Decídetexto: Mobile cessation support for Latino adults who smoke. A randomized clinical trial.

BACKGROUND: Latino adults experience multiple barriers to healthcare access and treatment that result in tobacco-related disparities. Mobile interventions have the potential to deliver smoking cessation treatment among Latino adults, the highest users of mobile technologies. RESEARCH QUESTION: Is Decídetexto, a culturally accommodated mobile health intervention, more effective for smoking cessation compared to standard care among Latino adults who smoke? STUDY DESIGN AND METHODS: A two-arm parallel group randomized clinical trial (RCT) was conducted in Kansas, New Jersey, and New York between October 2018 and September 2021. Eligible Latino adults who smoke (n=457) were randomly assigned to Decídetexto or a standard care group. The primary outcome was biochemically verified 7-day smoking abstinence at week 24. Secondary outcomes included self-reported 7-day smoking abstinence at weeks 12 and 24, and uptake and adherence of nicotine replacement therapy (NRT). RESULTS: Participants mean age was 48.7 (SD 11.1) years, 45.2% were female, and 50.3% smoked ≥10 cigarettes per day. Two hundred twenty-nine participants were assigned to Decídetexto and 228 to standard care. Treating those lost to follow-up as participants who continued smoking, 14.4% of participants in the Decídetexto group were biochemically verified abstinent at week 24 compared to 9.2% in the standard care group (OR 1.66 [95% CI, 0.93-2.97], p=0.09). Treating those lost to follow-up as participants who continued smoking, 34.1% of the participants in the Decídetexto group self-reported smoking abstinence at week 24 compared to 20.6% of participants in the standard care group (OR 1.99 [95%, 1.31-3.03]; p<0.001). Analyzing only participants who completed the assessment at week 24, 90.6% (174/192) of participants in the Decídetexto group self-reported using NRT for at least one day compared to 70.2% (139/198) of participants in standard care (OR 4.10 [95% CI, 2.31-7.28]; p<0.01). INTERPRETATION: Among Latino adults who smoke, the Decídetexto intervention was not associated with a statistically significant increase in biochemically verified abstinence at week 24. However, the Decídetexto intervention was associated with a statistically significant increase in self-reported 7-day smoking abstinence at weeks 12 and 24, and uptake of NRT. This RCT provides encouragement for the use of Decídetexto for smoking cessation among Latino adults. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03586596.

Measuring the individualization potential of treatment individualization rules: Application to rules built with a new parametric interaction model for parallel-group clinical trials.

For personalized medicine, we propose a general method of evaluating the potential performance of an individualized treatment rule in future clinical applications with new patients. We focus on rules that choose the most beneficial treatment for the patient out of two active (nonplacebo) treatments, which the clinician will prescribe regularly to the patient after the decision. We develop a measure of the individualization potential (IP) of a rule. The IP compares the expected effectiveness of the rule in a future clinical individualization setting versus the effectiveness of not trying individualization. We illustrate our evaluation method by explaining how to measure the IP of a useful type of individualized rules calculated through a new parametric interaction model of data from parallel-group clinical trials with continuous responses. Our interaction model implies a structural equation model we use to estimate the rule and its IP. We examine the IP both theoretically and with simulations when the estimated individualized rule is put into practice in new patients. Our individualization approach was superior to outcome-weighted machine learning according to simulations. We also show connections with crossover and N-of-1 trials. As a real data application, we estimate a rule for the individualization of treatments for diabetic macular edema and evaluate its IP.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Increased threat of urban arboviral diseases from Aedes aegypti mosquitoes in Colombia.

Objectives: Our study targets the potential of the local urban mosquito Aedes aegypti to experimentally transmit chikungunya virus (CHIKV), dengue virus (DENV), yellow fever virus (YFV), and Zika virus (ZIKV). Methods: We collected eggs and adults of Ae. aegypti in Medellín, Colombia (from February to March 2020) for mosquito experimental infections with DENV, CHIKV, YFV and ZIKV and viral detection using the BioMark Dynamic arrays system. Results: We show that Ae. aegypti from Medellín was more prone to become infected, to disseminate and transmit CHIKV and ZIKV than DENV and YFV. Conclusions: Thus, in Colombia, chikungunya is the most serious threat to public health based on our vector competence data.

pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells and mouse model.

Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment. Several new therapeutic approaches, including nanoparticle-assisted drug delivery, are being investigated by us and others. This study used pH-responsive nanoparticles encapsulated ERK inhibitor (SCH772984) and surface functionalized with tumor-penetrating peptide, iRGD, to target PDAC tumors. We used a small molecule, SCH772984, to target ERK1 and ERK2 in PDAC and other cancer cells. This nanocarrier efficiently released ERKi in hypoxic and low-pH environments. We also found that the free-GEM, which is functionally weak when combined with nanoencapsulated ERKi, led to significant synergistic treatment outcomes in vitro and in vivo. In particular, the combination approaches significantly enhanced the GEM effect in PDAC growth inhibition and prolonged survival of the animals in a genetically engineered KPC (LSL-KrasG12D/+/LSL-Trp53R172H/+/Pdx-1-Cre) pancreatic cancer mouse model, which is not observed in a single therapy. Mechanistically, we anticipate that the GEM efficacy was increased as ERKi blocks desmoplasia by impairing the production of desmoplastic regulatory factors in PDAC cells and KPC mouse tumors. Therefore, 2nd generation ERKi (SCH 772984)-iRGD-pHNPs are vital for the cellular response to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS.

