Sex differences in metabolic adaptation in infants with cyanotic congenital heart disease.

BACKGROUND: Female infants with congenital heart disease (CHD) face significantly higher postoperative mortality rates after adjusting for cardiac complexity. Sex differences in metabolic adaptation to cardiac stressors may be an early contributor to cardiac dysfunction. In adult diseases, hypoxic/ischemic cardiomyocytes undergo a cardioprotective metabolic shift from oxidative phosphorylation to glycolysis which appears to be regulated in a sexually dimorphic manner. We hypothesize sex differences in cardiac metabolism are present in cyanotic CHD and detectable as early as the infant period. METHODS: RNA sequencing was performed on blood samples (cyanotic CHD cases, n = 11; controls, n = 11) and analyzed using gene set enrichment analysis (GSEA). Global plasma metabolite profiling (UPLC-MS/MS) was performed using a larger representative cohort (cyanotic CHD, n = 27; non-cyanotic CHD, n = 11; unaffected controls, n = 12). RESULTS: Hallmark gene sets in glycolysis, fatty acid metabolism, and oxidative phosphorylation were significantly enriched in cyanotic CHD females compared to male counterparts, which was consistent with metabolomic differences between sexes. Minimal sex differences in metabolic pathways were observed in normoxic patients (both controls and non-cyanotic CHD cases). CONCLUSION: These observations suggest underlying differences in metabolic adaptation to chronic hypoxia between males and females with cyanotic CHD. IMPACT: Children with cyanotic CHD exhibit sex differences in utilization of glycolysis vs. fatty acid oxidation pathways to meet the high-energy demands of the heart in the neonatal period. Transcriptomic and metabolomic results suggest that under hypoxic conditions, males and females undergo metabolic shifts that are sexually dimorphic. These sex differences were not observed in neonates in normoxic conditions (i.e., non-cyanotic CHD and unaffected controls). The involved metabolic pathways are similar to those observed in advanced heart failure, suggesting metabolic adaptations beginning in the neonatal period may contribute to sex differences in infant survival.

Analysis of the Spread and Evolution of COVID-19 Mutations in Ecuador Using Open Data.

Currently, the analyses of and prediction using COVID-19-related data extracted from patient information repositories compiled by hospitals and health organizations are of paramount importance. These efforts significantly contribute to vaccine development and the formulation of contingency techniques, providing essential tools to prevent resurgence and to effectively manage the spread of the disease. In this context, the present research focuses on analyzing the biological information of the SARS-CoV-2 viral gene sequences and the clinical data of COVID-19-affected patients using publicly accessible data from Ecuador. This involves considering variables such as age, gender, and geographical location to understand the evolution of mutations and their distributions across Ecuadorian provinces. The Cross-Industry Standard Process for Data Mining (CRISP-DM) methodology is applied for data analysis. Various data preprocessing and statistical analysis techniques are employed, including Pearson correlation, the chi-square test, and analysis of variance (ANOVA). Statistical diagrams and charts are used to facilitate a better visualization of the results. The results illuminate the genetic diversity of the virus and its correlation with clinical variables, offering a comprehensive understanding of the dynamics of COVID-19 spread in Ecuador. Critical variables influencing population vulnerability are highlighted, and the findings underscore the significance of mutation monitoring and indicate a need for global expansion of the research area.

Kinetic Evaluation of the Production of Mead from a Non-Saccharomyces Strain.

There is a growing market for craft beverages with unique flavors. This study aimed to obtain a palate-pleasing mead derived from Pichia kudriavzevii 4A as a monoculture. Different culture media were evaluated to compare the fermentation kinetics and final products. The crucial factors in the medium were ~200 mg L-1 of yeast assimilable nitrogen and a pH of 3.5-5.0. A panel of judges favored the mead derived from Pichia kudriavzevii 4A (fermented in a medium with honey initially at 23 °Bx) over a commercial sample produced from Saccharomyces cerevisiae, considering its appearance, fruity and floral flavors (provided by esters, aldehydes, and higher alcohols), and balance between sweetness (given by the 82.91 g L-1 of residual sugars) and alcohol. The present mead had an 8.57% v/v ethanol concentration, was elaborated in 28 days, and reached a maximum biomass growth (2.40 g L-1) on the same fermentation day (6) that the minimum level of pH was reached. The biomass growth yield peaked at 24 and 48 h (~0.049 g g-1), while the ethanol yield peaked at 24 h (1.525 ± 0.332 g g-1), in both cases declining thereafter. The Gompertz model adequately describes the kinetics of sugar consumption and the generation of yeast biomass and ethanol. Pathogenic microorganisms, methanol, lead, and arsenic were absent in the mead. Thus, Pichia kudriavzevii 4A produced a safe and quality mead with probable consumer acceptance.

