Immersion of debrided diabetic foot ulcer tissue in electrochemically generated pH neutral hypochlorous acid significantly reduces the microbial bioburden: whole-genome sequencing of Staphylococcus aureus, the most prevalent species recovered.

BACKGROUND: Diabetic foot ulcer infections (DFUIs) are the leading cause of lower-limb amputations, mediated predominantly by Staphylococcus aureus. pH-neutral electrochemically generated hypochlorous acid (anolyte) is a non-toxic, microbiocidal agent with significant potential for wound disinfection. AIMS: To investigate both the effectiveness of anolyte for microbial bioburden reduction in debrided ulcer tissues and the population of resident S. aureus. METHODS: Fifty-one debrided tissues from 30 people with type II diabetes were aliquoted by wet weight and immersed in 1- or 10-mL volumes of anolyte (200 parts per million) or saline for 3 min. Microbial loads recovered were determined in colony forming units/g (cfu/g) of tissue following aerobic, anaerobic and staphylococcal-selective culture. Bacterial species were identified and 50 S. aureus isolates from 30 tissues underwent whole-genome sequencing (WGS). FINDINGS: The ulcers were predominantly superficial, lacking signs of infection (39/51, 76.5%). Of the 42/51 saline-treated tissues yielding ≥105 cfu/g, a microbial threshold reported to impede wound-healing, only 4/42 (9.5%) were clinically diagnosed DFUIs. Microbial loads from anolyte-treated tissues were significantly lower than saline-treated tissues using 1 mL (1065-fold, 2.0 log) and 10 mL (8216-fold, 2.1 log) immersion volumes (P<0.0005). S. aureus was the predominant species recovered (44/51, 86.3%) and 50 isolates underwent WGS. All were meticillin susceptible and comprised 12 sequence types (STs), predominantly ST1, ST5 and ST15. Whole-genome multi-locus sequence typing identified three clusters of closely related isolates from 10 patients indicating inter-patient transmission. CONCLUSIONS: Short immersions of debrided ulcer tissue in anolyte significantly reduced microbial bioburden: a potential novel DFUI treatment.

An emerging Panton-Valentine leukocidin-positive CC5-meticillin-resistant Staphylococcus aureus-IVc clone recovered from hospital and community settings over a 17-year period from 12 countries investigated by whole-genome sequencing.

BACKGROUND: A novel Panton-Valentine leukocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA) clonal complex (CC)5-MRSA-IVc ('Sri Lankan' clone) was recently described from Sri Lanka. Similar isolates caused a recent Irish hospital outbreak. AIM: To investigate the international dissemination and diversity of PVL-positive CC5-MRSA-IVc isolates from hospital and community settings using whole-genome sequencing (WGS). METHODS: Core-genome single nucleotide polymorphism (cgSNP) analysis, core-genome multi-locus sequence typing (cgMLST) and microarray-based detection of antimicrobial-resistance and virulence genes were used to investigate PVL-positive CC5-MRSA-IVc (N = 214 including 46 'Sri Lankan' clone) from hospital and community settings in 12 countries over 17 years. Comparators included 29 PVL-positive and 23 PVL-negative CC5/ST5-MRSA-I/II/IVa/IVc/IVg/V. RESULTS: Maximum-likelihood cgSNP analysis grouped 209/214 (97.7%) CC5-MRSA-IVc into Clade I; average of 110 cgSNPs between isolates. Clade III contained the five remaining CC5-MRSA-IVc; average of 92 cgSNPs between isolates. Clade II contained seven PVL-positive CC5-MRSA-IVa comparators, whereas the remaining 45 comparators formed an outlier group. Minimum-spanning cgMLST analysis revealed a comparably low average of 57 allelic differences between all CC5/ST5-MRSA-IVc. All 214 CC5/ST5-MRSA-IVc were identified as 'Sri Lankan' clone, predominantly spa type t002 (186/214) with low population diversity and harboured a similar range of virulence genes and variable antimicrobial-resistance genes. All 214 Sri Lankan clone isolates and Clade II comparators harboured a 9616-bp chromosomal PVL-encoding phage remnant, suggesting both arose from a PVL-positive meticillin-susceptible ancestor. Over half of Sri Lankan clone isolates were from infections (142/214), and where detailed metadata were available (168/214), most were community associated (85/168). CONCLUSIONS: Stable chromosomal retention of pvl may facilitate Sri-Lankan clone dissemination.

