An examination of bedtime media and excessive screen time by Canadian preschoolers during the COVID-19 pandemic.

BACKGROUND: Risky media use in terms of accumulating too much time in front of screens and usage before bedtime in early childhood is linked to developmental delays, reduced sleep quality, and unhealthy media use in later childhood and adulthood. For this reason, we examine patterns of media use in pre-school children and the extent to which child and family characteristics contribute to media use during the COVID-19 pandemic. METHODS: A cross-sectional study of digital media use by Canadian preschool-aged children (mean age = 3.45, N = 316) was conducted at the start of the COVID-19 pandemic between April and August of 2020. Parents completed a questionnaire and 24-h recall diary in the context of an ongoing study of child digital media use. From these responses we estimated hours of average daily screen time, screen time in the past 24 h, average daily mobile device use, and media use before bedtime. Parents also answered questions about their child (i.e., age, sex, temperament), family characteristics (parental mediation style, parental screen time, education, income), and contextual features of the pandemic (ex., remote work, shared childcare). Daycare closures were directly assessed using a government website. RESULTS: Our results indicate that 64% of preschoolers used more than 2 h of digital media hours/day on average during the pandemic. A majority (56%) of children were also exposed to media within the hour before bedtime. Logistic and multinomial regressions revealed that child age and temperament, restrictive parental mediation, as well as parent digital media use, education, satisfaction with the division of childcare, remote work, and number of siblings and family income were all correlates of risky digital media use by preschoolers. CONCLUSIONS: Our results suggest widespread risky media use by preschoolers during the pandemic. Parenting practices that include using more restrictive mediation strategies may foster benefits in regulating young children's screen time.

[Comparison of the urinary excretion of biomarkers of exposure to pyrethroids and pyrethrins between residents of urban and rural areas of the province of Quebec, Canada]. / Comparaison de l'excrétion urinaire de biomarqueurs d'exposition aux pyréthrinoïdes et aux pyréthrines chez les résidents de régions urbaine et rurale de la Province de Québec, Canada.

BACKGROUND: Residents of rural (agricultural) areas are often suspected of being exposed to higher levels of pesticides than residents of urban areas. However, only a limited number of studies have specifically evaluated the impact of the geographical area of residence on pyrethroid and pyrethrin exposure in the general population. This study aimed at comparing the levels of biomarkers of exposure between an urban and rural, adult and children, population of the Province of Quebec, Canada. METHODS: A total of 154 urban (Montreal) and 154 rural (Monteregie) participants provided a complete overnight timed-urine collection and filled a self-administered questionnaire. Urine samples were analyzed for pyrethroid and pyrethrin metabolites: cis- and trans-dichloro- and cis-dibromo- vinyldimethylcyclopropane carboxylic acids, phenoxy- and fluorophenoxy-benzoic acids and chrysanthemum dicarboxylic acid. Amounts of metabolites (pmol/12h par kilogram body weight) and their frequency of detection in the two populations were compared and interpreted with the help of the answers gathered by questionnaire. RESULTS: Adults and children from the rural area tended to excrete higher levels of the main urinary metabolites, the cis- and trans-dichlorovinyldimethylcyclopropane carboxylic acids and the phenoxybenzoic acid, than those living in the urban area. When the adults and children were combined, this difference was statistically significant for the phenoxybenzoic acid (p=0.020), marginally significant for the trans-dichlorovinyldimethylcyclopropane carboxylic acid (p=0.053) and nonsignificant for the cis-dichlorovinyldimethylcyclopropane carboxylic acid (p=0.158). The chrysanthemum dicarboxylic acid, the fluorophenoxybenzoic acid and the dibromovinyldimethylcyclopropane carboxylic acid were detected in much lower proportion but, in the case of the fluorophenoxybenzoic acid, the relative frequency of detection was statistically significantly higher (p<0.001) in the rural population. CONCLUSION: The presence of a baseline level of biomarkers in the urban and rural population confirms the ubiquity of pyrethroids and pyrethrins in the environment. However, in the rural adult and infantile population under study, other factors possibly contributed to slightly increase exposure compared to the urban population, namely the use of mosquito repellents and household insecticides as reported by questionnaire.

