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Di(2-ethylhexyl) phthalate (DEHP), as an endocrine disruptor, is often used as a plasticizer in various polyvinyl chloride plastic products and medical consumables. Epidemiological studies have shown that long-term large intake of DEHP may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and aggravates the progression of chronic liver injury. However, the effects of DEHP on hepatocellular carcinoma (HCC) are rarely studied. In this study, we sought to determine the effects of DEHP on HCC induced by carbon tetrachloride combined with diethylnitrosamine, and further study its molecular mechanism. It was found that DEHP exposure significantly promotes tumor immune escape and activates signaling pathways involved in related protein expression of tumor immune escape, including PD-L1, JAK2, and STAT3. In addition, the trends observed in the HepG2 cells assay are consistent with vivo conditions. In summary, DEHP may play a tumor-promoting role in HCC mice and IFN-γ stimulated HepG2 cells, which may be related to the JAK2/STAT3 signaling pathway.

This study aimed to evaluate the possible protective effects of quercetin, a natural flavonoid, against nephrotoxicity induced by Di (2-ethylhexyl) phthalate (DEHP) in kidney tissue of rats and human embryonic kidney (HEK) 293 cell line. The HEK-293 cells were treated with different concentrations of quercetin 24 h before treatment with monoethylhexyl phthalate (MEHP). Male rats were treated with 200-mg/kg DEHP, 200-mg/kg DEHP plus quercetin (50 and 100 mg/kg), and 200-mg/kg DEHP plus vitamin E (20 mg/kg) for 45 days by gavage. Quercetin treatment reduced cytotoxicity and oxidative damage inducing by MEHP in HEK-293 cells. The in vivo findings showed that 100-mg/kg quercetin significantly suppressed DEHP-induced kidney damage. For exploring the involved mechanisms, the expressions of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor kappa B (NFκB), and tumor necrosis factor alpha (TNFα) genes were determined via real-time Polymerase chain reaction (PCR) assay. High dose of quercetin significantly decreased the gene expressions of NF-κB and TNFα, whereas the alternations of Nrf2 and HO-1 gene expressions were not significant in quercetin groups in compared with DEHP group. These findings suggested that the suppression of DEHP-induced nephrotoxicity via quercetin is correlated, at least in part, with its potential to regulate NF-κB signaling pathway.

The use of iodine-131 S values based on reference computational phantoms with fixed thyroid model may lead to significant dosimetric errors in patients who may have different thyroid location from the reference phantoms. In the present study, we investigated individual thyroid location variation by examining the computed tomography image sets of 40 adult male and female patients. Subsequently, the thyroid location of the adult male and female mesh-type reference phantoms of the International Commission on Radiological Protection (ICRP) was adjusted to match each the highest, mean and the lowest locations of the thyroid observed in this dataset. The thyroid-adjusted phantoms were implemented into the Geant4 Monte Carlo code to calculate thyroid location-dependent iodine-131 S values (rT ← thyroid) for a total of 30 target regions. The maximum variation among the observed thyroid locations was 39 mm and 36 mm for male and female patients, respectively. The mean thyroid locations of both male and female patients showed a good agreement with the ICRP reference phantoms. The thyroid location-dependent Iodine-131 S values were significantly different from the reference phantoms for most target regions by up to a factor of 3. The use of thyroid location-dependent S values in dose reconstructions should help quantify the dosimetric uncertainty in epidemiologic investigations of patients receiving iodine-131 therapy for hyperthyroidism and thyroid cancer.

Di-(2-ethylhexyl) phthalate (DEHP) is one of the ubiquitous pollutants worldwide. This study aimed to clarify the potential thyroid disrupting effect of DEHP and explore the probable ameliorative effects of selenium nanoparticles (Se-NPs) and curcumin nanoparticles (CUR-NPs). Forty-two male albino rats were divided into seven groups (n = 6): Group I (negative control); group (II) orally received DEHP (500 mg/kg BW, dissolved in corn oil); Group (III) orally received Se-NPs (.2 mg/kg BW) in combination with DEHP; Group (IV) orally received CUR-NPs (15 mg/kg BW) alongside with DEHP; Group V (corn oil); Group VI (Se-NPs) and Group VII (CUR-NPs). The duration of the experiment was 30 days. DEHP administration significantly decreased serum free T4 and significantly increased serum free T3 as compared to control group, whereas thyroid-stimulating hormone showed no significant change. DEHP disrupted redox status leading to accumulation of malondialdehyde and depletion of reduced glutathione. Histologically, the effect of DEHP on thyroid follicles was confirmed by light and electron microscopic examination and morphometric analysis. Se-NPs slightly improved thyroid parameters as well as redox status. CUR-NPS reinstated the values of all studied thyroid parameters to nearly control levels. This research provides Se-NPs and CUR-NPs as novel protective agents against DEHP-thyroid disrupting effects.

Aristolochic acid I (AAI) is a natural bioactive substance found in plants from the Aristolochiaceae family and impairs spermatogenesis. However, whether AAI-induced spermatogenesis impairment starts at the early stages of spermatogenesis has not yet been determined. Spermatogonial stem cells (SSCs) are undifferentiated spermatogonia that balance self-renewing and differentiating divisions to maintain spermatogenesis throughout adult life and are the only adult stem cells capable of passing genes onto the next generation. The objective of this study was to investigate whether AAI impairs SSCs during the early stages of spermatogenesis. After AAI treatment, we observed looser, smaller and fewer colonies, decreased cell viability, a decreased relative cell proliferation index, and increased apoptosis in SSCs in a concentration- and/or time-dependent manner. Additionally, AAI promoted apoptosis in SSCs, which was accompanied by upregulation of caspase 3, P53 and BAX expression and downregulation of Bcl-2 expression, and suppressed autophagy, which was accompanied by upregulation of P62 expression and downregulation of ATG5 and LC3B expression, in a concentration-dependent manner. Then we found that AAI impaired spermatogenesis in rats, as identified by degeneration of the seminiferous epithelium, and increased apoptosis of testicular cells. Taken together, our findings demonstrate that AAI causes damage to SSCs and implicate apoptosis and autophagy in this process. The impairment of SSCs may contribute to AAI-induced testicular impairment. Our findings provide crucial information for the human application of botanical products containing trace amounts of AAI.

As human beings have been consistently exposed to bisphenol A (BPA) and bisphenol S (BPS) derived from various products, the intake of BPS/BPA to humans has been extensively studied. However, using conventional biological matrices such as urine, blood, or dissected skin to detect BPS/BPA in the human body system requires longer exposure time to them, hardly defines the pollutant source of the accumulated BPS/BPA, and is often invasive. Herein, our new approach i.e. fingerprint analysis quantitatively confirms the transfer of BPS/BPA from receipts (specific pollution source) to human skin only within receipt-handling of “20 s”. When receipts (fingertip region size; ~1 cm2) containing 100–300 μg of BPS or BPA are handled, 20–40 μg fingerprint-1 of BPS or BPA is transferred to human skin (fingertip). This transferred amount of BPS/BPA can still be toxic according to the toxicity test using water fleas. As a visual evidence, a fingerprint map that matches the distribution of the absorbed BPS/BPA is developed using a mass spectrometry imaging tool. This is the first study to analyze fingerprints to determine the incorporation mechanism of emerging pollutants. This study provides an efficient and non-invasive environmental forensic tool to analyze amounts and sources of hazardous substances.