Multiple distinct outbreaks of Panton-Valentine leucocidin-positive community-associated meticillin-resistant Staphylococcus aureus in Ireland investigated by whole-genome sequencing.

BACKGROUND: Panton-Valentine leucocidin (PVL)-positive community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) is increasingly associated with infection outbreaks. AIM: To investigate multiple suspected PVL-positive CA-MRSA outbreaks using whole-genome sequencing (WGS). METHODS: Forty-six suspected outbreak-associated isolates from 36 individuals at three separate Irish hospitals (H1-H3) and from separate incidents involving separate families associated with H2 were investigated by whole-genome multi-locus sequence typing (wgMLST). FINDINGS: Two clusters (CH1 and CH2) consisting of 8/10 and 6/6 PVL-positive t008 ST8-MRSA-IVa isolates from H1 and H2, respectively, were identified. Within each cluster, neighbouring isolates were separated by ≤5 allelic differences; however, ≥73 allelic differences were identified between the clusters, indicating two independent outbreaks. Isolates from the H3 maternity unit formed two clusters (CH3-SCI and CH3-SCII) composed of four PVL-negative t4667 ST5-MRSA-V and 14 PVL-positive t002 ST5-MRSA-IVc isolates, respectively. Within clusters, neighbouring isolates were separated by ≤24 allelic differences, whereas both clusters were separated by 1822 allelic differences, indicating two distinct H3 outbreaks. Eight PVL-positive t127 ST1-MRSA-V+fus and three PVL-negative t267 ST97-MRSA-V+fus isolates from two distinct H2-associated families FC1 (N = 4) and FC2 (N = 7) formed three separate clusters (FC1 (t127), FC2 (t127) and FC2 (t267)). Neighbouring isolates within clusters were closely related and exhibited ≤7 allelic differences. Intrafamilial transmission was apparent, but the detection of ≥48 allelic differences between clusters indicated no interfamilial transmission. CONCLUSION: The frequent importation of PVL-positive CA-MRSA into healthcare settings, transmission and association with outbreaks is a serious ongoing concern. WGS is a highly discriminatory, informative method for deciphering such outbreaks conclusively.

Pilot implementation of an electronic patient-reported outcome measure for planning and monitoring participation-focused care in early intervention.

BACKGROUND: Family-centered care is a valued approach to improving child and family outcomes in early intervention (EI), yet there is need to implement interventions that support information exchange for shared decision-making when planning and monitoring EI care. This study aims at estimating the feasibility, acceptability, and value of implementing the Young Children's Participation and Environment Measure (YC-PEM), a valid electronic patient-reported outcome (e-PRO) that is designed to support family engagement when planning care and monitoring outcomes of care. METHODS: Data were gathered from caregivers (N = 139) that were enrolled in a Phase 1 trial of the YC-PEM e-PRO as implemented within 1 month of their child's next EI evaluation of progress. YC-PEM e-PRO feasibility was estimated according to enrollment and completion rates, and mean completion time. Chi-square tests were used to examine parent perceptions of YC-PEM e-PRO acceptability by caregiver education and family income. Caregiver feedback via open-ended responses were content coded to inform intervention and protocol optimizations. YC-PEM e-PRO value was estimated via composite and item-level scores to capture the extent of participation difficulty in home and community activities, and common areas of need regarding caregivers desired change in their child's participation. RESULTS: Feasibility of implementing the YC-PEM e-PRO in routine EI care was mixed, as evidenced by low enrollment rates (21.0-29.2%), a high completion rate (85.3%), and limited missing data (80.6% of completed cases contained no missing data). More than half of the participants reported that the completion of the YC-PEM e-PRO was at least somewhat helpful, regardless of family income or caregiver education, providing support for its acceptability. As for its value, the YC-PEM e-PRO results were viewed by 64% of caregivers, whose desire for change most often pertained to the child's participation in non-discretionary activities at home and structured activities in the community. CONCLUSIONS: Results may support the implementation of YC-PEM e-PRO as a feasible, acceptable, and valued option for engaging families in planning the child's EI care. Results also inform select intervention and protocol optimizations prior to undertaking a multi-site pragmatic trial of its effectiveness on family engagement and shared decision-making within an EI clinical workflow. TRIAL REGISTRATION: Trial number: NCT03904797 . Trial registered at Clinicaltrials.gov . Registered 22 March 2019. Retrospectively registered.

