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Valve-sparing aortic root replacement with the David procedure is an alternative to the Bentall procedure in patients with aortic root aneurysm. The aim of this study was to describe our long-term experience with this technique and the predictive factors of late failure. Between January 1998 and August 2019, 300 consecutive patients underwent a David procedure. Clinical and echocardiographic early- and long-term outcomes were analyzed. Median follow-up was 7.0 years (range, 4.1-11.5), with 98.3% complete. Early mortality was 1%. No early valve-related reoperations occurred. There were 9 cardiac-related deaths and 22 reinterventions (19 valve-related). All patients survived reoperation. In 3 patients reintervention consisted of transcatheter aortic valve implantation. Overall survival rates were 95.3% (95% confidence interval [CI], 92.0-97.2), 91.1% (95% CI, 86.5-94.2), and 82.9% (95% CI, 75.3-88.4) at 5, 10, and 15 years, respectively. Freedom from postoperative aortic insufficiency (AI) grade ≥ 2 was 84.8% (95% CI, 79.9-88.6) and 74.3% (95% CI, 67.4-79.9) at 5 and 10 years, respectively. Freedom from reintervention for aortic valve disease was 97.1% (95% CI, 94.2-98.5), 92.9% (95% CI, 88.2-95.7), and 92.5% (95% CI, 87.1-95.7) at 5, 10, and 15 years, respectively. Preoperative AI ≥ 2 (hazard ratio, 1.782; 95% CI, 1.352-2.350) and a ventriculoaortic junction ≥ 29 mm (hazard ratio, 3.379; 95% CI, 1.726-6.616) were predictive factors for postoperative AI ≥ 2 in a multivariate analysis (P <.001). Preoperative AI ≥ 2 and a ventriculoaortic junction ≥ 29 mm were identified as risk factors for late postoperative AI ≥ 2. [Display omitted] [ABSTRACT FROM AUTHOR]

Rapid vascularization of clinical-size bone grafts is an unsolved challenge in regenerative medicine. Vascular endothelial growth factor-A (VEGF) is the master regulator of angiogenesis. Its over-expression by genetically modified human osteoprogenitors has been previously evaluated to drive vascularization in osteogenic grafts, but has been observed to cause paradoxical bone loss through excessive osteoclast recruitment. However, during bone development angiogenesis and osteogenesis are physiologically coupled by VEGF expression. Here we investigated whether the mode of VEGF delivery may be a key to recapitulate its physiological function. VEGF activity requires binding to the extracellular matrix, and heterogeneous levels of expression lead to localized microenvironments of excessive dose. Therefore we hypothesized that a homogeneous distribution of matrix-associated factor in the microenvironment may enable efficient coupling of angiogenesis and bone formation. This was achieved by decorating fibrin matrices with a cross-linkable engineered version of VEGF (TG-VEGF) that is released only by enzymatic cleavage by invading cells. In ectopic grafts, both TG-VEGF and VEGF-expressing progenitors similarly improved vascularization within the first week, but efficient bone formation was possible only in the factor-decorated matrices, whereas heterogenous, cell-based VEGF expression caused significant bone loss. In critical-size orthotopic calvaria defects, TG-VEGF effectively improved early vascular invasion, osteoprogenitor survival and differentiation, as well as bone repair compared to both controls and VEGF-expressing progenitors. In conclusion, homogenous distribution of matrix-associated VEGF protein preserves the physiological coupling of angiogenesis and osteogenesis, providing an attractive and clinically applicable strategy to engineer vascularized bone. The therapeutic regeneration of vascularized bone is an unsolved challenge in regenerative medicine. Stimulation of blood vessel growth by over-expression of VEGF has been associated with paradoxical bone loss, whereas angiogenesis and osteogenesis are physiologically coupled by VEGF during development. Here we found that controlling the distribution of VEGF dose in an osteogenic graft is key to recapitulate its physiological function. In fact, homogeneous decoration of fibrin matrices with engineered VEGF could improve both vascularization and bone formation in orthotopic critical-size defects, dispensing with the need for combined osteogenic factor delivery. VEGF-decorated fibrin matrices provide a readily translatable platform for engineering a controlled microenvironment for bone regeneration. [Display omitted] [ABSTRACT FROM AUTHOR]

The additive manufacturing technology known as Laser Metal Deposition (LMD) is achieving widespread diffusion, thanks to its capacity of repairing or manufacturing entirely new, highly customized functional parts with complex geometries. For this reason, researchers and practitioners are continuously trying to improve the productivity and quality of this process, in particular by applying cutting-edge machine learning and control approaches. The implementation of these methodologies requires the availability of a data management infrastructure, capable of communicating with multiple, heterogeneous sources (sensors and machines), logging such process data acquired at high speed, and exposing such information to machine learning and control functionalities. This work describes the Ground Control framework, a monitoring and control system architecture designed and implemented on LMD machines, which supports simultaneous acquisition of process data at frequencies up to 500 Hz (workpiece temperature, melt pool images and temperature, in-process 3D scans, and machine data) and control of laser power. This information is organized in a customized database, used for experimental characterization and optimization of the process. The results and performances of the designed system are described by examples extracted from real deposition experiment [ABSTRACT FROM AUTHOR]

To investigate whether the decrease in dyspnea in neuromuscular diseases after air stacking (AS) occurs mostly in patients with decreased inspiratory muscle force and ensuing chest wall restriction or heterogeneous ventilation across the lungs. Interventional, before-after study. A neurorehabilitation inpatient and outpatient center. Fifteen consecutive adult patients affected by neuromuscular diseases (N=15). AS treatment. Patients had vital capacity (VC) and sniff nasal inspiratory pressure (SNIP) measured. We measured Borg score, oxygen saturation, and ventilation heterogeneity across the lung as estimated from the difference between respiratory resistance at 5 and 19 Hz (R 5-19) with the forced oscillation technique before and 5, 30, 60, and 120 minutes after applying AS. Before AS, Borg score was significantly related to R 5-19 (r 2 0.46, P <.05) but not to VC % predicted, SNIP % predicted, and time since symptom onset. After AS, average Borg score gradually decreased (P =.005), whereas inspiratory flow resistance at 5 Hz, R 5-19, and inspiratory reactance at 5 Hz tended to improve, despite not reaching statistical significance. The decrease in dyspnea at 60 and 120 minutes after AS significantly correlated with baseline R 5-19 (r 2 0.49, P <.01 and r 2 0.29, P <.05, respectively), but not with VC % predicted, SNIP % predicted, time since symptom onset, and clinical severity score for patients affected by amyotrophic lateral sclerosis. These findings suggest that dyspnea in neuromuscular diseases is related to heterogeneous ventilation rather than inspiratory muscle force and/or lung volumes decrease. Restoring ventilation distribution across the lungs with AS appears to improve dyspnea. [ABSTRACT FROM AUTHOR]

