Illicit Fentanyl Use and Hepatitis C Virus Seroconversion Among People Who Inject Drugs in Tijuana and San Diego: Results From a Binational Cohort Study.

BACKGROUND: Illicitly manufactured fentanyl (IMF) increases overdose mortality, but its role in infectious disease transmission is unknown. We examined whether IMF use predicts hepatitis C virus (HCV) and human immunodeficiency virus (HIV) incidence among a cohort of people who inject drugs (PWID) in San Diego, California and Tijuana, Mexico. METHODS: PWID were recruited during 2020-2022, undergoing semi-annual interviewer-administered surveys and HIV and HCV serological rapid tests through 2024. Cox regression was conducted to examine predictors of seroconversion considering self-reported IMF use as a 6-month lagged, time-dependent covariate. RESULTS: Of 398 PWID at baseline, 67% resided in San Diego, 70% were male, median age was 43 years, 42% reported receptive needle sharing, and 25% reported using IMF. HCV incidence was 14.26 per 100 person-years (95% confidence interval [CI]: 11.49-17.02), and HIV incidence was 1.29 (95% CI: .49-2.10). IMF was associated with HCV seroconversion, with a univariable hazard ratio (HR) of 1.64 (95% CI: 1.09-2.40), and multivariable HR of 1.57 (95% CI: 1.03-2.40). The direction of the relationship with HIV was similar, albeit not significant (HR 2.39; 95% CI: .66-8.64). CONCLUSIONS: We document a novel association between IMF and HCV seroconversion among PWID in Tijuana-San Diego. Few HIV seroconversions (n = 10) precluded our ability to assess if a similar relationship held for HIV. IMF's short half-life may destabilize PWID-increasing the need for repeat dosing and sharing smoking materials and syringes. New preventive care approaches may reduce HCV transmission in the fentanyl era.

Short-term revision rate of Rigicon Testi10TM testicular prosthesis in adolescents and adults: a retrospective chart review.

Testicular prosthesis implantation is a valuable solution for the physical, cosmetic, and psychological challenges associated with testicular loss which may affect males of any age. We evaluated the safety and reliability of the new Rigicon Testi10TM testicular prosthesis in adults and adolescents by performing an IRB-approved retrospective study of data drawn from Patient Information Forms (PIFs). A total of 427 patients (382 adults and 45 adolescents) had at least one testicular prosthesis implanted. Only one adult patient required revision surgery due to rupture of the Rigicon Testi10 TM saline-filled prosthesis. A 40-year-old patient was found to have a leaking prosthesis approximately one week postoperatively, which was suspected to be due to inadvertently punctured by the surgeon during the sterile saline filling process. There were no post-implantation revisions required for adolescent patients. According to our results, Kaplan-Meier calculation of survival from removal or revision was 99.8% for all patients at 54 months (99.7% for adults and 100% for adolescents). The complication rates among patients in this study are lower than those reported in previous published studies. Our study underscores the generally safe nature of testicular prosthesis implantation, as well as the very rare incidence of revision surgery for this new device.

Changes in injecting versus smoking heroin, fentanyl, and methamphetamine among people who inject drugs in San Diego, California, 2020-2023.

BACKGROUND: Amidst an increasingly toxic drug supply in North America, people who inject drugs may be transitioning to smoking them. We aimed to assess changes in injecting and smoking opioids and methamphetamine among a cohort of people who inject drugs from San Diego, California. METHODS: Over five six-month periods spanning October 2020-April 2023, we assessed prevalence of injecting and smoking opioids or methamphetamine and whether participants used these drugs more frequently by smoking than injecting. Multivariable Poisson regression via generalized estimating equations was used to examine time trends. RESULTS: Of 362 participants, median age was 40 years; a minority were female (29%), Hispanic/Latinx/Mexican (45%), and housed (33%). Among this cohort, of whom 100% injected (and 84% injected and smoked) in period one (October 2020-April 2021), by period five (November 2022-April 2023), 34% only smoked, 59% injected and smoked, and 7% only injected. By period five, the adjusted relative risk (aRR) of injecting opioids was 0.41 (95% Confidence Interval [CI]: 0.33, 0.51) and the aRR for injecting methamphetamine was 0.50 (95% CI: 0.39, 0.63) compared to period one. Risks for smoking fentanyl rose significantly during period three (aRR=1.44, 95% CI: 1.06, 1.94), four (aRR=1.65, 95% CI: 1.24, 2.20) and five (aRR=1.90, 95% CI: 1.43, 2.53) compared to period one. Risks for smoking heroin and methamphetamine more frequently than injecting these drugs increased across all periods. CONCLUSIONS: Opioid and methamphetamine injection declined precipitously, with notable increases in smoking these drugs. Research is needed to understand the health consequences of these trends.

Changes in injecting versus smoking heroin, fentanyl, and methamphetamine among people who inject drugs in San Diego, California, 2020 to 2023.

