Evaluating the relationship of in utero nicotine exposure with hypoglycemia after delivery: An observational study.

BACKGROUND: Hypoglycemia in neonates is common and contributes to 4.0-5.8% of neonatal intensive care unit (NICU) admissions. In utero nicotine exposure is underexplored as a potential contributor to neonatal hypoglycemia. Rat models have shown that in utero nicotine exposure can be associated with a reduction in pancreatic beta cell mass, leading to glucose dysregulation. The primary aim of this work is to study the risk of developing hypoglycemia after birth in a population of in utero nicotine-exposed neonates. METHODS: We conducted a retrospective matched cohort study that augmented an existing dataset of neonates admitted to a level IV NICU with household-based in utero nicotine exposure (N = 335). Neonates in the control group parents denied household smoking (N = 325), were born within a 6-month timeframe, and were within a birthweight of 50 grams of a nicotine-exposed neonate. Data reviewed included gestational age, growth parameters, maternal history of diabetes, and glucose levels within the first three hours of life per unit protocol. RESULTS: 660 neonates were included in the analysis. In utero nicotine exposure demonstrated a 94.3% posterior probability (PP) for greater hypoglycemia risk (RR = 1.185, 95% CrI = [0.953, 1.445]). A 94.6% PP was demonstrated when neonates who were small for gestational age, intrauterine growth-restricted, and born to diabetic mothers were excluded (n = 482; RR = 1.271, 95% CrI = [0.946, 1.669]). CONCLUSION: Nicotine exposure in utero was found to be a potential risk factor for developing hypoglycemia after birth. Mechanisms of action should be explored, and additional research on in utero nicotine exposure risks should follow.

Defining recurrence of nonmelanoma skin cancer after Mohs micrographic surgery: Report of the American College of Mohs Surgery Registry and Outcomes Committee.

BACKGROUND: Standardized definitions and methods of surveillance for local recurrence of nonmelanoma skin cancer are critical in determining cure rates attributed to treatment modalities. OBJECTIVE: We sought to offer a standard definition of local recurrence after surgical treatment of nonmelanoma skin cancer and to propose an acceptable surveillance period and tracking methods. METHODS: A literature search was performed for background definitions of local recurrence and tracking methods. The American College of Mohs Surgery (ACMS) Registry and Outcomes Committee then conducted a modified Delphi process to arrive at consensus definitions. RESULTS: We define local recurrence as a tumor with comparable histology, with contiguity to the surgical scar after treatment, and that arises within the area of the previously treated tumor. LIMITATIONS: This project reports the results of a modified Delphi method process involving members of the ACMS. The model described may not be useful for nonexcision type treatments such as topical chemotherapy, electrodessication and curettage, or radiation treatment. CONCLUSIONS: Previous definitions of recurrence and surveillance methods after surgical treatment of nonmelanoma skin cancer are variable and nonstandard. We describe consensus standards for defining and tracking recurrence that should allow for consistent scientific evaluation and development of performance data in skin cancer outcomes registries.

The production of alpha/beta and gamma/delta double negative (DN) T-cells and their role in the maintenance of pregnancy.

The ability of the thymus gland to convert bone marrow-derived progenitor cells into single positive (SP) T-cells is well known. In this review we present evidence that the thymus, in addition to producing SP T-cells, also has a pathway for the production of double negative (DN) T-cells. The existence of this pathway was noted during our examination of relevant literature to determine the cause of sex steroid-induced thymocyte loss. In conducting this search our objective was to answer the question of whether thymocyte loss is the end product of a typical interaction between the reproductive and immune systems, or evidence that the two systems are incompatible. We can now report that "thymocyte loss" is a normal process that occurs during the production of DN T-cells. The DN T-cell pathway is unique in that it is mediated by thymic mast cells, and becomes functional following puberty. Sex steroids initiate the development of the pathway by binding to an estrogen receptor alpha located in the outer membrane of the mast cells, causing their activation. This results in their uptake of extracellular calcium, and the production and subsequent release of histamine and serotonin. Lymphatic vessels, located in the subcapsular region of the thymus, respond to the two vasodilators by undergoing a substantial and preferential uptake of gamma/delta and alpha/beta DN T- cells. These T- cells exit the thymus via efferent lymphatic vessels and enter the lymphatic system.The DN pathway is responsible for the production of three subsets of gamma/delta DN T-cells and one subset of alpha/beta DN T-cells. In postpubertal animals approximately 35 % of total thymocytes exit the thymus as DN T-cells, regardless of sex. In pregnant females, their levels undergo a dramatic increase. Gamma/delta DN T-cells produce cytokines that are essential for the maintenance of pregnancy.

