Oxytocin is a neuropeptide hormone that plays a key role in social behavior, stress regulation, and mental health. Synthetic oxytocin administration is a common obstetrical practice, and importantly, ...previous research has suggested that intrapartum exposure may increase the risk of neurodevelopmental disorders, such as autism spectrum disorder.
This study aimed to examine the association between synthetic oxytocin exposure during labor and autism spectrum disorder diagnosis in the child.
This population-based retrospective cohort study compared 2 cohorts of children: (1) all children born in British Columbia, Canada between April 1, 2000 and December 31, 2014 (n=414,336 births), and (2) all children delivered at Soroka University Medical Center in Be'er-Sheva, Israel between January 1, 2011 and December 31, 2019 (n=82,892 births). Nine different exposure groups were examined. Cox proportional hazards models were used to estimate crude and adjusted hazard ratios of autism spectrum disorder in both cohorts on the basis of induction and/or augmentation exposure status. To further control for confounding by indication, we conducted sensitivity analyses among a cohort of healthy, uncomplicated deliveries and among a group that was induced only for postdates. In addition, we stratified our analyses by infant sex to assess for potential sex differences.
In the British Columbia cohort, 170,013 of 414,336 deliveries (41.0%) were not induced or augmented, 107,543 (26.0%) were exposed to oxytocin, and 136,780 (33.0%) were induced or augmented but not exposed to oxytocin. In the Israel cohort, 51,790 of 82,892 deliveries (62.5%) were not induced or augmented, 28,852 (34.8%) were exposed to oxytocin, and 2250 (2.7%) were induced or augmented but not exposed to oxytocin. On adjusting for covariates in the main analysis, significant associations were observed in the Israel cohort, including adjusted hazard ratios of 1.51 (95% confidence interval, 1.20–1.90) for oxytocin-augmented births and 2.18 (95% confidence interval, 1.32–3.57) for those induced by means other than oxytocin and not augmented. However, oxytocin induction was not significantly associated with autism spectrum disorder in the Israel cohort. In the Canadian cohort, there were no statistically significant adjusted hazard ratios. Further, no significant sex differences were observed in the fully adjusted models.
This study supports that induction of labor through oxytocin administration does not increase the risk of autism spectrum disorder in the child. Our international comparison of 2 countries with differences in clinical practice regarding oxytocin administration for induction and/or augmentation suggests that previous studies reporting a significant association were likely confounded by the underlying indication for the induction.
In patients with penetrating neck injuries with clinical soft injury signs, and patients with hard signs of injury who do not require immediate surgery, CT angiography of the neck is the preferred ...imaging procedure to evaluate extent of injury. Other modalities, such as radiography and fluoroscopy, catheter-based angiography, ultrasound, and MR angiography have their place in the evaluation of the patient, depending on the specific clinical situation and question at hand. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Background: Triple-negative breast cancer (TNBC) poses a serious therapeutic challenge. Neoplastic transformation affects extracellular vesicle (EV) biogenesis and cancer cell-derived EVs may mediate ...immune modulation, chemo-resistance and metastasis. Cancer-associated mechanisms that regulate EV production and function require further investigation. This study aimed to enumerate and characterize the major EV subtypes released by a human TNBC cell line compared to a non-malignant breast epithelial cell line (nmBEC). Methods: Three EV sub-fractions were isolated from supernatants of TNBC cells (MDA-MB-231) and nmBECs (MCF/10A) by sequential centrifugation steps: 2000 xg (apoptotic body AB-enriched), 12000 xg (ectosome-enriched) and 120000 xg (exosome-enriched). EV marker expression was characterized by immunogold TEM and latex-bead-based flow cytometry. Quantification of EVs was performed by BCA protein assay and nanoparticle tracking analysis (NTA). Results: Mid-to-high-level expression of CD9, CD63 and CD81 was confined, as expected, to the exosome-enriched fractions of both cell types. Protein assays correlated poorly with NTA-based particle counts with the greatest discrepancies seen for AB- and ectosome-enriched fractions from both cell types. The release rate (Particles/cell/72 h) of ectosome- and exosome-enriched fractions from TNBC cells was several-fold greater than from nmBECs. Mean and mode particle sizes of ectosome- and exosome-enriched fractions were similar for TNBC cells compared to nmBECs. Summary/Conclusion: (1). A TNBC-derived cell line demonstrated higher release rate and similar size of ectosomes and exosomes compared to a non-cancer-derived breast epithelial cell line. (2). Careful quantitative and qualitative analysis of EV sub-fraction release from cultured TNBC cell lines and primary tumour cells has potential as a screening approach for novel anti-cancer agents and for discovery of EV-associated mechanisms of TNBC progression.
