Autophagy is a fundamental multi-tasking adaptive cellular degradation and recycling strategy. Following its causal implication in age-related decline, autophagy is currently among the most broadly ...studied and challenged mechanisms within aging research. Thanks to these efforts, new cellular nodes interconnected with this phylogenetically ancestral pathway and unexpected roles of autophagy-associated genetic products are unveiled daily, yet the history of functional adaptations of autophagy along its evolutive trail is poorly understood and documented. Autophagy is traditionally studied in canonical and research-wise convenient model organisms such as yeast and mice. However, unconventional animal models endowed with extended longevity and exemption from age-related diseases offer a privileged perspective to inquire into the role of autophagy in the evolution of longevity. In this mini review we retrace the appearance and functions evolved by autophagy in eukaryotic cells and its protective contribution in the pathophysiology of aging.
The interest toward Small Modular nuclear Reactors (SMRs) is growing, and the economic competitiveness of SMRs versus large reactors is a key topic. Leveraging a systematic literature review, this ...paper firstly provides an overview of “what we know” and “what we do not know” about the economics and finance of SMRs. Secondly, the paper develops a research agenda. Several documents discuss the economics of SMRs, highlighting how the size is not the only factor to consider in the comparison; remarkably, other factors (co-siting economies, modularisation, modularity, construction time, etc.) are relevant. The vast majority of the literature focuses on economic and financial performance indicators (e.g. Levelized Cost of Electricity, Net Present Value, and Internal Rate of Return) and SMR capital cost. Remarkably, very few documents deal with operating and decommissioning costs or take a programme (and its financing) rather than a “single project/plant/site” perspective. Furthermore, there is a gap in knowledge about the cost-benefit analysis of the “modular construction” and SMR decommissioning.
•There is a growing interest toward Small Modular nuclear Reactors (SMRs).•A relatively large number of documents about SMRs has been published so far.•Presents the state-of-the-art on economics and finance of land-based SMRs.•Identifies the most relevant gap in knowledge and provides a research agenda.•The research method is a systematic literature review.
Summary
Purpose: To estimate the prevalence of potentially severe drug–drug interactions (DDIs) and their relationship with age, sex and number of prescribed drugs.
Methods: We analysed all ...prescriptions dispensed from 1 January 2003 to 31 December 2003 to individuals aged 65 or more registered under the Local Health Authority of Lecco, a northern Italian province with a population of almost 330 000 persons. Elderly who received at least two co‐administered prescriptions were selected to assess the presence of DDIs.
Results: The prevalence of potentially severe DDIs was 16%, and rose with increasing patient’s age and number of drugs prescribed. At multivariate analysis, the adjusted odds ratios rose from 1·07 (95% CI 1·03–1·11) in patients aged 70–74 to 1·52 (95% CI 1·46–1·60) in those aged 85 or older. Elderly taking more than five drugs on a chronic basis had a statistically significant higher risk of sever DDIs than those receiving less than 3 or 3–5 such drugs.
Conclusions: The elderly constitutes a population at high risk of DDIs. As physicians still have some difficulty in managing this problem, it is essential to highlight for them, which factors raise the risk of DDIs.
ABSTRACT
We report the first extensive optical flux and spectral variability study of the TeV blazar TXS 0506 + 056 on intranight to long-term time-scales using BVRI data collected over 220 nights ...between 2017 January 21 to 2022 April 9 using eight optical ground-based telescopes. In our search for intraday variability (IDV), we have employed two statistical analysis techniques, the nested ANOVA test and the power enhanced F-test. We found the source was variable in 8 nights out of 35 in the R-band and in 2 of 14 in the V-band yielding duty cycles (DC) of 22.8 per cent and 14.3 per cent, respectively. Clear colour variation in V − R was seen in only 1 out of 14 observing nights, but no IDV was found in the more limited B, I, and B − I data. During our monitoring period the source showed a 1.18 mag variation in the R-band and similar variations are clearly seen at all optical wavelengths. We extracted the optical (BVRI) SEDs of the blazar for 44 nights when observations were carried out in all four of those wavebands. The mean spectral index (α) was determined to be 0.897 ± 0.171.
