Elucidation and Pharmacologic Targeting of Master Regulator Dependencies in Coexisting Diffuse Midline Glioma Subpopulations.

Diffuse Midline Gliomas (DMGs) are universally fatal, primarily pediatric malignancies affecting the midline structures of the central nervous system. Despite decades of clinical trials, treatment remains limited to palliative radiation therapy. A major challenge is the coexistence of molecularly distinct malignant cell states with potentially orthogonal drug sensitivities. To address this challenge, we leveraged established network-based methodologies to elucidate Master Regulator (MR) proteins representing mechanistic, non-oncogene dependencies of seven coexisting subpopulations identified by single-cell analysis-whose enrichment in essential genes was validated by pooled CRISPR/Cas9 screens. Perturbational profiles of 372 clinically relevant drugs helped identify those able to invert the activity of subpopulation-specific MRs for follow-up in vivo validation. While individual drugs predicted to target individual subpopulations-including avapritinib, larotrectinib, and ruxolitinib-produced only modest tumor growth reduction in orthotopic models, systemic co-administration induced significant survival extension, making this approach a valuable contribution to the rational design of combination therapy.

Coated Cotton Fabrics with Antibacterial and Anti-Inflammatory Silica Nanoparticles for Improving Wound Healing.

Herein, we report the preparation of bifunctional silica nanoparticles by covalent attachment of both an anti-inflammatory drug (ibuprofen) and an antibiotic (levofloxacin or norfloxacin) through amide groups. We also describe the coating of cotton fabrics with silica nanoparticles containing both ibuprofen and norfloxacin moieties linked by amide groups by using a one-step coating procedure under ultrasonic conditions. The functionalized nanoparticles and cotton fabrics have been characterized using spectroscopic and microscopic techniques. The functionalized nanoparticles and textiles have been treated with model proteases for the in situ release of the drugs by the amide bond enzymatic cleavage. Topical dermal applications in medical bandages are expected, which favor wound healing.

Comparación indirecta ajustada de zanubrutinib e ibrutinib en el tratamiento de primera línea de la leucemia linfocítica crónica / Adjusted indirect comparison of zanubrutinib and ibrutinib in first-line treatment of chronic lymphocytic leukemia

Objetivo el objetivo del presente trabajo fue realizar una comparación indirecta ajustada, según el perfil citogenético, en términos de eficacia, entre los distintos inhibidores de la tirosin cinasa de bruton empleados como monoterapia en primera línea para la leucemia linfocítica crónica. Asimismo, se evaluaron los resultados de seguridad considerados de interés para establecer si dichas opciones pueden ser consideras alternativas terapéuticas equivalentes. Método con fecha 10 de noviembre del 2022, se llevó a cabo una búsqueda bibliográfica en las bases de datos de Pubmed y Embase de ensayos clínicos fase III que estudiaran los inhibidores de la tirosin cinasa de Bruton en monoterapia en contexto de primera línea para la leucemia linfocítica crónica. Se incluyeron ensayos en los que se empleara la combinación de bendamustina y rituximab como comparador y que presentaran poblaciones y tiempos de seguimiento semejantes. Se combinaron mediante metaanálisis los resultados de los subgrupos según las características mutacionales clasificando a los pacientes en alto y bajo riesgo citogenético. Se desarrolló una comparación indirecta ajustada utilizando el método de Bucher. Se determinó la posible equivalencia terapéutica aplicando para ello la guía de alternativas terapéuticas equivalentes. Resultado de los 39 estudios obtenidos en la revisión, se seleccionaron 2 ensayos clínicos: uno para zanubrutinib y otro para ibrutinib. El resto de estudios no se incluyeron por incumplimiento de los criterios de inclusión. Los resultados obtenidos en la comparación indirecta ajustada para ambos subgrupos de riesgo citogenético no mostraron diferencias estadísticamente significativas. En cuanto a la seguridad, las diferencias más relevantes se encontraron en la incidencia de fibrilación auricular, hipertensión arterial y eventos cardiovasculares en los pacientes tratados con ibrutinib, y mayor incidencia de cánceres secundarios en los pacientes tratados con zanubrutinib (AU)