Daratumumab and Nelarabine Treatment as Salvage Therapy for T-Lymphoblastic Lymphoma: A Case Report.

T-cell lymphoblastic lymphoma is an uncommon lymphoid neoplasm in adults, although more frequent in children and teenagers, that often affects the mediastinum and bone marrow, requiring intensive chemotherapy protocols. Its prognosis is poor if a cure is not achieved with first-line treatments. We present a case report of a 19-year-old man diagnosed with this type of lymphoma due to significant respiratory distress and a mediastinal mass. He received treatment according to the hyper-CVAD regimen, with a complete metabolic response. However, seven months later a new mediastinal growth was observed, leading to salvage treatment with a combination of nelarabine and daratumumab. We observed not only refractoriness, but also leukemization, which prompted consideration of hematopoietic stem cell transplantation. Based on this case, we conducted a review of pharmacological treatment options for refractory or relapsed lymphoblastic lymphoma, as well as the role of radiotherapy in managing mediastinal disease. This case report highlights the limited evidence available regarding later-line treatments, with unusual reports regarding employing our combination of daratumumab and nelarabine, and emphasizes the importance of achieving cures in the first line of treatment.

Homicidio por combinación de métodos de asfixia / Homicide by combination of methods of asphyxiation

Introducción el homicidio por combinación de métodos de asfixia se observa mayoritariamente en las personas de edad avanzada o con algún impedimento físico capaz de contrarrestar la agresión. Material y métodos se realizó un estudio observacional retrospectivo sobre 634 autopsias, cinco cumplían las características de homicidios por combinación de métodos de asfixia. Resultados dos hombres y 3 mujeres, con edad promedio de 69 años, con estudios toxicológicos negativos, víctimas de un solo agresor, presentaron lesiones cutáneas periorificiales (bucales y nasales), hemorragias musculares en el tórax, fracturas costales, lesiones contusas en la cabeza, interpretadas como de sometimiento. Discusión en la combinación de métodos de asfixia, los hallazgos que deben ser vistos en conjunto son: traumatismos craneoencefálicos para someter a la víctima, lesiones cutáneas en el cuello, la cara, la cara interna de los labios, fracturas costales y lesiones por contrapresión en la espalda, los glúteos o los codos. Contextualizados en conjunto pueden explicar la dinámica de esta modalidad homicida. (AU)

Introduction Homicide by combination of suffocation methods is observed mainly in elderly people or with some physical impediment capable of counteracting the aggression. Material and methods A retrospective observational study was carried out on 634 autopsies. Five met the characteristics of homicides by combination of asphyxiation methods. Results Two men and three women, average age 69 years, with negative toxicological studies, victims of a single aggressor, presented peri orificial skin lesions (mouth and nose), muscle hemorrhages in the thorax, rib fractures, blunt injuries to the head interpreted as like submission. Discussion In the combination of asphyxia methods the findings that must be seen together: Head injuries to subdue the victim, skin lesions on the neck, face, inner face of the lips, rib fractures, and counter-pressure injuries to the back, buttocks, or elbows. Contextualized together, can explain the dynamics of this homicidal modality. (AU)

Virome analyses of Amblyomma cajennense and Rhipicephalus microplus ticks collected in Colombia.

Tick-borne viruses (TBV) have gained public health relevance in recent years due to the recognition of human-associated fatal cases and the increase in tick-borne disease and transmission. However, many tick species have not been studied for their potential to transmit pathogenic viruses, especially those found in Latin America. To gain better understanding of the tick virome, we conducted targeted amplification using broadly-reactive consensus-degenerate pan-viral targeting viruses from the genera Flavivirus, Bandavirus, Uukuvirus, and Orthonairovirus genus. Additionally, we conducted unbiased metagenomic analyses to investigate the presence of viral RNA sequences in Amblyomma cajennense, A. patinoi and Rhipicephalus microplus ticks collected from a horse slaughter plant in Medellín, Colombia. While no viral products were detected by PCR, results of the metagenomic analyses revealed the presence of viral genomes belonging to the genera Phlebovirus, Bandavirus, and Uukuvirus, including Lihan Tick Virus (LTV), which was previously reported in Rhipicephalus microplus from Colombia. Overall, the results emphasized the enormous utility of the next-generation sequencing in identifying virus genetic diversity presents in ticks and other species of vectors and reservoirs.