Background: Amidst a rapidly evolving drug supply in North America, people who inject drugs may be transitioning to smoking them. We aimed to assess changes in injecting and smoking heroin, fentanyl and methamphetamine among a cohort of people who injected drugs at baseline from San Diego, California. Methods: Over five six-month periods spanning October 2020-April 2023, we assessed prevalence of injecting and smoking opioids or methamphetamine and whether participants used these drugs more frequently by smoking than injecting. Multivariable Poisson regression via Generalized Estimating Equations was used to examine time trends. Results: Of 362 participants, median age was 40 years; most were male (72%), non-Hispanic (55%), and unhoused (67%). Among this cohort, of whom 100% injected (or injected and smoked) at baseline, by period five (two years later), 34% reported only smoking, while 59% injected and smoked, and 7% only injected. By period five, the adjusted relative risk (aRR) of injecting opioids was 0.41 (95% Confidence Interval [CI]: 0.33, 0.51) compared to period one, and the aRR for injecting methamphetamine was 0.50 (95% CI: 0.39, 0.63). Compared to period one, risks for smoking fentanyl rose significantly during period three (aRR=1.44, 95% CI: 1.06, 1.94), four (aRR=1.65, 95% CI: 1.24, 2.20) and five (aRR=1.90, 95% CI: 1.43, 2.53). Risks for smoking heroin and methamphetamine more frequently than injecting these drugs increased across all periods. Conclusions: Opioid and methamphetamine injection declined precipitously, with notable increases in smoking these drugs. Research is urgently needed to understand the health consequences of these trends.

Traqueostomía abierta en el sistema de salud de Malvinas Argentinas. Nuestra Experiencia / Open tracheostomy in Malvinas Argentinas health system. Our experience

Introducción: la traqueostomía es la abertura y el abocamiento de la tráquea al exterior realizada para lograr una vía aérea controlable y permeable. El abordaje puede ser percutáneo y abierto, bajo anestesia general o local, de forma urgente o programada. Objetivo: describir la técnica quirúrgica realizada habitualmente en el sistema de salud de Malvinas Argentinas y evaluar indicaciones y complicaciones. Materiales y métodos: estudio descriptivo retrospectivo que incluyó pacientes con traqueostomía, mayores de 18 años, sin distinción de sexo, realizada entre enero de 2015 y junio de 2018 en Malvinas Argentinas. Resultados: se operaron 72 pacientes, 11 anestesia local y 61 anestesia general; 15 urgencias y 57 programados. La edad promedio fue 34,7. La técnica utilizada fue abierta con incisión horizontal. Las principales indicaciones: intubación orotraqueal prolongada en 34 pacientes, síndrome obstructivo laríngeo agudo (SOLA) en 25 y destete dificultoso en 6. Las complicaciones más frecuentes: lesiones laringotraqueales en 9 pacientes, infección de herida quirúrgica en 5 y enfisema subcutáneo en 3. Discusión: la técnica abierta no es la única existente en la bibliografía, pero buenos resultados en nuestro servicio afirman su seguridad por mejor reconocimiento de estructuras anatómicas y abocamiento de la tráquea. No es posible concluir cuál técnica es superior con respecto a morbimortalidad. Existen diferencias en el lugar donde se realiza, y puede hacerse en quirófano o junto a la cama del paciente con adecuada asepsia. Conclusión: en la actualidad sigue siendo la técnica de elección para la realización de este procedimiento en nuestro servicio.

Introduction: Tracheostomy is the opening and entrance of the trachea to the outside carried out to achieve a controllable and patent airway. The approach can be percuta-neous and open, under general or local anesthesia, urgently or scheduled. Objective:Describe the surgical technique usually performed in Malvinas Argentinas Health System and evaluate indications and complications. Materials and methods: Retros-pective descriptive study, including of patients with tracheostomy, over 18 years of age, without distinction of sex, carried out between January 2015 and June 2018, in Malvinas Argentinas. Results: 72 patients underwent surgery, 11 local anesthesia, 61 general; 15 emergency, and 57 scheduled. Average age 34.7. The technique used was open with a horizontal incision. The main indications were prolonged orotra-cheal intubation in 34 patients, acute laryngeal obstructive syndrome (AOLS) in 25, and difficult weaning in 6. The most frequent complications were laryngotracheal injuries in 9 patients, surgical wound infection in 5, and subcutaneous emphysema in 3. Discussion: Open technique is not the only one existing in the literature, but the good results in our service confirm its safety due to better recognition of anatomical structures and opening of the trachea. It is not possible to conclude which technique is superior, with respect to morbidity and mortality. There are differences in the place where it is performed, and it can be done in the operating room or next to the patient's bed with adequate asepsis. Conclusion: Currently, it continues to be the technique of choice for performing this procedure in our service.

Cannabidiol at Nanomolar Concentrations Negatively Affects Signaling through the Adenosine A2A Receptor.