Objective The aim of this study was to perform an adjusted indirect treatment comparison, according to the cytogenetic profile, in terms of efficacy between different Bruton tyrosine kinase inhibitors used as first-line monotherapy for chronic lymphocytic leukemia. Safety outcomes considered of interest were also evaluated to establish whether these options can be considered equivalent therapeutic alternatives. Method A literature search was conducted in Pubmed and Embase on 10 November 2022 for phase III clinical trials studying Bruton's tyrosine kinase inhibitors in monotherapy in the first-line setting for CLL. Results were filtered according to whether the combination of bendamustine and rituximab was used as comparator and whether they had similar populations and follow-up times. Subgroup results were meta-analyzed according to mutational characteristics by classifying patients into high and low cytogenetic risk. An adjusted indirect comparison was developed using Bucher's method. Possible therapeutic equivalence was determined by applying the guide to equivalent therapeutic alternatives. Result Of the 39 studies obtained in the review, two clinical trials were selected: one for zanubrutinib and one for ibrutinib. The remaining studies were not included because they did not meet the inclusion criteria. The results obtained in the adjusted indirect treatment comparison for both cytogenetic risk subgroups showed no statistically significant differences. The most relevant safety differences were auricular fibrillation, hypertension and cardiovascular events in patients treated with ibrutinib and higher incidence of secondary cancers in patients treated with zanubrutinib. Applying the ATE guideline criteria, both treatments cannot be considered equivalent therapeutic alternatives (AU)

Adjusted indirect comparison of zanubrutinib and ibrutinib in first-line treatment of chronic lymphocytic leukemia. / Comparación indirecta ajustada de zanubrutinib e ibrutinib en el tratamiento de primera línea de la leucemia linfocítica crónica.

OBJECTIVE: The aim of this study was to perform an adjusted indirect treatment comparison, according to the cytogenetic profile, in terms of efficacy between different Bruton tyrosine kinase inhibitors used as first-line monotherapy for chronic lymphocytic leukemia. Safety outcomes considered of interest were also evaluated to establish whether these options can be considered equivalent therapeutic alternatives. METHOD: A literature search was conducted in Pubmed and Embase on 10 November 2022 for phase III clinical trials studying Bruton's tyrosine kinase inhibitors in monotherapy in the first-line setting for CLL. Results were filtered according to whether the combination of bendamustine and rituximab was used as comparator and whether they had similar populations and follow-up times. Subgroup results were meta-analyzed according to mutational characteristics by classifying patients into high and low cytogenetic risk. An adjusted indirect comparison was developed using Bucher's method. Possible therapeutic equivalence was determined by applying the guide to equivalent therapeutic alternatives. RESULT: Of the 39 studies obtained in the review, two clinical trials were selected: one for zanubrutinib and one for ibrutinib. The remaining studies were not included because they did not meet the inclusion criteria. The results obtained in the adjusted indirect treatment comparison for both cytogenetic risk subgroups showed no statistically significant differences. The most relevant safety differences were auricular fibrillation, hypertension and cardiovascular events in patients treated with ibrutinib and higher incidence of secondary cancers in patients treated with zanubrutinib. Applying the ATE guideline criteria, both treatments cannot be considered equivalent therapeutic alternatives. CONCLUSIONS: Assuming the uncertainty associated with the adjusted indirect comparison, zanubrutinib could be considered equivalent in efficacy to ibrutinib, however, the presence of differentiating safety features precludes assigning the two alternatives as equivalent therapeutic alternatives.

[Translated article] Adjusted indirect comparison of zanubrutinib and ibrutinib in first-line treatment of chronic lymphocytic leukemia.