Nicotine Delivery and Changes in Withdrawal and Craving During Acute Electronic Cigarette, Heated Tobacco Product, and Cigarette Use Among a Sample of Black and White People Who Smoke.

INTRODUCTION: E-cigarettes and heated tobacco products (HTPs) may serve as potential options for harm reduction for smokers if they possess reward profiles similar to cigarettes. Little is known about the abuse liability of HTPs and e-cigarettes versus cigarettes in racial/ethnic minority smokers. AIMS AND METHODS: Twenty-two nicotine-deprived people who smoke (black [n = 12] and white [n = 10]) completed three visits that included a standardized 10-puff bout followed by a 50-minute ad libitum use assessment with their usual brand cigarette (UBC), an e-cigarette, and HTP. Visits were completed in a randomized crossover design and were separated by a minimum 48-hour washout period. Assessments included plasma nicotine, Cmax, and reductions in craving and withdrawal. RESULTS: UBC delivered significantly greater levels of nicotine compared to the e-cigarette (p < .001) and HTP (p < .01) during both the standardized and ad libitum sessions. HTP delivered more nicotine than the e-cigarette during the standardized puffing session (p = .047) but not the ad libitum session. Only craving during the standardized puffing session and not the ad libitum session showed significant differences across products (p < .001) such that UBC resulted in the greatest reduction followed by HTP and e-cigarette. CONCLUSIONS: Despite greater nicotine delivery from the UBC compared to e-cigarette and HTP, participants reported reductions in craving and withdrawal across products, particularly following ad libitum use. IMPLICATIONS: Use of participant's UBCs (UBC) resulted in greater nicotine delivery compared to both the e-cigarette and HTP. Despite this relative difference in nicotine delivery, participants reported reductions in craving and withdrawal across products, particularly following ad libitum use. These findings suggest that in this sample of black and white people who smoke, HTPs and e-cigarettes provided significant relief from negative symptoms that maintain smoking.

Outbreak report of SARS-CoV-2 infection by airborne transmission: Epidemiologic and molecular evidence / Reporte de un brote de infección por SARS-CoV-2 por transmisión aérea: evidencia epidemiológica y molecular

Introduction: It has been shown that the transmission of SARS-CoV-2 occurs mainly by air, and the risk of infection is greater in closed spaces. Objective: To describe the epidemiology, virology and molecular characterization of a COVID-19 outbreak at a closed vaccination point during the third wave of SARS-CoV-2 in Colombia. Materials and methods: Diagnostic tests, interviews, sampling, cell cultures and viral sequencing were carried out, the latter being molecular characterization and lineage identification. Results: Seven workers were positive for SARS-CoV-2; among these, 3 samples were analyzed, plus an additional sample belonging to the mother of the presumed index case; all samples were identified with lineage B.1.625, with a maximum of 2 nucleotides difference between them. Conclusions: Variant B.1.625 was identified as the cause of the COVID-19 outbreak, and a co-worker was also identified as the index case. Unexpectedly, attending a vaccination day became a risk factor for acquiring the infection.

Introducción. Se ha demostrado que la transmisión de SARS-CoV-2 se produce principalmente por vía aérea y el riesgo de infección es mayor en espacios cerrados con alta concentración de personas; este último factor se presentó en algunos de los puestos de vacunación de la ciudad de Medellín. Objetivo. Describir la epidemiología, virología y caracterización molecular de un brote de COVID-19 en un punto de vacunación cerrado durante la tercera ola de SARS-CoV-2 en Colombia. Materiales y métodos. Se realizaron test diagnósticos, entrevistas, toma de muestras, aislamiento viral y secuenciación genómica. Con esta última, se hizo la caracterización molecular y se identificó el linaje. Resultados. Siete trabajadores fueron positivos para SARS-CoV-2, y de estos, tres muestras fueron secuenciadas, más una muestra adicional perteneciente a la madre del presunto caso índice. Todas las muestras fueron identificadas con el linaje B.1.625, con un máximo de dos nucleótidos de diferencia entre ellas. Conclusiones. Se identificó la variante B.1.625 como la causante del brote de COVID-19, y también un compañero de trabajo fue identificado como el caso índice. De forma imprevista, asistir a una jornada de vacunación se convirtió en un factor de riesgo para adquirir la infección.

