Benzo[a]pyrene promotes an epithelial-to-mesenchymal transition process in MCF10A cells and mammary tumor growth and brain metastasis in female mice.

Breast cancer is the most frequent neoplasia in developed countries and the leading cause of death in women worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process through which epithelial cells decrease or lose their epithelial characteristics and gain mesenchymal properties. EMT mediates tumor progression, because tumor cells acquire the capacity to execute the multiple steps of invasion and metastasis. Benzo[a]pyrene (B[a]P) is an environmental organic pollutant generated during the burning of fossil fuels, wood, and other organic materials. B[a]P exposition increases the incidence of breast cancer, and induces migration and/or invasion in MDA-MB-231 and MCF-7 breast cancer cells. However, the role of B[a]P in the induction of an EMT process and metastasis of mammary carcinoma cells has not been studied in detail. In this study, we demonstrate that B[a]P induces an EMT process in MCF10A mammary non-tumorigenic epithelial cells. In addition, B[a]P promotes the formation of larger tumors in Balb/cJ mice inoculated with 4T1 cells than in untreated mice and treated with dimethyl sulfoxide (DMSO). B[a]P also increases the number of mice with metastasis to brain and the total number of brain metastatic nodules in Balb/cJ mice inoculated with 4T1 cells compared with untreated mice and treated with DMSO. In conclusion, B[a]P induces an EMT process in MCF10A cells and the growth of mammary tumors and metastasis to brain in Balb/cJ mice inoculated with 4T1 cells.

An Insertion Within SIRPß1 Shows a Dual Effect Over Alzheimer's Disease Cognitive Decline Altering the Microglial Response.

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPß1, a surface receptor that triggers amyloid-ß(Aß) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPß1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPß1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPß1 protein isoform landscape compromising its ability to bind oligomeric Aß and its affinity for TYROBP. SIRPß1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aß ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPß1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPß1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aß. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPß1 structural variant might be considered as a potential modulator of this causative pathway.

Cambios en las características epidemiológicas y en el pronóstico de la hepatitis crónica B en personas que viven con VIH / Epidemiological characteristic and prognosis changes in chronic hepatitis B in people living with HIV

Introducción: La vacunación, los avances en el tratamiento frente al virus de la hepatitis B (VHB) y los cambios epidemiológicos producidos en España en las últimas décadas han podido modificar las características y el pronóstico de la hepatitis crónica B (HCB) en personas que viven con VIH (PVIH). Métodos: Estudio observacional retrospectivo donde se incluyeron PVIH-HCB en seguimiento en una unidad de referencia madrileña hasta el año 2019. Se comparó la incidencia y las características epidemiológicas y clínicas según el momento del diagnóstico (antes del año 2000 y posteriormente en periodos de cinco años). Además, se realizó un estudio longitudinal retrospectivo evaluando la tasa de mortalidad, descompensación hepática y factores asociados. Resultados: De 5.452 PVIH, 160 presentaban HCB en el momento basal (prevalencia 2,92%, IC 95%: 2,5-3,4), 85,6% hombres, edad mediana al diagnóstico 32,1 (27-37,2) años. La incidencia (2,4/100 pacientes-año) no varió en los diferentes periodos. Los pacientes diagnosticados antes del 2000 (n = 87) comparados con los diagnosticados entre 2015-2019 (n = 11) con mayor frecuencia eran nativos españoles (90,8 vs. 18,2%), habían consumido drogas intravenosas (55,2 vs. 0), tenían antecedentes de hepatitis C (40 vs. 9,1%) y delta (30,4 vs. 0) y mayor afectación hepática (24,1% cirróticos vs. 0). Tras un seguimiento de 20,4 años, 23 pacientes murieron (7,1/1.000 pacientes-año) y 19 presentaron descompensación hepática (4,9/1.000 pacientes-año), todos diagnosticados antes del año 2010. La mortalidad se asoció con mayor fibrosis hepática basal estimada por Fibroscan® (HR 1,06; IC 95%: 1,03-1,09). Conclusión: Las PVIH-HCB con diagnóstico previo al año 2000 son más frecuentemente de nacionalidad española, infectadas por vía parenteral y con mayor prevalencia de otras coinfecciones. Los pacientes diagnosticados antes del 2010 tienen peor pronóstico condicionado por presentar mayor grado de fibrosis hepática.(AU)