Background and Aims: Deep repetitive Transcranial Magnetic Stimulation (deep rTMS) over the bilateral insula and prefrontal cortex (PFC) can promote weight-loss in obesity, preventing cardiometabolic complications as Type 2 Diabetes (T2D). To investigate the changes in the functional brain integration after dTMS, we conducted a resting-state functional connectivity (rsFC) study in obesity.Methods and Results: This preliminary study was designed as a randomized, double-blind, sham-controlled study: 9 participants were treated with high-frequency stimulation (realTMS group), 8 were sham-treated (shamTMS group). Out of the 17 enrolled patients, 6 were affected by T2D. Resting-state fMRI scans were acquired at baseline (T0) and after the 5-week intervention (T1). Body weight was measured at three time points [T0, T1, 1-month follow-up visit (FU1)]. A mixed-model analysis showed a significant group-by-time interaction for body weight (p = .04), with a significant decrease (p < .001) in the realTMS group. The rsFC data revealed a significant increase of degree centrality for the realTMS group in the medial orbitofrontal cortex (mOFC) and a significant decrease in the occipital pole.Conclusion: An increase of whole-brain functional connections of the mOFC, together with the decrease of whole-brain functional connections with the occipital pole, may reflect a brain mechanism behind weight-loss through a diminished reactivity to bottom-up visual-sensory processes in favor of increased reliance on top-down decision-making processes.Trial Registration Number: ClinicalTrials.gov NCT03009695. [ABSTRACT FROM AUTHOR]

To determine the influence of cognitive functioning on gait recovery after total hip arthroplasty. Prospective cohort study. Rehabilitation hospital. Patients (N=40) who underwent a total hip arthroplasty, with normal cognitive functioning and without any other relevant medical condition, were recruited and studied before surgery and at the beginning and the end of the rehabilitation program. Gait speed (10-Meter Walk Test [10MWT]) and gait functional mobility (Timed Up and Go [TUG] test), measured at the time of discharge from the rehabilitation unit, were the primary outcomes. The candidate predictors were the cognitive and psychological variables collected in the presurgery phase, together with other potentially informative measures such as age, education, perceived pain, body mass index, presurgical gait speed and functional mobility. Our results suggest the existence of a direct relationship between cognitive functioning, with specific reference to high-level frontal executive functions, and the postoperative gait progress: the better the cognitive functioning in the preoperative phase, the better the course of recovery in terms of gait speed and functional mobility. In particular, the performance of the Frontal Assessment Battery test, together with age, perceived pain. Presurgical gait speed and functional mobility, was the best predictor of recovery of walking measured by 10MWT and TUG. The present study highlights the importance of cognitive functioning, together with clinical and demographic features, in the postsurgical recovery of walking, even in the absence of cognitive decline. In particular, these data show the crucial role of higher-order cognitive processes, such as executive functions, involved in the formulation of motor plans and their integration with proprioceptive and visual cues. [ABSTRACT FROM AUTHOR]

• COVID-19 lockdown led to a significant increase in residential electricity usage. • Shift in energy usage from morning peak to central hours registered during lockdown. • The study provides a set of daily load profiles for residential buildings. • Remote working can have a significant impact on energy use in residential buildings. • Findings can assist cities analysts, regulators and businesses in weighing effects of remote working. The COVID-19 pandemic had a profound impact on society, causing changes in various aspects of people's lives, including their energy use habits. This has prompted a need for checking and updating standard energy use profiles, particularly for residential electricity use. To address this topic, a study was conducted on 24 multifamily buildings in Milan, using clustering to extract patterns from a database of quarter-hourly electricity use data from 2019 to 2020. This study found an increase in electricity usage during the COVID-19 lockdown period for residential buildings, likely associated with the imposed restrictions. The research also highlighted a shift in energy usage from the morning peak to the central hours of the day during the working days of the lockdown period, while a gradual increase in electricity usage throughout the day and no morning peak was observed during the Autumn (post-COVID) period. The findings can assist regulators and businesses in weighing the benefits and drawbacks of remote working and provide modellers with a complete set of daily load profiles for an Italian residential case study. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the correlation between different haptoglobin (Hp) phenotypes and myocardial infarction characteristics as detected by cardiac magnetic resonance (CMR) in consecutive patients after ST-segment elevation myocardial infarction (STEMI). Hp is a plasma protein that prevents iron-mediated oxidative tissue damage. CMR has emerged as the gold standard technique to detect left ventricular ejection fraction (LVEF), extent of scar with late gadolinium enhancement (LGE) technique, microvascular obstruction (MVO), and myocardial hemorrhage (MH) in patients with STEMI treated by primary percutaneous coronary intervention (pPCI). A total of 145 consecutive STEMI patients (mean age 62.2 ± 10.3 years; 78% men) were prospectively enrolled and underwent Hp phenotyping and CMR assessment within 1 week after STEMI. CMR showed an area at risk (AAR) involving 26.6 ± 19.1% of left ventricular (LV) mass with a late LGE extent of 15.2 ± 13.1% of LV mass. MVO and MH occurred in 38 (26%) and 12 (8%) patients, respectively. Hp phenotypes 1-1, 2-1, 2-2 were observed in 15 (10%), 62 (43%), and 68 (47%), respectively. Multivariable analysis demonstrated that body mass index, Hp2-2, diabetes, and peak troponin I were independent predictors of MVO with Hp2-2 associated with the highest odds ratio (OR) (OR: 5.5 [95% confidence interval [CI]: 2.1 to 14.3; p < 0.001]). Hp2-2 significantly predicted both the presence (area under the curve [AUC]: 0.63 [95% CI: 0.53 to 0.72; p = 0.008]) and extent of MVO (AUC: 0.63 [95% CI: 0.54 to 0.72; p = 0.007]). Hp phenotype is an independent predictor of MVO. Therefore, Hp phenotyping could be used for risk stratification and may be useful in assessing new therapies to reduce myocardial reperfusion injury in patients with STEMI. [ABSTRACT FROM AUTHOR]

