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.
Throughout history, dozens of epidemics have appeared cyclically, often causing devastating effects. Some of them, such as plague, cholera, and tuberculosis, have led to significant social, economic, ...and political consequences, with evident repercussions on cities and architecture. In this regard, urban planning has played an essential role in improving life expectancy and limiting the spread of epidemics. This work aims to study the influence of prevalent pandemics on architecture and urbanism over the centuries to comprehend their response and adaption to new health and social requirements. Through a process of investigation and in-depth examination of the literature review, it has been possible to understand the impact of pandemics in cities. The appearance of the first preventive measures during the plague period, the urban interventions to combat the cholera outbreak, and the neat architectural features adopted following the appearance of tuberculosis are witnesses to this process. Professionals and academics are reflecting on the challenges of the Covid-19 pandemic, which will affect the practice of architecture and urban design. Thanks to the results obtained, it will be possible to reflect on the impact of the pandemic on contemporary cities, understand their potential resilience and hypothesise future strategies.
Psoriasis is an immune-mediated inflammatory skin disease that has been associated with cutaneous microbial dysbiosis by culture-dependent investigations and rRNA community profiling. We applied, for ...the first time, high-resolution shotgun metagenomics to characterise the microbiome of psoriatic and unaffected skin from 28 individuals. We demonstrate psoriatic ear sites have a decreased diversity and psoriasis is associated with an increase in
, but overall the microbiomes of psoriatic and unaffected sites display few discriminative features at the species level. Finer strain-level analysis reveals strain heterogeneity colonisation and functional variability providing the intriguing hypothesis of psoriatic niche-specific strain adaptation or selection. Furthermore, we accessed the poorly characterised, but abundant, clades with limited sequence information in public databases, including uncharacterised
spp. These results highlight the skins hidden diversity and suggests strain-level variations could be key determinants of the psoriatic microbiome. This illustrates the need for high-resolution analyses, particularly when identifying therapeutic targets. This work provides a baseline for microbiome studies in relation to the pathogenesis of psoriasis.
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.
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 ± 1.24 L/min (rest) to 9.41 ± 2.63 L/min (last step), PBF from 3.81 ± 1.41 L/min to 7.21 ± 2.93 L/min, and intrapulmonary shunt from 1.05 ± 0.96 L/min to 2.21 ± 2.28 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.
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.
In chronic heart failure, minute ventilation (
'
) for a given carbon dioxide production (
'
) 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
'
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relationship, analysed either as ratio or as slope, enables us to evaluate the causes and entity of the
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/perfusion mismatch. Moreover, the
'
axis intercept,
when
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is extrapolated to 0, embeds information on exercise-induced dead space changes, while the analysis of end-tidal and arterial CO
pressures provides knowledge about reflex activities. The
'
'
relationship has a relevant prognostic power either alone or, better, when included within prognostic scores. The
'
'
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
'
'
slope as percentage of the predicted value, due to age and gender interferences. Relevant attention is needed in
'
'
analysis in the presence of heart failure comorbidities. Finally,
'
'
abnormalities are relevant targets for treatment in heart failure.
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.
Plain Language Summary
Psoriasis is an immune-mediated disease primarily manifesting as skin redness and inflammation that affects 2–3% 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.
The objective of this study was to evaluate inert gas rebreathing (IGR) reliability in cardiac output (CO) measurement compared with Fick method and thermodilution. IGR is a noninvasive method for CO ...measurement; CO by IGR is calculated as pulmonary blood flow plus intrapulmonary shunt. IGR may be ideal for follow-up of patients with pulmonary hypertension (PH), sparing the need of repeated invasive right-sided cardiac catheterization. Right-sided cardiac catheterization with CO measurement by thermodilution, Fick method, and IGR was performed in 125 patients with possible PH by echocardiography. Patients were grouped according to right-sided cardiac catheterization–measured mean pulmonary and wedge pressures: normal pulmonary arterial pressure (n = 20, mean pulmonary arterial pressure = 18 ± 3 mm Hg, pulmonary capillary wedge pressure = 11 ± 5 mm Hg), PH and normal pulmonary capillary wedge pressure (PH-NW, n = 37 mean pulmonary arterial pressure = 42 ± 13 mm Hg, pulmonary capillary wedge pressure = 11 ± 6 mm Hg), and PH and high pulmonary capillary wedge pressure (PH-HW, n = 68, mean pulmonary arterial pressure = 37 ± 9 mm Hg, pulmonary capillary wedge pressure = 24 ± 6 mm Hg). Thermodilution and Fick measurements were comparable. Fick and IGR agreement was observed in normal pulmonary arterial pressure (CO = 4.10 ± 1.14 and 4.08 ± 0.97 L/min, respectively), whereas IGR overestimated Fick in patients with PH-NW and those with PH-HW because of intrapulmonary shunting overestimation in hypoxemic patients. When patients with arterial oxygen saturation (SO2 ) ≤90% were excluded, IGR and Fick agreement improved in PH-NW (CO = 4.90 ± 1.70 and 4.76 ± 1.35 L/min, respectively) and PH-HW (CO = 4.05 ± 1.04 and 4.10 ± 1.17 L/min, respectively). In hypoxemic patients, we estimated pulmonary shunt as Fick − pulmonary blood flow and calculated shunt as: −0.2423 × arterial SO2 + 21.373 L/min. In conclusion, IGR is reliable for CO measurement in patients with PH with arterial SO2 >90%. For patients with arterial SO2 ≤90%, a new formula for shunt calculation is proposed.
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