Interactions between water temperature and contaminant toxicity to freshwater fish.

Warming of freshwaters as a result of climate change is expected to have complex interactions with the toxicity of contaminants to aquatic organisms. The present study evaluated the effects of temperature on the acute toxicity of endosulfan, chlorpyrifos, and phenol to 3 warm water species of fish-silver perch, rainbowfish, and western carp gudgeon-and 1 cold water species, rainbow trout. Endosulfan was more toxic to silver perch at 30 °C and 35 °C than at 15 °C, 20 °C and 25 °C during short exposures of 24 h, but at 96 h, temperature had no effect on toxicity. Toxicity to rainbow trout increased with increasing temperature, whereas warm water species exhibited maximum toxicity at around 30 °C, decreasing again toward 35 °C. Chlorpyrifos became more toxic to all species with increasing temperature. Phenol toxicity to all species decreased at low to intermediate temperatures; but as temperatures increased further toward the upper thermal limit, phenol became more toxic. Increasing toxicity in the upper thermal range of cold water species may contribute to upstream range contraction in rivers with high toxicant loads. In contrast, warm water species may not exhibit a range shift within rivers as a result of interactions between temperature and toxicity. Catchment management to offset global warming at local scales may present opportunities to mitigate increased toxicity of contaminants to fish.

Co-treatment with the non-steroidal anti-androgen drug, flutamide and the natural estrogen, 17ß-estradiol does not lead to additive reproductive impairment in juvenile Murray rainbowfish (Melanotaenia fluviatilis).

The aim of this study was to investigate if the anti-androgen, flutamide, and the estrogen, 17ß-estradiol work together to feminize juvenile Murray rainbowfish (Melanotaenia fluviatilis). Fish (60 days post-hatch) were exposed to 25 ng/L 17ß-estradiol (E2), 25 µg/L flutamide (Flu low), 250 µg/L flutamide (Flu high), E2 + Flu low and E2 + Flu high. After 35 days of exposure, concentrations of sex steroid hormones, 17ß-estradiol and 11-keto testosterone (11-KT), were determined in the head; and vitellogenin (VTG) concentration was measured in the tail. The abdomens were used for histological investigation of the gonads. Treatment with E2 + Flu high resulted in reduction in body weights and lengths in males and condition factor in females. Intersex was noted in Flu high and E2 + Flu high treatments. Exposures to E2 and/or Flu (low and high) resulted in precocious oocyte development but inhibited sperm development. The 17ß-estradiol levels decreased significantly in the heads of both sexes after exposures to E2 and/or Flu (high and low). Flu high and E2 alone increased the 11-KT levels in both sexes. However, E2 + Flu low decreased 11-KT levels in males and increased them in females. Flutamide (low and high) induced VTG protein in the tails of both sexes. In males, VTG was not induced in the tail after exposure to E2. No significant effect of flutamide on E2-induced VTG concentration was noted. We conclude that co-treatment with flutamide and 17ß-estradiol does not lead to additive reproductive impairment in juvenile Murray rainbowfish.

Long-term exposures to di-n-butyl phthalate inhibit body growth and impair gonad development in juvenile Murray rainbowfish (Melanotaenia fluviatilis).

The aim of the present study was to evaluate whether long-term exposures to environmentally relevant concentrations of di-n-butyl phthalate (DnBP) disrupt the reproduction-based endpoints in juvenile Murray rainbowfish (Melanotaenia fluviatilis). Fish were exposed to 5, 15 or 50 µg l(-1) DnBP for 30, 60 and 90 days each, and the effects on survival, body growth, whole-body concentrations of sex steroid hormones and gonadal development were investigated. The lowest observed effective concentration to affect the condition factor after 90 days was 5 µg l(-1). Complete feminization of the gonad was noted in fish exposed to 5 µg l(-1) for 90 days and to 15 and 50 µg l(-1) of DnBP for 30 or 60 days. After 90 days of exposure to DnBP, the ovaries were regressed and immature as opposed to the control fish which were in early-vitellogenic stage. Testes, present only in fish exposed to 5 µg l(-1) of DnBP for 30 or 60 days, were immature in comparison to the control fish that contained testes in the mid-spermatogenic phase. The E2/11-KT ratio was significantly higher only after exposures to 5 µg l(-1) DnBP for 90 days and 50 µg l(-1) DnBP for 30 days. Our data suggest that exposures to 5 µg l(-1) DnBP for 30 days did not have profound effects on body growth and gonadal differentiation of fish. However, 30 days of exposure to 15 µg l(-1) could interfere with the gonad development and to 50 µg l(-1) could compromise the hormonal profile of juvenile fish.

