Nanoformulations in Pharmaceutical and Biomedical Applications: Green Perspectives.

This study provides a brief discussion of the major nanopharmaceuticals formulations as well as the impact of nanotechnology on the future of pharmaceuticals. Effective and eco-friendly strategies of biofabrication are also highlighted. Modern approaches to designing pharmaceutical nanoformulations (e.g., 3D printing, Phyto-Nanotechnology, Biomimetics/Bioinspiration, etc.) are outlined. This paper discusses the need to use natural resources for the "green" design of new nanoformulations with therapeutic efficiency. Nanopharmaceuticals research is still in its early stages, and the preparation of nanomaterials must be carefully considered. Therefore, safety and long-term effects of pharmaceutical nanoformulations must not be overlooked. The testing of nanopharmaceuticals represents an essential point in their further applications. Vegetal scaffolds obtained by decellularizing plant leaves represent a valuable, bioinspired model for nanopharmaceutical testing that avoids using animals. Nanoformulations are critical in various fields, especially in pharmacy, medicine, agriculture, and material science, due to their unique properties and advantages over conventional formulations that allows improved solubility, bioavailability, targeted drug delivery, controlled release, and reduced toxicity. Nanopharmaceuticals have transitioned from experimental stages to being a vital component of clinical practice, significantly improving outcomes in medical fields for cancer treatment, infectious diseases, neurological disorders, personalized medicine, and advanced diagnostics. Here are the key points highlighting their importance. The significant challenges, opportunities, and future directions are mentioned in the final section.

Effect of Acetylsalicylic Acid on Biological Properties of Novel Cement Based on Calcium Phosphate Doped with Ions of Strontium, Copper, and Zinc.

This study aimed to compare the biological properties of newly synthesized cements based on calcium phosphate with a commercially used cement, mineral trioxide aggregate (MTA). Strontium (Sr)-, Copper (Cu)-, and Zinc (Zn)-doped hydroxyapatite (miHAp) powder was obtained through hydrothermal synthesis and characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectrometry (EDX). Calcium phosphate cement (CPC) was produced by mixing miHAp powder with a 20 wt.% citric acid solution, followed by the assessment of its compressive strength, setting time, and in vitro bioactivity. Acetylsalicylic acid (ASA) was added to the CPC, resulting in CPCA. Biological tests were conducted on CPC, CPCA, and MTA. The biocompatibility of the cement extracts was evaluated in vitro using human dental pulp stem cells (hDPSCs) and in vivo using a zebrafish model. Antibiofilm and antimicrobial effect (quantified by CFUs/mL) were assessed against Streptococcus mutans and Lactobacillus rhamnosus. None of the tested materials showed toxicity, while CPCA even increased hDPSCs proliferation. CPCA showed a better safety profile than MTA and CPC, and no toxic or immunomodulatory effects on the zebrafish model. CPCA exhibited similar antibiofilm effects against S. mutans and L. rhamnosus to MTA.

Exploring real-world prescribing patterns for maintenance treatment in bipolar disorders: a focus on antidepressants and benzodiazepines.

OBJECTIVE: Bipolar disorders (BD) are characterized by highly recurrent nature, necessitating adequate maintenance treatment for long-term disorder control. This study aimed to investigate real-world prescribing patterns among outpatients with BD, focusing on the utilisation of antidepressants (AD) and benzodiazepines (BDZ). METHODS: We analysed prescription patterns of the five main groups of psychotropic medications (antipsychotics, mood stabilizers, AD, BDZ, and anticholinergic medications) and their relationships with basic socio-demographic and clinical data in a sample of 107 clinically stable BD outpatients (75.7% female, age 44.8 ± 11.7). RESULTS: Maintenance therapy predominantly involved polypharmacy (92.5%), with mood stabilizers (87.9%) and antipsychotics (80.4%, predominantly second-generation) being the most commonly prescribed. Our findings highlight a high percentage of patients prescribed AD (50.5%) and BDZ (54.2%). BDZ patients, compared to the non-BDZ group in maintenance treatment, were significantly older with longer psychiatric history and a decreased likelihood of comorbid personality disorder diagnoses. CONCLUSIONS: This study offers insights into prescribing practices within a university psychiatric clinic in the Western Balkans. The prevalent use of polypharmacy in real-world clinical settings, along with high percentage of patients prescribed AD and BDZ, suggests a gap between guideline recommendations and clinical practice, indicating a lack of consensus or standardized approaches in clinical practice.