OBJECTIVE: The aim of this study was to perform an adjusted indirect treatment comparison, according to the cytogenetic profile, in terms of efficacy between different Bruton tyrosine kinase inhibitors used as first-line monotherapy for chronic lymphocytic leukemia. Safety outcomes considered of interest were also evaluated to establish whether these options can be considered equivalent therapeutic alternatives. METHOD: A literature search was conducted in Pubmed and Embase on November 10, 2022 for phase III clinical trials studying Bruton tyrosine kinase inhibitors in monotherapy in the first-line setting for chronic lymphocytic leukemia. Results were filtered according to whether the combination of bendamustine and rituximab was used as comparator and whether they had similar populations and follow-up times. Subgroup results were meta-analyzed according to mutational characteristics by classifying patients into high and low cytogenetic risk. An adjusted indirect comparison was developed using Bucher's method. Possible therapeutic equivalence was determined by applying the guide to equivalent therapeutic alternatives. RESULT: Of the 39 studies obtained in the review, 2 clinical trials were selected: 1 for zanubrutinib and 1 for ibrutinib. The remaining studies were not included because they did not meet the inclusion criteria. The results obtained in the adjusted indirect treatment comparison for both cytogenetic risk subgroups showed no statistically significant differences. The most relevant safety differences were atrial fibrillation, hypertension, and cardiovascular events in patients treated with ibrutinib and higher incidence of secondary cancers in patients treated with zanubrutinib. Applying the equivalent therapeutic alternatives guideline criteria, both treatments cannot be considered equivalent therapeutic alternatives. CONCLUSIONS: Assuming the uncertainty associated with the adjusted indirect comparison, zanubrutinib could be considered equivalent in efficacy to ibrutinib, however, the presence of differentiating safety features precludes assigning the 2 alternatives as equivalent therapeutic alternatives.

Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators.

Due to their immunosuppressive role, tumor-infiltrating regulatory T cells (TI-Tregs) represent attractive immuno-oncology targets. Analysis of TI vs. peripheral Tregs (P-Tregs) from 36 patients, across four malignancies, identified 17 candidate master regulators (MRs) as mechanistic determinants of TI-Treg transcriptional state. Pooled CRISPR-Cas9 screening in vivo, using a chimeric hematopoietic stem cell transplant model, confirmed the essentiality of eight MRs in TI-Treg recruitment and/or retention without affecting other T cell subtypes, and targeting one of the most significant MRs (Trps1) by CRISPR KO significantly reduced ectopic tumor growth. Analysis of drugs capable of inverting TI-Treg MR activity identified low-dose gemcitabine as the top prediction. Indeed, gemcitabine treatment inhibited tumor growth in immunocompetent but not immunocompromised allografts, increased anti-PD-1 efficacy, and depleted MR-expressing TI-Tregs in vivo. This study provides key insight into Treg signaling, specifically in the context of cancer, and a generalizable strategy to systematically elucidate and target MR proteins in immunosuppressive subpopulations.

Bronchoscopy in Critically Ill COVID-19 Patients: Findings, Microbiological Profile, and Coinfection.

BACKGROUND: Bronchoscopy is a widely use technique in critically ill patients. Nosocomial coinfections are a cause of morbidity and mortality in intensive care units. OBJECTIVES: Our aim was to describe bronchoscopy findings and analyze microbiological profile and probably coinfection through bronchial aspirate (BA) samples in patients with coronavirus disease 2019 pneumonia requiring intensive care unit admission. METHODS: Retrospective observational study analyzing the BA samples collected from intubated patients with coronavirus disease 2019 in a referral Hospital (Spain). RESULTS: One hundred fifty-five consecutive BA samples were collected from 75 patients. Ninety (58%) were positive cultures for different microorganisms, 11 (7.1%) were polymicrobial, and 37 (23.7%) contained resistant microorganisms. There was a statistically significant association between increased days of orotracheal intubation and positive BA (18.9 vs. 10.9 d, P<0.01), polymicrobial infection (22.11 vs. 13.54, P<0.01) and isolation of resistant microorganisms (18.88 vs. 10.94, P<0.01). In 88% of the cases a new antibiotic or change in antibiotic treatment was made. CONCLUSION: Bronchoscopy in critically ill patient was safe and could be useful to manage these patients and conduct the microbiological study, that seems to be higher and different than in nonepidemic periods. The longer the intubation period, the greater the probability of coinfection, isolation of resistant microorganisms and polymicrobial infection.