Background: Despite the fact that tobacco is a well-recognized risk factor for pancreatic cancer, no study has yet reported on the association between environmental tobacco smoke (ETS) and this ...malignancy. We investigated the relationship between pancreatic cancer and childhood and adult exposure to ETS using a case-control study design. Methods: Our study population consisted of 583 pancreatic cancer cases and 4,813 population-based controls that were identified within 8 Canadian provinces between 1994 and 1997. Mail-out questionnaires were used to collect risk factor information and a lifetime residential and occupational history of exposure to ETS. Results: Among never smokers, those who were exposed to ETS both as a child and as an adult had an odds ratio of 1.21 (95% CI= 0.60-2.44) relative to those with no exposure. For active smoking, when the referent group consisted of never smokers who had not been regularly exposed to ETS, the risk increases were more pronounced with an increased number of years of smoking, cigarette pack-years, years since quit smoking, and average number of cigarettes smoked daily. Conclusions: Overall, our results are suggestive of a weak association between pancreatic cancer and ETS. Perhaps more importantly, they suggest that ETS smoking exposures may confound the risk of pancreatic cancer associated with active smoking measures commonly used in epidemiologic studies. Contexte : Bien que le tabac constitue un facteur de risque bien connu pour le cancer du pancréas, aucune étude n'a encore constaté d'association entre la fumée secondaire du tabac (FST) et ce type de tumeur maligne. À l'aide d'une étude cas-témoin, nous avons analysé la relation entre le cancer du pancréas et l'exposition à la FST durant l'enfance et à l'âge adulte. Méthode : La population à l'étude comprenait 583 cas de cancer du pancréas et 4 813 témoins représentatifs identifiés dans huit provinces canadiennes entre 1994 et 1997. Nous leur avons posté des questionnaires pour recueillir de l'information sur leurs facteurs de risque et leurs antécédents d'exposition à la FST, à la maison et au travail, au cours de leur vie. Résultats : Chez les personnes n'ayant jamais fumé, celles qui avaient été exposées à la FST durant l'enfance et à l'âge adulte avaient un rapport de cotes de 1,21 (IC de 95 % = 0,60-2,44) comparativement aux personnes non exposées. Pour les fumeurs actifs (comparés à un groupe de référence composé de personnes n'ayant jamais fumé et n'ayant pas été régulièrement exposées à la FST), l'accroissement du risque était plus prononcé avec le nombre d'années de tabagisme, le nombre de paquets de cigarettes par année, le nombre d'années depuis le renoncement au tabac et le nombre moyen de cigarettes fumées quotidiennement. Conclusions : Dans l'ensemble, nos résultats semblent indiquer une faible association entre le cancer du pancréas et la FST. Ils soulignent néanmoins un fait intéressant : l'exposition à la FST pourrait être un facteur de confusion dans les mesures couramment utilisées par les études épidémiologiques pour évaluer le risque de cancer du pancréas associé au tabagisme actif.
The analysis of exhaled breath components for indicators of inflammation and oxidative stress rarely has been applied to studies involving exposure to an environmental pollutant. The examination of ...exhaled substances as biomarkers of exposure and/or effect is extremely useful for human studies due to the noninvasive nature of the sample collection. We utilized exhaled breath analysis to demonstrate oxidative stress in humans exposed to the air pollutant ozone (O3). O3 has been hypothesized to exert oxidative stress by react- ing with lung biomolecules to form secondary reaction products such as hydrogen perox ide (H2O2) and carbonyl substances, and by inducing an influx of polymorphonuclear phagocytes (PMNs), which can release reactive oxygen species into the lung. We collected the exhaled breath of healthy human volunteer subjects (age 18-35 yr) immediately before and after exposure to air or 0.4 ppm O3 for 2 h with or without exercise. For assay of H2O2, breath condensate was collected in Tygon tubing submerged in an ice-water bath, and H2O2 was quantitated by a fluorescence assay. In a subset of subjects, exhaled carbonyls were examined by collection of exhaled breath into Tedlar bags. Breath carbonyls were subsequently derivatized and concentrated on column packing containing 2,4-dinitrophenylhydrazine, derivatives eluted, and analyzed by high-performance liquid chromatography with ultraviolet detection. The data showed an increase in exhaled breath H2O2 in O3-exposed, exercising subjects but not in subjects exposed to O3 without exer- cise. An increase in an aldehydic derivative that eluted with a similar retention time as derivatized acetaldehyde was found in the breath of O3-exposed subjects. These data sug gest that O3 exposure of humans in vivo can induce an oxidative stress as evidenced by increased formation of H2O2 and carbonyls. The analysis of exhaled breath was able to show the increased lung oxidative stress in an easy, noninvasive manner and has applicability to examining similar responses of humans exposed to other environmental pollutants either in controlled settings or in field studies.
We describe three related DNA alterations associated with transposon Tn10: precise excision of Tn10, nearly precise excision of Tn10 and precise excision of the nearly precise excision remnant. DNA ...sequence analysis shows that each of these alterations results in excision of all or part of the Tn10 element, and each involves specific repeat sequences at or near the ends of the element. Furthermore, all three events are structurally analogous: in each case, excision occurs between two short direct-repeat sequences, with resulting deletion of all intervening material plus one copy of the direct repeat; and in all three cases, the direct repeats involved occur at either end of an inverted repeat. Analysis of mutant Tn10 elements and characterization of bacterial host mutations suggest that all three types of excision events occur by pathways that are fundamentally distinct from the pathway(s) for Tn10-promoted transposition and other DNA rearrangements (deletions and inversions) actively promoted by the element. In addition, precise excision and nearly precise excision appear to occur by very closely related or identical pathways; and several lines of evidence suggest that the 1400 bp inverted repeats at the ends of Tn10 may play a structural role in both of these events. The third excision event appears to occur by yet another pathway.
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