Graphical abstract While often multicomponent reactions (MCR) are used for the diversity-oriented synthesis of racemic (or achiral) molecular entities, this short review describes two alternative approaches for accessing enantiopure products exploiting the power of biocatalysis. Enzymes or microorganisms may be used for preparing enantiopure MCR inputs or for resolving racemic (or achiral) MCR adducts. [ABSTRACT FROM AUTHOR]

• Cognitive profile and physician-based and patients-reported outcomes could have a considerable impact on the disease management and on treatment decision making. • According to the Control Preference Scale, more than 50% of patients who needed to change therapy chose a "collaborative" role in making treatment decision. • Cognitive profile with SDMT seems to influence patients' preference on treatment decision. Clinicians are increasingly recognizing the importance of shared decision-making in complex treatment choices, highlighting the importance of the patient's rationale and motivation for switching therapies. This study aimed to evaluate the association between different modalities of changing multiple sclerosis (MS) treatments, cognitive profile and attitude and preferences of patients concerning treatment choice. This multicenter cross-sectional study was conducted at 28 Italian MS centers in the period between June 2016 and June 2017. We screened all MS patients treated with any DMT, with a treatment compliance of at least 80% of therapy administered during the 3 last months who needed to modify MS therapy because of efficacy, safety or other reasons during a follow-up visit. At the time of switching the symbol digit modalities test (SDMT) and the Control Preference Scale (CPS) were evaluated. According to the CPS, patients were classified as "active" (i.e. who prefer making the medical decision themselves), "collaborative" (i.e. who prefer decisions be made jointly with the physician), or "passive" (i.e. who prefer the physician make the decision). Out of 13,657 patients recorded in the log, 409 (3%) changed therapy. Of these, 336 (2.5%) patients, 69.6% were female and with mean age 40.6 ± 10.5 years, were enrolled. According to the CPS score evaluation, a significant high percentage of patients (51.1%) were considered collaborative, 74 patients (22.5%) were passive, and 60 (18.2%) patients were active. Stratifying according to CPS results, we found a higher SDMT score among collaborative patients compared to active and passive ones (45.8 ± 12.3 versus 41.0 ± 13.2 versus 41.7 ± 12.8, p < 0.05). In this study, the CPS evaluation showed that more than 50% of patients who needed to change therapy chose a "collaborative" role in making treatment decision. Cognitive profile with SDMT seems to correlate with patients' preference on treatment decision, showing better scores in collaborative patients. [ABSTRACT FROM AUTHOR]

The growing health and economic burden of bone fractures, their intricate multiscale features and the existing knowledge gaps in the comprehension of micro-scale bone damage occurrence make fracture diagnosis a challenging issue. In this scenario, deep-learning and artificial intelligence embody the new frontier of healthcare system, by overcoming the subjectivity of clinicians in the analysis of medical images. However, the preliminary attempts in exploiting the power of machine learning algorithms such as neural networks are still limited to bone macro-scale, while there is an evident lack in their application to smaller scales, where damage starts nucleating. Currently, speculations at the micro-scale are only feasible with the aid of high-resolution imaging techniques, that are particularly time consuming in terms of output images analysis. In this context, this works aims at combining the visualization of the micro-crack propagation mechanism with the promising application of convolutional neural networks. The implemented artificial intelligence tool is based for the first time on a large number of human synchrotron images coming from healthy and osteoporotic femoral heads tested under micro-compression. The designed convolutional neural networks are able to automatically detect lacunae and micro-cracks at different compression levels with high accuracy levels; indeed, with the baseline setup, networks achieve more than 0.99 level of accuracy for both cracks and lacunae, and more than 0.87 of the meanIoU adopted as validation metric. This approach is particularly encouraging for the development of powerful recognition system to comprehend bone micro-damage initiation and propagation, paving the way to the application of machine learning studies to bone micromechanics. This could be additionally crucial for future patient specific micro-scale observations to be related to the clinical practice. [Display omitted] • The comprehension of bone micro-damage is crucial for bone fracture prevention. • The implementation of a VGG16 Neural Network is an optimal strategy to separately identify bone lacunae and micro-damages. • The implemented neural network increases the detected bone micro-features even in presence of artifact-affected synchrotron images. [ABSTRACT FROM AUTHOR]