Clinical outcomes in critically ill children on extracorporeal membrane oxygenation with severe thrombocytopenia.

INTRODUCTION: As international guidelines suggest keeping the platelet count between 50 and 100 × 109 cells/L in children on extracorporeal membrane oxygenation (ECMO), platelet transfusions are administered to two-thirds of ECMO days, and up to 70% of these patients still bleed. We aim to describe outcomes in critically ill children who develop severe thrombocytopenia on ECMO. METHODS: Single-center retrospective study, enrolling critically ill children on ECMO admitted at Children's Memorial Hermann, TX, between 1/2018 and 12/2022, with at least one platelet count below 50 × 109 cells/L (severe thrombocytopenia). Platelet counts were measured four times a day. We report platelet transfusion, bleeding, hemolysis, and clotting events within 6 h after transfusion, as well as ECMO duration and mortality. RESULTS: We enrolled 54 patients representing 337 ECMO days and 1190 platelet counts. Median weight was 3.7 kg and 54% were male. Severe thrombocytopenia was observed in 56% of platelet counts. Severe thrombocytopenia was not associated with bleeding in the subsequent 6 h (18% vs 20%, p = .95), but was associated with more frequent platelet transfusions (18% vs 11%, p = .001). There was no correlation between time spent with severe thrombocytopenia and the duration of ECMO (R2 = 0.03). While the time spent with severe thrombocytopenia was not associated with on-ECMO mortality rate (p = .36), there was an association with in-hospital mortality rate (p = .003). CONCLUSIONS: Our results indicate a restrictive platelet transfusion strategy is not associated with higher proportions of subsequent bleeding, duration of ECMO, or on-ECMO mortality rate. Multicenter studies are needed to evaluate further the appropriateness of this strategy.

Novel Image-Guided Percutaneous Lung Tissue Excision Device With Integrated Sealing of Blood Vessels and Airways: An In Vivo Preclinical Study.

OBJECTIVE: This study evaluated the efficacy of the Minimally Invasive Targeted Resection (MiTR) device, a novel electrosurgical instrument that allows for targeted excision of a lung abnormality while using bipolar radiofrequency (RF) energy to seal blood vessels and airways. METHODS: The MiTR system was evaluated in 7 acute and 2 chronic porcine (7-day) models to evaluate the efficacy of tissue excision with bipolar RF sealing of blood vessels and airways and application of an autologous blood patch into the excised tissue cavity. Air leak was recorded for all evaluations. The study was approved by the institutional ethical board. RESULTS: Nineteen lung tissue samples, measuring 2.5 cm long × 1.2 cm diameter, were excised. In 8 of 9 animals (89%), hemostasis and pneumostasis were observed visually at the completion of the procedure. In 2 of 2 chronic animals (100%), hemostasis and pneumostasis persisted for the 7-day observation period. Histologic examination of the excised samples showed preservation of the core parenchymal architecture without evident tissue damage of the samples that would impair pathologic analysis. CONCLUSIONS: Percutaneous resection of targeted lung tissue with the MiTR system demonstrated hemostasis and pneumostasis while obtaining a histologically intact sample. After regulatory approval, the use of this device could offer more tissue for analysis than a transthoracic needle biopsy or bronchoscopy and a far less invasive alternative to video-assisted thoracic surgery or thoracotomy. This may also expand patient and physician options for the early diagnosis and treatment of lung cancer.

Probing the evaporation dynamics of semi-volatile organic compounds to reveal the thermodynamics of liquid-liquid phase separated aerosol.

