Lectin-like Transcript-1 (LLT1) Expression in Oral Squamous Cell Carcinomas: Prognostic Significance and Relationship with the Tumor Immune Microenvironment.

Lectin-like transcript-1 (LLT1) expression is detected in different cancer types and is involved in immune evasion. The present study investigates the clinical relevance of tumoral and stromal LLT1 expression in oral squamous cell carcinoma (OSCC), and relationships with the immune infiltrate into the tumor immune microenvironment (TIME). Immunohistochemical analysis of LLT1 expression was performed in 124 OSCC specimens, together with PD-L1 expression and the infiltration of CD20+, CD4+, and CD8+ lymphocytes and CD68+ and CD163+-macrophages. Associations with clinicopathological variables, prognosis, and immune cell densities were further assessed. A total of 41 (33%) OSCC samples showed positive LLT1 staining in tumor cells and 55 (44%) positive LLT1 in tumor-infiltrating lymphocytes (TILs). Patients harboring tumor-intrinsic LLT1 expression exhibited poorer survival, suggesting an immunosuppressive role. Conversely, positive LLT1 expression in TILs was significantly associated with better disease-specific survival, and also an immune-active tumor microenvironment highly infiltrated by CD8+ T cells and M1/M2 macrophages. Furthermore, the combination of tumoral and stromal LLT1 was found to distinguish three prognostic categories (favorable, intermediate, and adverse; p = 0.029, Log-rank test). Together, these data demonstrate the prognostic relevance of tumoral and stromal LLT1 expression in OSCC, and its potential application to improve prognosis prediction and patient stratification.

Características clínicas y radiográficas de reabsorciones radiculares externas / Clinical and radiographic characterization of external root resorption

Introducción La siguiente revisión bibliográfica se realizó con el propósito de reconocer las características clínicas y radiográficas que deben ser evaluadas para el diagnóstico de las reabsorciones radiculares externas incluyendo también sus tratamientos. Metodología Se llevó a cabo una búsqueda en las bases de datos MEDLINE/PubMed, Cochrane Library y Google Scholar bajo el término , incluyendo estudios experimentales y revisiones bibliográficas desde 2010 a 2022 en español e inglés, incluyendo finalmente 17 artículos. Resultados Los resultados obtenidos señalaron que cada tipo de reabsorción radicular externa presenta características clínicas específicas que las diferencian. Estas diferencias son: para la reabsorción externa inflamatoria la vitalidad pulpar negativa; para la reabsorción externa de reemplazo la ausencia de movilidad y percusión metálica; para la reabsorción externa cervical una coloración rosada de la corona; la reabsorción externa superficial no presenta ningún tipo de sintomatología clínica y la reabsorción de colapso apical transitorio presenta un cambio de coloración transitorio. Conclusión Las reabsorciones radiculares externas requieren un diagnóstico preciso y temprano. Se debe realizar un examen clínico con énfasis en sondaje, coloración, movilidad y pruebas de vitalidad.

Introduction The following bibliographic review was carried out with the purpose of recognizing the clinical and radiographic characteristics that must be considered in the diagnosis of external root resorption, including treatments. Methods A bibliographic search was carried out in PubMed/Medline, Cochrane Library and Google Scholar databases under the term "external root resorption", from 2010 to 2022 in Spanish and English. Experimental studies and bibliographic reviews were selected, and finally 17 articles were included. Results The results obtained indicated that each type of resorption presents specific clinical characteristics that differentiate them, these are: for external inflammatory resorption a negative pulp vitality; for replacement external resorption the absence of mobility and metallic percussion; for cervical external resorption a pink coloration of the crown; superficial external resorption does not present any type of clinical symptoms and transient apical collapse presents a transient change in color. Conclusion External root resorptions require accurate and early diagnosis. A clinical examination should be performed with emphasis on the following: probing, coloration, mobility, and vitality tests.

Prevalence of Gastric Precursor Lesions in Countries With Differential Gastric Cancer Burden: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well-understood. We conducted a systematic review and meta-analysis to estimate the global prevalence of precursor lesions. METHODS: We estimated the prevalence of atrophic gastritis (AG), gastric intestinal metaplasia (IM), and dysplasia in regions with low, medium, and high GC incidence. Because IM is an advanced manifestation of AG, we assessed the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. Prevalence was sub-stratified by Helicobacter pylori infection, symptomatology, and period (<2000, 2000-2010, and >2010). RESULTS: Among the 582 articles that underwent full-text review, 166 studies met inclusion criteria. The global prevalence estimates of AG, IM, and dysplasia were 25.4%, 16.2%, and 2.0%, respectively, on the basis of 126 studies that reported the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. The prevalence of all precursor lesions was higher in high and medium compared with low GC incidence countries (P < .01). Prevalence of AG and IM was significantly higher among H pylori-infected individuals (P < .01) but not statistically different between symptomatic and asymptomatic individuals (P > .17). All precursors demonstrated a secular decrease in prevalence over time. CONCLUSIONS: Gastric precursor lesions have differences in prevalence in regions with differential GC incidence and are associated with H pylori infection. Because of the substantial prevalence of precursor lesions in both symptomatic and asymptomatic individuals, symptomatic evaluation may not be sufficient to identify individuals at risk. These estimates provide important insights for tailoring GC prevention strategies.

Glioma-Induced Alterations in Excitatory Neurons are Reversed by mTOR Inhibition.

Gliomas are highly aggressive brain tumors characterized by poor prognosis and composed of diffusely infiltrating tumor cells that intermingle with non-neoplastic cells in the tumor microenvironment, including neurons. Neurons are increasingly appreciated as important reactive components of the glioma microenvironment, due to their role in causing hallmark glioma symptoms, such as cognitive deficits and seizures, as well as their potential ability to drive glioma progression. Separately, mTOR signaling has been shown to have pleiotropic effects in the brain tumor microenvironment, including regulation of neuronal hyperexcitability. However, the local cellular-level effects of mTOR inhibition on glioma-induced neuronal alterations are not well understood. Here we employed neuron-specific profiling of ribosome-bound mRNA via 'RiboTag,' morphometric analysis of dendritic spines, and in vivo calcium imaging, along with pharmacological mTOR inhibition to investigate the impact of glioma burden and mTOR inhibition on these neuronal alterations. The RiboTag analysis of tumor-associated excitatory neurons showed a downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development, and an upregulation of transcripts encoding cytoskeletal proteins involved in dendritic spine turnover. Light and electron microscopy of tumor-associated excitatory neurons demonstrated marked decreases in dendritic spine density. In vivo two-photon calcium imaging in tumor-associated excitatory neurons revealed progressive alterations in neuronal activity, both at the population and single-neuron level, throughout tumor growth. This in vivo calcium imaging also revealed altered stimulus-evoked somatic calcium events, with changes in event rate, size, and temporal alignment to stimulus, which was most pronounced in neurons with high-tumor burden. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed the glioma-induced alterations on the excitatory neurons, including the alterations in ribosome-bound transcripts, dendritic spine density, and stimulus evoked responses seen by calcium imaging. These results point to mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma - manifested by alterations in ribosome-bound mRNA, dendritic spine density, and stimulus-evoked neuronal activity. Collectively, our work identifies the pathological changes that tumor-associated excitatory neurons experience as both hyperlocal and reversible under the influence of mTOR inhibition, providing a foundation for developing therapies targeting neuronal signaling in glioma.

Changes in smoking use and subsequent lung cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

BACKGROUND: Reducing cigarettes per day may lower the risk of lung cancer compared with continuing to smoke at the same intensity. Other changes in smoking behaviors, such as increasing cigarette consumption or quitting for a period and relapsing, may also affect lung cancer risk. METHODS: We examined changes in smoking status and cigarettes per day among 24 613 Finnish male smokers aged 50-69 years who participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Longitudinal data on smoking were collected during study follow-up visits 3 times a year (approximately every 4 months) between 1985 and 1993. Incident lung cancer patients through 2012 were identified by the Finnish Cancer Registry. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: Compared with smoking 20 cigarettes per day continuously across the intervention period, reducing an average of 5 cigarettes per day per year while smoking was associated with a 20% lower risk of lung cancer (95% CI = 0.71 to 0.90). A substantially lower risk of lung cancer was also observed when participants smoked at 50% (RR = 0.72, 95% CI = 0.57 to 0.90) and 10% (RR = 0.55, 95% CI = 0.36 to 0.83) of study visits, relative to smoked at 100% of study visits. CONCLUSIONS: Smokers may lower their risk of lung cancer by reducing smoking intensity (cigarettes per day while smoking) and the time they smoke. However, quitting smoking completely is the most effective way for smokers to reduce their risk of lung cancer.

Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

Low-intensity daily smoking and mortality risk among Mexican women.

OBJECTIVE: To examine the association between low-intensity smoking (10 or less cigarettes per day) and all-cause and cause-specific mortality risk among women who smoke and by age at cessation among women who previously smoked. METHODS: In this study, 104 717 female participants of the Mexican Teachers' Cohort Study were categorised according to self-reported smoking status at baseline (2006/2008) and were followed for mortality through 2019. We estimated HRs and 95% CIs for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models with age as the underlying time metric. RESULTS: Smoking as few as one to two cigarettes per day was associated with higher mortality risk for all causes (HR: 1.36; 95% CI 1.10 to 1.67) and all cancers (HR: 1.46; 95% CI 1.05 to 2.02), compared with never smoking. Similarly, slightly higher HRs were observed among participants smoking ≥3 cigarettes per day (all causes HR: 1.43; 95% CI 1.19 to 1.70; all cancers HR: 1.48; 95% CI 1.10 to 1.97; cardiovascular disease HR: 1.58; 95% CI 1.09 to 2.28). CONCLUSIONS: In this large study of Mexican women, low-intensity smoking was associated with higher mortality risk for all causes and all cancers. Interventions are needed to promote cessation among women who smoke at low-intensity in Mexico, regardless of how few cigarettes they smoke per day.

Personalized tumor vaccine for pancreatic cancer.

BACKGROUND: Pancreatic cancer is a highly lethal malignancy often presenting with advanced disease and characterized by resistance to standard chemotherapy. Immune-based therapies such checkpoint inhibition have been largely ineffective such that pancreatic cancer is categorized as an immunologically "cold tumor". In the present study, we examine the therapeutic efficacy of a personalized cancer vaccine in which tumor cells are fused with dendritic cells (DC) resulting in the broad induction of antitumor immunity. RESULTS: In the KPC spontaneous pancreatic cancer murine model, we demonstrated that vaccination with DC/KPC fusions led to expansion of pancreatic cancer specific lymphocytes with an activated phenotype. Remarkably, vaccination led to a reduction in tumor bulk and near doubling of median survival in this highly aggressive model. In a second murine pancreatic model (Panc02), vaccination with DC/tumor fusions similarly led to expansion of tumor antigen specific lymphocytes and their infiltration to the tumor site. Having shown efficacy in immunocompetent murine models, we subsequently demonstrated that DC/tumor fusions generated from primary human pancreatic cancer and autologous DCs potently stimulate tumor specific cytotoxic lymphocyte responses. CONCLUSIONS: DC/tumor fusions induce the activation and expansion of tumor reactive lymphocytes with the capacity to infiltrate into the pancreatic cancer tumor bed.

Association of exposure to environmental tobacco smoke at home and risk of mortality among US never smokers by race/ethnicity, education, and income.

Environmental tobacco smoke (ETS) increases the risk of mortality among nonsmokers. Yet, few studies have examined this association among racial/ethnic minorities or among people with less education or income. We assessed self-reported ETS exposure at home among never smoking participants (n = 110,945) of the 1991-2010 National Health Interview Surveys. Deaths through 2015 were identified by the National Death Index. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were estimated using Cox proportional hazards regression models with age as the underlying time metric and adjusted for sex, race/ethnicity, education, household income, body mass index, region of residence, and survey year. We further stratified all-cause mortality analyses by race/ethnicity, household income, and education. Relative to no ETS at home, every day exposure was associated with higher risk of all-cause mortality (HR = 1.33, 95%CI: 1.23, 1.45), with similar HRs observed across strata of education and income. HRs were similar among non-Hispanic Black (HR = 1.28, 95%CI: 1.08, 1.53) and non-Hispanic White adults (HR = 1.34, 95%CI: 1.21, 1.48) although somewhat higher among Hispanic adults (HR = 1.65, 95%CI: 1.29, 2.10; P for pairwise comparison = 0.04). ETS exposure at home is an important contributor to mortality across strata of race/ethnicity, education, and income in the US.

Evaluation of Indicators of a Vascular Access Device Program led by Nursing Professionals in a High-complexity University Hospital in Colombia / Evaluación de indicadores de un Programa de Dispositivos de Acceso Vascular liderado por profesionales de enfermería en un hospital universitario de alta complejidad en Colombia / Avaliação de indicadores de um Programa de Dispositivos de Acesso Vascular liderado por profissionais de enfermagem num hospital universitário de alta complexidade na Colômbia

Objective. This work sought to evaluate result indicators of the specialized vascular access program led by nursing during the period between 01 January 2018 and 31 December 2019 at Fundación Cardioinfantil -Instituto de Cardiología (Colombia). Methods. This was a retrospective descriptive study based on medical records of 1,210 patients who received insertion of vascular access devices by the specialized group of nurses. Result indicators are described. Results. Of all the patients who received insertion of a vascular access catheter, 53.1% were women, with mean age of 34.2 years, admitted to critical care services with cardiovascular problems and sepsis (90.2%). Placement of the peripherally inserted central catheter, midline and arterial was echo-guided between 91% and 100%, with a success rate on the first puncture of 66%. The average duration time of the peripherally inserted central catheter was 25.3 days, that of the midline catheter was 8 days, with a reach of 57% until the end of the treatment. The rate observed per catheter-days of overall phlebitis was 2.03, for positive blood culture of the central peripheral insertion device was 1.9 and thrombosis of 0.50; and arterial line thrombosis was 11.7. Conclusion. The Vascular Access Device Program led by nursing reported rational use of these elements with structured therapeutic purposes according with the complexity of the patients admitted to hospitalization. Improvement plans must be implemented to increase efficacy in post-admission insertion times, reduce infection rate and thrombosis through effective follow-up and control mechanisms.

Objetivo. Evaluar los indicadores de resultado del programa especializado de accesos vasculares liderado por enfermería durante el periodo comprendido entre enero 1ro de 2018 -diciembre 31 de 2019 en la Fundación Cardioinfantil -Instituto de Cardiología en Colombia. Métodos. Estudio descriptivo retrospectivo, con base en historias clínicas de 1210 pacientes que recibieron la inserción de dispositivos de acceso vascular por el grupo especializado de enfermeras. Se describen indicadores de resultado. Resultados. Del total de pacientes que recibieron la inserción de un catéter vía acceso vascular, el 53.1% fueron mujeres, con edad promedio de 34.2 años, admitidos en servicios de cuidado crítico con problemas cardiovasculares y sepsis (90.2%). La colocación del catéter central de inserción periférica, de línea media y arterial fue eco-guiada entre el 91-100%, con una tasa de éxito a la primera punción del 66%. El tiempo promedio de duración del catéter central de inserción periférica fue de 25.3 días, la del catéter de línea media fue de 8 días, con un alcance del 57% hasta el final del tratamiento. La tasa observada por días-catéter de flebitis global fue de 2.03, para hemocultivo positivo del dispositivo central de inserción periférica fue de 1.9 y trombosis de 0.50; y trombosis de la línea arterial fue de 11.7. Conclusión. El programa de dispositivos de acceso vascular liderado por enfermería reportó un uso racional de estos elementos con fines terapéuticos estructurados de acuerdo con la complejidad de los pacientes admitidos a hospitalización. Planes de mejora deben ser implementados con el fin de incrementar la eficacia en los tiempos de inserción pos-admisión, reducción de tasa de infección y trombosis mediante mecanismos efectivos de seguimiento y control.

Objetivo. Avaliar os indicadores de resultado do programa especializado de acessos vasculares liderado por enfermagem durante o período compreendido entre o dia 1° de janeiro de 2018 -dezembro 31 de 2019 na Fundação Cardio-infantil -Instituto de Cardiologia em Colômbia. Métodos. Estudo descritivo retrospectivo, com base nas histórias clínicas de 1210 pacientes que receberam a inserção de dispositivos de acesso vascular pelo grupo especializado de enfermeiras. Se descrevem indicadores de resultado. Resultados. Do total de pacientes que receberam a inserção de um cateter via acesso vascular, 53.1% foram mulheres, com idade média de 34.2 anos, admitidos em serviços de cuidado crítico com problemas cardiovasculares e sepses (90.2%). A colocação do cateter central de inserção periférica, de linha média e arterial foi ecoguiada entre 91-100%, com uma taxa de sucesso à primeira punção de 66%. O tempo médio de duração do cateter central de inserção periférica foi de 25.3 dias, a do cateter de linha média foi de 8 dias, com um alcance de 57% até o final do tratamento. A taxa observada por dias-cateter de flebites global foi de 2.03, para hemocultura positivo do dispositivo central de inserção periférica foi de 1.9 e trombose de 0.50; e trombose da linha arterial foi de 11.7. Conclusão. O programa de dispositivos de acesso vascular liderado por enfermagem reportou um uso racional destes elementos com fins terapêuticos estruturados de acordo com a complexidade dos pacientes admitidos a hospitalização. Planos de melhora devem ser implementados com o fim de incrementar a eficácia nos tempos de inserção pós-admissão, redução de taxa de infecção e trombose mediante mecanismos efetivos de seguimento e controle.

Embryonic ILC-poiesis across tissues.

The family of innate lymphoid cells (ILCs), consisting of Group 1 ILCs (natural killer cells and ILC1), ILC2, and ILC3, are critical effectors of innate immunity, inflammation, and homeostasis post-natally, but also exert essential functions before birth. Recent studies during critical developmental periods in the embryo have hinted at complex waves of tissue colonization, and highlighted the breadth of multipotent and committed ILC progenitors from both classic fetal hematopoietic organs such as the liver, as well as tissue sites such as the lung, thymus, and intestine. Assessment of the mechanisms driving cell fate and function of the ILC family in the embryo will be vital to the understanding ILC biology throughout fetal life and beyond.

Agreement between biopsy and renal function in pediatric patients with lupus nephritis. A retrospective study / Acuerdo entre biopsia y función renal en pacientes pediátricos con nefritis lúpica. Un estudio retrospectivo

ABSTRACT Introduction: Lupus nephritis (LN) is a consequence of Systemic Lupus Erythematosus (SLE). Renal biopsy is a potential prognostic biomarker for renal function. Objective: To correlate histopathological findings and renal function in children with LN. Materials and methods: A retrospective observational study was conducted on children with a histopathological diagnosis of NL. Patients with no follow-up registered were excluded. The kidney biopsy at diagnosis was evaluated using the ISN/RPS scale. The Kappa index was used to determine the level of agreement between renal failure (Glomerular Filtration Rate [GFR] < 60 mL/min/1.73 m2) and presence or absence of each index on the modified ISN/RPS scale. Results: A total of 57 patients with NL were treated from 2011 to 2018 at the institution. Of these, 40 (70%) met inclusion criteria, and 10 (25%) were male. The median age of NL diagnosis was 12.9 years (IQR, 11.1-14.9). Follow-up time was 2.3 years (IQR, 1.0-5.16). At diagnosis, karyorrhexis was the characteristic with highest level of agreement with renal failure (k = 0.1873 SE = 0.0759 P = .0068) and at the last follow-up, it was global segmental sclerosis (k = 0.1481 SE = 0.078 P = .0287). There was no difference in the GFR at the last follow-up and the presence of proteinuria at diagnosis (P = .3936). Conclusion: Renal biopsy findings may be an insufficient tool to predict renal function. Treat ment and prognosis of patients with NL should be done using other biomarkers and clinical signs. Prospective studies should be performed to confirm this hypothesis.

RESUMEN Introducción: La nefritis lúpica (NL) es una consecuencia del lupus eritematoso sistémico (LES). La biopsia renal es un potencial biomarcador de pronóstico de función renal. Objetivo: Correlacionar hallazgos histopatológicos y la función renal de los pacientes pediátricos con la NL. Materiales y métodos: Estudio observacional retrospectivo. Se incluyeron pacientes pediátricos con diagnóstico histopatológico de NL. Se excluyeron pacientes sin seguimiento por la institución. Se evaluó la biopsia renal al diagnóstico con la escala modificada de la International Society of Nephrology and the Renal Pathology Society (ISN/RPS). Se usó el índice kappa para determinar el nivel de acuerdo entre la falla renal (tasa de filtración glomerular [TFG] < 60 mL/min/1,73 m2) y la presencia o ausencia de cada índice de la escala modificada de la ISN/RPS. Resultados: Entre el 2011 y el 2018, 57 pacientes con NL fueron atendidos en la institución, 40 cumplieron con los criterios de inclusión, 10 (25%) eran de sexo masculino. La mediana de edad de diagnóstico de NL fue 12,9 arios (IQR 11,1 a 14,9). El tiempo de seguimiento fue de 2,3 años (IQR 1,0 a 5,16). Al diagnóstico, la cariorexis fue la característica de la escala con mayor nivel de acuerdo con la falla renal (k = 0,1873, EE = 0,0759, p = 0,0068) y al último seguimiento lo fue la esclerosis segmentaria global (k = 0,1481, EE = 0,078, p = 0,0287). No hubo diferencia en la TFG al último seguimiento y presencia de proteinuria al diagnóstico (p = 0,3936). Conclusión: La biopsia renal puede ser insuficiente para evaluar la predicción de la función renal. El tratamiento de pacientes con NL debe realizarse utilizando otros biomarcadores y signos clínicos. Deben hacerse estudios prospectivos que puedan confirmar esta hipótesis.

Concentrations of Cotinine and 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol (NNAL) in U.S. Non-Daily Cigarette Smokers.

BACKGROUND: Accumulating evidence suggests that non-daily smokers have higher disease and mortality risks than never smokers. Yet, the accuracy of self-reported non-daily cigarette smoking is poorly understood. METHODS: We examined the concordance between self-reported non-daily smoking and serum cotinine in 18,835 adult participants (20 years or older) of the 2007 to 2014 National Health and Nutrition Examination Surveys, in comparison with daily smokers and nonsmokers. We also analyzed concentrations of the urinary biomarker 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by smoking status. RESULTS: In the study sample, 77.8% (14,660) reported currently not smoking (nonsmokers), 18.3% (3,446) smoked every day (daily smokers), and 3.9% (729) smoked on some days of the past month (non-daily smokers). Just 2.1% of nonsmokers had cotinine concentrations in the active smoking range (>10 ng/mL), compared with 70.4% of non-daily and 98.8% of daily smokers. Non-daily smokers reported smoking a median of 24 cigarettes per month [interquartile range (IQR) = 9-60] and had substantially higher concentrations of NNAL (median = 72.5; IQR = 14.8-211.0 pg/mL) than nonsmokers (median = 0.4; IQR = 0.4-2.1 pg/mL), although lower than daily smokers (median = 294.0; IQR = 148.0-542.0 pg/mL). Among non-daily smokers, concentrations of cotinine and NNAL were positively correlated with days and cigarettes smoked per month (P < 0.001). CONCLUSIONS: We observed excellent concordance between self-reported non-daily cigarette smoking and concentrations of serum cotinine. IMPACT: These results provide evidence for the validity of self-reported non-daily smoking and indicate that non-daily smokers are exposed to substantial concentrations of carcinogenic nitrosamines regardless of the low number of cigarettes they smoke per month.

Leukemia vaccine overcomes limitations of checkpoint blockade by evoking clonal T cell responses in a murine acute myeloid leukemia model.

We have developed a personalized vaccine whereby patient derived leukemia cells are fused to autologous dendritic cells, evoking a polyclonal T cell response against shared and neo-antigens. We postulated that the dendritic cell (DC)/AML fusion vaccine would demonstrate synergy with checkpoint blockade by expanding tumor antigen specific lymphocytes that would provide a critical substrate for checkpoint blockade mediated activation. Using an immunocompetent murine leukemia model, we examined the immunologic response and therapeutic efficacy of vaccination in conjunction with checkpoint blockade with respect to leukemia engraftment, disease burden, survival and the induction of tumor specific immunity. Mice treated with checkpoint blockade alone had rapid leukemia progression and demonstrated only a modest extension of survival. Vaccination with DC/AML fusions resulted in the expansion of tumor specific lymphocytes and disease eradication in a subset of animals, while the combination of vaccination and checkpoint blockade induced a fully protective tumor specific immune response in all treated animals. Vaccination followed by checkpoint blockade resulted in upregulation of genes regulating activation and proliferation in memory and effector T cells. Long term survivors exhibited increased T cell clonal diversity and were resistant to subsequent tumor challenge. The combined DC/AML fusion vaccine and checkpoint blockade treatment offers unique synergy inducing the durable activation of leukemia specific immunity, protection from lethal tumor challenge and the selective expansion of tumor reactive clones.

Cambios fisiológicos durante el embarazo normal / Physiological Changes During a Normal Pregnancy

Resumen: El organismo de la mujer experimenta una serie de cambios fisiológicos, a todos niveles, que tienen la finalidad de adaptarse y dar respuesta a la gran demanda que representan las 40 semanas de gestación que durará la formación un nuevo ser humano en su interior. Dichos cambios ocurren de manera gradual, pero continua, a lo largo de todo el embarazo y van desde cambios cardiovasculares, digestivos, pulmonares, hematológicos y endocrinos, los cuales al final también terminan por revertirse de manera paulatina durante el puerperio. Los cambios fisiológicos se relacionan con el desarrollo de distintos síntomas, signos y alteraciones en la mujer embarazada, así como cambios en los parámetros de los estudios paraclínicos, lo cual hace que resulte especialmente relevante que el médico general o de primer contacto esté familiarizado con estos cambios y el momento en el que ocurren en el embarazo, para que pueda realizar una oportuna identificación de las alteraciones que pueden representar estados patológicos que resulten una amenaza para el bienestar materno y fetal. Por todo lo anterior, el objetivo de la presente revisión temática fue recopilar y describir los principales cambios fisiológicos que ocurren en la mujer durante el embarazo normal, así como los cambios que se presentan en los estudios paraclínicos más comunes.

Abstract: The woman's body undergoes a series of physiological changes at all levels that hace the purpose of adapting and responding to the the 40 weeks of gestation. These changes occur gradually, but in a continuously, throughout the pregnancy and range from cardiovascular, digestive, pulmonary, hematological and endocrine changes, which at the end also end up gradually reversing during the puerperium. The physiological changes are related to the development of different symptoms, signs and alterations in the pregnant woman, as well as changes in the parameters of the paraclinical studies, which makes it especially relevant for the general practitioner or first contact doctor to recognize these changes and the moment in which they occur in pregnancy so that they can make a timely identification of the alterations that can represent pathological states that are a threat to maternal and fetal well-being. For all of the above, the objective of this thematic review was to collect and describe the main physiological changes that occur in women during a normal pregnancy, as well as the changes that occur in the most common paraclinical studies.

Trends in cigarette brand preference among Mexican smokers: the rise of Pall Mall.

OBJECTIVE: To analyse trends in cigarette brand preference among Mexican smokers during the implementation period of key WHO's Framework Convention on Tobacco Control recommendations. METHODS: Data came from two nationally representative, comparable surveys, namely the Global Adult Tobacco Survey 2009 and 2015 and the National Survey on Addictions 2011 and 2016. Logistic models were used to estimate the adjusted prevalence of each brand purchased, as well as individual correlates of purchasing the single brand with a large growth over the study period. Multiple linear regressions were also employed to analyse cigarette prices across brands. RESULTS: Six brand families accounted for about 90% of the cigarette market, with Marlboro clearly dominating all brands at 54%-61%. Only the share of Pall Mall brand, however, registered a rapid increase over the period-from 1% in 2009 to 14% in 2016. Women and younger smokers (15-24 years) were more likely to prefer Pall Mall over other brands. While the typical price segmentation between international (premium) brands and national (discount) brands was observed, the price of Pall Mall is within the range of the latter. Importantly, most varieties of this brand include flavour capsule varieties (FCVs). CONCLUSIONS: This study suggests that the strong campaign of brand migration, the pricing strategy and the aggressive introduction of FCVs expanded Pall Mall in the Mexican cigarette market. Therefore, better control policies of cigarette contents and taxes that reduce price differentials across brands should be encouraged to promote public health.

Smoking trends in Mexico, 2002-2016: before and after the ratification of the WHO's Framework Convention on Tobacco Control.

INTRODUCTION: Mexico was the first Latin American country to ratify the Framework Convention on Tobacco Control (FCTC) in 2004, after which it implemented some key FCTC policies (e.g., taxes, smoke-free, pictorial warnings and ad bans). This study assessed trends in the prevalence of current, daily and non-daily smoking in Mexico before and after the implementation of key FCTC policies. METHODS: Data were analysed from two comparable, nationally representative surveys (i.e., the National Survey on Addictions 2002, 2011 and 2016, and the Global Adult Tobacco Survey 2009 and 2015). The pooled sample comprised 100 302 persons aged 15-65 years. Changes in the prevalence of current, daily and non-daily smoking were assessed. RESULTS: From 2002 to 2016, the prevalence of current smoking fell 11% in relative terms (from 21.5% to 19.0%). The decrease was registered between 2002 and 2009, and after that, a slight increase was observed (from 16.5% in 2009 to 19% in 2016). The prevalence of daily smoking decreased by about 50% between 2002 and 2016 (from 13.5% to 7.0%) with most of the decrease occurring by 2009. Conversely, the prevalence of non-daily smoking increased by 35% between 2009 and 2016 (from 8.8% to 11.9%). CONCLUSIONS: Full implementation of the FCTC is necessary to further reduce smoking. Specific interventions may be needed to target non-daily smokers, who now comprise more than half of current smokers in Mexico.

[Prevalence, proportion and correlates of flavorcapsule cigarette use in Mexico: results fromthe Ensanut 2018-19]. / Cigarros con cápsulas de sabor en México: prevalencia, proporción de uso entre fumadores y predictores de consumo. Ensanut 2018-19.

OBJECTIVE: To estimate the prevalence of flavor capsule cigarette, use among Mexicans who are 10 years and older, to determine the proportion of smokers who use flavor capsules, and to characterize the sociodemographic correlates of flavor capsule cigarette use. MATERIALS AND METHODS: Data came from the National Health and Nutrition Survey 2018-19. The prevalence and proportion of flavor capsule cigarette use were estimated by sex, age, education, and wealth. Poisson models were used to evaluate sociodemographic factors as-sociated with flavor capsule cigarette use. RESULTS: Among Mexicans,the prevalence of flavor capsule cigarettes use was 6.6%, which is 43% of all smokers. Women, adolescents, and young adults were more likely than other groups to use flavor capsule cigarettes. CONCLUSIONS: Mexicans report a high prevalence of flavor capsule cigarette use. Banning cigarettes with flavors may reduce the appeal of smoking, particularly for youth and women.

OBJETIVO: Calcular la prevalencia de consumo de cigarros con cápsula de sabor, la proporción de uso entre los usuarios de tabaco en la población mexicana de 10 años o más, y los factores asociados a su consumo. MATERIAL Y MÉTODOS: Se utilizó la Encuesta Nacional de Salud y Nutrición 2018-19. Se utilizó un modelo Poisson para obtener la razón de prevalen-cias del uso de cigarros con cápsulas de sabor ajustando por sexo, edad, educación e índice de bienestar. RESULTADOS: El 6.6% de los mexicanos fuma cigarros con cápsulas de sabor, lo que corresponde a 43% del total de usuarios de tabaco. Las mujeres, adolescentes y adultos jóvenes son los grupos con la mayor proporción de consumo. CONCLUSIONES: México tiene una alta prevalencia de consumo de cigarros con cápsula de sabor. Para reducirla, se deben implementar políticas para prohibir la venta de cigarros con saborizantes y eliminar los diseños atractivos en las cajetillas de los cigarros.

Cigarros con cápsulas de sabor en México: prevalencia, proporción de uso entre fumadores y predictores de consumo. Ensanut 2018-19 / Prevalence, proportion and correlates of flavor capsule cigarette use in Mexico: results from the Ensanut 2018-19

Resumen: Objetivo: Calcular la prevalencia de consumo de cigarros con cápsula de sabor, la proporción de uso entre los usuarios de tabaco en la población mexicana de 10 años o más, y los factores asociados a su consumo. Material y métodos: Se utilizó la Encuesta Nacional de Salud y Nutrición 2018-19. Se utilizó un modelo Poisson para obtener la razón de prevalencias del uso de cigarros con cápsulas de sabor ajustando por sexo, edad, educación e índice de bienestar. Resultados: El 6.6% de los mexicanos fuma cigarros con cápsulas de sabor, lo que corresponde a 43% del total de usuarios de tabaco. Las mujeres, adolescentes y adultos jóvenes son los grupos con la mayor proporción de consumo. Conclusiones: México tiene una alta prevalencia de consumo de cigarros con cápsula de sabor. Para reducirla, se deben implementar políticas para prohibir la venta de cigarros con saborizantes y eliminar los diseños atractivos en las cajetillas de los cigarros.

Abstract: Objective: To estimate the prevalence of flavor capsule cigarette, use among Mexicans who are 10 years and older, to determine the proportion of smokers who use flavor capsules, and to characterize the sociodemographic correlates of flavor capsule cigarette use. Materials and methods: Data came from the National Health and Nutrition Survey 2018-19. The prevalence and proportion of flavor capsule cigarette use were estimated by sex, age, education, and wealth. Poisson models were used to evaluate sociodemographic factors associated with flavor capsule cigarette use. Results: Among Mexicans, the prevalence of flavor capsule cigarettes use was 6.6%, which is 43% of all smokers. Women, adolescents, and young adults were more likely than other groups to use flavor capsule cigarettes. Conclusions: Mexicans report a high prevalence of flavor capsule cigarette use. Banning cigarettes with flavors may reduce the appeal of smoking, particularly for youth and women.

E-cigarette use frequency and motivations among current users in middle school.

INTRODUCTION: The popularity of electronic cigarettes (e-cigarettes) has increased worldwide among youth, even in countries like Mexico that ban them. This study aimed to assess the correlates of e-cigarette use frequency among Mexican students who currently use ecigarettes, as well as to describe their reasons for use. METHODS: Data were analyzed from a school-based survey of 57 public middle schools from the three largest cities in Mexico. Primary analyses were confined to those who used e-cigarettes in the prior 30 days. Censored binomial models for truncated distributions were estimated, regressing lifetime and past month frequency of use on participant sociodemographics, other substance use (smoking, alcohol, drugs), technophilia (appeal of new technologies), characteristics of e-cigarettes used, and family's and friends' use of nicotine products. RESULTS: Being male (APR = 1.93 95% CI 1.53-2.44), using drugs, (APR = 1.51 95% CI 1.03-2.20), higher technophilia (APR = 1.66 CI 1.21-2.29) and having a family member who uses e-cigarettes and cigarettes were associated with more frequent use in the last month. Students who preferred fruit and combined flavors had used e-cigarettes more often in their lifetime compared to students who preferred mint/menthol flavors. CONCLUSIONS: Some risk factors for more frequent e-cigarette use among Mexican youth are similar to those foudn in other countries (having relatives who use ecigarettes, using drugs, and use of fruit flavors). Additionally, the novel measure of technophilia was positively associated with frequency of e-cigarette use. The appeal of flavors, in particular, suggests the importance of reducing youth access to flavored products to impede product initiation and progression.