Candidacy and long-term outcomes of subcutaneous implantable cardioverter-defibrillators in current practice in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with Hypertrophic Cardiomyopathy (HCM) S-ICD is usually the preferred option as pacing is generally not indicated. However, limited data are available on its current practice adoption and long-term follow-up. METHODS: Consecutive HCM patients with S-ICD implanted between 2013 and 2021 in 3 international centers were enrolled in this observational study. Baseline, procedural and follow-up data were regularly collected. Efficacy and safety were compared with a cohort of HCM patients implanted with a tv-ICD. RESULTS: Seventy patients (64% males) were implanted with S-ICD at 41 ± 15 years, whereas 168 patients with tv-ICD at 49 ± 16 years. For S-ICD patients, mean ESC SCD risk score was 4,5 ± 1.9%: 25 (40%) at low-risk, 17 (27%) at intermediate and 20 (33%) at high-risk. Patients were followed-up for 5.1 ± 2.3 years. Two patients (0.6 per 100-person-years, vs 0.4 per 100 person-years with tv-ICD, p = 0.45) received an appropriate shock on VF, 17 (24%) were diagnosed with de-novo AF. Inappropriate shocks occurred in 4 patients (1.2 per 100-person-years, vs 0.9 per 100 person-years with tv-ICD, p = 0.74), all before Smart-Pass algorithm implementation. Four patients experienced device-related adverse events (1.2 per 100-person-years, vs 1 per 100 person-years with tv-ICD, p = 0.35%). CONCLUSIONS: S-ICDs were often implanted in patients with an overall low-intermediate ESC SCD risk, reflecting both the inclusion of additional risk markers and a lower decision threshold. S-ICDs in HCM patients followed for over 5 years showed to be effective in conversion of VF and safe. Greater scrutiny may be required to avoid overtreatment in patients with milder risk profiles.

NF-YA isoforms with alternative splicing of exon-5 in Aves.

NF-YA, the regulatory subunit of the trimeric CCAAT-binding transcription factor NF-Y, is present in vertebrates in two major alternative spliced isoforms: NF-YAl and NF-YAs, differing for the presence of exon-3. NF-YAx, a third isoform without exon-3/-5, was reported only in human neuronal cells and tumors. These events affect the Trans-Activation Domain. We provide here evidence for the expression of NF-YAx and for the existence of a new isoform, NF-YAg, skipping only exon-5. These isoforms are abundant in Aves, but not in reptiles, and are the prevalent transcripts in the initial phases of embryo development in chicken. Finally, we analyzed NF-YAg and NF-YAx amino acid sequence using AlphaFold: absence of exon-5 denotes a global reduction of ß-stranded elements, while removal of the disordered exon-3 sequence has limited effects on TAD architecture. These data identify an expanded program of NF-YA isoforms within the TAD in Aves, implying a role during early development.

Distorted stability pattern and chaotic features for quantized prey-predator-like dynamics.

Nonequilibrium and instability features of prey-predator-like systems associated to topological quantum domains emerging from a quantum phase-space description are investigated in the framework of the Weyl-Wigner quantum mechanics. Reporting about the generalized Wigner flow for one-dimensional Hamiltonian systems, H(x,k), constrained by ∂^{2}H/∂x∂k=0, the prey-predator dynamics driven by Lotka-Volterra (LV) equations is mapped onto the Heisenberg-Weyl noncommutative algebra, [x,k]=i, where the canonical variables x and k are related to the two-dimensional LV parameters, y=e^{-x} and z=e^{-k}. From the non-Liouvillian pattern driven by the associated Wigner currents, hyperbolic equilibrium and stability parameters for the prey-predator-like dynamics are then shown to be affected by quantum distortions over the classical background, in correspondence with nonstationarity and non-Liouvillianity properties quantified in terms of Wigner currents and Gaussian ensemble parameters. As an extension, considering the hypothesis of discretizing the time parameter, nonhyperbolic bifurcation regimes are identified and quantified in terms of z-y anisotropy and Gaussian parameters. The bifurcation diagrams exhibit, for quantum regimes, chaotic patterns highly dependent on Gaussian localization. Besides exemplifying a broad range of applications of the generalized Wigner information flow framework, our results extend, from the continuous (hyperbolic regime) to discrete (chaotic regime) domains, the procedure for quantifying the influence of quantum fluctuations over equilibrium and stability scenarios of LV driven systems.