Liquid-liquid phase separation (LLPS) is a thermodynamically driven process that occurs in mixtures of low miscibility material. LLPS is an important process in chemical, biological, and environmental systems. In atmospheric chemistry, LLPS in aerosol containing internally-mixed organic and inorganic particles has been an area of significant interest, with particles separating to form organic-rich and aqueous phases on dehydration. This alters the optical properties of the particles, has been connected to changes in the cloud nucleation ability of the aerosol, and potentially changes the reactivity of particles towards gas-phase oxidants. Although the chemical systems that undergo LLPS have become quite well-characterized, the properties and processes of LLPS particles are quite poorly understood. In this work, we characterize LLPS in aerosol particles containing ammonium sulfate and triethylene glycol (3EG), a semi-volatile organic molecule. We explore the relative humidity (RH) conditions under which LLPS occurs and characterize the rate of evaporation of 3EG from well-mixed and LLPS particles as a function of RH. We show that the evaporation rates vary with RH due to changes in chemical activity, however no clear change in the dynamics following LLPS are observed. We interpret our observations using a thermodynamic model (AIOMFAC) coupled with an evaporation model and show that a significant increase in the activity coefficient of 3EG as the RH decreases, required for LLPS to occur, obscures a clear step-change in the evaporation rates following LLPS. By characterizing the evaporation rates, we estimate the composition of the organic-rich phase and compare our results to thermodynamic predictions. This study is the first to explore the connection between LLPS and the chemical evolution of aerosol particles via the evaporation of semi-volatile organic material. Ultimately, we reveal that the thermodynamics of non-ideal mixing are primarily responsible for the controlling both the rate of evaporation and the onset of LLPS, with LLPS itself having limited impact on the rate of evaporation in a fluid system. These results have significant implications for understanding and predicting the lifetime of aerosol particles, their effect on cloud formation, and the chemical evolution of multiphase systems by particle-gas partitioning and heterogeneous reactions.

Teachers' teaching and professional competences assessment.

This research is part of a project led by the Catholic University of Santiago de Guayaquil (Ecuador) and the National Distance Education University - UNED (Spain) aiming at designing a teaching/professional competences training model for teachers. The purpose of this study is to assess the meaning of professional competences and their significance within teachers' teaching and training processes. Using the mixed methods approach, an ad hoc questionnaire was designed and given to discussion groups, achieving participation of more than a hundred teachers. Quantitative data analysis was carried out using the Logit model while Atlas ti 23 allowed analysis of the qualitative data. The results evidenced high scores in the competences evaluated, being leadership and research the lowest. In general, the teachers value, preferably, planning, communication, evaluation, methodology, digital, and tutoring competences, with a lower value among teachers ranging from 25 to 30 years old; those older than 55 stressed the importance of digital and innovation competences. Thus, it is recommended that training programs for teachers should focus on the set of related competences, especially on the digital competence, considering the challenges represented by investigation and pedagogical leadership.

New Horizons in Near-Zero Refractive Index Photonics and Hyperbolic Metamaterials.

The engineering of the spatial and temporal properties of both the electric permittivity and the refractive index of materials is at the core of photonics. When vanishing to zero, those two variables provide efficient knobs to control light-matter interactions. This Perspective aims at providing an overview of the state of the art and the challenges in emerging research areas where the use of near-zero refractive index and hyperbolic metamaterials is pivotal, in particular, light and thermal emission, nonlinear optics, sensing applications, and time-varying photonics.

Clinical Characteristics and Outcomes in Adults With Moderate-to-Severe Complexity Congenital Heart Disease Undergoing Palliation or Surgical Repair.

Background: Congenital heart disease (CHD) survival rate has improved dramatically due to advances in diagnostic and therapeutic techniques. However, concerning the unrepaired CHD population of moderate and severe complexity, the data regarding risk predictors and surgical outcomes are scarce. Our aim was to describe the surgical results and predictors of in-hospital outcomes in adult patients with moderate-to-severe complexity CHD that were not repaired in childhood. Methods: We conducted a retrospective cohort study that included 49 adult patients with moderate-to-complex CHD who were treated in a single medical centre. Clinical and echocardiographic variables were obtained on admission, after surgical procedures and during follow-up. Results: Most of the patients were female (66%). Left ventricular ejection fraction and right ventricular outflow tract fractional shortening were within the normal range. The median pulmonary artery systolic pressure was 37 (27-55) mm Hg. The median time was 118 (80-181) minutes for extracorporeal circulation and 76 (49-121) minutes for aortic cross-clamping. The most frequent complication was postoperative complete atrioventricular block (12.2%). In-hospital survival rate was 87.7%. The development of low cardiac output syndrome with predominant right ventricle failure in the postoperative period was the most important predictor of in-hospital death (P = 0.03). Conclusions: Deciding to treat adults with CHD is challenging in moderate and severe unrepaired cases. Adequate clinical, functional, and imaging evaluation is essential to determine each patient's suitability for surgical management and to achieve the best clinical outcome for this population.

