Redox cell signaling and hepatic progenitor cells.

Hepatic diseases are widespread in the world and organ transplantation is currently the only treatment for liver failure. New cell-based approaches have been considered, since stem cells may represent a possible source to treat liver diseases. Acute and chronic liver diseases are characterized by high production of reactive oxygen and nitrogen species, with consequent oxidative modifications of cellular macromolecules and alteration of signaling pathways, metabolism and cell cycle. Although considered harmful molecules, reactive species are involved in cell growth and differentiation processes, modulating the activity of transcription factors, which take part in stemness/proliferation. It is conceivable that redox balance may regulate the development of hepatic progenitor cells, function and survival in synchrony with metabolism during chronic liver diseases. This review aims to summarize diverse redox-sensitive signaling pathways involved in stem cell fate, highlighting the important role of hepatic progenitor cells as a possible source to treat end-stage liver disease for organ regeneration

Fast Neural Network Inference on FPGAs for Triggering on Long-Lived Particles at Colliders

Experimental particle physics demands a sophisticated trigger and acquisition system capable to efficiently retain the collisions of interest for further investigation. Heterogeneous computing with the employment of FPGA cards may emerge as a trending technology for the triggering strategy of the upcoming high-luminosity program of the Large Hadron Collider at CERN. In this context, we present two machine-learning algorithms for selecting events where neutral long-lived particles decay within the detector volume studying their accuracy and inference time when accelerated on commercially available Xilinx FPGA accelerator cards. The inference time is also confronted with a CPU- and GPU-based hardware setup. The proposed new algorithms are proven efficient for the considered benchmark physics scenario and their accuracy is found to not degrade when accelerated on the FPGA cards. The results indicate that all tested architectures fit within the latency requirements of a second-level trigger farm and that exploiting accelerator technologies for real-time processing of particle-physics collisions is a promising research field that deserves additional investigations, in particular with machine-learning models with a large number of trainable parameters.Comment: 12 pages, 9 figures, 2 table

DIRECT-ACTING antivirals restore systemic redox homeostasis in chronic HCV patients

Chronic hepatitis C therapy has completely changed in the last years due to the availability of direct-acting antivirals (DAAs). Removing the virus may be not enough since chronic infection deeply modifies immune system and cellular metabolism along decades of inflammation. Oxidative stress plays a significant role in maintaining systemic inflammation during chronic HCV infection. Other than removing the virus, effective therapy could counteract oxidative stress. This study investigated the impact of DAA treatment on circulating markers of oxidative stress and antioxidant defence in a cohort of patients affected by chronic hepatitis C. To this, an observational study on 196 patients who started therapy with DAA for HCV-related hepatitis was performed. Patients were assessed at baseline, 4 weeks after the initiation of therapy (4wks), at the end of treatment (EoT), and 12 weeks after the EoT (SVR12). Circulating oxidative stress was determined by measuring serum hydroxynonenal (HNE)- and malondialdehyde (MDA)-protein adducts, and 8-hydroxydeoxyguanosine (8-OHdG). Antioxidant status was evaluated by measuring the enzymatic activity and mRNA expression of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in peripheral blood mononuclear cells. We observed a reduction of serum 8-OHdG at 4wks, while the circulating level of both HNE- and MDA-protein adducts diminished at EoT; all these markers persisted low at SVR12. On the other side, we reported an increase in the enzymatic activity of all the antioxidant enzymes in PBMC at EoT and SVR12. Taking into account circulating 8-OHdG and antioxidant enzyme activities, patients with high fibrosis stage were those that had the most benefit from DAA therapy. To conclude, this study indicates that treatment with DAAs improves the circulating redox status of patients affected by chronic hepatitis C. This positive impact of DAA therapy may be related to its effectiveness on cutting down viremia and pro-inflammatory markers

Synergistic interaction of fatty acids and oxysterols impairs mitochondrial function and limits liver adaptation during nafld progression

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression. We demonstrated that the accumulation of specific non-enzymatic oxysterols in the liver of animals fed high-fat+high-cholesterol diet induces mitochondrial damage and depletion of proteins of the respiratory chain complexes. When tested in vitro, 5α-cholestane-3β,5,6β-triol (triol) combined to FFAs was able to reduce respiration in isolated liver mitochondria, induced apoptosis in primary hepatocytes, and down-regulated transcription factors involved in mitochondrial biogenesis. Finally, a lower protein content in the mitochondrial respiratory chain complexes was observed in human non-alcoholic steatohepatitis. In conclusion, hepatic accumulation of FFAs and non-enzymatic oxysterols synergistically facilitates development and progression of NAFLD by impairing mitochondrial function, energy balance and biogenesis adaptation to chronic injury