Noncommutative phase-space Lotka-Volterra dynamics: The quantum analog.

The Lotka-Volterra (LV) dynamics is investigated in the framework of the Weyl-Wigner (WW) quantum mechanics extended to one-dimensional Hamiltonian systems, H(x,k) constrained by the ∂^{2}H/∂x∂k=0 condition. Supported by the Heisenberg-Weyl noncommutative algebra, where [x,k]=i, the canonical variables x and k are interpreted in terms of the LV variables, y=e^{-x} and z=e^{-k}, eventually associated with the number of individuals in a closed competitive dynamics: the so-called prey-predator system. The WW framework provides the ground for identifying how classical and quantum evolution coexist at different scales and for quantifying quantum analog effects. Through the results from the associated Wigner currents, (non-)Liouvillian and stationary properties are described for thermodynamic and Gaussian quantum ensembles in order to account for the corrections due to quantum features over the classical phase-space pattern yielded by the Hamiltonian description of the LV dynamics. In particular, for Gaussian statistical ensembles, the Wigner flow framework provides the exact profile for the quantum modifications over the classical LV phase-space trajectories so that Gaussian quantum ensembles can be interpreted as an adequate Hilbert space state configuration for comparing quantum and classical regimes. The generality of the framework developed here extends the boundaries of the understanding of quantumlike effects on competitive microscopical biosystems.

Genomic landscape and immune-related gene expression profiling of epithelial ovarian cancer after neoadjuvant chemotherapy.

Platinum-based neoadjuvant chemotherapy followed by interval debulking surgery is an accepted treatment for patients with stage III or IV epithelial ovarian cancer who are not suitable for primary debulking surgery. The identification of suitable adjuvant treatments in these patients is an unmet need. Here, we explore potential genomic characteristics (mutational and immune-associated expression profiles) in a series of patients undergoing neoadjuvant chemotherapy. Tumor samples from biopsy and interval debulking surgery were analyzed for mutational landscape and immune profiling, together with detailed immunohistochemistry using different immune cell markers, and correlated with clinicopathological characteristics and potential response to neoadjuvant chemotherapy. No major differences in the mutational landscape were observed in paired biopsy and surgery samples. Genomic loss of heterozygosity was found to be higher in patients with total/near-total tumor response. The immune gene expression profile after neoadjuvant chemotherapy revealed activation of several immune regulation-related pathways in patients with no/minimal or partial response. In parallel, neoadjuvant therapy caused a significant increase of tumor-infiltrating lymphocyte population abundance, primarily due to an augmentation of the CD8+ T cell population. Remarkably, these changes occurred irrespective of potential homologous recombination defects, such as those associated with BRCA1/2 mutations. Our study strengthens the use of loss of heterozygosity as a biomarker of homologous repair deficiency. The changes of immune states during neoadjuvant chemotherapy reveal the dynamic nature of tumor-host immune interactions and suggest the potential use of immune checkpoint inhibitors or their combination with poly-ADP polymerase inhibitors in high stage and grade epithelial ovarian cancer patients undergoing neoadjuvant therapy.

Influence of Laboratory Index on match performance. A comparison study to evaluate physical performance in professional soccer players of an Italian Elite Team.

OBJECTIVE: It was hypothesized that activity exercise at professional levels could lead to an increase in metabolic levels and a decrease in performance parameters. These trends are explained by physical activity as a cellular stressor. SUBJECTS AND METHODS: We used an algorithm, Laboratory Index which evaluates salivary cortisol, CK and d-ROMs, collected previously from elite Italian soccer players, compared to InStat Index. The last one estimates analytically the athlete's performance in soccer pitch, applying the Heath Maps. RESULTS: A good agreement between the two Index was obtained, especially for two players, who showed an ideal combined trend. CONCLUSIONS: We would investigate the clinical and activity profile of soccer players with the aim of providing information for the development of training strategies. Also, the performances, during training and match time, are an objective evaluation of the athlete's physical preparation. As a consequence, the combination of two Index could be used for a new approach to the sports world.

