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Assessing the Safety and Efficacy of Lamotrigine as Anti-myotonic Agent in Myotonic Dystrophy Type 1 (DM1): A Longitudinal, Open-Label, Pilot Study
No full textIntroduction: Myotonia, defined as impaired relaxation of skeletal muscles after voluntary contraction or electrical stimulation, is a core feature of myotonic dystrophy type 1 (DM1) and can be highly disabling. The most used anti-myotonic drug, mexiletine, has limited availability and is associated with several side effects. Lamotrigine (LTG), an anti-epileptic drug that reduces voltage-sensitive sodium channel activity, has shown efficacy in treating myotonia in both in vitro models and patients with non-dystrophic myotonias. We aimed to investigate in a cohort of patients with DM1 the use of LTG as an anti-myotonic treatment in a real-world setting. Methods: We enrolled 14 consecutive adult patients with genetically confirmed DM1 and clinically significant myotonia impacting daily living (Myotonia Behaviour Scale, MBS > 1). LTG was administered in escalating doses, starting from 50 mg/day up to 200 mg/day. Efficacy was assessed using a linear mixed-effects model. Two functional timed tests [the 9-Hole Peg Test (9HPT) and the preparation of a coffee pot, devised by us and called the “Coffee Task” test] were performed at baseline (pre-treatment) and at each dose level. Safety data was also collected. Results: The mean age at enrollment was 40 years, and the mean disease duration was 12 years. LTG dosage had a significant positive effect on 9HPT performance at the maximum dose compared to baseline. Age and disease duration significantly influenced 9HPT results. No significant changes were observed in the other functional timed test. No serious adverse events were reported. Conclusion: This pilot, open-label study provides preliminary evidence for the efficacy and safety of LTG as an anti-myotonic treatment in patients with DM1. These findings support the need for larger, placebo-controlled trials to confirm its clinical utility
Rethinking Accountability in International Law: The role of Local Authorities in the Implementation of the European Convention on Human Rights
No full textThis article explores the evolving role of local authorities in the implementation and protection of human rights under the European Convention on Human Rights (ECHR). Drawing on extensive case law from the European Court of Human Rights (ECtHR), it illustrates how municipalities and regional bodies are increasingly recognised as both dutybearers and potential violators of Convention rights. The analysis spans key areas such as the protection of vulnerable individuals, freedom of expression and assembly, nondiscrimination, family life, procedural guarantees, education, environmental protection, and the governance of artificial intelligence. Despite their growing responsibilities, local authorities remain legally peripheral in international law, which continues to vest formal accountability solely in the State. The article critically examines this tension and considers emerging models of multilevel governance, particularly the European Union’s direct effect doctrine, as potential pathways for strengthening local accountability. It concludes that embedding human rights standards in local governance is both a legal obligation and a practical necessity, calling for clearer normative frameworks, capacity-building, and institutional support to align practice with the evolving multilevel human rights architectur
Polygenic scores and antidepressant treatment outcomes in major depression: a critical integrative review
No full textMajor depressive disorder (MDD) shows a large heterogeneity in antidepressant treatment outcome, a variability explained in part by common-variant liability captured by polygenic scores (PGSs). We performed a review of PubMed- and Google Scholar-indexed studies that related any PGS to treatment response, remission or resistance in adult MDD. Thirty-nine investigations met inclusion criteria. MDD-PGS emerged as the most consistently replicated predictor, each standard deviation increase raising non-remission odds by ∼10–14 % across six European trials and two biobank analyses. Schizophrenia genetic liability (SCZ-PGS) was uniformly detrimental under monoaminergic monotherapy (OR∼2.2 for top quintile) while possibly associated with improvement to electroconvulsive therapy (ECT) or lithium augmentation. Bipolar disorder PGS predicted faster lithium response (HR∼1.5), while attention-deficit/hyperactivity-disorder PGS was reliably associated with treatment-resistant depression (TRD) in multiple studies. PGSs for coronary-artery disease and stroke similarly reduced antidepressant efficacy and doubled TRD odds. Across traits, individual PGSs generally explained 85 % European), heterogeneous phenotyping and small discovery cohorts. Even so, PGSs may support pathway-specific treatment modifiers and justify prospective trials of genotype-guided lithium, ECT or augmentation with drugs modulating inflammation-metabolism. Scalable precision psychiatry will require multi-ancestry discovery, harmonised longitudinal outcomes and equitable implementation frameworks, but current evidence signals a realistic path from genomic insight to stratified care
Research-based persona narratives for targeted health interventions in the elderly population: a narrative review
Get PDFPhysical activity in people with borderline personality disorder: a study protocol for a randomised controlled trial
No full textPurpose. Treatments for mental disorders, such as pharmacotherapy and psychosocial interventions, do not always guarantee symptomatic remission. The effectiveness of Physical Activity (PA) in improving the psycho-physical health of individuals with various mental disorders is well-established; however, its effects on borderline personality disorder (BPD) have yet to be adequately studied. Currently, there are not approved pharmacological treatments for BPD, and access to effective psychotherapeutic interventions remains limited. This study aims to evaluate the efficacy of a PA programme as an adjunctive treatment for patients with BPD, in comparison with a control treatment. Objectives include reducing BPD symptoms and improving PA levels, as well as physical and psychological health. Methods. PABORD is a randomised controlled trial (RCT) targeting female outpatients aged 18-40 with a diagnosis of BPD. The intervention group (n=32) will participate in a structured 12-week PA programme, supervised by a sports physician and preceded by three psychoeducational sessions on healthy eating habits. The control group (n=32) will receive 8 parallel psychoeducational sessions focusing on PA, diet, and the risks associated with sedentary behaviour. Standardised assessments will be conducted at baseline, at the end of the intervention, and three months post-intervention. Results. Not yet available. Discussion and conclusions. The PA programme is expected to outperform the control treatment in terms of health status and PA levels at the end of the intervention. Repeated clinical assessments will aid in identifying psychosocial factors associated with the maintenance of PA. The study may provide valuable insights that could improve therapeutic options for patients with BPD
