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Drought stress represents a major constraint with significant impacts on wheat crop globally. The use of plant growth-promoting bacteria (PGPB) has emerged as a promising strategy to alleviate the detrimental impacts of water stress and enhance plant development. We investigated 24 strains from diverse ecosystems, assessed for PGP traits and tolerance ability to abiotic stresses (drought, salinity, temperature, pH, heavy metals, pollutants, herbicides, and fungicides). The most effective bacterial strains Providencia vermicola ME1, Pantoea agglomerans Pa, Pseudomonas knackmussi MR6, and Bacillus sp D13 were chosen. Furthermore, these strains exhibited PGP activities under osmotic stress (0, 10, 20, and 30% PEG-6000). The impact of these osmotolerant PGPBs on wheat (Triticum durum L.) growth under drought stress was assessed at two plant growth stages. In an in vitro wheat seed germination experiment, bacterial inoculation significantly enhanced germination parameters. In pot experiments, the potential of these bacteria was evaluated in wheat plants under three treatments: Well-watered (100% field capacity), moderate stress (50% FC), and severe stress (25% FC). Results showed a significant decline in wheat growth parameters under increasing water stress for uninoculated seedlings. In contrast, bacterial inoculation mitigated these adverse effects, significantly improving morphological parameters and chlorophyll pigment contents under the stress conditions. While malondialdehyde (lipid peroxidation) and proline contents increased significantly with drought intensity, they decreased after bacterial inoculation. The antioxidant enzyme activities (GPX, CAT, and SOD) in plants decreased after bacterial inoculation. The increased root colonization capacity observed under water stress was attributed to their ability to favorable adaptations in a stressful environment. This study highlighted the potential of selected PGPB to alleviate water stress effects on wheat, promoting practical applications aimed at enhancing crop resilience under conditions of water shortage.

The primary staple of the Algerian population is wheat, and due to climate change, it is necessary to look for wheat genotypes with a high yield, drought and heat tolerance, and disease resistance, in addition to high quality for bread-making and other foodstuffs. Our objective of this study was to investigate 17 genotypes of Triticum aestivum L., including 10 traditionally cultivated, 2 recently introduced, and 5 currently in development, with the goal of identifying those exhibiting high-quality attributes for breadmaking and superior technological properties, while maintaining low levels of immunoreactive gluten. We conducted analyses on chemical composition, immunoreactive gluten content, as well as the secondary structure of proteins and the conformation of starch in flours obtained from different wheat bread genotypes grown in similar watering and other conditions. Additionally, the rheological characteristics of the dough were measured using an alveograph and rheoviscosimeter. We also explored the physical properties and technological attributes relevant to the bread-making process. The major results indicated low heterogeneity among genotypes concerning immunoreactivity. The characteristics of 17 Triticum aestivum L. genotypes form four groups included: Group A: Traditional, recently, or not yet cultivated in Algeria, with the highest β-sheet, W values, and protein contents; B: Highest protein content, lowest β-sheet, and medium W and P/L values. C: Four of the traditional, recently, or not yet cultivated genotypes with the highest bread specific volume, low protein, and W and P/L values. Group D: Traditional genotypes, with the lowest specific volume of bread and a low protein content. Some of the traditional cultivated wheat genotypes in Algeria could be changed, although almost all the drought and disease resistant genotypes could be used for bread-making, which was excellent news because of global warming.

The intricate interplay between the developing placenta and fetal-maternal interactions is critical for pregnancy outcomes. Despite advancements, gaps persist in understanding biomechanics, transport processes, and blood circulation parameters, all of which are crucial for safe pregnancies. Moreover, the complexity of fetal-maternal interactions led to conflicting data and methodological variations. This review presents a comprehensive overview of current knowledge on fetal-maternal interface structures, with a particular focus on the first trimester. More in detail, the embryological development, structural characteristics, and physiological functions of placental chorionic plate and villi, fetal membranes and umbilical cord are discussed. Furthermore, a description of the main structures and features of maternal and fetal fluid dynamic exchanges is provided. However, ethical constraints and technological limitations pose still challenges to studying early placental development directly, which calls for sophisticated in vitro, microfluidic organotypic models for advancing our understanding. For this, knowledge about key in vivo parameters are necessary for their design. In this scenario, the integration of data from later gestational stages and mathematical/computational simulations have proven to be useful tools. Notwithstanding, further research into cellular and molecular mechanisms at the fetal-maternal interface is essential for enhancing prenatal care and improving maternal and fetal health outcomes.