Objectives Bisphenol A (BPA) is the most used colour developer in thermal paper for cashiers receipts, labels, and tickets. BPA can migrate onto the skin and be absorbed when handling these papers. BPA is a known endocrine disruptor and is therefore being replaced in thermal paper by some alternatives such as Bisphenol S (BPS), D-8, and Pergafast 201® (PF201). To our knowledge, no studies have characterized skin permeation of these BPA alternatives. Methods We measured/characterized skin absorption for BPA, BPS, D-8, and PF201 through ex vivo human skin using flow-through diffusion cells according to OECD guideline 428. Skin samples were 7–12 per test substance from three different skin donors. Skin metabolism was studied for BPA. Dermal absorption was expressed as the amount of the BPA alternatives in the receptor fluid over applied dose in percent (%). Results The absorbed dose after 24 h of exposure was 25% for BPA, 17% for D-8, 0.4% for BPS, and Conclusions Skin absorption was in decreasing order: BPA > D-8 >> BPS > PF201. These results are in agreement with their log Kow and molecular weights. We provided here the necessary data to estimate the extent of skin absorption of BPA analogues, which is a necessary step in risk assessment, and ultimately evaluate public health risks posed by D-8, BPS, and PF201.

Cadmium (Cd) exposure may induce chronic intoxication, but the harm of cadmium in rice to human at chronic low-level Cd exposure remains unclear. This study employed a mouse model to investigate the toxicity and mechanism of cadmium in rice and CdCl2. After 8-week exposure to Cd (CdCl2 and Cd-contaminated rice), the biochemical indicators and oxidation indicators in the serum and liver of mice were determined, and used mRNA sequencing to investigate the mechanism of different forms of Cd. Results showed that the cadmium concentration of the liver in the CdCl2 + Rice-N group (CdCl2 mixed with feed and normal rice, 0.4mg/kg.bw) was higher than that in the Rice-H group (0.4mg/kg.bw). However, the cadmium concentration of the kidneys in the Rice-H group was higher than that in the CdCl2 + Rice-N group. Our study demonstrated that Cd-treated (Cd in rice and CdCl2) ICR mice generated obviously tissues injury, such as the increased biochemical studies, the activity of antioxidant enzymes debasement. Simultaneously, our data also indicated that there existed difference of the hepatic toxicity between Cd in rice and CdCl2. By means of transcriptomics, we discovered that CdCl2 and Cd in rice may affect different gene expression at the molecular level. We hope to provide some theoretical basis for the revision of food security standards.

Tramadol is a synthetic opioid analgesic used for moderate-to-severe pain structurally related to codeine and morphine, where their analgesic mechanism is a result of opioid and non-opioid mechanisms. This study was designed to evaluate the effects of Moringa oleifera leaves extract (MLE) on tramadol-induced testicular toxicity, sperm changes, testicular damage, and oxidative stress in male rats. Forty male albino rats were divided into four groups and treated for 4 weeks (group 1, as control; group 2, MLE; group 3, tramadol; group 4, MLE + tramadol). The relative body weight, relative testes weight, serum total testosterone, luteinizing hormone, follicle-stimulating hormone, sperm counts, vitality, total sperm motility, catalase, and superoxide dismutase activities were significantly decreased in tramadol-treated group when compared with the control group. In contrast, sperm abnormality, immotile sperm percent, testicular injury, and TBARS concentration in testes were significantly increased in the tramadol-treated group. In addition, histopathological examination for the tramadol-treated group has shown incomplete spermatogenesis, moderate degeneration in some seminiferous tubules with a significant decrease in the number of spermatogenic cells and depletion of Leydig cells. The administration of MLE with tramadol ameliorates the testicular toxicity, injury, sperm count, abnormalities, and oxidative stress induced by tramadol.

Diethylhexyl phthalate (DEHP) is known as a persistent environmental pollutant. However, the possible effects of DEHP on human neural tube defects (NTDs) remain elusive. We set out to investigate the exposure of DEHP in human and explore the association of DEHP and NTDs. The level of DEHP in maternal urine was measured and analyzed by GC-MS. To further validate the results in human NTDs, chick embryos were used as animal models. Viability, reactive oxygen species (ROS) level, oxidative stress indicators and apoptosis were detected in DEHP-treated chick embryos. Our research revealed that the detection ratio of positive DEHP and its metabolites in maternal urine were observed dramatically higher in NTDs population than that in normal controls (P

—Corona virus is a virus capable of mutating very quickly and many other viruses that arise due to mutations of this virus. To find out the location of corona virus mutations of one type to another, DNA sequences can be aligned using the Needleman-Wunsch algorithm. Corona virus data was taken from Genbank National Center for Biotechnology Information from 1985-1992. The Needleman-Wunsch algorithm is a global alignment algorithm in which alignment is performed to all sequences with the complexity of O (mn) and is capable of producing optimal alignment. An important step in this reserach is the sequence alignment of two corona viruses using the Needleman-Wunsch algorithm. Second, identification of the location of mutations from the DNA of the virus. The result of this reserach is an alignment and the location of mutations of both sequences. The results of identification DNA mutation can be used to find out other viruses mutation corona virus as well as can be used in the field of health as a reference for the manufacture of drugs for corona virus mutation outcome.

We have investigated the in vitro metabolism of pectenotoxin-2 (PTX-2) using primary hepatocytes from Wistar rats in suspension. Purified PTX-2 was rapidly metabolized. Two major and several minor oxidized PTX-2 metabolites were formed, none of which had retention times corresponding to PTX-1, -11, or −13. Hydrolysis products, such as PTX-2 seco acid, were not observed. Preliminary multi-stage LC-MS analyses indicated that the major hepatic PTX-2 metabolites resulted from the insertion of an oxygen atom at the positions C-19 to C-24, or at C-44. The rapid oxidative metabolism may explain the low oral toxicity of PTXs observed in vivo studies., Highlights • PTX-2 is rapidly metabolized in rat hepatocytes. • Two major and several minor oxidized PTX-2 metabolites were formed. • The results may explain the low oral toxicity of PTXs observed in vivo studies.