Search for Quasiparticle Scattering in the Quark-Gluon Plasma with Jet Splittings in pp and Pb-Pb Collisions at sNN =5.02 TeV
No full textThe ALICE Collaboration reports measurements of the large relative transverse momentum (kT) component of jet substructure in pp and Pb-Pb collisions at center-of-mass energy per nucleon pair sNN=5.02 TeV. Enhancement in the yield of such large-kT emissions in head-on Pb-Pb collisions is predicted to arise from partonic scattering with quasiparticles of the quark-gluon plasma. The analysis utilizes charged-particle jets reconstructed by the anti-kT algorithm with resolution parameter R=0.2 in the transverse-momentum interval 60<80 GeV/c. The soft drop and dynamical grooming algorithms are used to identify high transverse momentum splittings in the jet shower. Comparison of measurements in Pb-Pb and pp collisions shows medium-induced narrowing, corresponding to yield suppression of high-kT splittings, in contrast to the expectation of yield enhancement due to quasiparticle scattering. The measurements are compared to theoretical model calculations incorporating jet modification due to jet-medium interactions ("jet quenching"), both with and without quasiparticle scattering effects. These measurements provide new insight into the underlying mechanisms and theoretical modeling of jet quenching
Kidney Autotransplantation and “Debranch-First” Technique for Thoracoabdominal Stent-Graft Infection
Get PDFObjective: To present the surgical management of a 22-year-old patient with midaortic syndrome, symptomatic for claudication and renovascular hypertension, with infected aortic and renal stent grafts. Key Steps: Procedures were performed as follows: 1) right renal autotransplantation through a transperitoneal approach and midline abdominal incision; 2) thoracotomy with left visceral rotation and visceral vessel exposure; 3) left-heart bypass and “debranch-first” technique, with warm blood perfusion for the splanchnic vessels and cold Custodiol solution for renal perfusion; 4) aortic replacement with a tubular xenopericardium graft; and 5) separate reattachment of visceral vessel to the main tubular graft. Potential Pitfalls: Recurrent infections of the xenopericardium graft, kidney parenchyma loss, and major complications such as spinal cord ischemia, represent potential pitfalls to this procedure. Take-Home Message: Kidney autotransplantation allows right renal–infected stent graft removal before in situ thoracoabdominal reconstruction through left thoracoabdominal access, preserving renal function against renovascular hypertension
Combined Multilayered Amniotic Membrane Graft and Fibrin Glue as a Surgical Management of Limbal Dermoid Cyst
No full textBackground/Objectives: To report the cosmetic, clinical, and visual outcomes of a combined surgical approach for treating a corneal/limbal dermoid using excision and a three-layered amniotic membrane graft with fibrin glue. Methods: An 18-year-old female presented with impaired vision and ocular discomfort caused by a prominent dome-shaped limbal congenital dermoid on the inferotemporal cornea, resulting in a significant aesthetic concern. A full assessment, including refraction, best-corrected visual acuity (BCVA), corneal topography, aberrometry and anterior segment OCT (AS-OCT) was conducted to plan the surgical approach. The dermoid was excised under peribulbar anaesthesia using manual lamellar dissection, followed by the application of 0.02% Mitomycin C and a multilayered amniotic membrane graft with fibrin glue. A bandage contact lens was applied and removed after three weeks, with postoperative treatment including topical antibiotics and steroids. Follow-ups were conducted on day 1, at 1 week, 3 weeks, 2 months, 6 months, 1 year, and 2 years. Results: Histopathological examination confirmed the mesoblastic nature of the lesion. Significant improvements in BCVA and ocular symptoms were observed. Corneal topography showed ocular surface regularization with reduction of high order aberrations and point spread function. AS-OCT showed complete integration of the amniotic membrane, with full epithelial coverage of the defect. The healing process was uneventful and the ocular surface remained stable throughout the entire follow-up, without complications or recurrence. Conclusions: This approach of dermoid excision, multilayered amniotic membrane and fibrin glue restored vision effectively, with notable improvements in ocular surface and cosmetic outcomes, without recurrence over two years
L'autonomia della responsabilità dell'ente
No full textL'autonomia della responsabilità dell'ente per mancata identificazione dell'autore del reato-presupposto quale scelta di politica criminale: critica; inapplicabilità della esimente della particolare tenuità del fatt
Management and Burden of Hidradenitis Suppurativa: An Italian Hybrid Real-World Study
No full textIntroduction: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease that severely impacts quality of life and carries a substantial economic burden. Methods: This multicenter observational study generated real-world evidence on HS in Italy, focusing on clinical profiles, management, and costs. Data were collected from 50 adults at four specialized centers, combining primary data with retrospective administrative data. Results: Patients with moderate-to-severe disease had longer diagnostic delays (median 1.8 versus 0.7 years), lower symptom control (40.7% versus 95.2%), and worse quality of life (Dermatology Life Quality Index: 11.8 versus 8.0) than those with mild disease. Furthermore, HS was associated with higher costs in moderate-to-severe cases, including greater direct (€2214 versus €873) and indirect expenses (€2435 versus €262). Conclusions: The findings highlight the social and economic burden of HS and emphasize the need for increased healthcare awareness for earlier diagnosis and better management