Early intervention service intensity and young children's home participation.

BACKGROUND: Young children with developmental disabilities and delays spend significant amounts of time at home, show decreased participation in home-based activities, and receive home-based early intervention services to improve participation in activities. Yet, knowledge about the relationship between EI service use and children's home participation in activities remains poorly understood but needed for program improvement. The purpose of this study was to understand the relationships between EI service use and children's home participation. METHODS: In a cross-sectional design, data were gathered from caregivers (N = 139) who enrolled in a pilot trial of the Young Children's Participation in Environment Measure (YC-PEM) electronic patient-reported outcome (e-PRO), as implemented within 1 month of their child's next EI progress evaluation. A series of path analytic models were used to estimate EI service intensity as a predictor of parent-reported young children's home participation 1) frequency, 2) level of involvement, and 3) desired change, adjusting for family and child social and functional characteristics. Models included caregiver perceptions of home environmental support to test its indirect (i.e., mediation) effects on the relationship between EI service intensity and each of the three home participation dimensions. RESULTS: All three models fit the data well (comparative fit index = 1.00). EI service intensity was not a significant predictor of participation frequency. However, EI service intensity had a significant direct effect on a child's participation according to level of involvement and desired change, explaining between 13.3-33.5% of the variance in home participation. Caregiver perceptions of environmental support had a small yet significant indirect effect on the relationship between EI service intensity and level of involvement and desired change; these models explained between 18.5-38.1% of the variance in home participation. CONCLUSIONS: EI service intensity has important links with involvement in and desired change for home-based activities. Caregiver perceptions of environmental support appears to be a factor in the relationship between EI service intensity and home participation. Results warrant longitudinal replication with a control group, which would be possible with the implementation of the YC-PEM e-PRO in a routine EI clinical workflow. TRIAL RETROSPECTIVELY REGISTERED: NCT03904797 .

The LAPLAP study: a randomized placebo-controlled clinical trial assessing postoperative functional recovery using intraperitoneal local anaesthetic in laparoscopic colorectal surgery.

AIM: Postoperative pain remains a major factor in recovery from colorectal resection. There is increasing interest in opioid-sparing analgesia, and intraperitoneal local anaesthetic (IPLA) has recently been shown to be useful in minor laparoscopic and open colorectal procedures. The aim of this study was to evaluate the impact of IPLA on functional recovery following major laparoscopic surgery. In this controlled trial, mobility, as measured by the De Morton Mobility Index (DEMMI), was used as a surrogate for postoperative functional recovery. METHOD: Patients undergoing laparoscopic colorectal resection were randomized either to continuous ropivacaine (0.2% at 4-6 ml/h) or to saline (0.9%) which were administered via intraperitoneal catheter for 3 days postoperatively. Results were analysed in a double-blind manner. DEMMIs were assessed on postoperative days 1, 2, 3, 7 and 30, and data on pain, opioid consumption, gut and respiratory function, length of stay (LOS) and complications were recorded. RESULTS: Ninety-six patients were recruited. There was no difference in primary outcome (i.e., functional recovery) between IPLA and placebo groups. Opioid consumption and LOS were similar between groups, and no differences were found for any secondary outcome measure. There were no adverse events related to ropivacaine. CONCLUSION: Infusional intraperitoneal local anaesthetic appears to be safe but does not improve functional recovery or analgesic consumption following elective laparoscopic colorectal surgery, in the setting of an established enhanced recovery programme.