Therapeutic over-expression of Vascular Endothelial Growth Factor (VEGF) by transduced progenitors is a promising strategy to efficiently induce angiogenesis in ischemic tissues (e.g. limb muscle and myocardium), but tight control over the micro-environmental distribution of the dose is required to avoid induction of angioma-like tumors. Therapeutic VEGF release was achieved by purified transduced adipose mesenchymal stromal cells (ASC) that homogeneously produce specific VEGF levels, inducing only normal angiogenesis after injection in non-ischemic tissues. However, the therapeutic potential of this approach mostly in the cardiac field is limited by the poor cell survival and the restricted area of effect confined to the cell-injection site. The implantation of cells previously organized in vitro in 3D engineered tissues could overcome these issues. Here we hypothesized that collagen sponge-based construct (patch), generated by ASC expressing controlled VEGF levels, can function as delivery device to induce angiogenesis in surrounding areas (extrinsic vascularization). A 7-mm-thick acellular collagen scaffold (empty), sutured beneath the patch, provided a controlled and reproducible model to clearly investigate the ongoing angiogenesis in subcutaneous mice pockets. VEGF-expressing ASC significantly increased the capillary in-growth inside both the patch itself and the empty scaffold compared to naïve cells, leading to significantly improved survival of implanted cells. These data suggest that this strategy confers control (i) on angiogenesis efficacy and safety by means of ASC expressing therapeutic VEGF levels and (ii) over the treated area through the specific localization in an engineered collagen sponge-based patch. Statement of Significance Development of efficient pro-angiogenic therapies to restore the micro-vascularization in ischemic tissues is still an open issue. Although extensively investigated, the promising approach based on injections of progenitors transduced to over-express Vascular Endothelial Growth Factor (VEGF) has still several limitations: (i) need of a tight control over the microenvironmental VEGF dose to avoid angioma-like tumor growth; (ii) poor implanted cell survival; (iii) effect area restricted mainly to the injection sites. Here, we aimed to overcome these drawbacks by generating a novel cell-based controlled VEGF delivery device. In particular, transduced mesenchymal cells, purified to release a sustained, safe and efficient VEGF dose, were organized in three-dimensional engineered tissues to improve cell survival and provide a uniform vascularization throughout both the mm-thick implanted constructs themselves and the surrounding area. [ABSTRACT FROM AUTHOR]

Background: Assessment of vascular endothelial function lacks consistency, and microvascular endothelial function has been only partly assessed in heart failure with preserved ejection fraction (HFpEF).Methods: The study population consisted of 90 patients: 45 had well documented HFpEF, and 45 had hypertension and no history or evidence of heart failure. Patients with hypertension but no heart failure were matched with HFpEF patients for age, sex, and diabetes. They served as control subjects. All patients underwent 2-dimensional Doppler echocardiography and vascular function measurements, including assessment of arterial wave reflections and arterial stiffness, brachial artery flow-mediated dilation (FMD), and forearm cutaneous blood flow with the use of a laser Doppler flow probe at rest and after release of arterial occlusion for 5 minutes.Results: Brachial artery FMD was lower in HFpEF than in control subjects (median (IQR) 3.6 (0.4-7.4) vs. 7.2 (3.2-17.2)%, P = .001). Forearm cutaneous blood flow at rest was similar in HFpEF and control subjects (P = .68). After release of arterial occlusion, forearm cutaneous peak blood flow was lower in HFpEF than in control subjects (P = .03). Estimated aortic systolic and mean blood pressures were similar in HFpEF and control subjects, whereas pulse pressure and pressure augmentation were greater in HFPEF than in control subjects (both P < .05).Conclusion: Compared with hypertensive control subjects, patients with HFpEF had a depressed endothelial function in the forearm vasculature and microvasculature. [ABSTRACT FROM AUTHOR]

Different variables concur to the outdoor comfort assessment and, among them, the Mean Radiant Temperature ( T mr ) represents the most challenging one to experimentally evaluate. According to the scientific literature, the most accurate method for in-field T mr calculation is integral radiation measurements with three net radiometers. Nevertheless, net radiometers are expensive sensors and their implementation on large scale may be hindered by their price. To provide a cost-effective alternative some researchers proposed the use of globe thermometers. Globe thermometers are affordable sensors but typically exploited indoors, and their accuracy in urban settings is still under investigation. The scope of this work is to provide information regarding the extent to which globe thermometers can substitute net radiometers in the evaluation of the T mr in outdoor urban settings. To this purpose, an experimental comparison has been performed between the T mr calculated using net radiometers, assumed as a reference, and using two different globe thermometers: a standard 150 mm black globe and a grey 50 mm globe. The results revealed that the black globe tends to overestimate the T mr while the grey globe mainly underestimates it. Moreover, the analyses evidenced a wide fluctuation in the profile of the T mr calculated using globe thermometers, due to the rapid variation of meteorological parameters and the globes' long response time. To improve the fit between globe thermometers and net radiometers' response, regressive functions have been proposed, resulting in a significant enhancement of the adherence between T mr calculated using the standard black globe's measurements and the reference T mr . • T mr is key parameter for outdoor thermal comfort assessment in urban settings. • Globe thermometers cannot directly substitute net radiometers to assess the T mr. • A regression equation is used to assess the T mr from the standard globe thermometer. • In 90.4% of cases, the equation results in a negligible error for T mr. • This result decreases greatly the cost and number of required sensors. [ABSTRACT FROM AUTHOR]

Survival after cardiac arrest depends on prompt and effective cardiopulmonary resuscitation (CPR). Resuscitative teams are more frequently using mechanical chest compression devices, as documented in physiologic and experimental data, suggesting that these devices are more effective than manual CPR. A 41-year-old male patient presented with an ST-elevation myocardial infarction with cardiac arrest. The patient was immediately resuscitated by manual chest compressions; CPR was continued with a mechanical chest compression device (LUCAS 2). The patient had experienced a 15-minute period of “low-flow” without “no-flow” episode. After a discussion with the heart team, we decided that the patient was a candidate for extracorporeal membrane oxygenation (ECMO) therapy. During the ECMO implantation, we noticed that while performing transesophageal echocardiography, chest compressions were ineffective with the machine. After the ECMO implantation, we observed myocardial damage in the right-sided heart cavities. The present case report illustrates the likelihood that the mechanical chest compression device has limitations that might contribute to inadequate CPR. Therefore, rescuers should consider the efficacy of their chest compression through a continuous hemodynamic monitoring during CPR. [ABSTRACT FROM AUTHOR]