Post-discharge follow-up using text messaging within an enhanced recovery program after colorectal surgery.

INTRODUCTION: Enhanced recovery after surgery programs (ERP) often lead to early discharge and return to home. In terms of risk management, extended surveillance is recommended. Surveillance using text messages (TM) has been validated for minor operations in ambulatory surgery. The goal of this study was to evaluate the feasibility of home surveillance by TM after colorectal surgery within an ERP. METHODS: This prospective multicenter study involved the University hospitals of Clermont-Ferrand, Grenoble, Marseille and Lyon Sud between November 2014 and September 2015. All patients underwent colorectal surgery within an ERP. Post-discharge, patients received TM (4 simple questions with regard to pain, bowel movements, temperature and phlebitis) on days 1, 3 and 5. If there was abnormal or lack of response, an automatic alert was sent to the attending physician via Internet and the patient was contacted immediately. RESULTS: One hundred and eleven patients were included. Responses were obtained within a median of 12 (1-422) minutes, and 90% of patients answered all TM. There were 48 alerts: 56% because of pain and 40% due to absence of response to the TM. Alerts led to in-hospital care for 4% of patients including three re-hospitalizations and two unplanned re-operations. The median satisfaction score (85% of patients responded) was 5 on a scale of 1 to 5. CONCLUSION: This study suggests the possibility, as for ambulatory surgery, to use test messaging for post-discharge home surveillance for patients undergoing colorectal surgery within an ERP.

Insulin prevention of altered muscarinic receptor-G protein coupling in diabetic rat atria.

Right atria from rats rendered diabetic by injection of streptozocin (STZ-D) for 8-10 wk are supersensitive to the negative chronotropic effects of muscarinic agonists but have decreased levels of muscarinic receptors and acetylcholinesterase activity. Insulin treatment completely prevents the development of these changes. The proportion of atrial muscarinic receptors displaying high-affinity agonist binding is lower in STZ-D rats; however, the sensitivity of high-affinity agonist binding to regulation by a guanine nucleotide (5'-guanylylimidodiphosphate) is greater in atria from diabetic rats. Again, insulin treatment eliminates these differences. These findings indicate that alterations in atrial muscarinic systems in STZ-D rats are a consequence of the elaboration of the diabetic state and suggest that an alteration of functional muscarinic receptor-G protein coupling contributes to the altered physiological responsiveness of the heart in diabetes.

Influence of N-ethylmaleimide on cholinoceptors and responses in longitudinal muscles from guinea-pig ileum.

1 The binding of carbamylcholine to membranes prepared from the longitudinal muscle of guinea-pig ileum was determined from its inhibition of the binding of [3H]-3-quinuclidinyl benzilate. Carbamylcholine binding was resolved into high and low affinity components with apparent dissociation constants of 0.11 +/- 0.02 and 11 +/- 1 microM; 42% of the receptors displayed high affinity carbamylcholine binding. 2 Alkylation of longitudinal muscle membranes with N-ethylmaleimide increased muscarinic receptor affinity for carbamylcholine in a manner consistent with a conversion of low affinity to high affinity receptors. After exposure the muscle membrane fragments to 1 mM N-ethylmaleimide for 20 min at 35 degrees C, carbamylcholine binding was resolved into two components with apparent dissociation constants of 0.11 +/- 0.01 and 9 +/- 2 microM, with 74% of the receptors displaying the higher affinity. 3 Exposure of longitudinal membranes mounted in an organ chamber to 1 mM N-ethylmaleimide for 30s depressed isometric contractions in response to acetylcholine by 80%, while contractions induced by K+ and Ba2+ were reduced by less than 20% and 10%, respectively. Acetylcholine dose-response curves were shifted to the right while Ba2+ curves were unaffected. 4 It is suggested that N-ethylmaleimide has a selective effect on muscarinic responses in the longitudinal muscle by disrupting processes occurring after receptor occupancy but before the induction of phospholipid turnover or calcium influx in the postsynaptic membrane.

Exposure of remote maritime populations to coplanar PCBs.

Two remote maritime populations were evaluated for their biological exposure to organochlorines in 1989-1990. Because of their high intake of seafood, these two populations have high biological levels. One hundred nine breast milk samples from Inuit women from Arctic Québec were analyzed to determine levels of polychlorodibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) including non-ortho, mono-ortho, and di-ortho congeners. Total 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEqs) for PCBs were 3.5 times higher in Inuit milk samples than in 96 Caucasian milk samples. Among the 185 fishermen from the Lower North Shore of the Gulf of the St. Lawrence River, we evaluated 10 highly exposed fishermen for their coplanar PCB blood levels. Total TEqs were 900 ng/kg for highly exposed individuals with 36 ng/kg for controls. In these two nonoccupationally exposed populations, coplanar PCBs make a larger contribution to the TEq than PCDDs and PCDFs. However, the mono-ortho penta CB No. 118 is the major contributor for the total toxicity.

Interobserver variation in the computed tomographic evaluation of mediastinal lymph node size in patients with potentially resectable lung cancer. Canadian Lung Oncology Group.

OBJECTIVE: To measure the reliability of the assessment of mediastinal lymph node size in computed tomographic (CT) scans of the thorax. DESIGN: Observer agreement study in which radiologists, blinded to one anothers' interpretation, were randomized to read 30 scans each. POPULATION: Sixty scans from patients with apparently operable non-small cell carcinoma of the lung were read by radiologists responsible for clinical interpretation (clinical radiologists) and four radiologists with a special interest in thoracic CT (study radiologists). MEASUREMENTS: Radiologists measured the size of left and right superior mediastinal nodes, aortic nodes, and the subcarinal nodes and, on the basis of whether any nodes accessible to mediastinoscopy were greater than 1 cm, recommended whether mediastinoscopy be undertaken. Agreement was quantified using kappa, a measure of chance-corrected agreement. RESULTS: Among all radiologists, agreement on whether there were any nodes larger than 1 cm for right superior mediastinal nodes was 0.68; for left superior mediastinal nodes it was 0.28; for aortic pulmonary nodes it was 0.62; for subcarinal nodes it was 0.58; and for any node greater than 1 cm and accessible to mediastinoscopy it was 0.61. The agreement was very similar when the analysis was restricted to the study radiologists. CONCLUSION: Although the good level of overall agreement suggests that CT provides useful information in the evaluation of mediastinal lymph node size, the disagreement was sufficient that it likely contributes to suboptimal sensitivity and specificity of CT in detecting tumor spread reported in previous studies.

A toxicokinetic model to assess the risk of azinphosmethyl exposure in humans through measures of urinary elimination of alkylphosphates.

Azinphosmethyl (APM) is one of the most common insecticides used in fruit farming. The object of this paper is to develop a quick and practical test for assessing the risk for humans coming into contact with APM. It has been shown that the principal component of occupational and/or accidental exposure is through the skin (C. A. Franklin et al., 1981, J. Toxicol. Environ. Health 7, 715-731), but our approach is applicable to exposures via any route or a combination of routes. The method proposed in the present paper can accommodate a single-event exposure or repeated exposures over long periods. Urinary alkylphosphate (AP) metabolites are reliable bioindicators of the presence of APM in the body; they are easily accessible and can be used to estimate APM body burden. We developed a simple toxicokinetic model to link the time varying APM body burden to absorbed doses and to rates of elimination in the form of AP urinary metabolites. Using this model and data available in the literature, we are able to propose a "no observed adverse effect level" (NOAEL) for APM body levels and for corresponding absorbed doses. We have established that after a single exposure, the safe limit corresponding to the NOAEL is reached at a cumulative 0.215 mumoles AP/kg bw eliminated in urine in the first 24 hours following the beginning of exposure. For repeated daily exposures at steady state, the corresponding urinary AP metabolite level is equal to a cumulative 0.266 mumoles AP/kg bw eliminated per 24 hours.