Bisphenol A (BPA) is a high production volume chemical that has wide industrial applications, especially as a color developer in thermal papers. The present study focused on the determination of levels of BPA in thermal receipts collected from different locations in Akure, Nigeria, and the estimation of daily intake of BPA through dermal absorption. Thermal receipts were collected from different locations, and the levels of extracted BPA were determined using fluorescence spectroscopy. The daily intake of BPA was estimated, and the amount was compared with the reference value. BPA was detected in all the samples analyzed with levels ranging from 1.50 to 3.16 mg/g. These values were lower than the values detected in thermal receipts obtained from other countries. The estimated mean daily intakes of BPA by dermal absorption due to handling of thermal receipts were 0.20 and 9.89 μg/day for the general population and the occupationally exposed individuals, respectively, and were much lower than the reference value of 50 μg/kg bw/day provided by the European Food Safety Authority. This indicates that dermal exposure to BPA is not a serious health risk to the population.

Bisphenol A (BPA) is an endocrine disruptor frequently detected in human biofluids. Dermal absorption of BPA from thermal paper receipts occurs but BPA pharmacokinetics following dermal exposure is not understood. To compare the pharmacokinetics of dermal and dietary BPA exposure, six male participants handled simulated receipts containing relevant levels of BPA (isotope-labeled BPA-d16) for 5 min, followed by hand-washing 2 h later. Urine (0–48 h) and serum (0–7.5 h) were monitored for free and total BPA-d16. One week later, participants returned for a dietary administration with monitoring as above. One participant repeated the dermal administration with extended monitoring of urine (9 days) and serum (2 days). After dietary exposure, urine total BPA-d16 peaked within 5 h and quickly cleared within 24 h. After dermal exposure, cumulative excretion increased linearly for 2 days, and half the participants still had detectable urinary total BPA-d16 after 1 week. The participant repeating the dermal exposur...

Thermal paper contains potentially toxic compounds such as bisphenol A (BPA), which is used as a color developer. BPA has been reported in thermal paper in concentrations up to 42,600 μg g−1. The exposure to BPA via dermal transfer has been recently discussed as a significant contribution to the overall human exposure and the estimated daily intake (EDI) has been reported up to 218 μg d−1. BPA has been also detected in recycled paper with concentrations up to 46 μg g−1. Due to the fact that BPA is a known endocrine disruptor and migrates from materials, regulatory restrictions have been established to prevent risks for the human health. As a consequence, structural analogues, such as bisphenol S (BPS) have been introduced into the market. Little is known about the presence and toxicity of these emerging replacements, and concern has risen about them. The present review gives an overview of the occurrence and levels of BPA and replacements in thermal paper. BPA is still the most common color developer found in thermal paper, followed by BPS. The analytical methods used for quantification of BPA and BPA replacements in paper products are also reviewed. BPA is transferred from thermal paper products to the finger pads upon handling it. Paper-skin transfer followed by penetration of BPA depends on conditions (e.g. greasiness of fingers and use of hand cream). It is, however, still debated whether thermal paper as a source for human exposure contributes significantly to the overall internal BPA exposure.

Background: Bisphenol A (BPA) is a high-production-volume chemical associated with a wide range of health outcomes in animal and human studies. BPA is used as a developer in thermal paper products, including cash register receipt paper; however, little is known about exposure of cashiers to BPA and alternative compounds in receipt paper. Objective: We determined whether handling receipt paper results in measurable absorption of BPA or the BPA alternatives bisphenol S (BPS) and 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP). Methods: Cashiers (n = 77) and non-cashiers (n = 25) were recruited from the Raleigh–Durham–Chapel Hill region of North Carolina during 2011–2013. Receipts were analyzed for the presence of BPA or alternatives considered for use in thermal paper. In cashiers, total urine and serum BPA, BPS, and BPSIP levels in post-shift samples (collected ≤ 2 hr after completing a shift) were compared with pre-shift samples. Levels of these compounds in urine from cashiers were compared to levels in urine from non-cashiers. Results: Each receipt contained 1–2% by weight of the paper of BPA, BPS, or BPSIP. The post-shift geometric mean total urinary BPS concentration was significantly higher than the pre-shift mean in 33 cashiers who handled receipts containing BPS. The mean urine BPA concentrations in 31 cashiers who handled BPA receipts were as likely to decrease as to increase after a shift, but the mean post-shift concentrations were significantly higher than those in non-cashiers. BPSIP was detected more frequently in the urine of cashiers handling BPSIP receipts than in the urine of non-cashiers. Only a few cashiers had detectable levels of total BPA or BPS in serum, whereas BPSIP tended to be detected more frequently. Conclusions: Thermal receipt paper is a potential source of occupational exposure to BPA, BPS, and BPSIP. Citation: Thayer KA, Taylor KW, Garantziotis S, Schurman SH, Kissling GE, Hunt D, Herbert B, Church R, Jankowich R, Churchwell MI, Scheri RC, Birnbaum LS, Bucher JR. 2016. Bisphenol A, bisphenol S, and 4-hydro​xyphenyl 4-isopro​oxyphenyl​sulfone (BPSIP) in urine and blood of cashiers. Environ Health Perspect 124:437–444; http://dx.doi.org/10.1289/ehp.1409427

Some thermal paper receipts, commonly referred to as cash register receipts, contain high levels of bisphenol A (BPA). The goal of this study is to investigate whether increased contact with thermal paper receipts is associated with an increase in urinary BPA excretion. Individuals from the NHANES 2003-2004 survey were stratified based on occupation to compare urinary BPA excretion levels. The first major finding demonstrates that individuals with potential occupational exposure to thermal paper receipts are more likely to have detectable levels of urinary BPA compared to individuals with unlikely occupational exposure (p-value0.001). The second major finding is that females with potential occupational exposure to thermal paper receipts have significantly higher levels of urinary BPA excretion (geometric mean (GM): 5.45 μg/L, 95% CI: (4.02, 7.39)) compared to females with unlikely occupational exposure (GM: 2.16 μg/L, 95% CI: (1.73, 2.70)). This association continues to remain statistically significant when controlling for creatinine, race, body mass index (BMI), and age. Notably, there was no statistically significant association between occupation and urinary BPA excretion among males. These results suggest that exposure to BPA from thermal paper should be considered when determining aggregate BPA exposure.

Bisphenol A (BPA) is an endocrine disrupting environmental chemical. Urinary concentrations of BPA were measured in samples collected nationwide from Chinese young adults. The geometric mean urinary concentration of BPA in Chinese young adults was 2.23 ng/mL. The estimated daily exposure dose for BPA was 64.8 ng/kg bw/day. Contributions of various BPA sources to exposure in Chinese young adults were estimated. Dietary intake was the primary exposure pathway. The contribution of dietary intake, indoor dust, paper products and personal care products to BPA intake was 72.5 %, 0.74 %, 0.98 %, 0.22 % of the total exposure dose, respectively. This is the first study on the occurrence of BPA in young adults from most provinces and autonomous regions of China. The results can be used to establish a database for BPA exposure assessment for Chinese general population.

