Toxoplasma gondii chronic infection in rodent secondary hosts has been reported to lead to a loss of innate, hard-wired fear toward cats, its primary host. However the generality of this response ...across T. gondii strains and the underlying mechanism for this pathogen-mediated behavioral change remain unknown. To begin exploring these questions, we evaluated the effects of infection with two previously uninvestigated isolates from the three major North American clonal lineages of T. gondii, Type III and an attenuated strain of Type I. Using an hour-long open field activity assay optimized for this purpose, we measured mouse aversion toward predator and non-predator urines. We show that loss of innate aversion of cat urine is a general trait caused by infection with any of the three major clonal lineages of parasite. Surprisingly, we found that infection with the attenuated Type I parasite results in sustained loss of aversion at times post infection when neither parasite nor ongoing brain inflammation were detectable. This suggests that T. gondii-mediated interruption of mouse innate aversion toward cat urine may occur during early acute infection in a permanent manner, not requiring persistence of parasite cysts or continuing brain inflammation.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has redemonstrated the importance of work as a determinant of health. During the pandemic, extant disparities were accentuated as the ...workforce was divided into the roughly 50% who could safely work from home and those who could not. With the spotlight on work, one might wonder where all the occupational epidemiologists have gone. To answer, we point to diminished research support and more limited workplace access that have led many epidemiologists to shift away from a focus on workers toward other vulnerable populations. Here we build on the renewed interest in work as a driver of health and inequality during the pandemic to highlight contributions of occupational epidemiology to public health. We consider: 1) etiological studies of chronic disease based on employment records to define cohorts and reconstruct long-term exposure; 2) studies of hypothetical interventions that are particularly appropriate for evaluating potential regulations to reduce workplace exposures; and 3) studies of disparities that take advantage of work as a potential source of social stratification and economic opportunity. As we have learned during the COVID-19 pandemic, workplaces can become venues for public health messaging and delivering interventions to enumerated populations of adults. By starting with COVID-19 prevention policies for the workplace, we have a chance to better protect public health.
Objectives Most studies of carpal tunnel syndrome (CTS) incidence and prevalence among workers have been limited by small sample sizes or restricted to a small subset of jobs. We established a common ...CTS case definition and then pooled CTS prevalence and incidence data across six prospective studies of musculoskeletal outcomes to measure CTS frequency and allow better studies of etiology. Methods Six research groups collected prospective data at >50 workplaces including symptoms characteristic of CTS and electrodiagnostic studies (EDS) of the median and ulnar nerves across the dominant wrist. While study designs and the timing of data collection varied across groups, we were able to create a common CTS case definition incorporating both symptoms and EDS results from data that were collected in all studies. Results At the time of enrollment, 7.8% of 4321 subjects met our case definition and were considered prevalent cases of CTS. During 8833 person-years of follow-up, an additional 204 subjects met the CTS case definition for an overall incidence rate of 2.3 CTS cases per 100 person-years. Conclusions Both prevalent and incident CTS were common in data pooled across multiple studies and sites. The large number of incident cases in this prospective study provides adequate power for future exposure— response analyses to identify work- and non-work-related risk factors for CTS. The prospective nature allows determination of the temporal relations necessary for causal inference.
Upon natural infection with pathogens or vaccination, antibodies are produced by a process called affinity maturation. As affinity maturation ensues, average affinity values between an antibody and ...ligand increase with time. Purified antibodies isolated from serum are invariably heterogeneous with respect to their affinity for the ligands they bind, whether macromolecular antigens or haptens (low molecular weight approximations of epitopes on antigens). However, less is known about how the extent of this heterogeneity evolves with time during affinity maturation. To shed light on this issue, we have taken advantage of previously published data from Eisen and Siskind (1964). Using the ratio of the strongest to the weakest binding subsets as a metric of heterogeneity (or affinity inequality), we analyzed antibodies isolated from individual serum samples. The ratios were initially as high as 50-fold, and decreased over a few weeks after a single injection of small antigen doses to around unity. This decrease in the effective heterogeneity of antibody affinities with time is consistent with Darwinian evolution in the strong selection limit. By contrast, neither the average affinity nor the heterogeneity evolves much with time for high doses of antigen, as competition between clones of the same affinity is minimal.
