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Pramipexole Augmentation for Treatment-Resistant Unipolar Depression Not Responding to Aripiprazole Augmentation
No full textBackground: At least 50% of patients with treatment-resistant depression (TRD) fail to respond to antidepressant augmentation with aripiprazole (AA), currently the augmentation strategy with the best evidence of efficacy. The present observational study investigated whether pramipexole augmentation (PA) might be useful for patients who failed AA. Methods: We compared the short- and long-term effectiveness and safety of PA in 81 consecutively recruited unipolar patients with TRD, 58 (71.6%) not previously treated with AA (UAA) and 23 (28.4%) who previously failed AA (FAA). Results: The FAA and UAA groups did not differ significantly in terms of remission, response, improvement, and general functioning at 12 and 24 weeks and in terms of freedom from relapse at 12 and 24 months. The response rates at 24 weeks were 69.6% (n = 16) and 77.6% (n = 45), and the remission rates were 60.9% (n = 14) and 74.1% (n = 43), respectively. The rates of sustained response at 24 months were 72.7% (n = 8) and 84.2% (n = 16), respectively. The 2 groups did not differ significantly on safety outcomes (acceptability, tolerability, suicidality and suicide attempts) in the short and long term. Conclusions: Our study showed that the off-label use of PA may be a promising treatment for patients with unipolar TRD who had previously failed respond to AA. The present findings are preliminary and should be interpreted with caution due to study limitations, including the flexibility of the add-on schedule and the small sample size of patients followed up for 12 and 24 months, and need to be confirmed in larger studies
Three‐year treatment with anti‐CGRP monoclonal antibodies modifies migraine course: the prospective, multicenter I‐GRAINE study
No full textThe impact of multimorbidity on Quality of Life in inflammatory myopathies: A cluster analysis from the COVAD dataset
Get PDFObjective: The presence of comorbidities can substantially affect patients’ quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. Methods: We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs) and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined basic multimorbidity (BM) as the presence of ≥2 non-rheumatic chronic conditions and complex multimorbidity (CM) as the presence of ≥3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical clustering on principal components was performed for grouping. Results: Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (odds ratio [OR]: 1.62 vs oAIRDs and 2.95 vs HCs, P<0.01), BM (OR: 1.66 vs oAIRDs and 3.52 vs HCs, P<0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, P<0.01) and mental health disorders (MHDs) (OR: 1.33 vs oAIRDs and 2.63 vs HCs, P<0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all P<0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. Conclusion: Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches
From volcanic ashes to magnetic zeolites: unravelling the iron oxide phase transitions by magnetic and advanced structural characterization
No full textVolcanic ashes, rich in iron-containing phases, present an underexplored resource for creating functional materials. In this study, we investigate the hydrothermal transformation of volcanic ashes from Mount Etna (Sicily, Italy) into magnetic zeolites, exploring both structural and magnetic evolution. By combining X-ray absorption spectroscopy (Fe K-edge) and magnetometry, we reveal how the phase transition from olivine to magnetite-like phases, and hematite influences the magnetic behaviour. We observe distinct changes in iron oxidation states, coordination, and the emergence of antiferromagnetic contributions. This work highlights the potential of volcanic ashes as a sustainable source for designing advanced materials with tunable magnetic properties
Arbitration Tax Procedure for the Settlement of Tax Treaty-Related Disputes: Critical Insights about a Diffused Resort to the Final Offer Arbitration Model with Respect to the Balance Between the Target of a Mandatory and Binding Decision on the Parties Involved, and the Guarantee of Taxpayers’ Participation Rights
No full textThis essay critically examines the increasing use of the final offer arbitration (FOA) procedure in resolving tax treaty-related disputes in international and EU tax law. It explores the comparative experiences outlined by article 25(5) of the OECD Model, the OECD MLI (Part VI) and the EU Directive No. 1852/2017 (EU DRD), highlighting both advantages and challenges of the FOA model. The analysis focuses on whether an arbitration panel can be recognized as a referral body under article 267 of the TFEU, especially when questions of EU law interpretation arise, referencing the Achmea judgment by the Court of Justice of the European Union (CJEU). The essay also evaluates the CJEU’s potential interpretative role regarding the EU DRD when national courts of EU Member States submit preliminary rulings. Finally, it considers the position and participatory rights of taxpayers within the arbitration process, noting that the EU DRD, as EU secondary law, must uphold the principles and procedural guarantees enshrined in the European Charter of Fundamental Rights
