LCDs predispose proteins to a prion-like behaviour due to their tendency to form amyloid-like structures typical of proteinopathies. Protein post-translational modifications (PTMs) can influence phase transition through two main events: i) destabilizing or augmenting multivalent interactions between phase-separating macromolecules; ii) recruiting or excluding other proteins and/or nucleic acids into/from the condensate. In this manuscript we summarize the existing evidence describing how PTM can modulate LLPS thus favouring or counteracting proteinopathies at the base of neurodegeneration in ALS.
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BACKGROUND: Several studies have investigated the efficacy of balneotherapy in atopic dermatitis (AD), including a pediatric open randomized clinical trial conducted at the Comano thermal spring water center, which showed a significant reduction in AD severity and an improvement of the quality of life. However, so far many studies on balneotherapy in pediatric AD have included relatively small populations without identifying patients' characteristics associated with their response. The aim of the present study was to identify any features associated with the clinical response to the Comano thermal spring water balneotherapy in a large cohort of pediatric AD patients. METHODS: An observational study was conducted on 867 children aged ≤16 years (females 50.5%, mean patient's age 5.9 years, standard deviation ±3.6 years) with mild to severe AD who underwent balneotherapy at the Comano thermal spring water center (Comano, Trentino, Italy) from April to October 2014. Patients were stratified according to their disease severity, which was evaluated using five SCORing Atopic Dermatitis (SCORAD) categories before and immediately after a thermal spring water balneotherapy course. Potential characteristics associated with the patients' clinical response to Comano thermal spring water balneotherapy were investigated. RESULTS: A statistically significant improvement in AD severity was observed after Comano thermal spring water balneotherapy (p < 0.0001). A significantly higher percentage of patients achieving improvement in AD severity was reported among children ≤4 years old (p < 0.0001) with early-onset AD (p < 0.0001), severe AD (p < 0.0001) or coexistent reported food allergies (p < 0.01). The therapy was well tolerated, and no relevant adverse effects were reported during the treatment course. CONCLUSIONS: Comano thermal spring water balneotherapy is a safe complementary treatment for pediatric patients with AD, as it was able to reduce the disease severity, especially in children ≤4 years old, with early onset AD, severe AD or concomitant food allergies.
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Balneología , Dermatitis Atópica/terapia , Niño , Preescolar , Dermatitis Atópica/complicaciones , Femenino , Hipersensibilidad a los Alimentos/complicaciones , Humanos , Italia , Masculino , Índice de Severidad de la EnfermedadRESUMEN
During the COVID-19 pandemic, the use of protective masks has been essential to reduce contagions. However, public opinion is that there is an associated subjective shortness of breath. We evaluated cardiorespiratory parameters at rest and during maximal exertion to highlight any differences with the use of protective masks.12 healthy subjects performed three identical cardiopulmonary exercise tests, one without wearing a protective mask, one wearing a surgical mask and one with a filtering face piece particles class 2 (FFP2) mask. Dyspnoea was assessed using the Borg scale. Standard pulmonary function tests were also performed.All the subjects (40.8±12.4â years; six male) completed the protocol with no adverse events. Spirometry showed a progressive reduction of forced expiratory volume in 1â s (FEV1) and forced vital capacity (FVC) from no mask to surgical to FFP2 (FEV1: 3.94±0.91â L, 3.23±0.81â L, 2.94±0.98â L; FVC: 4.70±1.21â L, 3.77±1.02â L, 3.52±1.21â L; p<0.001). Rest ventilation, O2 uptake (VË O2 ) and CO2 production (VË CO2 ) were progressively lower, with a reduction in respiratory rate. At peak exercise, subjects had a progressively higher Borg scale when wearing surgical and FFP2 masks. Accordingly, at peak exercise, VË O2 (31.0±23.4â mL·kg-1·min-1, 27.5±6.9â mL·kg-1·min-1, 28.2±8.8â mL·kg-1·min-1; p=0.001), ventilation (92±26 L, 76±22 L, 72±21â L; p=0.003), respiratory rate (42±8 breaths·min-1, 38±5 breaths·min-1, 37±4 breaths·min-1; p=0.04) and tidal volume (2.28±0.72â L, 2.05±0.60â L, 1.96±0.65â L; p=0.001) were gradually lower. There was no significant difference in oxygen saturation.Protective masks are associated with significant but modest worsening of spirometry and cardiorespiratory parameters at rest and peak exercise. The effect is driven by a ventilation reduction due to increased airflow resistance. However, because exercise ventilatory limitation is far from being reached, their use is safe even during maximal exercise, with a slight reduction in performance.
