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Background: In recent decades, machine-learning (ML) technologies have advanced the management of high-dimensional and complex cancer data by developing reliable and user-friendly automated diagnostic tools for clinical applications. Immunohistochemistry (IHC) is an essential staining method that enables the identification of cellular origins by analyzing the expression of specific antigens within tissue samples. The aim of this study was to identify a model that could predict histopathological diagnoses based on specific immunohistochemical markers., Methods: The XGBoost learning model was applied, where the input variable (target variable) was the histopathological diagnosis and the predictors (independent variables influencing the target variable) were the immunohistochemical markers., Results: Our study demonstrated a precision rate of 85.97% within the dataset, indicating a high level of performance and suggesting that the model is generally reliable in producing accurate predictions., Conclusions: This study demonstrated the feasibility and clinical efficacy of utilizing the probabilistic decision tree algorithm to differentiate tumor diagnoses according to immunohistochemistry profiles.

Artificial intelligence (AI) is a reality of our times, and it has been successfully implemented in all fields, including medicine. As a relatively new domain, all efforts are directed towards creating algorithms applicable in most medical specialties. Pathology, as one of the most important areas of interest for precision medicine, has received significant attention in the development and implementation of AI algorithms. This focus is especially important for achieving accurate diagnoses. Moreover, immunohistochemistry (IHC) serves as a complementary diagnostic tool in pathology. It can be further augmented through the application of deep learning (DL) and machine learning (ML) algorithms for assessing and analyzing immunohistochemical markers. Such advancements can aid in delineating targeted therapeutic approaches and prognostic stratification. This article explores the applications and integration of various AI software programs and platforms used in immunohistochemical analysis. It concludes by highlighting the application of these technologies to pathologies such as breast, prostate, lung, melanocytic proliferations, and hematologic conditions. Additionally, it underscores the necessity for further innovative diagnostic algorithms to assist physicians in the diagnostic process.

Three-dimensional (3D) bioprinting is the use of computer-controlled transfer processes for assembling bioinks (cell clusters or materials loaded with cells) into structures of prescribed 3D organization. The correct bioprinting parameters ensure a fast and accurate bioink deposition without exposing the cells to harsh conditions. This study seeks to optimize pneumatic extrusion-based bioprinting based on hydrogel flow rate and extrusion speed measurements. We measured the rate of the hydrogel flow through a cylindrical nozzle and used non-Newtonian hydrodynamics to fit the results. From the videos of free-hanging hydrogel strands delivered from a stationary print head, we inferred the extrusion speed, defined as the speed of advancement of newly formed strands. Then, we relied on volume conservation to evaluate the extrudate swell ratio. The theoretical analysis enabled us to compute the extrusion speed for pressures not tested experimentally as well as the printing speed needed to deposit hydrogel filaments of a given diameter. Finally, the proposed methodology was tested experimentally by analyzing the morphology of triple-layered square-grid hydrogel constructs printed at various applied pressures while the printing speeds matched the corresponding extrusion speeds. Taken together, the results of this study suggest that preliminary measurements and theoretical analyses can simplify the search for the optimal bioprinting parameters.

Contamination of the aqueous environment caused by the presence of heavy metal ions and oils is a growing concern that must be addressed to reduce their detrimental impact on living organisms and safeguard the environment. Recent efficient and environmentally friendly remediation methods for the treatment of water are based on third-generation bioaerogels as emerging applications for the removal of heavy metal ions and oils from aqueous systems. The peculiarities of these materials are various, considering their high specific surface area and low density, together with a highly porous three-dimensional structure and tunable surface chemistry. This review illustrates the recent progress in aerogels developed from cellulose and chitosan as emerging materials in water treatment. The potential of aerogel-based adsorbents for wastewater treatment is reported in terms of adsorption efficacy and reusability. Despite various gaps affecting the manufacturing and production costs of aerogels that actually limit their successful implementation in the market, the research progress suggests that bio-based aerogels are ready to be used in water-treatment applications in the near future.

