Time Of Last Exposure Research Articles

P-470 Impact of patient characteristics at ovarian tissue cryopreservation on follicle activation and survival

Abstract Study question Does first-line chemotherapy prior to ovarian tissue cryopreservation and diseases impact on the signaling pathways governing follicle activation and survival in pre-pubertal and adult patients? Summary answer Chemotherapy increases follicle apoptosis rate without affecting early follicular activation. Moreover, damages varied according to the time of last exposure and the diseases. What is known already Chemotherapeutic agents can impair the ovarian stockpile inducing a decrease of the reproductive potential of female cancer survivors. Among fertility preservation methods, cortical tissue cryopreservation is offered in patients who already started their treatment or cannot postpone it, and it is currently the only available procedure for pre-pubertal patients. Few studies did not report negative impact of prior first-line chemotherapy on ovarian tissue cryopreservation outcomes, the consequences of the treatment on the follicle activation in human remain to be further investigated. Identifying the signaling modifications induced by chemotherapy exposure is essential to address this question. Study design, size, duration Fragments of cryopreserved ovarian tissue from young adult (12-29 years old, n = 8) and pre-pubertal (3-10 years old, n = 7) cancer patients donated for research were thawed and cultured for 24h. Analyses of the follicle and stroma survival, as well as the PI3K/AKT/mTOR and Hippo signaling pathways were conducted at thawing and after culture. The different patients were grouped according to their pubertal stage and those who received chemotherapy before ovarian banking were compared to non-exposed patients. Participants/materials, setting, methods To assess the distribution and morphology of the follicles, the structure of the stroma, and the apoptosis, histological investigations were performed through follicular counting, Sirius Red staining, immunostaining, and TUNEL staining. The PI3K/AKT/mTOR and Hippo signaling pathways were investigated to explore the follicular activation among the different groups by gene expression and protein analyses on isolated follicles and cortex, respectively. Main results and the role of chance The deleterious impact of chemotherapy exposure prior to tissue banking was observed specifically on quiescent follicles by TUNEL staining at thawing and after culture in both adult and pre-pubertal patients. After 24h of culture, tissues previously exposed to chemotherapy displayed a higher rate of follicles containing DNA damages than the non-exposed fragments in adults (40.9% versus 19.1%), and pre-pubertal (48.3% versus 17.6%) patients. The atresia rates and DNA damages appeared to be lower into the tissue of patients that received their last cure 4-5 months before the cryopreservation among the treated adult and pre-pubertal groups. DNA reparation mechanisms were assessed through gH2Ax staining and revealed a correlation with the diseases as a higher phosphorylation rate of H2Ax protein was observed in tissues from acute leukemia patients compare to the others at thawing (p = 0.009) and after 24h (p < 0.001). Although protein analyses on Kit Ligand, key regulator of the follicle activation, showed an increase of expression into the groups treated by chemotherapy, genes and protein involved in the PI3K/AKT/mTOR and Hippo pathways showed similar expression levels in the chemo-treated groups compared to the non-exposed groups, irrespective of the age. Limitations, reasons for caution The study of follicle survival was limited to histological analyses, while follicular activation evaluations were limited to the evaluation of two main signaling, PI3K/AKT/mTOR and Hippo. Moreover, considering the heterogeneity of the human model, and the limited number of patients included, the results should be interpreted with caution. Wider implications of the findings Our results highlight the deleterious impact of previous chemotherapeutic treatment on follicle survival without affecting follicular activation. Besides sustaining the “burn out effect” theory, our results suggested that the time of last exposure and the pathology of the patient could impact the outcomes of the cryopreserved ovarian tissue. Trial registration number not applicable

Coronavirus Disease (COVID-19) Outbreak among Islamic Missionaries in Terengganu state of Malaysia in 2020.