Contexte: Grâce aux avancées réalisées en matière de techniques diagnostiques et thérapeutiques, la survie des patients atteints d'une cardiopathie congénitale s'est considérablement améliorée. Cependant, en ce qui concerne les personnes atteintes d'une cardiopathie congénitale non corrigée présentant une complexité modérée ou extrême, les données portant sur les facteurs de risque prédictifs ainsi que sur les résultats chirurgicaux sont rares. Notre objectif était de décrire les résultats chirurgicaux ainsi que les facteurs prédictifs des résultats obtenus en milieu hospitalier chez les patients adultes atteints d'une cardiopathie congénitale présentant une complexité modérée ou extrême qui n'a pas été corrigée pendant l'enfance. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant 49 patients adultes atteints d'une cardiopathie congénitale modérée ou complexe qui ont reçu leurs traitements dans un seul centre médical. Les variables cliniques et échocardiographiques ont été obtenues au moment de l'admission, après les interventions chirurgicales et pendant la période de suivi. Résultats: Les patients étaient en majorité des femmes (66 %). La fraction d'éjection du ventricule gauche ainsi que la fraction de raccourcissement de la voie d'éjection ventriculaire droite sont demeurées dans les limites de la normale. La pression systolique médiane de l'artère pulmonaire a été de 37 mmHg (27-55 mmHg). Le temps médian écoulé pour la circulation extracorporelle a été de 118 minutes (80-181 minutes) et pour le clampage de la crosse aortique, de 76 minutes (49-121 minutes). Le bloc auriculo-ventriculaire postopératoire complet a été la complication la plus fréquente (12,2 %). Le taux de survie en milieu hospitalier a été de 87,7 %. Le développement du syndrome du faible débit cardiaque accompagné d'une insuffisance prédominante du ventricule droit durant la période postopératoire a constitué le principal facteur prédictif de décès à l'hôpital (p = 0,03). Conclusion: Il est difficile de traiter les adultes qui présentent une cardiopathie congénitale modérée ou sévère non corrigée. Il est essentiel que les évaluations cliniques, fonctionnelles et par imagerie soient réalisées de façon adéquate pour déterminer si une prise en charge chirurgicale convient aux patients et pour garantir les meilleurs résultats cliniques chez ces derniers.

Exploration of semen quality analyzed by casa-mot systems of brahman bulls infected with BLV and BHV-1.

Enzootic bovine leukosis virus (BLV) and bovine herpesvirus 1 (BHV-1) are very important infectious agents for the livestock industry worldwide. The present study aimed to explore the association between natural exposure to BLV and BHV-1 with sperm quality analyzed by Computer-Assisted Semen Analysis (CASA) systems. Ten sexually mature Brahman bulls, with sanitary status BLV+/BHV-1+ (n = 2), BLV-/BHV-1+ (n = 6) and BLV-/BHV-1- (n = 2) were evaluated twice, 30 days apart. Results showed that sanitary status of each bull was not associated with semen quality. It was found that the quality of the semen from the second collection was better due to the interruption of sexual rest. The evidence thus revealed that a bull infected with BLV generated good-quality contaminated semen and, therefore, that it is essential to detect contaminated seminal samples to prevent the spread of BLV. A multivariate analysis showed the presence of four sperm subpopulations in Brahman bulls that differ significantly in their kinematic patterns and with respect to sanitary status (P < 0.05), indicating that infection-free and seronegative bulls present the best kinematic parameters, which improved discrimination of sperm quality according to sanitary status. Overall, the analyses indicate that the seropositive-infected bulls with BLV and BHV-1 should be excluded from beef cattle farms.

Cardiac Laterality: Surgical Results of Right Atrial Isomerism.

Right atrial isomerism (RAI) is a complex entity with varying diagnostic and treatment outcomes due to its rarity. Treatment options range from palliative to corrective surgeries, resulting in heterogeneous outcomes. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted, including patients diagnosed with RAI who underwent cardiac surgery. Their follow-up was from 1 January 2010 to 31 March 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients were included, the median age was 4 years (IQR 2-9.2) and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock-Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). We did not find any factors associated with negative outcomes in these patients. The overall survival was 86.8%, with a better outcome in those who did not require reintubation (log rank, p < 0.01). The survival of RAI was similar to other centers. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.

Senning Procedure: Conceptualization in the Wet Lab.

Training congenital heart surgeons today is challenging for themselves and their mentors. The situation becomes even more complicated while teaching complex surgical procedures. Senning operation is one of the most ingenious intracardiac techniques. We consider this surgical technique a worthy example to stand out the potential advantage of wet lab training. This article demonstrates the simulation of the Senning procedure in an explanted porcine model.