Study uncovers prescribing practices in a Western Balkans university psychiatric clinic, revealing high polypharmacy prevalence (92.5%) among clinically stable bipolar disorder (BD) outpatients.Most BD outpatients received mood stabilizers, particularly lamotrigine, and second-generation antipsychotics, notably olanzapine, with a minority on monotherapy.Antidepressant and benzodiazepine usage was notably high despite guidelines favouring monotherapy, reflecting challenges in managing residual morbidity.AD usage in BD type I is discouraged due to risks, while their use in BD type II is considered in certain scenarios, emphasising tailored treatment.High mean daily BDZ dose (approximately 3.5mg lorazepam equivalents) in non-acute outpatient BD maintenance therapy raises concerns about potential long-term implications for patient health and underscores the need for vigilant monitoring of prescribing practices.

Microbial adhesion and viability on novel CAD/CAM framework materials for implant-supported hybrid prostheses.

The aim of the study was to investigate the adhesion and viability of Streptococcus oralis and Candida albicans under in vitro conditions on CAD/CAM framework materials for implant-supported hybrid prostheses. Twenty-nine specimens were prepared from each of three different materials: ZR (zirconia), PEEK (polyether ether ketone) and CoCr4 (CoCr4 alloy). The experimental part included surface roughness (SR) and contact angle of water (CAW) measurements, followed by colony forming unit (CFU), cell viability assay and scanning electron microscopy (SEM) analyses of Strep. oralis and C. albicans biofilms on the materials' surfaces. Kruskal-Wallis and one-way analysis of variance (ANOVA) tests were used for differences between materials, and the correlation between measurements was estimated using Spearman's correlation coefficient. PEEK specimens revealed higher SR, CAW and CFU mean values, than ZR and CoCr4 specimens. Strong positive correlation was found between SR and CFU and between CAW and CFU for both microbial species. Cell viability assay revealed similar values for both species across materials. Higher numbers of Strep. oralis and C. albicans on PEEK specimens confirm the impact of the higher surface roughness and contact angle values on the microbial adhesion and describes PEEK as less desirable than ZR and CoCr4 from microbiological aspect.

Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway.

BACKGROUND: There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. METHODS: We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. RESULTS: The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465). CONCLUSIONS: The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

A replication study of JTC bias, genetic liability for psychosis and delusional ideation.

BACKGROUND: This study attempted to replicate whether a bias in probabilistic reasoning, or 'jumping to conclusions'(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation. METHODS: Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses. RESULTS: JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46-5.17 for siblings and aRR: 5.07 CI 95% 4.13-6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67-8.51, and in patients: 2.15 CI 95% 0.94-4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences. CONCLUSIONS: These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.

Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings.

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

A review of applications of operational research in healthcare coordination in disaster management.

Many disasters that have happened in the last decades, including the latest COVID-19 pandemic, have caused a shortage of healthcare resources and change in healthcare operations. Given these impacts, the Operational Research (OR) community has applied various approaches to improve the emergency medical responses. Coordination of healthcare facilities is one of the emergency medical response strategies to ensure the continued provision of medical services during disasters. Although the existing literature reviews of OR approaches have included the perspective of healthcare management, they focused mostly on the application of OR in disaster operations and logistics management. The importance of coordination in healthcare systems during disasters is well recognised in the literature, but to the best of our knowledge there has been no review of the published research in this area. This study provides a focused literature review of the OR contributions in the coordination in healthcare systems during disasters. Definitions of the terms in use in this field are provided. An overall descriptive statistics of the reviewed articles is given, followed by the review of the presented research problems, disaster types, and developed methodologies. The main characteristics of models for the coordination in the healthcare system are described. Measures of coordination effectiveness that denote healthcare resilience are discussed. Based on our findings, we suggest future research directions in the context of existing models extension, and application and development of other methodologies with the aim to provide a solid basis for OR research in the healthcare disaster management.

Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene-environment interaction. The EUGEI study.

BACKGROUND: First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes. METHODS: We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS. RESULTS: In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group. CONCLUSIONS: The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene-environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

Maintenance phase treatment of psychotic disorders in outpatients from Serbia - focus on long-term benzodiazepine use.

