Gedeon Richter (Hungary)

A kutatás célja annak vizsgálata volt, hogy az egyetemek és munkahelyek között miért alakul ki időbeli késés a mesterséges intelligencia (MI) és digitális technológiák átvételében, valamint hogyan lehet ezt mérsékelni. Eredményeink szerint a vállalatok gyorsabban alkalmazzák az új eszközöket, míg az oktatási intézményekben az akkreditációs és szervezeti korlátok lassítják az adaptációt. A hallgatók gyakran önállóan vagy munkahelyi környezetben sajátítják el a szükséges digitális készségeket, míg az oktatók informális csatornákból értesülnek az új trendekről. A tudástranszfer gyorsítása érdekében kulcsfontosságú a felsőoktatás és a munkaadók közötti együttműködés, közös kurzusok, mentorprogramok és szakmai partnerségek kialakítása. A tanulmány rámutat, hogy a digitális eszközök integrációja hozzájárulhat a pályakezdők felkészítéséhez a munkaerőpiac aktuális igényeire.

Objectives: The goal of this study was to investigate lipid goal achievement rates in very high-risk patients over six months using high-intensity rosuvastatin or rosuvastatin/ezetimibe combination lipid-lowering therapy. Methods: This prospective, observational study was conducted on the patients of 150 general and 60 specialist practices. Our analysis included 3017 patients (47% women) who completed six months of therapy. Of these, 55.5% had pre-existing cardiovascular disease, 35.6% had cerebrovascular disease, and 20.4% had peripheral vascular disease. Results: At six months, in patients receiving rosuvastatin monotherapy (20.5%), the 1.8 LDL-C achievement rate was 37%; in those taking the fix rosuvastatin/ezetimibe combination (63.7%), it was 52%, and the 1.4 level attainment proved to be 11% and 22%, respectively. The rates of LDL-C reduction of at least 50% were 32% and 42%, respectively. Overall, non-HDL-C goal achievement rates were higher than when LDL-C was calculated using the Martin-Hopkins or Sampson methods but similar to those calculated with the Friedewald formula. When patients were stratified by triglyceride quartiles, non-HDL-C goal achievement rates were significantly higher (p < 0.001) in cases with triglyceride levels below 1.2 mmol/L. Conversely, Friedewald-calculated LDL-C (F-LDL-C) goal achievement rates were significantly higher (p < 0.001) in patients with triglyceride levels above 1.7 mmol/L. Conclusions: Our findings suggest that the consistent use of fixed high-intensity statin and ezetimibe combinations can improve lipid goal achievement. However, comparing the achievement of LDL-C goals (calculated by three methods) and non-HDL-C goals also confirmed that the common practice of automatically adding 0.8 mmol/L to the calculated LDL-C value to determine non-HDL-C leads to inaccuracies, particularly in the lower triglyceride ranges.

Aminoglycoside antibiotics remain indispensable despite their ototoxicity. Like other sensorineural forms, aminoglycoside-induced hearing loss (AGIHL) has no effective pharmacotherapy. Oxidative stress, apoptosis, excitotoxicity and inflammation are key pathological factors of the disease. We hypothesised that selegiline, an irreversible monoamine oxidase-B (MAO-B) inhibitor used in Parkinson’s disease, could be repurposed as an otoprotective agent against AGIHL and its effect on dopamine (DA) release from lateral olivocochlear (LOC) fibres, the efferent division of a protective feedback loop plays a major role in the protection against excitotoxicity. Selegiline mitigated AGIHL in BALB/c mice in a dose-dependent manner at different auditory brainstem response frequencies, including 16 kHz, the hearing sensitivity optimum of the animals. It also enhanced the action potential-evoked DA release from LOC efferents in mouse cochlear preparation dose-dependently. Inhibition of DA reuptake contributed to its basic effect of saving DA from metabolism. Among four selegiline analogues tested, the one that increased LOC DA release also provided otoprotection. In contrast, neither safinamide (a reversible MAO-B inhibitor) nor LJP-1207 (a selective semicarbazide-sensitive amine oxidase/vascular-adhesion protein 1 (SSAO/VAP1) inhibitor) prevented AGIHL, despite their antioxidant and anti-inflammatory properties. The reversibility or lack of MAO-B inhibition in safinamide and LJP-1207, respectively, as well as the absence of the propargylamine moiety with known intrinsic neuroprotective activity in both molecules, may explain their ineffectiveness. Selegiline, or certain propargylamine analogues of it, offer a promising therapy against AGIHL by addressing its multifactorial pathology through antioxidant, antiapoptotic, neuroprotective, and anti-inflammatory actions, while enhancing endogenous DAergic protective mechanisms.

