EVALUATION OF THE HEALTH RISK ASSOCIATED WITH EXPOSURE TO CHLOROFORM IN INDOOR SWIMMING POOLS

The exposure of swimmers to chloroform (CHCl₅) was investigated in indoor swimming pools of the Quebec City region along with the associated carcinogenic risk. Six training sessions involving 52 competition swimmers (11 to 20 yr old) were conducted in 3 different pools, while 12 adult leisure swimmers attended 5 sessions, each held in a different pool. For each session, water and ambient air CHCl₃ concentrations were measured and CHCl₃ levels in alveolar air samples (CHCl₃ALV) collected from swimmers prior to entering the swimming pool premises and after 15, 35, and 60 min of swimming. Mean water concentrations varied from 18 µg/L to 80 µg/L, while those in air ranged from 78 µg/m3 to 329 µg/m3. Multiple linear regression analyses revealed that CHCl₃ALV values in competition swimmers were strongly correlated to ambient air and water levels, and to a lesser degree to the intensity of training. Only ambient air concentration was positively correlated to CHCl₃ALV in the leisure group. Concentrations of CHCl₃ metabo lites bound to hepatic and renal macromolecules, estimated using a physiologically based pharmacokinetic (PBPK) model, were 1.6 and 1.9 times higher for the competition swimmers than for the leisure swimmers, respectively. The highest hepatic concentration predicted in competition swimmers, 0.22 µg CHCl equivalents/kg of tissue, was at least 10,000 times lower than the smallest no observed³effect level for liver tumors in animals. Data indicate that the safety margin is therefore very large, for competitive swimmers as well as for leisure swimmers.     

Teaching residents screening,brief intervention,and referral to treatment (SBIRT) skills for alcohol use: Using chart-stimulated recall to assess curricular impact

ABSTRACT

Background: Screening, brief intervention, and referral to treatment (SBIRT) improves identification and intervention for patients at risk for developing an alcohol use disorder (AUD). Residency curriculum is designed to teach SBIRT skills, but resources are needed to promote skill implementation. The electronic health record (EHR) can facilitate implementation through integration of decision-support tools. The authors developed electronic tools to facilitate documentation of alcohol assessment and brief intervention and to reinforce skills from an SBIRT curriculum. This prospective cohort study assessed primary care internal medicine residents' use of SBIRT skills and EHR tools in practice using chart-stimulated recall (CSR). Methods: Postgraduate year 2 and 3 residents received a 5-hour SBIRT curriculum with skills practice and instruction on SBIRT electronic tools. Participants were then given a list of their patients seen in a 1-year period who were drinking at/above the recommended limit. Trainees selected 3 patients to review with a faculty member in a CSR. Faculty used a 24-item chart checklist to assess application of SBIRT skills and electronic tool use and met with residents to complete a CSR interview. CSR interview notes were analyzed qualitatively to understand application of SBIRT skills and EHR tool use. Results: Eighteen of 20 residents participated in the CSR, and 5 faculty reviewed 46 patient charts. Residents documented alcohol use (84.2% of charts) and assessment of quantity/frequency of use (71.0%) but were less likely to document assessment for an AUD (34%), an appropriate plan (50.0%), or follow-up (55%). Few residents used EHR tools. Residents reported barriers in addressing alcohol use, including lack of knowledge, patient barriers, and time constraints. Conclusions: More intensive training in SBIRT with opportunities for practice and feedback may be necessary for residents to consistently apply SBIRT skills in practice. EHR tools need to be better integrated into the clinic workflow in order to be useful.     

