Search

To evaluate the effectiveness of vortioxetine in major depressive disorder (MDD) when used as a first-line versus second-line treatment or later.This was a post-hoc analysis of three 3-month non-interventional, prospective studies of vortioxetine in MDD - REVIDA (Malaysia, Philippines, Singapore, Thailand), PREVIDA (Pakistan) and TREVIDA (Taiwan). Improvements in depressive symptoms (PHQ-9, CGI-S), cognitive function (PDQ-D) and work productivity (WPAI) were compared between studies, and in a pooled analysis of patients using vortioxetine as the first line versus second-line treatment or later. Safety was compared between studies.Overall, 798 patients were analyzed (PREVIDA = 425, REVIDA = 130, TREVIDA = 243). Most patients in PREVIDA (60.5%)/REVIDA (57.4%) used vortioxetine as first-line treatment versus TREVIDA (21.8%). Generally, greater improvements from baseline were observed across outcome measures in PREVIDA/REVIDA versus TREVIDA (Month 3,In the Asian real-world setting, vortioxetine showed greater improvements in depressive and cognitive symptoms, work functioning, and response and remission rates when used as first-line versus second-line treatment or later. Vortioxetine was well-tolerated irrespective of the study population across Asia.

The TREVIDA study aimed to evaluate vortioxetine for the treatment of major depressive disorder (MDD) in Taiwanese adults.Patients with active depressive episode were recruited in this non-interventional, prospective, multi-site study conducted between June 2019 and August 2020 in Taiwan. Patient eligibility was independent of the physician's decision to prescribe vortioxetine for an MDD episode. Vortioxetine was initiated on the first visit. Depression severity, cognitive function, work productivity, functioning and safety were evaluated over 3 months.Overall, 242 patients were analyzed. At baseline, 70.7% and 90.4% of patients had moderately severe-to-severe depression based on PHQ-9 (Patient Health Questionnaire-9) and TDQ (Taiwanese Depression Questionnaire), respectively. By Month 3, significant improvements from baseline in depression severity (mean [SD] changes in PHQ-9, TDQ and CGI-S [Clinical Global Impression-Severity]: -6.3 [7.3]; -13.2 [14.0]; -1.5 [1.3], respectively), cognitive function (mean [SD] change in PDQ-D: -8.0 [17.5]), functioning (mean [SD] change in SDS: -5.4 [7.6]), and presenteeism (38.9% from 56.3%), work productivity loss (40.9% from 58.7%) and activity impairment (43.2% from 61.0%) were observed (Vortioxetine reduced depression severity and improved cognitive function, work productivity, and functioning in Taiwanese patients with MDD in the real-world setting. Vortioxetine was well-tolerated in this Taiwanese population.

Fetal hypoxia is a common risk factor that has been associated with a range of CNS disorders including epilepsy, schizophrenia, and autism. Cellular and molecular mechanisms through which hypoxia may damage the developing brain are incompletely understood but are likely to involve disruption of the laminar organization of the cerebral cortex. Lysophosphatidic acid (LPA) is a bioactive lipid capable of cortical influences via one or more of six cognate G protein-coupled receptors, LPA 1–6 , several of which are enriched in fetal neural progenitor cells (NPCs). Here we report that fetal hypoxia induces cortical disruption via increased LPA 1 signaling involving stereotyped effects on NPCs: N -cadherin disruption, displacement of mitotic NPCs, and impaired neuronal migration, as assessed both ex vivo and in vivo. Importantly, genetic removal or pharmacological inhibition of LPA 1 prevented the occurrence of these hypoxia-induced phenomena. Hypoxia resulted in overactivation of LPA 1 through selective inhibition of G protein-coupled receptor kinase 2 expression and activation of downstream pathways including G αi and Ras-related C3 botulinum toxin substrate 1. These data identify stereotyped and selective hypoxia-induced cerebral cortical disruption requiring LPA 1 signaling, inhibition of which can reduce or prevent disease-associated sequelae, and may take us closer to therapeutic treatment of fetal hypoxia-induced CNS disorders and possibly other forms of hypoxic injury.

INTRODUCTION Cognitive dysfunction has been significantly associated with functional impairment in patients with major depressive disorder (MDD). METHODS This is a subgroup analysis of 211 Malaysian patients recruited from the multicountry, multicenter, cross-sectional Cognitive Dysfunction in Asian patients with Depression (CogDAD) study. Depression severity, cognitive dysfunction, and functional disability were assessed and compared with the overall CogDAD study population. Factors associated with functional disability were also evaluated in this Malaysian patient population. RESULTS Approximately half of the Malaysian patients were in their first depressive episode, with the majority being treated for mild-to-moderate depression. Furthermore, Malaysian patients experienced cognitive dysfunction, with self-reported Perceived Deficits Questionnaire (PDQ-D) scores falling within the third quartile of PDQ-D severity. Malaysian patients also reported functional disability evidenced by a mean total Sheehan Disability Scale (SDS) score of 11.47 ± 6.68, with the highest SDS score reported in the "Social Life/Leisure Activities" domain. Compared with the overall CogDAD study population, the Malaysian patient population had comparable patient demographics in terms of marital and working status; outcome scores for PHQ-9 (9-item Patient Health Questionnaire for self-reported depression severity), PDQ-D and SDS; and worst perceived cognitive dysfunction reported in the "Attention/Concentration" domain. Factors found to be significantly associated with functional disability were PDQ-D score, sick leave taken, and antidepressant treatment (P

The de novo formation of secretory lumens plays an important role during organogenesis. It involves the establishment of a cellular apical pole(1) and the elongation of luminal cavities(2). The molecular parameters controlling cell polarization have been heavily scrutinized(3-5). In particular, signalling from the extracellular matrix (ECM) proved essential to the proper localization of the apical pole by directed protein transport(6). However, little is known about the regulation of the shape and the directional development of lumen into tubes. We demonstrate that the spatial scaffolding of cells by ECM can control tube shapes and can direct their elongation. We developed a minimal organ approach comprising of hepatocyte doublets cultured in artificial microniches to precisely control the spatial organization of cellular adhesions in three dimensions. This approach revealed a mechanism by which the spatial repartition of integrin-based adhesion can elicit an anisotropic intercellular mechanical stress guiding the osmotically driven elongation of lumens in the direction of minimal tension. This mechanical guidance accounts for the different morphologies of lumen in various microenvironmental conditions.

The liver is unique in its capacity to regenerate after injury, during which hepatocytes actively divide and establish cell-cell contacts through cell adhesion complexes. Here, we demonstrate that the loss of α-catenin, a well-established adhesion component, dramatically disrupts liver regeneration. Using a partial hepatectomy model, we show that regenerated livers from α-catenin knockdown mice are grossly larger than control regenerated livers, with an increase in cell size and proliferation. This increased proliferation correlated with increased YAP activation, implicating α-catenin in the Hippo/YAP pathway. Additionally, α-catenin knockdown mice exhibited a phenotype reminiscent of clinical cholestasis, with drastically altered bile canaliculi, elevated levels of bile components and signs of jaundice and inflammation. The disrupted regenerative capacity is a result of actin cytoskeletal disorganisation, leading to a loss of apical microvilli, dilated lumens in the bile canaliculi, and leaky tight junctions. This study illuminates a novel, essential role for α-catenin in liver regeneration., Singapore. Agency for Science, Technology and Research