Nucleic acid testing (NAT), as a molecular diagnostic technique, including nucleic acid extraction, amplification and detection, plays a fundamental role in medical diagnosis for timely medical treatment. However, current NAT technologies require relatively high-end instrumentation, skilled personnel, and are time-consuming. These drawbacks mean conventional NAT becomes impractical in many resource-limited disease-endemic settings, leading to an urgent need to develop a fast and portable NAT diagnostic tool. Paper-based devices are typically robust, cost-effective and user-friendly, holding a great potential for NAT at the point of care. In view of the escalating demand for the low cost diagnostic devices, we highlight the beneficial use of paper as a platform for NAT, the current state of its development, and the existing challenges preventing its widespread use. We suggest a strategy involving integrating all three steps of NAT into one single paper-based sample-to-answer diagnostic device for rapid medical diagnostics in the near future.

Bisphenol A (BPA) is widely used in industrial products. Due to the toxicity of this compound, and to comply with restrictions and regulations, manufacturers have progressively replaced it by substitutes. One of the main substitutes used is bisphenol S (BPS). Despite increasing use in many products, the effects of BPS on human health have been little investigated, and studies on percutaneous BPS absorption and particularly toxicokinetic data are lacking. However, the endocrine-disrupting activity of BPA and BPS appears comparable. Dermal contact is a significant source of occupational exposure and is the main route during handling of bisphenol-containing receipts by cashiers. Here, percutaneous BPS absorption was investigated and compared to that of BPA. Experiments were performed according to OECD guidelines. Test compounds dissolved in a vehicle - acetone, artificial sebum or water – were applied in vitro to fresh human skin samples in static Franz diffusion cells. Flux, cumulative absorbed dose and distribution of dose recovered were measured. BPA absorption was vehicle-dependent ranging from 3% with sebum to 41% with water. BPS absorption was much lower than BPA absorption whatever the vehicle tested (less than 1% of applied dose). However, depending on the vehicle 20% to 47% of the applied BPS dose remained in the skin, and was consequently potentially absorbable. Both BPA and BPS were mainly absorbed without biotransformation. Taken together, these results indicate that workers may be exposed to BPS through skin when handling products containing it. This exposure is of concern as its toxicity is currently incompletely understood.

Examination covered 245 individuals and included characteristics of endocrine state of pulp and paper plant workers over 2011-2012, in comparison with data from 1990, as well as comparison with reference groups of male workers with no contact with chemical'industry in Arkhangelsk. Findings are both in main and reference groups general decrease in levels of cortisol, thyroxin;progesterone, testosterone, insulin, somatotropin and increased serum level of estradiol. With that, inside both groups, reliable tendencies to increased levels of cortisol, thyroxin, insulin, SSH and lower concentration of progesterone in the pulp and paper plant workers vs. the reference group members. Positive tendency was absence of abnormal concentrations of insulin, SSH and lower frequency of high cortisol levels in the pulp and paper plant workers nowadays.

Bisphenol A (BPA) is a high-production-volume chemical with endocrine disrupting properties commonly used as color developer in thermal paper. Concerns about the potential hazards of human BPA exposure have led to the increasing utilization of alternatives such as bisphenol S (BPS) and bisphenol F (BPF). This study was designed to assess: (i) BPA, BPS, and BPF concentrations in 112 thermal paper receipts from Brazil, France, and Spain by liquid chromatography coupled to mass spectrometry (LC-MS); and (ii) hormone-like activities of these receipts using two receptor-specific bioassays, the E-Screen for (anti-)estrogenicity and PALM luciferase assay for (anti-)androgenicity. BPA was present in 95.3% of receipts from Spain, 90.9% of those from Brazil, and 51.1% of those from France at concentrations up to 20.27 mg/g of paper. Only two samples from Brazil, two from Spain, and ten from France had a BPS concentration ranging from 6.46 to 13.29 mg/g; no BPA or BPS was detected in 27.7% of French samples. No BPF was detected in any receipt. Estrogenic activity was observed in all samples from Brazil and Spain and in 74.5% of those from France. Anti-androgenic activity was observed in > 90% of samples from Brazil and Spain and in 53.2% of those from France. Only 25.5% of French samples were negative for both estrogenic and anti-androgenic activity. Estrogenic and anti-androgenic activities per gram of paper were up to 1.411 µM estradiol (E2) equivalent units (E2eq) and up to 359.5 mM procymidone equivalent units (Proceq), respectively. BPA but not BPS concentrations were positively correlated with both estrogenic and anti-androgenic activities. BPA still dominates the thermal paper market in Brazil and Spain, and BPS appears to be one of the main alternatives in France. There is an urgent need to evaluate the safety of alternatives proposed to replace BPA as developer in thermal printing. The large proportion of samples with hormonal activity calls for the adoption of preventive measures.

Background Parturition and the initial postpartum period are important moments in the reproductive cycle of dogs. Methods A study assessed the effect of ADAPTIL, a dog-appeasing pheromone, on maternal behaviour during peripartum. Bitches were continuously exposed to ADAPTIL (n=20) or placebo (n=21) in double-blinded conditions from an average of about seven days before parturition up to 21 days postpartum. Differences in maternal behaviour in relation to the treatment were evaluated by the observation of specific activities through video recordings, such as the time spent by the bitch in close contact with the puppies, oronasal interaction and nursing duration and position. Videos were recorded at four time points (W0: within the first 48 hours of whelping; W1: one week after parturition; W2: two weeks after parturition; and W3: three weeks after parturition). In addition, the perception of breeders in relation to the quality of maternal care, puppies’ wellbeing and overall relationship between the bitches and the puppies was evaluated using Visual Analogue Scale at the same time points. Moreover, the daily activity of the bitches was measured by using an electronic device (FitBark dog activity trackers, Kansas City, Missouri). Results For all observed maternal behaviours, there was a steady decrease in levels as the puppies developed, independently of treatment. However, bitches exposed to ADAPTIL tended to nurse significantly more in lying position, while those exposed to the placebo nursed more in a seated position, especially at W1 (P=0.06) and W3 (P=0.005). According to the breeders, the attention scores of bitches towards puppies were significantly higher in ADAPTIL than in the placebo group at each time point (P=0.01). Moreover, a difference according to parity was observed (P=0.004), with greater attention score displayed by primiparous bitches exposed to ADAPTIL compared with placebo on W0 (P=0.02), W1 and W3 (P

Ricin is a highly-toxic compound derived from castor plant beans. Several incidents involving contamination of residences and buildings due to ricin production or dissemination have occurred in recent years. The goal of this study was to determine whether ricin bioactivity could be attenuated in reasonable time via simple modifications of the indoor environment. Attenuation was assessed on six different materials as a function of temperature, relative humidity (RH), and contact time, using both a pure and crude preparation of the toxin. Ricin bioactivity was quantified via a cytotoxicity assay, and attenuation determined as the difference in ricin recovered from test and positive controls. The results showed that pure ricin could be attenuated successfully, while the crude ricin was generally more persistent and results more variable. We found no significant attenuation in crude ricin after two weeks at typical indoor environmental conditions, except on steel. Attenuation mostly improved with increasing temperature, but the effect of RH varied. For pure ricin, heat treatments at 40°C for 5 days or 50°C for 2–3 days achieved greater than 96% attenuation on steel. In contrast, appreciable recovery of the crude ricin preparation still occurred at 40°C after two weeks.