Background: Despite all the available treatments, psoriasis remains incurable; therefore, finding personalized therapies is a continuous challenge. Psoriasis is linked to a gut microbiota imbalance, highlighting the importance of the gut-skin axis and its inflammatory mediators. Restoring this imbalance can open new perspectives in psoriasis therapy. We investigated the effect of purified IgY raised against pathological human bacteria antibiotic-resistant in induced murine psoriatic dermatitis (PSO)., Methods: To evaluate the immune portrayal in an imiquimod experimental model, before and after IgY treatment, xMAP array and flow cytometry were used., Results: There were significant changes in IL-1α,β, IL-5, IL-6, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17a, IFN-γ, TNF-α, IP-10/CXCL10, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, MIG/CXCL9, and KC/CXCL1 serum levels. T (CD3ε + ), B (CD19 + ) and NK (NK1.1 + ) cells were also quantified. In our model, TNF-α, IL-6, and IL-1β cytokines and CXCL1 chemokine have extremely high circulatory levels in the PSO group. Upon experimental therapy, the cytokine serum values were not different between IgY-treated groups and spontaneously remitted PSO., Conclusions: Using the murine model of psoriatic dermatitis, we show that the orally purified IgY treatment can lead to an improvement in skin lesion healing along with the normalization of cellular and humoral immune parameters.

An increasing number of aerogels as nanostructured highly porous materials are entering the market in every day products, with an attractive portfolio of properties for emerging applications ranging from health care and leisure to electronics, cosmetics, energy, agriculture, food and environmental. However, the novelty in properties and forms of aerogels makes the development of a legislative framework particularly challenging for ensuring the safe development and use of nano-enabled products. The presented safety regulatory Compendium intends to share knowledge with the international aerogels community, as well as end-users and stakeholders, on the regulatory and safe handling procedures, as best safety practices, to be followed during the production process, handling, transport and end-use of aerogel-based formulations to mitigate human and environmental risks considering lack of data availability for this purpose in general.

Dental implant insertion requires the preparation of the implant bed via surgical drilling. During this stage, irrigation is essential to avoid thermal damage to the surrounding bone. Surgical guides enhance the accuracy of the implant site preparation, but they mask the drilling site, hampering coolant delivery. A variety of designs are aimed at improving the coolant access to the target site. Using standard dental implant simulation software, this paper presents an in-house design and 3D printing workflow for building surgical guides that incorporate a coolant channel directed toward the entry point of the burr. The proposed design was evaluated in terms of the bone temperature elevations caused by drilling performed at 1500 rpm, under an axial load of 2 kg, and irrigation with 40 mL/min of saline solution at 25 °C. Temperature measurements were performed on porcine femoral pieces, in the middle of the cortical bone layer, at 1 mm from the edge of the osteotomy. The mean temperature rise was 3.2 °C for a cylindrical sleeve guide, 2.7 °C for a C-shaped open-sleeve guide, and 2.1 °C for the guide with an incorporated coolant channel. According to a one-way ANOVA, the differences between these means were marginally insignificant ( p = 0.056). The individual values of the peak temperature change remained below the bone damage threshold (10 °C) in all cases. Remarkably, the distribution of the recorded temperatures was the narrowest for the guide with internal irrigation, suggesting that, besides the most effective cooling, it provides the most precise control of the intraosseous temperature. Further studies could test different design variants, experimental models (including live animals), and might involve computer simulations of the bone temperature field.

Artificial Intelligence (AI) has emerged as a transformative technology with immense potential in the field of medicine. By leveraging machine learning and deep learning, AI can assist in diagnosis, treatment selection, and patient monitoring, enabling more accurate and efficient healthcare delivery. The widespread implementation of AI in healthcare has the role to revolutionize patients' outcomes and transform the way healthcare is practiced, leading to improved accessibility, affordability, and quality of care. This article explores the diverse applications and reviews the current state of AI adoption in healthcare. It concludes by emphasizing the need for collaboration between physicians and technology experts to harness the full potential of AI.