Current fluctuations in stochastically resetting particle systems

We consider a system of non-interacting particles on a line with initial positions distributed uniformly with density $\rho$ on the negative half-line. We consider two different models: (i) each particle performs independent Brownian motion with stochastic resetting to its initial position with rate $r$ and (ii) each particle performs run and tumble motion, and with rate $r$ its position gets reset to its initial value and simultaneously its velocity gets randomised. We study the effects of resetting on the distribution $P(Q,t)$ of the integrated particle current $Q$ up to time $t$ through the origin (from left to right). We study both the annealed and the quenched current distributions and in both cases, we find that resetting induces a stationary limiting distribution of the current at long times. However, we show that the approach to the stationary state of the current distribution in the annealed and the quenched cases are drastically different for both models. In the annealed case, the whole distribution $P_{\rm an}(Q,t)$ approaches its stationary limit uniformly for all $Q$. In contrast, the quenched distribution $P_{\rm qu}(Q,t)$ attains its stationary form for $Q<Q_{\rm crit}(t)$, while it remains time-dependent for $Q > Q_{\rm crit}(t)$. We show that $Q_{\rm crit}(t)$ increases linearly with $t$ for large $t$. On the scale where $Q \sim Q_{\rm crit}(t)$, we show that $P_{\rm qu}(Q,t)$ has an unusual large deviation form with a rate function that has a third-order phase transition at the critical point. We have computed the associated rate functions analytically for both models. Using an importance sampling method that allows to probe probabilities as tiny as $10^{-14000}$, we were able to compute numerically this non-analytic rate function for the resetting Brownian dynamics and found excellent agreement with our analytical prediction.Comment: 26 pages, 6 figure

Social Support Mediates the Relationship between Body Image Distress and Depressive Symptoms in Prostate Cancer Patients

Treatments for prostate cancer (PCa), the second most common cancer in men, may affect the body image (BI) of patients, increasing the risk of negative mental health outcomes. However, an enabling social support network may be a protective factor against the effects of BI distress on health. Therefore, the present study examined the mediating role of social support in the relationship between BI distress and depressive symptoms. Data were retrospectively collected from 197 PCa patients aged from 48 to 79 years (M = 67.19; SD = 6.83). The statistical package for the social sciences with PROCESS Macro was used to assess the direct and mediating effects with bias-corrected bootstrapping (10,000 samples). Results showed that BI distress was positively associated with depressive symptoms and that social support partially mediated this relationship. Moreover, among the different sources of social support, only friend support significantly mediated the association between BI distress and depressive symptoms. This study sheds light on the crucial role of social support as a dimension that can promote health in PCa patients

Diagnosis and Treatment of Pulmonary Disease in Sea Turtles (Caretta caretta)

The aim of this study was to describe the clinical signs, radiographic, endoscopic and CT findings, cytological and microbiological findings and treatments of pulmonary diseases in sea turtles, in order to obtain an accurate diagnosis that avoids unnecessary therapy and antibiotic-resistance phenomena. In total, 14 loggerheads (Caretta caretta), with clinical and/or radiographic findings of pulmonary pathology, were assessed through various combinations of clinical, radiological, CT, endoscopic examination and bronchoalveolar lavage, which recovered fluid for cytologic and microbiologic analysis. In all cases, radiographic examination led to a diagnosis of pulmonary disorders—4 unilateral and 10 bilateral. All bacteria cultured were identified as Gram-negative. Antibiotic resistance was greater than 70% for all beta-lactams tested. In addition, all bacterial strains were 100% resistant to colistin sulfate and tetracycline. Specific antibiotic therapies were formulated for seven sea turtles using Enrofloxacin, and for four sea turtles using ceftazidime. In two turtles, antibiotic therapy was not included due to the presence of antibiotic resistance against all the antibiotics evaluated. In both cases, the coupage technique and environmental management allowed the resolution of the lung disease without antibiotics. All 14 sea turtles were released back into the sea. Radiographic examination must be considered the gold standard for screening sea turtles that show respiratory signs or abnormal buoyancy. Susceptibility testing with antimicrobials allowed appropriate therapy, including the reduction of antibiotic-resistance

