5 research outputs found
PYRIDOXINE-dependent epilepsy (PDE): An observational study of neonatal cases on the role of pyridoxine in patients treated with standard anti-seizure medications
No full textBackground: The main objective of this study was to evaluate the neurological consequences of delayed pyridoxine administration in patients diagnosed with Pyridoxin Dependent Epilepsies (PDE). Materials and Methods: We reviewed 29 articles, comprising 52 genetically diagnosed PDE cases, ensuring data homogeneity. Three additional cases were included from the General Pediatric Operative Unit of San Marco Hospital. Data collection considered factors like age at the first seizure's onset, EEG reports, genetic analyses, and more. Based on the response to first-line antiseizure medications, patients were categorized into four distinct groups. Follow-up evaluations employed various scales to ascertain neurological, cognitive, and psychomotor developments. Results: Our study includes 55 patients (28 males and 27 females), among whom 15 were excluded for the lack of follow-up data. 21 patients were categorized as "Responder with Relapse", 11 as "Resistant", 6 as "Pyridoxine First Approach", and 2 as "Responders". The neurological outcome revealed 37,5 % with no neurological effects, 37,5 % showed complications in two developmental areas, 15 % in one, and 10 % in all areas. The statistical analysis highlighted a positive correlation between the time elapsed from the administration of pyridoxine after the first seizure and worse neurological outcomes. On the other hand, a significant association was found between an extended latency period (that is, the time that elapsed between the onset of the first seizure and its recurrence) and worse neurological outcomes in patients who received an unfavorable score on the neurological evaluation noted in a subsequent follow-up. Conclusions: The study highlights the importance of early recognition and intervention in PDE. Existing medical protocols frequently overlook the timely diagnosis of PDE. Immediate administration of pyridoxine, guided by a swift diagnosis in the presence of typical symptoms, might improve long-term neurological outcomes, and further studies should evaluate the outcome of PDE neonates promptly treated with Pyridoxine
The ‘Other-in-Self’: Love, Ecological Interconnectedness, and Socioemotional Vulnerability in Richard Flanagan’s The Living Sea of Waking Dreams
No full textThis article investigates Richard Flanagan’s latest novel The Living Sea of Waking Dreams (2020) through a psychological, philosophical, and ecocritical lens, focusing on how the author depicts an era of ecological crisis and social distancing. Written during the Covid-19 pandemics, Flanagan’s novel is a family drama about three middle-aged siblings that are facing their mother’s ordeal with a lethal disease in a context of climate change and related environmental catastrophes. Anna, whose point of view orients the narrative perspective, is repulsed by a human being’s hovering between life and death. Feeling uncomfortable while sitting at her mother’s bedside, she compulsively scrolls on her phone without paying attention to the images of burning forests and dead animals that fill her Instagram. Even when pieces of her own body begin to vanish because of an inexplicable fantastic phenomenon, she gets stuck in a state of psychoemotional paralysis. In my analysis of the novel, I will highlight how ecological issues are intertwined with the postcolonial discourse, and the personal histories of characters who experience different forms of alienation as a psychological state and social phenomenon. Drawing on philosophical concepts such as ecophobia, Ego- and Eco-resiliency, multidirectional eco-memory, and on the eco-ontology framework developed by Roberto Marchesini, I will discuss how Flanagan creates a fictional world in which ‘the Other in the Self’ is a key to prevent the physical and moral annihilation of the human
Two‐year effectiveness and safety of golimumab in ulcerative colitis: An IG‐IBD study
No full textBackground: Few data exist regarding the long-term effectiveness of golimumab in ulcerative colitis. No data have been reported on real-world continuous clinical response.Objective: This study aimed to describe the long-term outcomes in a large cohort of patients on golimumab who had ulcerative colitis.Methods: Consecutive patients with active ulcerative colitis, started on golimumab, were enrolled and prospectively followed up. The primary end point was to evaluate the long-term persistence on golimumab therapy.Results: A total of 173 patients with ulcerative colitis were studied. Of these, 79.2% were steroid dependent, and 46.3% were naive to anti-tumour necrosis factor alpha agents. The median duration of golimumab therapy was 52 weeks (range: 4-142 weeks). The cumulative probability of maintaining golimumab treatment was 47.3% and 22.5% at 54 and 108 weeks, respectively. Biological-naive status (odds ratio [OR] = 3.02, 95% confidence interval [CI]: 1.44-6.29; p = 0.003) and being able to discontinue steroids at Week 8 (OR = 3.32, 95% CI: 1.34-8.30; p = 0.010) and Week 14 (OR = 2.94, 95% CI: 1.08-8.02; p = 0.036) were associated with longer persistence on therapy. At Week 54, 65/124 (52.4%) postinduction responders were in continuous clinical response. A continuous clinical response was associated with a lower likelihood of golimumab discontinuation throughout the subsequent year of therapy (p < 0.01). Overall, 40 (23.1%) patients were in clinical remission at the last follow-up visit. Twenty-six adverse events were recorded, leading to golimumab withdrawal in 9.2% of patients.Conclusions: Biological-naive status and not requiring steroids at Weeks 8 and 14 seem to be associated with a longer persistence on golimumab therapy in ulcerative colitis
Author Correction: Differential diagnosis of neurodegenerative dementias with the explainable MRI based machine learning algorithm MUQUBIA
No full textLocalized Wnt-signaling promotes asymmetric NuMA-dependent oriented divisions and unequal apportioning of mitochondria
No full textIn multicellular organisms, the execution of developmental and homeostatic programs often relies on asymmetric cell divisions. These divisions require the alignment of the mitotic spindle axis to cortical polarity cues, and the unequal partitioning of cellular components between progeny cells. Asymmetric divisions are orchestrated by signals from the niche frequently presented in a directional manner, such as Wnt signals. Here we employ bioengineered Wnt-niches to demonstrate that in metaphase NuMA/dynein microtubule motors form a complex with activated LRP6 and β-catenin at the cortical sites of Wnt activation to orient cell division perpendicularly. We show that engagement of LRP6 co-receptors by Wnt ligands locally stabilizes actomyosin contractility through the accumulation of myosin1C. Additionally, we describe a proteomic-based approach to identify mitotic protein complexes enriched at the Wnt-contact site, revealing that mitochondria polarize toward localized Wnt3a sources and are asymmetrically apportioned to the Wnt-proximal daughter cell during Wnt-mediated asymmetric cell division of embryonic stem cells. Mechanistically, we show that CENP-F is required for mitochondria polarization towards localized sites of Wnt3a activation, and that deletion of the Wnt-co-receptor LRP6 impairs the asymmetric apportioning of mitochondria. Our findings enhance the understanding of mitotic Wnt-signaling and elucidate fundamental principles underlying Wnt-dependent mitochondrial polarization.
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