Perfluorononanoic acid (PFNA) is a ubiquitous and persistent environmental contaminant. Although its levels in the environment and in humans are lower than those of perfluorooctane sulfonate (PFOS) or perfluorooctanoic acid (PFOA), a steady trend of increases in the general population in recent years has drawn considerable interest and concern. Previous studies with PFOS and PFOA have indicated developmental toxicity in laboratory rodent models. The current study extends the evaluation of these adverse outcomes to PFNA in mice. PFNA was given to timed-pregnant CD-1 mice by oral gavage daily on gestational day 1-17 at 1, 3, 5 or 10mg/kg; controls received water vehicle. Dams given 10mg/kg PFNA could not carry their pregnancy successfully and effects of this dose group were not followed. Similar to PFOS and PFOA, PFNA at 5mg/kg or lower doses produced hepatomegaly in the pregnant dams, but did not affect the number of implantations, fetal viability, or fetal weight. Mouse pups were born alive and postnatal survival in the 1 and 3mg/kg PFNA groups was not different from that in controls. In contrast, although most of the pups were also born alive in the 5mg/kg PFNA group, 80% of these neonates died in the first 10 days of life. The pattern of PFNA-induced neonatal death differed somewhat from those elicited by PFOS or PFOA. A majority of the PFNA-exposed pups survived a few days longer after birth than those exposed to PFOS or PFOA, which typically died within the first 2 days of postnatal life. Surviving neonates exposed to PFNA exhibited dose-dependent delays in eye opening and onset of puberty. In addition, increased liver weight seen in PFNA-exposed offspring persisted into adulthood and was likely related to the persistence of the chemical in the tissue. Evaluation of gene expression in fetal and neonatal livers revealed robust activation of peroxisome proliferator-activated receptor-alpha (PPARα) target genes by PFNA that resembled the responses of PFOA. Our results indicate that developmental toxicity of PFNA in mice is comparable to that of PFOS and PFOA, and that these adverse effects are likely common to perfluoroalkyl acids that persist in the body.

Adverse intrauterine environments have been associated with increased risk of later cardiovascular disease and hypertension. In an animal model using diverse developmental toxicants, we measured blood pressure (BP), renal nephron endowment, renal glucocorticoid receptor (GR) gene expression, and serum aldosterone in offspring of pregnant Sprague Dawley rats exposed to dexamethasone (Dex), perfluorooctane sulfonate (PFOS), atrazine, perfluorononanoic acid (PFNA), arsenic, or nicotine. BP was assessed by tail cuff photoplethysmography, nephron endowment by confocal microscopy, and renal GR mRNA by qPCR. BP was also measured by telemetry, and corticosterone (CORT) was measured in resting or restrained Dex and atrazine offspring. Treated dams gained less weight during treatment in all groups except arsenic. There were chemical- and sex-specific effects on birth weight, but offspring body weights were similar by weaning. BP was higher in Dex, PFOS, atrazine, and PFNA male offspring by 710 weeks. Female offspring exhibited elevated BP at 10 weeks for PFNA and arsenic, and at 37 weeks for Dex, PFOS, and atrazine. Dex, PFOS, and atrazine offspring still exhibited elevated BP at 5265 weeks of age; others did not. Elevated BP was associated with lower nephron counts. Dex, PFOS, and atrazine offspring had elevated renal GR gene expression. Elevations in BP were also observed in Dex and atrazine offspring by radiotelemetry. Atrazine offspring exhibited enhanced CORT response to restraint. Elevated offspring BP was induced by maternal exposure to toxicants. Because all treatments affected maternal gestational weight gain, maternal stress may be a common underlying factor in these observations.

The exponential rise in people living longer but requiring residential care is adding pressure to already overstretched aged care nurses. Consequently, a person-centred care culture in residential care remains aspirational, rather than a reality. For nursing students in Australia and elsewhere, clinical placements in aged care facilities are under-utilised due to negative perceptions about the likelihood for learning. Creative strategies to engage students to safely challenge ageist thinking and to inspire enthusiasm for learning in this context are needed.The purpose of this thematic review of the literature is to better understand challenges related to learning in aged care settings and identify innovative strategies to enhance nursing student learning experiences in residential aged care placements.A literature review was undertaken in 2019 using CINAHL, PUBMED, Elsevier, Medline, ProQuest and Google Scholar. The search was limited to papers that were peer reviewed, in English, and published between 2001 and the date of review (mid-2019) in order to situate the review in the new millennium.47 articles and books were included in the review that introduce solutions and innovative strategies that could be used to improve students' attitudes to learning in aged care and from older people. The literature review was categorized into three main themes, including: barriers to working with older people; the need for pedagogical change to foster empathy; and innovative strategies to address barriers.These themes are useful to consider in designing engaging learning and teaching for nursing students to be effective in working in aged care.