Dysgeusia and health-related quality of life of cancer patients receiving chemotherapy: A cross-sectional study.

The aim of the study was to evaluate taste disorders in patients receiving chemotherapy and to assess the impact of dysgeusia on patients' health-related quality of life (HRQOL). A total of 289 patients with a diagnosis of malignant solid or haematological cancer undergoing chemotherapy completed a questionnaire assessing dysgeusia and HRQOL. Sixty-four per cent of patients developed dysgeusia after and during chemotherapy. A statistically significant correlation was found between type of cancer and dysgeusia (p = .012), moreover a statistically significant association was found between type of chemotherapy and occurrence of dysgeusia (p = .031). Patients with dysgeusia had a worse overall HRQOL than those who did not have dysgeusia, and the association between HRQOL and dysgeusia was also statistically significant (p = .003). Patients with dysgeusia had a higher probability of having a worse HRQOL (p = .002). In line with previous studies, we observed a significant correlation between chemotherapy and dysgeusia. Furthermore, this study found that cancer patients with dysgeusia have a lower quality of life. In particular the domains "role," "social aspect," "nausea-vomiting" and "appetite" are most influenced by dysgeusia. Improving the communication and information to patients considered at higher risk of developing dysgeusia can have a positive impact on patients' quality of life.

Peripheral neuropathy associated with levodopa-carbidopa intestinal infusion: a long-term prospective assessment.

BACKGROUND AND PURPOSE: Subacute and chronic peripheral neuropathies (PNP) have been reported in Parkinson's disease (PD) patients treated with levodopa/carbidopa intestinal gel infusion (LCIG), although several aspects of their incidence and pathogenesis still remain to be clarified. This study main objective is to prospectively report the 2-year incidence of PNP in patients treated with LCIG. METHODS AND RESULTS: The clinical, hematological, nutritional and electrophysiological assessments of 33 consecutive patients have been prospectively collected and evaluated. At baseline (before the start of LCIG therapy), 3/33 (9%) patients showed symptomatic PNP and 7/33 (21%) subclinical PNP. During a follow-up of 24.36 ± 12.18 months, 2/23 patients with normal baseline clinical-electrophysiological assessment developed a subacute PNP, 2/23 developed a chronic PNP and 7/23 developed a subclinical PNP. LCIG was immediately halted in the subacute cases, while the infusion therapy was not interrupted in chronic and subclinical forms. All PNP were supplemented with vitamin B1 and B12, showing a clinical improvement and/or substantial stability at the following evaluations. Higher levodopa-equivalent daily dose (P: 0.024) and homocysteine levels (P: 0.041) were found in chronic PNP, while no correlations were observed with vitamin B12, folate and UPDRS values. A trend towards BMI reduction was observed in both PNP and unaffected subjects and one patient developed a symptomatic PNP associated with a relevant weight loss. CONCLUSIONS: Serial clinical-electrophysiological evaluations are mandatory in patients treated with LCIG, given the possible risk of subacute and chronic PNP. No clear causative factors has been recognized in the subacute forms, whilst homocysteine-mediated neurotoxicity seems to underlie the pathogenesis of chronic forms.

Effects of high Zn and Pb concentrations on Phragmites australis (Cav.) Trin. Ex. Steudel: Photosynthetic performance and metal accumulation capacity under controlled conditions.

The response of Phragmites australis (Cav.) Trin. Ex. Steudel to zinc (Zn) and lead (Pb) was studied separately in two hydroponic tests, during a three weeks experiment. The effects on ecophysiology and biomass partitioning were evaluated during the metal treatments and at the recovery, and total metal content and accumulation capacity in different plant organs were assessed. Zn and Pb had different effects on the overall measured parameters, highlighting different mechanism of action. In particular, Zn concentration was higher in roots and, being a micronutrient, it was translocated into leaves, producing a reduction of assimilation rate, stomatal conductance (-71.9 and -81.3% respect to the control plant respectively), and a strong down regulation of photosystems functionality both at PSII and PSI level. Otherwise, Pb was accumulated mainly in the more lignified tissue such as rhizomes, with slightly effect on gas exchange. Chlorophyll a fluorescence highlighted that Pb inhibits the electron transfer process at the PSI donor side, without recovery after the removal of the metal stress. Despite these physiological limitations, P. australis showed a high capacity to accumulate both metals, and only slight reduction of biomass, being therefore a suitable species for phytoremediation interventions.