Background Between 2001 and 2010, five research groups conducted coordinated prospective studies of carpal tunnel syndrome (CTS) incidence among US workers from various industries and collected ...detailed subject-level exposure information with follow-up of symptoms, electrophysiological measures and job changes. Objective This analysis examined the associations between workplace biomechanical factors and incidence of dominant-hand CTS, adjusting for personal risk factors. Methods 2474 participants, without CTS or possible polyneuropathy at enrolment, were followed up to 6.5 years (5102 person-years). Individual workplace exposure measures of the dominant hand were collected for each task and included force, repetition, duty cycle and posture. Task exposures were combined across the workweek using time-weighted averaging to estimate job-level exposures. CTS case-criteria were based on symptoms and results of electrophysiological testing. HRs were estimated using Cox proportional hazard models. Results After adjustment for covariates, analyst (HR=2.17; 95% CI 1.38 to 3.43) and worker (HR=2.08; 95% CI 1.31 to 3.39) estimated peak hand force, forceful repetition rate (HR=1.84; 95% CI 1.19 to 2.86) and per cent time spent (eg, duty cycle) in forceful hand exertions (HR=2.05; 95% CI 1.34 to 3.15) were associated with increased risk of incident CTS. Associations were not observed between total hand repetition rate, per cent duration of all hand exertions, or wrist posture and incident CTS. Conclusions In this prospective multicentre study of production and service workers, measures of exposure to forceful hand exertion were associated with incident CTS after controlling for important covariates. These findings may influence the design of workplace safety programmes for preventing work-related CTS.
Abstract
In previous studies, investigators have reported increased risks of specific cancers associated with exposure to metalworking fluids (MWFs). In this report we broadly examine the incidence ...of 14 types of cancer, with a focus on digestive, respiratory, and hormonal cancers, in the United Auto Workers–General Motors (UAW-GM) cohort, a cohort of workers exposed to MWFs (1973–2015). The cohort included 39,132 workers followed for cancer incidence. Cox models yielded estimates of adjusted hazard ratios, with categorical variables for lagged cumulative exposure to 3 types of MWF (straight, soluble, and synthetic). We fitted penalized splines to examine the shape of the exposure-response relationships. There were 7,809 incident cancer cases of interest. Oil-based straight and soluble MWFs were each modestly associated with all cancers combined. Exposure-response patterns were consistent with prior reports from this cohort, and results for splined exposures generally reflected their categorically modeled counterparts. We found significantly increased incidence of stomach and kidney cancer with higher levels of straight MWF exposure and increased rectal and prostate cancer with increasing water-based synthetic MWF exposure. Only non-Hodgkin lymphoma and prostate cancer were associated with soluble MWF. All results for colon and lung cancers were null. Our results provide updated evidence for associations between MWF exposure and incidence of several types of cancer.
Objectives Shift work, such as alternating day and nights, causes chronobiologic disruptions which may cause an increase in hypertension risk. However, the relative contributions of the components of ...shift work ‒ such as shift type (eg, night work) and rotations (ie, switching of shift times; day to night) ‒ on this association are not clear. To address this question, we constructed novel definitions of night work and rotational work and assessed their associations with risk of incident hypertension. Methods A cohort of 2151 workers at eight aluminum manufacturing facilities previously studied for cardiovascular disease was followed from 2003 through 2013 for incident hypertension, as defined by ICD-9 insurance claims codes. Detailed time-registry data was used to classify each worker's history of rotational and night work. The associations between recent rotational work and night work in the last 12 months and incident hypertension were estimated using adjusted Cox proportional hazards models. Results Elevated hazard ratios (HR) were observed for all levels of recent night work (>0-5, >5-50, >50-95, >95-100%) compared with non-night workers, and among all levels of rotational work (<1, 1-10, >10-20, >20-30, and >30%) compared with those working <1% rotational work. In models for considering the combination of night and rotational work, workers with mostly night work and frequent rotations (≥50% night and ≥10% rotation) had the highest risk of hypertension compared to non-night workers HR 4.00, 95% confidence interval (CI )1.69-9.52. Conclusions Our results suggest recent night and rotational work may both be associated with higher rates of incident hypertension.