Infección natural por SARS-CoV-2 en gatos y perros domésticos de personas con diagnóstico de COVID-19 en el Valle de Aburrá, Antioquia / Natural SARS-CoV- 2 infection in domestic cats and dogs of humans diagnosed with COVID-19 in Valle de Aburrá, Antioquia

Introducción. El síndrome respiratorio agudo grave causado por el nuevo coronavirus SARS-CoV-2 es causa de la emergencia sanitaria por la pandemia de COVID-19. Si bien el humano es el principal huésped vulnerable, en estudios experimentales y reportes de infección natural, se han encontrado casos de zoonosis inversa de SARS-CoV-2 en animales. Objetivo. Evaluar la infección natural por SARS-CoV-2 en gatos y perros de propietarios con diagnóstico de COVID-19 en el Valle de Aburrá, Antioquia, Colombia. Materiales y métodos. La circulación del SARS-CoV-2 se evaluó por RT-qPCR y RT-PCR en muestras de frotis nasofaríngeos y orofaríngeos de gatos y perros cuyos propietarios se encontraban dentro del periodo de los 14 días de aislamiento. Los casos positivos se verificaron amplificando fragmentos de los genes RdRp, N y E; se secuenció el gen RdRp y se analizó filogenéticamente. Resultados. De 80 animales evaluados, seis gatos y tres perros fueron casos confirmados de infección natural por SARS-CoV-2. Los animales no presentaron signos clínicos y sus propietarios, que padecían la infección, reportaron únicamente signos leves de la enfermedad sin complicaciones clínicas. En el análisis de una de las secuencias, se encontró un polimorfismo de un solo nucleótido (SNP) con un cambio en la posición 647, con sustitución del aminoácido serina (S) por una isoleucina (I). Los casos se presentaron en los municipios de Caldas, Medellín y Envigado. Conclusiones. Se infiere que la infección natural en los gatos y perros se asocia al contacto directo con un paciente con COVID-19. No obstante, no es posible determinar la virulencia del virus en este huésped, ni su capacidad de transmisión zoonótica o entre especie.

Introduction: The severe acute respiratory syndrome caused by the new coronavirus SARS-CoV-2 is the cause of the health emergency due to the COVID-19 pandemic. Although humans are the main susceptible host, experimental studies and reported cases of natural infection have evidenced scenarios of SARS-CoV-2 reverse zoonosis in animals. Objective: To evaluate the natural infection of SARS-CoV-2 in cats and dogs with owners diagnosed with COVID-19 in the Valle de Aburrá subregion in Antioquia, Colombia. Materials and methods. The circulation of SARS-CoV-2 was evaluated by RT-qPCR and RT-PCR in samples of nasopharyngeal and oropharyngeal smears from cats and dogs whose owners presented latent COVID-19 infection. Positive cases were verified through amplification of N, E and RdRp gene fragments; with the latter being sequenced and the phylogenetically analyzed. Results. From 80 tested animals, 6 cats and 3 dogs resulted positive for natural SARS-CoV-2 infection. These animals did not show any clinical signs; and their infected owners only reported mild signs of COVID-19, without clinical complications. Regarding analysis of one of the sequences, a single nucleotide polymorphism (SNP) was found, with a substitution in position 647, resulting in the change of the amino acid serine (S) for isoleucine (I). The cases occurred in the municipalities of Caldas, Medellín and Envigado. Conclusions. It is inferred that natural infection in cats and dogs is associated with direct contact with a positive COVID-19 patient.

Dyadic Analysis of Emotional Intimate Partner Violence: An Estimation of Dyadic Patterns and Influencing Individual, Family, and Couple Factors

Background: The co-occurrence of intimate partner violence (IPV) has been usually determined by co-occurring reports of perpetration and victimization, but still not considering the interdependence of both members’ reports. The current research aimed to analyze the dyadic patterns of IPV perpetration and victimization, considering the influence of sexism toward women, family functioning, and relationship duration. Method: The sample involved 242 couples heterosexual couples. The Actor-Partner Interdependence Model was calculated to analyze the violent dynamics in the couple. For males, a couple-oriented pattern was identified, but for females the pattern was between couple-oriented and actor-only pattern. Results: These patterns remained stable when personal, family, and relational variables were included in the model, which present different effects on perpetration and victimization: males’ hostile sexism predicted higher levels of male IPV perpetration and victimization as well as higher levels of male and female victimization via male perpetration. Regarding family functioning, higher family good functioning predicted lower IPV perpetration in males and lower victimization in females. Finally, relationship length predicted higher levels of IPV perpetration of both couple members and higher victimization via perpetration. Conclusions: These results are discussed in light of the interdependence of couple members’ IPV perpetration and victimization. (AU)

Antecedentes: La coocurrencia de la violencia en la pareja (IPV) suele establecerse con el informe de ambos miembros de la pareja, pero rara vez se tiene en cuenta la interdependencia entre sus respuestas. El objetivo del trabajo ha sido analizar los patrones diádicos de la IPV teniendo en cuenta el sexismo hacia las mujeres, la funcionalidad familiar y la duración de la relación. Método: La muestra estaba compuesta por 242 parejas heterosexuales, utilizándose el Actor-Partner Interdependence Model para analizar los patrones diádicos. En el caso de los hombres se identificó el patrón orientado a la díada, mientras que el patrón de las mujeres parecía encontrarse entre el orientado a la díada y al actor. Resultados: Estos patrones se mantuvieron tras haber incluido el sexismo, el funcionamiento familiar y la duración de la relación: el sexismo hostil de los hombres predecía mayores niveles de perpetración en ellos y de victimización en ambos a través de la perpetración de los hombres. El buen funcionamiento familiar predecía una menor perpetración en los hombres y victimización en las mujeres. Finalmente la duración de la relación predijo mayores niveles de perpetración y victimización a través de la perpetración en ambos miembros de la pareja. Conclusiones: Se discuten los resultados a partir de la interdependencia de la IPV de ambos miembros de la pareja. (AU)

Immune characterization of a Colombian family cluster with SARS-CoV-2 infection / Caracterización inmunológica de un grupo familiar colombiano con infección por SARS-CoV-2

Abstract | Introduction: Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARS- CoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited. Objective: To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection. Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay. Results: During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin. Conclusion: Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.