Early diagnosis of hearing loss: otoacoustic emissions evoked by distortion products and pure-tone audiometry: Preliminary findings.

OBJECTIVE: Literary studies underline the effectiveness of distortion product otoacoustic emissions (DPOAEs), which are not affected by the collaboration of the subject examined, in the early diagnosis of hearing loss. Aim of the study is to compare the objective technique of DPOAEs with respect to the pure-tone audiometry in early diagnosis of hearing loss. MATERIALS AND METHODS: The clinical research was carried out on 852 workers. All subjects underwent pure-tone audiometry, tympanometry and distortion products. RESULTS: The results show: a) a prevalence of subjects with impaired DPOAEs higher than the prevalence of subjects with impaired audiometries in the studied samples; and, after division by gender: b) a prevalence of subjects with impaired DPOAEs higher than the prevalence of subjects with impaired audiometries only in men; c) a prevalence of impaired DPOAEs and of impaired audiometries in men higher than in women. CONCLUSIONS: The results suggest the higher effectiveness of DPOAEs compared to pure-tone audiometry in making an early diagnosis of hearing loss.

Type I cell ROS kinetics under hypoxia in the intact mouse carotid body ex vivo: a FRET-based study.

Reactive oxygen species (ROS) mainly originating from NADPH oxidases have been shown to be involved in the carotid body (CB) oxygen-sensing cascade. For measuring ROS kinetics, type I cells of the mouse CB in an ex vivo preparation were transfected with the ROS sensor construct FRET-HSP33. After 2 days of tissue culture, type I cells expressed FRET-HSP33 as shown by immunohistochemistry. In one population of CBs, 5 min of hypoxia induced a significant and reversible decrease of type I cell ROS levels (n = 9 CBs; P < 0.015), which could be inhibited by 4-(2-aminoethyl)benzensulfonylfluorid (AEBSF), a highly specific inhibitor of the NADPH oxidase subunits p47(phox) and p67(phox). In another population of CBs, however, 5 min of hypoxia induced a significant and reversible increase of ROS levels in type I cells (n = 8 CBs; P < 0.05), which was slightly enhanced by administration of 3 mM AEBSF. These different ROS kinetics seemed to coincide with different mice breeding conditions. Type I cells of both populations showed a typical hypoxia-induced membrane potential (MP) depolarization, which could be inhibited by 3 mM AEBSF. ROS and MP closely followed the hypoxic decrease in CB tissue oxygen as measured with an O2-sensitive dye. We conclude that attenuated p47(phox) subunit activity of the NADPH oxidase under hypoxia is the physiological trigger for type I cell MP depolarization probably due to ROS decrease, whereas the observed ROS increase has no influence on type I cell MP kinetics under hypoxia.

Saccharomyces cerevisiae fungemia, a possible consequence of the treatment of Clostridium difficile colitis with a probioticum.

The yeast Saccharomyces boulardii is a biotherapeutic agent used for the prevention and treatment of several gastrointestinal diseases, such as diarrhoea caused by Clostridium difficile, in addition to the antibiotic therapy. In this study we report a case of Saccharomyces cerevisiae fungemia in a patient with Clostridium difficile-associated diarrhoea (CDAD) treated orally with S. boulardii in association with vancomycin. The identification of the S. cerevisiae was confirmed by molecular technique. Fungemia is a rare, but a serious complication to treatment with probiotics. We believe it is important to remind the clinicians of this risk when prescribing probiotics, especially to immunocompromised patients.

Role of first pass and delayed enhancement in assessment of segmental functional recovery after acute myocardial infarction.