Objective Sports people always strive to avoid injury. Sports shoe designs in many sports have been shown to affect traction and injury rates. The aim of this study is to demonstrate the differing stiffness and torque in rugby boots that are designed for the same effect. Methods Five different types of rugby shoes commonly worn by scrum forwards were laboratory tested for rotational stiffness and peak torque on a natural playing surface generating force patterns that would be consistent with a rugby scrum. Results The overall internal rotation peak torque was 57.75±6.26Nm while that of external rotation was 56.55±4.36Nm. The Peak internal and external rotational stiffness were 0.696±0.1 and 0.708±0.06Nm/deg respectively. Our results, when compared to rotational stiffness and peak torques of football shoes published in the literature, show that shoes worn by rugby players exert higher rotational and peak torque stiffness compared to football shoes when tested on the same natural surfaces. There was significant difference between the tested rugby shoes brands. Conclusion In our opinion, to maximize potential performance and lower the potential of non-contact injury, care should be taken in choosing boots with stiffness appropriate to the players main playing role. [ABSTRACT FROM AUTHOR]

Abstract: Background and aim: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear. Methods and results: Fifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4+HLA-DR+ and CCR5+ T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets. Conclusion: HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which ‘classic’ CV risk factors give a continuous contribution, together with immunological factors (CD4+HLA-DR+ T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis. [Copyright &y& Elsevier]

Abstract: Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis. [Copyright &y& Elsevier]

Background: No biological marker is currently available for evaluating pulmonary involvement and/or for monitoring the clinical course of sarcoidosis. The present pilot study focused on possible relationships between circulating plasma levels of surfactant protein type B (SP-B) and plasma receptor for advanced glycation end products (RAGE) and lung function abnormalities in patients with pulmonary sarcoidosis, since both SP-B and RAGE have been previously suggested as lung injury markers. The plasmatic levels of these two proteins were also investigated with respect to functional capacity, as assessed by a cardiopulmonary exercise test (CPET). Methods: Thirty pulmonary sarcoidosis outpatients and fifteen volunteers (Control Group) underwent lung function tests and CPET. Resting SP-B and RAGE plasma levels were also determined. Patients were then categorized according to the severity of their pulmonary involvement, as assessed in terms of lung diffusion for carbon monoxide (DLCO) values. Results: Group B showed SP-B levels higher and RAGE levels lower than Group A and Control Group (p < 0.01). Group A showed lower RAGE levels than Control Group (p < 0.01), whereas SP-B levels did not differ between these two groups. A significant univariate relationship was found between both SP-B and RAGE and several lung function data, particularly with DLCO (SP-B Vs DLCO: r: -0.437, p = 0.016; RAGE Vs DLCO: r: -0.451, p = 0.012). Conclusions: Circulating plasma levels of SP-B and RAGE showed an opposite behavior in patients with pulmonary sarcoidosis. SP-B values are directly related to alveolar unit damage, supporting a possible role of SP-B as a marker of disease severity in these patients. Differently, RAGE decreases in severe sarcoidosis, suggesting more complex underlying mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: The strontium is an alkaline earth metal found in nature as trace element. Chemically similar to calcium, it is known to be involved in the human bone mineral metabolism. The strontium ranelate has been approved in therapy as drug with both anti-resorption and anabolic effects on bone tissues. Since few data in vivo are available, we used Danio rerio as animal model to evaluate the effects of strontium on skeletal development. First, toxicity assay performed on zebrafish embryos estimated the LC50 around 6mM. Since several zebrafish bones are formed from cartilage mineralization, we evaluated whether strontium affects cartilage development during embryogenesis. Strontium does not perturb the development of the cartilage tissues before the endochondral osteogenesis takes place. About the mineralization process, we evidentiated an increase of vertebral mineralization respect to controls at lower strontium concentrations whereas higher concentration inhibited mineral deposition in dose dependent fashion. Our results evidentiated, in addition, that the calcium/strontium rate but not the absolute level of strontium modulates the mineralization process during embryonic osteogenesis. Zebrafish represents an excellent animal model to study the role of micronutrients in the development of the tissues/organs because the ions are not absorbed by intestine but assumed by skin diffusion. [Copyright &y& Elsevier]

Objective: Moderate to severe aortic regurgitation is occurring in 20% to 30% of cases after transcatheter aortic valve implantation. Methods: The purpose of the study was to investigate the impact of a prospective policy of “oversizing” the Edwards SAPIEN bioprosthesis (Edwards Lifesciences LLC, Irvine, Calif) relative to the diameter of the aortic annulus on the rate and severity of aortic regurgitation in 28 consecutive patients initially considered eligible for transcatheter aortic valve implantation on the basis of angiography, multislice computed tomography, and transthoracic echocardiography. This policy included the systematic use of transesophageal echocardiography to exclude borderline patients and the modification of the procedure to use the larger device possible. The results were studied on an individual patient basis. Results: Because 6 of 28 patients (21%) had an annulus diameter greater than 24 mm by transesophageal echocardiography, 22 patients underwent implantation of the Edwards SAPIEN prosthesis. In 6 of 22 patients, the procedure was adapted to follow our “oversizing” policy. As a result, the “prosthesis/annulus cover index” was 12.4% ± 4.3%. The procedure was successful in 21 of 22 patients (95%), and 18 patients were available for echocardiography at 1 month. Although a moderate to severe aortic regurgitation was observed pretreatment in 4 of 18 patients (22%), it was no longer the case at 1 month (0/18, 0%; P = .03). The improvement was secondary to a disappearance of the aortic regurgitation in all 7 patients with a significant aortic regurgitation at pretreatment, whereas the new aortic regurgitations appearing in 5 of the 11 patients with no aortic regurgitation at pretreatment were only mild aortic regurgitations. Conclusions: In patients with a successful implantation of an Edwards SAPIEN valve, a simple “oversizing” policy based on a systematic use of transesophageal echocardiography and modification of the procedure may prevent the occurrence of moderate and severe aortic regurgitations. [Copyright &y& Elsevier]