Effects of short-term exposure to the model anti-androgen, flutamide on reproductive function based endpoints in female Murray rainbowfish (Melanotaenia fluviatilis).

The aim of the present study was to evaluate the responses of female Murray rainbowfish (Melanotaenia fluviatilis) to the model anti-androgen, flutamide in a short-term exposure. Adult female Murray rainbowfish were exposed to nominal (measured) concentrations of 125 (104), 250 (163), 500 (378) and 1000 (769) µg/L of flutamide for seven days in a semi-static set-up. Plasma vitellogenin (VTG), 11-keto testosterone (11-KT) and 17ß-estradiol (E2) concentrations, brain aromatase activity and ovarian histology were assessed following the exposure. No treatment-related mortality was found in rainbowfish and there was no effect of flutamide on the developmental stage of the ovaries. Histological investigation revealed absence of mature oocytes in flutamide-treated fish. In addition, a significant reduction in the sizes of the vitellogenic oocytes was found after treatment with 500 and 1000 µg/L flutamide. The circulating levels of VTG and the activity of aromatase in the brain were also significantly reduced in fish treated with 500 and 1000 µg/L flutamide. Treatment with higher concentrations of flutamide reduced the levels of 11-KT and E2 in plasma. The results from this study demonstrate that a short-term exposure to the model anti-androgen, flutamide can adversely affect the reproductive function based on end-points such as plasma VTG, 11-KT and E2; brain aromatase activity and sizes of the oocytes in female Murray rainbowfish. Further, a positive correlation between these experimental variables suggests hormonal imbalance.

Assessing levels of halogenated organic compounds in mass-stranded long-finned pilot whales (Globicephala melas) from Australia.

Pollution is a threat to the health of marine mammals worldwide. Mass-strandings are poorly understood, but often involve pilot whales. However, there is limited information regarding pollution in long-finned pilot whales from Australia. Consequently, the profiles and levels of several pollutant classes were investigated in blubber of Tasmanian long-finned pilot whales. DDX levels were highest in all groups, followed by PCBs or MeO-PBDEs and lowest for PBDEs. The concentrations of all pollutants decreased with age in males. This is at least partly due to the growth dilution effect although it might also be caused by decreasing levels of PCBs, PBDEs, DDXs, HCB and CHLs in the environment. Fetus/mother ratios of higher chlorinated PCBs increased with the duration of pregnancy suggesting a preference for offloading via gestation rather than through lactation. Overall, the highest pollutant levels were found in the youngest animals.

Arginine and citrulline protect intestinal cell monolayer tight junctions from hypoxia-induced injury in piglets.

BACKGROUND: Arginine (Arg) is deficient in the serum of the preterm neonate and is lower in those developing intestinal ischemia. We investigated whether Arg or its precursor, citrulline (Cit), protects intestinal tight junctions (TJs) from hypoxia (HX) and determined whether inducible nitric oxide (NO) plays a role. METHODS: Neonatal piglet jejunal IPEC-J2 cell monolayers were treated with Arg or Cit, reversible and irreversible NO synthetase (NOS) inhibitors, and were exposed to HX. TJs were assessed by serial measurements of transepithelial electrical resistance (TEER), flux of inulin-fluorescein isothiocyanate, and immunofluorescent staining of TJ proteins. RESULTS: We found that Arg and Cit were protective against HX-related damage. At the final time point (14 h), the mean TEER ratio (TEER as compared with baseline) for Arg + HX and Cit + HX was significantly higher than that for HX alone. Both Arg and Cit were associated with decreased inulin flux across hypoxic monolayers and qualitatively preserved TJ proteins. Irreversible inhibition of NOS blocked this protective effect. Lipid peroxidation assay showed that our model did not produce oxidant injury. CONCLUSION: Arg and Cit, via a mechanism dependent on NO donation, protected intestinal epithelial integrity.