Introduction: Due to hepatitis B virus (HBV) treatment and vaccination during the last decades in Spain, epidemiological and prognosis of chronic hepatitis B (CHB) may have changed. Methods: Retrospective review of CHB–HIV coinfected patients in a single reference center in Madrid until year 2019. We compared incidence, epidemiological and clinical characteristics according diagnosis period (before 2000, 2000–2004, 2005–2009, 2010–2014, 2015–2019). A retrospective longitudinal study was done to assess mortality, related risk factors and hepatic decompensation. Results: Out of 5452 PLHIV, 160 had CHB (prevalence 2.92%; 95% CI: 2.5–3.4), 85.6% were men, median age 32.1 (27–37.2). Incidence rate did not change over the years (2.4/100 patients-year). PLHIV with CHB diagnosed before year 2000 (n = 87) compared with those diagnosed between 2015 and 2019 (n = 11) were more often native-Spanish (90.8% vs. 18.2%), had infected using intravenous drugs (55.2% vs. 0), were coinfected with hepatitis C (40% vs. 9.1%) or hepatitis delta virus (30.4% vs. 0) and had more severe liver disease (cirrhosis 24.1% vs. 0). After a median follow-up of 20.4 years, 23 patients died (7.1/1000 patients-year) and 19 had liver decompensation (4.9/1000 patients-year). All deaths and liver decompensation occurred in patients diagnosed before year 2010. Mortality was associated with higher liver fibrosis in Fibroscan® (HR 1.06, 95% CI: 1.03–1.09). Conclusion: The epidemiology of CHB in PLHIV in our cohort is changing with less native Spanish, more sexually transmitted cases and less coinfection with other hepatotropic virus. Patients diagnosed before 2010 have worst prognosis related to higher grades of liver fibrosis.(AU)

Mesenchymal stromal cell therapy for COVID-19 acute respiratory distress syndrome: a double-blind randomised controlled trial.

Mesenchymal stromal cells (MSC) have immunomodulatory and tissue-regenerative properties and have shown promising results in acute respiratory distress syndrome (ARDS) of multiple causes, including COVID-19. We conducted a randomised (1:1), placebo-controlled, double-blind clinical trial to assess the efficacy and safety of one bone marrow-derived MSC infusion in twenty patients with moderate to severe ARDS caused by COVID-19. The primary endpoint (increase in PaO2/FiO2 ratio from baseline to day 7, MSC 83.3 versus placebo 57.6) was not statistically significant, although a clinical improvement at day 7 in the WHO scale was observed in MSC patients (5, 50% vs 0, 0%, p = 0.033). Median time to discontinuation of supplemental oxygen was also shorter in the experimental arm (14 versus 23 days, p = 0.007), resulting in a shorter hospital stay (17.5 versus 28 days, p = 0.042). No significant differences were observed for other efficacy or safety secondary endpoints. No infusion or treatment-related serious adverse events occurred during the one-year follow-up. This study did not meet the primary endpoint of PaO2/FiO2 increase by day 7, although it suggests that MSC are safe in COVID-19 ARDS and may accelerate patients' clinical recovery and hospital discharge. Larger studies are warranted to elucidate their role in ARDS and other inflammatory lung disorders.Trial Registration: EudraCT Number: 2020-002193-27, registered on July 14th, 2020, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002193-27/ES . NCT number: NCT04615429, registered on November 4th, 2020, https://clinicaltrials.gov/ct2/show/NCT04615429 .

Adults with metabolically healthy overweight or obesity present more brown adipose tissue and higher thermogenesis than their metabolically unhealthy counterparts.