PURPOSE: Assessing myocardial viability is crucial in decision making and prognostic restratification after acute myocardial infarction (MI). A number of noninvasive imaging modalities have been employed in viability identification, but contrast-enhanced magnetic resonance (MR) imaging has been shown to be extremely accurate because of its transmural resolution and precise definition of microvascular obstruction. Our purpose was to assess functional recovery after acute MI, with special focus on the role of infarct transmurality and microvascular obstruction. MATERIALS AND METHODS: Forty-six consecutive patients with first acute MI, reperfused by primary percutaneous transluminal coronary angioplasty (PTCA) (n=40) or fibrinolysis (n=6), underwent MR imaging within the first week to assess oedema, microvascular obstruction, function and viability and then again after 4-6 months to assess functional recovery and scar. RESULTS: At first MR examination, postcontrast images were analysed according to three patterns, based on a combination of first-pass and delayed-enhancement data: pattern 1 (normal first pass and late hyperenhancement <50% thickness) identified viable myocardium, whereas pattern 2 (late hyperenhancement >50% thickness, with or without first-pass perfusion defect) and pattern 3 (perfusion defect at first pass and late hypoenhancement) recognised nonviable myocardium, with 93% sensitivity, 75% specificity, 92% positive predictive value and 78% negative predictive value for identifying viable tissue. Furthermore, by dividing pattern 2 into two subpatterns, 2A and 2B, based on absence or presence of microvascular obstruction in >50% transmural infarcts, we were able to better identify the segments without recovery or that were nonviable with a 1.39 relative risk of failed recovery. CONCLUSIONS: After acute MI, not all infarcts with transmurality >50% can be considered nonviable; microvascular obstruction detected at first pass can help to better stratify these cases.

Deployment of self-expandable stents in aneurysmatic cerebral vessels: comparison of different computational approaches for interventional planning.

In the last few years, there has been a growing focus on faster computational methods to support clinicians in planning stenting procedures. This study investigates the possibility of introducing computational approximations in modelling stent deployment in aneurysmatic cerebral vessels to achieve simulations compatible with the constraints of real clinical workflows. The release of a self-expandable stent in a simplified aneurysmatic vessel was modelled in four different initial positions. Six progressively simplified modelling approaches (based on Finite Element method and Fast Virtual Stenting--FVS) have been used. Comparing accuracy of the results, the final configuration of the stent is more affected by neglecting mechanical properties of materials (FVS) than by adopting 1D instead of 3D stent models. Nevertheless, the differences showed are acceptable compared to those achieved by considering different stent initial positions. Regarding computational costs, simulations involving 1D stent features are the only ones feasible in clinical context.

Conserved ram seminal plasma proteins bind to the sperm membrane and repair cryopreservation damage.

Whole seminal plasma (SP) enhances the function and fertility of frozen/thawed ram sperm. The objective of the current study was to investigate whether SP proteins capable of binding to molecules from the sperm plasma membrane were conserved among ram breeds, and whether these proteins were sufficient to overcome cryopreservation-induced reductions in sperm quality. Whole ram SP, obtained from rams of various breeds, improved progressive motility of frozen/thawed sperm at all times evaluated (P < 0.05); however, it did not improve total motility (15 min, P = 0.480; 30 min, P = 0.764; and 45 min, P = 0.795). To identify SP proteins responsible for this effect, a new method was developed to retain SP proteins that bound specifically to the sperm membrane by immobilization of sperm membrane proteins. These proteins specifically bound to the sperm surface, especially the acrosomal region. Lactotransferrin, epididymal secretory protein E1, Synaptosomal-associated protein 29, and RSVP-20 were identified (mass spectrometry) in this fraction. The retained SP proteins fraction repaired ultrastructural damage of frozen/thawed sperm and, with the addition of fructose, significantly improved motility of frozen/thawed sperm. We concluded that SP proteins that bound to the sperm membrane were conserved among ram breeds, and that when added to frozen/thawed semen (along with an energy source), they repaired ram sperm damage and enhanced sperm motility.

Risk of pulmonary aspiration with laryngeal mask airway and tracheal tube: analysis on 65 712 procedures with positive pressure ventilation.