Tinea capitis caused by dermatophytes: a 15-year retrospective study from a Mississippi Dermatology Clinic.

Tinea capitis is a highly contagious disorder occurring predominantly in children. Presentation is variable and, as such, mycologic confirmation of dermatophyte infection would be useful in targeting specific therapy and implementing preventive measures to interrupt spread of infection. This retrospective study was performed at an outpatient dermatology clinic in Jackson, Mississippi, over a 15-year period (1983-1998). Dermatophyte infections were confirmed using scalp scrapings cultured on Mycosel Agar containing cycloheximide and chloramphenicol. Cultures were performed on 1220 patients of all ages presenting with signs and symptoms suggestive of tinea capitis. Of the total patients meeting the inclusion criteria, 66% were younger than 13 years. Overall, 39% (478/1220) had positive cultures for dermatophytes, with black individuals having the highest percentage of positive cultures (87% [414/478]). In addition to a review of findings, we examine the impact of a cultural diagnosis of dermatophyte infection on the treatment and prevention of this highly contagious infection.

Benthic macroinvertebrate assemblages in remediated wetlands around Sydney, Australia.

To investigate potential high organisational level impacts of persistent organic pollution in the wetlands in the Sydney Olympic Park (SOP) remediated site, the benthic macroinvertebrate assemblages of seven wetlands within SOP and two off-site reference wetlands were examined. Sediment cores were collected, stained and preserved from each study site and the macroinvertebrates identified to the appropriate taxonomic level (Class, Order, Family, Subfamily). Data were analysed for taxon richness and macroinvertebrate abundance and multivariate techniques were used to identify chemical/physical characteristics of the sediment, which were important influences on the differences in the assemblage between study sites. Macroinvertebrate abundance was highly variable between study sites and taxon richness was low across all sites. Oligochaetes, nematodes, ostracods and chironomids were the most common taxa found and were the most important in influencing differences between the macroinvertebrate assemblages among the study sites. Sediment grain size and chemical characteristics of the sediments (ΣPAH, ΣPCB, TCDDeq and heavy metal concentrations) were important in separating the study sites based on taxon richness and abundance. Canonical correspondence analysis separated the macroinvertebrate assemblages at newly two created wetlands from those at other study sites including the urban reference sites. Increased sediment POP contamination (particularly as measured TCDDeq and ΣDDT concentrations) is a likely contributor in excluding pollution sensitive taxa and, therefore, alterations to benthic macroinvertebrate assemblages. Further, the influence of TOC suggests the significance of catchment inputs in contributing to changes in macroinvertebrate assemblage. The SOP remediation led to the establishment of wetlands with benthic communities representative of those expected in urban wetlands.

Distribution of inorganic and organic contaminants in sediments from Sydney Olympic Park and the surrounding Sydney metropolitan area.

Organic and inorganic contamination was assessed for sediments from wetlands and water bodies within the Sydney Olympic Park (SOP, remediated sites) and its surroundings (unremediated sites) and urban reference sites in the Sydney Basin. Among the seven elements analysed (As, Cd, Cr, Cu, Pb, Ni and Zn), Zn concentrations were the highest, followed by Pb, Cu and Cr in the sediments of SOP. Significantly higher concentrations (p < 0.05) of DDTs were found in sediments of the Homebush Bay and Parramatta River sites compared with the urban reference sites, mainly due to past manufacturing of DDT in the Homebush Bay area. However, no significant differences (p > 0.05) in concentrations were found for polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) as well as DDTs between sediments from SOP and the urban reference sites. Source indicators suggest that PAHs in the sediments originated from combustion processes. Two distinct groups of dioxin profiles were observed within SOP and its surroundings. Levels of dioxins were more than 100 pg WHO-TEQ/g dry weight of sediment at five sites adjacent to the SOP boundaries. Based on the findings of the chemical profiles of the contaminants, the remediated sites in SOP can be regarded as similar to the urban reference sites within the Sydney Basin, while the adjacent unremediated sites have higher concentrations, especially of dioxins, that could still affect organisms in the aquatic environment.