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COVID-19 , Máscaras , Ejercicio Físico , Prueba de Esfuerzo , Humanos , Masculino , Pandemias , SARS-CoV-2RESUMEN
In chronic heart failure, minute ventilation (V'E) for a given carbon dioxide production (V'CO2 ) might be abnormally high during exercise due to increased dead space ventilation, lung stiffness, chemo- and metaboreflex sensitivity, early metabolic acidosis and abnormal pulmonary haemodynamics. The V'E versus V'CO2 relationship, analysed either as ratio or as slope, enables us to evaluate the causes and entity of the V'E/perfusion mismatch. Moreover, the V'E axis intercept, i.e. when V'CO2 is extrapolated to 0, embeds information on exercise-induced dead space changes, while the analysis of end-tidal and arterial CO2 pressures provides knowledge about reflex activities. The V'E versus V'CO2 relationship has a relevant prognostic power either alone or, better, when included within prognostic scores. The V'E versus V'CO2 slope is reported as an absolute number with a recognised cut-off prognostic value of 35, except for specific diseases such as hypertrophic cardiomyopathy and idiopathic cardiomyopathy, where a lower cut-off has been suggested. However, nowadays, it is more appropriate to report V'E versus V'CO2 slope as percentage of the predicted value, due to age and gender interferences. Relevant attention is needed in V'E versus V'CO2 analysis in the presence of heart failure comorbidities. Finally, V'E versus V'CO2 abnormalities are relevant targets for treatment in heart failure.
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Dióxido de Carbono , Insuficiencia Cardíaca , Ejercicio Físico , Prueba de Esfuerzo , Tolerancia al Ejercicio , Insuficiencia Cardíaca/diagnóstico , HumanosRESUMEN
AIMS: Peak exercise oxygen uptake (VO2 ) and cardiac output (CO) are strong prognostic indexes in heart failure (HF) but unrelated to real-life physical activity, which is associated to submaximal effort. METHODS AND RESULTS: We analysed maximal cardiopulmonary exercise test with rest, mid-exercise, and peak exercise non-invasive CO measurements (inert gas rebreathing) of 231 HF patients and 265 healthy volunteers. HF patients were grouped according to exercise capacity (peak VO2 < 50% and ≥50% pred, Groups 1 and 2). To account for observed differences, data regarding VO2 , CO, stroke volume (SV), and artero-venous O2 content difference [ΔC(a-v)O2 ] were adjusted by age, gender, and body mass index. A multiple regression analysis was performed to predict peak VO2 from mid-exercise cardiopulmonary exercise test and CO parameters among HF patients. Rest VO2 was lower in HF compared with healthy subjects; meanwhile, Group 1 patients had the lowest CO and highest ΔC(a-v)O2 . At mid-exercise, Group 1 patients achieved a lower VO2 , CO, and SV [0.69 (interquartile range 0.57-0.80) L/min; 5.59 (4.83-6.67) L/min; 62 (51-73) mL] than Group 2 [0.94 (0.83-1.1) L/min; 7.6 (6.56-9.01) L/min; 77 (66-92) mL] and healthy subjects [1.15 (0.93-1.30) L/min; 9.33 (8.07-10.81) L/min; 87 (77-102) mL]. Rest to mid-exercise SV increase was lower in Group 1 than Group 2 (P = 0.001) and healthy subjects (P < 0.001). At mid-exercise, ΔC(a-v)O2 was higher in Group 2 [13.6 (11.8-15.4) mL/100 mL] vs. healthy patients [11.6 (10.4-13.2) mL/100 mL] (P = 0.002) but not different from Group 1 [13.6 (12.0-14.9) mL/100 mL]. At peak exercise, Group 1 patients achieved a lower VO2 , CO, and SV than Group 2 and healthy subjects. ΔC(a-v)O2 was the highest in Group 2. At multivariate analysis, a model comprising mid-exercise VO2 , carbon dioxide production (VCO2 ), CO, haemoglobin, and weight predicted peak VO2 , P < 0.001. Mid-exercise VO2 and CO, haemoglobin, and weight added statistically significantly to the prediction, P < 0.050. CONCLUSIONS: Mid-exercise VO2 and CO portend peak exercise values and identify severe HF patients. Their evaluation could be clinically useful.