The production of aerogels for different applications has been widely known, but the use of polysaccharide-based aerogels for pharmaceutical applications, specifically as drug carriers for wound healing, is being recently explored. The main focus of this work is the production and characterization of drug-loaded aerogel capsules through prilling in tandem with supercritical extraction. In particular, drug-loaded particles were produced by a recently developed inverse gelation method through prilling in a coaxial configuration. Particles were loaded with ketoprofen lysinate, which was used as a model drug. The core-shell particles manufactured by prilling were subjected to a supercritical drying process with CO 2 that led to capsules formed by a wide hollow cavity and a tunable thin aerogel layer (40 μm) made of alginate, which presented good textural properties in terms of porosity (89.9% and 95.3%) and a surface area up to 417.0 m 2 /g. Such properties allowed the hollow aerogel particles to absorb a high amount of wound fluid moving very quickly (less than 30 s) into a conformable hydrogel in the wound cavity, prolonging drug release (till 72 h) due to the in situ formed hydrogel that acted as a barrier to drug diffusion.

Air displacement plethysmography (ADP) is a widespread technique for assessing global obesity in both health and disease. The reliability of ADP has been demonstrated by studies focused on duplicate trials. The present study was purported to evaluate learning effects on the reliability of body composition assessment using the BOD POD system, the sole commercially available ADP instrument. To this end, quadruplicate trials were performed on a group of 105 subjects (51 women and 54 men). We estimated measurement error from pairs of consecutive trials-(1,2), (2,3), and (3,4)-to test the hypothesis that early measurements are subject to larger errors. Indeed, statistical analysis revealed that measures of reliability inferred from the first two trials were inferior to those computed for the other pairs of contiguous trials: for percent body fat (%BF), the standard error of measurement (SEM) was 1.04% for pair (1,2), 0.71% for pair (2,3), and 0.66% for pair (3,4); the two-way random effects model intraclass correlation coefficient (ICC) was 0.991 for pair (1,2), and 0.996 for pairs (2,3) and (3,4). Our findings suggest that, at least for novice subjects, the first ADP test should be regarded as a practice trial. When the remaining trials were pooled together, the reliability indices of single ADP tests were the following: ICC = 0.996, SEM = 0.70%, and minimum detectable change (MDC) = 1.93% for %BF, and ICC = 0.999, SEM = 0.49 kg, and MDC = 1.35 kg for fat-free mass (FFM). Thus, the present study pleads for eliminating learning effects to further increase the reliability of ADP.

Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) localized to the cell surface and the tissue extracellular matrix (ECM). It is composed of disaccharides containing glucuronic acid and N-acetylglucosamine, is synthesized by the HA synthase (HAS) enzymes and is degraded by hyaluronidase (HYAL) or reactive oxygen and nitrogen species (ROS/RNS) actions. HA is deposited as a high molecular weight (HMW) polymer and degraded to low molecular weight (LMW) fragments and oligosaccharides. HA affects biological functions by interacting with HA-binding proteins (hyaladherins). HMW HA is anti-inflammatory, immunosuppressive, and antiangiogenic, whereas LMW HA has pro-inflammatory, pro-angiogenetic, and oncogenic effects. ROS/RNS naturally degrade HMW HA, albeit at enhanced levels during tissue injury and inflammatory processes. Thus, the degradation of endothelial glycocalyx HA by increased ROS challenges vascular integrity and can initiate several disease progressions. Conversely, HA exerts a vital role in wound healing through ROS-mediated HA modifications, which affect the innate immune system. The normal turnover of HA protects against matrix rigidification. Insufficient turnover leads to increased tissue rigidity, leading to tissue dysfunction. Both endogenous and exogenous HMW HA have a scavenging capacity against ROS. The interactions of ROS/RNS with HA are more complex than presently perceived and present an important research topic.

For elite athletes, monitoring body composition is important for maximizing performance without health risks. Amplitude (A)-mode ultrasound (AUS) has attracted increasing attention as an alternative to skinfold thickness measurements commonly used for assessing the amount of body fat in athletes. AUS accuracy and precision, however, depend on the formula used to predict body fat percentage (%BF) from subcutaneous fat layer thicknesses. Therefore, this study evaluates the accuracy of the 1-point biceps (B1), 9-sites Parrillo, 3-sites Jackson and Pollock (JP3), and 7-sites Jackson and Pollock (JP7) formulas. Relying on the previous validation of the JP3 formula in college-aged male athletes, we took AUS measurements in 54 professional soccer players (aged 22.9 ± 3.83 y, mean ± SD) and compared the results given by different formulas. The Kruskal-Wallis test indicated significant differences ( p < 10 -6 ), and Conover's post hoc test revealed that the JP3 and JP7 data come from the same distribution, whereas the data given by B1 and P9 differ from all the others. Lin's concordance correlation coefficients for B1 vs. JP7, P9 vs. JP7, and JP3 vs. JP7 were 0.464, 0.341, and 0.909, respectively. The Bland-Altman analysis indicated mean differences of -0.5 %BF between JP3 and JP7, 4.7 %BF between P9 and JP7, and 3.1 %BF between B1 and JP7. This study suggests that JP7 and JP3 are equally valid, whereas P9 and B1 overestimate %BF in athletes.