Contamination and screening level toxicity of sediments from remediated and unremediated wetlands near Sydney, Australia.

The present study assessed contamination and toxicity of sediments from seven remediated and remnant wetland sites within Sydney Olympic Park, Australia, and four unremediated sites adjacent to its boundary using chemical analysis and a luminescent bacterial biosensor assay (Escherichia coli). Concentrations of metals (Pb, Cr, Cu, Ni, Zn, Cd, and As) and persistent organic chemicals (DDT and its metabolites, dichlorodiphenyldichloroethane and dichlorodiphenyldichloroethylene; polycyclic aromatic hydrocarbons; polychlorinated biphenyls; and polychlorinated dibenzo-p-dioxins and dibenzofurans) in sediments and their pore-water samples were determined. Zinc concentrations were the highest of the metals in the sediments (84-618 mg/kg), and at eight sites, metal concentrations in sediments exceeded the Australian ecological trigger values for Pb, Zn, and Ni. Concentrations of organic contaminants in the sediments exceeded the trigger values at all 11 sites for DDTs, at 6 sites for polycyclic aromatic hydrocarbons, and 5 sites for polychlorinated biphenyls. Sediment samples from the four unremediated sites outside the Sydney Olympic Park had dioxin concentrations greater than 200 pg (toxic equivalency per gram). The same four sites were identified as contaminated in pore-water toxicity tests with the luminescent biosensor, generally consistent with the bioavailable fractions of the contaminants (pore-water and Tenax extraction data), as well as dioxin levels, in the sediments. Preliminary toxicity identification and evaluation tests of the pore water from the four sites outside the park demonstrated that organic contaminants were the main cause of toxicity to E. coli, with no evidence that metals contributed to the toxicity of the pore water.

Effects of temperature on ventilatory behavior of fish exposed to sublethal concentrations of endosulfan and chlorpyrifos.

The ventilation amplitude and frequency of silver perch Bidyanus bidyanus, and the ventilation frequency of rainbow fish Melanotaenia duboulayi and rainbow trout Oncorhynchus mykiss, were determined at different temperatures upon exposure to endosulfan and chlorpyrifos, respectively. Silver perch and rainbow fish were tested at 15, 20, 25, 30, and 35 degrees C, while rainbow trout was tested at 10, 15, 20, and 25 degrees C. Although some trend of increasing amplitudes with increasing temperature was evident; there was no significant temperature response of ventilation frequency rates over time in silver perch pre-exposed to 10 microg L(-1) endosulfan for 18 h. The rate of ventilation frequency of rainbow fish pre-exposed to 200 microg L(-1) of chlorpyrifos for 96 h was lower in treatments than in the control at 15 degrees C. However, between 20 and 35 degrees C, rates were significantly higher in the treatments than those of the control. In rainbow trout pre-exposed to 100 microg L(-1) of chlorpyrifos, the rates of frequency were significantly lower than those of controls in temperatures between 10 and 20 degrees C but higher at 25 degrees C. The amplitude of silver perch seemed to increase with the increase in temperature; however, the corresponding temperature quotient values at various temperature regimes and over exposure time showed no significant differences. The ventilation frequency of rainbow fish and rainbow trout significantly increased at the higher test temperatures, and their corresponding temperature quotient values for both fish also increased at the elevated temperatures.

The estrogen-injected female mouse: new insight into the etiology of PCOS.