Resumen | Introducción. Se han descrito diferentes marcadores inmunológicos durante la COVID-19, los cuales persisten incluso después de la convalecencia y se asocian con los estadios clínicos de la infección. Sin embargo, aún son pocos los estudios orientados al análisis exhaustivo de las alteraciones del sistema inmunológico en el curso de la infección. Objetivo. Evaluar la producción de citocinas proinflamatorias, la reacción de anticuerpos, y el fenotipo y la función de las células NK y los linfocitos T en una familia colombiana con infección por SARS-CoV-2. Materiales y métodos. Se evaluaron las citocinas proinflamatorias mediante RT-PCR y ELISA; la frecuencia, el fenotipo y la función de las células NK (en cocultivos con células K562) y linfocitos T CD8+ (estimulados con péptidos spike/RdRp) mediante citometría de flujo, y los anticuerpos anti-SARS-CoV-2, mediante inmunofluorescencia indirecta y prueba de neutralización por reducción de placa. Resultados. Durante la COVID-19 hubo una producción elevada de citocinas proinflamatorias, con disminución de las células NK CD56 bright y reacción citotóxica. Comparados con los controles sanos, los individuos infectados presentaron con gran frecuencia linfocitos T CD8+ disfuncionales CD38+HLA-DR-. Además, en los linfocitos T CD8+ estimulados con péptidos virales, predominó una reacción monofuncional con gran producción de IL-10 durante la fase aguda y una reacción bifuncional caracterizada por la coexpresión de CD107a y granzima B o perforina durante la convalecencia. Conclusión. Aunque la reacción inflamatoria caracteriza la infección por SARS-CoV-2, hay otras alteraciones fenotípicas y funcionales en células NK y linfocitos T CD8+ que podrían asociarse con la progresión de la infección. Se requieren estudios adicionales para entender estas alteraciones y guiar futuras estrategias de inmunoterapia.

Aislamiento y caracterización de una cepa temprana de SARS-CoV-2 durante la epidemia de 2020 en Medellín, Colombia / Isolation and characterization of an early SARS-CoV-2 isolate from the 2020 epidemic in Medellín, Colombia

Introducción. El nuevo coronavirus causante de un brote de enfermedad respiratoria aguda en China en diciembre de 2019 se identificó como SARS-CoV-2. La enfermedad, denominada COVID-19, fue declarada pandemia por la Organización Mundial de la Salud (OMS). El primer caso de COVID-19 en Colombia se reportó el 6 de marzo de 2020; en este estudio se caracterizó un aislamiento temprano del virus SARS-CoV-2 de una muestra recolectada en abril de 2020. Objetivos. Describir y caracterizar una cepa temprana a partir de un aislamiento de SARS-CoV-2 durante la pandemia en Colombia. Materiales y métodos. Se obtuvo una muestra de un paciente con COVID-19 confirmada por qRT-PCR; la muestra fue inoculada en diferentes líneas celulares hasta la aparición del efecto citopático. Para confirmar la presencia de SARS-CoV-2 en el cultivo, se utilizó la qRT-PCR a partir de los sobrenadantes, la inmunofluorescencia indirecta (IFI) en células Vero-E6, así como microscopía electrónica y secuenciación de nueva generación (next-generation sequencing). Resultados. Se confirmó el aislamiento de SARS-CoV-2 en células Vero-E6 por la aparición del efecto citopático tres días después de la infección, así como mediante la qRT-PCR y la IFI positiva con suero de paciente convaleciente positivo para SARS-CoV-2. Además, en las imágenes de microscopía electrónica de trasmisión y de barrido de células infectadas se observaron estructuras compatibles con viriones de SARS-CoV-2. Por último, se obtuvo la secuencia completa del genoma, lo que permitió clasificar el aislamiento como linaje B.1.5. Conclusiones. La evidencia presentada en este artículo permite confirmar el primer aislamiento de SARS-CoV-2 en Colombia. Además, muestra que esta cepa se comporta en cultivo celular de manera similar a lo reportado en la literatura para otros aislamientos y que su composición genética está acorde con la variante predominante en el mundo. Finalmente, se resalta la importancia que tiene el aislamiento viral para la detección de anticuerpos, para la caracterización genotípica y fenotípica de la cepa y para probar compuestos con potencial antiviral.