BACKGROUND: There is a subset of individuals with overweight/obesity characterized by a lower risk of cardiometabolic complications, the so-called metabolically healthy overweight/obesity (MHOO) phenotype. Despite the relatively higher levels of subcutaneous adipose tissue and lower visceral adipose tissue observed in individuals with MHOO than individuals with metabolically unhealthy overweight/obesity (MUOO), little is known about the differences in brown adipose tissue (BAT). METHODS: This study included 53 young adults (28 women) with a body mass index (BMI) ≥25 kg/m2 which were classified as MHOO (n = 34) or MUOO (n = 19). BAT was assessed through a static 18F-FDG positron emission tomography/computed tomography scan after a 2-h personalized cooling protocol. Energy expenditure, skin temperature, and thermal perception were assessed during a standardized mixed meal test (3.5 h) and a 1-h personalized cold exposure. Body composition was assessed by dual-energy x-ray absorptiometry, energy intake was determined during an ad libitum meal test and dietary recalls, and physical activity levels were determined by a wrist-worn accelerometer. FINDINGS: Participants with MHOO presented higher BAT volume (+124%, P = 0.008), SUVmean (+63%, P = 0.001), and SUVpeak (+133%, P = 0.003) than MUOO, despite having similar BAT mean radiodensity (P = 0.354). In addition, individuals with MHOO exhibited marginally higher meal-induced thermogenesis (P = 0.096) and cold-induced thermogenesis (+158%, P = 0.050). Moreover, MHOO participants showed higher supraclavicular skin temperature than MUOO during the first hour of the postprandial period and during the cold exposure, while no statistically significant differences were observed in other skin temperature parameters. We observed no statistically significant differences between MHOO and MUOO in thermal perception, body composition, outdoor ambient temperature exposure, resting metabolic rate, energy intake, or physical activity levels. INTERPRETATION: Adults with MHOO present higher BAT volume and activity than MUOO. The higher meal- and cold-induced thermogenesis and cold-induced supraclavicular skin temperature are compatible with a higher BAT activity. Overall, these results suggest that BAT presence and activity might be linked to a healthier phenotype in young adults with overweight or obesity. FUNDING: See acknowledgments section.

The role of veterinarians in zoonosis prevention: Advising families of immunocompromised children with pets.

Background: Pet ownership is widespread, offering numerous benefits to individuals and families. However, the risk of zoonotic diseases must be carefully considered, especially for immunosuppressed patients. Knowledge gaps in preventive measures for zoonoses have been identified, underscoring the vital role of veterinarians in addressing this issue. Objectives: This study aimed to assess the knowledge and recommendations of veterinarians regarding pet ownership by immunocompromised individuals. Additionally, we compared these insights with responses from European healthcare professionals specializing in pediatric transplant recipients. Methods: We conducted an observational, cross-sectional study involving small animal veterinarians in Spain. An online survey was administered to gather information on veterinarians' knowledge of zoonoses and their recommendations for immunocompromised pet owners. Results: A survey of 514 individuals was collected from experienced veterinarians mainly working in primary care clinics. Surprisingly, 63% of respondents did not routinely inquire about the presence of immunocompromised individuals among pet owners, although 54% offered specific recommendations for this group. Most respondents adhered to deworming guidelines for pets owned by immunocompromised individuals and demonstrated sound practices in Leishmania and Leptospira prevention, as well as the avoidance of raw food. However, gaps were noted concerning Bordetella bronchiseptica vaccination. Notably, veterinarians outperformed medical professionals in their knowledge of zoonotic cases and identification of zoonotic microorganisms. The presence of specific recommendations in veterinary clinics was viewed positively by nearly all respondents. Conclusions: Our findings indicate that veterinarians possess a superior understanding of zoonotic pathogens and exhibit greater proficiency in diagnosing zoonoses compared with physicians. They stay well-informed about recommendations outlined in established guidelines and are more likely to provide written recommendations in their clinics than physicians. Nevertheless, knowledge gaps among veterinarians emphasize the need for enhanced communication between medical and veterinary professionals. Reinforcing the "One Health" concept is imperative, with veterinarians playing a pivotal role in this collaborative effort.

Epidemiological characteristic and prognosis changes in chronic hepatitis B in people living with HIV.