Intento de suicidio con metanfetamina endovenosa y chemsex / Attempted Suicide with Intravenous Methamphetamine and Chemsex

RESUMEN Introducción: El trastorno de déficit de atención e hiperactividad no diagnosticado es una condición comórbida frecuente en los trastornos por abuso de sustancias, y tiene un importante impacto en la vida de los pacientes, pues incrementa el riesgo de abuso de sustancias y el riesgo derivado de conductas impulsivas. En el momento actual no existen trabajos que estudien la relación entre el TDAH y el fenómeno emergente del chemsex, es decir, el uso de sustancias psicoactivas en el contexto de fiestas sexuales para maximizar el tiempo de práctica sexual y de las experiencias subjetivas. En estas sesiones se usan diferentes sustancias como, por ejemplo, las catinonas sintéticas como la mefedrona, que podría inducir complicaciones médicas y psiquiátricas como psicosis, agresividad e ideación suicida. Caso: Un varón de 44 arios ingresó en la unidad de agudos de psiquiatría tras un segundo intento de suicidio de alto riesgo con el uso de metanfetamina endovenosa mezclada con un ácido queratolítico, en el contexto de un episodio depresivo y práctica activa de sesiones de chemsex con una frecuencia semanal, en las que tomaba mefedrona vía transrectal, que provoca episodios puntuales de psicosis tóxica autolimatada. Se objetivó clínica compatible con TDAH no diagnosticado, y se aplicaron ASRS-V1.1 y WURS, que indicaron TDAH. Se ajustó el tratamiento antidepresivo y remitieron los síntomas depresivos y la ideación autolítica. Discusión: La búsqueda de síntomas de TDAH «ocultos¼ en el contexto del abuso de sustancias es importante para no retrasar diagnósticos con importancia esencial y prevenir complicaciones. Complicaciones médicas y psiquiátricas relacionadas con la práctica del chemsex se han comunicado en Europa y recientemente en España, donde es un fenómeno emergente que preocupa. Se describen el intento de suicidio con metanfetamina, síntomas depresivos y psicóticos, abuso de sustancias y complicaciones médicas.

ABSTRACT Background: Undiagnosed attention deficit and hyperactivity disorder (ADHD) is frequent in the substance abuse disorder population, and has an intense repercussion in the daily life of the patients. That condition increases the risk of substance abuse disorders and risk conducts derived from impulsivity. There are not yet studies linking ADHD and the new emergent phenomenon of chemsex, that is, the action of use the intravenous injection of substances in sex parties, with the objective of maximising the practising time and sexual experience. In these sessions, different types of drug are used, for example, synthetic cathinone or mephedrone, and may lead to diverse medical and psychiatric complications like psychosis, aggressiveness and suicide ideation. Case: We report the case of a 44-year-old man admitted into a psychiatric unit, presenting with 2nd time suicidal high risk attempt using intravenous methamphetamine and a dissolvent acid in the context of a depressive episode, after practising chemsex sessions almost every weekend with psychoactive substances taken orally, intravenously and intrarectally. The patient also presented psychotic symptoms from the use of these drugs. When we interviewed the patient during his hospital stay, we observed that there were symptoms of a possible attention and hyperactivity deficit, which was confirmed by study with ASRS-V1.1 and WURS scales. After three weeks, the patient improved substantially as his depressive symptoms and autolytic ideation disappeared. Discussion: Look for "hidden" symptoms in substance abuse disorder patients. It is impor-tant not to delay important diagnostic tests and to prevent complications. Psychiatric and medical conditions related to chemsex have been reported in several European cities, and recently in Spain where it is an emergent phenomenon and a problem concerning medical and political institutions. The suicide attempt with metamphetamine and acid taken intravenously in the case we report, depressive and psychotic symptoms, addiction, suicide attempts and medical complications are described.