Classifying infants and toddlers with developmental vulnerability: who is most likely to receive early intervention?

BACKGROUND: Infants and toddlers with developmental difficulties represent a heterogeneous group who often receives early intervention (EI). Notable population heterogeneity exists and complicates unmet need and effectiveness research. However, a mix of relatively homogeneous clinically policy relevant 'subgroups' may create the apparent heterogeneity. To date, methodological challenges have impeded identifying these potential groups and their policy-relevance. METHODS: From the 2005-2006 National Survey of Children with Special Health Care Needs, we derived a sample (n = 965) of infants and toddlers with parent-reported developmental difficulties. We used latent class analysis (LCA) to identify subgroups of developmental vulnerability based upon functional, social and biological characteristics that would make children eligible for EI. Mixture modelling estimated the likelihood of each subgroup receiving parent-reported EI, controlling for race/ethnicity, child's age, and state of residence. RESULTS: LCA identified four distinct subgroups of developmental vulnerability: developmental disability (Group 1), mild developmental delay (Group 2), socially at risk with behaviour problems (Group 3), and socially at risk with functional vision difficulties (Group 4). Black, non-Hispanic children are significantly more likely than their white counterparts to be in Group 3 (ß = 1.52, P = 0.001) or group 4 (ß = 1.83, P < 0.001). Compared with children with a mild developmental delay (Group 2), children in group 1 (ß = -0.61, P < 0.001), group 3 (ß = -0.47, P = 0.001) and group 4 (ß = -0.38, P = 0.009) are significantly less likely to receive EI. CONCLUSIONS: Racial and ethnic differences exist with regard to membership in developmental vulnerability subgroups. Observed inconsistencies in access to EI suggest the need for improved surveillance, referral and outreach.

Providing predictive testing for Huntington disease via telehealth: results of a pilot study in British Columbia, Canada.

Predictive testing (PT) for Huntington disease (HD) usually requires several in-person appointments which acts as a barrier to testing for those from remote regions. This pilot study reports the use of telehealth PT to examine whether such telehealth testing improves access to HD PT while maintaining quality of care and support. Individuals underwent PT via the telehealth protocol or standard in-person protocol and were asked to complete surveys regarding their experience. Results reveal no significant differences between the in-person-tested and telehealth-tested groups with respect to quality of care, information, counselling and support. The majority of participants in both groups stated that pre-test counselling had provided them with sufficient knowledge about the advantages and disadvantages of undergoing testing, the opportunity to ask questions, and the ability to make an informed decision. The majority of participants in both groups were satisfied by the manner in which results were delivered and stated they had received sufficient information regarding the implications of these results. This study reveals that telehealth PT improves access while maintaining quality of care and support.

Maternal depression and perceived social support as predictors of cognitive function trajectories during the first 3 years of life for preterm infants in Wisconsin.

