A Transition in the Accretion Properties of Radio-Loud Active Nuclei

We present evidence for the presence of a transition in the accretion properties of radio-loud sources. For a sample of radio galaxies and radio-loud quasars, selected based on their extended radio properties, the accretion rate is estimated from the black hole mass and nuclear luminosity. The inferred distribution is bimodal, with paucity of sources at accretion rates, in Eddington units, of order ~ 10^{-2} - assuming a radiative efficiency of 10 per cent - and possibly spanning one-two orders of magnitude. Selection biases are unlikely to be responsible for such behavior; we discuss possible physical explanations, including a fast transition to low accretion rates, a change in the accretion mode/actual accretion rate/radiative efficiency, the lack of stable disc solutions at intermediate accretion rates or the inefficiency of the jet formation processes in geometrically thin flows. This transition might be analogous to spectral states (and jet) transitions in black hole binary systems.Comment: 14 pages, 4 figures - Accepted for publication in MNRA

Fluctuations in warfarin dose response after heart valve surgery: implications for cardiac rehabilitation

In patients undergoing heart valve surgery (HVS) who require warfarin therapy, the maintenance of low variability in the level of anticoagulation early after operation is generally difficult. Aim of this study was to evaluate the time in therapeutic range (TTR) in HVS patients receiving oral anticoagulation therapy (OAT) during phase I-II of cardiac rehabilitation (CR), and, secondly, to identify clinical variables associated with inadequate anticoagulation. Methods: Observational study of consecutive in-hospital patients directly tracked from a cardiac surgery unit to a CR facility. OAT was monitored both in terms of administered warfarin doses and resulted INR values, from day 1 to day 15 after operation. Clinical variables were tested in a logistic regression model for the prediction of inadequate anticoagulation, defined as the presence of nontherapeutic INRs for ≥5 days between day 8 and 15. Results: Eighty-one patients (males 56%, age 62±19 yrs.), following valvuloplasty (37%), mechanical (17%), and bioprosthetic (45%) valve replacement were considered. The prescribed warfarin dosages were significantly higher from day 1 to day 7 than from day 8 to day 15 (4.6±3.6 and 3.0±1.1 mg respectively, p< 0.001). Overall, TTR was 6±3 days, while time with elevated and lower INRs accounted for 1.3±1.6 and 8.0±3.5 days respectively. At day 7, only 25% of patients (n= 20) showed a therapeutic INR value. Inadequate anticoagulation between postoperative day 8 and 15 was displayed in 41 (51%) patients, with hypertension as the only independent predictor (p< 0.001) at multivariate analysis. Conclusions: Despite intensive monitoring, half of patients have nontherapeutic INR values (mainly subtherapeutic) in the first two weeks after HVS while on warfarin. Giving the high risk of completing the hospitalization phase without a stable OAT in many patients, both cardiac surgeons and cardiologists should not miss the opportunity to improve patients education, and consider a direct track to anticoagulation management services after discharge

The impact of the two-year COVID-19 pandemic on hospital admission and readmissions of children and adolescents because of mental health problems

PurposeThis study aimed to investigate the specific risk factors and psycho-social and clinical features of hospitalized neuropsychiatric patients during the COVID pandemic and to analyze the hospital readmission phenomenon, which, according to recent studies, increased in frequency during the first pandemic period.Patients and methodsThis observational retrospective cohort study examined 375 patients aged between 0 and 17 years who were hospitalized between 1 February 2018 and 31 March 2022 due to neuropsychiatric issues. The majority of the patients were girls: there were 265 girls compared to 110 boys (M = 13.9 years; SD 2.30 years). The total sample was divided into two groups: the pre-COVID-19 group (160 inpatients hospitalized between February 2018 and February 2020) and the COVID-19 group (215 inpatients hospitalized between March 2020 and March 2022). To explore the readmission phenomenon (second aim), we selected from the two groups of patients with at least one hospital readmission within 365 days after the first discharge. Multiple variables (sociodemographic, clinical, psychological, and related to hospitalization) were collected for each patient by reviewing their medical records.ResultsThe risk factors for mental health disorders were similar between the two groups, except for the significantly increased use of electronic devices in the COVID-19 group, increasing from 8.8% in the pre-COVID-19 group to 29.2% in the COVID-19 group. Patients suffering from eating disorders increased from 11.3% in the pre-COVID-19 group to 23.8% in the COVID-19 group. Hospital readmissions nearly increased from 16.7% in the 2-year pre-COVID-19 period to 26.2% in the 2-year COVID-19 period. A total of 75% of patients hospitalized three or more times in the last 2 years and 85.7% of the so-called “revolving door” patients (with relapse within 3 months after discharge) were identified in the COVID-19 group. However, the comparison between the two groups of patients readmitted before and during the COVID-19 pandemic did not show any differences in terms of sociodemographic and clinical characteristics.ConclusionIn conclusion, there was a significant increase in hospital readmissions, but these results suggest the need for better coordination between hospital and territorial services in managing the complexity of mental health problems related to situations arising from the COVID-19 pandemic and the necessity to implement prevention strategies and services