Non invasive evaluation of cardiomechanics in patients undergoing MitrClip procedure

Abstract BACKGROUND: In the last recent years a new percutaneous procedure, the MitraClip, has been validated for the treatment of mitral regurgitation. MitraClip procedure is a promising alternative for patients unsuitable for surgery as it reduces the risk of death related to surgery ensuring a similar result. Few data are present in literature about the variation of hemodynamic parameters and ventricular coupling after Mitraclip implantation. METHODS: Hemodynamic data of 18 patients enrolled for MitraClip procedure were retrospectively reviewed and analyzed. Echocardiographic measurements were obtained the day before the procedure (T0) and 21 ± 3 days after the procedure (T1), including evaluation of Ejection Fraction, mitral valve regurgitation severity and mechanism, forward Stroke Volume, left atrial volume, estimated systolic pulmonary pressure, non invasive echocardiographic estimation of single beat ventricular elastance (Es(sb)), arterial elastance (Ea) measured as systolic pressure • 0.9/ Stroke Volume, ventricular arterial coupling (Ea/Es(sb) ratio). Data were expressed as median and interquartile range. Measures obtained before and after the procedure were compared using Wilcoxon non parametric test for paired samples. RESULTS: Mitraclip procedure was effective in reducing regurgitation. We observed an amelioration of echocardiographic parameters with a reduction of estimated systolic pulmonary pressure (45 to 37,5 p = 0,0002) and left atrial volume (110 to 93 p = 0,0001). Despite a few cases decreasing in ejection fraction (37 to 35 p = 0,035), the maintained ventricular arterial coupling after the procedure (P = 0,67) was associated with an increasing in forward stroke volume (60,3 to 78 p = 0,05). CONCLUSION: MitraClip is effective in reducing mitral valve regurgitation and determines an amelioration of hemodynamic parameters with preservation of ventricular arterial couplin

Management of severe head injury with brain exposure in three loggerhead sea turtles Caretta caretta

The loggerhead Caretta caretta is the most common sea turtle in the Mediterranean. Currently, sea turtles are considered endangered, mainly due to the impact of human activities. Among traumatic lesions, those involving the skull, if complicated by brain exposure, are often life-threatening. In these cases, death could be the outcome of direct trauma of the cerebral tissue or of secondary meningoencephalitis. This uncontrolled study aims to evaluate the use of a plantderived dressing (1 Primary Wound Dressing®) in 3 sea turtles with severe lesions of the skull exposing the brain. Following surgical curettage, the treatment protocol involved exclusive use of the plant-derived dressing applied on the wound surface as the primary dressing, daily for the first month and then every other day until the end of treatment. The wound and peri-wound skin were covered with a simple secondary dressing without any active compound (non-woven gauze with petroleum jelly). Data presented herein show an excellent healing process in all 3 cases and no side effects due to contact of the medication with the cerebral tissue

A cross-sectional study on demoralization in prostate cancer patients: The role of masculine self-esteem, depression, and resilience

Purpose: The current cross-sectional study had three objectives: (1) to assess the prevalence of depression and demoralization in a sample of prostate cancer (PCa) patients; (2) to examine whether masculine self-esteem and depression were associated with demoralization; and (3) to evaluate the role of resilience as a factor buffering the effects of masculine self-esteem and depression on demoralization. Methods: 197 PCa patients aged 48 to 79 years (M = 67.19; SD = 6.83) answered questions about masculine self-esteem, depression, resilience, and demoralization. An ANOVA was conducted to examine whether the association between demoralization and depressive symptoms was linear. A chi-square test was calculated to determine differences between depression and demoralization. Finally, a hierarchical multiple linear regression analysis with interaction terms was conducted to examine the associations between masculine self-esteem, depression, resilience, and demoralization. Results: Depression scores increased linearly with demoralization severity, but demoralization scores were higher than depression scores (21.3% vs. 15.2%). Lower scores on masculine self-esteem and higher scores on depressive symptoms were associated with greater demoralization. Resilience significantly moderated the association between masculine self-esteem and demoralization, but not between depression and demoralization. Conclusion: Assessment of depression, masculine self-esteem, resilience, and demoralization in the clinical setting is critical for improving the mental health status of PCa patients