OAR@UM Community:

Editorial : The role of alcohol in modifying behavior

Sun, 01 Jan 2023 00:00:00 GMT

Title: Editorial : The role of alcohol in modifying behavior Authors: Peters, Jamie; Trabace, Luigia; Di Giovanni, Giuseppe Abstract: This special topic presents experimental work on the effects of alcohol (ethanol) on the brain, and how these effects impact behavior across multiple domains. The World Health Organization (WHO) estimates that 2.3 billion people regularly consume alcohol, making alcohol one of the most widely used drugs in human society (WHO, 2022). Alcohol consumption has both acute and long-term effects on behavior. Whereas most of the acute effects are rewarding, if higher doses are consumed, negative effects including motor and cognitive impairment can occur and can be lasting.

An in vitro study simulating prophylactic anticoagulation in haemophilia A and B

Thu, 01 Jan 2026 00:00:00 GMT

Title: An in vitro study simulating prophylactic anticoagulation in haemophilia A and B Authors: Riva, Nicoletta; Vella, Kevin; Hickey, Kieron; Debattista, Nigel; Grima, Carmel; Borg-Aquilina, Denise; Camilleri, Liberato; Guo, Jiong Jiong; Gatt, Alexander Abstract: Introduction: Patients with haemophilia A (HA) and haemophilia B (HB) are at increased bleeding risk. A recent guidance document suggests considering pharmacological thromboprophylaxis on a case-by-case basis in these patients undergoing surgery at high-risk of venous thromboembolism. This study aimed to assess the effect of prophylactic doses of three anticoagulants (enoxaparin, rivaroxaban and unfractionated heparin [UFH]) on in vitro models of HA and HB. Methods: FVIII- and FIX-deficient plasma were spiked with FVIII and FIX concentrates to mimic severe, moderate and mild HA (FVIII concentrations < 1%, 1.2% and 17.0%, respectively) and HB (FIX concentrations < 1%, 3.9% and 22.9%, respectively). Each pool was spiked with enoxaparin (concentration range 0.3–0.4 IU/mL), rivaroxaban (50–100 ng/mL) and UFH (0.2–0.3 IU/mL). The following assays were performed: prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin generation (using the semi-automated fluorogenic calibrated automated thrombin generation assay [CAT]). Results: The PT was not significantly affected by the anticoagulants. A significant prolongation of the APTT was observed; UFH showed the greatest increase, followed by rivaroxaban and enoxaparin. All anticoagulants impacted on the CAT curves. UFH showed the greatest reduction of the endogenous thrombin potential; rivaroxaban showed the greatest increase of lag time and time to peak. Peak thrombin and velocity index were similarly reduced by rivaroxaban and UFH, whereas enoxaparin was associated with smaller changes in all parameters. Conclusion: A significant effect of three prophylactic anticoagulants was observed in factor-deficient plasmas. This study provides further insight into this topic and supports the concept of an individualised approach to haemophilia patients.

Novel semi-synthetic cannabinoids detected in the local recreational market : a look into CC9 products prior to change in legal status

Thu, 01 Jan 2026 00:00:00 GMT

Title: Novel semi-synthetic cannabinoids detected in the local recreational market : a look into CC9 products prior to change in legal status Abstract: The rapid diversification of the novel psychoactive substance (NPS) market presents severe challenges to global public health agencies and forensic laboratories, which are frequently forced to operate without certified reference materials or established toxicological data. In Malta, the semi-synthetic cannabinoid (SSC) hexahydrocannabinol C9 derivative, or HHC-C9 (CC9), has recently emerged on the recreational drug market as a legal alternative to Δ9-tetrahydrocannabinol (Δ9-THC). CC9 possesses a high risk for toxicological overstimulation of the central nervous system via full agonism at the cannabinoid receptor type 1 (CB1). This study establishes a foundational qualitative screening and semi-quantitative profiling protocol for CC9 utilising gas chromatography-mass spectrometry (GC-MS). In the absence of commercial reference standards, a standard model was developed and validated within the Department of Chemistry Forensic Analysis Laboratory and Toxicology. Methodological separation was successfully achieved under optimised chromatographic conditions, identifying a highly reproducible retention time of 15.421 minutes. Diagnostic electron ionization (EI) mass spectral profiling resolved a distinct fragmentation fingerprint for CC9, characterized by prominent, structurally significant diagnostic ions at m/z 260, 329, and 372. The validated method was applied to conduct a local market surveillance study, analysing eight commercial samples. CC9 was definitively identified across all samples analysed. The total chemical and chromatographic homogeneity observed among the samples strongly indicates a centralised, highly standardised, and industrially scale supply chain supplying the local market, rather than small-batch localised synthesis. This research provides the essential baseline data required to for a simple foundation for advanced forensic surveillance methodologies within the national landscape. Description: B.Sc. (Hons)(Melit.)

Motor dysfunction phenotypes in a drosophila model validate DAO as an ALS gene

Thu, 01 Jan 2026 00:00:00 GMT

Title: Motor dysfunction phenotypes in a drosophila model validate DAO as an ALS gene Authors: Tabone, Sylvana; Cacciottolo, Rebecca; Cauchi, Ruben J. Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by progressive motor neuron (MN) loss. Although rare pathogenic variants in the D-amino acid oxidase (DAO) gene have been proposed to cause familial ALS, inconsistent findings across mammalian models have hindered functional validation. Here, we establish and characterise a Drosophila model of DAO loss-of-function by targeting its highly conserved orthologue, Daao1. Constitutive Daao1 knockdown caused early developmental lethality, while surviving adult escapers exhibited profound flight and climbing impairments. Contrary to expectations, Daao1 deficiency did not elevate D-serine levels in larval or adult brains, and simultaneous knockdown of serine racemase (Srr), the enzyme responsible for D-serine synthesis, failed to rescue locomotor phenotypes. Tissue-specific silencing revealed that Daao1 is essential within both MNs and muscles, but not glia, for maintaining motor performance. RNA-seq of Daao1-deficient flies uncovered widespread transcriptional dysregulation affecting metabolism, peptide transport, immune activation and developmental pathways, accompanied by alternative splicing changes in genes required for neuronal morphology and synaptic organisation. Consistent with these molecular alterations, neuromuscular junctions (NMJs) displayed reduced axonal branching and bouton numbers, indicating disrupted neuromuscular connectivity. Remarkably, ubiquitous expression of human DAO rescued lethality and motor defects, demonstrating functional conservation and supporting a role for DAO in maintaining neuromuscular health. Together, our findings reveal a previously unrecognised, D-serine-independent role for DAO in neuromuscular integrity and provide functional evidence connecting DAO dysfunction to ALS-relevant phenotypes. The DAO-ALS Drosophila model provides a powerful platform for mechanistic studies and for evaluating human DAO variants of uncertain significance in ALS.