A biologically based dynamic model for predicting the disposition of methanol and its metabolites in animals and humans.

A multicompartment biologically based dynamic model was developed to describe the time evolution of methanol and its metabolites in the whole body and in accessible biological matrices of rats, monkeys, and humans following different exposure scenarios. The dynamic of intercompartment exchanges was described mathematically by a mass balance differential equation system. The model's conceptual and functional representation was the same for rats, monkeys, and humans, but relevant published data specific to the species of interest served to determine the critical parameters of the kinetics. Simulations provided a close approximation to kinetic data available in the published literature. The average pulmonary absorption fraction of methanol was estimated to be 0.60 in rats, 0.69 in monkeys, and 0.58-0.82 in human volunteers. The corresponding average elimination half-life of absorbed methanol through metabolism to formaldehyde was estimated to be 1.3, 0.7-3.2, and 1.7 h. Saturation of methanol metabolism appeared to occur at a lower exposure in rats than in monkeys and humans. Also, the main species difference in the kinetics was attributed to a metabolism rate constant of whole body formaldehyde to formate estimated to be twice as high in rats as in monkeys. Inversely, in monkeys and in humans, a larger fraction of body burden of formaldehyde is rapidly transferred to a long-term component. The latter represents the formaldehyde that (directly or after oxidation to formate) binds to various endogenous molecules or is taken up by the tetrahydrofolic-acid-dependent one-carbon pathway to become the building block of synthetic pathways. This model can be used to quantitatively relate methanol or its metabolites in biological matrices to the absorbed dose and tissue burden at any point in time in rats, monkeys, and humans for different exposures, thus reducing uncertainties in the dose-response relationship, and animal-to-human and exposure scenario comparisons. The model, adapted to kinetic data in human volunteers exposed acutely to methanol vapors, predicts that 8-h inhalation exposures ranging from 500 to 2000 ppm, without physical activities, are needed to increase concentrations of blood formate and urinary formic acid above mean background values reported by various authors (4.9-10.3 and 6.3-13 mg/liter, respectively). This leaves blood and urinary methanol concentrations as the most sensitive biomarkers of absorbed methanol.

Whole-cell and perforated patch recordings of four distinct K+ currents in acutely dispersed coeliac-superior mesenteric ganglia neurons of adult rats.

Properties and modulation of outward membrane currents in sympathetic neurons acutely dispersed from coeliac-superior mesenteric ganglia (C-SMG) of adult rats were examined using both the whole-cell variant of the patch-clamp technique and the perforated patch approach. Under voltage-clamp, four distinct outward currents were observed: a transient outward current (IA), a voltage-dependent sustained outward current consisting of a Ca(2+)-dependent component (IKCa) and a Ca(2+)-insensitive component (IKV), and a muscarinic agonist-sensitive outward current (IM). IA was isolated by digital subtraction, and characterized by very rapid activation at potentials more positive than -60 mV and by fast and complete voltage-dependent inactivation. Half inactivation potential (Vh) and slope factor (K) were -76 mV and 8.3 mV, respectively. IA was not affected by removal of external Ca2+, 1 mM tetraethylammonium ions, muscarinic agonists, or 8-bromo-cyclic AMP, but was suppressed by 4-aminopyridine (1 mM). Depolarizing pulses from of a holding potential of -50 or -60 mV to potentials more positive than -25 mV concomitantly activated two, independent sustained outward currents which decayed slowly; one exhibited voltage-dependent activation similar to the delayed rectifier current (IKV) and the other being triggered by Ca2+ influx into the cell (IKCa). The addition of tetraethylammonium ions (1 mM) strongly reduced the amplitude of the sustained outward currents. IM was characterized as a noninactivating time- and voltage-dependent outward current which activated at membrane potentials more positive than -60 mV and slowly turned off when the membrane was hyperpolarized back to -60 mV, and was suppressed by muscarinic agonists. The rank order of potency of the agonists tested was: oxotremorine > muscarine > bethanechol.

