Alteraciones citogenéticas en trabajadores de campo expuestos habitualmente a pesticidas en granjas de flores de Bogotá

Se determinó la frecuencia de alteraciones citogenéticas (micronúcleos y aberracionescromosómicas), deficiencias en la reparación del ADN y actividad de la acetilcolinesterasacomo biomarcadores de exposición a plaguicidas organofosforados y carbamatos entrabajadoras de cultivos de flores en Bogotá. Se realizó un estudio descriptivo en 31 trabajadorascon riesgo ocupacional de exposición a plaguicidas y 30 sin riesgo; la información se obtuvopor medio de una entrevistaFrequency of cytogenetic alterations (micronuclei and chromosome aberrations), DNA repairdeficiencies and acetylcholinesterase activity was determined for field workers in Bogotá,Colombia. These workers were regularly exposed to organophosphate and carbamateinsecticides while employed on farms for flower growing. Interviews were conducted with 31workers associated with occupational risk of pesticides exposure and 30 without exposure. Astandard cytogenetic assay was used to determine chromosome aberrations and micronucleifrequencie

Alteraciones citogenéticas en trabajadoras con riesgo ocupacional de exposición a plaguicidas en cultivos de flores en Bogotá.

Frequency of cytogenetic alterations (micronuclei and chromosome aberrations), DNA repair deficiencies and acetylcholinesterase activity was determined for field workers in Bogotá, Colombia. These workers were regularly exposed to organophosphate and carbamate insecticides while employed on farms for flower growing. Interviews were conducted with 31 workers associated with occupational risk of pesticides exposure and 30 without exposure. A standard cytogenetic assay was used to determine chromosome aberrations and micronuclei frequencies. In addition, a challenge assay assessed response to gamma-rays as an indication of DNA repair deficiencies--cells were exposed to gamma-rays in vitro and the frequencies of chromosome aberrations in post-irradiation metaphase cells were quantified. The data were evaluated for percentage of aberrant cells, cells with chromosome aberrations and frequencies of chromatid breaks per 100 metaphase cells in each worker. The exposed group had a significantly higher frequency of cells with chromosome aberrations and micronuclei as compared with the non-exposed group (p = 0.02). However, the challenge assay did not indicate a significant difference (p > 0.1). These findings require confirmation by further analytical studies involving larger sample. Cytogenetic and toxicological studies, in conjunction with thorough clinical examination are recommended.Se determinó la frecuencia de alteraciones citogenéticas (micronúcleos y aberraciones cromosómicas), deficiencias en la reparación del ADN y actividad de la acetilcolinesterasa como biomarcadores de exposición a plaguicidas organofosforados y carbamatos en trabajadoras de cultivos de flores en Bogotá. Se realizó un estudio descriptivo en 31 trabajadoras con riesgo ocupacional de exposición a plaguicidas y 30 sin riesgo; la información se obtuvo por medio de una entrevista. Se emplearon como pruebas citogenéticas estándar la frecuencia de aberraciones cromosómicas y de micronúcleos; la prueba de reto (challenge assay) se utilizó para determinar la respuesta a los rayos gamma y como indicador de deficiencias en la reparación del ADN. Los datos se analizaron por porcentaje de células aberrantes, frecuencia de aberraciones cromosómicas y rompimiento cromatídico en 100 células en metafase analizadas en cada trabajadora. En los ensayos citogenéticos, se encontró que el grupo expuesto presentó frecuencias mayores de células con aberraciones cromosómicas y micronúcleos que el grupo no expuesto, con diferencias significativas (p=0,02); sin embargo, con la prueba de reto, la diferencia no fue significativa (p>0,1). Estos hallazgos requieren ser confirmados por estudios de tipo analítico que involucren exámenes clínicos; además, es necesario un mayor número de biomarcadores para la monitorización de trabajadores expuestos a plaguicidas en cualquier situación