Parent polychlorinated biphenyls (PCBs) have been shown to induce cellular oxidative stress. However, the effects of PCB active metabolites have not been extensively investigated. Parent PCBs are first converted to hydroquinone metabolites via cytochrome P-450-catalyzed hydroxylation, and the hydroquinone metabolites are then further oxidized into the corresponding quinone metabolites. Quinones are responsible for a wide range of toxic effects because of their high reactivity. Previous studies have suggested that reactive oxygen species (ROS) play important roles in multiple toxic mechanisms. In this context, the present study was undertaken to investigate oxidative stress resulting from treatment with PCB quinones in HepG2 cells. The protective effects resulting from co-administration of dihydrolipoic acid (DH-LA) were also investigated. We have found that exposure to PCB quinones leads to: (1) a decrease in cell viability; (2) an increase in both the total ROS production and superoxide production; (3) only 3Cl-PCBQ caused significant increase in the thiobarbituric acid reactive substances (TBARS) level; (4) an increase in SOD activity and a decrease in catalase activity; and (5) a decrease in GST activity and GSH level. We have also found that quinones possessing a higher number of chlorine atoms on the quinone ring display a greater activity and that DH-LA is an effective protective agent as it diminishes PCB quinone-induced cellular oxidative stress.

BACKGROUNDBirth weight in humans has been inversely associated with adult disease risk. Results of animal studies have varied depending on species, strain, and treatment.METHODSWe compared birth weight and adult health in offspring following 50% maternal undernutrition on gestation days (GD) 1-15 (UN1-15) or GD 10-21 (UN10-21) in Sprague Dawley and Wistar rats. Offspring from food-deprived dams were weighed and cross-fostered to control dams. Litters were weighed during lactation and initiating at weaning males were fed either control or a high-fat diet. Young and mature adult offspring were evaluated for obesity, blood pressure (BP), insulin response to oral glucose, and serum lipids. Nephron endowment, renal glucocorticoid receptor, and renin-aldosterone-angiotensin system components were measured.RESULTSThe UN10-21 groups had birth weights lower than controls and transient catch up growth by weaning. Neither strain demonstrated obesity or dyslipidemia following prenatal undernutrition, but long-term body weight deficits occurred in the UN groups of both strains. High-fat diet fed offspring gained more weight than control offspring without an effect of prenatal nutrition. Sprague Dawley were slightly more susceptible than Wistar rats to altered insulin response and increased BP following gestational undernutrition. Nephron endowment in Sprague Dawley but not Wistar offspring was lower in the UN10-21 groups. Glucocorticoid and renin-aldosterone-angiotensin system pathways were not altered.CONCLUSIONSThe most consistent effect of maternal undernutrition was elevated BP in offspring. Long-term health effects occurred with undernutrition during either window, but the UN10-21 period resulted in lower birth weight and more severe adult health effects.

p,p′-Dichlordiphenyldichloroethylene (DDE) is a metabolite of the insecticide dichlorodiphenyltrichloroethane (DDT), an organochloride which was massively used from its discovery in 1939 until the early 1970's. Due to the tremendous half-life of DDT and DDE, both substances are to date environmentally relevant. Furthermore, DDT is still employed in many African countries in the context of the WHO's antimalaria campaign. In amphibians, DDE was found to act as antiandrogenic endocrine disrupting chemical (EDC), whereas in other species DDE was found to act as an estrogen. To determine the mode of action (MOA) of DDE in adult male Xenopus laevis, we exposed adult male frogs to different concentrations of DDE, as well as to the estrogenic EDC ethinylestradiol (EE2) and the antiandrogenic fungicide vinclozolin (VIN) for four consecutive nights. We then analyzed the mate calling behavior, which was previously shown to be affected by (anti)androgenic and (anti)estrogenic EDC in a MOA-specific manner, in order to assess whether DDE exposure results in estrogen-specific or antiandrogen-specific alterations of the mate calling behavior. Our results demonstrate that DDE alters the reproductive behavior of male X. laevis. Lowered sexual arousal of exposed males was indicated by a decreased production of advertisement calls and higher amounts of calls that suggest a sexually unaroused state of the males. Our results further indicate that DDE can display both, estrogenic and antiandrogenic MOA, either of which can have adverse effects on reproductive physiology and behavior in X. laevis. The disruption of the affected mating behavior, which is crucial for a successful reproduction, might result in a reduced reproductive success of DDE exposed animals.