Alpha 1- and alpha 2-adrenoceptor agonist-induced contraction in rat mesenteric artery upon removal of endothelium.

Contractile response to norepinephrine, methoxamine and clonidine were determined in rat mesenteric arteries with and without an intact endothelium. Removal of the endothelial cell layer markedly enhanced the maximum contractile effect of norepinephrine (2.8 fold), methoxamine (4.0 fold) and clonidine (13.0 fold). Furthermore, there was a significant decrease in the EC50 values for these agonists. These findings indicate that both alpha 1- and alpha 2-adrenoceptor agonists can induce contraction of mesenteric arteries which is modulated by the endothelial cell layer.

The toxicokinetics of pyrene and its metabolites in rats.

Five experiments were conducted in male Sprague-Dawley rats regarding the kinetic of urinary excretion of 1-hydroxypyrene (1-OHP) following i.v., oral and dermal exposure to 0.5-50 micromol/kg pyrene either as a single substance or as mixture of various polycyclic aromatic hydrocarbons (PAH). Frequent urine collections over 48 h after exposure and a tissue versus time distribution experiment using [14C]pyrene allowed to define the kinetic profile of both pyrene and 1-OHP. For all exposure routes, there is a linear relationship over two orders of magnitude between the dose of pyrene and the urinary excretion of 1-OHP. Differences in biliary/urinary 1-OHP excretion ratio in canulated rats (3) versus faecal/urinary 1-OHP excretion ratio in non-canulated rats (0.6) indicate major enterohepatic recirculation of the metabolite. Half-lives of both pyrene and 1-OHP in all measured tissues were all comprised between 3.1 and 5.4 h, and 5.2-6.7 h, respectively, so that no long term accumulation would be predicted from these values for any tissue. Binary and ternary mixtures involving naphthalene and benzo(a)pyrene in addition to pyrene has no influence on the urinary excretion profile of 1-OHP. All these observations led to the proposal of a dynamic compartment model of pyrene and metabolite flows indicating that following rapid initial distribution to fatty tissues, pyrene is rapidly biotransformed into various metabolites and undergoes major enterohepatic recycling. Part of the initially formed and part of the recirculated 1-OHP eventually undergoes urinary excretion such that close to 60% of pyrene is eliminated as metabolites in urine by 24 h after injection while 20% is excreted in the faeces over the same period.

Role of neuronal and extraneuronal uptake in responses of rabbit iris dilator muscle to levarterenol and phenylephrine.

The roles of neuronal and extraneuronal uptake mechanisms in the response of iris dilator muscles of rabbit to levarterenol (norepinephrine) and phenylephrine were investigated. Chemical denervation with 6-hydroxydopamine was used to eliminate neuronal uptake. Exposure to corticosterone prior to and during exposure to levarterenol or phenylephrine was used to assess the importance of extraneuronal uptake. Dose-response curves and ED50 values for levarterenol or phenylephrine in control and 6-hydroxydopamine-denervated tissues, both in the presence and absence of corticosterone, are shown. Curves illustrating the decay of tension on washout of levarterenol or phenylephrine from treated tissues were analyzed. 6-Hydroxydopamine denervation affected the response to levarterenol more than that to phenylephrine. Washout of both agonists was slower after 6-hydroxydopamine pretreatment, and washout of phenylephrine was more rapid when corticosterone was present. These data indicate that extraneuronal uptake in iris dilator muscles was more important in determining the response to phenylephrine than to levarterenol and that neuronal uptake was more important in determining tissue responsiveness to levarterenol than to phenylephrine.

Clinical, physiological and radiological features of asthma with incomplete reversibility of airflow obstruction compared with those of COPD.