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Insuficiencia Cardíaca , Consumo de Oxígeno , Gasto Cardíaco , Ejercicio Físico , Prueba de Esfuerzo , HumanosRESUMEN
Subcellular compartmentalization contributes to the organization of a plethora of molecular events occurring within cells. This can be achieved in membraneless organelles generated through liquid-liquid phase separation (LLPS), a demixing process that separates and concentrates cellular reactions. RNA is often a critical factor in mediating LLPS. Recent evidence indicates that DNA damage response foci are membraneless structures formed via LLPS and modulated by noncoding transcripts synthesized at DNA damage sites. Neurodegeneration is often associated with DNA damage, and dysfunctional LLPS events can lead to the formation of toxic aggregates. In this review, we discuss those gene products involved in neurodegeneration that undergo LLPS and their involvement in the DNA damage response.
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Daño del ADN/genética , Degeneración Nerviosa/genética , Orgánulos/genética , Transcripción Genética , Humanos , Extracción Líquido-Líquido , Degeneración Nerviosa/patología , Orgánulos/química , Transición de FaseRESUMEN
Heart failure is a complex syndrome affecting several organs including kidney, lungs, liver, brain muscles and sympathetic system. Each of these organs might contribute to its severity and prognosis. The prognosis assessment is critical for a correct heart failure management. It has already been demonstrated that a single parameter is weaker for prognosis than different parameters combined. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score has been built and validated for heart failure with reduced ejection fraction (HFrEF) patients by considering cardiopulmonary exercise test data combined with clinical, laboratory and echocardiographic measurements. The betablockers treatment is a milestone in the HFrEF management. In the MECKI score database, the association of betablockers treatment with outcome has been investigated in different settings.
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Antagonistas Adrenérgicos beta/uso terapéutico , Capacidad Cardiovascular , Técnicas de Apoyo para la Decisión , Tolerancia al Ejercicio , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas Adrenérgicos beta/efectos adversos , Biomarcadores/sangre , Bases de Datos Factuales , Ecocardiografía , Prueba de Esfuerzo , Insuficiencia Cardíaca/fisiopatología , Humanos , Consumo de Oxígeno , Valor Predictivo de las Pruebas , Recuperación de la Función , Reproducibilidad de los Resultados , Resultado del TratamientoRESUMEN
BACKGROUND: Cardiopulmonary exercise testing allows the assessment of integrative cardiopulmonary response to exercise. AIMS: The aim of the study was to better understand the exercise physiology in pulmonary arterial hypertension related to adult congenital heart disease compared to non-adult congenital heart disease patients by means of cardiopulmonary exercise testing parameters. METHODS: The present is a multicentre retrospective study which includes pulmonary hypertension group 1 and group 4 patients. All subjects underwent full clinical and instrumental evaluation, including cardiopulmonary exercise testing and right heart catheterization. RESULTS: One hundred and sixty-seven pulmonary hypertension patients (93 women and 74 men, 57 adult congenital heart disease and 110 non-adult congenital heart disease) were enrolled. Adult congenital