•Groups of Epilepsy Specialist Nurses can efficaciously function in a hospital.•The Epilepsy Specialist Nurse offers holistic care to patients and their carers.•The Epilepsy Specialist Nurse acts as ...liaison among members of the team.•The Epilepsy Specialist Nurse role is heterogeneous and influenced by the context.•Updated description of the role is necessary for its implementation and regulation.
To describe the role and activities of epilepsy specialist nurses (ESNs) operating as a team in the setting of a hospital specialising in the diagnosis and management of seizure disorders.
We conducted a descriptive mixed-methods embedded single case study. We recruited 9 ESNs, 14 of their professional colleagues and 9 ‘key informants’ to analyse their perceptions of the role and activities of ESNs. We collected data through interviews, questionnaires, observations, and documentation. The study was conducted at the Filadelfia Epilepsy Hospital, Denmark.
The team of ESNs offers holistic care to patients and their caregivers regarding the clinical, social, and emotional aspects of epilepsy. The ESNs are integrated in a multidisciplinary team and promote collaboration among the team members. ESNs also contribute to organisational aspects and perform research activities.
A structured group of ESNs can operate effectively and extensively in a specialised hospital setting. Our findings contribute to clarifying the description of the ESN’s role, and provide an example of how ESNs can be incorporated into a hospital’s organisational structure.
It has been hypothesized that a replication associated repair pathway operates on base damage and single strand breaks (SSB) at replication forks. In this study, we present the isolation from the ...nuclei of human cycling cells of a multiprotein complex containing most of the essential components of base excision repair (BER)/SSBR, including APE1, UNG2, XRCC1 and POLβ, DNA PK, replicative POLα, δ and ε, DNA ligase 1 and cell cycle regulatory protein cyclin A. Co-immunoprecipitation revealed that in this complex DNA repair proteins are physically associated to cyclin A and to DNA replication proteins including MCM7. This complex is endowed with DNA polymerase and protein kinase activity and is able to perform BER of uracil and AP sites. This finding suggests that a preassembled DNA repair machinery is constitutively active in cycling cells and is ready to be recruited at base damage and breaks occurring at replication forks.
Hypertension (HTN) is common among obese children and adolescents and increases their cardiovascular risk later in adulthood. The aim of the study was to evaluate the prevalence of HTN identified by ...office blood pressure (BP) measurement and ambulatory BP monitoring (ABPM) in a cohort of obese children and adolescents and its association with anthropometric and glycometabolic indices.
Seventy consecutive obese Caucasian children and adolescents aged 7–16 years were enrolled. Patients underwent ABPM, echocardiogram and carotid ultrasonography. Sex- and age-adjusted logistic multivariable analysis models were used to assess the association between HOMA-IR, HOMA-β, QUICKI with HTN at ABPM. Receiver Operation Curve (ROC) analysis with Youden J statistics was used to identify the optimal HOMA-IR, HOMA-β and QUICKI cut-off to predict HTN at ABPM. Hypertensive office BP was found in 25.7% of obese patients. ABPM diagnosed HTN in 34.9% of patients: 20.6% of obese patients had masked HTN (MHTN), and 12.7% had white coat HTN (WCH). Hypertensive obese patients (according to ABPM) had higher HOMA-IR and HOMA-β, and a lower QUICKI than normotensive subjects. HOMA-IR, HOMA-β and QUICKI predicted HTN at ABPM in obese patients in age- and sex-adjusted logistic multivariable models. Optimal cut-offs to predict HTN at ABPM in obese patients were: HOMA-IR ≥ 3.30, HOMA-β ≥ 226.7 and QUICKI <0.33, with high sensitivity.
A sequential testing strategy applying office BP and glycometabolic indices can identify hypertensive obese pediatric patients with high diagnostic accuracy and potentially reducing costs. This strategy needs validation in an external and larger cohort.
