Default Mode Network alterations in alexithymia: An EEG power spectra and connectivity study

Recent neuroimaging studies have shown that alexithymia is characterized by functional alterations in different brain areas [e.g., posterior cingulate cortex (PCC)], during emotional/social tasks. However, only few data are available about alexithymic cortical networking features during resting state (RS). We have investigated the modifications of electroencephalographic (EEG) power spectra and EEG functional connectivity in the default mode network (DMN) in subjects with alexithymia. Eighteen subjects with alexithymia and eighteen subjects without alexithymia matched for age and gender were enrolled. EEG was recorded during 5 min of RS. EEG analyses were conducted by means of the exact Low Resolution Electric Tomography software (eLORETA). Compared to controls, alexithymic subjects showed a decrease of alpha power in the right PCC. In the connectivity analysis, compared to controls, alexithymic subjects showed a decrease of alpha connectivity between: (i) right anterior cingulate cortex and right PCC, (ii) right frontal lobe and right PCC, and (iii) right parietal lobe and right temporal lobe. Finally, mediation models showed that the association between alexithymia and EEG connectivity values was directed and was not mediated by psychopathology severity. Taken together, our results could reflect the neurophysiological substrate of some core features of alexithymia, such as the impairment in emotional awareness

The DNA Alkylguanine DNA Alkyltransferase-2 (AGT-2) Of Caenorhabditis Elegans Is Involved In Meiosis And Early Development Under Physiological Conditions

DNA alkylguanine DNA alkyltransferases (AGTs) are evolutionary conserved proteins that repair alkylation damage in DNA, counteracting the effects of agents inducing such lesions. Over the last years AGTs have raised considerable interest for both the peculiarity of their molecular mechanism and their relevance in cancer biology. AGT knock out mice show increased tumour incidence in response to alkylating agents, and over-expression of the human AGT protein in cancer cells is frequently associated with resistance to alkylating chemotherapy. While all data available point to a function of AGT proteins in the cell response to alkylation lesions, we report for the first time that one of the two AGT paralogs of the model organism C. elegans, called AGT-2, also plays unexpected roles in meiosis and early development under physiological conditions. Our data suggest a role for AGT-2 in conversion of homologous recombination intermediates into post-strand exchange products in meiosis, and show that agt-2 gene down-regulation, or treatment of animals with an AGT inhibitor results in increased number of germ cells that are incompatible with producing viable offspring and are eliminated by apoptosis. These results suggest possible functions for AGTs in cell processes distinct from repair of alkylating damage

Universal and Specific Services for University Students with Specific Learning Disabilities: The Relation to Study Approach, Academic Achievement, and Satisfaction

In recent years, an increasing number of students with specific learning disabilities (SLDs) have enrolled in universities. The present exploratory study examined the frequency of use and appreciation of universal (open to every student) and specific services (offered to students with SLDs) and their relation to age, academic achievement, satisfaction, self-efficacy, and use of self-regulated learning (SRL) strategies. Participants were 147 Italian university students with SLD diagnoses (42 males; mean age: 22.49, SD = 3.29). Results showed that, overall, the frequency of use and appreciation of specific services were positively related to academic satisfaction, self-efficacy, and SRL strategies. Furthermore, frequency of use of compensatory tools and dispensatory measures was positively associated with academic achievement. These findings suggest that universities play an important role in supporting students with SLDs during their academic years by providing them with useful services and accommodations

Optimizing indices of atrial fibrillation susceptibility and burden to evaluate atrial fibrillation severity, risk and outcomes.