1,4,6,7-Tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridines are potent antagonists of the P2X7 receptor, a key regulator of neuroinflammation associated with depression. Two clinical candidates, JNJ-54175446 and JNJ-55308942 were developed based on this scaffold, together with a stereoselective synthesis involving a one-pot [3 + 2] cycloaddition/Cope-elimination cascade. Besides challenging regioselectivity, this route raises safety concerns, as both steps involve hazardous reagents. Herein, we report a two-step continuous-flow strategy for the synthesis of this valuable scaffold, which enables access to intermediates of JNJ-54175446 and JNJ-55308942 via temperature-controlled regioselectivity. Applying the optimized conditions, yields of 48% (58% regioselectivity) and 45% (91% regioselectivity) were achieved, respectively. The method ensures safe utilization of azide in the cycloaddition, and uses a safer oxidant for the elimination, offering a scalable and affordable alternative synthetic route.

BackgroundMeasurement-based care (MBC) is widely recommended in psychiatry but remains underutilized in routine clinical settings. The Transdiagnostic Global Impression – Psychopathology (TGI-P) scale was developed to provide a brief yet comprehensive assessment of 10 core transdiagnostic symptom domains. To support more inclusive care and promote patient and caregiver engagement in treatment planning, two new versions of the TGI-P, that is, a patient-rated and a separate informant-rated, were developed, complementing the previously published clinician-rated version.MethodsThe patient and informant versions mirror the original clinician-rated TGI-P, assessing the identical 10 domains using a seven-point Likert severity scale, with results displayed via a personalized symptom map. A user satisfaction/feasibility study was conducted with 50 participants (25 patients and 25 caregivers) from the UK and US. After completing the scale, participants provided feedback on its clarity, usability, emotional impact, and comparative utility.ResultsMost participants completed the scale in less than 5 min. Instructions were considered clear, and the format was rated easy to follow. Response options were deemed appropriate by 86% of participants, and the visual output was widely appreciated. While one-third reported mild emotional triggering, overall burden was described as manageable. Approximately, three-quarters of participants rated the TGI-P as equal to or better than other tools they had used.ConclusionsTGI-P patient and informant versions were developed and, informed by the feasibility study, refined to offer brief, user-friendly tools that support multi-informant assessment as input to MBC. Both versions of the TGI-P, with their graphical output, may support shared understanding and collaborative decision making among clinicians, patients, and caregivers. A validation study of the TGI-P is underway.

IntroductionNegative symptoms are a key aspect of schizophrenia, significantly impacting a patient’s functioning and quality of life. These symptoms are deemed predominant when they dominate the clinical picture and positive symptoms are only minimally present. As articulated in the most recent guidance by the European Psychiatric Association, including self-report measures is encouraged in negative symptom studies as they can further complement the observer-rated scales when assessing negative symptoms of schizophrenia.ObjectivesThe objective of the poster is to compare the views of patients vs. doctors regarding predominant negative symptoms during a 1-year observational study.MethodsThis was a 1-year-long, prospective, multicentric cohort study with three visits after baseline at 3, 6 and 12 months. Adult outpatients with a schizophrenia diagnosis according to the International Classification of Diseases 10th edition who exhibited predominant negative symptoms according to clinical judgement were included. Patients received pharmacological and some non-pharmacological treatment as usual.The primary outcome measure was the modified Short Assessment of Negative Domains (m-SAND), an anamnesis-based scale that is composed of 7 items: two positive items (delusions and hallucinations) which make the m-SAND Positive sub-scale (m-SAND-P) and five negative items (anhedonia, alogia, avolition, asociality and affective flattening) which make the m-SAND Negative sub-scale (m-SAND-N) Each item is rated from 0 to 5 (not observed; mild; moderate; moderately severe; severe; and extreme). Other measurements included the Self-evaluation of Negative Symptoms (SNS), a validated scale that provides meaningful information regarding the patients’ own perception of their negative symptoms.Least squares (LS) means were calculated for the change from baseline to final visit using a mixed model for repeated measures (MMRM).Results188 patients were included in the study. The mean age was 39.8 years and 65% of patients were men. The mean duration of illness was 12 years. At baseline, patients rated alogia and apathy (mean SNS score: 5.7) to be the most severe and then asociality (5.5). In contrast, doctors found affective blunting (mean m-SAND total score: 4.3), apathy (4.2) and anhedonia (4.0) to be the most severe.After the end of the observational period all negative symptom sub-domains improved significantly according to both the patients’ and doctors’ views. The latter group reported -1.9 LS mean change from baseline in apathy, -1.8 in anhedonia, and -1.7 in asociality (all p-value <0.0001). Patients felt most change in alogia and asociality (-2.7), and apathy and anhedonia (-2.4).ConclusionsIn summary, both patients and doctors reported significant improvement in predominant negative symptoms. Nonetheless, there were some differences how they perceived severity and change in the specific domains.Disclosure of InterestJ. Dragasek: None Declared, Z. Dombi Employee of: Gedeon Richter Plc., K. Acsai: None Declared, V. Dzurilla Employee of: Gedeon Richter Plc., Á. Barabássy Employee of: Gedeon Richter Plc.