State Indoor Tanning Laws and Adolescent Indoor Tanning

Objectives. Recently, several state indoor tanning laws, including age restrictions, were promulgated to reduce indoor tanning among minors. We examined the effects of these laws on adolescent indoor tanning.Methods. We used nationally representative data from the 2009 and 2011 national Youth Risk Behavior Surveys (n = 31 835). Using multivariable logistic regression, we examined the association between state indoor tanning laws and indoor tanning among US high school students.Results. Female students in states with indoor tanning laws were less likely to engage in indoor tanning than those in states without any laws. We observed a stronger association among female students in states with systems access, parental permission, and age restriction laws than among those in states without any laws. We found no significant association among female students in states with only systems access and parental permission laws or among male students.Conclusions. Indoor tanning laws, particularly those including age restrictions, may be effective in reducing indoor tanning among female high school students, for whom rates are the highest. Such reductions have the potential to reduce the health and economic burden of skin cancer.Skin cancer is the most common cancer in the United States. Approximately 3.5 million cases of nonmelanoma skin cancers are treated annually, while more than 60 000 melanomas are diagnosed annually.1,2 In addition, skin cancer poses a substantial economic burden, with annual direct medical costs of treatment estimated at $1.7 billion in 2004.3 During the past decade, while most cancers decreased, melanoma increased, especially among young adult women.4 Indoor tanning is thought to be partially responsible for this increase.4–6 Indoor tanning before age 35 years increases the risk of melanoma by 59%,5,7 and indoor tanning before age 25 years increases the risk of basal cell carcinoma by 40% and squamous cell carcinoma by 102%.8 Despite these known health risks, indoor tanning is common among adolescents—6.2% of male high school students and 20.9% of female high school students engaged in indoor tanning in 2011.9In recent years, several states have enacted laws restricting youth access to indoor tanning and laws aimed at reducing consumers’ risk, including facility and operator responsibilities, safety and equipment standards, enforcement authority, and penalties.10 Previous studies that were primarily focused on youth access laws found poor compliance rates among tanning facilities for parental permission laws.11–13 In addition, such laws were ineffective in reducing indoor tanning among adolescents.14,15 Since these earlier studies were conducted, the number of states implementing youth access laws, particularly age restrictions, has increased substantially.16 Although some evidence has suggested that age restrictions may reduce access to indoor tanning among minors,17 no national or international studies have examined the effects these laws have on adolescent indoor tanning behavior. We examined the association between state indoor tanning laws, including age restrictions, and indoor tanning among high school students.     

The perception of work stressors is related to reduced parasympathetic activity

Purpose  

The aim was to examine the perception of work stressors in relation to ambulatory measures of heart rate variability (HRV).     

The cannabinoid CB1 receptor inverse agonist, rimonabant, modifies body weight and adiponectin function in diet-induced obese rats as a consequence of reduced food intake

The cannabinoid CB1 receptor inverse agonist rimonabant induces hypophagia and body weight loss. Reduced body weight may potentially be due to decreased food intake or to direct metabolic effects of drug administration on energy expenditure. This study uses a paired-feeding protocol to quantify the contributions of energy intake to rimonabant-induced body weight loss. Diet-induced obese (DIO) rats were dosed with rimonabant (3, 10 mg/kg PO once daily) and matched with pair-fed controls. Food intake and body weight were measured daily. Blood samples and adipose tissue were collected on day 15 for measurement of plasma adiponectin and adiponectin mRNA levels. DIO rats treated with rimonabant and pair-fed controls showed very similar changes in body weight. Although tolerance developed to the anorectic effect of rimonabant, total food intake was significantly decreased over the 14-day study period and fully accounted for the observed reductions in body weight. Adiponectin mRNA and plasma adiponectin were elevated in vehicle-treated chow-fed animals compared to obese controls, and did not differ between rimonabant-treated and pair-fed animals. The similarities between rimonabant-treated and pair-fed animals in body weight loss and the absence of differences in measures of adiponectin activity between drug-treated and pair-fed animals suggest that the outcomes of this experiment were solely mediated by the drug-induced reduction in food intake.     

Effects of the antimalarial drug dihydroartemisinin (DHA) on rat embryos in vitro

Artemisinin derivatives are not currently recommended for use during the first trimester of pregnancy because they cause embryo death and some abnormalities in early pregnancy in animals. We studied the effects of dihydroartemisinin (DHA) in rat whole embryo cultures (WEC). DHA was added to the culture medium for the entire 48-h culture, 1.5 h at the beginning or at the end of the culture at 0.01-2 microg/mL. DHA affected primarily red blood cells during yolk sac hematopoiesis. Higher concentrations and longer exposure inhibited angiogenesis. Tissue damage (cell deaths) and effects on embryo morphology (neural tube, branchial arches, somites and caudal region defects) were attributed to these events. The viability of severely affected embryos beyond the 48-h assay is uncertain. These results help explain findings from animal data and provide evidence that the yolk sac is highly susceptible to artemisinin compounds. Extrapolating results to pregnant women exposed in the first trimester remains difficult. Pharmacovigilance and further studies of the mechanism of damage are needed.     