Background: Malaysia experienced an outbreak of COVID-19 after Islamic missionaries returned from religious gathering in Sri Petaling Mosque, Kuala Lumpur. The outbreak extended to the state of Terengganu which also resulted in an outbreak in a private Islamic institution known as BKMQ (an anonymized name) in Kuala Terengganu District.Materials and Methods: A descriptive cross-sectional study was conducted to describe the characteristics of COVID-19 cases and the experience of COVID-19 outbreak containment in BKMQ.Results: There were six individuals diagnosed with COVID-19 in BKMQ. Majority of them were male (83.3%), in the age group of 20 to <40 years old (50.0%) and had fever as their symptom (50.0%). The time of last exposure to diagnosis among majority of cases were 12 days, and majority of cases (66.6%) stayed in hospital between 20 days to less than 40 days.Conclusion: The transmission of virus was postulated to be through household exposure and vehicle sharing. Prompt action, immediate lockdown and inter-agencies collaboration were the key factors in successfully controlling the spread of COVID-19 in the institution and community.International Journal of Human and Health Sciences Vol. 05 No. 04 October’21 Page: 491-498

The influence of intensity and timing of daily light exposure on subjective and objective sleep in adolescents with an evening circadian preference

Study objectivesThe aim of the present study is to examine the relationship between light and sleep, in adolescents with an evening circadian preference. MethodsFor a period of seven days, ninety-nine adolescents wore a wrist actigraph to assess light exposure and objective sleep and completed a sleep diary to assess subjective sleep. ResultsLower average light intensity across the preceding 24 h was associated with a later sleep onset (p < 0.01) and a later next-day sleep offset (p < 0.05). A later time of last exposure to more than 10 lux was associated with a later sleep onset (p < 0.001) and a shorter objective total sleep time (p < 0.001), as well as a later bedtime (p < 0.001) and a shorter subjective total sleep time (p < 0.001). Furthermore, exploratory analyses found that lower average early morning light exposure (between 4 and 9 AM) was associated with later sleep onset (p < 0.05), a later next-day sleep offset (p < 0.05), and a later next-day waketime (p < 0.01), lower average afternoon light exposure (between 2 and 7 PM) was associated with a later next-day sleep offset (p < 0.05), and lower average evening light exposure (between 7 PM and 12 AM) was associated with longer subjective total sleep time (p < 0.01). ConclusionThis study highlights the importance of light exposure, particularly the timing of light exposure, for establishing healthy patterns of sleep among adolescents with a propensity for a delayed bedtime and waketime. These findings provide additional evidence for targeting light exposure when designing interventions to improve adolescent sleep.

User Guide for Luminescence Sampling in Archaeological and Geological Contexts

AbstractLuminescence dating provides a direct age estimate of the time of last exposure of quartz or feldspar minerals to light or heat and has been successfully applied to deposits, rock surfaces, and fired materials in a number of archaeological and geological settings. Sampling strategies are diverse and can be customized depending on local circumstances, although all sediment samples need to include a light-safe sample and material for dose-rate determination. The accuracy and precision of luminescence dating results are directly related to the type and quality of the material sampled and sample collection methods in the field. Selection of target material for dating should include considerations of adequacy of resetting of the luminescence signal (optical and thermal bleaching), the ability to characterize the radioactive environment surrounding the sample (dose rate), and the lack of evidence for post-depositional mixing (bioturbation in soils and sediment). Sample strategies for collection of samples from sedimentary settings and fired materials are discussed. This paper should be used as a guide for luminescence sampling and is meant to provide essential background information on how to properly collect samples and on the types of materials suitable for luminescence dating.

Circulating Soluble CD27 and CD30 in Workers Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)

Previous studies suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings remain inconclusive. There is a need for mechanistic studies to evaluate the biologic plausibility of this association. In this cross-sectional study, we investigated changes in plasma levels of interleukin 1 receptor antagonist (IL1RA) and soluble (s)CD27 and sCD30 which have been found to be predictive of lymphoma, among workers of a cohort occupationally exposed to TCDD. Eighty-five workers who had been exposed to TCDD more than 30 years before blood collection were included in the current investigation. Plasma level of the markers was measured by ELISA. Current plasma levels of TCDD were determined by high-resolution gas chromatography/isotope dilution high-resolution mass spectrometry. TCDD blood levels at time of last exposure were estimated using a one-compartment first order kinetic model. Exposure-response analyses showed no significant association between blood levels of sCD27, and sCD30 and current and estimated TCDD levels at time of last exposure. IL1RA showed a borderline significant decrease with increasing plasma TCDD levels (P = 0.07), which reached formal statistical significance when excluding subjects with chronic diseases. In conclusion, no clear dose-response relationship was observed between the measured markers and TCDD level. However, there was a suggestion that markers in particular IL1RA tended to decrease with increasing TCDD levels. This observation is consistent with our earlier observation on decreasing cytokine levels, suggesting immunosuppression, with increasing exposures. These findings possibly provide new insights in the etiology of NHL and the mechanisms through which TCDD can increase lymphoma risk.