A novel de novo HCN1 loss-of-function mutation in genetic generalized epilepsy causing increased neuronal excitability

Abstract The causes of genetic epilepsies are unknown in the majority of patients. HCN ion channels have a widespread expression in neurons and increasing evidence demonstrates their functional involvement in human epilepsies. Among the four known isoforms, HCN1 is the most expressed in the neocortex and hippocampus and de novo HCN1 point mutations have been recently associated with early infantile epileptic encephalopathy. So far, HCN1 mutations have not been reported in patients with idiopathic epilepsy. Using a Next Generation Sequencing approach, we identified the de novo heterozygous p.Leu157Val (c.469C > G) novel mutation in HCN1 in an adult male patient affected by genetic generalized epilepsy (GGE), with normal cognitive development. Electrophysiological analysis in heterologous expression model (CHO cells) and in neurons revealed that L157V is a loss-of-function, dominant negative mutation causing reduced HCN1 contribution to net inward current and responsible for an increased neuronal firing rate and excitability, potentially predisposing to epilepsy. These data represent the first evidence that autosomal dominant missense mutations of HCN1 can also be involved in GGE, without the characteristics of epileptic encephalopathy reported previously. It will be important to include HCN1 screening in patients with GGE, in order to extend the knowledge of the genetic causes of idiopathic epilepsies, thus paving the way for the identification of innovative therapeutic strategies

Therapeutic Value and Innovation of a Drug and Criteria for Evaluation: A Multidisciplinary Experience in the Veneto Region

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Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis

Background &amp; aims: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. Methods: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. Results: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. Conclusions: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. Impact and implications: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis

A quasar-galaxy mixing diagram: quasar spectral energy distribution shapes in the optical to near-infrared

We define a quasar-galaxy mixing diagram using the slopes of their spectral energy distributions (SEDs) from 1 \u3bcm to 3000 \uc5 and from 1 to 3 \u3bcm in the rest frame. The mixing diagram can easily distinguish among quasar-dominated, galaxy-dominated and reddening-dominated SED shapes. By studying the position of the 413 XMM-selected type 1 AGN in the wide-field `Cosmic Evolution Survey' in the mixing diagram, we find that a combination of the Elvis et al. mean quasar SED with various contributions from galaxy emission and some dust reddening is remarkably effective in describing the SED shape from 0.3 to 3 \u3bcm for large ranges of redshift, luminosity, black hole mass and Eddington ratio of type 1 AGN. In particular, the location in the mixing diagram of the highest luminosity AGN is very close (within 1\u3c3) to that of the Elvis et al. SED template. The mixing diagram can also be used to estimate the host galaxy fraction and reddening in quasar. We also show examples of some outliers which might be AGN in different evolutionary stages compared to the majority of AGN in the quasar-host galaxy co-evolution cycle

The main actors involved in parasitization of Heliothis virescens larva

At the moment of parasitization by another insect, the host Heliothis larva is able to defend itself by the activation of humoral and cellular defenses characterized by unusual reactions of hemocytes in response to external stimuli. Here, we have combined light and electron microscopy, staining reactions, and immunocytochemical characterization to analyze the activation and deactivation of one of the most important immune responses involved in invertebrates defense, i.e., melanin production and deposition. The insect host/parasitoid system is a good model to study these events. The activated granulocytes of the host insect are a major repository of amyloid fibrils forming a lattice in the cell. Subsequently, the exocytosed amyloid lattice constitutes the template for melanin deposition in the hemocel. Furthermore, cross-talk between immune and neuroendocrine systems mediated by hormones, cytokines, and neuromodulators with the activation of stress-sensoring circuits to produce and release molecules such as adrenocorticotropin hormone, alpha melanocyte-stimulating hormone, and neutral endopeptidase occurs. Thus, parasitization promotes massive morphological and physiological modifications in the host insect hemocytes and mimics general stress conditions in which phenomena such as amyloid fibril formation, melanin polymerization, pro-inflammatory cytokine production, and activation of the adrenocorticotropin hormone system occur. These events observed in invertebrates are also reported in the literature for vertebrates, suggesting that this network of mechanisms and responses is maintained throughout evolution

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons