Aberrant spliceosome activity via elevated intron retention and upregulation and phosphorylation of SF3B1 in chronic lymphocytic leukemia.

Splicing factor 3b subunit 1 (SF3B1) is the largest subunit and core component of the spliceosome. Inhibition of SF3B1 was associated with an increase in broad intron retention (IR) on most transcripts, suggesting that IR can be used as a marker of spliceosome inhibition in chronic lymphocytic leukemia (CLL) cells. Furthermore, we separately analyzed exonic and intronic mapped reads on annotated RNA-sequencing transcripts obtained from B cells (n = 98 CLL patients) and healthy volunteers (n = 9). We measured intron/exon ratio to use that as a surrogate for alternative RNA splicing (ARS) and found that 66% of CLL-B cell transcripts had significant IR elevation compared with normal B cells (NBCs) and that correlated with mRNA downregulation and low expression levels. Transcripts with the highest IR levels belonged to biological pathways associated with gene expression and RNA splicing. A >2-fold increase of active pSF3B1 was observed in CLL-B cells compared with NBCs. Additionally, when the CLL-B cells were treated with macrolides (pladienolide-B), a significant decrease in pSF3B1, but not total SF3B1 protein, was observed. These findings suggest that IR/ARS is increased in CLL, which is associated with SF3B1 phosphorylation and susceptibility to SF3B1 inhibitors. These data provide additional support to the relevance of ARS in carcinogenesis and evidence of pSF3B1 participation in this process.

Characterization of polyphenols and carbohydrates exuded by Phaeodactylum tricornutum diatom grown under Cu stress.

This study is focused on analysing polyphenols and carbohydrates released by Phaeodactylum tricornutum (P. tricornutum) diatoms cultured in natural seawater enriched with sublethal and lethal Cu doses. Cu concentrations of 0.31, 0.79 and 1.57 µM reduced cell densities by 37, 82 and 91%, respectively, compared to the control. The total sum of all identified polyphenols and total carbohydrates released by cells grown under lethal Cu levels increased up to 18.8 and 107.4 times, respectively, compared to data from a control experiment. Four different in vitro assays were used to estimate the antioxidant activities of the extracellular compounds: 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical inhibition, cupric ion reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power and Cu complexing ability (CCA). The highest antioxidant activities were observed in the Cu lethal treatments, where the CCA assay exhibited a greater increase (up to 32.2 times higher than that found in the control experiment) to reduce the concentration of free Cu in the medium and its toxicity. The presence of Cu stimulated the release of polyphenols and carbohydrates to the medium as a detoxification mechanism to survive under lethal levels of Cu regulating its speciation.

Public health surveillance and the data, information, knowledge, intelligence and wisdom paradigm / Vigilancia de salud pública y el paradigma de datos, información, conocimiento, inteligencia y sabiduría / Vigilância em saúde pública e o paradigma de dados, informações, conhecimento, inteligência e sabedoria

ABSTRACT This article points out deficiencies in present-day definitions of public health surveillance, which include data collection, analysis, interpretation and dissemination, but not public health action. Controlling a public health problem of concern requires a public health response that goes beyond information dissemination. It is undesirable to have public health divided into data generation processes (public health surveillance) and data use processes (public health response), managed by two separate groups (surveillance experts and policy-makers). It is time to rethink the need to modernize the definition of public health surveillance, inspired by the authors' enhanced Data, Information, Knowledge, Intelligence and Wisdom model. Our recommendations include expanding the scope of public health surveillance beyond information dissemination to comprise actionable knowledge (intelligence); mandating surveillance experts to assist policy-makers in making evidence-informed decisions; encouraging surveillance experts to become policy-makers; and incorporating public health literacy training - from data to knowledge to wisdom - into the curricula for all public health professionals. Work on modernizing the scope and definition of public health surveillance will be a good starting point.

RESUMEN En este artículo se señalan las deficiencias de las definiciones actuales de la vigilancia de salud pública, que incluyen la recopilación, el análisis, la interpretación y la difusión de los datos, pero no las medidas de salud pública. El control de un problema de salud pública de interés exige una respuesta de salud pública que vaya más allá de la difusión de información. No es deseable que la salud pública esté dividida por un lado en procesos de generación de datos (vigilancia de salud pública) y por otro en procesos de uso de datos (respuesta de salud pública), gestionados por dos grupos diferentes (expertos en vigilancia y responsables de la formulación de políticas). Ha llegado el momento de replantear la necesidad de modernizar la definición de la vigilancia de salud pública tomando como referencia el modelo mejorado de Datos, Información, Conocimiento, Inteligencia y Sabiduría de los autores. Entre las recomendaciones que se proponen se encuentran las de ampliar el alcance de la vigilancia de salud pública más allá de la difusión de información para que incluya también el conocimiento aplicable (inteligencia); instar a los expertos en vigilancia a que presten ayuda a los responsables de la formulación de políticas en la toma de decisiones basadas en la evidencia; alentar a los expertos en vigilancia a que se conviertan en responsables de la formulación de políticas; e incorporar la formación en conocimientos básicos de salud pública (desde los datos hasta los conocimientos y la sabiduría) en los planes de estudio de todos los profesionales de la salud pública. Un buen punto de partida será trabajar en la modernización del alcance y la definición de la vigilancia de salud pública.

RESUMO Este artigo aponta deficiências nas definições atuais de vigilância em saúde pública, que incluem coleta, análise, interpretação e disseminação de dados, mas não ações de saúde pública. O controle de um problema preocupante de saúde pública exige uma resposta de saúde pública que vá além da disseminação de informações. A saúde pública não deve ser dividida em processos de geração de dados (vigilância em saúde pública) e processos de uso de dados (resposta de saúde pública) gerenciados por dois grupos distintos (especialistas em vigilância e formuladores de políticas). É hora de repensar a necessidade de modernizar a definição de vigilância em saúde pública, inspirada no modelo aprimorado de Dados, Informações, Conhecimento, Inteligência e Sabedoria dos autores. Nossas recomendações incluem: expansão do escopo da vigilância em saúde pública para além da disseminação de informações, de modo a abranger conhecimentos acionáveis (inteligência); obrigatoriedade de que os especialistas em vigilância auxiliem os formuladores de políticas na tomada de decisões baseadas em evidências; incentivo para que os especialistas em vigilância se tornem formuladores de políticas; e incorporação de capacitação em letramento em saúde pública (partindo dos dados para o conhecimento e em seguida para a sabedoria) nos currículos de todos os profissionais de saúde pública. O trabalho de modernizar o escopo e a definição de vigilância em saúde pública será um bom ponto de partida.

Bacteremia by non-O1/non-O139 Vibrio cholerae: Case description and literature review / Bacteriemia por Vibrio cholerae no-O1/no-O139: descripción de un caso y revisión de la literatura

Bacteremia by non-O1/non-O139 Vibrio cholerae is a rare entity associated with high mortality rates. We report a case of non-O1/non-O139 V. cholerae bacteremia confirmed by polymerase chain reaction and agglutination tests. The clinicoepidemiological characteristics and therapeutic options for this infection are also described.

La bacteriemia por Vibrio cholerae no-O1/no-O139 es una entidad poco frecuente que se asocia con altas tasas de mortalidad. Se reporta un caso de bacteriemia por V. cholerae no-O1/no-O139 confirmado por reacción en cadena de la polimerasa y test de aglutinación. Se describen las características clinicoepidemiológicas y las opciones terapéuticas para esta infección.

Copper toxicity leads to accumulation of free amino acids and polyphenols in Phaeodactylum tricornutum diatoms.

This work is focused on the effect of lethal and sub-lethal copper (Cu) concentrations on the free amino acid and polyphenol production by the marine diatom Phaeodactylum tricornutum (P. tricornutum) after 12, 18, and 21 days of exposure. The concentrations of 10 amino acids (arginine, aspartic acid, glutamic acid, histidine, lysine, methionine, proline, valine, isoleucine, and phenylalanine) and 10 polyphenols (gallic acid, protocatechuic acid, p-coumaric acid, ferulic acid, catechin, vanillic acid, epicatechin syringic acid, rutin, and gentisic acid) were measured by RP-HPLC. Under lethal doses of Cu, free amino acids reached levels significantly higher than those in the control cells (up to 21.9 times higher), where histidine and methionine showed the highest increases (up to 37.4 and 65.8 times higher, respectively). The total phenolic content also increased up to 11.3 and 5.59 times higher compared to the reference cells, showing gallic acid the highest increase (45.8 times greater). The antioxidant activities of cells exposed to Cu were also enhanced with increasing doses of Cu(II). They were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging ability (RSA), cupric ion reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays. Malonaldehyde (MDA) exhibited the same tendency: cells grown at the highest lethal Cu concentration yielded the highest MDA level. These findings reflect the involvement of amino acids and polyphenols in protective mechanisms to overcome the toxicity of copper in marine microalgae.

Predictors and Management of Relapse to Axicabtagene Ciloleucel in Patients with Aggressive B-cell Lymphoma.

OBJECTIVE/BACKGROUND: Despite the success of chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive non-Hodgkin lymphoma (aNHL), some patients still fail treatment, and their prognosis is dismal. METHODS: We performed a retrospective study of aNHL patients treated with axicabtagene ciloleucel (axi-cel) at two Mayo Clinic centers between 2018 and 2020. We evaluated predictive factors, toxicities, and responses to salvage regimens after CAR T-cell therapy. RESULTS: Thirty-four patients received axi-cel with a median length of hospitalization of 14 days. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 91% and 41% of patients, respectively. Furthermore, 71% of patients responded to therapy, with 53% achieving a complete response (CR). The CRS grade and absolute lymphocyte count at leukapheresis (ALCLeuk) correlated with CR and overall survival (OS), respectively. After a median follow-up of 6.8 months (interquartile range [IQR] 4.6-14.9), 15 patients (44%) showed progressive disease (PD). Most patients (60%) progressed during the first 3 months and had persistent CD19 tumor expression. Elevated C-reactive protein at baseline increased the risk of PD, whereas elevated ferritin increased PD and mortality risk. Twelve patients received salvage therapy, but only three responded. Median OS of relapsed/refractory patients to axi-cel was 3 months (IQR 1.3-5.1). CONCLUSION: The grade of CRS and ALCLeuk correlated with better outcomes to axi-cel therapy. In addition, elevated inflammatory markers at baseline were associated with PD and shorter survival. Relapses after treatment frequently occur within months after axi-cel infusion; they confer a poor prognosis and create an urgent need for novel and effective treatment options in this patient population.

Incidence of hypertension in young transgender people after a 5-year follow-up: association with gender-affirming hormonal therapy.

In order to assess the risk of hypertension development, we performed a retrospective analysis of the clinical records of consecutive transgender patients who began gender-affirming hormonal therapy in our Outpatient Gender Identity Clinic with <30 years of age and had a follow-up >5 years. 149 transgender women treated with estradiol and 153 transgender men treated with testosterone were included; 129 of the transgender women received also androgen blockers (54 spironolactone, 49 cyproterone acetate and 26 LHRH agonists). The annual incidence of hypertension in young transgender men (1.18%) seemed comparable to that of the general population. In young transgender women, it seemed higher (2.14%); we found that the choice of androgen blocker had a remarkable effect, with a highly significant increase in patients treated with cyproterone acetate (4.90%) vs. the rest (0.80%); the adjusted hazard-ratio was 0.227 (p = 0.001). Correlation, logistic regression and mediation analyses were performed for the associations of the available clinical variables with the increase in systolic blood pressure and the onset of hypertension, but besides the use of cyproterone acetate, only the ponderal gain was found significant (Spearman's r: 0.361, p < 0.001); with a 36.7% mediation effect (31.2-42.3%). Cyproterone acetate has additional known risks, such as meningioma; although we cannot conclusively prove that it has a role in the development of hypertension, we conclude that the use of cyproterone acetate for this indication should be reconsidered.

Incidence of thrombosis in relapsed/refractory B-cell lymphoma treated with axicabtagene ciloleucel: Mayo Clinic experience.

Chimeric antigen receptor (CAR) T-cell therapy is effective in relapsed/refractory large B-cell lymphoma and results in a unique toxicity profile, namely cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. The hyper-inflammatory state associated with these toxicities has been suggested to increase the risk of thrombosis. We conducted a retrospective analysis of patients treated with axicabtagene ciloleucel (axi-cel) to assess the rate of thrombosis with axi-cel therapy from the time of CAR T-cell infusion until the end of hospitalization, when performed in the inpatient setting, or up to day +30 when performed in the outpatient setting. Ninety-two (95%) of 97 patients were hospitalized during axi-cel therapy and 85 (88%) developed CRS. Fifty-five patients (57%) received concurrent anticoagulation (53 as prophylaxis). Patients with prior VTE did not have progression or evidence of new VTE. Only 2 (2.1%) patients developed VTE. These results demonstrate a low-risk for thrombosis in axi-cel recipients.

Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Trial NCT0231576.

Ibrutinib-based therapies are costly and require continuous administration. We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-naïve CLL patients to receive ibrutinib plus obinutuzumab, followed by single-agent ibrutinib. Patients could discontinue ibrutinib after 36 months with sustained complete response (CR). We evaluated treatment safety, efficacy, and outcomes after ibrutinib discontinuation. The overall response rate was 100%, 28% achieved a CR, and 12.5% achieved bone marrow undetectable minimal residual disease. At a three-year median follow-up, 91% remain in remission with 100% overall survival. Five patients in sustained CR stopped ibrutinib and have not progressed. Eight non-CR patients discontinued for other reasons, with only two progressing. The treatment was safe, with a lower IRR rate. All patients responded to treatment with longer time-to-progression after discontinuation of ibrutinib. Our data support the evaluation of ibrutinib discontinuation strategies in more extensive clinical trials (https://Clinicaltrials.gov Identifier https://clinicaltrials.gov/ct2/show/NCT02315768).

Análisis de impacto presupuestal de la vacunación contra COVID-19 en América Latina / Analysis of budgetary impact of COVID-19 vaccination in Latin America / Análise do impacto orçamentário da vacinação contra a COVID-19 na América Latina

RESUMEN Objetivo. Estimar el impacto presupuestal de la vacunación contra COVID-19 en seis países de América Latina: Argentina, Brasil, Chile, Colombia, México y Perú, durante el periodo 2021-2022. Métodos. Se evaluaron las vacunas de Sinopharm (BBIBP-CorV), Janssen (JNJ-78436735), Instituto de Gamaleya (Gam-COVID-Vac), Sinovac (CoronaVac), CanSino (Convidecia), AstraZeneca (Vaxzevria), Moderna (mRNA-1273) y Pfizer (BNT162b2), según disponibilidad para cada país. Se adoptó la perspectiva del sistema de salud, de manera que solo se incluyeron costos médicos directos. El horizonte temporal se adoptó teniendo en cuenta los tiempos de implementación de cada plan de vacunación, excluyendo menores de 16 años y gestantes. Se incluyeron los siguientes costos: costo de la vacunación y aplicación, costos de la hospitalización general aislamiento, cuidado intermedio e intensivo. Se compararon dos escenarios de vacunación: 1) Población que desea vacunarse (según las encuestas nacionales) y 2) Población que debería vacunarse (total susceptible de vacunación). Los costos agregados para cada escenario de vacunación se compararon con el escenario de no vacunación. Adicionalmente, se realizaron análisis de sensibilidad determinísticos y probabilísticos. Resultados. Los diferentes esquemas de vacunación contra COVID-19 disponibles en América Latina generan ahorros potenciales que oscilan entre USD 100 y USD 1 500 millones de dólares por país para el período 2021-2022, asumiendo que se logra implementar en su totalidad el plan de vacunación previsto en cada país. Conclusiones. La vacunación contra COVID-19 es una estrategia que además de reducir la morbilidad y mortalidad para Latinoamérica, genera ahorros potenciales para los sistemas de salud en la región.

ABSTRACT Objective. To estimate the budgetary impact of COVID-19 vaccination in six Latin American countries: Argentina, Brazil, Chile, Colombia, Mexico, and Peru, during the 2021-2022 biennium. Methods. Vaccines from Sinopharm (BBIBP-CorV), Janssen (JNJ-78436735), Gamaleya Institute (Gam-COVID-Vac), Sinovac (CoronaVac), CanSino (Convidecia), AstraZeneca (Vaxzevria), Moderna (mRNA-1273), and Pfizer (BNT162b2) were evaluated, according to their availability in each country. The health system perspective was adopted, so that only direct health care costs were included. The time horizon adopted took into account the implementation times of each vaccination plan, excluding children under 16 years of age and pregnant persons. The following costs were included: cost of vaccination/vaccine administration and costs of hospitalization (general isolation, stepdown care, and intensive care). Two vaccination scenarios were compared: 1) population wanting to be vaccinated (according to national surveys); and 2) population that should be vaccinated (total population susceptible to vaccination). The aggregate costs for each vaccination scenario were compared with the no-vaccination scenario. Deterministic and probabilistic sensitivity analyses were also performed. Results. The different COVID-19 vaccination regimens available in Latin America generate potential savings ranging from USD 100 million to USD 1.5 billion per country for the 2021-2022 biennium, assuming that the vaccination plan proposed for each country is fully implemented. Conclusions. COVID-19 vaccination is a strategy that not only reduces morbidity and mortality in Latin America, but also generates potential savings for health systems in the region.