BACKGROUND: Among families of infants born preterm, the association between post-natal depression and children's cognitive function is not well understood, but thought to be compromised. The purpose of this study is to investigate maternal depressive symptoms and perceived social support as predictors of children's cognitive function trajectories. METHODS: This is a longitudinal study of a sample of infants born preterm (less than 37 weeks) in Wisconsin. This study includes 130 infants who were hospitalized in one of three Wisconsin neonatal intensive care units in 2002-2005 and followed until 36 months of age. Maternal depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Social support was measured using the Maternal Support Scale. Children's cognitive function was measured using the Bayley Scales of Infant Development, 2nd Edition, and the Stanford-Binet Intelligence Scale, 5th Edition. RESULTS: Children's cognitive function trajectories declined initially and then increased. Being female (coefficient = 5.14, SE = 1.89) and non-poor (coefficient = 11.26, SE = 5.78), and having a mother who has a graduate degree (coefficient = 7.67, SE = 3.37) was associated with higher levels of cognition initially. Being white was associated with a more optimal cognitive trajectory. Although depression did not predict children's cognitive trajectories, the presence of clinically elevated depressive symptoms at 9 months post term was associated with lower cognitive functioning at 16 months when mothers reported low social support. CONCLUSION: Post-natal depressive symptoms appear to have a meaningful, dynamic influence on the cognitive outcomes of children born preterm, above and beyond family socio-demographic risk when the presence and timing of perceived social support are considered. Interventions to ameliorate developmental risk associated with preterm birth should include repeated assessments of maternal social support and post-natal depression and be targeted towards socially disadvantaged families.

Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine model of aortic aneurysm.

Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic lymphocytes. However, GZMB can also be produced by other cell types and is capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent mechanism involving ECM cleavage. The murine serine protease inhibitor, Serpina3n (SA3N), is an extracellular inhibitor of GZMB. In the present study, administration of SA3N was assessed using a mouse Angiotensin II-induced AAA model. Mice were injected with SA3N (0-120 µg/kg) before pump implantation. A significant dose-dependent reduction in the frequency of aortic rupture and death was observed in mice that received SA3N treatment compared with controls. Reduced degradation of the proteoglycan decorin was observed while collagen density was increased in the aortas of mice receiving SA3N treatment compared with controls. In vitro studies confirmed that decorin, which regulates collagen spacing and fibrillogenesis, is cleaved by GZMB and that its cleavage can be prevented by SA3N. In conclusion, SA3N inhibits GZMB-mediated decorin degradation leading to enhanced collagen remodelling and reinforcement of the adventitia, thereby reducing the overall rate of rupture and death in a mouse model of AAA.

Mechanisms and management of doxorubicin cardiotoxicity.

Doxorubicin is an effective anti-tumor agent with a cumulative dose-dependent cardiotoxicity. In addition to its principal toxic mechanisms involving iron and redox reactions, recent studies have described new mechanisms of doxorubicin-induced cell death, including abnormal protein processing, hyper-activated innate immune responses, inhibition of neuregulin-1 (NRG1)/ErbB(HER) signalling, impaired progenitor cell renewal/cardiac repair, and decreased vasculogenesis. Although multiple mechanisms involved in doxorubicin cardiotoxicity have been studied, there is presently no clinically proven treatment established for doxorubicin cardiomyopathy. Iron chelator dexrazoxane, angiotensin converting enzyme (ACE) inhibitors, and ß-blockade have been proposed as potential preventive strategies for doxorubicin cardiotoxicity. Novel approaches such as anti-miR-146 or recombinant NRG1 to increase cardiomyocyte resistance to toxicity may be of interest in the future.

Cytochrome p450 2C enzymes contribute to peritransplant ischemic injury and cardiac allograft vasculopathy.

Peritransplant ischemia and reperfusion (I/R) injury contributes to posttransplant vascular dysfunction and cardiac allograft vasculopathy (CAV). We have previously shown that cytochrome p450 (CYP) 2C inhibition significantly reduces I/R-induced myocardial infarction and postischemic vascular dysfunction. In the latter study, pretreatment with sulfaphenazole (SP), a specific inhibitor of CYP 2C, restored postischemic NO-mediated, endothelium-dependent vasodilation and reduced vascular superoxide production. Given the association between I/R injury, early vascular dysfunction and CAV, we hypothesized that CYP 2C may also contribute to the onset of CAV. Lewis-to-Fisher rat heterotopic heart transplants were performed. Donors and recipients were treated with 5 mg/kg SP or vehicle control 1 h prior to surgery. SP did not affect posttransplant morbidity, mortality or weight gain. Coronary blood vessels from rats treated with SP exhibited significantly reduced luminal narrowing and demonstrated a corresponding decrease in smooth muscle cell (SMC) proliferation compared to controls. SP did not reduce diffuse, focal, epicardial, endocardial or perivascular immune infiltration nor did it significantly alter TUNEL positivity in myocardial, endothelial or SMC populations. In conclusion, CYP 2C contributes to SMC proliferation CAV without affecting general immune infiltration.