Background: The risk of reoperation on the autograft and homograft is the major long-term drawback of the Ross procedure. The incidence and clinical implications of reoperations after the Ross procedure are reported. Methods: Between March 1992 and February 2010, 336 consecutive patients had a Ross procedure (mean follow-up, 6.2 ± 4.9 years). Autograft implant technique was freestanding root replacement in 269 patients, subcoronary implantation in 52 patients and a modified root replacement with the autograft included in a Valsalva tube graft in 15. Results: Subsequently, 38 patients (11.3%) underwent reoperations, for autograft dilatation in 23 and a significant autograft insufficiency in 9, at 9.6 ± 3.7 years and 2.6 ± 3.9 years, respectively. Aortic and pulmonary infective endocarditis occurred in 3 patients. Three patients underwent a non valve-related cardiac reoperation. Three patients received a transcatheter pulmonary valve implantation after 12.2 ± 1.7 years. At 15 years, freedoms for autograft and homograft explantation (with 95% confidence interval) were 83.3% (77.4%- to 9.2%) and 92.8% (87.6% to 97.9%), respectively. Native aortic valve regurgitation, indexed aortic annulus diameter exceeding 1.35 cm/m2 and autograft diameter were risk factors for dilated autograft reoperation (hazard ratio, 3.23 [95% confidence interval, 1.19 to 8.81], p = 0.02; 3.83 [0.9 to 16.33], p = 0.07 and 1.2 per mm [1.01 to 1.41], p = 0.03), respectively. Conclusions: Autograft dilatation was the leading cause of reoperation in patients who underwent root replacement. Long-term follow-up is mandatory to determine whether modifications of the operative technique could limit autograft dilatation. [Copyright &y& Elsevier]

BACKGROUND: Patients with heart failure with preserved ejection fraction (HFpEF) may present with Pulmonary hypertension (PH) and functional mitral regurgitation (MR). Whether PH is linked to the presence of functional MR has not been investigated in HFpEF patients. METHODS AND RESULTS: Systolic pulmonary artery pressure (sPAP) and functional MR were assessed by 2-dimensional Doppler echocardiography in 70 ambulatory HFpEF patients and 70 hypertensive control subjects free of organic mitral valve lesions, significant valve disease, and comorbid conditions associated with PH. Whereas none of control subjects had more than trivial MR, 21 patients with HFpEF had functional MR (mean mitral effective regurgitant orifice, regurgitant volume, and regurgitant fraction 7 ± 3 mm,(2) 15 ± 8 mL, and 28 ± 14%, respectively). Pulmonary hypertension (sPAP >35 mm Hg) was significantly more prevalent in HFpEF patients with functional MR than in HFpEF patients without functional MR (62 vs 22%; P = .002). Functional MR remained an independent predictor of PH in HFpEF patients (P = .004) after adjustment on mitral E wave to e' mitral annulus velocity ratio (E/e'; P = .022) and left atrial volume index (P = .025). Systolic PAP and E/e' were greater in HFpEF patients than in control subjects (35 ± 9 vs 29 ± 8 mm Hg [P < .0001] and 13 ± 6 vs 11 ± 5 [P = .018], respectively). Systolic PAP remained greater in HFpEF patients than in control subjects after adjusting for E/e' (P = .002). CONCLUSIONS: Pulmonary hypertension appears to be linked to the presence of functional MR in HFpEF patients. [ABSTRACT FROM AUTHOR]

Summary: Discovering new drugs to treat tuberculosis more efficiently and to overcome multidrug resistance is a world health priority. To find antimycobacterial scaffolds, we screened a kinase inhibitor library of more than 12,000 compounds using an integrated strategy involving whole cell-based assays with Corynebacterium glutamicum and Mycobacterium tuberculosis, and a target-based assay with the protein kinase PknA. Seventeen “hits” came from the whole cell-based screening approach, from which three displayed minimal inhibitory concentrations (MIC) against M. tuberculosis below 10μM and were non-mutagenic and non-cytotoxic. Two of these hits were specific for M. tuberculosis versus C. glutamicum and none of them was found to inhibit the essential serine/threonine protein kinases, PknA and PknB present in both bacteria. One of the most active hits, VI-18469, had a benzoquinoxaline pharmacophore while another, VI-9376, is structurally related to a new class of antimycobacterial agents, the benzothiazinones (BTZ). Like the BTZ, VI-9376 was shown to act on the essential enzyme decaprenylphosphoryl-β-D-ribose 2′-epimerase, DprE1, required for arabinan synthesis. [Copyright &y& Elsevier]

Objective: The Ross procedure is widely used for aortic valve disease in patients who are still growing and young adults with active lifestyles or the desire for pregnancy. The need for autograft reoperation remains the principal limitation of the procedure. Autograft inclusion in a polyester tube prosthesis has been proposed with good postoperative results, but the durability of these technical modifications has not been assessed. We report the midterm results of pulmonary autograft reinforcement with a Valsalva Gelweave Dacron tube (Terumo Cardiovascular Systems Inc, Ann Arbor, Mich). Methods: Since 1992, we have performed 322 Ross operations; 12 patients underwent a modified Ross procedure with the autograft included in a Valsalva Gelweave Dacron tube. The mean age of these patients was 29.7 ± 10.8 years (range, 15.3–46.5 years). The mean aortic crossclamp time was 126 ± 11 minutes (range, 110–142 minutes). The mean follow-up was 4 ± 1.4 years (range 1.7–5.8 years). Results: No perioperative deaths were observed, and all patients are alive and doing well. No significant autograft regurgitation was recorded during follow-up. The mean diameters of the autograft annulus and the neosinus of Valsalva were 23.3 ± 2.6 mm and 32.6 ± 3.3 mm, respectively, at discharge, and 24.0 ± 1.9 mm and 33.6 ± 3.3 mm, respectively, at the last control (P = .32 and P = .08, respectively). Conclusion: These results support that this technical modification of the Ross operation might be proposed for patients at risk of autograft dilatation when an inclusion technique is not feasible. [Copyright &y& Elsevier]