Estudio citogenético de 38 pacientes con síndrome de turner

Among 36 patients with Turner syndrome diagnosis, 20 had the classical karyotype 45, XO and one had 45, X O/46, X X . The remainder 17 patients had different structural aberrations: ten had one or two lines with long arm isochrornosomes, eight of which were 45,XO mosaicism; one patient had 46,X.del (Xp) or 46, X, tel (Xq) because of total lack of the short arm; three had different percentages of monosomic lines and X rings: 45, X0/46, X, r (X); two had structural aberrations of the Y chromosome: 45, X0/46, and  45,XO/46, X, idic (Yq), and one had 45,X0/46,X,f(X). These patients were referred for clinical and cytogenetic evaluation to the Genetic Group of Colombian National Institute of Health during  the 1.977-1983 period. Observations about the possible origin of chromosomal abnormalities, parental ages, patient's ages, motive of consultation and clinical findings are discussed.De 38 pacientes con síndrome de Turner, 20 presentaron el cariotipo clásico 45,X0 y una el mosaico 45,X0/46,XX. Las otras 17 pacientes mostraron diferentes anomalías estructurales: diez tenían una o dos líneas con isocromosomas de brazos largos, ocho de ellas con mosaicismo 45,X0; una paciente presentó 46,X, deI (Xp) o 46,X,tel (Xq) por tratarse de una falta total de brazos cortos; tres mostraron diferentes porcentajes de líneas monosómicas y anillos X: 45,X0/46,X.dXI; dos pacientes tenían anomalías estructurales d el cromosoma Y: 45,X/46, XY nf y 45.X0/46.X.idic (Yq) y una paciente mostró 45,X0/46,X.f (X). Estas pacientes fueron remitidas para evaluación clínica y citogenetica al Grupo de Gen6tica del Instituto Nacional de Salud de Colombia, de 1977 a 1983. Se discuten algunas observaciones sobre el posible origen de las anomalías cromosómicas, la edad de los padres, las edades y motivos de consulta de las pacientes y los hallazgos clínico

Retardo mental ligado al sexo. Presencia y ausencia de X frágil

In three non related families we evaluated 15 patients with a similar clinical picture consisting of mental retardation, macroorchidism and minor anomalies. This picture showed a sex linked pattern of inheritance. In two families a fragility of the X chromosome at the band q27 was evident. In the third family it mas impossible to demostrate the X fragility, and it is clear that the disease was transmitted by a male. The phenotypic, cytogenetic, and psychological findigs are presented. Some aspects related to this form of sex-linked mental retardation are discussed as welas the as the transmission by a normal male in the two types of families: those with and those without the fragil X.En tres familias no relacionadas se evaluaron 15 pacientes con un mismo cuadro clínico, consistente en retardo mental, macroorquidismo y anomalías menores, que presentan un patrón herencia ligada al sexo. En dos de las familias es evidente una fragilidad del cromosoma X en la banda q27. En la tercera familia fue imposible demostrar la fragilidad del X. En esta se observó la transmisión de la enfermedad por un varón normal

An automated, online feasibility randomized controlled trial of a just-in-time adaptive intervention for smoking cessation (Quit Sense)

Introduction: Learned smoking cues from a smoker’s environment are a major cause of lapse and relapse. Quit Sense, a theory-guided Just-In-Time Adaptive Intervention smartphone app, aims to help smokers learn about their situational smoking cues and provide in-the-moment support to help manage these when quitting. Methods: A two-arm feasibility randomized controlled trial (N = 209) to estimate parameters to inform a definitive evaluation. Smoker’s willing to make a quit attempt were recruited using online paid-for adverts and randomized to “usual care” (text message referral to NHS SmokeFree website) or “usual care” plus a text message invitation to install Quit Sense. Procedures, excluding manual follow-up for nonresponders, were automated. Follow-up at 6 weeks and 6 months included feasibility, intervention engagement, smoking-related, and economic outcomes. Abstinence was verified using cotinine assessment from posted saliva samples. Results: Self-reported smoking outcome completion rates at 6 months were 77% (95% CI 71%, 82%), viable saliva sample return rate was 39% (95% CI 24%, 54%), and health economic data 70% (95% CI 64%, 77%). Among Quit Sense participants, 75% (95% CI 67%, 83%) installed the app and set a quit date and, of those, 51% engaged for more than one week. The 6-month biochemically verified sustained abstinence rate (anticipated primary outcome for definitive trial), was 11.5% (12/104) among Quit Sense participants and 2.9% (3/105) for usual care (adjusted odds ratio = 4.57, 95% CIs 1.23, 16.94). No evidence of between-group differences in hypothesized mechanisms of action was found. Conclusions: Evaluation feasibility was demonstrated alongside evidence supporting the effectiveness potential of Quit Sense. Implications: Running a primarily automated trial to initially evaluate Quit Sense was feasible, resulting in modest recruitment costs and researcher time, and high trial engagement. When invited, as part of trial participation, to install a smoking cessation app, most participants are likely to do so, and, for those using Quit Sense, an estimated one-half will engage with it for more than 1 week. Evidence that Quit Sense may increase verified abstinence at 6-month follow-up, relative to usual care, was generated, although low saliva return rates to verify smoking status contributed to considerable imprecision in the effect size estimate

A smoking cessation smartphone app that delivers real-time ‘context aware’ behavioural support: the Quit Sense feasibility RCT

BackgroundDuring a quit attempt, cues from a smoker’s environment are a major cause of brief smoking lapses, which increase the risk of relapse. Quit Sense is a theory-guided Just-In-Time Adaptive Intervention smartphone app, providing smokers with the means to learn about their environmental smoking cues and provides ‘in the moment’ support to help them manage these during a quit attempt.ObjectiveTo undertake a feasibility randomised controlled trial to estimate key parameters to inform a definitive randomised controlled trial of Quit Sense.DesignA parallel, two-arm randomised controlled trial with a qualitative process evaluation and a ‘Study Within A Trial’ evaluating incentives on attrition. The research team were blind to allocation except for the study statistician, database developers and lead researcher. Participants were not blind to allocation.SettingOnline with recruitment, enrolment, randomisation and data collection (excluding manual telephone follow-up) automated through the study website.ParticipantsSmokers (323 screened, 297 eligible, 209 enrolled) recruited via online adverts on Google search, Facebook and Instagram.InterventionsParticipants were allocated to ‘usual care’ arm (n = 105; text message referral to the National Health Service SmokeFree website) or ‘usual care’ plus Quit Sense (n = 104), via a text message invitation to install the Quit Sense app.Main outcome measuresFollow-up at 6 weeks and 6 months post enrolment was undertaken by automated text messages with an online questionnaire link and, for non-responders, by telephone. Definitive trial progression criteria were met if a priori thresholds were included in or lower than the 95% confidence interval of the estimate. Measures included health economic and outcome data completion rates (progression criterion #1 threshold: ≥ 70%), including biochemical validation rates (progression criterion #2 threshold: ≥ 70%), recruitment costs, app installation (progression criterion #3 threshold: ≥ 70%) and engagement rates (progression criterion #4 threshold: ≥ 60%), biochemically verified 6-month abstinence and hypothesised mechanisms of action and participant views of the app (qualitative).ResultsSelf-reported smoking outcome completion rates were 77% (95% confidence interval 71% to 82%) and health economic data (resource use and quality of life) 70% (95% CI 64% to 77%) at 6 months. Return rate of viable saliva samples for abstinence verification was 39% (95% CI 24% to 54%). The per-participant recruitment cost was £19.20, which included advert (£5.82) and running costs (£13.38). In the Quit Sense arm, 75% (95% CI 67% to 83%; 78/104) installed the app and, of these, 100% set a quit date within the app and 51% engaged with it for more than 1 week. The rate of 6-month biochemically verified sustained abstinence, which we anticipated would be used as a primary outcome in a future study, was 11.5% (12/104) in the Quit Sense arm and 2.9% (3/105) in the usual care arm (estimated effect size: adjusted odds ratio = 4.57, 95% CIs 1.23 to 16.94). There was no evidence of between-arm differences in hypothesised mechanisms of action. Three out of four progression criteria were met.The Study Within A Trial analysis found a £20 versus £10 incentive did not significantly increase follow-up rates though reduced the need for manual follow-up and increased response speed. The process evaluation identified several potential pathways to abstinence for Quit Sense, factors which led to disengagement with the app, and app improvement suggestions.LimitationsBiochemical validation rates were lower than anticipated and imbalanced between arms. COVID-19-related restrictions likely limited opportunities for Quit Sense to provide location tailored support.ConclusionsThe trial design and procedures demonstrated feasibility and evidence was generated supporting the efficacy potential of Quit Sense.Future workProgression to a definitive trial is warranted providing improved biochemical validation rates.Trial registrationThis trial is registered as ISRCTN12326962

Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes

Type I interferons (IFNs) are important for host defense from viral infections, acting to restrict viral production in infected cells and to promote antiviral immune responses. However, the type I IFN system has also been associated with severe lung inflammatory disease in response to respiratory syncytial virus (RSV). Which cells produce type I IFNs upon RSV infection and how this directs immune responses to the virus, and potentially results in pathological inflammation, is unclear. Here, we show that alveolar macrophages (AMs) are the major source of type I IFNs upon RSV infection in mice. AMs detect RSV via mitochondrial antiviral signaling protein (MAVS)–coupled retinoic acid–inducible gene 1 (RIG-I)–like receptors (RLRs), and loss of MAVS greatly compromises innate immune restriction of RSV. This is largely attributable to loss of type I IFN–dependent induction of monocyte chemoattractants and subsequent reduced recruitment of inflammatory monocytes (infMo) to the lungs. Notably, the latter have potent antiviral activity and are essential to control infection and lessen disease severity. Thus, infMo recruitment constitutes an important and hitherto underappreciated, cell-extrinsic mechanism of type I IFN–mediated antiviral activity. Dysregulation of this system of host antiviral defense may underlie the development of RSV-induced severe lung inflammation

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Alteraciones citogenéticas en trabajadores de campo expuestos habitualmente a pesticidas en granjas de flores de Bogotá

Se determinó la frecuencia de alteraciones citogenéticas (micronúcleos y aberracionescromosómicas), deficiencias en la reparación del ADN y actividad de la acetilcolinesterasacomo biomarcadores de exposición a plaguicidas organofosforados y carbamatos entrabajadoras de cultivos de flores en Bogotá. Se realizó un estudio descriptivo en 31 trabajadorascon riesgo ocupacional de exposición a plaguicidas y 30 sin riesgo; la información se obtuvopor medio de una entrevistaFrequency of cytogenetic alterations (micronuclei and chromosome aberrations), DNA repairdeficiencies and acetylcholinesterase activity was determined for field workers in Bogotá,Colombia. These workers were regularly exposed to organophosphate and carbamateinsecticides while employed on farms for flower growing. Interviews were conducted with 31workers associated with occupational risk of pesticides exposure and 30 without exposure. Astandard cytogenetic assay was used to determine chromosome aberrations and micronucleifrequencie

Estudio bioquímico y genetico de la enfermedad trofoblastica gestacional

IP 1101-04-11874Contrato 151-2002Impacto social: La presente investigación representa uno de los estudios adelantados sobre la enfermedad en nuestro país, su enfoque multidisciplinario es un análisis integral que cubre aspectos socioculturales, clínicos, moleculares y epidemiológicos que muestran el impacto de tiene la mola en el campo de la salud sexual y reproductiv