OBJECTIVES: To compare clinical features, pulmonary function and high-resolution computed chest tomography (HRCT) findings of asthmatic patients with a component of incomplete reversibility of airflow obstruction (AIRAO) with those of patients with smoking-induced chronic obstructive pulmonary disease (COPD). METHODS: Thirteen patients with COPD (six males and seven females, mean age 59 years, mean smoking 50.5 pack-years) and 14 patients with AIRAO (six males and eight females, mean age 52 years) despite optimal treatment, with no significant smoking history (mean 1.5 pack-years) and no significant environmental exposure or any other respiratory disease, were studied. Patients had respiratory questionnaires, pulmonary function tests, allergy skin-prick tests and an HRCT to evaluate possible parenchymal or bronchial abnormalities. Eight patients in each group also had exercise tests. All patients were stable at the time of the study. RESULTS: As expected, atopy was more prevalent in AIRAO (n=13) than in COPD (n=1) patients. Mean forced expiratory volume in 1 s (FEV1) and forced vital capacity (percentage of predicted value) were 39% and 61%, respectively, in COPD patients and 49% and 71%, respectively, in AIRAO patients; FEV1 improved by 18% in COPD patients and and by 22% in AIRAO patients after use of inhaled salbutamol. Mean functional residual capacity was greater in COPD patients than in AIRAO patients (178% versus 144% of the predicted value), while the mean carbon monoxide diffusing capacity of the lungs (DLCO) was lower in COPD patients than in AIRAO patients (62% versus 89% of the predicted value). Exercise tolerance was similar in both groups, as were postexercise changes in arterial oxygen pressure (PaO2). Emphysematous changes were observed in COPD patients and AIRAO patients who had evaluable HRCTs (10 versus two patients, although very mild in asthma), bronchial dilations (zero versus six patients), bronchial wall thickening (two versus eight patients) and an acinar pattern (one versus five patients). Mean thickness of the large airway wall to outer diameter (intermediary bronchus) ratio was 0.176 in COPD and 0.183 in AIRAO (P>0.05). CONCLUSIONS: Asthma may lead to physiological features similar to COPD but may be distinguished by demonstrating a preserved DLCO and a higher ratio of airway to parenchymal abnormalities on HRCT scan.

Urinary excretion kinetics of 1-hydroxypyrene in volunteers exposed to pyrene by the oral and dermal route.

Two well-informed human volunteers were exposed to 500 micrograms pyrene by ingestion and by dermal application, in two separate experiments. Urinary measurements of 1-hydroxypyrene (1-OHP) were performed on all micturitions taken at intervals of 0.5-4 h for a total period of 48 h after dosing. Following the absorption phase, 1-OHP is excreted with a first order apparent half-life of approximately 12 h for both volunteers and both exposure routes. These results compare well with other previously published studies. A more refined analysis of the data was performed using a two-compartment toxicokinetic model for 'pyrene' (its fraction eventually excreted as 1-OHP). As it was found that a classical first-order system did not adequately fit the data, a non-linear term was introduced in the model for the elimination of urinary 1-OHP. Computer iteration performed on the oral absorption data allowed an estimation of various toxicokinetic parameter values. The mean intercompartmental exchange (k12 and k21) and elimination coefficients were 0.010, 0.006 and 0.012 min-1, respectively. The first two values compare well with those previously published for the rat, whereas the latter is smaller in humans. These values were used to satisfactorily simulate the experimental data for both routes of exposure, adjusting only for kabs which was estimated at 0.014 and 0.0029 min-1 for the oral and dermal exposure, respectively. The proposed model generates new hypotheses on the metabolism of pyrene. The information collected will contribute to the validation of the utilisation of 1-OHP as a biological indicator of exposure to pyrene.

Health risk assessment for inuit newborns exposed to dioxin-like compounds through breast feeding.

Inuit people living in the Arctic receive an unusually high dose of dioxin-like compounds through their traditional diet, which comprises large amounts of fatty tissues from various sea mammal species. During breast feeding, the mother transfers part of their body burden to its newborn. We estimated the impact of breast feeding on the body burden of Inuit from birth to age 75 years. Simulations performed with a toxicokinetic model revealed that breast feeding strongly influences body burden during childhood but not after age 20 years. Liver and adipose tissue concentrations expected in Inuit are well below those which induced severe adverse health effects in laboratory animals, e.g. cancer and reproduction. However, these concentrations approach levels generating subtle effects on reproductive systems.