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Dynamic functional network connectivity impairment in bipolar disorder and its relationship with global functioning
No full text: Abnormal functional connectivity (FC) has been consistently associated with bipolar disorders (BD). Classical FC analyses assume stationarity of brain interactions, although connectivity actually varies over time. Here, we examined alterations in dynamic functional network connectivity (dFNC) in BD, their associations with symptom severity and global functioning, and potential differences between bipolar disorder type I (BD1) and type II (BD2). In this case-control study, we investigated dFNC in 57 patients with BD (29 BD1, 28 BD2) and 43 healthy controls (HCs). Most patients were euthymic at scanning (∼86 %), with only a minority showing residual depressive or hypomanic/mixed symptoms. Resting-state fMRI data were decomposed with spatially constrained independent component analysis and analyzed using a sliding-window approach. Meta-state metrics-number of meta-states, transitions, total distance, and span-were derived and compared across groups. Correlations with clinical measures and Global Assessment of Functioning (GAF) scores were tested. Dynamic metrics (number of meta-states, state transitions, and total distance) were reduced in BD relative to HCs, with the greatest reduction in BD1, followed by BD2. State span did not differ between groups. Across the BD sample, higher GAF scores were positively associated with greater dynamic fluidity, whereas no significant associations emerged with standard symptom scales. In conclusion, BD is characterized by a graded disruption of the spatio-temporal dynamics of large-scale brain networks, most pronounced in BD1. Reduced neural flexibility is linked to poorer global functioning, suggesting that dFNC meta-state metrics may provide clinically relevant markers of illness burden in bipolar disorder
Magnon-Magnon Interaction Induced by Dynamic Coupling in a Hybrid Magnonic Crystal
No full textWe report a combined experimental and numerical investigation of spin-wave dynamics in a hybrid magnonic crystal
consisting of a CoFeB artificial spin ice (ASI) of stadium-shaped nanoelements patterned atop a continuous NiFe film separated by a 5 nm Al2O3 spacer. Using Brillouin light scattering spectroscopy, we probe the frequency dependence of thermal spin waves as functions of applied magnetic field and wavevector, revealing the decisive role of interlayer dipolar coupling in the magnetization dynamics. Micromagnetic simulations complement the experiments, showing a strong interplay between ASI edge modes and backward volume modes in the NiFe film. The contrast in saturation magnetization between CoFeB and NiFe enhances this coupling, leading to a pronounced hybridization manifested as a triplet of peaks in the BLS spectrapredicted by simulations and observed experimentally. This magnon−magnon coupling persists over a wide magnetic field range, shaping both the spin-wave dispersion at fixed fields and the full frequency-field response throughout the magnetic hysteresis loop. Our findings establish how ASI geometry can selectively enhance specific spin-wave wavelengths in the underlying film, thereby boosting their amplitude and identifying them as preferential channels for spin wave transmission and manipulation
Albuterol-budesonide rescue inhaler for asthma: Patterns of use and safety in the MANDALA trial
No full textBackground: The MANDALA study (NCT03769090) in moderate-to-severe asthma served as the basis of the Food and Drug Administration's 2023 approval of albuterol-budesonide 180/160 μg pressurized metered-dose inhaler for the as-needed treatment or prevention of bronchoconstriction and to reduce exacerbation risk in patients with asthma aged 18 years or older. Clinicians would benefit from an understanding of the patterns of use of albuterol-budesonide vs albuterol and overall inhaled corticosteroid (ICS) exposure when ICS-containing rescue therapies are used alongside ICS-based maintenance therapies.
Objective: To evaluate patterns of as-needed use and safety profiles of albuterol-budesonide 180/160 μg vs albuterol 180 μg, using data from MANDALA.
Methods: Study medication use was patient-documented using an electronic diary. Safety was assessed as adverse events. Patterns of study medication use (2 inhalations = 1 dose) were summarized as mean percentages of days in which inhalations per day fell within predefined categories (0, 1-2, 3-4, 5-6, 7-8, 9-10, 11-12, and >12).