RESUMO Objetivo. Estimar o impacto orçamentário da vacinação contra a COVID-19 em seis países da América Latina: Argentina, Brasil, Chile, Colômbia, México e Peru, no período 2021-2022. Métodos. Foram avaliadas as vacinas da Sinopharm (BBIBP-CorV), Janssen (JNJ-78436735), Instituto Gamaleya (Gam-COVID-Vac), Sinovac (CoronaVac), CanSino (Convidecia), AstraZeneca (Vaxzevria), Moderna (mRNA-1273) e Pfizer (BNT162b2), conforme a disponibilidade para cada país. Adotou-se a perspectiva do sistema de saúde, de forma que só foram incluídos custos médicos diretos. O horizonte temporal foi adotado levando em consideração os tempos de implementação de cada plano de vacinação, excluindo crianças menores de 16 anos e gestantes. Foram incluídos os seguintes custos: custos de vacinação e aplicação, custos gerais de hospitalização, isolamento, e cuidados intermediários e intensivos. Compararam-se dois cenários de vacinação: 1) população disposta a se vacinar (com base em pesquisas nacionais) e 2) população que deveria ser vacinada (total elegível de vacinação). Os custos agregados para cada cenário de vacinação foram comparados com o cenário de não vacinação. Além disso, foram realizadas análises de sensibilidade determinísticas e probabilísticas. Resultados. Os diferentes esquemas de vacinação contra a COVID-19 disponíveis na América Latina geram economias potenciais entre 100 milhões e 1,5 bilhão de dólares por país para o período 2021-2022, considerando a implementação completa do plano de vacinação previsto em cada país. Conclusões. A vacinação contra a COVID-19 é uma estratégia que, além de reduzir a morbidade e a mortalidade na América Latina, gera economias potenciais para os sistemas de saúde da região.

Prevalencia de síndrome de burnout en anestesiología y cirugía ortopédica en un centro en Chile / Burnout prevalence in anesthesiology and orthopedic surgery in a center in Chile

Resumen Objetivo: Evaluar el agotamiento emocional o cansancio emocional, realización personal y despersonalización en el quehacer de los médicos del Servicio de Traumatología y Pabellón Central del Hospital Hernán Henríquez Aravena (HHHA) y Departamento de Cirugía de la Universidad de La Frontera, Temuco, Chile. Materiales y Método: Corte transversal. 48 sujetos: 10 residentes de traumatología y 8 de anestesiología, 12 anestesiólogos y 18 traumatólogos académicos asistenciales. Se aplicó bajo consentimiento informado: Inventario de Maslash (MBI). Análisis: tendencia central, porcentaje, así como t de student y coeficientes de alfa de Cronbach. Resultados: La prevalencia global del síndrome de burnout es 97%, por dimensiones, cansancio emocional mostró una prevalencia del 100%; baja realización personal en el trabajo 100% y despersonalización 91,6%. Para traumatología: cansancio emocional mostró prevalencia 100%; baja realización personal en el trabajo 100%, y despersonalización 82%. Para anestesiología: cansancio emocional mostró prevalencia 75%; baja realización personal en el trabajo 30% y despersonalización 30%. Existen diferencias significativas en cansancio emocional siendo mayor en género femenino y en quienes duermen menos de 7 h. El coeficiente de alpha de Cronbach del MBI fue de 0,7. Conclusión: Tanto residentes como académicos asistenciales de traumatología y anestesiología mostraron un elevado cansancio emocional que coexiste con una baja realización personal en el trabajo y alta despersonalización. En Chile, las políticas de protección están principalmente enfocadas en la Seguridad y Salud Ocupacional con la gestión de los riesgos, pero no se observan políticas de protección al estrés y salud mental que involucren contención y apoyo a la labor terapéutica de los profesionales de la medicina.

Aim: To assess levels of burnout, including emotional exhaustion, personal accomplishment and depersonalization, in the daily work of academic doctors in the Orthopedic Surgery Service and Central Surgery Service of the Hospital Hernán Henríquez Aravena (HHHA) and Surgery Department in the Universidad de La Frontera, Temuco, Chile. Materials and Method: Cross-sectional study. 48 subjects participated: 10 residents in orthopedic surgery, 8 residents in anesthesiology, 12 academic anesthesiologists and 18 academic orthopedic surgeons. Instruments applied under informed consent: Maslach Burnout Inventory (MBI). Analysis: Measures of central tendency and percentage, independent sample t-tests. Cronbach's alpha coefficients of the MBI. Results: The overall prevalence of burnout syndrome is 97%, whereas by dimensions, emotional exhaustion showed a prevalence of 100%, low personal accomplishment at work 100% and depersonalization 91.6%. For orthopedic surgery by dimensions: emotional exhaustion showed a prevalence of 100%, low personal accomplishment at work 100% and depersonalization 82%. For anesthesiology: emotional exhaustion showed a prevalence of 75%, low personal accomplishment at work 30% and depersonalization 30%. Only gender and hours of sleep showed significant differences in emotional exhaustion, with higher scores for women and those who slept less than 7 hours. 0.7 Cronbach's alpha of the MBI. Conclusión: There is excessive emotional fatigue, low job felt accomplishment and depersonalization in orthopedic surgery residents and academic. In anesthesiology, emotional high exhaustion coexists with low personal accomplishment values and depersonalization high. In Chile, protection policies are mainly focused on Occupational Safety and Health with risk management, but there are no stress protection and mental health policies involving containment and support for the therapeutic work of medical professionals.

Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development.

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

Critical reflections on the Municipal Epidemiological Resilience Index used for public policy decision-making regarding the control of the COVID-19 pandemic in Colombia

On June 2, 2021, the Colombian Ministry of Health and Social Protection, through Resolution No. 777, laid down the requirements to resume all restricted economic and social activities. Similarly, said Resolution established the Municipal Epidemiological Resilience Index (IREM by its acronym in Spanish) as a tool to support decision-making regarding this economic reactivation amid the third epidemic peak of COVID-19 in the country. The purpose of this article is to perform a critical analysis of the technical aspects of the IREM and to explore the feasibility of its implementation as a support for the resumption of economic and social activities as proposed in the Resolution. The present critical analysis emphasizes on the lack of a clear definition of epidemiological resilience that is consistent with the scientific literature. Furthermore, the face and content validity of the index, as well as the construct validity of the index and of its dimensions, are called into question and, therefore, the feasibility of using it to determine said resumption.

El 2 de junio de 2021, el Ministerio de Salud y Protección Social de Colombia expidió la Resolución 777, mediante la cual se determinan las condiciones para el reinicio de todas las actividades económicas y sociales restringidas. Asimismo, en esta resolución se define el Índice de resiliencia epidemiológica municipal (IREM) como la herramienta para apoyar la toma de decisiones relacionadas con esta reactivación económica en medio del tercer pico epidémico de la COVID-19 en el país. El objetivo de este artículo es hacer un análisis crítico de los aspectos técnicos del IREM y explorar la conveniencia de su implementación como soporte del reinicio de las actividades económicas y sociales propuesto en la resolución. Dentro de este análisis crítico se destaca la falta de una clara definición de resiliencia epidemiológica que se ajuste a la literatura científica. Además, se cuestiona tanto la validez de apariencia, contenido y constructo del índice global, como la validez del constructo de sus dimensiones y, por tanto, la pertinencia de usarlo como herramienta para definir dicho reinicio.

Perspectives on Organelle Interaction, Protein Dysregulation, and Cancer Disease.

In recent decades, compelling evidence has emerged showing that organelles are not static structures but rather form a highly dynamic cellular network and exchange information through membrane contact sites. Although high-throughput techniques facilitate identification of novel contact sites (e.g., organelle-organelle and organelle-vesicle interactions), little is known about their impact on cellular physiology. Moreover, even less is known about how the dysregulation of these structures impacts on cellular function and therefore, disease. Particularly, cancer cells display altered signaling pathways involving several cell organelles; however, the relevance of interorganelle communication in oncogenesis and/or cancer progression remains largely unknown. This review will focus on organelle contacts relevant to cancer pathogenesis. We will highlight specific proteins and protein families residing in these organelle-interfaces that are known to be involved in cancer-related processes. First, we will review the relevance of endoplasmic reticulum (ER)-mitochondria interactions. This section will focus on mitochondria-associated membranes (MAMs) and particularly the tethering proteins at the ER-mitochondria interphase, as well as their role in cancer disease progression. Subsequently, the role of Ca2+ at the ER-mitochondria interphase in cancer disease progression will be discussed. Members of the Bcl-2 protein family, key regulators of cell death, also modulate Ca2+ transport pathways at the ER-mitochondria interphase. Furthermore, we will review the role of ER-mitochondria communication in the regulation of proteostasis, focusing on the ER stress sensor PERK (PRKR-like ER kinase), which exerts dual roles in cancer. Second, we will review the relevance of ER and mitochondria interactions with other organelles. This section will focus on peroxisome and lysosome organelle interactions and their impact on cancer disease progression. In this context, the peroxisome biogenesis factor (PEX) gene family has been linked to cancer. Moreover, the autophagy-lysosome system is emerging as a driving force in the progression of numerous human cancers. Thus, we will summarize our current understanding of the role of each of these organelles and their communication, highlighting how alterations in organelle interfaces participate in cancer development and progression. A better understanding of specific organelle communication sites and their relevant proteins may help to identify potential pharmacological targets for novel therapies in cancer control.

Impact of hypoalbuminemia on the prognosis of relapsed/refractory B-cell lymphoma treated with axicabtagene ciloleucel.