400 Circulating soluble CD27 and CD30 in workers exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)

ObjectivesPrevious studies suggest that 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings remain inconclusive. There is a need for mechanistic studies to evaluate...

117 Metabolomics experiment among workers exposed to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)

ObjectivesPrevious occupational studies suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings are inconclusive. Mechanistic studies using global biochemical profiling (metabolomics) could provide supporting evidence...

Serum metabolomic pertubations among workers exposed to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD)

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with multiple health effects. Mechanistic studies using metabolomics could provide supporting evidence for such associations by identifying relevant biological pathways. In this study, we investigated metabolic perturbations in a cohort of TCDD exposed workers to better understand TCDD related health effects. Eighty one workers who had been exposed to TCDD in the past and 63 nonexposed workers were included in the study. Serum metabolites were detected using ultra high pressure liquid chromatography coupled online to a Q-TOF Premier mass spectrometer with a scan range of 70-1,000 m/z. Current plasma levels of TCDD were determined by high-resolution gas chromatography/isotope dilution high resolution mass spectrometry. TCDD blood levels at the time of last exposure were estimated using a one-compartment first order kinetic model. Differentially expressed metabolites were identified using linear regression models, partial least squares regression (PLSr) and a regression-based Bayesian variable selection approach. Features that were present in all quality control samples and had a coefficient of variation <30% were included in the analyses (n = 421 features). Adjusted linear regression analysis showed several significant perturbations (n = 27; P < 0.05) but these observations did not survive multiple testing correction (q value > 0.05). PLSr analyses and Bayesian variable selection regression analyses revealed no obvious metabolic perturbations associated with TCDD levels. This is the first metabolomic analysis related to TCDD exposure in humans. No significant metabolic features were identified. It is concluded that TCDD exposure at levels present in this study does not lead to significant perturbations of the serum metabolome.

Changes in lymphocyte subsets in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Objectives2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to have toxic effects on the haematopoietic system in animals but epidemiological studies in humans have shown inconsistent results. In this cross-sectional study we investigated changes...

Predictive model accuracy in estimating last Δ9-tetrahydrocannabinol (THC) intake from plasma and whole blood cannabinoid concentrations in chronic, daily cannabis smokers administered subchronic oral THC

BackgroundDetermining time since last cannabis/Δ9-tetrahydrocannabinol (THC) exposure is important in clinical, workplace, and forensic settings. Mathematical models calculating time of last exposure from whole blood concentrations typically employ a theoretical 0.5 whole blood-to-plasma (WB/P) ratio. No studies previously evaluated predictive models utilizing empirically-derived WB/P ratios, or whole blood cannabinoid pharmacokinetics after subchronic THC dosing. MethodsTen male chronic, daily cannabis smokers received escalating around-the-clock oral THC (40–120mg daily) for 8 days. Cannabinoids were quantified in whole blood and plasma by two-dimensional gas chromatography–mass spectrometry. ResultsMaximum whole blood THC occurred 3.0h after the first oral THC dose and 103.5h (4.3 days) during multiple THC dosing. Median WB/P ratios were THC 0.63 (n=196), 11-hydroxy-THC 0.60 (n=189), and 11-nor-9-carboxy-THC (THCCOOH) 0.55 (n=200). Predictive models utilizing these WB/P ratios accurately estimated last cannabis exposure in 96% and 100% of specimens collected within 1–5h after a single oral THC dose and throughout multiple dosing, respectively. Models were only 60% and 12.5% accurate 12.5 and 22.5h after the last THC dose, respectively. ConclusionsPredictive models estimating time since last cannabis intake from whole blood and plasma cannabinoid concentrations were inaccurate during abstinence, but highly accurate during active THC dosing. THC redistribution from large cannabinoid body stores and high circulating THCCOOH concentrations create different pharmacokinetic profiles than those in less than daily cannabis smokers that were used to derive the models. Thus, the models do not accurately predict time of last THC intake in individuals consuming THC daily.