INTRODUCTION: Due to hepatitis B virus (HBV) treatment and vaccination during the last decades in Spain, epidemiological and prognosis of chronic hepatitis B (CHB) may have changed. METHODS: Retrospective review of CHB-HIV coinfected patients in a single reference center in Madrid until year 2019. We compared incidence, epidemiological and clinical characteristics according diagnosis period (before 2000, 2000-2004, 2005-2009, 2010-2014, 2015-2019). A retrospective longitudinal study was done to assess mortality, related risk factors and hepatic decompensation. RESULTS: Out of 5452 PLHIV, 160 had CHB (prevalence 2.92%; 95%CI 2.5-3.4), 85.6% were men, median age 32.1 (27-37.2). Incidence rate did not change over the years (2.4/100 patients-year). PLHIV with CHB diagnosed before year 2000 (n = 87) compared with those diagnosed between 2015 and 2019 (n = 11) were more often native-Spanish (90.8% vs. 18.2%), had infected using intravenous drugs (55.2% vs. 0), were coinfected with hepatitis C (40% vs. 9.1%) or hepatitis delta virus (30.4% vs. 0) and had more severe liver disease (cirrhosis 24.1% vs. 0). After a median follow-up of 20.4 years, 23 patients died (7.1/1000 patients-year) and 19 had liver decompensation (4.9/1000 patients-year). All deaths and liver decompensation occurred in patients diagnosed before year 2010. Mortality was associated with higher liver fibrosis in Fibroscan® (HR 1.06, 95% CI 1.03-1.09). CONCLUSION: The epidemiology of CHB in PLHIV in our cohort is changing with less native Spanish, more sexually transmitted cases and less coinfection with other hepatotropic virus. Patients diagnosed before 2010 have worst prognosis related to higher grades of liver fibrosis.

Leukaemic Presentation of Small-Cell Alk-Positive Anaplastic Large Cell Lymphoma in a Young Woman-Report of a Case with 9-Year Survival.

Anaplastic large cell lymphoma (ALCL) with leukaemic presentation (either ab initio or along the course of the disease) has been rarely reported. Irrespective of ALK expression in the neoplastic cells, it features a dismal prognosis. We report a rare case of leukaemic, small cell variant ALK-positive ALCL with 9-year survival in a young woman who was treated upfront with corticosteroids and standard chemotherapy, and review thoroughly the previously published cases. Such an unexpected, good outcome hints at the existence of different clinical subgroups in the leukaemic variant of ALK-positive ALCL.

Influence of the dental arch and number of cutting-off and rescanning mesh holes on the accuracy of implant scans in partially edentulous situations.

OBJECTIVES: To evaluate the influence of the dental arch and cutting-off and rescanning procedures on the accuracy of complete-arch implant scans in partially edentulous arches. MATERIAL AND METHODS: A maxillary and a mandibular partially edentulous typodont with implant abutment analogs placed in the right and left first molar and right central incisor sites were digitized to create reference models by using an industrial optical scanner (7 Series Desktop Scanner; Dentalwings). Two experimental groups were scanned using an intraoral scanner (IOS) (TRIOS 4; 3Shape A/S): the Maxillary group (Mx) and the Mandibular group (Mb). Four subgroups were generated depending on the number of rescanned mesh holes: No holes (Mx-G0, Mb-G0), 1 hole (Mx-G1, Mb-G1), 2 holes (Mx-G2, Mb-G2) and 3 holes (Mx-G3, Mb-G3). A 3-dimensional metrology software (Geomagic Control X; 3D Systems) was used to measure the difference between the reference and the experimental scans computing the root mean square (RMS) error calculation. Two-way ANOVA and a post-hoc Tukey test were used to analyze the trueness data (α=0.05). Levene test was used to evaluate the prevision (α=0.05). RESULTS: The Mx group obtained a trueness mean value of 54 ± 17 µm and a mean precision value of 54 ± 17 µm, while the Mb group presented a trueness mean value of 67 ± 23 µm and a mean precision value of 66 ± 22 µm. The Mx group demonstrated significantly better trueness than the Mb group (P<.001). The G0 and G1 subgroups had the highest trueness values among the subgroups tested. No significant difference was observed between G0 and G1, G1 and G2, and G2 and G3 subgroups in trueness and precision. However, the G0 had significantly better trueness and precision values compared to G2 and G3 subgroups. In addition, the G1 had significantly better trueness values than the G3 subgroup. However, the Levene test revealed no difference in the precision mean values among the subgroups tested. CONCLUSIONS: Implant scanning trueness was affected by the dental arch and the number of rescanned mesh holes using the IOS tested. A higher number of rescanned mesh holes decreased the scanning trueness. The stitching algorithm of the IOS software tested after the mesh hole scan demonstrated a significant error, especially when multiples mesh holes are involved in the same arch. CLINICAL SIGNIFICANCE: Given that cutting-off and rescanning techniques can reduce trueness, clinicians should consider whether these techniques are necessary in complete digital workflows. This is particularly important when fabricating multiple single implant-supported restorations in the same arch.