Among plant disease management strategies, biological control is a sustainable alternative to the use of chemicals for the control of vascular wilt caused by Fusarium oxysporum. Fusarium wilt is the most devastating disease affecting a wide variety of plants. Bacillus species are the most widely used biological control candidates for the control of these fungal diseases. This review describes the pathogenicity of F. oxysporum, its virulence mechanisms, and host plant–pathogen interactions. The control means deployed by Bacillus species inhibit or kill these phytopathogens. Bacillus spp. produce a wide range of secondary metabolites, including volatile and non-volatile organic compounds. Biocontrol potential is achieved through direct antimicrobial activity, the induction of the host plant’s immune response (Induced Systemic Resistance), and competition for nutrients and space. In addition, parameters governing the selection of effective biocontrol agents and their survival in plant microbial communities are discussed. The influence of the microbiota on the establishment and development of biocontrol agents can assess the potential of these treatments and facilitate the development of effective biopesticides during their field application.

Surgically addressing tumors poses a challenge, requiring a tailored, multidisciplinary approach for each patient based on the unique aspects of their case. Innovative therapeutic regimens combined to reliable reconstructive methods can contribute to an extended patient's life expectancy. This study presents a detailed comparative investigation of near-infrared therapy protocols, examining the impact of non-fractionated and fractionated irradiation regimens on cancer treatment. The therapy is based on the implantation of graphene oxide/poly(lactic-co-glycolic acid) three-dimensional printed scaffolds, exploring their versatile applications in oncology by the examination of pro-inflammatory cytokine secretion, immune response, and in vitro and in vivo tumor therapy. The investigation into cell death patterns (apoptosis vs necrosis) underlines the pivotal role of protocol selection underscores the critical influence of treatment duration on cell fate, establishing a crucial parameter in therapeutic decision-making. In vivo experiments corroborated the profound impact of protocol selection on tumor response. The fractionated regimen emerged as the standout performer, achieving a substantial reduction in tumor size over time, surpassing the efficacy of the non-fractionated approach. Additionally, the fractionated regimen exhibited efficacy also in targeting tumors in proximity but not in direct contact to the scaffolds. Our results address a critical gap in current research, highlighting the absence of a standardized protocol for optimizing the outcome of photodynamic therapy. The findings underscore the importance of personalized treatment strategies in achieving optimal therapeutic efficacy for precision cancer therapy.

Abstract: This article sheds light on role of intertextuality in reflecting some of the major thematic concerns in Ghada Samman’s Beirut Nightmares. Through a matrix of different texts, she attempts to convey the honorific experience of her narrator during the Lebanese Civil War. Samman exposes the impact of civil war on the daily life and the psychology of her major character. Thus, intertextuality serves as an important thematic tool that contributes in providing a nuanced understanding of the narrator’s tragic experience. Samman weaves myths and literary texts in her narrative in order to comment on the devastating situation resulted from this internal conflict. She highlights the dialogical relationship between her work and previous ones to locate the narrator’s experience within a broader historical and literary context. In this study, Beirut Nightmares is understood through its dependency on prior works to explore themes of confinement, fear, issues of artistic creativity and destruction. Samman’s use of a web of texts enables her to evoke similar feelings within a different socio-cultural context. Accordingly, intertextuality contributes in creating different levels of understanding regarding the narrator’s suffering. Keywords: Intertextuality, Beirut Nightmares, Ghada Samman, Civil War.

Abstract Background The secretome of mesenchymal stromal cells isolated from the amniotic membrane (hAMSCs) has been extensively studied for its in vitro immunomodulatory activity as well as for the treatment of several preclinical models of immune-related disorders. The bioactive molecules within the hAMSCs secretome are capable of modulating the immune response and thus contribute to stimulating regenerative processes. At present, only a few studies have attempted to define the composition of the secretome, and several approaches, including multi-omics, are underway in an attempt to precisely define its composition and possibly identify key factors responsible for the therapeutic effect. Methods In this study, we characterized the protein composition of the hAMSCs secretome by a filter-aided sample preparation (FASP) digestion and liquid chromatography-high resolution mass spectrometry (LC–MS) approach. Data were processed for gene ontology classification and functional protein interaction analysis by bioinformatics tools. Results Proteomic analysis of the hAMSCs secretome resulted in the identification of 1521 total proteins, including 662 unique elements. A number of 157 elements, corresponding to 23.7%, were found as repeatedly characterizing the hAMSCs secretome, and those that resulted as significantly over-represented were involved in immunomodulation, hemostasis, development and remodeling of the extracellular matrix molecular pathways. Conclusions Overall, our characterization enriches the landscape of hAMSCs with new information that could enable a better understanding of the mechanisms of action underlying the therapeutic efficacy of the hAMSCs secretome while also providing a basis for its therapeutic translation.