Plasma Cytokine Concentrations in Workers Exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Objectives: Few epidemiological studies have studied the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on blood cytokine levels. In this study we investigated changes in plasma levels of a large panel of cytokines, chemokines, and growth factors among workers from a Dutch historical cohort occupationally exposed to chlorophenoxy herbicides and contaminants including TCDD. Methods: Eighty-five workers who had been exposed to either high (n = 47) or low (n = 38) TCDD levels more than 30 years before serum collection were included in the current investigation. Plasma level of 16 cytokines, 10 chemokines, and 6 growth factors were measured. Current plasma levels of TCDD (TCDDcurrent) were determined by high-resolution gas chromatography/isotope-dilution high-resolution mass spectrometry. TCDD blood levels at the time of last exposure (TCDDmax) were estimated using a one-compartment first order kinetic model. Results: Blood levels of most analytes had a negative association with current and estimated past maximum TCDD levels. These decreases reached formal statistical significance for fractalkine, transforming growth factor alpha (TGF-α), and fibroblast growth factor 2 (FGF2) with increasing TCDD levels. Conclusion: Our study showed a general reduction in most analyte levels with the strongest effects for fractalkine, FGF2, and TGF-α. These findings suggest that TCDD exposure could suppress the immune system and that chemokine and growth factor-dependent cellular pathway changes by TCDD may play role in TCDD toxicity and associated health effects.

Long-term effects on humoral immunity among workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

ObjectivesEpidemiological studies have shown inconsistent effects on immunological parameters in subjects exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this study we investigated changes in humoral immunity and prevalence of atopic diseases among...

Dioxin and diabetes mellitus: an analysis of the combined NIOSH and Ranch Hand data

OBJECTIVESTo reanalyze in a similar manner the two principal studies of TCDD (tetrachlorodibenzo-p-dioxin) and diabetes in an attempt to reconcile disparate results.METHODSData from 990 United States Air Force veterans (Ranch...

Establishing efficient partner notification periods for patients with chlamydia.

To delineate chlamydia partner notification periods with high proportions of infected, untreated sexual partners, and to evaluate relevant Centers for Disease Control (CDC) recommendations. Disease Intervention Specialists (DIS) offered contact tracing services to all chlamydia patients (N = 1,309) reported in Colorado Springs between July 1996 and June 1997. Patients were asked to identify sexual partners during the 180 days preceding treatment. Partners were actively sought by DIS and offered DNA amplification testing. Of 1,309 patients, 1,109 were interviewed, resulting in 2,293 named partners. Two fifths of eligible partners were located; inability to examine partners was related to time of last exposure and to frequency of sexual exposure. Of located partners, 95% were tested with DNA amplification technology. Adherence to CDC criteria identified 88% of infected, untreated partners; the other 12% consisted mainly of epidemiologically important asymptomatic men whose infection is seldom identified by current public health interventions. The chlamydia partner notification recommendations of the CDC are adequate, but miss men with long-standing infection. These men contribute to entrenched chlamydia endemicity; targeted programs to screen high-risk men merit serious consideration.

Test of thermoluminescence dating of buried soils from Mt. Kenya, Kenya

We have applied the partial bleach (R-Gamma) thermoluminescence (TL) dating method to four organic-rich Ab horizons of buried soils from Mount Kenya. Our objective was to test the feasibility of directly measuring the time of last exposure to sunlight of the fine-grained silicate minerals within these horizons. The resulting apparent ages for three samples of 1.2±0.3, 6±2 and 10±2 ka (1 std. dev.) are in general agreement with associated 14C age estimates from buried whole soil (paleosol) samples. The fourth sample, of an age (though unknown) presumed to lie beyond the 14C dating limit, yielded a TL age estimate of 60±20 ka. Notwithstanding some limitations, these results are encouraging and imply that with simple refinements, this TL method is capable of directly dating accurately such buried soils, probably to well beyond the ≈ 40 ka 14C dating limit.