Lifestyles, arterial aging, and its relationship with the intestinal and oral microbiota (MIVAS III study): a research protocol for a cross-sectional multicenter study.

Background: The microbiota is increasingly recognized as a significant factor in the pathophysiology of many diseases, including cardiometabolic diseases, with lifestyles probably exerting the greatest influence on the composition of the human microbiome. The main objectives of the study are to analyze the association of lifestyles (diet, physical activity, tobacco, and alcohol) with the gut and oral microbiota, arterial aging, and cognitive function in subjects without cardiovascular disease in the Iberian Peninsula. In addition, the study will examine the mediating role of the microbiome in mediating the association between lifestyles and arterial aging as well as cognitive function. Methods and analysis: MIVAS III is a multicenter cross-sectional study that will take place in the Iberian Peninsula. One thousand subjects aged between 45 and 74 years without cardiovascular disease will be selected. The main variables are demographic information, anthropometric measurements, and habits (tobacco and alcohol). Dietary patterns will be assessed using a frequency consumption questionnaire (FFQ) and the Mediterranean diet adherence questionnaire. Physical activity levels will be evaluated using the International Physical Activity Questionnaire (IPAQ), Marshall Questionnaire, and an Accelerometer (Actigraph). Body composition will be measured using the Inbody 230 impedance meter. Arterial aging will be assessed through various means, including measuring medium intimate carotid thickness using the Sonosite Micromax, conducting analysis with pulse wave velocity (PWA), and measuring pulse wave velocity (cf-PWV) using the Sphygmocor System. Additional cardiovascular indicators such as Cardio Ankle Vascular Index (CAVI), ba-PWV, and ankle-brachial index (Vasera VS-2000®) will also be examined. The study will analyze the intestinal microbiota using the OMNIgene GUT kit (OMR-200) and profile the microbiome through massive sequencing of the 16S rRNA gene. Linear discriminant analysis (LDA), effect size (LEfSe), and compositional analysis, such as ANCOM-BC, will be used to identify differentially abundant taxa between groups. After rarefying the samples, further analyses will be conducted using MicrobiomeAnalyst and R v.4.2.1 software. These analyses will include various aspects, such as assessing α and ß diversity, conducting abundance profiling, and performing clustering analysis. Discussion: Lifestyle acts as a modifier of microbiota composition. However, there are no conclusive results demonstrating the mediating effect of the microbiota in the relationship between lifestyles and cardiovascular diseases. Understanding this relationship may facilitate the implementation of strategies for improving population health by modifying the gut and oral microbiota. Trial registration: clinicaltrials.gov/ct2/show/NCT04924907, ClinicalTrials.gov, identifier: NCT04924907. Registered on 21 April 2021.

Bisphenol A increases the size of primary mammary tumors and promotes metastasis in a murine model of breast cancer.

Triple negative breast cancer (TNBC) is a subtype of breast tumor characterized for the absence of estrogen and progesterone receptors expression and low HER2/neu expression. Bisphenol A (BPA) is an endocrine disrupting chemical with estrogenic activity that has been associated with increasing rates of breast cancer. Moreover, BPA is a solid organic synthetic chemical employed in the manufacture of many consumer products, epoxy resins and polycarbonate plastics including baby bottles, containers for food and beverages, and the lining of beverage cans. The G-protein-coupled estrogen receptor (GPER) is activated by endogenous hormones and synthetic ligands, such as BPA. GPER is expressed in TNBC cells and its expression is associated with larger tumor size, metastasis and worse survival prognosis. In breast cancer cells, BPA induces activation of signal transduction pathways that mediates migration and invasion via GPER in human TNBC MDA-MB-231 cells. In this study, we demonstrate that BPA induces an increase of GPER expression and its translocation from cytosol to cytoplasmic membrane, metalloproteinase (MMP)-2 and MMP-9 secretion, migration and invasion in murine TNBC 4T1 cells. In a murine TNBC model "in vivo" using 4T1 cells, BPA induces the formation of mammary tumors with more weight and volume, and an increase in the number of mice with metastasis to lung and nodules in lung compared with tumors and metastasis to lung of untreated Balb/cJ mice. In conclusion, our findings demonstrate that BPA mediates the growth of mammary primary tumors and metastasis to lung in a murine model of breast cancer.