Cannabidiol (CBD) is a phytocannabinoid with potential as a therapy for a variety of diseases. CBD may act via cannabinoid receptors but also via other G-protein-coupled receptors (GPCRs), including the adenosine A2A receptor. Homogenous binding and signaling assays in Chinese hamster ovary (CHO) cells expressing the human version of the A2A receptor were performed to address the effect of CBD on receptor functionality. CBD was not able to compete for the binding of a SCH 442416 derivative labeled with a red emitting fluorescent probe that is a selective antagonist that binds to the orthosteric site of the receptor. However, CBD reduced the effect of the selective A2A receptor agonist, CGS 21680, on Gs-coupling and on the activation of the mitogen activated kinase signaling pathway. It is suggested that CBD is a negative allosteric modulator of the A2A receptor.

Disparities in cardio-oncology: Implication of angiogenesis, inflammation, and chemotherapy.

Cancers and cardiovascular diseases are the top two causes of death in the United States. Over the past decades, novel therapies have slowed the cancer mortality rate, yet cardiac failures have risen due to the toxicity of cancer treatments. The mechanisms behind this relationship are poorly understood and it is crucial that we properly treat patients at risk of developing cardiac failure in response to cancer treatments. Currently, we rely on early-stage biomarkers of inflammation and angiogenesis to detect cardiotoxicity before it becomes irreversible. Identification of such biomarkers allows healthcare professionals to decrease the adverse effects of cancer therapies. Angiogenesis and inflammation have a systemic influence on the heart and vasculature following cancer therapy. In the field of cardio-oncology, there has been a recent emphasis on gender and racial disparities in cardiotoxicity and the impact of these disparities on disease outcomes, but there is a scarcity of data on how cardiotoxicity varies across diverse populations. Here, we will discuss how current markers of angiogenesis and inflammation induced by cancer therapy are related to disparities in cardiovascular health.

EVALUATION OF THE INCLUSION OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN A TELEMEDICINE DIABETIC RETINOPATHY SCREENING PROGRAM: A Real Clinical Practice.

PURPOSE: To evaluate whether combining spectral domain optical coherence tomography with monoscopic fundus photography using a nonmydriatic camera (MFP-NMC) improves the accuracy of diabetic macular edema (DME) referrals in a teleophthalmology diabetic retinopathy screening program. METHODS: We conducted a cross-sectional study with all diabetic patients aged 18 years or older who attended screening from September 2016 to December 2017. We assessed DME according to the three MFP-NMC and the four spectral domain optical coherence tomography criteria. The sensitivity and specificity obtained for each criterion were estimated by comparing them with the ground truth of DME. RESULTS: This study included 3,918 eyes (1,925 patients; median age, 66 years; interquartile range, 58-73; females, 40.7%; once-screened, 68.1%). The prevalence of DME ranged from 1.22% to 1.83% and 1.54% to 8.77% on MFP-NMC and spectral domain optical coherence tomography, respectively. Sensitivity barely reached 50% in MFP-NMC and less for the quantitative criteria of spectral domain optical coherence tomography. When macular thickening and anatomical signs of DME were considered, sensitivity increased to 88.3% and the false DMEs and non-gradable images were reduced. CONCLUSION: Macular thickening and anatomical signs showed the highest suitability for screening, with a sensitivity of 88.3% and a specificity of 99.8%. Notably, MFP-NMC alone missed half of the true DMEs that lacked indirect signs.

"A lotta people switched playing hard ball to playing Russian roulette": Experiences with rising overdose incidence caused by drug supply changes during the COVID-19 pandemic in the San Diego-Tijuana border metroplex.

Background: People who use drugs (PWUD) in the San Diego, USA and Tijuana, Mexico metroplex face high overdose risk related to historic methamphetamine use and relatively recent fentanyl introduction into local drug supplies. The personal overdose experiences of PWUD in this region are understudied, however, and may have been influenced by the COVID pandemic. Methods: From September-November 2021, we conducted 28 qualitative interviews among PWUD ≥18 years old sampled from an ongoing cohort study in the San Diego-Tijuana metroplex. Interviews explored overdose experiences and changes in the drug supply. Thematic analysis of coded interview transcripts explored overdose experiences, perspectives on drug supply changes, interactions with harm reduction services, and naloxone access. Results: Among 28 participants, 13 had experienced an overdose. Participants discussed rising levels of fentanyl in local drug supplies and increasing overdose incidents in their social networks. Participants discussed a general shift from injecting heroin to smoking fentanyl in their networks. Participants' most common concerns included having consistent access to a safe and potent drug supply and naloxone. Conclusion: Participants prioritized adapting to drug supply changes and preventing overdose compared to other health concerns, such as HIV and COVID-19. Efforts to address overdose in this region could benefit from drug checking services and expanded, equitable delivery of naloxone.

Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations.