Introduction: SARS-CoV-2 has been identified as the new coronavirus causing an outbreak of acute respiratory disease in China in December, 2019. This disease, currently named COVID-19, has been declared as a pandemic by the World Health Organization (WHO). The first case of COVID-19 in Colombia was reported on March 6, 2020. Here we characterize an early SARS-CoV-2 isolate from the pandemic recovered in April, 2020. Objective: To describe the isolation and characterization of an early SARS-CoV-2 isolate from the epidemic in Colombia. Materials and methods: A nasopharyngeal specimen from a COVID-19 positive patient was inoculated on different cell lines. To confirm the presence of SARS-CoV-2 on cultures we used qRT-PCR, indirect immunofluorescence assay, transmission and scanning electron microscopy, and next-generation sequencing. Results: We determined the isolation of SARS-CoV-2 in Vero-E6 cells by the appearance of the cytopathic effect three days post-infection and confirmed it by the positive results in the qRT-PCR and the immunofluorescence with convalescent serum. Transmission and scanning electron microscopy images obtained from infected cells showed the presence of structures compatible with SARS-CoV-2. Finally, a complete genome sequence obtained by next-generation sequencing allowed classifying the isolate as B.1.5 lineage. Conclusion: The evidence presented in this article confirms the first isolation of SARS-CoV-2 in Colombia. In addition, it shows that this strain behaves in cell culture in a similar way to that reported in the literature for other isolates and that its genetic composition is consistent with the predominant variant in the world. Finally, points out the importance of viral isolation for the detection of neutralizing antibodies, for the genotypic and phenotypic characterization of the strain and for testing compounds with antiviral potential.

The actor-partner interdependence model in the study of aggression and victimization within couples: an empirical examination in 361 dyads / El modelo de interdependencia actor-pareja en el estudio de la agresión y la victimización en la pareja: un estudio empírico de 361 díadas

Studies of intimate partner violence (IPV) have generally focused on only one partner. Although this has allowed advances in scientific knowledge on the causes of IPV, currently recent literature is demanding the need to study both members of the couple. Methodologically, the study of dyads requires the use of appropriate statistical techniques to avoid possible systematic biases (for example, type I error due to dependence of observations). We used the Actor-Partner Interdependence Model to study aggression and victimization in 361 heterosexual couples of young adults. The results indicated, on the one hand, that self-reported mutual aggression was found in more than 50% of the couples. On the other hand, we found that participants' victimization was largely predicted by their own aggressive behavior towards the other member of the couple. While this result suggests the existence of a victim-offender overlap, it may also hide an upwards victimization scores bias: when participants are aggressive toward their partners, they may bias their victimization scores upwards to justify their levels of aggression ("I was aggressive because I felt victimized")

Los estudios sobre la violencia de pareja (en inglés IPV) generalmente han centrado sus análisis sólo en uno de los miembros. Aunque esto ha permitido avanzar en el conocimiento de las causas de la IPV, la literatura reciente ha señalado la necesidad de estudiar a los dos miembros de la pareja. Metodológicamente el estudio de las parejas requiere el uso de técnicas estadísticas apropiadas para evitar posibles sesgos sistemáticos (por ejemplo, error tipo I debido a la dependencia de las observaciones). En este estudio utilizamos el modelo de interdependencia actor-pareja para el estudio de la agresión y la victimización en 361 parejas jóvenes heterosexuales de jóvenes adultos. Los resultados indicaban, por una parte, que había agresión mutua autoinformada en más de la mitad de las parejas. Por otro lado, encontramos que el principal predictor de la victimización de los participantes fue su propio comportamiento agresivo hacia el otro miembro de la pareja. Este resultado sugiere que la víctima y el agresor son la misma persona. Sin embargo, también puede ocultar un posible sesgo al alza de las puntuaciones de victimización: cuando los participantes son agresivos con sus parejas, pueden sesgar al alza sus puntuaciones de victimización para justificar sus niveles de agresión ("Fui agresivo porque me sentí victimizado")

Autopsias en casos sospechosos de SARS-CoV-2 / Autopsies of suspected SARS-CoV-2 cases

La medicina forense debe contemplar la posibilidad de que fallecidos por causas violentas o desconocidas puedan estar infectados por el virus SARS-CoV-2, o que el diagnóstico de la enfermedad tenga implicaciones legales, lo que exige un conocimiento adecuado de la epidemiología de la enfermedad, de las medidas de protección, de la toma de muestras y de las características anatomopatológicas. La práctica de autopsias en fallecidos por COVID-19 se ha visto limitada por las obligadas medidas preventivas frente al contagio y por la necesidad de disponer de instalaciones con nivel de protección frente a riesgos biológicos de nivel 3, de modo que las series publicadas hasta la fecha son escasas, y parciales, con abordajes limitados (autopsia mínimamente invasiva o biopsia con aguja gruesa). En este artículo se hace una revisión de los aspectos de la fisiopatología de la enfermedad que tienen repercusión en la infectividad de los tejidos y fluidos del cadáver, de las medidas de prevención del riesgo biológico, de la toma de muestras y de los hallazgos patológicos, tanto macroscópicos como microscópicos, asociados a la muerte provocada por la infección por el virus SARS-CoV-2