We compared the risk of pulmonary aspiration in patients whose lungs were mechanically ventilated through a laryngeal mask airway (35 630 procedures) or tracheal tube (30 082 procedures). Three cases of pulmonary aspiration occurred with the laryngeal mask airway and seven with the tracheal tube. There were no deaths related to pulmonary aspiration. The incidence and outcome of pulmonary aspiration detected in this study were similar to those previously reported. The adjusted odds ratio (OR) for pulmonary aspiration with the laryngeal mask airway was 1.06 (95% CI 0.20-5.62). Unplanned surgery (OR 30.5, 95% CI 8.6-108.9) and male sex (OR 8.6, 95% CI 1.1-68) were associated with an increased risk of aspiration and age < 14 years with a reduced risk (OR 0.21, 95% CI 0.07-0.64). There were contraindications and exclusions to the use of the laryngeal mask airway but in this selected population the use of an laryngeal mask airway was not associated with an increased risk of pulmonary aspiration compared with a tracheal tube.

A dosimetry procedure based on storage phosphors with short fading time.

Problem of retrieving data on exposure to radiation from storage phosphors characterised by short fading time in unpredictably long exposure times is addressed from a numerical point of view. A simple algorithm is presented for the case of first kinetic order. Extension to a generic kinetic order is possible provided a suitable characterisation of the fading features is performed. Simulations are also presented where temperature and reading effects, as well as error measurements, are taken into account.

Plasma 17-alpha-OH-progesterone in female workers exposed to urban pollutants.

The aim of this study is to evaluate whether occupational exposure to urban pollutants could cause alteration in plasma 17-alpha-OH-P levels in female workers. After excluding the subjects with the principal confounding factors, traffic police and controls were matched by age, working life, age of menarche, menstrual cycle day, BMI, drinking habits, habitual consumption of soy and Italian coffee. 68 traffic police and 82 controls (7th day; follicular phase of the ovarian cycle), 37 traffic police and 20 controls (21st day; lutheal phase of the ovarian cycle) were included in the study and matched for the above mentioned variables. In follicular and lutheal phase of ovarian cycle, 17-alpha-OH-P mean levels and the distribution of 17-alpha-OH-P values were significantly higher in traffic police vs. controls. A higher instance of mental health disorders in traffic police vs. controls was found, although the difference was not significant. Considering that the potential confounding effect of extraneous factors was controlled by restricting the study population and by matching traffic police vs. controls on the above mentioned variables, our results suggest that occupational exposure to urban pollutants may alter plasma 17-alpha-OH-P concentrations. 17-alpha-OH-P could be used in an occupational setting as an early biomarker of exposure to urban pollutants, valuable for a group, even before the onset of related pathologies.

Effect of tidal volume and respiratory rate on the power of breathing calculation.

BACKGROUND: The power of breathing (PoB) is used to estimate the mechanical workload of the respiratory system. Aim of this study was to investigate the effect of different tidal volume-respiratory rate combinations on the PoB when the elastic load is constant. In order to assure strict control of the experimental conditions, the PoB was calculated on an airway pressure-volume curve in mechanically ventilated patients. METHODS: Ten patients received three different tidal volume-respiratory rate combinations while minute ventilation was constant. Respiratory mechanics, PoB and its elastic and resistive components were calculated. Alternative methods to estimate the elastic workload were assessed: elastic work of breathing per litre per minute, elastic workload index (the square root of elastic work of breathing multiplied by respiratory rate) and elastic double product of the respiratory system (the elastic pressure multiplied by respiratory rate). RESULTS: Despite constant elastance and minute ventilation, the elastic PoB showed an increment greater than 200% from the lower to the greater tidal volume, accounting for approximately 80% of the whole PoB increment. On the contrary, elastic work of breathing per litre per minute, elastic workload index and elastic double product did not change. CONCLUSION: Changes in breathing pattern markedly affect the PoB despite constant mechanical load. Other indexes could assess the elastic workload without tidal volume dependence. Power of breathing use should be avoided to compare different mechanical loads or efficiencies of the respiratory muscles when tidal volume is variable.