Introduction: Prescribing trends in maintenance therapy of patients with primary psychotic disorders (PSD) may vary worldwide. Present study aimed to investigate prescription patterns in a sample of outpatients with PSD from Serbia.Methods: In a sample of 73 PSD outpatients we analysed the rate of antipsychotic polypharmacy and psychotropic polypharmacy, concomitant continual benzodiazepine use, and associations between therapy, psychotic symptoms and quality of life.Results: Maintenance therapy (median daily dose 321 mg of chlorpromazine equivalents) predominantly consisted of monotherapy with second generation antipsychotics (45.2%), followed by antipsychotic polypharmacy based on first and second generation combination (25.0%). The median number of psychotropic drugs was 3. Benzodiazepines were continually prescribed to more than 60% of patients (mean daily dose 2.9 ± 2.0 mg lorazepam equivalents). Patients with benzodiazepine use had significantly more psychotropic medications and more antipsychotic polypharmacy, poorer quality of life and more severe psychopathology in comparison to another group.Conclusion: The present study demonstrated new information regarding the prescription patterns of psychotropic drugs in outpatients with PSD in Serbia, amplified with clinically relevant information. This study also revealed distinct prescription patterns concerning antipsychotic/benzodiazepine polypharmacy. Overall, such findings are likely to contribute to improving clinical practice and care for patients with PSD in general.KeypointsPresent exploratory research aimed to elucidate trends of antipsychotics polypharmacy and concomitant use of psychotropic medications including benzodiazepines in the maintenance treatment of outpatients with schizophrenia and other psychotic disorders, amplified with clinically relevant information (symptoms and quality of life).'Antipsychotic (AP) polypharmacy' was defined as concurrent use of more than one AP for at least 1 month; 'Psychotropic polypharmacy' was defined as the combination of AP and a different class of psychotropic drugs medication for at least one month.The median number of prescribed psychotropic drugs was 3 (mean 3.1 ± 1.1) and the average AP daily dose was moderate (median 321 mg of chlorpromazine equivalents). However, the rates of AP polypharmacy (45.2%) and benzodiazepine prescription on a continual basis (>60%) found in our sample could be considered relatively high.Outpatients with higher AP daily dose and higher BPRS symptom score were receiving more benzodiazepines.For improvement of the local, as well as general clinical practice and care for patients with psychotic disorders, and for education in psychiatry, such analyses need to be done on a regular basis and on larger samples.

Sex differences in facial emotion recognition in health and psychotic disorders.

BACKGROUND: Previous studies examining sex-differences in facial emotion recognition (FER) in psychosis yielded inconsistent results. Although females are considered to be superior in FER in health, it remains unclear whether the specific sex-difference is present in psychosis. We aimed to examine whether women and men differ in FER ability in health and in psychosis, and to explore potential sex differences in the illness' effects on FER. METHODS: Remitted psychotic patients and controls were assessed using the CANTAB Emotion Recognition Task (ERT) examining accuracies/response latencies in identifying basic emotional expressions. General linear model was performed to assess the effects of group, sex and their interactions on ERT performance. RESULTS: Healthy females showed FER advantage in comparison to healthy males, while the aforementioned sex-difference was not observed in remitted psychotic patients. Our results also demonstrated the existence of overall FER deficit in psychosis in comparison to healthy controls, as well as the differential illness' effects on the recognition accuracy of facial expression of anger in males and females-suggesting that females with psychotic disorders undergo more profound deterioration of FER ability than their male counterparts. CONCLUSION: The assessment of sex-differences in FER and other important features of psychosis is important for better understanding of its neurobiological basis and for the development of targeted treatments for improved functioning.

Ageing with HIV - a periodontal perspective.

The importance of oral microflora composition in HIV-infected patients is well recognized. However, no studies so far have dealt with age-related changes in periodontal pathogens occurrence in HIV+ individuals. The aim of the present study was to assess and compare temporal changes of bacteria frequency in younger (≤35 years) and older (≥50 years) HIV-infected and non-infected individuals. Bacterial DNA was isolated from buccal swabs of 30 younger and 30 older subjects in both HIV+ and HIV- groups. By means of PCR the following microorganisms were detected: Aggregatibacter actinomycetemcomitans, Eikenella corrodens, Peptostreptococcus micros, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Treponema denticola. Oral and periodontal examinations were performed in all subjects. The prevalence of microorganisms was significantly higher in HIV+ patients compared to controls, and their distribution showed a notable shift. The decreasing incidence in HIV- subjects was: Pi>Pm>Pg>Aa>Ec>Tf>Td whilst in HIV+ it was: Pi>Pm>Ec>Pg>Tf>Aa>Td. Oral manifestations of HIV infection were more frequent in older compared to younger patients. All measured values of clinical periodontal parameters were significantly higher in older compared to younger HIV+ patients. Ageing in HIV+ subjects is accompanied with a substantial increase and rearrangements of periodontal microflora, potentially aggravating oral and systemic health.

Sulfanilamide in solution and liposome vesicles; in vitro release and UV-stability studies.