BACKGROUND: Intravenous pharmacokinetics and oral bioavailability of cannabidiol (CBD) with different formulations have not been investigated in horses and may represent a starting point for clinical studies. OBJECTIVES: To describe pharmacokinetics after intravenous and oral administrations with oil and micellar formulations and simulate different treatments. STUDY DESIGN: Single intravenous experiment and two-way randomised oral experiments, Latin-square design. METHODS: Eight healthy horses received intravenous CBD at 1.00 mg/kg dose, oral CBD in sesame oil and in micellar formulation, both at 10.00 mg/kg. Concentrations were measured using LC-MS/MS and fitted by nonlinear mixed effect modelling. Parameters obtained were used to simulate single and multiple treatments at steady state. RESULTS: Intravenous and oral concentrations were simultaneously fitted using a three-compartment model. Final estimates indicate that CBD has a volume of distribution of 36 L/kg associated with a systemic clearance of 1.46 L/h/kg and half-lives ranged between 24 and 34 h. Oral bioavailability was close to 14% for both oral administrations. Simulated dose regimen of CBD every 12 and 24 h predicted similar percentages to reach effective plasma concentration with both oral formulation at 10.00 mg/kg. MAIN LIMITATIONS: A small horse population was used (8 horses per trial). CONCLUSIONS AND CLINICAL IMPORTANCE: Oral bioavailability was low at the doses studied but fell within the range described for horse and other species. CBD had a high steady-state volume of distribution, a high clearance and long half-lives. No adverse reactions were detected at any dose or route. The micellar formulation showed a faster absorption and higher concentration peak, while the oil formulation presented lower levels, but more maintained over time. Simulations predicted that both could be useful in multiple oral dose treatments. These results indicated that CBD could be of interest, but further studies are needed to evaluate its clinical use in horses.

Effect of temperature in the degradation of cannabinoids: From a brief residence in the gas chromatography inlet port to a longer period in thermal treatments.

The substantial increase in legalization and subsequent regulation of cannabis has intensified the control and analytical monitoring of cannabis products to assure sample quality and control the cannabinoid content of the crop. In this sense, the restriction on cultivating legal cannabis plants has been limited to 0.2-0.3% of Δ9-THC content, depending on the host country's laws. Thereby, cannabis flowers containing more than this limit are considered illicit drug-type cultivations and require the obtention of specific permits to work with them. The official method established by the European Commission set the gas chromatography/flame ionization detector (GC-FID) as the proper instrument to analyze the delta-9 tetrahydrocannabinol (Δ9-THC) content. In the present work, the potential drawbacks associated with the utilization of the official method for the evaluation of the Δ9-THC content have been described. Thus, the effect of the GC injector port temperature in the degradation of cannabinoids was evaluated, observing the degradation of CBD by 20%, generating Δ9-THC and CBN as by-products. Likewise, 17.2% of Δ9-THC was degraded, producing CBN as a by-product. Therefore, despite the brief residence of cannabinoids in the GC inlet, the effect of temperature is noteworthy and must be considered. Derivatization of cannabinoids should be a mandatory step to prevent the thermal degradation of cannabinoids, assuring the accuracy of the results. Furthermore, the evaluation of cannabinoid degradation thermally treated for longer periods of time was carried out. The kinetic degradation of CBD was evaluated in this way, observing a degradation of 0.22 µg/L per second. At the same time, the kinetics of the appearance of Δ9-THC demonstrates the intermediate nature of this cannabinoid, being degraded at 0.03 s-1 µM-1. The degradation of CBD also produced CBN and CBE as by-products.

Calidad de la formación en el postgrado de especialización en pediatría clínica de la FCM-UNA: un estudio de percepciones de sus estudiantes, actuales y graduados / Quality of training in the postgraduate specialization in clinical pediatrics of the FCM-UNA: a study of perceptions of its current students and graduates

Introducción: Los procesos de acreditación de la calidad de los programas de formación de médicos tienen importancia en cuanto al impulso que pueden dar a la formación de mejores profesionales. El reconocimiento de la calidad educativa de un determinado programa o carrera por parte de los organismos facultados, como la Agencia Nacional de Evaluación y Acreditación de la Educación Superior (ANEAES) es una garantía del cumplimiento de los criterios mínimos de calidad establecidos. Sin embargo, la calidad de un postgrado no solo es valorada por el cumplimiento de los criterios de calidad mínimos establecidos por los organismos encargados, sino por otros criterios como serían la percepción de los estudiantes, actuales y graduados sobre la calidad de la formación ofrecida por el mismo. Objetivos: El presente trabajo tiene como objetivo general estudiar la calidad de la formación en el Postgrado de Especialización en Pediatría Clínica de la FCM-UNA, a partir de las percepciones de sus estudiantes, actuales y graduados. Materiales y métodos: La metodología se enmarca en la tradición cualitativa de investigación social y en su instrumentación se incluye la realización de entrevistas semiestructuradas aplicadas a los estudiantes actuales (residentes) y graduados (egresados) del programa, así como el desarrollo, implementación y análisis de matrices, con la discusión de los resultados correspondientes a cada una de ellas. Resultados: Los resultados obtenidos muestran que la mayor parte de los estudiantes, actuales y egresados, del Postgrado de Especialización en Pediatría Clínica de la FCM UNA, perciben que la formación en este es de buena a mediana calidad. Los factores que inciden positivamente en la percepción de la calidad de la formación son: el ámbito de desarrollo del programa, el plan de estudios, las actividades académicas, la calidad de la composición y el desempeño del plantel docente, así como las relaciones interpersonales, tanto con los docentes como con sus pares; con algunas excepciones puntuales. La inclusión en el currículum de los aspectos relativos a la responsabilidad social universitaria también tuvo una incidencia positiva. Los factores que incidieron negativamente en la percepción de la calidad de la formación fueron: la carga horaria excesiva, el sistema de evaluación exigente, las falencias en la infraestructura y las tareas de asistencia social, en desmedro de la optimización del tiempo para la formación. En lo referente a la incidencia de la pandemia de COVID 19 en la calidad de la formación, las percepciones fueron dispares al interior de los casos de estudio que cursaron el postgrado durante la misma, con elementos negativos y llamativamente algunos elementos positivos. A la hora de sopesar en qué medida los factores positivos y negativos incidieron globalmente en la percepción de la calidad de la formación, se evidenció que, a pesar del reconocimiento de la existencia de varios factores negativos, los primeros primaron sobre los segundos. Esto hace que la mayoría de los estudiantes actuales y egresados manifiesten su satisfacción con el postgrado y los graduados con su desempeño autónomo al cumplir con sus expectativas. Conclusión: La mayor parte de los estudiantes, actuales y graduados del Postgrado de especialización en Pediatría Clínica de la FCM UNA, perciben que la formación en el mismo es de buena a mediana calidad, con aspectos a mejorar que son mencionados en las recomendaciones.