Summary: Background: This study estimated the healthcare resource utilisation and costs of chronic obstructive pulmonary disease (COPD) patients, staged by severity, in the Italian pneumology departments (PDs). Methods: The project was a multi-centre observational study conducted in 11 Italian PDs throughout the country. A total of 268 patients were recruited and followed prospectively for 1 year. For the purpose of analysis, patients were divided into four groups according to the severity at onset: [•] mild COPD (stage I)—postbronchodilator FEV1/FVC <70% and FEV1 ⩾ 80% of predicted; [•] moderate COPD (stage II)—postbronchodilator FEV1/FVC <70% and 50% ⩽FEV1< 80% of predicted; [•] severe COPD (stage III)—postbronchodilator FEV1/FVC <70% and 30% ⩽FEV1 <50% of predicted; [•] very severe COPD (stage IV)—postbronchodilator FEV1/FVC <70% and FEV1 <30% of predicted, or clinical signs of either respiratory or cardiac failure. Results: Subgroups differed significantly in the main demographic and clinical variables. Broadly, higher severity was associated with older age, longer disease duration, and more frequent exacerbations. Patients with severe COPD used more resources for almost all services than those with mild and moderate forms. The annual average cost per patient was €3040.2 (€1046.7 for mild, €2319.0 for moderate, €3572.1 for severe and €5033.3 for very severe forms). Conclusions: This study offers some information on the healthcare costs of COPD induced by PDs in Italy, potentially useful for decision-making in the health care services. Resources and costs rose significantly with disease severity. [Copyright &y& Elsevier]

BACKGROUND: Mixed cryoglobulinemia is a multisystem disorder associated strongly with hepatitis C virus (HCV) infection. The kidney frequently is involved, and glomerulonephritis represents the key factor affecting prognosis. METHODS: Clinical, serological, immunogenetic, and morphological data were collected retrospectively from medical records of 146 patients with cryoglobulinemic glomerulonephritis who underwent biopsies in 25 Italian centers and 34 cryoglobulinemic controls without renal involvement. RESULTS: Eighty-seven percent of patients were infected with HCV; genotype 1b was more frequent than genotype 2 (55% versus 43%). Diffuse membranoproliferative glomerulonephritis was the most prevalent histological pattern (83%). Type II cryoglobulin (immunoglobulin Mkappa [IgMkappa]/IgG) was detected in 74.4% of cases. The remainder had type III (polyclonal IgM/IgG) cryoglobulins. A multivariate Cox proportional hazard model showed that age, serum creatinine level, and proteinuria at the onset of renal disease were associated independently with risk for developing severe renal failure at follow-up. Overall survival at 10 years was about 80%. Kaplan-Meier survival curves were worsened by a basal creatinine value greater than 1.5 mg/dL (>133 mumol/L), but were unaffected by sex and HCV infection. Cardiovascular disease was the cause of death in more than 60% of patients. CONCLUSION: Data confirm the close association between mixed cryoglobulinemia and HCV infection and between glomerulonephritis and type II cryoglobulin. Survival profiles are better than previously reported in the literature, probably because of improvement in therapeutic regimens. Causes of death reflect this improvement in survival, with an increased prevalence of cardiovascular events compared with infectious complications and hepatic failure, which were predominant in the past. [ABSTRACT FROM AUTHOR]

Herbs have been used for voice care since ancient times and many herbal remedies are still in use in every geographical areas and cultures, both as traditional medicine and as sources of botanicals used in commercial products. Many of these plants are used as extracts and other phytopreparates, and a full phytochemical analysis is sometimes incomplete or lacking. The mechanisms of action of these botanicals include antibacterial, anti-inflammatory, mucolytic, and other general activities; nevertheless, mechanisms that could be specifically referred to voice are often unknown, as well as the corresponding molecular targets and therefore a rational approach in the use of these remedies is hard to be applied by phoniatricians. To address this problem, we collected information on plants used for voice care from several different geographical areas, using both literature data and a pool of contributors from an international network of artistic phoniatrics and vocologists. The plants have been organized in a database (Herbs for Voice Database) and classified according to the natural compounds contained in them, their molecular targets and the pathologies they are recommended for. This first database contains 44 plants, 101 phytocompounds, and 32 recognized molecular targets. The distribution of herbs and phytocompounds according to the botanical families, their known biological activity, traditional uses, and molecular targets were analyzed. In particular, data analysis shows that the somatosensory and pain receptor Transient Receptor Potential Ankyrin 1 ion channel is targeted by a large number of different phytochemicals contained in the herbs for voice, and could therefore be involved in a mechanism of action common to many plants. [ABSTRACT FROM AUTHOR]

The investigation of plant assemblages growing in urban ecosystems offers the chance to observe new interactions among biodiversity, urban planning and public health, in the context of a changing world with increasing city surfaces and populations. In this context, the aim of this work is the study of floristic, ecological and functional diversity of land use types of Milan, such as a) Built-up areas (urbanized and productive zones), b) Roads (borders and flowerbed of main boulevards and avenues), c) Railways (tracks borders, stations and adjacencies) and d) Green areas (parks, gardens, and orchards). A floristic survey was performed through stratified sampling and a floristic database was built. The following bioecological information was added to each sampling location: species richness, %alien species, %families, %life forms, functional diversity, %Grime's CSR strategies, Ellenberg's indicator values (EIVs), urbanity index and functional diversity estimators. Differences among land use types were detected with linear mixed models. In total, about 300 taxa were recorded, and 34 % of the species surveyed were aliens. The Railways were prominent with regard to several traits such as floristic richness, number of insect-pollinated species, mean EIV for light and soil reaction and functional diversity estimators. On the other hand, the urbanity index was the lowest in Railways. In general, Urban areas and Roads had lower trait values, while Green areas had intermediate performances. Our results showed that despite the expected high presence of ruderal and alien species, typical of disturbed environments, the urban landscapes of Milan are diversified in their ecological functions and included areas rich in uncommon species limited to peculiar habitats. The railway landscape of Milan represents a reservoir and refuge for many native species, incorporating microhabitats not present in other city landscapes. Therefore, railway areas should be included in the planning of green networks to improve connectivity and support the nature in urban landscapes. [ABSTRACT FROM AUTHOR]

Reimplantation of the largest patent intercostal arteries is usually performed during thoracoabdominal aortic aneurysm repair. This may lead to aneurysmal evolution of the intercostal arteries patch. We report the successful percutaneous endovascular repair in 4 Marfan patients of aneurysms of the intercostal arteries patch that developed after thoracoabdominal aortic aneurysm repair (Crawford type II) during a mean delay of 70 months (range, 48 to 91 months). All patients had previously undergone one or several aortic surgical procedures and had patent subclavian and hypogastric arterial networks. No in-hospital deaths or spinal cord ischemic injuries occurred, which emphasizes the importance of the vascular collateral network. [ABSTRACT FROM AUTHOR]