Forensic physicians should consider the possibility that people who have died from violent or unknown causes may be infected by the virus SARS-CoV-2, or that the diagnosis of the disease has legal implications, which requires adequate knowledge of the epidemiology of the disease, protective measures, adequate sampling and the pathological characteristics. The practice of autopsies on people who have died from COVID-19 has been limited by the mandatory preventive measures against contagion and by the need for facilities with a level of protection against level-3 biological risk, and therefore series published to date are scarce and partial,with limited approaches (minimally invasive autopsy or needle biopsy). This article reviews the aspects of the pathophysiology of the disease that have an impact on the infectivity of the body's tissues and fluids, measures for preventing biological risk, taking samples and pathological findings, both macroscopic and microscopic, associated with death caused by infection with the SARS-CoV-2 virus

Considering the effect of sexism on psychological intimate partner violence: a study with imprisoned men / El efecto del sexismo en la violencia psicológica de pareja: un estudio con reclusos

Psychological intimate partner violence (IPV) is the most prevalent form of IPV and is often thought to precede physical IPV. However, psychological IPV often occurs independently of other forms of IPV, and it can often emerge during routine relationship interactions. Using data from imprisoned male offenders we investigate the effect of hostile and benevolent sexist attitudes on psychological IPV and the hypothesized mediating role of positive attitudes toward IPV and this effect when accounting for broader risk factors at the levels of community (social disorder), family-of-origin (conflictive climate in family of origin), and personality (antisocial personality traits) variables. The sample involved 196 male inmates of the Penitentiary Center of Villabona (Asturias, Spain). Structural equation models result showed significant total, direct and indirect effect of hostile sexism on psychological IPV, but not of benevolent sexism. When individual, family-of-origin, and community variables were considered, however, hostile sexism showed only an indirect effect on psychological IPV via positive attitudes toward abuse. These results are discussed in light of the debate of the role of sexist attitudes in the psychological IPV explanation when broader models are considered

La violencia de pareja (VP) psicológica es la forma más prevalente de VP y habitualmente suele preceder a la VP física. Sin embargo, la VP psicológica ocurre a menudo independientemente de otras formas de VP y puede darse en interacciones rutinarias con la pareja. Utilizando datos de hombres recluidos en prisión, hemos investigado el efecto del sexismo hostil y benevolente sobre la VP psicológica, así como el rol mediador de las actitudes positivas hacia el abuso de la pareja. Hemos investigado también ese efecto cuando están presentes otros factores de riesgo de VP psicológica señalados en la literatura reciente están presentes: comunidad (desorden social), familia de origen (clima conflictivo en la familia de origen) y factores individuales (rasgos de personalidad antisocial). Participaron en el estudio 196 hombres internos en el Centro Penitenciario de Villabona (Asturias, España). Los resultados de los modelos de ecuaciones estructurales estimados indican un efecto total, directo e indirecto significativo del sexismo hostil sobre la VP psicológica, pero no del sexismo benevolente. Cuando las variables de la comunidad, la familia de origen y factores individuales se incorporaron al modelo únicamente el efecto indirecto del sexismo hostil a través de las actitudes positivas hacia el abuso siguió siendo significativo. Los resultados se discuten en relación con el debate sobre el rol de las actitudes sexistas sobre la VP psicológica en el marco de modelos más generales de violencia

Identificación de mutaciones asociadas con resistencia a inhibidores de la transferencia de cadena de integrasa en pacientes VIH-1 positivos naive para tratamiento antirretroviral en Medellín, Colombia / Identification of mutations associated with resistance to Integrase Strand Transfer Inhibitors (INSTI) in ART-naïve HIV- 1 patients in Medellin, Colombia

Objetivo: Estimar las frecuencias de mutaciones y de polimorfismos adicionales asociados con resistencia a los fármacos inhibidores de la integrasa del virus de inmunodeficiencia humana tipo 1 (VIH-1). Metodología: Estudio descriptivo, de corte transversal, en individuos VIH-1 positivos de la ciudad de Medellín, quienes no habían recibido tratamiento antirretroviral. En ellos se determinó, a través del método de 2-dideoxinucleótidos y el sistema ABI3730XL, la secuencia del gen de la integrasa del VIH-1 a partir del ARN viral circulante, la cual fue analizada en la base de datos de resistencia a medicamentos antirretrovirales de la Universidad de Stanford y según reportes de literatura científica. Resultados: Se encontraron las siguientes mutaciones (con sus respectivas frecuencias): una mutación mayor, E138K (1/46), tres mutaciones accesorias G163E (3/46), L74I (3/50) y E157Q (2/48), una mutación no polimórfica A128T (1/49) y otras dos mutaciones potencialmente asociadas con resistencia a inhibidores de integrasa S230N (9/39) y S119P/R/T (4/47, 2/47 y 14/47, respectivamente). Conclusiones: En las secuencias analizadas, llama la atención la presencia de al menos una mutación asociada a resistencia a inhibidores de integrasa en el 14% de los individuos estudiados, sugiriendo una pobre presión selectiva de este tipo de fármacos en la población viral circulante en la zona.

