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Leong, T.

Publications and source records attributed to Leong, T..

4 recordsLinked to original sources

Impact of opioid-based versus opioid-free anaesthesia on postoperative recovery, circulating inflammatory cytokines and brain-derived neurotrophic factor.

Background Opioid-free anaesthesia (OFA) has emerged as an alternative to opioid-based anaesthesia (OBA), but its benefit over OBA for postoperative quality of recovery (QoR) remains unclear. To address this question while limiting variability inherent in clinical studies, such as analgesic regimens and patient psychosocial factors, we investigated the effects of OFA versus OBA on postoperative recovery in a controlled preclinical mouse model. Methods Adult male and female C57BL/6J mice underwent laparotomy or sham procedures under isoflurane anaesthesia, and were randomly assigned to saline (control), fentanyl (OBA), or dexmedetomidine (OFA) as intraoperative analgesic adjuncts. All mice received multimodal postoperative analgesia, including carprofen. We adapted a standardised multidimensional recovery model using six behavioural endpoints reflecting human QoR domains: body weight, food intake, locomotor activity, mechanical sensitivity, sucrose preference, and social interaction. These endpoints were assessed on postoperative days 1, 2, 3, and 7. Plasma inflammatory cytokine and brain-derived neurotrophic factor (BDNF) concentrations were also measured in parallel as potential biological correlates of recovery. Results Over the study period, we observed no treatment effect across behavioural endpoints in laparotomised mice, including body weight (P=0.157), food intake (P=0.884), locomotor activity (P=0.864), mechanical sensitivity (P=0.628), sucrose preference (P=0.615), and social interaction (P=0.442). Composite QoR scores did not differ between OFA and OBA groups (P=0.569), with no differences in postoperative circulating inflammatory cytokine or BDNF concentrations. Conclusions Dexmedetomidine-based OFA and fentanyl-based OBA produced similar postoperative behavioural recovery, circulating inflammatory cytokine and BDNF trajectories in laparotomised mice receiving multimodal postoperative analgesia.

animal behavior and cognition↗

A Wireless Wearable Platform for Intravenous Drug Self-Administration in Freely Behaving Rats

Studying how drugs act on neuronal circuits requires delivering them with temporal precision while behavior proceeds undisturbed, a combination that tethered infusion systems cannot provide. We developed WEARIT (Wireless Equipment for Autonomous Rat Infusion Tasks), a wearable, tetherless infusion platform that gives freely moving rats intravenous access under either remote or closed-loop operant control. The device houses a reservoir, miniaturized pump, rechargeable battery and Bluetooth circuitry in a 3D-printed enclosure worn on the back. By measuring spontaneous locomotion, amphetamine-induced hyperlocomotion and food-reinforced operant responding, we show that WEARIT leaves these behaviors unchanged. Remotely triggered fentanyl infusions yielded reliable delivery with physiological responses confirmed by pulse oximetry, and self-administration acquisition and dose-response functions were comparable to conventional tethered systems. WEARIT removes a longstanding constraint on intravenous pharmacology, opening self-administration paradigms to naturalistic and enriched environments and to concurrent imaging or optogenetic manipulation of the circuits engaged by drug reinforcement.

neuroscience↗

Hemodynamic traveling waves transport musical codes faster than language codes via shared bilateral streams

What takes precedence in our brain: music or language? Here we used rapid phase-encoded fMRI to explore spatiotemporal brain dynamics during naturalistic music and language tasks, seeking to track down the entire perception-to-production process and compare the speed of information transfer between the two domains. We found largely shared streams of traveling waves bilaterally, along which musical codes were transported faster than language codes for identical visual input.

neuroscience↗

Early immune pressure imposed by tissue resident memory T cells sculpts tumour evolution in non-small cell lung cancer

Tissue-resident memory T cells (TRM) provide immune defence against local infection and can inhibit cancer progression. However, it is unclear to what extent chronic inflammation impacts TRM activation and how the immune pressure exerted by TRM affects developing tumours in humans. We performed deep profiling of lung cancers arising in never-smokers (NS) and ever-smokers (ES), finding evidence of enhanced TRM immunosurveillance in ES lung. Only tumours arising in ES patients underwent clonal immune escape, even when evaluating cancers with similar tumour mutational burden to NS patients, suggesting that the timing of immune pressure exerted by TRM is a critical factor in the evolution of tumour immune evasion. Tumours grown in T cell quiescent NS lungs displayed little evidence of immune evasion and had fewer neoantigens with low diversity, paradoxically making them amenable to treatment with agonist of the costimulatory molecule, ICOS. These data demonstrate local environmental insults enhance TRM immunosurveillance of human tissue, shape the evolution of tumour immunogenicity and that this interplay informs effective immunotherapeutic modalities.

cancer biology↗