Aim: In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible for primary and acquired drug resistance. This study aimed to assess the inter-tumoral, intra-tumoral, and intra-lesional heterogeneity of known druggable targets in metastatic RCC (mRCC). Methods: The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context. Results: High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher for the mTOR pathway proteins. Combined immunophenotypical expression patterns and their correlations with the immune context were uncovered [i.e., mTOR expression in the metastases positively correlated with PD-L1 expression in tumor-infiltrating lymphocytes (TILs), P = 0.019; MET expression was related to PD-1 expression on TILs (P = 0.041, ρ = 0.41) and peritumoral lymphocytes (RILs; P = 0.013, ρ = 0.49)], suggesting the possibility of predicting drug response or resistance to tyrosine kinase, mTOR, or immune checkpoint inhibitors. Conclusions: In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed for their reliable translation into clinical practice. The easy-to-use immunohistochemical method of the present study allowed the identification of different combined expression patterns, providing cues for planning the management of systemic treatment combinations and sequences in an mRCC patient population. The quantitative heterogeneity of the investigated biomarkers suggests that multiple intralesional assays are needed to consider the assessment reliable for clinical considerations.

Abstract Background Traumatic brain injury (TBI) is a leading cause of death and long-term disability worldwide. In addition to primary brain damage, systemic immune alterations occur, with evidence for dysregulated immune responses in aggravating TBI outcome and complications. However, immune dysfunction following TBI has been only partially understood, especially in the elderly who represent a substantial proportion of TBI patients and worst outcome. Therefore, we aimed to conduct an in-depth immunological characterization of TBI patients, by evaluating both adaptive (T and B lymphocytes) and innate (NK and monocytes) immune cells of peripheral blood mononuclear cells (PBMC) collected acutely ( 65 yo) patients, compared to age-matched controls, and also the levels of inflammatory biomarkers. Results Our data show that young respond differently than elderly to TBI, highlighting the immune unfavourable status of elderly compared to young patients. While in young only CD4 T lymphocytes are activated by TBI, in elderly both CD4 and CD8 T cells are affected, and are induced to differentiate into subtypes with low cytotoxic activity, such as central memory CD4 T cells and memory precursor effector CD8 T cells. Moreover, TBI enhances the frequency of subsets that have not been previously investigated in TBI, namely the double negative CD27- IgD- and CD38-CD24- B lymphocytes, and CD56dim CD16- NK cells, both in young and elderly patients. TBI reduces the production of pro-inflammatory cytokines TNF-α and IL-6, and the expression of HLA-DM, HLA-DR, CD86/B7-2 in monocytes, suggesting a compromised ability to drive a pro-inflammatory response and to efficiently act as antigen presenting cells. Conclusions We described the acute immunological response induced by TBI and its relation with injury severity, which could contribute to pathologic evolution and possibly outcome. The focus on age-related immunological differences could help design specific therapeutic interventions based on patients’ characteristics.

Lung fibrosis is a complex process, with unknown underlying mechanisms, involving various triggers, diseases and stimuli. Different cell types (epithelial cells, endothelial cells, fibroblasts and macrophages) interact dynamically through multiple signalling pathways, including biochemical/molecular and mechanical signals, such as stiffness, affecting cell function and differentiation. Idiopathic pulmonary fibrosis (IPF) is the most common fibrosing interstitial lung disease (fILD), characterised by a notably high mortality. Unfortunately, effective treatments for advanced fILD, and especially IPF and non-IPF progressive fibrosing phenotype ILD, are still lacking. The development of pharmacological therapies faces challenges due to limited knowledge of fibrosis pathogenesis and the absence of pre-clinical models accurately representing the complex features of the disease. To address these challenges, new model systems have been developed to enhance the translatability of preclinical drug testing and bridge the gap to human clinical trials. The use of two- and three-dimensional in vitro cultures derived from healthy or diseased individuals allows for a better understanding of the underlying mechanisms responsible for lung fibrosis. Additionally, microfluidics systems, which replicate the respiratory system's physiology ex vivo, offer promising opportunities for the development of effective therapies, especially for IPF.