Objective A dearth of studies focusing on young women (

Thermal paper contains potentially toxic additives, such as bisphenol A (BPA), as a common color developer. Because of its known endocrine disrupting effects, structural analogues to BPA, such as bisphenol S (BPS), D-8 and Pergafast 201, have been used as alternatives, but little is known about the presence and toxicological effects of alternatives other than BPS. In this study, thermal paper is screened by direct probe ambient mass spectrometry (rapid pre-screening method not requiring sample preparation) and by liquid chromatography (LC) with high resolution time-of flight (TOF-MS) mass spectrometry. Cash receipts and other thermal paper products (cinema tickets, boarding passes and luggage tags) were analyzed. Besides BPA and BPS, other developers only recently reported (Pergafast 201, D-8) or to the best of our knowledge not reported before (D-90, TGSA, BPS-MAE) were frequently found as well as some related unreported impurities (2,4-BPS that is a BPS related impurity and a TGSA related impurity). To gain some insight into the potential estrogenicity of the detected developers, a selection of extracts was further analyzed using a LC-nanofractionation platform in combination with cell-based bioassay testing. These preliminary results seems to indicate very low or absence of estrogenic activity for Pergafast 201, D-8, D-90, TGSA and BPS-MAE in comparison to BPA and BPS, although further dose-response tests with authentic standards are required to confirm these results. Compounds for which standards were available were also tested for developmental toxicity and neurotoxicity using zebrafish (Danio rerio) embryos. TGSA and D-8 induced similar teratogenic effects as BPA in zebrafish embryos. BPS and 2,4-BPS did not induce any developmental effects but 2,4-BPS did alter the locomotor activity at the tested concentration. Our findings suggest that the alternatives used as alternatives to BPA (except BPS) might not be estrogenic. However, TGSA and D-8 showed abnormal developmental effects similar to BPA.

Bisphenol A (BPA) is found in polycarbonate plastic and epoxy resins and is used in a variety of commercial and consumer products. The leaching of BPA can result in human exposure via inhalation, ingestion, and dermal routes. As a result, humans have been exposed in their home and work environment to BPA. Conventional methods for BPA exposure assessment rely on cumbersome laboratory instrumentation with high capital and operational expenditures which limit the number of samples that can be analyzed. We report here the design of a compact portable colorimetric paper-based biosensing device with integrated sampling/analysis units for field-based measurements of BPA in indoor dust. The system employs interchangeable low-cost paper-based enzyme sensors as a test zone for BPA detection interfaced with an air-sampling cassette as a sample collection area. The sensor response was concentration-dependent with a detection limit of 0.28 μg/g. The sensor was validated with the conventional gas chromatography method and used to detect BPA exposure in household dust. BPA concentrations ranged from 0.05 to 3.87 μg/g in 57 household dust samples when both methods were used. The potential of this method for field measurements of dust samples is discussed.

Pulp and paper mill effluents (PPMEs) have been shown to increase gonad size, cause early maturation, and disrupt hormone functions in native and non-native Chilean fish. In this study, we assessed reproductive (plasma vitellogenin; VTG, gonad development) and metabolic (ethoxyresorufin-. O-deethylase activity; EROD) end points, relative liver size (LSI) and condition factor (K) of juvenile female and male rainbow trout exposed to effluents. Unlike previous studies, which have focus either on the specific effects of effluent on fish in laboratory exposures or biotic population statuses downstream of discharge sites, we simultaneously assessed the impacts of PPMES on trout using two approaches: (1) laboratory exposures of tertiary treated PPME produced from processing Eucalyptus globulus or Pinus radiata; and (2) in situ bioassay downstream of the combined discharge of the same pulp mill. Despite an increase in the average gonadosomatic index (GSI) in exposed fish, no statistical differences in gonad size between exposed and unexposed individuals was detected. However, both female and male fish exposed to effluents showed significantly higher concentrations of plasma VTG, so more in fish exposed to Eucalyptus-based effluent when compared to Pinus PPME. In addition, male fish showed intersex characteristics in all exposure assays (Eucaliptus and Pinus) and, despite the low concentration of effluent in the river (

Alternatives to bisphenol A (BPA) are more and more used in thermal paper receipts. To get an overview of the situation in Switzerland, 124 thermal paper receipts were collected and analyzed. Whereas BPA was detected in most samples (n=100), some alternatives, namely bisphenol S (BPS), Pergafast® 201 and D-8 have been found in 4, 11 and 9 samples respectively. As no or few data on their endocrine activity are available, these chemicals and bisphenol F (BPF) were tested in vitro using the H295R steroidogenesis assay. 17β-Estradiol production was induced by BPA and BPF, whereas free testosterone production was inhibited by BPA and BPS. Both non-bisphenol substances did not show significant effects. The binding affinity to 16 proteins and the toxicological potential (TP) were further calculated in silico using VirtualToxLab™. TP values lay between 0.269 and 0.476 and the main target was the estrogen receptor β (84.4 nM to 1.33 μM). A substitution of BPA by BPF and BPS should be thus considered with caution, since they exhibit almost a similar endocrine activity as BPA. D-8 and Pergafast® 201 could be alternatives to replace BPA, however further analyses are needed to better characterize their effects on the hormonal system.

The aim of the study was to assess occupational exposure to bisphenol A in Finland. Five companies took part in the research project: two paint factories (liquid and powder paints), a composite product factory, a thermal paper factory, and a tractor factory. Exposure was assessed by measuring total bisphenol A excretion (free and conjugated) from urine samples, and its concentrations in the air. The results revealed the specific work tasks in two of five companies in which significant occupational exposure to bisphenol A may occur. In the manufacturing of liquid paint hardener, urine samples collected after the working day showed bisphenol A levels of up to 100-170 µg l-1. Workers in thermal paper manufacturing were also exposed to bisphenol A, especially those working in the manufacture of coating material and operating coating machines. Median concentrations of the post-shift urine samples of coating machine workers were in the range of 130-250 µg l-1. The highest bisphenol A concentrations were in the range of 1000-1500 µg l-1. Recommendations for more effective personal protection resulted in decreased exposure, particularly among coating machine operators. In the rest of the companies, urinary bisphenol A levels were typically in the range of those of the general population. Bisphenol A concentrations in air samples were typically low (