INTRODUCTION: Hypoalbuminemia is a known adverse prognostic factor in lymphomas. Yet, it is unknown if axicabtagene ciloleucel (axi-cel) overcomes the adverse prognostic impact of hypoalbuminemia in relapsed/refractory large B-cell lymphoma. METHODS: We conducted a retrospective analysis across three Mayo Clinic centers to assess the relationship of hypoalbuminemia (defined as a serum albumin (SA) levels ≤ 3.5 g/dL) on outcomes of patients treated with axi-cel. RESULTS: This analysis included 81 patients. Two patients had no available SA levels preceding axi-cel infusion. Eighteen patients (22.8%) had hypoalbuminemia with a median SA of 3.3 g/dL. Patients with normal SA had a statistically higher ORR than those without hypoalbuminemia (P = .018). There was no difference in 1-year PFS and OS between the group with hypoalbuminemia and the group with normal SA levels (48% vs 49%, P = .81) and (74% vs 73%, P = .97), respectively. There was no difference in the severity or median duration of cytokine release syndrome or neurotoxicity between the two groups. CONCLUSION: Notwithstanding the limitations related to the relatively small sample size, axi-cel therapy appears to overcome the adverse effect of hypoalbuminemia on OS and PFS. Large multicenter clinical studies are certainly needed to validate these findings.

Brote de Salmonella entérica subsp. entérica serovar Give asociado con enfermedad transmitida por alimentos en Vichada, Colombia, 2015 / An outbreak of Salmonella entérica subsp. entérica serovar Give associated with foodborne illness in the department of Vichada, Colombia, 2015

Resumen | Introducción. Salmonella entérica subsp. entérica serovar Give se encuentra en mamíferos rumiantes, cerdos, aves y ambientes acuáticos, pero rara vez en humanos. En Colombia este serotipo ocupó el decimoprimer lugar en frecuencia en la vigilancia por laboratorio de la enfermedad diarreica aguda entre el 2000 y el 2013. Objetivo. Caracterizar el fenotipo y el genotipo de S. Give en aislamientos relacionados con un brote de enfermedad transmitida por alimentos en el departamento de Vichada en la quinta semana epidemiológica del 2015. Materiales y métodos. Se buscó Salmonella spp. en 37 muestras de materia fecal con el método de estudio del Instituto Nacional de Salud. La muestra de sardinas enlatadas fue procesada según la norma ISO6579:2002 Cor.1:2004. Se determinó el serotipo en los aislamientos confirmados mediante serología o PCR en tiempo real, y se hicieron pruebas de sensibilidad a antimicrobianos y electroforesis en gel de campo pulsado con las enzimas Xbal y BlnI. Resultados. Todos los aislamientos de origen humano (11) y el aislamiento del alimento (1), se identificaron como S. Give y este último presentó resistencia a la tetraciclina. El análisis por PFGE-XbaI agrupó bajo el patrón COIN15JEXX01.0005 diez aislamientos de origen humano y a los restantes bajo el COIN15JEXX01.0006, con un 96,3 % de similitud. Los resultados de todos los aislamientos se confirmaron con la enzima BlnI; cuatro de ellos (tres humanos y el del alimento) se agruparon bajo el patrón COIN15JEXA26.002, con un porcentaje de similitud del 95,65 %. Conclusión. El estudio confirmó que las sardinas enlatadas se relacionaron con la transmisión de S. Give en el brote, que es el tercero ocasionado por este serotipo en Colombia.

Abstract | Introduction: Salmonella enterica subsp. enterica serovar Give is found in ruminants, pigs, poultry, and aquatic environments, but rarely in humans. In Colombia, this serotype was ranked 11th. in the laboratory surveillance of acute diarrheal disease between 2000 and 2013. Objective: To characterize phenotypic and genotypic isolates of Salmonella related to an outbreak of foodborne Illness in the department Vichada in the fifth epidemiological week of 2015. Materials and methods: Following the Instituto Nacional de Salud method, we tested 37 fecal samples for Salmonella spp. while the sample of canned sardines was processed according to the ISO 6579:2002 Cor.1:2004 standard. The isolates were confirmed by serology and/or real-time PCR, antimicrobial susceptibility tests, and pulsed-field gel electrophoresis with the XbaI and BlnI enzymes. Results: All human isolates (11) and that from food (1) were identified as S. Give. The food isolate exhibited tetracycline resistance. PFGE analysis with XbaI grouped ten isolates from samples of human origin in pattern COIN15JEXX01.0005 and the remaining isolates in COIN15JEXX01.0006 with 96.3% similarity. All isolates were confirmed with the BlnI enzyme, and four (three human isolates and the one from food) were matched to the pattern COIN15JEXA26.002 with 95.65% similarity. Conclusion: Our study confirmed that canned sardines were related to the transmission of S. Give in the outbreak, which is the third one caused by this serotype in Colombia.