Prenatal chemical exposure has frequently been associated with reduced fetal growth although results have been inconsistent. Most studies associate single pollutant exposure to this health outcome, even though this does not reflect real life situations as humans are exposed to many pollutants during their life time. The objective of this study is to investigate the association between prenatal exposure to a mixture of persistent environmental chemicals and birth weight using multipollutant models.We combined exposure biomarker data measured in cord blood samples of 1579 women from four Flemish birth cohorts collected over a 10 years’ time period. The common set of available and detectable exposure measures in these cohorts are three polychlorinated biphenyls (PCB) congeners (138, 153 and 180), hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (p,p’-DDE) and the metals cadmium and lead. Multiple linear regression (MLR), Bayesian Information Criterion (BIC), penalized regression using minimax concave penalty (MCP) and Bayesian Adaptive Sampling (BAS) were applied to assess the influence of multiple pollutants in a single analysis on birth weight, adjusted for a priori selected covariates.In the pooled dataset, a median (P25-P75) birth weight and gestational age of 3420 (3140–3700) grams and 39 (39–40) weeks was observed respectively. The median contaminant levels in cord blood were: 15.8, 26.5, 18.0, 16.9 and 91.5 ng/g lipid for PCB 138, PCB 153, PCB 180, HCB and p,p’-DDE, respectively, 0.075 µg/L for cadmium and 9.7 µg/L for lead. According to the applied statistical methods for multipollutant assessment, p,p’-DDE and PCB 180 were most consistently associated with birth weight. In addition, PCB 153 was selected when applying MCP and BAS. An inverse association with birth weight was found for the PCB congeners, while an increased birth weight was observed for elevated levels of p,p’-DDE.Assessing the health risk of combinations of exposure biomarkers reflects better real-world situations and thereby allows more effective risk assessment. Our results add to the existing evidence based on detrimental effects of PCBs on birth weight and indicate a possible increase in birth weight due to p,p’-DDE (while correcting for PCBs).

Perfluorobutyrate (PFBA) is a perfluoroalkyl acid (PFAA) found in the environment. Previous studies have indicated developmental toxicity of PFAAs (perfluorooctane sulfonate [PFOS] and perfluorooctanoate [PFOA]); the current study examines that of PFBA. PFBA/NH4(+) was given to timed-pregnant CD-1 mice by oral gavage daily from gestational day (GD) 1 to 17 at 35, 175, or 350 mg/kg (chosen to approximate the developmentally toxic doses of PFOA); controls received water. At GD 18, serum levels of PFBA were 3.8, 4.4, and 2.5 microg/ml, respectively, in the three treated groups. PFBA did not significantly affect maternal weight gain, number of implantations, fetal viability, fetus weight, or incidence of fetal malformations. Incidence of full-litter loss was significantly greater in the 350 mg/kg group, and maternal liver weights were significantly increased in the 175 and 350 mg/kg groups. In contrast to PFOA and PFOS, PFBA exposure during pregnancy did not adversely affect neonatal survival or postnatal growth. Liver enlargement was detected in the PFBA-exposed pups on postnatal day (PD) 1, but not by PD 10. Expression of selected hepatic genes in PFBA-exposed pups at PD 1 did not reveal any significant changes from controls. A significant delay in eye-opening in offspring was detected in all three PFBA groups, and slight delays in the onset of puberty were noted in the 175 and 350 mg/kg groups. These data suggest that exposure to PFBA during pregnancy in the mouse did not produce developmental toxicity comparable to that observed with PFOA, in part, due to rapid elimination of the chemical.