Introduction: The quality accreditation processes of medical training programs are important in terms of the boost they can give to the training of better professionals. Recognition of the educational quality of a certain program or career by authorized bodies, such as the National Agency for the Evaluation and Accreditation of Higher Education (ANEAES) is a guarantee of compliance with the minimum established quality criteria. However, the quality of a postgraduate course is not only assessed by compliance with the minimum quality criteria established by the bodies in charge, but by other criteria such as the perception of current and graduate students about the quality of the training offered by the same. Objectives: The general objective is to study the quality of training in the Postgraduate Specialization in Clinical Pediatrics of the FCM-UNA, based on the perceptions of its current and graduate students. Materials and methods: The methodology is part of the qualitative tradition of social research and its instrumentation includes semi-structured interviews applied to current students (residents) and graduates of the program, as well as the development, implementation and analysis of matrices, with the discussion of the results corresponding to each of them. Results: The results obtained show that most of the students, current and graduates, of the Postgraduate Specialization in Clinical Pediatrics of the FCM UNA, perceive that the training is of good to medium quality. Factors that positively affect the perception of the quality of training are: the scope of development of the program, the study plan, academic activities, quality of the composition and performance of the teaching staff, as well as interpersonal relationships, both with teachers and with their peers; with some specific exceptions. The inclusion in the curriculum of aspects related to university social responsibility also had a positive impact. Factors that negatively affected perception of the quality of training were: excessive workload, the demanding evaluation system, shortcomings in the infrastructure and the tasks of social service, to the detriment of time dedicated to optimizing training. Regarding the incidence of the COVID 19 pandemic on the quality of training, perceptions were uneven within the case studies that took the postgraduate course during it, with negative elements and strikingly some positive elements. When weighing up the extent to which the positive and negative factors had a global impact on the perception of the quality of training, it was shown that, despite the recognition of the existence of several negative factors, the former prevailed over the latter. This makes the majority of current students and graduates express their satisfaction with the postgraduate course and graduates with their autonomous performance in meeting their expectations. Conclusion: Most of the students, current and graduates of the Postgraduate specialization in Clinical Pediatrics of the FCM UNA, perceive that the training in it is of good to medium quality, with aspects to improve that are mentioned in the recommendations.

Generation of two induced pluripotent stem cell lines carrying the phospholamban R14del mutation for modeling ARVD/C.

The phospholamban (PLN) R14del mutation is associated with arrhythmogenic right ventricular dysplasia (ARVD/C). ARVD/C is a cardiac disease characterized by arrhythmias and structural abnormalities in the right ventricle. Because PLN is a regulator of calcium release, this mutation can have deleterious effects on tissue integrity and contraction. This mutation is a trinucleotide (AGA) deletion that leads to an arginine deletion at position 14 of the PLN structure. Here we show two lines carrying this mutation with typical iPSC morphology, pluripotency, karyotype, ability to differentiate into the three germ layers in vitro, and readily availability for studying pathological mechanisms or ARVD/C.

Long-Acting Injectable Human Immunodeficiency Virus Pre-Exposure Prophylaxis Preferred Over Other Modalities Among People Who Inject Drugs: Findings from a Qualitative Study in California.