Bioluminescent Saccharomyces cerevisiae yeast- based bioreporters were used to monitor bisphenol A and other estrogenic chemicals in thermal paper samples collected mainly from Finland on two occasions in 2010/2011, and 2013. The bisphenol A-targeted (BPA-R) and the human oestrogen receptor (hERα) bioreporters were applied to ana- lyse both non-treated and extracted paper samples. Bisphenol A was readily bioavailable to the yeast bioreporters on the non-treated paper samples without any pre-treatment. Detect- ed concentrations ranged from a detection limit of 9-142 μg/g to over 20 mg/g of bisphenol A equivalents in the thermal papers. Low bisphenol A likeactivities were detected in many samples, and were considered to be caused by residual bisphenol A or other types of bisphenols, such as bisphenol S. Most of the thermal paper samples were toxic to the yeast bioreporters. The toxicity did not, however, depend on the bisphenol A concentration of the samples. The yeast bioreporters were demonstrated to be a robust and cost- efficient method to monitor thermal paper samples for their bisphenol A content and estrogenicity. Thermal paper was considered as a potential BPA source for both human expo- sure and environmental emission.

In this paper, Graphene oxide@SiO2@CeO2 hybrid nanosheets (GSCs) have been successfully synthesized by the wet-chemical strategy. TEM, FITR and XPS were applied to characterize the morphology and composition of the nanosheets. The colorimetric assay of these nanosheets indicated that they possessed high intrinsic peroxidase activity, which should be ascribed to the combination of graphene oxide and CeO2. A fully integrated reagentless bioactive paper based on GSCs was fabricated, which were able to simultaneously detect glucose, lactate, uric acid and cholesterol. The results demonstrated that GSCs have great potential as an alternative to the commonly employed peroxidase in daily nursing and general physical examination.

Middle East Respiratory Syndrome Corona Virus (MERSCoV) have been reported in Arabian peninsula and sporadic cases in Europe and Asia. This study was conducted to evaluate the genetic analysis of this virus in human and camel at the first time in Iraq. Two hundred samples were collected from camels and human who suffering from respiratory symptoms, these samples treated with RNA extraction kit then amplification the genetic material by PCR which give 5% positive results. The amplicon then sequenced, registration in gene bank of NCBI for getting accession numbers. The local strains give close relationship with neighbor countries as Saudi Arabia and Jordan strains when using MEGA analysis software.

Bisphenol A (BPA) is a widely used chemical in the production of many polycarbonate plastics, epoxy resin linings for food and beverage containers and thermal papers. Oral intakes from the contaminated diets were considered as the predominant source of BPA exposure for humans. However, due to the high levels of BPA on thermal receipts and their wide applications in our daily life, the amount of BPA be transferred to the skin after holding thermal paper should not be underestimated, particularly for cashiers. To investigate the contribution of BPA exposure levels via the dermal contact route and the relationship between BPA exposure level and oxidative DNA damage, six male volunteers were recruited and required to simulate the cashiers' work and handle the thermal receipts during the study period. Triclosan (TCS, an antimicrobial compound used widely in personal health and skin care products) was applied as a reference compound. Their urinary BPA, TCS and 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations were determined by high performance liquid chromatography/ tandem spectrometer (LC/MS/MS). The results showed that after handling the thermal receipts, the urinary BPA concentrations of volunteers increased 3 times of those before the experimental period. But TCS levels in urine kept stable. There existed a correlation between BPA exposure and 8-OHdG (R2 = 0.237, p

A number of high molecular weight (HMW) lignin derivatives possessing varied chemical properties were screened for their biological effects in order to obtain more information on the possible structural features of HMW lignin-related effects. The studied compounds were both commercial and in-house extracted lignin derivatives. Bioassays used include reverse electron transport (RET), Vibrio fischeri, Daphnia magna , and juvenile rainbow trout ( Oncorhynchus mykiss) hepatocytes. The studied lignin derivatives inhibited the in vitro systems and luminescence of V. fischeri bacteria to some extent–daphnids were not affected. It seems that, at least in the RET assay, certain pH-dependent functional groups in lignin may be of importance regarding the biological effects.

Sex determination in the American alligator depends on the incubation temperature experienced during a thermo-sensitive period (TSP), although sex determination can be ‘reversed’ by embryonic exposure to an estrogenic compound. Thus, temperature and estrogenic signals play essential roles during temperature-dependent sex determination (TSD). The genetic basis for TSD is poorly understood, although previous studies observed that many of the genes associated with genetic sex determination (GSD) are expressed in species with TSD. Heat shock proteins (HSPs), good candidates because of their temperature-sensitive expression, have not been examined in regard to TSD but HSPs have the ability to modify steroid receptor function. A number of HSP cDNAs (HSP27, DNAJ, HSP40, HSP47, HSP60, HSP70A, HSP70B, HSP70C, HSP75, HSP90α, HSP90β, and HSP108) as well as cold-inducible RNA binding protein (CIRBP) and HSP-binding protein (HSPBP) were cloned, and expression of their mRNA in the gonadal-adrenal-mesonephros complex (GAM) was investigated. Embryonic and neonatal GAMs exhibited mRNA for all of the HSPs examined during and after the TSP. One-month-old GAMs were separated into 3 portions (gonad, adrenal gland, and mesonephros), and sexual dimorphism in the mRNA expression of gonadal HSP27 (male > female), gonadal HSP70A (male < female), and adrenal HSP90α (male > female) was observed. These findings provide new insights on TSD and suggest that further studies examining the role of HSPs during gonadal development are needed.

Screening for congenital hypothyroidism for all newborns of the former western parts of the city of Berlin was instituted in 1978 by determination of the TSH levels in dried filter paper blood spots of the 3rd to 5th day of life. Since 1991 the newborns of the former eastern parts have been also included in the same screening program. From 1978 to 1995 a total number of 104 newborns with permanent congenital hypothyroidism have been detected resulting in a prevalence of congenital hypothyroidism of 1:3800. The etiological diagnosis of hypothyroidism was made by imaging studies (ultrasonography or 99mTc scintigraphy) and assessment of serum thyroglobulin and thyroid hormone levels. Using this approach in 37 children (30 female, 7 male) the diagnosis of athyrosis, in 20 children (15 female, 5 male) the diagnosis of ectopy and in 21 children (18 female, 3 male) the diagnosis of thyroid hypoplasia was made, 16 children (8 female, 8 male) had a normally sized gland and 4 (1 female, 3 male) had congenital goiter. In 86% of all patients the age at onset of thyroxine (L-T4) replacement therapy was 8 or 9 days of life (3-42 days) and the median initial L-T4 dose was 14 micrograms/kg/day (10-16 micrograms/kg/day). The intellectual outcome of 77 children (2-16 years) was studied and normal scores for the intelligence (IQ) and developmental (DQ) quotients were found in 71 (92%). Outcome was not correlated to the age at onset of treatment, the initial dose and the severity of hypothyroidism, but there was a positive correlation of the socioeconomic status of the family and the IQ of the patients. The results of the screening program in Berlin document that an early and efficient thyroxine replacement can normalize the intellectual outcome of patients with congenital hypothyroidism independent of the severity of the disease as assessed by the residual thyroid function detectable at diagnosis.