Aortic Arch Reconstruction Using Nonvalved Femoral Vein Homograft in High-Risk Neonates.

Aortic arch obstruction is often present with complex concomitant congenital heart defects (CHDs). The use of nonvalved femoral vein homograft (FVH) to reconstruct the aortic arch has distinct surgical advantages, including simplified reconstruction. We present an intraoperative video of a Yasui procedure utilizing FVH for aortic reconstruction in a 12-day-old (2.2 kg) neonate with right ventricular outflow tract obstruction, malalignment ventricular septal defect, aortic valve atresia, aortic arch hypoplasia, atrial septal defect, and ductal dependent systemic circulation. Further, we report outcomes for a series of three additional neonatal patients with complex CHD and aortic arch obstruction who underwent FVH arch reconstruction.

Abordaje terapéutico de cardiopatías congénitas en el síndrome de Down / Congenital heart disease in Down's syndrome

Resumen Antecedentes: El síndrome de Down es la anomalía cromosómica más frecuente y se asocia con defectos cardiacos congénitos, elementos clínicos de una alta morbilidad y mortalidad infantil. Objetivo: Describir los desenlaces clínicos de los pacientes con síndrome de Down sometidos a cirugía e intervencionismo como tratamiento de las cardiopatías congénitas en esta institución. Material y métodos: Estudio retrospectivo que incluyó pacientes menores de 18 años con síndrome de Down y patología cardiaca asociada durante los últimos 10 años. Las variables estudiadas fueron: peso, talla, sexo, edad, tipo de cardiopatía, procedimiento correctivo, tiempo de estancia intrahospitalaria y en unidad de terapia intensiva, morbilidad y mortalidad. Resultados: 368 pacientes pediátricos fueron llevados a corrección quirúrgica o intervencionista, de los cuales 197 (54%) pertenecían al sexo femenino, la mediana de edad fue de 24 meses (rango intercuartílico [RIQ]: 14-48) en el grupo quirúrgico y de 36 meses (RIQ: 17-85) en el intervencionista. Las cardiopatías congénitas más frecuentes fueron: persistencia del conducto arterioso (31%), comunicación interventricular (28%), canal atrioventricular (CAV) (20%), comunicación interauricular (16%) y tetralogía de Fallot con el 4% respectivamente. La estancia hospitalaria fue de 9 días (RIQ: 7-15) en el grupo quirúrgico y de 3 días (RIQ: 2-5) en el hemodinámico. Las morbilidades fueron infección postoperatoria en 30 pacientes (14%) y en 19 pacientes (9%) bloqueo atrioventricular completo. La mortalidad global incluyendo tanto el quirúrgico como el intervencionista fue del 2%. Conclusiones: Los resultados terapéuticos, quirúrgicos e intervencionistas, en los niños con síndrome de Down y cardiopatías congénitas han mejorado en forma muy satisfactoria. Es de destacar la menor prevalencia del CAV en la población mexicana. Es indispensable realizar evaluación cardiológica a los niños con síndrome de Down y aquellos con cardiopatías congénitas llevarlos a corrección de manera oportuna para favorecer la sobrevida y calidad de vida.

Abstract Background: Down syndrome is the most common chromosomal abnormality, it is associated with a wide variety of congenital heart defects, being considered as clinical elements of high infant morbidity and mortality. Objective: To describe the clinical outcomes of patients with Down syndrome undergoing surgery and interventionism as treatment for congenital heart disease at this Institution. Material and methods: 368 patients with Down syndrome and associated congenital heart disease were diagnosed. The variables studied were weight, stature, sex, age, type of heart disease, corrective procedure, length of stay in the hospital and intensive care unit, morbidity and mortality. Results: 368 pediatric patients underwent surgical or interventional correction. Of which 197 (54%) were female, the median age was 24 months (interquartile range [IQR]: 14-48) in the surgical group and 36 months (IQR: 17-85) in the interventional group. The most frequent congenital heart diseases were: PCA (31%), IVC (28%), CAV (20%), ASD (16%) and tetralogy of Fallot with 4% respectively. Hospital stay was 9 days (IQR: 7-15) in the surgical group and 3 days (IQR: 2-5) in the hemodynamic group. Morbidities were postoperative infection in 30 patients (14%) and complete atrioventricular block in 19 patients (9%). Overall mortality including both surgical and interventional was 2%. Conclusions: The therapeutic, surgical and interventional results in children with Down syndrome and congenital heart disease have improved very satisfactorily. The lower prevalence of the atrioventricular canal in the Mexican population is noteworthy. It is essential to carry out a cardiological evaluation of children with Down syndrome and those with congenital heart disease to correct them in a timely manner to promote survival and quality of life.