Effects of Sulfate Limitation on Photosynthesis and Cell Composition of Unicellular Marine Microalgae of Different Phylogenies
Get PDFSulfur (S) is an essential macroelement for photosynthetic organisms and is acquired as sulfate and assimilated as sulfide into cysteine through a highly demanding reductive process. S is a key component of proteins, lipids, and various other cellular metabolites and plays a direct role in photosynthesis, both in the electron transport and in carbon fixation reactions. Despite such central functions, most of our knowledge on S metabolism is focused on plant species, while in microalgae it is still fragmented, particularly concerning their huge phylogenetic diversity. Here, we investigated responses to continuous low sulfate availability in three marine microalgae, two Chlorophytes, Tetraselmis suecica and Dunaliella salina, and the diatom Phaeodactylum tricornutum, by characterizing their growth, photosynthesis, elemental, and macromolecular composition. As a general trend, all the microalgae acclimated to the low sulfate medium prioritized the allocation of available resources to photosynthesis. By modulating their pigment content per cell and the stoichiometry of their photosynthetic apparatus, S-limited cells kept in vivo photosynthetic activity close to that of control cultures. Conversely, growth and cell composition were modulated in a species-specific manner. Results are discussed also in an evolutionary perspective, taking into consideration that, throughout Earth's history, sulfate concentration significantly increased from ancient to modern oceans, and such variation was paralleled by changes in the ecological abundances between algal groups, with the red algae lineage of present-day oceans supplanting the green algae, more abundant in the past
Brachial plexus schwannomas
No full textBACKGROUND: Schwannoma is a rare tumor that can be found in the brachial plexus. Despite the fact it is benign it can cause inflammatory reaction or compression of the nerves’ fascicles causing altered muscular or sensitive performance of the upper limb. Diagnosis of Schwannoma in the brachial plexus is difficult due to confounding interpretation with other lesions, that makes important magnetic resonance imaging (MRI) and histopathological examination for a complete diagnostic assessment. Surgical treatment is challenging, but, currently, microsurgical approach using the microscope, microsurgical tools and skills allow tumor removal with an acceptable risk of injury to neurovascular structures. METHODS: In our multicenter study we reported brachial plexus Schwannoma of six patients treated by surgical excision. Medical records and MRI data of all patients were reviewed and outcomes analyzed. RESULTS: We confirm that current precise surgical techniques represent an important approach to remove Schwannomas occurring around brachial plexus. CONCLUSIONS: Schwannomas of the brachial plexus are curable lesions and the use of precise surgical techniques allows these tumors to be removed with minimal morbidity
Myocardial Ischemia/Reperfusion Injury: Molecular Insights, Forensic Perspectives, and Therapeutic Horizons
Get PDFAcute myocardial infarction (AMI) remains the leading cause of death worldwide, with myocardial ischemia/reperfusion injury (MIRI) emerging as a significant factor influencing patient outcomes despite timely reperfusion therapy. MIRI refers to paradoxical myocardial damage that occurs upon restoration of coronary blood flow and is driven by complex inflammatory, oxidative, and metabolic mechanisms, which can exacerbate infarct size (IS), contributing to adverse outcomes. This review explores the molecular and cellular pathophysiology of MIRI, emphasizing both its clinical and forensic relevance. The principal mechanisms discussed include oxidative stress and mitochondrial dysfunction, calcium overload and ion homeostasis imbalance, inflammatory responses, with particular focus on the NLRP3 inflammasome and cytokine pathways, and multiple forms of cell death (apoptosis, necroptosis, pyroptosis, and autophagy). Additionally, the authors present original immunohistochemical findings from autopsy cases of patients who suffered ST-segment elevation myocardial infarction (STEMI) and underwent percutaneous coronary intervention (PCI), but subsequently died. These findings underscore that successful reperfusion does not completely prevent delayed complications, like arrhythmias, ventricular fibrillation (VF), and sudden cardiac death (SCD), often caused by secondary MIRI-related mechanisms. Moreover, the case series highlight the diagnostic value of inflammatory markers for pathologists in identifying MIRI as a contributing factor in such fatalities. Finally, immunotherapeutic strategies—including IL-1 and IL-6 inhibitors such as Canakinumab and Tocilizumab—are reviewed for their potential to reduce cardiovascular events and mitigate the effects of MIRI. The review advocates for continued multidisciplinary research aimed at improving our understanding of MIRI, developing effective treatments, and informing forensic investigations of reperfusion-related deaths