BACKGROUND: Female mice and rats injected with estrogen perinatally become anovulatory and develop follicular cysts. The current consensus is that this adverse response to estrogen involves the hypothalamus and occurs because of an estrogen-induced alteration in the GnRH delivery system. Whether or not this is true has yet to be firmly established. The present study examined an alternate possibility in which anovulation and cyst development occurs through an estrogen-induced disruption in the immune system, achieved through the intermediation of the thymus gland. METHODS, RESULTS AND CONCLUSION: A putative role for the thymus in estrogen-induced anovulation and follicular cyst formation (a model of PCOS) was examined in female mice by removing the gland prior to estrogen injection. Whereas all intact, female mice injected with 20 microg estrogen at 5-7 days of age had ovaries with follicular cysts, no cysts were observed in animals in which thymectomy at 3 days of age preceded estrogen injection. In fact, after restoring immune function by thymocyte replacement, the majority of thymectomized, estrogen-injected mice had ovaries with corpora lutea. Thus, when estrogen is unable to act on the thymus, ovulation occurs and follicular cysts do not develop. This implicates the thymus in the cysts' genesis and discounts the role of the hypothalamus. Subsequent research established that the disease is transferable by lymphocyte infusion. Transfer took place between 100-day-old estrogen-injected and 15-day-old naïve mice only when recipients were thymectomized at 3 days of age. Thus, a prerequisite for cyst formation is the absence of regulatory T cells. Their absence in donor mice was judged to be the result of an estrogen-induced increase in the thymus' vascular permeability, causing de facto circumvention of the final stages of regulatory T cell development. The human thymus has a similar vulnerability to steroid action during the fetal stage. We propose that in utero exposure to excessive levels of steroids such as estrogen has a long-term effect on the ability of the thymus to produce regulatory T cells. In female offspring this can lead to PCOS.

Bioactivity of POPs and their effects in mosquitofish in Sydney Olympic Park, Australia.

The site of the 2000 Olympic Games (Sydney Olympic Park (SOP), Sydney, Australia) was contaminated by persistent organic pollutants (POPs) prior to remediation in the 1990s. This study investigates the bioactivity of POPs in the sediment and water of wetlands across SOP by in vitro 2,3,7,8-TCDD equivalence (TCDDeq) measurement (H4IIE cell line bioassay). Further, it examines whether disturbance of these sediments is likely to mobilise ligands for this receptor into the water column. Exposure to aryl hydrocarbon receptor (AhR) ligands was measured in vivo using hepatic cytochrome P4501A (CYP1A) induction (EROD) in the mosquitofish (Gambusia holbrooki). Aqueous TCDDeq ranged from 0.013 to 0.057 pM in SOP wetlands which was significantly (p<0.05) less that in urban reference sites. These concentrations were not correlated to physical or chemical characteristics of the wetlands. In the sediments, TCDDeq ranged from 0.0016 to 7.06 microg/kg and these were not significantly (p>or=0.05) different to that measured in urban reference sites. Simulated disturbance of small quantities of sediment in water samples significantly (p<0.05) increased the levels of TCDDeq measured in the water. Sediment TCDDeq was correlated to sediment SigmaPAH concentration in 2006 and sediment SigmaPCB, SigmaDDT concentrations and fine sediment grain size in 2005. While fish at one SOP wetland had hepatic EROD activity elevated above the estimated basal level for this species, these were at the lower end of the range measured in urban impacted, non-remediated wetlands. EROD activity was positively correlated with both the sediment SigmaPCB load and aqueous TCDDeq. Increased catchment size was correlated with increased EROD activity suggesting an even spread of POPs throughout the residential areas of the Sydney metropolitan area. The concentration of bioactive POPs in the wetlands of SOP is therefore low relative to urban reference sites demonstrating the ongoing success of the remediation program.

The effects of three organic chemicals on the upper thermal tolerances of four freshwater fishes.

The upper temperature tolerance limits of four freshwater fish species, silver perch Bidyanus bidyanus, eastern rainbowfish Melanotaenia duboulayi, western carp gudgeon Hypseleotris klunzingeri, and rainbow trout Oncorhynchus mykiss, were determined using the critical thermal maximum (CTMaximum) method. The CTMaximum tests were carried out with unexposed fish and fish exposed to sublethal concentrations of endosulfan, chlorpyrifos, and phenol to determine whether or not the CTMaximum was affected. The CTMaximum temperature of B. bidyanus decreased by 2.8, 3.8, and 0.3 degrees C on exposure to endosulfan, chlorpyrifos, and phenol, respectively. Similarly, in M. duboulayi, the CTMaximum was decreased by 4.1, 2.5, and 0 degrees C, while in H. klunzingeri it decreased by 3.1, 4.3, and 0.1degrees C, respectively, and in O. mykiss by 4.8, 5.9, and 0.7 degrees C, respectively. Exposure to sublethal test concentrations of endosulfan and chlorpyrifos caused significant (p < or = 0.0001) reductions in CTMaximum values for all fish species compared to that of unexposed fish. However, exposure to phenol did not cause any significant (p > or = 0.05) change of CTMaximum temperatures.