Results: The safety population included 981 patients randomized to as-needed albuterol-budesonide and 981 to as-needed albuterol. Patients adhered to maintenance therapy regimens on a mean of more than or equal to 75% of days. Use of as-needed study drug was similar in both groups (mean of 2.6 and 2.8 inhalations/d of albuterol-budesonide and albuterol, respectively). High daily use (≥8 inhalations/d) or long-term high daily use (≥7 consecutive days) was rare. Adverse event frequencies (ICS-associated and not) were low and comparable between groups, regardless of mean daily as-needed use.
Conclusion: Patterns of use and safety profiles were similar between as-needed albuterol-budesonide and albuterol
Recent advances in experimental and clinical applications of chest electrical impedance tomography: a narrative review
No full textThe achieved technological maturity of electrical impedance tomography (EIT) and the clinical need of the information provided by this functional imaging method has intensified research activities on the medical use of chest EIT. The recent years have witnessed an accelerated research covering not only the experimental setting but also the clinical environment with the major focus on mechanically ventilated patients, both in the perioperative period or as part of the intensive care treatment. Patients of all age groups are being included in clinical investigations and studies using EIT. The major objectives for use of EIT are the monitoring of regional lung and cardiovascular function, identification of adverse events (pneumothorax, alveolar overdistension and collapse, pulmonary embolism) and guidance for individualised therapy (selection of ventilator setting, positioning and physical therapy). Our review describes the most recent achievements of experimental and clinical research on chest EIT. The provided information helps to identify the current hot topics in EIT research and to guide further improvements of EIT technology and applications that are still needed to enforce the establishment of chest EIT in routine patient care
Extracellular vesicles in cardiac surgery: unlocking new frontiers in cardioprotection and patient outcomes
No full textCardiac surgery, while life-saving, induces profound physiological stress due to ischemia–reperfusion injury (IRI), systemic inflammation, and endothelial dysfunction, particularly in procedures involving cardiopulmonary bypass. In this complex setting, extracellular vesicles (EVs) have emerged as both biomarkers and potential mediators of cardiovascular injury and repair. This narrative review explores the multifaceted roles of EVs in cardiac surgery, with a focus on coronary artery bypass grafting (CABG) and valve repair or replacement. The review examines the diagnostic and therapeutic implications of circulating EVs and their role in graft patency, perioperative complications, myocardial protection, and vascular remodeling. We summarize current evidence regarding the biogenesis, classification, and engineering of EVs, highlighting their ability to transport bioactive molecules that modulate inflammation, coagulation, and apoptosis. In CABG, EVs have been linked to systemic inflammatory response, myocardial injury, and postoperative cognitive dysfunction. In valvular heart surgery and transcatheter procedures, endothelial- and platelet-derived EVs correlate with endothelial injury, shear stress, and postoperative outcomes. Preclinical studies indicate that stem cell-derived EVs exert cardioprotective effects by reducing apoptosis, promoting angiogenesis, and reprogramming macrophages. EVs represent a promising frontier in cardiac surgery, offering opportunities for risk stratification, real-time monitoring, and novel therapeutic strategies. Further translational research and standardized clinical protocols are needed to integrate EV profiling into perioperative care and to explore the full potential of EV-based therapies in cardioprotection and vascular healing
Microglia drive synaptic and functional connectivity deficits in the Ts65Dn mouse model of Down syndrome by affecting inhibition
No full textMicroglia, the resident immune cells of the brain, play a crucial role in sculpting neuronal circuits during development, and their dysfunction is increasingly implicated in neurodevelopmental disorders such as Down syndrome (DS). Here, we reveal a previously unrecognized pathological mechanism whereby microglia contribute to synaptic and neuronal activity deficits in DS: a selective disruption of microglia–interneuron interactions. Using primary neuron–microglia co-cultures from Ts65Dn mice, we