•Hypertension is common among obese children and adolescents.•Masked hypertension in common obese children and adolescents and can only be diagnosed using ambulatory blood pressure monitoring (ABPM).•Hypertension is strongly associated with altered glycometabolic indices (HOMA-IR, HOMA-β and QUICKI).•Altered HOMA-IR, HOMA-β and QUICKI can identify obese pediatric subjects with hypertension with high sensitivity.•Combining office blood pressure and glycometabolic assessment can accurately diagnose obese children and adolescents with hypertension.
Dolichoectasia of the basilar artery is a characteristic finding of Fabry disease. However, its prevalence, severity, and course have been poorly studied. This study quantitatively evaluated, by MRA, ...a panel of basilar artery parameters in a large cohort of patients with Fabry disease.
Basilar artery mean diameter, curved length, "origin-to-end" linear distance (linear length), and tortuosity index (curved length ÷ linear length - 1) were retrospectively measured on 1.5T MRA studies of 110 patients with Fabry disease (mean age, 39.4 ± 18.6 years; 40 males) and 108 control patients (mean age, 42.0 ± 18.2 years; 40 males).
Patients with Fabry disease had increased basilar artery mean diameter (
< .001) and basilar artery linear length (
= .02) compared with control patients. Basilar artery curved length and tortuosity index correlated with age in both groups (
< .001), whereas basilar artery linear length correlated with age only in patients with Fabry disease (
= .002). Patients with Fabry disease showed a basilar artery curved length mean increase of 4.2% (9.7% in male patients with Fabry disease versus male control patients), whereas the basilar artery mean diameter had a mean increase of 12.4% (14.3% in male patients with Fabry disease versus male control patients). Male patients with Fabry disease had increased basilar artery mean diameter, curved length, and tortuosity index compared with female patients with Fabry disease (
= .04,
= .02, and
< .001, respectively) and male control patients (
< .001,
= .01, and
= .006, respectively). Female patients with Fabry disease demonstrated an age-dependent increase of basilar artery mean diameter that became significant (
< .001) compared with female control patients above the age of 45 years.
The basilar artery of patients with FD is subjected to major remodeling that differs according to age and sex, thus providing interesting clues about the pathophysiology of cerebral vessels in Fabry disease.
To assess cortical inhibitory and excitatory mechanisms in obsessive-compulsive disorder (OCD).
Transcranial magnetic stimulation (TMS) studies have found decreased neuronal inhibition and a reduced ...cortical silent period in the primary motor area in Tourette's syndrome, focal dystonia, and other disorders believed to involve dysfunction of subcortical structures, including the basal ganglia. Dysfunction of the basal ganglia and linked regions also has been implicated in OCD, which has significant clinical and familial overlap with tic disorders.
We applied the TMS techniques previously used in Tourette's syndrome to a group of 16 OCD patients (seven unmedicated) and 11 age-matched healthy volunteers extensively screened for psychopathology. Measures of motor cortex excitability included resting and active motor threshold, cortical silent period duration, and intracortical inhibition and facilitation using a paired-pulse TMS technique with a subthreshold conditioning stimulus.
Similar to recent findings in Tourette's syndrome and focal dystonia, this study reports significantly decreased intracortical inhibition (ICI) relative to the volunteers at interstimulus intervals from 2 to 5 msec. We also found decreased active and resting motor evoked potential threshold in the OCD patients, another indication of increased cortical excitability. Neither abnormality appeared medication related. The decreases in ICI and motor threshold were greatest in OCD patients with comorbid tics, but remained significant in patients without tics.
The data suggest abnormal cortical excitability in obsessive-compulsive disorder. These findings are congruent with the hypothesis that Tourette's syndrome and obsessive-compulsive disorder (OCD) are analogous disorders with overlapping dysfunction in corticobasal circuits. Patients with tic-related OCD may have more abnormal motor cortex excitability than OCD patients without tics.
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