Langerhans cells (LCs) constitute a cellular immune network across the epidermis. Because they are located at the skin barrier, they are considered immune sentinels of the skin. These antigen-presenting cells are capable of migrating to skin draining lymph nodes to prime adaptive immune cells, namely T- and B-lymphocytes, which will ultimately lead to a broad range of immune responses. Moreover, LCs have been shown to possess important roles in the anti-cancer immune responses. Indeed, the literature nicely highlights the role of LCs in melanoma. In line with this, LCs have been found in melanoma tissues where they contribute to the local immune response. Moreover, the immunogenic properties of LCs render them attractive targets for designing vaccines to treat melanoma and autoimmune diseases. Overall, future studies will help to enlarge the portfolio of immune properties of LCs, and aid the prognosis and development of novel therapeutic approaches to treating skin pathologies, including cancers.

The incidence of melanoma, a very aggressive skin cancer, has increased over the past few decades. Although there are well-established clinical, dermoscopic and histopathological criteria, the diagnosis is often performed late, which has important implications on the patient's clinical outcome. Unfortunately, melanoma is one of the most challenging tumors to diagnose because it is a heterogeneous neoplasm at the clinical, histopathological, and molecular level. The use of reliable biomarkers for the diagnosis and monitoring of disease progression is becoming a standard of care in modern medicine. In this review, we discuss the latest studies, which highlight findings from the genomics, epitranscriptomics, proteomics and metabolomics areas, pointing out different genes, molecules and cells as potential diagnostic and prognostic biomarkers in cutaneous melanoma.

Skin cancer, which includes the most frequent malignant non-melanoma carcinomas (basal cell carcinoma, BCC, and squamous cell carcinoma, SCC), along with the difficult to treat cutaneous melanoma (CM), pose important worldwide issues for the health care system. Despite the improved anti-cancer armamentarium and the latest scientific achievements, many skin cancer patients fail to respond to therapies, due to the remarkable heterogeneity of cutaneous tumors, calling for even more sophisticated biomarker discovery and patient monitoring approaches. Droplet digital polymerase chain reaction (ddPCR), a robust method for detecting and quantifying low-abundance nucleic acids, has recently emerged as a powerful technology for skin cancer analysis in tissue and liquid biopsies (LBs). The ddPCR method, being capable of analyzing various biological samples, has proved to be efficient in studying variations in gene sequences, including copy number variations (CNVs) and point mutations, DNA methylation, circulatory miRNome, and transcriptome dynamics. Moreover, ddPCR can be designed as a dynamic platform for individualized cancer detection and monitoring therapy efficacy. Here, we present the latest scientific studies applying ddPCR in dermato-oncology, highlighting the potential of this technology for skin cancer biomarker discovery and validation in the context of personalized medicine. The benefits and challenges associated with ddPCR implementation in the clinical setting, mainly when analyzing LBs, are also discussed.

Platelet-rich plasma (PRP) represents a novel therapy tested and is used more and more frequently in dermatology and cosmetic surgery for a variety of conditions, including androgenic alopecia (AGA), a common condition with a complex pathogenesis involving genetic factors, hormonal status and inflammation. We performed an extensive literature search which retrieved 15 clinical trials concerning the use in AGA of PRP therapy, alone or in combination, in male, female or mixed patient groups. A quantitative statistical meta-analysis of n = 17 trial groups proved significant increases in hair density from 141.9 ± 108.2 to 177.5 ± 129.7 hairs/cm 2 (mean ± SD) following PRP ( p = 0.0004). To the best of our knowledge, this is the first meta-analysis that proved a statistically significant correlation between the number of PRP treatments per month and the percentage change in hair density ( r = 0.5, p = 0.03), as well as a negative correlation between the mean age of treatment group and the percentage change in hair density ( r = -0.56, p = 0.016). Other factors considered for analysis were the PRP preparation method, amount used per treatment, hair diameter, terminal hairs and pull test. We conclude that PRP represents a valuable and effective therapy for AGA in both males and females if patients are rigorously selected.