Attempted suicide with intravenous methamphetamine and chemsex.

BACKGROUND: Undiagnosed attention deficit and hyperactivity disorder (ADHD) is frequent in the substance abuse disorder population, and has an intense repercussion in the daily life of the patients. That condition increases the risk of substance abuse disorders and risk conducts derived from impulsivity. There are not yet studies linking ADHD and the new emergent phenomenon of chemsex, that is, the action of use the intravenous injection of substances in sex parties, with the objective of maximising the practising time and sexual experience. In these sessions, different types of drug are used, for example, synthetic cathinone or mephedrone, and may lead to diverse medical and psychiatric complications like psychosis, aggressiveness and suicide ideation. CASE: We report the case of a 44-year-old man admitted into a psychiatric unit, presenting with 2nd time suicidal high risk attempt using intravenous methamphetamine and a dissolvent acid in the context of a depressive episode, after practising chemsex sessions almost every weekend with psychoactive substances taken orally, intravenously and intrarectally. The patient also presented psychotic symptoms from the use of these drugs. When we interviewed the patient during his hospital stay, we observed that there were symptoms of a possible attention and hyperactivity deficit, which was confirmed by study with ASRS-V1.1 and WURS scales. After three weeks, the patient improved substantially as his depressive symptoms and autolytic ideation disappeared. DISCUSSION: Look for "hidden" symptoms in substance abuse disorder patients. It is important not to delay important diagnostic tests and to prevent complications. Psychiatric and medical conditions related to chemsex have been reported in several European cities, and recently in Spain where it is an emergent phenomenon and a problem concerning medical and political institutions. The suicide attempt with metamphetamine and acid taken intravenously in the case we report, depressive and psychotic symptoms, addiction, suicide attempts and medical complications are described.

Recent Advances in Alkaline Exchange Membrane Water Electrolysis and Electrode Manufacturing.

Water electrolysis to obtain hydrogen in combination with intermittent renewable energy resources is an emerging sustainable alternative to fossil fuels. Among the available electrolyzer technologies, anion exchange membrane water electrolysis (AEMWE) has been paid much attention because of its advantageous behavior compared to other more traditional approaches such as solid oxide electrolyzer cells, and alkaline or proton exchange membrane water electrolyzers. Recently, very promising results have been obtained in the AEMWE technology. This review paper is focused on recent advances in membrane electrode assembly components, paying particular attention to the preparation methods for catalyst coated on gas diffusion layers, which has not been previously reported in the literature for this type of electrolyzers. The most successful methodologies utilized for the preparation of catalysts, including co-precipitation, electrodeposition, sol-gel, hydrothermal, chemical vapor deposition, atomic layer deposition, ion beam sputtering, and magnetron sputtering deposition techniques, have been detailed. Besides a description of these procedures, in this review, we also present a critical appraisal of the efficiency of the water electrolysis carried out with cells fitted with electrodes prepared with these procedures. Based on this analysis, a critical comparison of cell performance is carried out, and future prospects and expected developments of the AEMWE are discussed.

The ultrastructure of infectious L-type bovine spongiform encephalopathy prions constrains molecular models.