[How to provide a Public Health response with a multidisciplinary approach based on the COVID-19 period.] / Cómo dar una respuesta de Salud Pública con un enfoque multidisciplinar, basándose en la experiencia del período de la COVID-19.

The establishment of regulatory measures and restrictions to take control of the COVID-19 pandemic generated uncertainty and a request for information among the population. To address this demand, the Public Health Department (DGSPCC) of the Government of La Rioja (Spain) created a multidisciplinary work group. This group worked in a coordinated multidisciplinary manner to respond to general inquiries and doubts, generate risk assessments of multitudinous events, and create guides and summaries of preventive measures. Every event was assessed individually and, based on the corresponding risk assignment, a recommendation for its execution or the need for additional measures was issued. In any case, citizens were encouraged to behave cautiously to avoid potential risks of spreading the SARS-CoV-2 virus. Our goal was to report a multidisciplinary collaborative experience in the area of public health.

En el seno de la Dirección General de Salud Pública, Consumo y Cuidados (DGSPCC) del Gobierno de La Rioja se articuló un procedimiento de actuación, siendo su finalidad dar respuesta a la ciudadanía ante la gran incertidumbre surgida como consecuencia de las medidas y restricciones para el control de la pandemia de la COVID-19. Se desarrolló un trabajo coordinado de colaboración multidisciplinar para responder consultas y dudas, evaluar el riesgo en la celebración de eventos multitudinarios y elaborar guías para la difusión de medidas preventivas. Tras la evaluación de cada caso, se establecía una gradación del riesgo y, de acuerdo con ello, se recomendaba la realización del evento, la adopción de medidas adicionales o la suspensión del mismo. En todo momento se apelaba al deber de cautela y protección de la ciudadanía para adoptar las medidas necesarias con el fin de evitar la generación de riesgos de propagación del virus SARS-CoV-2. El objetivo de este trabajo fue comunicar la experiencia de la colaboración multiprofesional en el ámbito de la Salud Pública.

COVID-19 Y su relación con factores sociodemográficos en la etapa pre-vacunatoria, provincia de Tucumán, Argentina, 2020-2021 / COVID-19 and its relationship with sociodemographic factors in the pre-vaccination period in Tucumán Province, Argentina, 2020-2021

RESUMEN INTRODUCCIÓN El impacto de COVID-19 en una población puede explicarse a través de los factores sociodemográficos y las respuestas de intervención. El objetivo fue evaluarlo en la provincia de Tucumán en la etapa previa a la vacunación. Se analizó la incidencia, letalidad y mortalidad de COVID-19 a nivel provincial y departamental, y se identificaron los factores sociodemográficos asociados. MÉTODOS Se realizó un estudio observacional de tipo ecológico con fuentes de datos secundarias en Tucumán. El período fue de marzo de 2020 a marzo de 2021. RESULTADOS Se registró una tasa de incidencia de COVID-19 de 4941 por 100 000 habitantes y una tasa de mortalidad de 93,29 por 100 000 habitantes. La incidencia de casos fue similar en varones y mujeres, y el grupo de 30 a 49 años presentó las tasas más altas. La tasa de mortalidad y letalidad en varones fue mayor que en mujeres, y en ambos sexos el grupo de 80 años o más presentó las mayores tasas. A nivel departamental, Capital, Tafí Viejo, Cruz Alta y Yerba Buena tuvieron las tasas de incidencia más altas. Burruyacú, Monteros y Trancas registraron las mayores tasas de mortalidad y letalidad. La incidencia de casos se vio afectada por la densidad poblacional y por el porcentaje de personas en hogares con alguna necesidad básica insatisfecha. DISCUSIÓN Se resalta la importancia de conocer la estructura, funcionalidad e identidad de las ciudades para comprender mejor su capacidad de resiliencia y adaptación frente a eventos como COVID-19.