heart disease patients had higher pulmonary pressure (mean pulmonary arterial pressure: 59.8 ± 19.5 mmHg vs 44.6 ± 16.5 mmHg, p < 0.001) and lower pulmonary blood flow (pulmonary blood flow: 3.3 (2.1-4.3) l/min vs 4.5 (3.8-5.4) l/min, p < 0.001). At cardiopulmonary exercise testing they had lower peak oxygen uptake/kg (12.8 ± 3.8 ml/kg/min vs 15.5 ± 4.2 ml/kg/min, p < 0.001) and higher ventilation/carbon dioxide elimination slope (53.2 (43.3-64.8) vs 44.0 (34.6-51.6), p < 0.001). When patients were paired for gender and peak oxygen uptake ( ± 1 ml/kg/min), obtaining 44 pairs, adult congenital heart disease patients had higher pulmonary pressure (mean pulmonary arterial pressure: 58.4 ± 20.2 mmHg vs 42.8 ± 16.8 mmHg, p < 0.001) and ventilation/carbon dioxide elimination slope (51.2 (43.4-63.6) vs 44.9 (35.4-55.1), p = 0.033). CONCLUSIONS: In pulmonary arterial hypertension-adult congenital heart disease patients, pulmonary pressure and ventilation/carbon dioxide elimination slope are higher compared to non-adult congenital heart disease pulmonary hypertension patients, while pulmonary blood flow and peak oxygen uptake are lower. After matching patients for gender and peak oxygen uptake, pulmonary pressure and ventilation/carbon dioxide elimination remain higher in adult congenital heart disease patients suggesting that the long-term adaptation to high pulmonary pressure, hypoxia and low pulmonary blood flow, as well as a persisting shunt has, at least partially, preserved exercise performance of pulmonary arterial hypertension-adult congenital heart disease patients.
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Tolerancia al Ejercicio , Cardiopatías Congénitas/fisiopatología , Consumo de Oxígeno , Hipertensión Arterial Pulmonar/fisiopatología , Adaptación Fisiológica , Adulto , Anciano , Presión Arterial , Cateterismo Cardíaco , Prueba de Esfuerzo , Femenino , Alemania , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico , Humanos , Italia , Masculino , Persona de Mediana Edad , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/etiología , Arteria Pulmonar/fisiopatología , Estudios RetrospectivosAsunto(s)
Ejercicio Físico/fisiología , Insuficiencia Cardíaca/sangre , Proteína 1 Similar al Receptor de Interleucina-1/sangre , Péptido Natriurético Encefálico/sangre , Volumen Sistólico/fisiología , Anciano , Biomarcadores/sangre , Prueba de Esfuerzo , Femenino , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Índice de Severidad de la EnfermedadRESUMEN
Despite recent advances in the therapeutic management of patients affected by pulmonary arterial hypertension (PAH), survival remains poor. Prompt identification of the disease, especially in subjects at increased risk of developing PAH, and prognostic stratification of patients are a necessary target of clinical practice but remain challenging. Cardiopulmonary exercise test (CPET) parameters, particularly peak oxygen uptake, end-tidal carbon dioxide tension and the minute ventilation/carbon dioxide production relationship, emerged as new prognostic tools for PAH patients. Moreover, CPET provides a comprehensive pathophysiological evaluation of patients' exercise limitation and dyspnoea, which are the main and early symptoms of the disease. This review focuses on the role of CPET in the management of PAH patients, reporting guideline recommendations for CPET and discussing the pathophysiology of exercise limitation and the most recent use of CPET in the diagnosis, prognosis and therapeutic targeting of PAH.