Bisphenol A (BPA) is an endocrine and metabolic disruptor commonly employed as a color developer in thermal papers. Consequently, BPA derived from thermal papers has been considered an important source of exposure for humans, since this chemical may migrate from paper to skin upon contact. Further, due to recent restrictions on BPA use in some countries, it has been replaced by a new analogue, bisphenol S (BPS). The aim of the present study was to determine levels of BPA and BPS in 190 different thermal receipts, randomly collected from different locations in Sao Paulo State, Brazil, including receipts from supermarkets, general and fast-food restaurants, gas stations, bus and airplane tickets, and credit card and bank accounts. BPA and/or BPS were detected in 98% of samples at concentrations ranging from below the quantification limit to 4.3% (mg/100 mg paper). The obtained values were higher than amounts previously reported in other countries. The estimated daily intake through dermal absorption from handling of thermal receipt papers was estimated on the basis of concentrations and frequencies of handling of papers by humans in both the general population and occupationally exposed individuals. Fifth percentile, median, and 95th percentile daily intakes by the general population were 0.44, 1.42, and 2 μg/d, respectively, whereas the corresponding values for occupationally exposed population are 21.8, 71 and 101 μg/d. The potential adverse consequences of elevated occupational exposure are currently being examined.

International audience; Purpose: As an essential component of polycarbonate plastics and epoxy resins, Bisphenol A (BPA) is found in numerous industrial and consumer products. BPA may cause adverse health effects because of its endocrine activity. General population exposure to this compound mainly through diet is well documented. Thermal paper was also identified as a source of BPA through dermal intake. In this study, we investigated whether frequent contact with thermal paper is associated with an increase in urinary BPA excretion.Methods: We evaluated the exposure to BPA in cashiers and in non-occupationally exposed workers from several workplaces. Urinary BPA was quantified in free (unconjugated) and total (unconjugated plus conjugated) forms in 24-h and spot urine samples using LC–MS/MS. BPA concentration in thermal paper was also measured from each workplace. In addition, participants provided information on job, food and drink, tobacco consumption and hands wash during the sampling period through a questionnaire.Results: Urine samples were collected from 90 cashiers and 44 controls. Free and total BPA were detected in all samples. The median urinary total BPA concentration was 3.54 µg/L (2.89 µg/g creatinine) for controls and 8.92 µg/L (6.76 µg/g creatinine) for cashiers. For the free BPA, the median urinary concentration was 0.20 µg/L (0.21 µg/g creatinine) for controls and 0.28 µg/L (0.22 µg/g creatinine) for cashiers. Any correlation was found between the urinary concentration levels and the number of thermal receipts handled. Hand washes frequency, age, job length of service and tobacco consumption had also no effect on the BPA excretions.Conclusion:A significant increase in urinary total BPA concentration was observed for cashiers handling daily thermal paper receipts. However, no significant increase was observed in urinary free BPA concentration. These findings are particularly interesting for risk assessment since all available data on occupational exposure to BPA through thermal paper were obtained from models or from simulated experiments.

Bisphenol A (BPA) is well known for its use in plastic manufacture and thermal paper production despite its risk of health toxicity as an endocrine disruptor in humans. Since the publication of new legislation regarding the use of BPA, manufacturers have begun to replace BPA with other phenolic molecules such as bisphenol F (BPF) and bisphenol B (BPB), but there are no guarantees regarding the health safety of these compounds at this time. In this context, a very simple, cheap and fast surface-enhanced Raman scattering (SERS) method was developed for the sensitive detection of these molecules in spiked tap water solutions. Silver nanoparticles were used as SERS substrates. An original strategy was employed to circumvent the issue of the affinity of bisphenols for metallic surfaces and the silver nanoparticles surface was functionalized using pyridine in order to improve again the sensitivity of the detection. Semi-quantitative detections were performed in tap water solutions at a concentrations range from 0.25 to 20 μg L(-1) for BPA and BPB and from 5 to 100 μg L(-1) for BPF. Moreover, a feasibility study for performing a multiplex-SERS detection of these molecules was also performed before successfully implementing the developed SERS method on real samples.

In our work, low potential and sensitive electrochemiluminescence (ECL) detection for CA153 on MCF-7 cell surface was firstly achieved based on a microfluidic paper-based analytical device. Au nanoflowers were grown in paper working electrode (PWE) to construct the ECL platform for primary antibodies immobilizing. After MCF-7 cells were captured in the modified PWE, and subsequently recognized with ECL signal substance labeled secondary antibodies, the sandwich-type cell sensor was fabricated. Graphene quantum dots (GQDs) loaded surface villous Au nanocages were synthesized as the ECL signal substance, and characterized by scanning electron microscope. The specific villous surface structure for Au nanocage permitted more GQDs being carried and electrons transporting, which largely benefited for the ECL performance. As the un-negligible impendence for MCF-7 cell would definitely influence the ECL signal, CA153 labeled HMEpic cell was used as the control cell to obtain more accurate determination result. This low-cost and fast strategy showed acceptable biocompatibility and stability, and will be promising for cellular immunochemistry.

Background: Some ganglioside complexes (GSCs) are target antigens for serum antibodies in patients with Guillain–Barre syndrome (GBS). Anti-GSC antibodies may be associated with particular clinical features of GBS. Objective: To investigate antibodies to GSCs in the sera of patients with Miller Fisher syndrome (MFS) characterised by elevation of the IgG anti-GQ1b antibody. Results: In all, 7 of 12 (58%) consecutive patients with MFS were found to have IgG antibodies to GSCs containing GQ1b, of whom 5 had IgG antibodies to GQ1b-GM1 complex (GQ1b/GM1) and 2 had antibodies to GQ1b/GD1a; 4 of 5 patients without sensory symptoms had anti-GQ1b/GM1 antibodies. Conclusions: At least three different specificities in MFS-associated antibodies, GQ1b-specific, anti-GQ1b/GM1-positive and anti-GQ1b/GD1a-positive, were observed. In patients with MFS not only GQ1b itself but also clustered epitopes of GSCs, including GQ1b, may be considered to be prime target antigens for serum antibodies. A tendency to escape sensory disturbances is shown by anti-GQ1b/GM1-positive MFS.