ABSTRACT INTRODUCTION The population impact of COVID-19 can be explained by socio-demographic factors and the intervention responses. The objective was to evaluate it in the province of Tucumán in the pre-vaccination stage. Incidence, lethality and mortality of COVID-19 at province and department level were analyzed, identifying associated socio-demographic factors. METHODS An observational ecological study was conducted in Tucumán using secondary data sources. The period of study was from March 2020 to March 2021. RESULTS There was an incidence rate of COVID-19 of 4941 per 100000 inhabitants and a mortality rate of 93.29 per 100000 inhabitants. The incidence of cases was similar among males and females, and the age group between 30 and 49 years showed the highest rates. Mortality and lethality were higher in men than in women, and in both sexes the age group of 80 years and over presented the highest rates. At department level, Capital, Tafí Viejo, Cruz Alta and Yerba Buena had the highest incidence rates. Burruyacú, Monteros and Trancas had the highest mortality and lethality rates. The incidence of cases was affected by population density and by the percentage of people living in households with an unsatisfied basic need. DISCUSSION This work highlights the importance of knowing the structure, functionality and identity of cities to better understand their resilience and adaptation capacity in the face of events such as COVID-19.

Cómo dar una respuesta de Salud Pública con un enfoque multidisciplinar, basándose en la experiencia del período de la COVID-19 / How to provide a Public Health response with a multidisciplinary approach based on the COVID-19 period

En el seno de la Dirección General de Salud Pública, Consumo y Cuidados (DGSPCC) del Gobierno de La Rioja se articuló un procedi-miento de actuación, siendo su finalidad dar respuesta a la ciudadanía ante la gran incertidumbre surgida como consecuencia delas medidas y restricciones para el control de la pandemia de la COVID-19. Se desarrolló un trabajo coordinado de colaboración mul-tidisciplinar para responder consultas y dudas, evaluar el riesgo en la celebración de eventos multitudinarios y elaborar guías parala difusión de medidas preventivas. Tras la evaluación de cada caso, se establecía una gradación del riesgo y, de acuerdo con ello, serecomendaba la realización del evento, la adopción de medidas adicionales o la suspensión del mismo. En todo momento se apelabaal deber de cautela y protección de la ciudadanía para adoptar las medidas necesarias con el fin de evitar la generación de riesgosde propagación del virus SARS-CoV-2. El objetivo de este trabajo fue comunicar la experiencia de la colaboración multiprofesional enel ámbito de la Salud Pública.(AU)

The establishment of regulatory measures and restrictions to take control of the COVID-19 pandemic generated uncertainty and arequest for information among the population. To address this demand, the Public Health Department (DGSPCC) of the Governmentof La Rioja (Spain) created a multidisciplinary work group. This group worked in a coordinated multidisciplinary manner to respond togeneral inquiries and doubts, generate risk assessments of multitudinous events, and create guides and summaries of preventive me-asures. Every event was assessed individually and, based on the corresponding risk assignment, a recommendation for its executionor the need for additional measures was issued. In any case, citizens were encouraged to behave cautiously to avoid potential risksof spreading the SARS-CoV-2 virus. Our goal was to report a multidisciplinary collaborative experience in the area of public health.(AU)

Use of Monoclonal Antibodies in Immunocompromised Patients Hospitalized with Severe COVID-19: A Retrospective Multicenter Cohort.

OBJECTIVE: We aim to describe the safety and efficacy of sotrovimab in severe cases of COVID-19 in immunocompromised hosts. METHODS: We used a retrospective multicenter cohort including immunocompromised hospitalized patients with severe COVID-19 treated with sotrovimab between October 2021 and December 2021. RESULTS: We included 32 patients. The main immunocompromising conditions were solid organ transplantation (46.9%) and hematological malignancy (37.5%). Seven patients (21.9%) had respiratory progression: 12.5% died and 9.4% required mechanical ventilation. Patients treated within the first 14 days of their symptoms had a lower progression rate: 12.0% vs. 57.1%, p = 0.029. No adverse event was attributed to sotrovimab. CONCLUSIONS: Sotrovimab was safe and may be effective in its use for immunocompromised patients with severe COVID-19. More studies are needed to confirm these preliminary data.

Dynamic state of plasmid genomic architectures resulting from XerC/D-mediated site-specific recombination in Acinetobacter baumannii Rep_3 superfamily resistance plasmids carrying blaOXA-58 - and TnaphA6-resistance modules.