The main goal of this study was to develop a liposome formulation with sulfanilamide and to investigate the liposomes impact on its release and stability to the UV-A/UV-B and UV-C irradiation. Liposome dispersions with incorporated sulfanilamide were prepared by thin-film hydration method and liposomes role to the sulfanilamide release was investigated by using a dialysis method. Comparatively, sulfanilamide in phosphate buffer solution was subject to release study as well to the UV irradiation providing for the possibilities of kinetics analysis. In vitro drug release study demonstrated that 20% of sulfanilamide was released from liposomes within 1 h that is approximately twice as slower as in the case of dissolved sulfanilamide in phosphate buffer solution. The kinetic release process can be described by Korsmeyer-Peppas model and according to the value of diffusion release exponent it can be concluded that drug release mechanism is based on the phenomenon of diffusion. The sulfanilamide degradation in phosphate buffer solution and liposomes is related to the formation of UV-induced degradation products that are identified by UHPLC/MS analysis as: sulfanilic acid, aniline and benzidine. The UV-induced sulfanilamide degradation in the phosphate buffer solution and liposome vesicles fits the first- order kinetic model. The degradation rate constants are dependent on the involved UV photons energy input as well as sulfanilamide microenvironment. Liposome microenvironment provides better irradiation sulfanilamide stability. The obtained results suggest that liposomes might be promising carriers for delayed sulfanilamide delivery and may serve as a basis for further research.

[Endovenous ablation of saphenous vein varicosis]. / Endovenöse Ablation der Stammvenenvarikose.

In the past 15 years, the minimally invasive endovenous treatments of varicose veins have been widely accepted. The efficacy of the different endovenous methods and the minimal post operative side effects are meanwhile well documented in a large number of evidence based publications. The recent NICE Guidelines (2013) considering the varicose vein treatment recommend in case of an insufficiency of saphenous veins first the endovenous thermal ablation with radiofrequency or laser, then the ultrasound guided sclerotherapy and as the third line the classic surgical treatment with stripping and high ligation.

Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase.

BACKGROUND: We aimed to characterize newer antiseizure medications (ASMs)-induced hepatotoxicity in children and identify signals of disproportionate reporting of hepatotoxicity-related adverse drug events (ADEs). RESEARCH DESIGN AND METHODS: Case reports reported to VigiBase were accessed using Empirica™ Signal software. To summarize characteristics of the retrieved cases, descriptive statistics were used. A disproportionality analysis was conducted using the Multi-item Gamma Poisson Shrinker algorithm, which calculates Empirical Bayesian Geometric Mean value and its lower and upper 95% confidence limits (EB05 and EB95, respectively). EB05 > 2, N > 0 was considered a signal. RESULTS: Based on 870 analyzed cases, a higher proportion of cases was reported in girls than in boys and in patients aged 2-11 years than in other age groups. Most cases were serious. In 25 cases, hepatotoxicity resulted in death. A high proportion of patients (n = 275, 31.61%) experienced hypersensitivity reactions, mostly due to lamotrigine. The disproportionality analysis yielded 17 signals concerning felbamate, lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and topiramate. Four signals were for severe liver injury and concerned felbamate, lamotrigine, levetiracetam, and topiramate. Gender-biased reporting frequency was detected for four ASM-ADE combinations. CONCLUSION: Our results should serve to raise clinicians' awareness about the potential association between several newer ASMs and drug-induced liver injury in children.

Exploring the antimicrobial and antioxidant potential of bacterial cellulose-cerium oxide nanoparticles hydrogel: Design, characterization and biomedical properties.

Bacterial cellulose (BC) is a promising natural polymer prized for its biocompatibility, microporosity, transparency, conformability, elasticity, and ability to maintain a moist wound environment while absorbing exudates. These attributes make BC an attractive material in biomedical applications, particularly in skin tissue repair. However, its lack of inherent antimicrobial activity limits its effectiveness. In this study, BC was enhanced by incorporating cerium (IV)-oxide (CeO2) nanoparticles, resulting in a series of bacterial cellulose-CeO2 (BC-CeO2) composite materials. Characterization via FESEM, XRD, and FTIR confirmed the successful synthesis of the composites. Notably, BC-CeO2-1 exhibited no cytotoxic or genotoxic effects on peripheral blood lymphocytes, and it additionally protected cells from genotoxic and cytotoxic effects in H2O2-treated cultures. Redox parameters in blood plasma samples displayed concentration and time-dependent trends in PAB and LPP assays. The incorporation of CeO2 nanoparticles also bolstered antimicrobial activity, expanding the potential biomedical applications of these composites.

Neuro-fuzzy prediction model of occupational injuries in mining.