Background: Studies of autoworkers exposed to straight metalworking fluids report excess risks of several cancers. These studies, however, have not addressed the healthy-worker survivor effect. Most ...methods proposed to address this bias do not consider that it may be caused by time-varying confounders affected by prior exposure. G-estimation of accelerated failure-time models was developed to handle this issue but has never been applied to account for the healthy-worker survivor effect. Methods: We compare results from Cox models and g-estimation in 38,747 autoworkers exposed to straight metalworking fluids. Exposure was defined based on job records and air samples. We examine relationships between duration of exposure and mortality from all causes, cancers, ischemic heart disease, and chronic obstructive pulmonary disease (COPD). Results: In standard models, hazard ratios were elevated for cancers of the larynx, prostate, and rectum, but below or approximately equal to 1.0 for all other outcomes considered. Adjustment for the healthy-worker survivor effect using time off work, employment status, time since hire, and restriction to inactive workers after 15 years of follow-up did not substantially change the hazard ratios. However, g-estimation yielded higher hazard ratios than standard Cox models for most outcomes. Exposure was related to increased risks of mortality from all causes combined, heart disease, COPD, and all cancers, as well as lung and prostate cancers. Conclusions: G-estimation may provide a better control for the healthy-worker survivor effect than standard methods.
Background Between 2001 and 2010, six research groups conducted coordinated multiyear, prospective studies of carpal tunnel syndrome (CTS) incidence in US workers from various industries and ...collected detailed subject-level exposure information with follow-up symptom, physical examination, electrophysiological measures and job changes. Objective This analysis of the pooled cohort examined the incidence of dominant-hand CTS in relation to demographic characteristics and estimated associations with occupational psychosocial factors and years worked, adjusting for confounding by personal risk factors. Methods 3515 participants, without baseline CTS, were followed-up to 7 years. Case criteria included symptoms and an electrodiagnostic study consistent with CTS. Adjusted HRs were estimated in Cox proportional hazard models. Workplace biomechanical factors were collected but not evaluated in this analysis. Results Women were at elevated risk for CTS (HR=1.30; 95% CI 0.98 to 1.72), and the incidence of CTS increased linearly with both age and body mass index (BMI) over most of the observed range. High job strain increased risk (HR=1.86; 95% CI 1.11 to 3.14), and social support was protective (HR=0.54; 95% CI 0.31 to 0.95). There was an inverse relationship with years worked among recent hires with the highest incidence in the first 3.5 years of work (HR=3.08; 95% CI 1.55 to 6.12). Conclusions Personal factors associated with an increased risk of developing CTS were BMI, age and being a woman. Workplace risk factors were high job strain, while social support was protective. The inverse relationship between CTS incidence and years worked among recent hires suggests the presence of a healthy worker survivor effect in the cohort.
BACKGROUND:If less healthy workers terminate employment earlier, thus accumulating less exposure, yet remain at greater risk of the health outcome, estimated health effects of cumulative exposure ...will be biased downward. If exposure also affects termination of employment, then the bias cannot be addressed using conventional methods. We examined these conditions as a prelude to a reanalysis of lung cancer mortality in the Diesel Exhaust in Miners Study.
METHODS:We applied an accelerated failure time model to assess the effect of exposures to respirable elemental carbon (a surrogate for diesel) on time to termination of employment among nonmetal miners who ever worked underground (n = 8,307). We then applied the parametric g-formula to assess how possible interventions setting respirable elemental carbon exposure limits would have changed lifetime risk of lung cancer, adjusting for time-varying employment status.
RESULTS:Median time to termination was 36% shorter (95% confidence interval = 33%, 39%), per interquartile range width increase in respirable elemental carbon exposure. Lung cancer risk decreased with more stringent interventions, with a risk ratio of 0.8 (95% confidence interval = 0.5, 1.1) comparing a limit of ≤25 µg/m respirable elemental carbon to no intervention. The fraction of cases attributable to diesel exposure was 27% in this population.
CONCLUSIONS:The g-formula controlled for time-varying confounding by employment status, the signature of healthy worker survivor bias, which was also affected by diesel exposure. It also offers an alternative approach to risk assessment for estimating excess cumulative risk, and the impact of interventions based entirely on an observed population.
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