show that while trisomy in neurons drives excitatory synaptic deficits and major microglial morphological changes, microglial trisomy disrupts the regulation of inhibitory synapses in a cellautonomous manner. To investigate these pathological interactions in vivo, we developed a novel spatial distribution analysis tool that, combined with chemogenetic approaches targeting parvalbumin (PV) interneurons in Ts65Dn mice, allowed us to reveal a disrupted microglia–PV interneuron crosstalk characterized by reduced physical association and impaired microglial responsiveness to PV
activity. Finally, by targeting microglia via P2Y12 receptor inhibition, we restored cortical connectivity, rescued PV interneuron function, and improved cognitive performance in Ts65Dn mice. Overall, these findings establish microglia–interneuron dysregulation as a key driver of neuronal activity and synaptic dysfunction in the Ts65Dn mouse model of DS and identify the microglia as a promising therapeutic target to counter circuit dysfunction and cognitive deficit
Filosofia della letteratura
No full textIl volume ripercorre la storia dei rapporti tra filosofia e letteratura attraverso i secoli, e i movimenti culturali, per poi presnetare le questioni attuali
Tuberculosis and the perils of historical amnesia
No full textIn a recent Comment published in
The Lancet, Hans Henri P Kluge emphasised
the urgency of addressing drugresistant
tuberculosis in the WHO
European region. Although the health
security framing underscores important
risks, it might overlook the deeper
historical and structural forces that
have long shaped the persistence of
tuberculosis
Detecting Small Airways Dysfunction in Asthma: Rationale, Findings, and Future of ATLANTIS
No full textSmall airway dysfunction (SAD) is both common and clinically relevant in patients with asthma. However, there is no recognized "gold standard" approach for the identification of SAD in clinical practice. The ATLANTIS (AssessmenT of smalL Airways involvemeNT In aSthma) study was a prospective (1-year follow-up), multicenter, international observational study that aimed to identify the best, or best combination of biomarkers, physiological tests, and imaging markers for the determination of the presence of SAD, and to evaluate the contribution of SAD across all asthma severities to meaningful clinical asthma outcomes. A large number of analyses from the ATLANTIS study have been conducted or are planned. This narrative review summarizes the key findings to date and the future directions. Perhaps the most important finding so far is that a "toolbox" of spirometry, oscillometry, and a small airways dysfunction questionnaire can detect SAD with high accuracy (area under the receiver operating characteristic curve 0.96 and positive likelihood ratio 12.8). Further, collaboration with other consortia has demonstrated the use of oscillometry to identify asthma phenotypes. We advocate the adoption of the ATLANTIS toolbox into interventional studies in asthma-and if validated, this could form a useful part of research and daily clinical practice
Combined and cross-modal effects of acoustic and indoor air quality conditions on sensory and cognitive responses of university students
No full textIndoor Environmental Quality (IEQ) plays a crucial role in occupant well-being, particularly in educational settings where suboptimal IEQ impacts students’ cognitive abilities and ultimately their quality of learning. Although research into IEQ in educational settings has increased recently, studies that concurrently examine indoor air quality (IAQ) and acoustic domains remain scarce.
This study adopted a multi-domain approach by investigating the combined effects of these two domains on university students’ cognitive abilities, as well as their cross-modal impacts on soundscape and IAQ assessments. In laboratory conditions, 29 students were exposed to two ventilation regimes which led to two bio-effluent levels represented by two CO2 concentrations (800 and 3000 ppm), and four auditory conditions representative of both mechanical and natural ventilation conditions (Quiet, Babble noise, Mechanical Ventilation noise, and Birdsongs) while performing a calculation task and completing assessments soundscape and IAQ perception.
The results revealed a combined effect of IAQ and acoustics on calculation performance, with response times slowing down in quiet as bio-effluents increased. Moreover, only for a high bio-effluent level, response time was faster in Babble noise compared to Quiet or Birdsongs. We speculated that these effects could be explained by the arousal theory. No cross-modal effects of the two domains were found for assessments, while changes in one domain influenced the corresponding perceptual evaluation. Overall, cognitive performance seems to be mediated by an increase in sound-induced arousal, consistent with the Yerkes-Dodson law, with the arousal-performance curve further modulated by IAQ levels