The acquisition of bla OXA genes encoding different carbapenem-hydrolyzing class-D ß-lactamases (CHDL) represents a main determinant of carbapenem resistance in the nosocomial pathogen Acinetobacter baumannii. The blaOXA-58 gene, in particular, is generally embedded in similar resistance modules (RM) carried by plasmids unique to the Acinetobacter genus lacking self-transferability. The ample variations in the immediate genomic contexts in which blaOXA-58 -containing RMs are inserted among these plasmids, and the almost invariable presence at their borders of non-identical 28-bp sequences potentially recognized by the host XerC and XerD tyrosine recombinases (pXerC/D-like sites), suggested an involvement of these sites in the lateral mobilization of the gene structures they encircle. However, whether and how these pXerC/D sites participate in this process is only beginning to be understood. Here, we used a series of experimental approaches to analyze the contribution of pXerC/D-mediated site-specific recombination to the generation of structural diversity between resistance plasmids carrying pXerC/D-bounded bla OXA-58- and TnaphA6-containing RM harbored by two phylogenetically- and epidemiologically-closely related A. baumannii strains of our collection, Ab242 and Ab825, during adaptation to the hospital environment. Our analysis disclosed the existence of different bona fide pairs of recombinationally-active pXerC/D sites in these plasmids, some mediating reversible intramolecular inversions and others reversible plasmid fusions/resolutions. All of the identified recombinationally-active pairs shared identical GGTGTA sequences at the cr spacer separating the XerC- and XerD-binding regions. The fusion of two Ab825 plasmids mediated by a pair of recombinationally-active pXerC/D sites displaying sequence differences at the cr spacer could be inferred on the basis of sequence comparison analysis, but no evidence of reversibility could be obtained in this case. The reversible plasmid genome rearrangements mediated by recombinationally-active pairs of pXerC/D sites reported here probably represents an ancient mechanism of generating structural diversity in the Acinetobacter plasmid pool. This recursive process could facilitate a rapid adaptation of an eventual bacterial host to changing environments, and has certainly contributed to the evolution of Acinetobacter plasmids and the capture and dissemination of bla OXA-58 genes among Acinetobacter and non-Acinetobacter populations co-residing in the hospital niche.

Influence of print orientation and wet-dry storage time on the intaglio accuracy of additively manufactured occlusal devices.

STATEMENT OF PROBLEM: Different factors can affect the manufacturing accuracy of additively manufactured dental devices; however, the influence of print orientation and wet-dry storage time on their intaglio accuracy remains uncertain. PURPOSE: The purpose of this in vitro study was to assess the effect of print orientation (0, 45, 70, and 90 degrees) and wet-dry storage time (0, 30, 60, and 90 days) on the intaglio accuracy of additively manufactured occlusal devices. MATERIAL AND METHODS: An occlusal device design was obtained in a standard tessellation language (STL) file format (control file) which was used to fabricate all the specimens by using a stereolithography printer (Form 3+) and a biocompatible resin material (Dental LT Clear Resin, V2). Four groups were created based on the print orientation used to manufacture the specimens: 0, 45, 70, and 90 degrees. Each group was divided into 4 subgroups depending on the time elapsed between manufacturing and accuracy evaluation: 0, 30, 60, and 90 days. For the subgroup 0, a desktop scanner (T710) was used to digitize all the specimens. The 30-day subgroup specimens were stored for 30 days with the following daily storage protocol: 16 hours inside a dry lightproof container, followed by 8 hours in artificial saliva (1700-0305 Artificial Saliva) inside the same lightproof container. The specimens were then digitized by following the same procedures used for subgroup 0. For the subgroups 60 and 90, the identical procedures described for subgroup 30 were completed but after 60 and 90 days of storage, respectively. The reference STL file was used to measure the intaglio discrepancy with the experimental scans obtained among the different subgroups by using the root mean square error calculation. Two-way ANOVA and post hoc Tukey pairwise comparison tests were used to analyze the data (α=.05). RESULTS: Print orientation (P<.001) and usage time (P<.001) were significant predictors of the trueness value obtained. Additionally, the 0-degree print orientation at day 0 group demonstrated the best trueness value among all the groups tested (P<.05). No significant trueness discrepancies were found among the 45-, 70-, and 90-degree print orientation, or among the 30, 60, and 90 days of storage. A significant precision difference was found in the variance between print orientation groups across usage time subgroups. CONCLUSIONS: The print orientation and wet-dry storage times tested influenced the trueness and precision of the intaglio surfaces of the occlusal devices manufactured with the 3D printer and material selected.