Bovine spongiform encephalopathy (BSE) is a prion disease of cattle that is caused by the misfolding of the cellular prion protein (PrPC) into an infectious conformation (PrPSc). PrPC is a predominantly α-helical membrane protein that misfolds into a ß-sheet rich, infectious state, which has a high propensity to self-assemble into amyloid fibrils. Three strains of BSE prions can cause prion disease in cattle, including classical BSE (C-type) and two atypical strains, named L-type and H-type BSE. To date, there is no detailed information available about the structure of any of the infectious BSE prion strains. In this study, we purified L-type BSE prions from transgenic mouse brains and investigated their biochemical and ultrastructural characteristics using electron microscopy, image processing, and immunogold labeling techniques. By using phosphotungstate anions (PTA) to precipitate PrPSc combined with sucrose gradient centrifugation, a high yield of proteinase K-resistant BSE amyloid fibrils was obtained. A morphological examination using electron microscopy, two-dimensional class averages, and three-dimensional reconstructions revealed two structural classes of L-type BSE amyloid fibrils; fibrils that consisted of two protofilaments with a central gap and an average width of 22.5 nm and one-protofilament fibrils that were 10.6 nm wide. The one-protofilament fibrils were found to be more abundant compared to the thicker two-protofilament fibrils. Both fibrillar assemblies were successfully decorated with monoclonal antibodies against N- and C-terminal epitopes of PrP using immunogold-labeling techniques, confirming the presence of polypeptides that span residues 100-110 to 227-237. The fact that the one-protofilament fibrils contain both N- and C-terminal PrP epitopes constrains molecular models for the structure of the infectious conformer in favour of a compact four-rung ß-solenoid fold.

Racing to immunity: Journey to a COVID-19 vaccine and lessons for the future.

SARS-CoV-2 is the novel coronavirus behind the COVID-19 pandemic. Since its emergence, the global scientific community has mobilized to study this virus, and an overwhelming effort to identify COVID-19 treatments is currently ongoing for a variety of therapeutics and prophylactics. To better understand these efforts, we compiled a list of all COVID-19 vaccines undergoing preclinical and clinical testing using the WHO and ClinicalTrials.gov database, with details surrounding trial design and location. The most advanced vaccines are discussed in more detail, with a focus on their technology, advantages and disadvantages, as well as any available recent clinical findings. We also cover some of the primary challenges, safety concerns and public responses to COVID-19 vaccine trials, and consider what this can mean for the future. By compiling this information, we aim to facilitate a more thorough understanding of the extensive COVID-19 clinical testing vaccine landscape as it unfolds, and better highlight some of the complexities and challenges being faced by the joint effort of the scientific community in finding a prophylactic against COVID-19.

Epithelial TLR4 Signaling Activates DUOX2 to Induce Microbiota-Driven Tumorigenesis.

BACKGROUND & AIMS: Chronic colonic inflammation leads to dysplasia and cancer in patients with inflammatory bowel disease. We have described the critical role of innate immune signaling via Toll-like receptor 4 (TLR4) in the pathogenesis of dysplasia and cancer. In the current study, we interrogate the intersection of TLR4 signaling, epithelial redox activity, and the microbiota in colitis-associated neoplasia. METHODS: Inflammatory bowel disease and colorectal cancer data sets were analyzed for expression of TLR4, dual oxidase 2 (DUOX2), and NADPH oxidase 1 (NOX1). Epithelial production of hydrogen peroxide (H2O2) was analyzed in murine colonic epithelial cells and colonoid cultures. Colorectal cancer models were carried out in villin-TLR4 mice, carrying a constitutively active form of TLR4, their littermates, and villin-TLR4 mice backcrossed to DUOXA-knockout mice. The role of the TLR4-shaped microbiota in tumor development was tested in wild-type germ-free mice. RESULTS: Activation of epithelial TLR4 was associated with up-regulation of DUOX2 and NOX1 in inflammatory bowel disease and colorectal cancer. DUOX2 was exquisitely dependent on TLR4 signaling and mediated the production of epithelial H2O2. Epithelial H2O2 was significantly increased in villin-TLR4 mice; TLR4-dependent tumorigenesis required the presence of DUOX2 and a microbiota. Mucosa-associated microbiota transferred from villin-TLR4 mice to wild-type germ-free mice caused increased H2O2 production and tumorigenesis. CONCLUSIONS: Increased TLR4 signaling in colitis drives expression of DUOX2 and epithelial production of H2O2. The local milieu imprints the mucosal microbiota and imbues it with pathogenic properties demonstrated by enhanced epithelial reactive oxygen species and increased development of colitis-associated tumors. The inter-relationship between epithelial reactive oxygen species and tumor-promoting microbiota requires a 2-pronged strategy to reduce the risk of dysplasia in colitis patients.