People who inject drugs (PWID) have extraordinarily low uptake of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) despite high levels of need. Long-acting PrEP modalities hold promise for HIV prevention among PWID, but product preferences remain poorly understood. From September to November 2021, we conducted qualitative interviews with 28 HIV-negative, adult (≥18 years) PWID in San Diego County, CA, to explore their perspectives on daily oral PrEP pills and long-acting PrEP modalities (i.e., injections, implants, intravaginal rings, and broadly neutralizing antibodies), which we explained using standard scripts. Thematic analysis identified variations in PrEP modality interest and acceptability. We identified three key factors across the 28 interviews that appeared to influence PrEP modality preferences: perceived convenience of use, invasiveness, and familiarity (based on past experience). Overall, most participants preferred injectable PrEP over other modalities because they viewed injectable medications as convenient, noninvasive, and familiar. While injectable PrEP was recently approved for use in the United States and was most the acceptable PrEP modality in this sample, our findings suggest that intervention and implementation research is urgently needed to improve our understanding of strategies that could support access, uptake, and sustained adherence to longer-acting PrEP for PWID.

Evaluando la experiencia local: primeros 50 casos de reparo endovascular de aneurismas aórticos en Manizales, Colombia / Local experience evaluation: first 50 cases of endovascular repair of aortic aneurysms in Manizales, Colombia

Introducción. En las últimas décadas, la terapia endovascular en aneurismas aórticos abdominales ha ganado un papel representativo en los escenarios quirúrgicos, lo que nos motivó a conocer los resultados de este procedimiento en nuestra población. Métodos. Estudio analítico retrospectivo en el cual se incluyeron los primeros 50 casos de aneurismas aórticos abdominales con terapia endovascular, en la ciudad de Manizales, Colombia, entre los años 2015 y 2021. Se describió la población estudiada, la relación de los antecedentes prequirúrgicos con las complicaciones posoperatorias, la estancia hospitalaria y la mortalidad. Resultados.La edad promedio fue de 73 años, el sexo predominante fue el femenino (72 %), el aneurisma fusiforme fue el tipo más frecuente (63,3 %), con un diámetro promedio de 70 mm (+/- 17,3 mm). En relación con los antecedentes, el más frecuente fue hipertensión arterial (86 %), encontrándose una asociación entre la presencia de enfermedad pulmonar obstructiva crónica e hipertensión arterial con las complicaciones. Se encontró también relación entre el valor de creatinina con las complicaciones. Las complicaciones tempranas fueron de carácter leve en la mayoría de los casos (30,6 %), a diferencia de las tardías, que fueron principalmente graves (12,5 %), asociadas a una mortalidad del 10,2 % y una estancia hospitalaria promedio de 10,8 días (mediana de 5 días). Conclusiones. La población analizada tiene una alta carga de morbilidad, en la cual factores como los antecedentes médicos prequirúrgicos y la función renal, se asocian con una mayor morbilidad postquirúrgica y mortalidad.

Introduction. In recent decades, endovascular therapy in abdominal aortic aneurysms has gained a representative role in surgical scenarios, which motivated us to learn about the results of this procedure in our population. Methods. Retrospective analytical study, which included the first 50 cases of abdominal aortic aneurysms with endovascular therapy, in the city of Manizales, Colombia, between 2015 and 2021. The study population was described as the relationship between pre-surgical history and post-operative complications, hospital stay and mortality. Results. The average age was 73 years, the predominant sex was female (72%), the fusiform aneurysm was the most frequent type (63.3%), with an average diameter of 70 mm (± 17.3 mm). In relation to history, the most frequent was arterial hypertension (86%), finding an association between the presence of chronic obstructive pulmonary disease and arterial hypertension with complications. A relationship was also found between the creatinine value and complications. Early complications were mild in most cases (30.6%), unlike late complications, which were mainly serious (12.5%), associated with a mortality of 10.2% and a hospital stay average of 10.8 days (median of 5 days). Conclusions. The analyzed population has a high burden of morbidity, in which factors such as pre-surgical medical history and renal function are associated with greater post-surgical morbidity and mortality.

Identification of sequence changes in myosin II that adjust muscle contraction velocity.

The speed of muscle contraction is related to body size; muscles in larger species contract at slower rates. Since contraction speed is a property of the myosin isoform expressed in a muscle, we investigated how sequence changes in a range of muscle myosin II isoforms enable this slower rate of muscle contraction. We considered 798 sequences from 13 mammalian myosin II isoforms to identify any adaptation to increasing body mass. We identified a correlation between body mass and sequence divergence for the motor domain of the 4 major adult myosin II isoforms (ß/Type I, IIa, IIb, and IIx), suggesting that these isoforms have adapted to increasing body mass. In contrast, the non-muscle and developmental isoforms show no correlation of sequence divergence with body mass. Analysis of the motor domain sequence of ß-myosin (predominant myosin in Type I/slow and cardiac muscle) from 67 mammals from 2 distinct clades identifies 16 sites, out of 800, associated with body mass (padj < 0.05) but not with the clade (padj > 0.05). Both clades change the same small set of amino acids, in the same order from small to large mammals, suggesting a limited number of ways in which contraction velocity can be successfully manipulated. To test this relationship, the 9 sites that differ between human and rat were mutated in the human ß-myosin to match the rat sequence. Biochemical analysis revealed that the rat-human ß-myosin chimera functioned like the native rat myosin with a 2-fold increase in both motility and in the rate of ADP release from the actin-myosin crossbridge (the step that limits contraction velocity). Thus, these sequence changes indicate adaptation of ß-myosin as species mass increased to enable a reduced contraction velocity and heart rate.