Pheochromocytoma is a catecholamine-secreting tumor associated with clinical presentations ranging from paroxysmal hypertension to intractable cardiogenic shock. We report the use of central extracorporeal life support (ECLS) in a young woman admitted to the intensive care unit with cardiogenic shock. Her medical history included neurofibromatosis type I and pheochromocytoma. ECLS was needed because of severe left ventricular failure and inotropic therapy unresponsiveness. ECLS permitted full recovery of left ventricular function. Right adrenelectomy was performed 4 months later. In this case, central ECLS was used to treat pheochromocytoma-induced cardiogenic shock complicated by pulmonary edema. [ABSTRACT FROM AUTHOR]

The authors conducted a retrospective study of 1857 consecutive pregnant women with positive screening for anti-cytomegalovirus (CMV) immunoglobulin M (IgM) antibodies to determine weather diagnostic and confirmatory laboratory tests in conjunction with prenatal counseling by a physician affected the rate of Induced abortions in women with positive CMV IgM antibody titers. [ABSTRACT FROM PUBLISHER]

• The addition of lamotrigine induce a Brugada pattern on the electrocardiogram. • SCN9A variant was responsible for the epileptic syndrome. • SCN9A might be responsible for the Brugada pattern when challenged by lamotrigine. A 30-year-old man presented with intellectual disability associated with epilepsy. The epilepsy was initially treated with sodium valproate and since he was 28 years-old with lamotrigine. With the addition of lamotrigine, a pattern of Brugada syndrome appeared on the electrocardiogram. The family history was positive for epilepsy from the motheŕs side, who had never been treated with lamotrigine. Determine the genetic cause of the intellectual disability, epilepsy and Brugada syndrome of the patient and try to establish a possible correlation between the genetic background and the Brugada syndrome pattern under lamotrigine treatment. A standard karyotype, array comparative genomic hybridization and two different NGS panels have done to the index case to identify the genetic causes of the intellectual disability, epilepsy and Brugada syndrome pattern. Genetic analyses in the family identified a de novo duplication of 1.3 Mb in 8p21.3 as well as two novel heterozygous rare variants in SCN9A and AKAP9 genes, both inherited from the mother. We hypothesize that in this family the SCN9A variant was responsible for the epileptic syndrome. In addition, given that SCN9A is lightly expressed in the heart tissue, we postulate that this SCN9A variant, alone or in combination with AKAP9 variant, might be responsible for the Brugada pattern when challenged by lamotrigine. [ABSTRACT FROM AUTHOR]

• The introduction of increasingly effective treatments has changed the MS scenario. • This study investigated the reasons that brought about modification of treatment. • In our study, out of 13,657 patients, 336 (3%) modified treatment. • 90.2% switched, 8.9% temporarily discontinued, and 0.9% permanently discontinued. • Efficacy remains the main driving force behind switching in 58.4% of patients. clinical factors and frequency of disease-modifying therapy (DMT) changes/interruptions in relapsing-remitting multiple sclerosis (RRMS) patients have not been well defined. The aim of this study was to describe reasons of MS treatment modifications in a large cohort of Italian MS patients. this multicenter, cross-sectional non interventional study (SWITCH) conducted at 28 Italian MS centers, screened, by visit/telephone contact between June 2016 and June 2017, all RRMS patients receiving stable DMT treatment and enrolled patients with change in DMT treatment. out of 13,657 recorded in the log, 409 (3%) changed therapy. Of these, 336 (2.5%), met the study criteria and were considered eligible. Among 303 (90.2% of 336) patients switching, the most common reason was "lack of efficacy" (58.4% of 303). Among 30 (8.9%) patients who interrupted treatment temporarily, the most common reason was pregnancy (40.0% of 30). Out of 3 (0.9%) patients who discontinued treatment permanently, 2 (66.7%) had as first reason as "patient decision". Multivariate analysis showed that EDSS was the only variable with statistically significant effect on changing treatments (r = 8.33; p -value of Type III Sum of Squares = 0.016). in our study, 303 (90.2% of eligible patients) switched treatment, 30 (8.9%) interrupted treatment temporarily, and 3 (0.9%) discontinued treatment permanently. Efficacy remains the main driving force behind switching behavior, as the primary aim of treatment is to be disease free or reduce disease activity. [ABSTRACT FROM AUTHOR]

Objective: This study explores the hypothesis that cognitive expectations of catching influenza-like symptoms increase the chances of developing the symptoms over the winter season.Design: Self-reported data from 247 healthy volunteers were obtained twice, before and after the winter season. In the first assessment, expectations about developing influenza-like symptoms in the incoming months were charted. This data was matched with a post-winter assessment of the actual development of the symptoms.Results: The odds of developing symptoms were highly associated with the expectations declared months before (OR = 1.776), and the association remained stable (OR = 1.453) even when accounting for previous influenza-like illnesses and the perception of general health. In contrast with previous findings, perceived stress was not associated with symptom development.Conclusions: These results support the hypothesis of a self-fulfilling prophecy mechanism related to influenza-like symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Whole-body cryotherapy refers to brief exposure to very cold air for treating symptoms of various illnesses. In sports medicine, whole-body cryotherapy is administered to improve recovery from muscular trauma. As specific studies are lacking, we measured cardiac markers in 10 top-level rugby players of the Italian National team before and after a 1-week course of daily sessions of whole-body cryotherapy. All subjects continued with the same training workload as that of the previous weeks. N-terminal pro B-type natriuretic peptide (NTproBNP) levels increased but remained within the normal range, whilst troponin I (TnI) and high sensitivity C-reactive protein (hsCRP) were unchanged. Whole-body cryotherapy did not impair cardiac function in this sample of elite athletes. [Copyright &y& Elsevier]