Clinical genetics, a board-certified specialty, is now fully integrated into medical practice. Rapid advances in this field have been translated and transferred almost instantly, via the media, into the public domain. Not unexpectedly, the informed public (often prematurely) have developed immediate expectations of benefitting from these new developments. Hence, physicians are expected to be sufficiently well informed and up-to-date to provide or to refer for appropriate genetic counseling, evaluation, or laboratory testing. Certainly, genetic considerations are necessary in every family.Genetics has a role in virtually every disorder, in causation, predisposition and susceptibility, immune response, modulation, or reaction to medical treatment. It is estimated that each of us carries at least 20 harmful genes. About 1 in 13 conceptions results in a conceptus with a chromosome abnormality,50 whereas about 50% of first-trimester spontaneous abortions are associated with such defects.7 Clinically significant chromosomal defects occur in 0.65% of all births, an additional 0.2% being born with balanced structural chromosome rearrangements that have implications for reproduction later in life. Between 5.6% and 11.5% of stillbirths and neonatal deaths are associated with chromosome defects.2 Three percent to four percent of all births are associated with a major congenital malformation, mental retardation, or genetic disorder, a rate that doubles by 7 to 8 years of age, given later-appearing or later-diagnosed genetic disorders.44Genetic counseling is a communication process concerning the occurrence and the risks of recurrence of genetic disorders within a family. Such counseling aims to provide the patient with a clear and comprehensive understanding of all the important implications and possible options of the disorder in question, to facilitate rational decision making.44 The basis and guidelines for genetic counseling have been extensively reviewed and are not covered here.43, 44 Indications for genetic counseling are summarized below: 1Advanced maternal age2Abnormal maternal serum triple screen3Abnormal ultrasound evaluation during pregnancy4A previous fetus or child with a genetic disorder or congenital defect5Parent with a genetic disorder6Family history of a specific genetic disorder7A maternal disorder with or without specific drug treatment associated with an increased risk of congenital defects8A maternal disorder in which pregnancy could threaten maternal or fetal life or health9Known or possible carriers of specific harmful genes (including ethnic-related disorders)10Exposure to teratogenic drugs, infections, x-rays, toxins, or occupational hazards during or before pregnancy11Known or suspected consanguinity12Consideration of presymptomatic/predictive laboratory testingPreconception care and counseling, with appropriate anticipatory guidance, is important in the identification of risk factors, disease states, and potential teratogens, and prompts the offering of carrier and prenatal diagnostic testing. The availability of first-trimester prenatal diagnosis and the advent of presymptomatic diagnosis by DNA analysis has created increasing opportunities to avoid disorders characterized by early death, severe disease, or irreparable mental retardation. Periconceptional maternal folic acid supplementation has now been shown conclusively to provide a high protective effect against neural tube defects.38, 41Certain maternal disease states, including diabetes, lupus, and myotonic muscular dystrophy, impose their own specific potential maternal, fetal, neonatal, and other complications. So far as pregnancy and fetal defects are concerned, the preconception visit provides important opportunities for intervention, avoidance, or prevention. The patients' ethnicity and medical and genetic family history are key elements in this evaluation. Patients with prolonged infertility of unknown cause or recurrent spontaneous abortion, who may have a 3% to 10% risk of a parental chromosome abnormality,55, 60 require chromosome analysis, as do their spouses. Virtually all ethnic groups carry some “genetic burden.”40 For example, whites have a risk of about 1 in 25 for carrying the gene for cystic fibrosis (CF). Ashkenazi Jews have a risk of about 1 in 30 for carrying the gene for Tay-Sachs disease and a risk of about 1 in 12 for carrying the gene for Gaucher's disease.DNA testing for carrier states are now readily available at major diagnostic centers. These relatively inexpensive and accurate tests enable more precise genetic counseling, information that becomes important for those who might select prenatal diagnosis as an option, or for couples who prefer to avoid the possibilities of abortion and prefer artificial insemination from a donor known not to carry that specific gene. In the future, preimplantation diagnosis may require discussion during the preconception visit, because technically this now is a reality. With the traditional modes of inheritance come several nontraditional modes and mechanisms of inheritance that often pose complex issues in genetic counseling.

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were euthanized on GD 21 and mice on GD 18. PFOS levels in maternal serum and in maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately fourfold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high-dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects, including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium, were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.