Carcinoma del glomus carotideo. Serie de casos / Carcinoma of the carotid glomus. Case series

Introducción. El carcinoma del glomus carotideo es infrecuente y se presenta en el 6 % de los paragangliomas carotideos. Suele haber dificultad en su diagnóstico preoperatorio y no se diferencia fácilmente de su contraparte benigna, lo que puede conllevar a complicaciones quirúrgicas. Este trabajo describe la experiencia en su abordaje clínico y quirúrgico en una serie de casos, además de una revisión de la literatura profundizando en su diagnóstico, abordaje terapéutico, sobrevida y mortalidad. Métodos. De los pacientes operados por glomus carotideos durante un periodo de 20 años, se identificaron aquellos llevados a cirugía por carcinoma. Se realizó una búsqueda bibliográfica extensa en PubMed, haciendo énfasis en diagnóstico y tratamiento. Resultados. De un total de 139 pacientes sometidos a cirugía de resección de tumor del cuerpo carotideo, tres pacientes (2,2 %) presentaron carcinoma. Dos tenían metástasis cervicales y uno metástasis hepáticas. Uno presentaba glomus bilateral asociado a trastorno genético de origen familiar. Se realizó cirugía y adyuvancia en todos los casos. Discusión. El diagnóstico diferencial preoperatorio entre glomus benigno y maligno es difícil, por lo cual deben buscarse hallazgos clínicos o factores de riesgo que puedan sugerir malignidad. Las imágenes pocas veces muestran características claras de invasión vascular. Siempre que sea posible, en el tratamiento del cáncer del glomus carotideo, debe realizarse resección quirúrgica, acompañada de un vaciamiento funcional de cuello, dejando la radioterapia, la quimioterapia y la hormonoterapia como terapias adyuvantes

Introduction. Carcinoma of the carotid glomus is rare and occurs in 6% of carotid paragangliomas. There is often difficulty in its preoperative diagnosis, and it is not easily differentiated from its benign counterpart, which can lead to surgical complications. This study describes the experience in its clinical and surgical approach in a series of cases, as well as a review of the literature of its diagnosis, therapeutic approach, survival, and mortality.Methods. Of the patients operated for carotid glomus over a 20-year period, those undergoing surgery for carcinoma were identified. An extensive literature search was conducted in PubMed, with an emphasis on diagnosis and treatment.Results. Out of a total of 139 patients who underwent carotid body tumor resection surgery, three patients (2.2%) had carcinoma. Two had cervical metastases and one had liver metastases. One had bilateral glomus associated with a genetic disorder of familial origin. Surgery and adjuvant surgery were performed in all cases.Discussion. The preoperative differential diagnosis between benign and malignant glomus is difficult, for which clinical findings or risk factors that may suggest malignancy should be sought. Images rarely show clear features of vascular invasion. Whenever possible in the treatment of carotid glomus cancer, surgical resection should be performed, accompanied by a functional neck dissection, leaving radiotherapy, chemotherapy, and hormone therapy as adjuvant therapies

Oligosacáridos y polisacáridos no digeribles: una fuente de salud para los adultos mayores / Non-digestible oligosaccharides and polysaccharides: a source of health for older people

RESUMEN Los adultos mayores son especialmente vulnerables a sufrir enfermedades asociadas al tracto gastrointestinal, ya que el envejecimiento conlleva naturalmente a un desbalance en la diversidad y cantidad de los microorganismos presentes en el intestino. Por ello, la suplementación de su dieta con oligosacáridos y polisacáridos no digestibles (OPND) ha cobrado gran relevancia científica. Esto, con el propósito de prevenir y revertir, en parte, los cambios negativos en la microbiota intestinal derivados del envejecimiento. Se ha observado que la suplementación de OPND en adultos mayores genera variados beneficios, entre los que destacan una mejora en el sistema inmune, una mayor absorción de calcio, reducción en la incidencia de alergias, reducción de la constipación y una disminución en los niveles de glicemia y colesterol sanguíneos. Debido a que, los efectos del consumo de OPND en adultos mayores han sido escasamente discutidos en la literatura científica en idioma castellano, el propósito de esta revisión es abordar el tema haciendo énfasis en la realidad chilena y latinoamericana. Ello, con miras a fomentar la incorporación de OPND en alimentos y programas de alimentación dirigidos específicamente a personas de la tercera edad.

ABSTRACT Since aging naturally leads to an imbalance in the diversity and quantity of microorganisms present in the intestine, older people are particularly vulnerable to diseases associated with the gastrointestinal tract. Thus, supplementing the diet of elderly persons with non-digestible oligosaccharides and polysaccharides (OPND) has gained scientific relevance. Supplementation aims to prevent and (partially) revert the negative changes in intestinal microbiota due to aging. It has been observed that OPND supplementation in older adults provides several benefits, including an improvement in the immune system, increased calcium absorption, a reduction in the incidence of allergies, a reduction in constipation and a decrease in blood levels of cholesterol and glucose. Because the effects of OPND supplementation in older adults has been scarcely discussed in the scientific literature in the Spanish language, the purpose of this review is to address the issue with emphasis on the Chilean and Latin-American reality. The article promotes the incorporation of OPND in processed food and feeding programs specifically designed for older people in Latin America.

Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB1, CB2 and CB1/CB2 heteromer receptors.

BACKGROUND: Recent approved medicines whose active principles are Δ9Tetrahidrocannabinol (Δ9-THC) and/or cannabidiol (CBD) open novel perspectives for other phytocannabinoids also present in Cannabis sativa L. varieties. Furthermore, solid data on the potential benefits of acidic and varinic phytocannabinoids in a variety of diseases are already available. Mode of action of cannabigerol (CBG), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabidivarin (CBDV) and cannabigerivarin (CBGV) is, to the very least, partial. HYPOTHESIS/PURPOSE: Cannabinoid CB1 or CB2 receptors, which belong to the G-protein-coupled receptor (GPCR) family, are important mediators of the action of those cannabinoids. Pure CBG, CBDA, CBGA, CBDV and CBGV from Cannabis sativa L. are differentially acting on CB1 or CB2 cannabinoid receptors. STUDY DESIGN: Determination of the affinity of phytocannabinoids for cannabinoid receptors and functional assessment of effects promoted by these compounds when interacting with cannabinoid receptors. METHODS: A heterologous system expressing the human versions of CB1 and/or CB2 receptors was used. Binding to membranes was measured using radioligands and binding to living cells using a homogenous time resolved fluorescence resonance energy transfer (HTRF) assay. Four different functional outputs were assayed: determination of cAMP levels and of extracellular-signal-related-kinase phosphorylation, label-free dynamic mass redistribution (DMR) and ß-arrestin recruitment. RESULTS: Affinity of cannabinoids depend on the ligand of reference and may be different in membranes and in living cells. All tested phytocannabinoids have agonist-like behavior but behaved as inverse-agonists in the presence of selective receptor agonists. CBGV displayed enhanced potency in many of the functional outputs. However, the most interesting result was a biased signaling that correlated with differential affinity, i.e. the overall results suggest that the binding mode of each ligand leads to specific receptor conformations underlying biased signaling outputs. CONCLUSION: Results here reported and the recent elucidation of the three-dimensional structure of CB1 and CB2 receptors help understanding the mechanism of action that might be protective and the molecular drug-receptor interactions underlying biased signaling.

Tromboembolia pulmonar como complicación de COVID-19 en el puerperio. Reporte de un caso / Pulmonary thromboembolism as a complication of COVID-19 in the puerperium. Report of a case

December 31,2019 an outbreak of pneumonía caused by a new coronavirus designated as SARS-CoV-2 was detected in the city of Wuhan (China). From a clinical point of view, it was found that patients can develop from a mild condition in the upper respiratory tract to severe pneumonía that are associated with respiratory distress progressing to severe respiratory failure. It has been described that the infection predisposes to hypercoagulability phenomena and venous thrombosis, recognizing pulmonary thromboembolism (PE) as the most frequent. Pregnancy is a physiological state with a high risk for the development of thromboembolic complications, increasing the risk factors for PTE during delivery and the puerperium. In the context of the association of SARS- CoV-2 infection and pregnancy, there are few reports around the world as it is a recent pathology. In Mexico, according to official epidemiological records, COVID-19 has become the leading cause of maternal death, surpassing preclimactic events and obstetric hemorrhage, which until a few months ago were the leading cause. We present the case of a patient diagnosed with the new coronavirus who, during the middle puerperium, develops pulmonary thromboembolism, causing her death.

El 31 de diciembre de 2019, se detectó en la ciudad de Wuhan (China) un brote de neumonía por un nuevo coronavirus designado como SARS-CoV-2. Desde el punto de vista clínico se encontró que los pacientes pueden desarrollar desde un cuadro leve de afección en vías respiratorias altas hasta cuadros de neumonía grave que se asocian a distrés respiratorio progresando a insuficiencia respiratoria grave. Se ha descrito que la infección predispone a fenómenos de hipercoagulabilidad y trombosis de localización venosa, reconociendo el tromboembolismo pulmonar (TEP) como el más frecuente. El embarazo es un estado fisiológico con alto riesgo para el desarrollo de complicaciones tromboembólicas, aumentando los factores de riesgo para TEP durante el parto y puerperio. En el contexto de la asociación de infección por SARS-CoV-2 y embarazo existen pocos informes alrededor del mundo al ser una patología reciente. En México, según registros epidemiológicos oficiales, el COVID-19 se ha convertido en la principal causa de muerte materna superando a los eventos preclámpticos y la hemorragia obstétrica, que hasta hace algunos meses, eran la primera causa. Se presenta el caso de una paciente diagnosticada con el nuevo coronavirus que, en el curso del puerperio mediato, desarrolla tromboembolia pulmonar causándole la muerte.