Herramientas digitales para la obtención de registros, posicionamiento y articulación virtual de modelos / Digital tools for obtaining records, positioning and virtual articulation of casts

La siguiente revisión bibliográfica busca describir las alternativas digitales disponibles para la obtención de registros, posicionamiento y articulación virtual de modelos junto con ejemplificar algunos softwares que permitan la implementación de estas tecnologías en su trabajo diario. Se realizó una búsqueda de literatura en las bases de datos: Pubmed, LILACS, SciELO y Cochrane Library. Finalmente, luego de ser filtrados los resultados, se utilizaron un total de 36 publicaciones. Existen diversas herramientas disponibles actualmente para digitalizar una gran cantidad de técnicas que solo hasta hace algunos años eran realizadas manualmente por un operador. Algunas de ellas, facilitan una inmersión paulatina al mundo virtual del odontólogo novato ya que carecen de altos costos y recur-sos. Se sugiere que los odontólogos implementen estas tecnologías en su trabajo habitual según cada caso particular.

The following literature review seeks to bring together the digital alternatives available for obtaining records, positioning and virtual articulation of models together with exemplifying some softwares to allow the implementation of these technologies in their daily workflow. A literature search was carried out in the following databases: Pubmed, LILACS, SciELO and Cochrane Library. Finally, after the results were filtered, a total of 36 publications were used. There are various tools currently available to digitize a large number of techniques that were only performed manually by an operator until a few years ago. Some of them facilitate a gradual immersion into the virtual world of the novice dentist since they lack high costs and resources. It is suggested that dentists implement these technologies into daily dental practice according to each particular case.

Characterization of Novel Selected Microalgae for Antioxidant Activity and Polyphenols, Amino Acids, and Carbohydrates.

The biochemical composition of three novel selected microalgae strains (Chlorophyta) was evaluated to confirm their potential possibilities as new sustainably produced biomass with nutritional, functional, and/or biomedical properties. Extracts from cultured Pseudopediastrum boryanum, Chloromonas cf. reticulata, and Chloroidium saccharophilum exhibited higher radical scavenging activity of DPPH (1,1-diphenyl-2-picrylhydrazyl) when compared to butylated hydroxytoluene (BHT), but lower than butylated hydroxyanisole (BHA). Total phenolic compounds and amino acids were determined by newly developed RP-HPLC methods. Total phenolic contents, as µg g-1 of dry biomass, reached 27.1 for C. cf. reticulata, 26.4 for P. boryanum, and 55.8 for C. saccharophilum. Percentages of total analysed amino acids were 24.3, 32.1, and 18.5% of dry biomass, respectively, presenting high values for essential amino acids reaching 54.1, 72.6, and 61.2%, respectively. Glutamic acid was the most abundant free amino acid in all microalgae samples, followed by proline and lysine in C. saccharophilum and P. boryanum, and methionine and lysine in C. reticulata. Soluble carbohydrates in aqueous extracts ranged from 39.6 for C. saccharophilum to 49.3% for C. reticulata, increasing values to 45.1 for C. saccharophilum and 52.7% for P. boryanum in acid hydrolysates of dried biomass. Results confirmed the potential possibilities of these microalgae strains.

C-reactive protein and ferritin levels and length of intensive care unit stay in patients with B-cell lymphomas treated with axicabtagene ciloleucel.

OBJECTIVE/BACKGROUND: Chimeric antigen receptor (CAR) T-cell is an effective therapy in relapsed/refractory large B-cell lymphomas that, due to its unique toxicities, often requires escalation of care to the intensive care unit (ICU) setting. C-reactive protein (CRP) and ferritin are serum inflammatory markers associated with onset and persistence of CAR T-cell-related toxicity. METHODS: We retrospectively analyzed 34 patients treated with axicabtagene ciloleucel (axi-cel) who were divided into two groups: patients requiring admission to the ICU during initial hospitalization (n = 13, 38%) and those who did not (n = 21, 62%). Primary objective was to examine possible relationships between serum ferritin and/or CRP levels with the need for, and length of, ICU stay between these groups. RESULTS: All 13 patients admitted to the ICU developed cytokine release syndrome (CRS) and 11 of them also developed neurotoxicity (NT). Of the 21 patients in the non-ICU group, 18 developed CRS and 5 patients developed NT. Grade of CRS and NT were higher in ICU versus non-ICU patients (p = .03 and .001, respectively). There was no correlation between CRP levels at time of ICU admission and length of ICU stay (correlation of 0.41, p = .17). Yet, there was an association between serum ferritin levels and length of ICU stay (R2 = 0.73) which did not reach statistical significance (correlation of 0.21, p = .49). CONCLUSION: Notwithstanding the limitations of the small sample size, our study suggests that an elevated ferritin level at the time of escalation of medical care may be possibly indicative of anticipated prolonged ICU hospitalization in patients treated with axi-cel. A large multicenter study is certainly needed to confirm this observation.