Release of functional fibroblast growth factor-2 from artificial inclusion bodies.

Growth factors are required for cell proliferation and differentiation under physiological conditions but especially in the context of regenerative medicine. The time-prolonged administration of those factors has been explored using different sustained drug delivery systems. These platforms include natural materials such as bacterial inclusion bodies (IBs) that contain chaperones and other bacterial components that might favour protein release. Being successful from a functional point of view, IBs pose regulatory concerns to clinical applications because of the mentioned presence of bacterial cell components, including endotoxins. We have here explored the release and activity of the human fibroblast growth factor-2 (hFGF-2) from a novel synthetic material, namely artificial IBs. Being chemically homogenous and compliant with regulatory restrictions, we wondered if these materials would effectively release functional proteins in absence of accompanying bacterial agents. The data provided here fully supports that artificial hFGF-2 IBs act as true and efficient secretory granules and they slowly disintegrate in cell culture to promote wound healing in an in vitro wound healing model. Free from undesired bacterial components, artificial inclusion bodies show promises as delivery agents in regenerative medicine.

Anti-inflammatory Cotton Fabrics and Silica Nanoparticles with Potential Topical Medical Applications.

The preparation of functional cotton fabrics and silica nanoparticles by direct covalent linking of nonsteroidal anti-inflammatory drugs (salicylic acid, ibuprofen, and diclofenac) through an amide group is reported. Moreover, the coating of cotton fabrics with silica nanoparticles functionalized with such antiinflamatory agents is found to increase the roughness of the surface, providing hydrophobicity to the modified fabrics. This property is enhanced by the addition of fluorinated alkyl silane in the co-condensation process to form the coating solution. Characterization of the functionalized nanoparticles and cotton textiles is accomplished by microscopic and spectroscopic techniques. The treatment of functionalized nanoparticles and cotton fabrics with model proteases and leukocytes from animal origin results in the in situ release of the drug by the selective enzymatic cleavage of the amide bond. Topical cutaneous applications in wound dressings and cream formulations for the acceleration of wound healing are envisaged.

Attempted Suicide with Intravenous Methamphetamine and Chemsex. / Intento de suicidio con metanfetamina endovenosa y chemsex.

BACKGROUND: Undiagnosed attention deficit and hyperactivity disorder (ADHD) is frequent in the substance abuse disorder population, and has an intense repercussion in the daily life of the patients. That condition increases the risk of substance abuse disorders and risk conducts derived from impulsivity. There are not yet studies linking ADHD and the new emergent phenomenon of chemsex, that is, the action of use the intravenous injection of substances in sex parties, with the objective of maximising the practising time and sexual experience. In these sessions, different types of drug are used, for example, synthetic cathinone or mephedrone, and may lead to diverse medical and psychiatric complications like psychosis, aggressiveness and suicide ideation. CASE: We report the case of a 44-year-old man admitted into a psychiatric unit, presenting with 2nd time suicidal high risk attempt using intravenous methamphetamine and a dissolvent acid in the context of a depressive episode, after practising chemsex sessions almost every weekend with psychoactive substances taken orally, intravenously and intrarectally. The patient also presented psychotic symptoms from the use of these drugs. When we interviewed the patient during his hospital stay, we observed that there were symptoms of a possible attention and hyperactivity deficit, which was confirmed by study with ASRS-V1.1 and WURS scales. After three weeks, the patient improved substantially as his depressive symptoms and autolytic ideation disappeared. DISCUSSION: Look for "hidden" symptoms in substance abuse disorder patients. It is important not to delay important diagnostic tests and to prevent complications. Psychiatric and medical conditions related to chemsex have been reported in several European cities, and recently in Spain where it is an emergent phenomenon and a problem concerning medical and political institutions. The suicide attempt with metamphetamine and acid taken intravenously in the case we report, depressive and psychotic symptoms, addiction, suicide attempts and medical complications are described.