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Presión Arterial , Prueba de Esfuerzo , Tolerancia al Ejercicio , Hipertensión Pulmonar/diagnóstico , Pulmón/fisiopatología , Arteria Pulmonar/fisiopatología , Humanos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/terapia , Valor Predictivo de las Pruebas , PronósticoRESUMEN
BACKGROUND: Pulmonary hypertension (PH) patients show, during exercise, an excessive increase in ventilation (VE) compared to carbon dioxide output (VCO2), determining a high VE/VCO2 slope. There are several possible causes, including an elevated dead space ventilation (VD), VE/perfusion (Q) mismatch and/or an enhanced peripheral or central chemoreceptor activity. We evaluated the causes of exercise hyperventilation in PH patients. METHODS: Eighteen group I and IV PH patients underwent cardiopulmonary exercise test with blood gas analysis at every minute. VE, alveolar ventilation (VA) and VD vs. VCO2 relationship were calculated. Resting chemoreceptor sensitivity was analyzed through hypoxia/hypercapnia tests. RESULTS: PeakVO2 and VE/VCO2 slopes were 1.06±0.24l/min and 39.1±9.0, respectively. Throughout the exercise, 30% of VE was due to VD. VE/VCO2 slope significantly correlated with VD/VCO2 slope (r=0.82, p<0.001) but not with VA/VCO2 slope (r=0.3, p=ns). Peak exercise end-tidal CO2 (PetCO2) correlated with VD/VCO2 slope (r=-0.79, p<0.001) and VE/VCO2 slope (r=-0.91, p<0.001). Dead space(DS)/Tidal volume and P(arterial-et)CO2 were elevated without arterial hypoxemia suggesting a high VE/Q mismatch. Chemoreceptor peripheral response to hypoxia and central CO2 response were both enhanced being peripheral responses to hypoxia and hypercapnia 0.416±0.402 (normal ref values=0.285±0.221) l/min/O2Sat and 0.076±0.047 (0.066±0.430) l/min/mmHg, respectively; central hypercapnic chemosensitivity was 4.475±3.99 (2.352±0.936) l/min/mmHg. CONCLUSIONS: Increased DS, VE/Q mismatch and chemorecptor response are among the main mechanisms involved in exercise hyperventilation in PH. ClinicalTrial.govNCT02892981.
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Prueba de Esfuerzo/métodos , Ejercicio Físico/fisiología , Hipertensión Pulmonar/fisiopatología , Hiperventilación/fisiopatología , Embolia Pulmonar/fisiopatología , Adulto , Anciano , Enfermedad Crónica , Tolerancia al Ejercicio/fisiología , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/epidemiología , Hiperventilación/diagnóstico , Hiperventilación/epidemiología , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/epidemiologíaRESUMEN
AIMS: The two main symptoms referred by chronic heart failure (HF) patients as the causes of exercise termination during maximal cardiopulmonary exercise testing (CPET) are muscular fatigue and dyspnoea. So far, a physiological explanation why some HF patients end exercise because of dyspnoea and others because of fatigue is not available. We assessed whether patients referring dyspnoea or muscular fatigue may be distinguished by different ventilator or haemodynamic behaviours during exercise. METHODS AND RESULTS: We analysed exercise data of 170 consecutive HF patients with reduced left ventricular ejection fraction in stable clinical condition. All patients underwent maximal CPET and a second maximal CPET with measurement of cardiac output by inert gas rebreathing at peak exercise. Thirty-eight (age 65.0 ± 11.1 years) and 132 (65.1 ± 11.4 years) patients terminated CPET because of dyspnoea and fatigue, respectively. Haemodynamic and cardiorespiratory parameters were the same in fatigue and dyspnoea patients. VO2 was 10.4 ± 3.2 and 10.5 ± 3.3 mL/min/kg at the anaerobic threshold and 15.5 ± 4.8 and 15.4 ± 4.3 at peak, in fatigue and dyspnoea patients, respectively. In fatigue and dyspnoea patients, peak heart rate was 110 ± 22 and 114 ± 22 beats/min, and VE/VCO2 and VO2 /work relationship slopes were 31.2 ± 6.8 and 30.6 ± 8.2 and 10.6 ± 4.2 and 11.4 ± 5.5 L/min/W, respectively. Peak cardiac output was 6.68 ± 2.51 and 6.21 ± 2.55 L/min (P = NS for all). CONCLUSIONS: In chronic HF patients in stable clinical condition, fatigue and dyspnoea as reasons of exercise termination do not highlight different ventilatory or haemodynamic patterns during effort.