Background: Oral squamous cell carcinoma (OSCC) is a common cancer with high morbidity and mortality. Alterations of antitumor immune responses are involved in the development of this malignancy, and investigation of immune changes in the peripheral blood of OSCC patients has aroused the interest of researchers., Methods: In our study, we assessed the proportions of CD3+ total T lymphocytes, CD3+CD4+ helper T lymphocytes, CD3+CD8+ suppressor/cytotoxic T lymphocytes, CD3-CD19+ total B lymphocytes, and CD3-CD16+CD56+ NK cells in the peripheral blood of OSCC patients., Results: The data obtained both pre- and post-therapy showed a similar level of total CD3+ T lymphocytes in OSCC patients and control subjects, pinpointing the stability of this immune parameter. On the other hand, pre-therapeutic data showed a lower proportion of helper T lymphocytes (CD4+), a significantly higher level of cytotoxic/suppressive T lymphocytes (CD8+), and a much lower CD4+ T lymphocyte/CD8+ T lymphocyte ratio compared to control subjects. Conversely, evaluation of circulating NK (CD16+) cells showed a markedly higher pre-therapeutic level compared to the control group., Conclusions: Our results related to immune changes in the peripheral blood add new information to this complex universe of connections between immuno-inflammatory processes and carcinogenesis.

The by-product resulting from the production of the sea-buckthorn ( Hippophae rhamnoides ) juice may be a functional food ingredient, being a valuable source of bioactive compounds, such as polyphenols, flavonoids, minerals, and fatty acids. For checking this hypothesis, two extracts were obtained by two different methods using 50% ethyl alcohol solvent, namely through maceration-recirculation (E-SBM) and through ultrasound extraction (E-SBUS), followed by concentration. Next, sea-buckthorn waste (SB sample), extracts (E-SBM and E-SBUS samples) and the residues obtained from the extractions (R-SBM and R-SBUS samples) were characterized for the total polyphenols, flavonoid content, antioxidant capacity, mineral contents, and fatty acids profile. The results show that polyphenols and flavonoids were extracted better by the ultrasound process than the other methods. Additionally, the antioxidant activity of the E-SBUS sample was 91% higher (expressed in Trolox equivalents) and approximately 45% higher (expressed in Fe 2+ equivalents) than that of the E-SBM sample. Regarding the extraction of minerals, it was found that both concentrated extracts had almost 25% of the RDI value of K and Mg, and also that the content of Zn, Mn, and Fe is significant. Additionally, it was found that the residues (R-SBM and R-SBUS) contain important quantities of Zn, Cu, Mn, Ca, and Fe. The general conclusion is that using the ultrasound extraction method, followed by a process of concentrating the extract, a superior recovery of sea-buckthorn by-product resulting from the juice extraction can be achieved.

The impact of dietary phytoestrogens on human health has been a topic of continuous debate since their discovery. Nowadays, based on their presumptive beneficial effects, the amount of phytoestrogens consumed in the daily diet has increased considerably worldwide. Thus, there is a growing need for scientific data regarding their mode of action in the human body. Recently, new insights of phytoestrogens' bioavailability and metabolism have demonstrated an inter-and intra-population heterogeneity of final metabolites' production. In addition, the phytoestrogens may have the ability to modulate epigenetic mechanisms that control gene expression. This review highlights the complexity and particularity of the metabolism of each class of phytoestrogens, pointing out the diversity of their bioactive gut metabolites. Futhermore, it presents emerging scientific data which suggest that, among well-known genistein and resveratrol, other phytoestrogens and their gut metabolites can act as epigenetic modulators with a possible impact on human health. The interconnection of dietary phytoestrogens' consumption with gut microbiota composition, epigenome and related preventive mechanisms is discussed. The current challenges and future perspectives in designing relevant research directions to explore the potential health benefits of dietary phytoestrogens are also explored.