Background: Post-traumatic amnesia (PTA) tests that record different PTA durations in the same patient, thereby raising measurement accuracy issues, have been reported previously. A major problem lies in determining the end point of PTA. Aims: To delineate areas of discrepancy in PTA tests and to provide independent verification for a criterion signalling emergence from PTA. Methods: In a randomised design, two related PTA procedures were compared, one purportedly more difficult (Westmead PTA Scale, WPTAS) than the other (Modified Oxford PTA Scale, MOPTAS). Eighty two patients in the early stages of PTA were examined daily until emergence, by using the Galveston Orientation and Amnesia Test (GOAT) and the WPTAS/MOPTAS. A short battery of cognitive and behavioural measurements was made on three occasions: at the early stage of PTA (time 1), towards the end of PTA when the maximum score (12/12) was first obtained (time 2) and at the traditional criterion for emergence (scoring 12/12 for 3 consecutive days; time 3). Results: No significant difference was recorded in PTA duration between the MOPTAS and WPTAS. Both scales recorded longer PTA durations than the GOAT. By using Kaplan–Meier survival analyses, the WPTAS was found to show a more protracted pattern of emergence at the end stage of PTA than the MOPTAS. A time lag of ⩾1 week in the resolution of disorientation as compared with amnesia was observed in 59% cases. Significant improvements occurred on all independent measurements between time 1 and time 2, but on only 2 of 5 cognitive measurements between time 2 and time 3. Conclusions: Although no significant differences in the duration of PTA on the MOPTAS/WPTAS were recorded, emergence from the late stages of PTA occurred more promptly with the MOPTAS. The need for inclusion of both orientation and memory items in PTA tests is highlighted by the frequency of disorientation–amnesia dissociations. The patterns of results on the independent measures suggest that patients who are in PTA for > 4 weeks have probably emerged from PTA when they first score 12/12 on the MOPTAS/WPTAS, and this criterion can replace the traditional criterion.

Worldwide, wild fish living in rivers receiving municipal and industrial discharges may experience endocrine disruption as a result of exposure to anthropogenic pollutants. The purpose of this study was to evaluate the hormonal status of wild fish in a U.S. river receiving unbleached kraft and recycled pulp mill effluent (Pearl River at Bogalusa, LA). We evaluated two alternative hypotheses: the effluent contained constituents that suppressed male and female reproduction, or it contained an androgenic substance that masculinized females. To evaluate the likelihood of fish exposure to effluent, we marked 697 longear sunfish (Lepomis megalotis) over a 2-year period; 83% of recaptured fish were found at the site of initial capture, and only one fish migrated from an effluent-receiving site to a reference site. We can reasonably assume that fish captured from an effluent-receiving site are residents, not transitory migrants. To diagnose endocrine disruption, we measured sex steroid hormone [17beta-estradiol (E2), testosterone (T), and 11-ketotestosterone (11KT)] and vitellogenin (VTG) concentrations in male and female longear sunfish captured at two sites upstream and two sites downstream of the effluent outfall. Kraft pulp mill effluent did not affect male reproductive physiology but did suppress female T and VTG levels when effluent constitutedor=1% of river flow. Masculinization was not observed. Longear sunfish in the Pearl River experience moderate reproductive suppression in response to unbleached kraft and recycled pulp mill effluent.

Objective: To assess visual search and recognition of roadside targets and safety errors during a landmark and traffic sign identification task in drivers with Alzheimer's disease. Methods: 33 drivers with probable Alzheimer's disease of mild severity and 137 neurologically normal older adults underwent a battery of visual and cognitive tests and were asked to report detection of specific landmarks and traffic signs along a segment of an experimental drive. Results: The drivers with mild Alzheimer's disease identified significantly fewer landmarks and traffic signs and made more at-fault safety errors during the task than control subjects. Roadside target identification performance and safety errors were predicted by scores on standardised tests of visual and cognitive function. Conclusions: Drivers with Alzheimer's disease are impaired in a task of visual search and recognition of roadside targets; the demands of these targets on visual perception, attention, executive functions, and memory probably increase the cognitive load, worsening driving safety.

Background: Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) is favoured over bilateral globus pallidus internus (Gpi) DBS for symptomatic treatment of advanced Parkinson's disease (PD) due to the possibility of reducing medication, despite lack of definitive comparative evidence. Objective: To analyse outcomes after one year of bilateral Gpi or STN DBS, with consideration of influence of selection bias on the pattern of postsurgical medication change. Methods: The first patients to undergo bilateral Gpi (n = 10) or STN (n = 10) DBS at our centre were studied. They were assessed presurgically and one year after surgery (CAPIT protocol). Results: Before surgery the Gpi DBS group had more dyskinesias and received lower doses of medication. At one year, mean reduction in UPDRS off medication score was 35% and 39% in the Gpi and STN groups, respectively (non-significant difference). Dyskinesias reduced in proportion to presurgical severity. The levodopa equivalent dose was significantly reduced only in the STN group (24%). This study high-lights the absence of significant differences between the groups in clinical scales and medication dose at one year. In the multivariate analysis of predictive factors for off-state motor improvement, the presurgical levodopa equivalent dose showed a direct relation in the STN and an inverse relation in the Gpi group. Conclusion: Differences in the patterns of medication change after Gpi and STN DBS may be partly due to a patient selection bias. Both procedures may be equally useful for different subgroups of patients with advanced PD, Gpi DBS especially for patients with lower threshold for dyskinesia.

Objectives: To characterise the clinical features, emergency pre-paediatric intensive care (PIC) treatment, and course of status epilepticus (SE) in children admitted to PIC. This may provide insight into reasons for admission to PIC and provide a framework for the development of strategies that decrease the requirement for intensive care. Design: Cross sectional, retrospective study. Setting: A tertiary paediatric institution's intensive care unit. Participants: The admission database and all discharge summaries of each admission to a tertiary paediatric institution's PIC over a three year period were searched for children aged between 29 days and 15 years with a diagnosis of SE or related diagnoses. The case notes of potential cases of SE were systematically reviewed, and clinical and demographic data extracted using a standard data collection form. Results: Most children with SE admitted to PIC are aged less than 5 years, male to female ratio 1:1, and most (77%) will have had no previous episodes of SE. Prolonged febrile convulsions, SE related to central nervous system infection, and SE associated with epilepsy occur in similar proportions. Contrary to the Advanced Paediatric Life Support guidelines many children admitted to PIC for SE receive over two doses, or inadequate doses, of benzodiazepine. There is a risk of respiratory depression following administration of over two doses of benzodiazepine (χ2 = 3.4, p = 0.066). Children with SE admitted to PIC who had prehospital emergency treatment are more likely to receive over two doses of benzodiazepines (χ2 = 11.5, p = 0.001), and to subsequently develop respiratory insufficiency (χ2 = 6.2, p = 0.01). Mortality is low. Further study is required to determine the morbidity associated with SE in childhood requiring intensive care. Conclusions: As the risk of respiratory depression is greater with more than two doses of benzodiazepines, clinicians should not disregard prehospital treatment of SE. As pre-PIC treatment of SE is inadequate in many cases, appropriate audit and modifications of standard guidelines are required.