Aim: To estimate the frequencies of major and accessory mutations, as well as additional polymorphisms associated with resistance to human immunodeficiency virus type 1 (VIH-1) integrase strand transfer inhibitors. Materials and methods: Descriptive cross-sectional study, focused on HIV-1 positive individuals from Medellín, recruited between 2013 and 2015, and that had not received antiretroviral therapy. In these patients, the sequence from HIV-1 integrase was determined from circulating viral RNA through Sanger chain termination method with the ABI3730XL system, and the sequences were analyzed using the HIV Drug Resistance Database from the University of Stanford, together with previous literature reports. Results: The following mutations associated with resistance to integrase strand transfer inhibitors, along with its respective frequencies, were found: one major mutation, E138K (1/46), three accessory mutations, G163E (3/46), L74I (3/50) and E157Q (2/48); one non-polymorphic mutation, A128T (1/49); and two mutations potentially associated with resistance to integrase strand transfer inhibitors, S230N (9/39) and S119P/R/T (4/47, 2/47 and 14/47, respectively). Conclusions: In the sequences analyzed, it is noteworthy the presence of at least one mutation related with resistance to integrase inhibitors in 14% of the studied patients, suggesting a poor selective pressure of this kind of drugs in the circulating viral population in our region.

Síndrome del seno cavernoso como inicio de un linfoma de Burkitt: a propósito de un caso y revisión de la bibliografía / Cavernous sinus syndrome as the initial symptom of Burkitts lymphoma: a case report and literature review

Introducción. El seno cavernoso es una estructura de la base craneal que alberga varias estructuras nerviosas y vasculares. De su afectación se deriva el síndrome del seno cavernoso, una combinación de alteraciones oculomotoras y de las dos primeras ramas del trigémino, frecuentemente acompañadas de dolor o proptosis. La infiltración por un linfoma de Burkitt es una causa infrecuente de este síndrome. Caso clínico. Varón de 43 años, portador del virus de la inmunodeficiencia humana, con buen control de la enfermedad, que desarrolla un cuadro consistente en oftalmoplejía dolorosa progresiva en presencia de adenopatía laterocervical. Las pruebas complementarias permiten el diagnóstico de linfoma de Burkitt con extensión extranodal al seno cavernoso. También se realiza una revisión de los casos publicados en Medline: se recogen un total de 15 casos y se describen sus características epidemiológicas, forma de presentación, afectación extracraneal en el momento del diagnóstico y evolución clínica. Conclusiones. El linfoma de Burkitt es un síndrome linfoproliferativo de alto grado. Su forma asociada a inmunodeficiencia es una importante causa de morbimortalidad en este subgrupo de pacientes. En los casos analizados en la bibliografía, la edad de presentación fue variable y la forma de inicio fue una oftalmoplejía dolorosa progresiva o un síndrome de numb chin. Fue infrecuente una afectación exclusiva del seno cavernoso, pero en ese caso conllevaba un mal pronóstico. Es importante descartar un origen primario extracraneal y no confundirlo con un síndrome de Tolosa-Hunt idiopático que retrasaría el inicio del tratamiento antitumoral

Introduction. The cavernous sinus is a structure in the base of the skull that houses several nerve and vascular structures. Its compromise leads to cavernous sinus syndrome, which is a combination of oculomotor disorders and others affecting the first two trigeminal branches, often accompanied by pain or proptosis. Infiltration due to Burkitts lymphoma is a rare cause of this syndrome. CASE Report. A 43-year-old male, carrier of human immunodeficiency virus, with good control of the disease, who developed a clinical picture consisting of progressive painful ophthalmoplegia in the presence of a laterocervical adenopathy. Complementary tests allowed a diagnosis of Burkitts lymphoma with extranodal extension to the cavernous sinus. A review of the cases published in Medline was also carried out: a total of 15 cases were detected and their epidemiological characteristics, form of presentation, extracranial involvement at the time of diagnosis and clinical progression were described. Conclusions. Burkitts lymphoma is a high-grade lymphoproliferative syndrome. Its form associated with immunodeficiency is an important cause of morbidity and mortality in this subgroup of patients. In the cases analysed in the literature, the age of presentation varied and the form of onset was a progressive painful ophthalmoplegia or numb chin syndrome. Exclusive involvement of the cavernous sinus was infrequent, but in that case it entailed a poor prognosis. It is important to rule out a primary extracranial origin and not to confuse it with an idiopathic Tolosa-Hunt syndrome that would delay the beginning of antitumour treatment