Objectives. This study investigates the possibility of developing a unique model for predicting work-related injuries in Serbian underground coal mines using neural networks and fuzzy logic theory. Accidents are common due to the unique nature of underground mineral extraction involving people, machinery and limited workplaces. Methods. A universal model for predicting occupational accidents takes into account influential factors such as organizational aspects, personal and collective protective equipment, on-the-job training and leadership factors. The selected networks achieved a prediction accuracy of >90%. Results. The study successfully identifies potential risks and critical worker groups leading to injuries. The sensitivity analysis provides insights for targeted safety measures and improved organizational practices. Conclusion. This data-driven approach makes a valuable contribution to safety in the mining industry. Implementation of the predictive model can reduce injuries and machine damage, and improve worker well-being.

Drug-induced liver injury associated with the use of newer antiseizure medications in the elderly: an analysis of data from VigiBase.

BACKGROUND: Data on drug-induced liver injury (DILI) caused by newer antiseizure medications (ASMs) in the elderly are scarce and mainly come from literature case reports. We analyzed Individual Case Safety Reports (ICSRs) of DILI in elderly patients treated with newer ASMs reported to VigiBase. RESEARCH DESIGN AND METHODS: Empirica™ Signal software was used to retrieve ICSRs reported to VigiBase up to 31 December 2021 and to calculate Empirical Bayesian Geometric Mean and corresponding 90% confidence intervals (EB05, EB95) for each drug-event pair. EB05 > 2, N > 0 was considered a signal. Analysis by age subgroups and gender was performed to assess the influence of these factors on ICSR characteristics and identified signals. RESULTS: There were 1399 ICSRs reporting 1947 events of hepatotoxicity. 56.97% of the reports were reported in females, 67.05% were serious, and 3.36% resulted in death. For one or more events of hepatotoxicity, signals were detected for lamotrigine, levetiracetam, oxcarbazepine, topiramate, and zonisamide. Age- and gender-biased reporting frequency was identified for topiramate-induced hyperammonemia, with disproportionally higher reporting frequency in ≥75-year-old male patients. CONCLUSIONS: The results of our study indicate differences among newer ASMs in their potential to cause DILI in the elderly. Further studies are needed to confirm the associations identified in this study.

Organic and Biogenic Nanocarriers as Bio-Friendly Systems for Bioactive Compounds' Delivery: State-of-the Art and Challenges.

"Green" strategies to build up novel organic nanocarriers with bioperformance are modern trends in nanotechnology. In this way, the valorization of bio-wastes and the use of living systems to develop multifunctional organic and biogenic nanocarriers (OBNs) have revolutionized the nanotechnological and biomedical fields. This paper is a comprehensive review related to OBNs for bioactives' delivery, providing an overview of the reports on the past two decades. In the first part, several classes of bioactive compounds and their therapeutic role are briefly presented. A broad section is dedicated to the main categories of organic and biogenic nanocarriers. The major challenges regarding the eco-design and the fate of OBNs are suggested to overcome some toxicity-related drawbacks. Future directions and opportunities, and finding "green" solutions for solving the problems related to nanocarriers, are outlined in the final of this paper. We believe that through this review, we will capture the attention of the readers and will open new perspectives for new solutions/ideas for the discovery of more efficient and "green" ways in developing novel bioperformant nanocarriers for transporting bioactive agents.

Theory of Mind in Typical Adults: Sex-Differences and Its Associations with Anxiety and Depression Symptoms.

OBJECTIVE: Despite an increased interest in research of theory of mind (ToM) in recent years - both related to psychopathology (depression and anxiety spectrum disorders) and within the typical adults, the existing literature is scarce and presents some conflicting results. Present study aimed to explore sex differences in ToM, alongside its associations with current anxiety and depression symptoms, in a large sample of typical adults collected online. METHOD: Participants completed the 15-minutes survey obtaining socio-demographic data, current self-reported depression and anxiety symptom severity, and ToM ability (the Reading the Mind in the Eyes Task). The sample comprised 605 participants -mostly younger adults, women, and high school graduate/student population. RESULTS: The majority of participants reported minimal/mild depressive and anxiety symptoms that were significantly more severe in women. Women also displayed significantly better overall ToM ability than men. Significant negative correlation between the severity of current depressive and anxiety symptoms and ToM ability was also observed, but only in individuals expressing the symptoms requiring clinical attention (such association was absent in those exhibiting minimal/mild symptoms). CONCLUSIONS: Present research adds to the existing knowledge on the association between ToM ability, anxiety, and depressive symptoms in typical adults as well as on the sex-differences in this important social cognitive domain. Exploring the factors representing indicators of vulnerability for depression-anxiety spectrum disorders is important for their timely detection and treatment.