Summary: Mesenchymal stromal cells (MSCs) are known for their immunomodulatory activity. Here, we report that MSCs isolated from the amniotic membrane of human term placenta (hAMSCs) impact CD8 T cell fate through a multifaceted mechanism. We observed that hAMSCs are able to impact the metabolism of naive CD8 lymphocytes by downregulating the phosphorylation of mTOR and AKT, thus blocking cell differentiation. This effect is due to the ability of hAMSCs to reduce the expression of two receptors, IL-12Rβ1 and IL-2RA, resulting in reduced phosphorylation of STAT4 and STAT5. In addition, hAMSCs reduce the expression of two transcriptional factors, Tbet and Eomes, directly involved in early effector cell commitment. Our results unravel an unknown feature of MSCs, offering alternative mechanistic insights into the effects of MSCs for the treatment of diseases characterized by an altered activation of memory subsets, such as autoimmune diseases and graft versus host disease.

The Madden–Julian Oscillation (MJO) is one of the main sources of sub-seasonal atmospheric predictability in the tropical region. The MJO affects precipitation over highly populated areas, especially around southern India. Therefore, predicting its phase and intensity is important as it has a high societal impact. Indices of the MJO can be derived from the first principal components of zonal wind and outgoing longwave radiation (OLR) in the tropics (RMM1 and RMM2 indices). The amplitude and phase of the MJO are derived from those indices. Our goal is to forecast these two indices on a sub-seasonal timescale. This study aims to provide an ensemble forecast of MJO indices from analogs of the atmospheric circulation, computed from the geopotential at 500 hPa (Z500) by using a stochastic weather generator (SWG). We generate an ensemble of 100 members for the MJO amplitude for sub-seasonal lead times (from 2 to 4 weeks). Then we evaluate the skill of the ensemble forecast and the ensemble mean using probabilistic scores and deterministic skill scores. According to score-based criteria, we find that a reasonable forecast of the MJO index could be achieved within 40 d lead times for the different seasons. We compare our SWG forecast with other forecasts of the MJO. The comparison shows that the SWG forecast has skill compared to ECMWF forecasts for lead times above 20 d and better skill compared to machine learning forecasts for small lead times.

Background It is possible to induce immunomodulation in HER2-positive breast cancer (BC) by modifying the route of administration of trastuzumab.Methods In this multicenter randomized phase II trial, all enrolled patients (pts) with T2–T4d HER2-positive BC received 3 cycles of neoadjuvant treatment (NAT) with fluorouracil, epirubicin and cyclophosphamide every 3 weeks (q21), followed by docetaxel/pertuzumab plus intravenous trastuzumab (arm A) or, docetaxel/pertuzumab plus subcutaneous (SC) trastuzumab (arm B) q21x4 cycles. After surgical operation, each pt was treated with trastuzumab q21x14 cycles using the same SC or intravenous formulation of NAT. Primary endpoint was the proportion of subjects with high stromal tumor-infiltrating lymphocytes (sTILs) in postneoadjuvant residual disease (RD).Results Sixty-three pts (31 (arm A) and 32 (arm B)) were enrolled. Pathological complete response was obtained by 20/31 pts (64.5%; 95% CI 45.4% to 80.1%) in arm A and 19/32 pts (59.4%; 95% CI 40.1% to 76.3%) in arm B. High sTILs were observed in 27% and 46% of postneoadjuvant residual tumors in arms A and B, respectively. CD8+ T cells increased significantly in RDs of both arms (p=0.014 and 0.002 for arm A and B, respectively), whereas a significant decline in the level of CD4+ FoxP3+ regulatory T cells was observed only in arm B (p=0.016). A significant upregulation of PD-1 on sTILs was found in RD of pts enrolled in arm B (p=0.012), while programmed death-ligand 1 (PD-L1) was significantly overexpressed in residual tumors of arm A (p=0.02). A strong negative correlation was reported in arm B between expression of PD-L1 on pretreatment sTILs and CD3 expression on sTILs in RD (τ: −0.73). Grade≥3 AE incidence rates were similar between the two arms.Conclusions SC trastuzumab induced relevant sTILs enrichment, with favorable variations of immune parameters in HER2-positive BC pts with RD after NAT. Novel immunotherapy strategies should be tested to achieve SC-specific, antitumor immune response.Trial registration number NCT03144947, and EudraCT number: 2016-000435-41.