Atrial fibrillation (AF) has heterogeneous patterns of presentation concerning symptoms, duration of episodes, AF burden, and the tendency to progress towards the terminal step of permanent AF. AF is associated with a risk of stroke/thromboembolism traditionally considered dependent on patient-level risk factors rather than AF type, AF burden, or other characterizations. However, the time spent in AF appears related to an incremental risk of stroke, as suggested by the higher risk of stroke in patients with clinical AF vs. subclinical episodes and in patients with non-paroxysmal AF vs. paroxysmal AF. In patients with device-detected atrial tachyarrhythmias, AF burden is a dynamic process with potential transitions from a lower to a higher maximum daily arrhythmia burden, thus justifying monitoring its temporal evolution. In clinical terms, the appearance of the first episode of AF, the characterization of the arrhythmia in a specific AF type, the progression of AF, and the response to rhythm control therapies, as well as the clinical outcomes, are all conditioned by underlying heart disease, risk factors, and comorbidities. Improved understanding is needed on how to monitor and modulate the effect of factors that condition AF susceptibility and modulate AF-associated outcomes. The increasing use of wearables and apps in practice and clinical research may be useful to predict and quantify AF burden and assess AF susceptibility at the individual patient level. This may help us reveal why AF stops and starts again, or why AF episodes, or burden, cluster. Additionally, whether the distribution of burden is associated with variations in the propensity to thrombosis or other clinical adverse events. Combining the improved methods for data analysis, clinical and translational science could be the basis for the early identification of the subset of patients at risk of progressing to a longer duration/higher burden of AF and the associated adverse outcomes

Comparing Outcomes in Asymptomatic and Symptomatic Atrial Fibrillation: A Systematic Review and Meta-Analysis of 81,462 Patients

Background: In atrial fibrillation (AF) patients, the presence of symptoms can guide the decision between rate or rhythm control therapy, but it is still unclear if AF-related outcomes are determined by symptomatic status of their clinical presentation. Methods: We performed a systematic review and metanalysis following the PRISMA recommendations on available studies that compared asymptomatic to symptomatic AF reporting data on all-cause mortality, cardiovascular death, and thromboembolic events (TEs). We included studies with a total number of patients enrolled equal to or greater than 200, with a minimum follow-up period of six months. Results: From the initial 5476 results retrieved after duplicates\u2019 removal, a total of 10 studies were selected. Overall, 81,462 patients were included, of which 21,007 (26%) were asymptomatic, while 60,455 (74%) were symptomatic. No differences were found between symptomatic and asymptomatic patients regarding the risks of all-cause death (odds ratio (OR) 1.03, 95% confidence interval (CI) 0.81\u20131.32), and cardiovascular death (OR 0.87, 95% CI 0.54\u20131.39). No differences between symptomatic and asymptomatic groups were evident for stroke (OR 1.22, 95% CI 0.77\u20131.93) and stroke/TE (OR 1.06, 95% CI 0.86\u20131.31) risks. Conclusions: Mortality and stroke/TE events in AF patients were unrelated to symptomatic status of their clinical presentation. Adoption of management strategies in AF patients should not be based on symptomatic clinical status

Nanocrystals as an effective strategy to improve Pomalidomide bioavailability in rodent

Pomalidomide (POM) is an FDA-approved immunomodulatory imide drug (IMiDs) an it is effectively used in the treatment of multiple myeloma. IMiDs are analogs of the drug thalidomide and they have been repurposed for the treatment of several diseases such as psoriatic arthritis and Kaposi Sarcoma. In recent years, IMiDs have been also evaluated as a new treatment for neurological disorders with an inflammatory and neuroinflammatory component. POM draws particular interest for its potent anti-TNF-α activity at significantly lower concentrations than the parent compound thalidomide. However, POM's low water solubility underpins its low gastrointestinal permeability resulting in irregular and poor absorption. The purpose of this work was to prepare a POM nanocrystal-based formulation that could efficiently improve POM's plasma and brain concentration after intraperitoneal injection. POM nanocrystals prepared as a nanosuspension by the media milling method showed a mean diameter of 219 nm and a polydispersity index of 0.21. POM's nanocrystal solubility value (22.97 µg/mL) in phosphate buffer was about 1.58 folds higher than the POM raw powder. Finally, in vivo studies conducted in adult Male Sprague-Dawley rats indicated that POM nanocrystal ensured higher and longer-lasting drug levels in plasma and brain when compared with POM coarse suspension