Epigenetic alterations have emerged as essential contributors in the pathogenesis of various human diseases, including cutaneous melanoma (CM). Unlike genetic changes, epigenetic modifications are highly dynamic and reversible and thus easy to regulate. Here, we present a comprehensive review of the latest research findings on the role of genetic and epigenetic alterations in CM initiation and development. We believe that a better understanding of how aberrant DNA methylation and histone modifications, along with other molecular processes, affect the genesis and clinical behavior of CM can provide the clinical management of this disease a wide range of diagnostic and prognostic biomarkers, as well as potential therapeutic targets that can be used to prevent or abrogate drug resistance. We will also approach the modalities by which these epigenetic alterations can be used to customize the therapeutic algorithms in CM, the current status of epi-therapies, and the preliminary results of epigenetic and traditional combinatorial pharmacological approaches in this fatal disease.

Psoriasis has a multifactorial pathogenesis and recently it was shown that alterations in the skin and intestinal microbiome are involved in the pathogenesis of psoriasis. Therefore, microbiome restoration becomes a promising preventive/therapy strategy in psoriasis. In our pre-clinical study design using a mice model of induced psoriatic dermatitis (Ps) we have tested the proof-of-concept that IgY raised against pathological human bacteria resistant to antibiotics can alleviate psoriatic lesions and restore deregulated immune cell parameters. Besides clinical evaluation of the mice and histology of the developed psoriatic lesions, cellular immune parameters were monitored. Immune cells populations/subpopulations from peripheral blood and spleen cell suspensions that follow the clinical improvement were assessed using flow cytometry. We have quantified T lymphocytes (CD3ε + ) with T-helper (CD4 + CD8 - ) and T-suppressor/cytotoxic (CD8a + CD4 - ) subsets, B lymphocytes (CD3ε - CD19 + ) and NK cells (CD3ε - NK1.1 + ). Improved clinical evolution of the induced Ps along with the restoration of immune cells parameters were obtained when orally IgY was administered. We pin-point that IgY specific compound can be used as a possible pre-biotic-like alternative adjuvant in psoriasis.

The present review discusses recent data regarding rodent models of spinal cord and peripheral nerve injuries in terms of gait analysis using the CatWalk system (CW), an automated and exceptionally reliable system for assessing gait abnormalities and motor coordination. CW is a good tool for both studying improvements in the walking of animals after suffering a peripheral nerve and spinal cord lesion and to select the best therapies and procedures after tissue destruction, given that it provides objective and quantifiable data. Most studies using CW for gait analysis that were published in recent years focus on injuries inflicted in the peripheral nerve, spinal cord, and brain. CW has been used in the assessment of rodent motor function through high-resolution videos, whereby specialized software was used to measure several aspects of the animal's gait, and the main characteristics of the automated system are presented here. CW was developed to assess footfall and gait changes, and it can calculate many parameters based on footprints and time. However, given the multitude of parameters, it is necessary to evaluate which are the most important under the employed experimental circumstances. By selecting appropriate animal models and evaluating peripheral nerve and spinal cord lesion regeneration using standardized methods, suggestions for new therapies can be provided, which represents the translation of this methodology into clinical application.

Basal cell carcinoma (BCC) is the most common malignant skin tumor. BCC displays a different behavior compared with other neoplasms, has a slow evolution, and metastasizes very rarely, but sometimes it causes an important local destruction. Chronic ultraviolet exposure along with genetic factors are the most important risk factors involved in BCC development. Mutations in the PTCH1 gene are associated with Gorlin syndrome, an autosomal dominant disorder characterized by the occurrence of multiple BCCs, but are also the most frequent mutations observed in sporadic BCCs. PTCH1 encodes for PTCH1 protein, the most important negative regulator of the Hedgehog (Hh) pathway. There are numerous studies confirming Hh pathway involvement in BCC pathogenesis. Although Hh pathway has been intensively investigated, it remains incompletely elucidated. Recent studies on BCC tumorigenesis have shown that in addition to Hh pathway, there are other signaling pathways involved in BCC development. In this review, we present recent advances in BCC carcinogenesis.

Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provoking hemorrhagic stroke. Genetic variants are linked to increased risk for stroke in cocaine abuse. The fact that case reports on cannabis-induced stroke usually refer to the young population is very alarming., Competing Interests: The authors declare no conflict of interest.