Many preclinical studies have shown that birth-associated tissues, cells and their secreted factors, otherwise known as perinatal derivatives (PnD), possess various biological properties that make them suitable therapeutic candidates for the treatment of numerous pathological conditions. Nevertheless, in the field of PnD research, there is a lack of critical evaluation of the PnD standardization process: from preparation to in vitro testing, an issue that may ultimately delay clinical translation. In this paper, we present the PnD e-questionnaire developed to assess the current state of the art of methods used in the published literature for the procurement, isolation, culturing preservation and characterization of PnD in vitro. Furthermore, we also propose a consensus for the scientific community on the minimal criteria that should be reported to facilitate standardization, reproducibility and transparency of data in PnD research. Lastly, based on the data from the PnD e-questionnaire, we recommend to provide adequate information on the characterization of the PnD. The PnD e-questionnaire is now freely available to the scientific community in order to guide researchers on the minimal criteria that should be clearly reported in their manuscripts. This review is a collaborative effort from the COST SPRINT action (CA17116), which aims to guide future research to facilitate the translation of basic research findings on PnD into clinical practice.

Palbociclib is in early-stage clinical testing in advanced hepatocellular carcinoma (HCC). Here, we investigated whether the anti-tumor activity of palbociclib, which prevents the CDK4/6-mediated phosphorylation of RB1 but simultaneously activates AKT signaling, could be improved by its combination with a PI3K/AKT/mTOR inhibitor in liver cancer models. The selective pan-AKT inhibitor, MK-2206, or the microRNA-199a-3p were tested in combination with palbociclib in HCC cell lines and in the TG221 HCC transgenic mouse model. The combination palbociclib/MK-2206 was highly effective, but too toxic to be tolerated by mice. Conversely, the combination miR-199a-3p mimics/palbociclib not only induced a complete or partial regression of tumor lesions, but was also well tolerated. After 3 weeks of treatment, the combination produced a significant reduction in number and size of tumor nodules in comparison with palbociclib or miR-199a-3p mimics used as single agents. Moreover, we also reported the efficacy of this combination against sorafenib-resistant cells in vitro and in vivo. At the molecular level, the combination caused the simultaneous decrease of the phosphorylation of both RB1 and of AKT. Our findings provide pre-clinical evidence for the efficacy of the combination miR-199a-3p/palbociclib as anti-HCC treatment or as a new approach to overcome sorafenib resistance.

The Madden–Julian Oscillation (MJO) is a major source of predictability on the sub-seasonal (10 to 90 d) timescale. An improved forecast of the MJO may have important socioeconomic impacts due to the influence of MJO on both tropical and extratropical weather extremes. Although in the last decades state-of-the-art climate models have proved their capability for forecasting the MJO exceeding the 5-week prediction skill, there is still room for improving the prediction. In this study we use multiple linear regression (MLR) and a machine learning (ML) algorithm as post-processing methods to improve the forecast of the model that currently holds the best MJO forecasting performance, the European Centre for Medium-Range Weather Forecasts (ECMWF) model. We find that both MLR and ML improve the MJO prediction and that ML outperforms MLR. The largest improvement is in the prediction of the MJO geographical location and intensity.