The effects of the 5-HT2C receptor antagonist SB242084 on locomotor activity induced by selective, or mixed, indirect serotonergic and dopaminergic agonists

Rationale The 5-HT_2C receptor modulates mesolimbic dopamine (DA) function and the expression of DA-dependent behaviors, including stimulant-induced hyperactivity. The 5-HT_2C receptor may also be involved in drug-induced locomotion that is 5-HT-dependent.Objectives This study investigated the effects of the 5-HT_2C receptor antagonist 6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline (SB242084) on hyperlocomotion induced by psychomotor stimulants with selective, or mixed, actions on serotonergic and/or dopaminergic systems.Materials and methods Male Sprague–Dawley rats were treated in the presence or absence of SB242084 with releasers/reuptake inhibitors of DA (amphetamine and methylphenidate), 5-HT (fenfluramine and citalopram), or both 5-HT and DA (MDMA and cocaine). In addition, the effects of SB242084 combined with nicotine, morphine, or the 5-HT_1A/1B receptor agonist RU24969 were examined. Locomotor activity was recorded for 2 h.Results SB242084 potentiated hyperactivity induced by MDMA (2.5–5 mg/kg), amphetamine (0.5 mg/kg), fenfluramine (5 mg/kg), cocaine (10 mg/kg), and methylphenidate (5 mg/kg). SB242084 modestly potentiated nicotine-induced (0.2–0.4 mg/kg) and morphine-induced (2.5 mg/kg) hyperactivity. SB242084 failed to influence hyperactivity induced by RU24969 (0.5–1 mg/kg) or citalopram (10–20mg/kg).Conclusion SB242084 potentiated the locomotor stimulant effects of both indirect DA and 5-HT agonists. This potentiation may reflect two distinct mechanisms. The first involves direct enhancement of DA activity as shown by potentiation of the effects of amphetamine and methylphenidate. The second mechanism reflects an unmasking of stimulatory 5-HT receptors activated by 5-HT releasers (possibly 5-HT_1B/2A) through blockade of inhibitory 5-HT_2C receptors. The failure of SB242084 to potentiate the effect of citalopram might reflect differences between changes in synaptic levels of 5-HT produced by release compared to reuptake inhibition.     

Falling through the cracks: contraceptive needs of female sex workers in Cambodia and Laos

Background

Condom is the only method promoted for dual protection among female sex workers (FSWs) in most Asian countries, which may be insufficient to prevent pregnancies given FSWs' high frequency of sexual intercourse.

Study Design

Data were obtained from independent cross-sectional surveillance surveys conducted in Cambodia and Laos. Random samples of FSWs provided behavioral information.

Results

Respondents numbered 592 in Cambodia and 1421 in Laos. In Cambodia, 28.2% had abortions in the past year despite reporting 99.0% condom use at last commercial sex. Abortion increased with the number of clients, inconsistent condom use, recent condom breakage and recent forced unprotected sex with clients. In Laos, 26.0% of all FSWs had ever aborted as had 89.4% of those who had been pregnant in the past 6 months.

Conclusions

FSWs experience higher frequency of abortion than women from the general population. FSWs' reportedly high rate of condom use is insufficient to prevent pregnancies.     

Characterization of isoprostane signaling: evidence for a unique coordination profile of 8-iso-PGF(2alpha) with the thromboxane A(2) receptor, and activation of a separate cAMP-dependent inhibitory pathway in human platelets

Since isoprostanes are thought to participate in the pathogenesis of thrombosis, presumably through their interaction with thromboxane receptors (TPRs), we examined the ability of 8-iso-PGF(2alpha) to bind/signal through TPRs. Using TPR expressing HEK cells, it was found that 8-iso-PGF(2alpha) mobilized calcium and bound TPRs with a dissociation constant (K(d)) of 57 nM. Interestingly, site-directed-mutagenesis revealed that 8-iso-PGF(2alpha) has a unique coordination profile with TPRs. Thus, while Phe184 and Asp193 are shared by both 8-iso-PGF(2alpha) and classical TPR ligands, Phe196 was found to be required only for 8-iso-PGF(2alpha) binding. Functional studies also revealed interesting results. Namely, that 8-iso-PGF(2alpha) signals in human platelets through both a stimulatory (TPR-dependent) and an inhibitory (cAMP-dependent) pathway. Consistent with the existence of two signaling pathways, platelets were also found to possess two separate binding sites for 8-iso-PGF(2alpha). While the stimulatory site is represented by TPRs, the second cAMP inhibitory site is presently unidentified, but does not involve receptors for PGI(2), PGD(2) or PGE(2). In summary, these studies provide the first documentation that: (1) 8-iso-PGF(2alpha) coordinates with Phe184, Asp193 and Phe196 on platelet TPRs; (2) Phe196 serves as a unique TPR binding site for 8-iso-PGF(2alpha); (3) 8-iso-PGF(2alpha) signals through both stimulatory and inhibitory pathways in platelets; (4) 8-iso-PGF(2alpha) inhibits human platelet activation through a cAMP-dependent mechanism; (5) 8-iso-PGF(2alpha) interacts with platelets at two separate binding sites. Collectively, these results provide evidence for a novel isoprostane function in platelets which is mediated through a cAMP-coupled receptor.