The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS, C8F17SO3-) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated with 1, 5, 10, 15, and 20 mg/kg PFOS from GD 1 to GD 18. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. In the highest dosage groups (10 mg/kg for rat and 20 mg/kg for mouse), the neonates became pale, inactive, and moribund within 30-60 min, and all died soon afterward. In the 5 mg/kg (rat) and 15 mg/kg (mouse) dosage groups, the neonates also became moribund but survived for a longer period of time (8-12 h). Over 95% of these animals died within 24 h. Approximately 50% of offspring died at 3 mg/kg for rat and 10 mg/kg for mouse. Cross-fostering the PFOS-exposed rat neonates (5 mg/kg) to control nursing dams failed to improve survival. Serum concentrations of PFOS in newborn rats mirrored the maternal administered dosage and were similar to those in the maternal circulation at GD 21; PFOS levels in the surviving neonates declined in the ensuing days. Small but significant and persistent growth lags were detected in surviving rat and mouse pups exposed to PFOS prenatally, and slight delays in eye opening were noted. Significant increases in liver weight were observed in the PFOS-exposed mouse pups. Serum thyroxine levels were suppressed in the PFOS-treated rat pups, although triiodothyronine and thyroid-stimulating hormone [TSH] levels were not altered. Choline acetyltransferase activity (an enzyme that is sensitive to thyroid status) in the prefrontal cortex of rat pups exposed to PFOS prenatally was slightly reduced, but activity in the hippocampus was not affected. Development of learning, determined by T-maze delayed alternation in weanling rats, was not affected by PFOS exposure. These results indicate that in utero exposure to PFOS severely compromised postnatal survival of neonatal rats and mice, and caused delays in growth and development that were accompanied by hypothyroxinemia in the surviving rat pups.

The critical period for increased neonatal mortality induced by perfluorooctane sulfonate (PFOS) exposure was evaluated in the rat. Timed-pregnant Sprague-Dawley rats were treated by oral gavage with 25 mg/kg/d PFOS/K(+) on four consecutive days (gestation days (GD) 2-5, 6-9, 10-13, 14-17, or 17-20) or with 0, 25, or 50 mg/kg/d PFOS/K(+) on GD 19-20. Controls received vehicle (10 ml/kg 0.5% Tween-20) on these days. Maternal weight gain was reduced in treated animals during dosing, as were food and water consumption. Following a 4-day treatment, litter size at birth was unaffected while pup weight was similarly reduced in the three earliest PFOS groups. All PFOS groups experienced decreases in survival while controls remained near 100%. Neonatal survival decreased in groups dosed later during gestation, approaching 100% with dosing on GD 17-20. Most deaths occurred before postnatal day (PND) 4, with the majority in the first 24 hours. Maternal serum PFOS levels on GD 21 were higher in groups exhibiting higher mortality. Following a 2-day treatment, PFOS groups experienced significant pup mortality by PND 1. Neonatal mortality continued through PND 5, when survival was 98, 66, and 3% for the 0, 25, and 50 mg/kg groups, respectively. Pup weight was reduced in treated groups with surviving litters. Gross dissection and histological examination of lungs revealed differences in maturation between control and treated animals on PND 0. We conclude that exposure to PFOS late in gestation is sufficient to induce 100% pup mortality and that inhibition of lung maturation may be involved.

ABSTRACT The role of the dormant-like viable but nonculturable (VBNC) condition in the etiology of bacterial infection was examined using a plant system. The plant-pathogenic bacterium Ralstonia solanacearum was first shown to enter into the VBNC state both in response to cupric sulfate when in a saline solution and when placed in autoclaved soil. To determine if the VBNC condition is related to pathogenesis, the physiological status of bacteria recovered from different regions of inoculated tomato plants was determined at different stages of infection. The fraction of in planta bacteria that were VBNC increased during infection and became greater than 99% by the late stage of disease. The possibility that soil-dwelling VBNC bacteria may resuscitate and infect plants was also examined. When tomato seeds were germinated in sterile soil that contained VBNC but no detectable culturable forms of R. solanacearumcells, resuscitation was observed to occur in soil adjacent to plant roots; these resuscitated bacteria were able to infect plants. This is the first report of R. solanacearum entering the VBNC state and of resuscitation of any VBNC plant-pathogenic bacteria and provides evidence that the VBNC state may be involved in explaining the persistent nature of some infections.