Drought stress represents a major constraint with significant impacts on wheat crop globally. The use of plant growth-promoting bacteria (PGPB) has emerged as a promising strategy to alleviate the detrimental impacts of water stress and enhance plant development. We investigated 24 strains from diverse ecosystems, assessed for PGP traits and tolerance ability to abiotic stresses (drought, salinity, temperature, pH, heavy metals, pollutants, herbicides, and fungicides). The most effective bacterial strains Providencia vermicola ME1, Pantoea agglomerans Pa, Pseudomonas knackmussi MR6, and Bacillus sp D13 were chosen. Furthermore, these strains exhibited PGP activities under osmotic stress (0, 10, 20, and 30% PEG-6000). The impact of these osmotolerant PGPBs on wheat (Triticum durum L.) growth under drought stress was assessed at two plant growth stages. In an in vitro wheat seed germination experiment, bacterial inoculation significantly enhanced germination parameters. In pot experiments, the potential of these bacteria was evaluated in wheat plants under three treatments: Wellwatered (100% field capacity), moderate stress (50% FC), and severe stress (25% FC). Results showed a significant decline in wheat growth parameters under increasing water stress for uninoculated seedlings. In contrast, bacterial inoculation mitigated these adverse effects, significantly improving morphological parameters and chlorophyll pigment contents under the stress conditions. While malondialdehyde (lipid peroxidation) and proline contents increased significantly with drought intensity, they decreased afterbacterial inoculation. The antioxidant enzyme activities (GPX, CAT, and SOD) in plants decreased after bacterial inoculation. The increased root colonization capacity observed under water stress was attributed to their ability to favorable adaptations in a stressful environment. This study highlighted the potential of selected PGPB to alleviate water stress effects on wheat, promoting practical applications aimed at enhancing crop resilience under conditions of water shortage. [ABSTRACT FROM AUTHOR]

The potential clinical applications of human amniotic membrane (hAM) and human amniotic epithelial cells (hAECs) in the field of regenerative medicine have been known in literature since long. However, it has yet to be elucidated whether hAM contains different anatomical regions with different plasticity and differentiation potential. Recently, for the first time, we highlighted many differences in terms of morphology, marker expression, and differentiation capabilities among four distinct anatomical regions of hAM, demonstrating peculiar functional features in hAEC populations. The aim of this study was to investigate in situ the ultrastructure of the four different regions of hAM by means of transmission electron microscopy (TEM) to deeply understand their peculiar characteristics and to investigate the presence and localization of secretory products because to our knowledge, there are no similar studies in the literature. The results of this study confirm our previous observations of hAM heterogeneity and highlight for the first time that hAM can produce extracellular vesicles (EVs) in a heterogeneous manner. These findings should be considered to increase efficiency of hAM applications within a therapeutic context.

Introduction Tobacco use among youth is a real public health concern in most developing countries. To provide recent epidemiological data regarding tobacco use among this specific population, a national survey was conducted in Tunisia in 2021. We aimed to determine cigarette smoking prevalence in Tunisian adolescents and assess associated factors. Objectives We aimed to determine cigarette smoking prevalence in Tunisian adolescents and assess associated factors. Methods Data from the Mediterranean school survey on alcohol and other drugs (MedSPAD 2021) were used. Based on three-stage stratification sampling method, first and second grade high school students were enrolled. A self-administered standardized questionnaire was used and weighted prevalence estimates for cigarette smoking “at least once in a lifetime” were studied. Binary logistic regression model was used to assess associated factors and Adjusted Odds Ratios (AORs) were presented. The independent factors included were: sex, area of residence, private or public sector, alcohol and cannabis use, and being exposed to tobacco smoking in family and peer’s environment. Epidata and STATA software were used for data entry and statistical analysis, respectively. Results Among 6.201 participants with a mean age of 16.8 years, 60.4% were girls; the prevalence of cigarette smoking was 24,75% 95% CI [23.24,26.32], significantly higher among boys (41.1% versus 14.2%, p

Introduction The emergence of New Psycho-active Substances (NPS) such as Synthetic cannabinoid and cathinone, represents a challenging issue for drug policy globally. In order to set up new adjusted measures to limit this phenomenon extension, objective epidemiologic indicators are requested. Objectives We aimed to determine the prevalence of Synthetic cannabinoid and cathinone consumption in Tunisian adolescents by gender and regional distribution. Methods Data from the Mediterranean school survey on alcohol and other drugs (MedSPAD III-2021) were used. Based on three-stage stratification sampling method, high school teenagers in first and second grades of secondary education, were enrolled. Data collection was performed using a self-administered standardized questionnaire. We examined weighted prevalence estimates of NPS use at least once in a lifetime (Synthetic cannabinoid and cathinone) by gender and regional distribution. Epi data software was used for data entry and all statistical analysis were performed with STATA software. Results The survey included 6201 adolescents with a mean age of 16.8 years and a sex ratio female/male of 1.5. Synthetic cannabinoid’s use was reported by 1.9%, 95% CI [1.57-2.39] of students, with statistically significant difference between boys (4.1%) and girls (0.6%), p-value