Pulmonary arterial hypertension in children with congenital heart disease: a deeper look into the role of endothelial progenitor cells and circulating endothelial cells to assess disease severity.

Endothelial progenitor cells and circulating endothelial cells have been proposed as useful markers of severity and disease progression in certain vascular diseases, including pulmonary arterial hypertension. Our study focused on evaluating the levels of circulating endothelial progenitor cells and circulating endothelial cells in patients with congenital left-to-right shunts and pulmonary hypertension undergoing definitive repair. Endothelial progenitor cells (identified by simultaneous co-expression of CD45dim, CD34 + and KDR2 + surface antibodies) and circulating endothelial cells (identified by simultaneous co-expression of inherent antibodies CD45-, CD31+, CD146 + and CD105+) were prospectively measured in seventy-four children (including children with Down syndrome), median age six years (2.75-10), with clinically significant left-to-right shunts undergoing transcatheter or surgical repair and compared to thirty healthy controls. Endothelial progenitor cells and, particularly, circulating endothelial cells were significantly higher in children with heart disease and pulmonary arterial hypertension when compared to controls. Endothelial progenitor cells showed significant correlation with pulmonary vascular resistance index when measured both systemically (r = 0.259; p = 0.026) and in the superior vena cava (r = 0.302; p = 0.009). Children with Down syndrome showed a stronger correlation between systemic cellularity and pulmonary vascular resistance index (r = 0.829; p = 0.002). Endothelial progenitor cells were reduced along their transit through the lung, whereas circulating endothelial cells did not suffer any modification across the pulmonary circulation. In children with yet to be repaired left-to-right shunts, endothelial progenitor cells and circulating endothelial cell counts are increased compared to healthy subjects.

Institutional violence from police militarization and drug cartel wars as a 'Big Event' and its influence on drug use harms and HIV risk in people who inject drugs on the U.S.-Mexico border.

BACKGROUND: Globally, the US-Mexico Border is one of the largest drug trafficking regions, with Ciudad Juarez (CJ) and El Paso (EP) making up the second-largest border crossing in the world. Border communities are places where the risk of drug use harm and infectious diseases such as HIV are augmented due to the confluence of factors operating across the physical, social, economic and policy environment. Although the two cities are economically, culturally, and socially intertwined, each has distinct criminal justice systems and policy practices aimed at curtailing substance use. Between 2008 and 2011, the CJ/EP region experienced an unprecedented level of violence that stemmed from the intersection of police militarization and drug cartel wars, which profoundly shaped every aspect of life. Little research has documented the impact of drug cartel wars on the drug use and health harms of people who inject drugs (PWID) living in CJ and EP. The purpose of the study is to understand the effect that the drug cartel war had on the drug use harms and HIV risk of PWID. METHODS: We conducted 40 in-depth interviews with people who inject drugs who resided in CJ or EP and had used heroin or crack cocaine in the last 30 days, and asked how police militarization and drug cartel war affected their daily lives. The risk environment framework informed the analysis and interpretation of findings. RESULTS: Findings indicated that the risk environment was profoundly altered as PWID residing in CJ experienced profound changes in their daily lives that promoted engagement in behaviors that increased drug use and health harms including HIV risk, exacerbated trauma, and prevented use of substance use treatment and harm reduction services. The risk environment was also altered in EP, where PWID experienced drug supply shortages, violent policing practices, and reduced availability of harm reduction services. Findings underscore the permeability of risk environments across geographical borders. CONCLUSION: The intersection of law enforcement militarization and drug cartel wars can be conceptualized as a 'big event' because it disrupts the drug market economy, leads to drug shortages, promotes entrance into the drug market economy by people who use drugs, reshapes drug use sites, and constrains the provision of harm reduction services. The stability of the harm reduction system in CJ was negatively impacted and limited the ability of individuals to reduce harm. Our findings show that drug cartel wars render the CJ/EP region extremely susceptible to drug use and health harms, while also creating vulnerability by severely restricting its ability to respond. Traditional recommendations to intervene to limit the impact of risk environments on the drug use harms of PWID need to be reconsidered in the context of drug cartel wars.