Introduction Non-Medical Use of Anxiolytics (NMUA) and sedatives is a focus of scientific interest worldwide. In Tunisia, no national epidemiological data related to this issue, are published. Objectives We aimed to determine the prevalence of NMUA in Tunisian adolescents and assess specificities from a gender scope. Methods Data from the 2021-Mediterranean school Survey on Alcohol and other Drugs (MedSPAD) were used. Based on random sampling method (three-stage stratification), high school teenagers in first and second year of secondary education, were enrolled. Data were collected using a self-administered standardized questionnaire assessing socio-demographic characteristics, and specific questions related to NMUA (among adolescents and close environment), perceived accessibility and initiation age. We studied weighted prevalence estimates of NMUA at least once in a lifetime, presented with 95% Confidence Interval (CI). Epi data software was used for data entry and statistical analysis was performed with STATA software. Results The survey included 6.201 adolescents with a mean age of 16.8 years and sex ratio F/M equal to 1.5. Only half of surveyed adolescents, perceived accessibility to NMUA as “impossible” and almost 20% had at least one family member or friend using a nonmedical prescription of anxiolytics. The overall prevalence of NMUA was (8.4%; 95% CI [7.6-9.2]), significantly higher among girls (9.8% Vs 6.1%, p-value

Introduction Despite its well-known acute and long-term harmful effects on a person’s mental health and well-being, alcohol remains the most commonly used psychoactive substance among adolescents after tobacco products in many countries. Objectives We aimed at studying the prevalence of alcohol use, and identify associated factors in Tunisian high school adolescents. Methods We used national data from the 2021-Mediterranean School Survey Project on Alcohol and Other Drugs (MedSPAD). Based on a clustered two-stage stratification sampling method, a representative sample of teenagers aged 16 to 18 years, was selected. Data collection was performed using a self-administered standardized questionnaire, assessing socio-demographic characteristics and risky behaviours, and including questions about alcoholic beverages patterns of use. Binary logistic regression model was used to assess associated factors and adjusted Odds Ratios (AORs) were presented with 95% confidence intervals (CI). Cspro software was used for data entry and all statistical analysis were performed with STATA software. Results A total of 6201 adolescents with a mean age of 16.8 years and a sex ratio female/male of 1.5 were enrolled. Lifetime prevalence of alcoholic beverages consumption was 8.0%, 95% CI [7.0, 9,1] (n=6196). The prevalence of alcohol consumption during the previous year and month were 5.1 % and 1.7% respectively. Cocktails and beer were the most frequently consumed beverages. Prevalence of alcohol use was significantly associated with tobacco, cannabis and e-cigarettes use (AOR 9.5, 6.0 and 1.9 respectively; p≤10-3), a higher frequency of nights spent away from home, school absenteeism for non-medical reasons and enrolment in the private sector. Alcohol intoxication was reported by 2.9% of respondents during their lifetime. Early onset was reported by 17.2% of respondents for alcohol use and 10.1% for alcohol intoxication. Conclusions Although the prevalence of alcohol use was relatively low among Tunisian adolescents compared to European adolescents, early onset- indicating an increased risk of developing an alcohol use disorder- warrant the implementation of primary prevention interventions through mental health promotion and life skill trainings to halt these trends and avert the raising burden of morbidity and mortality attributable to alcohol use. Disclosure of Interest None Declared

Introduction Cannabis use is wrongly deemed “safe” by teenagers worldwide, despite its increased tetrahydrocannabinoids content and its psychosocial and cognitive harmful effectts. Objectives We aimed to estimate the prevalence of cannabis use, identify associated factors among Tunisian adolescents and assess the risk of problem cannabis use among users. Methods The 2021-Mediterranean School Survey Project on Alcohol and Other Drugs (MedSPAD) is a national survey, targeting Tunisian high school adolescents aged 16 to 18 years. Based on a self-administered questionnaire, adolescents were asked about their engagement in several risky behaviours including cannabis use. The 6-item Cannabis Abuse Screening Test (CAST) was intended for users to assess the risk of problem cannabis use. Binary logistic regression was performed to identify factors associated to cannabis use and Adjusted Odds Ratios (AORs) were presented with correspondent 95% confidence intervals (CI). Cspro and STATA software were used for data entry and analysis respectively. Results Among 6201 participants (girls: 60.4%), lifetime prevalence of cannabis use was 7.9% ,95% CI [7.0, 8.9] significantly higher among boys (16.1 % Vs. 2.5 % in girls, p