Nebraska experience.

Nebraska agencies and public health organizations collaboratively addressed cyanobacterial issues for the first time after two dogs died within hours of drinking water from a small private lake south of Omaha on May 4, 2004. A necropsy on one of the dogs revealed that the cause of death was due to ingestion of Microcystin toxins. Within two weeks after the dog deaths, state and local officials jointly developed strategies for monitoring cyanobacterial blooms and issuing public health alerts and advisories. Weekly sampling of public lakes for microcystin toxins and cyanobacteria was initiated during the week of May 17, 2004. ELISA laboratory equipment and supplies were purchased to achieve a quick turnaround time for measuring weekly lake samples for total microcystins so that public health advisories and alerts could be issued prior to each weekend's recreational activities. A conservative approach was selected to protect human health, pets, and livestock, which included collecting worst-case samples from cyanobacterial blooms; freezing and thawing of samples to lyse algal cells and release toxins prior to laboratory analysis; and using action levels of 15 ppb and 2 ppb of total microcystins, respectively, for issuing health alerts and health advisories. During 2004, five dog deaths, numerous wildlife and livestock deaths, and more than 50 accounts of human skin rashes, lesions, or gastrointestinal illnesses were reported at Nebraska lakes. Health alerts were issued for 26 lakes and health advisories for 69 lakes. Four lakes were on health alert for 12 or more weeks. The primary cyanobacterial bloom-forming genera identified in Nebraska lakes were Anabaena, Aphanizomenon, and Microcystis. Preliminary assessments of lake water quality data indicated that lower lake levels from the recent drought and low nitrogen to phosphorus ratios may have contributed, in part, to the increased numbers of cyanobacterial complaints and problems that occurred in 2004.

The impact of CVB3 infection on host cell biology.

CVB3 myocarditis can lead to dilated cardiomyopath (DCM). DCM is one of the leading causes of the need for heart transplantation, so it is important to understand the life cycle of CVB3 and its interactions with the host cell. Infection causes rapid death of host cardiomyocytes by altering normal cellular homeostasis for the efficient release of progeny virion. In this chapter, we will examine the impact that CVB3 replication has on host cell biology, from events that take place at receptor ligation to progeny virus release. The primary focus will be on the myriad of signalling pathways that are activated at all stages of virus replication and their downstream effects. We will also discuss some of the extracellular effects of infection as well as immune and matrixmetalloprotease activation. Interactions of host cell proteins with the 5' untranslated region (UTR) are required for translation and replication of CVB3. These interactions do not always benefit the virus since the interactions of a 28-kDa host protein with the 5' UTR are thought to be responsible for inhibitory activity against CVB3. Finally, we will discuss how the elucidation of the different stages of replication has provided the opportunity to develop novel strategies for combating CVB3 infection.

Cross-cultural comparisons of obesity and growth in Prader-Willi syndrome.

Introduction The present study reports cross-cultural comparisons of body mass index (BMI) and growth in Prader-Willi syndrome, a neurodevelopmental disorder associated with obesity, growth restriction and mild learning disability. Our objectives were to: (1) compare rates of obesity in adults with Prader-Willi syndrome (PWS) in France, with data available from Belgium, the UK and the USA; (2) compare growth of French children with PWS with their counterparts in Germany and the USA; and (3) evaluate the contribution of genetic, medical and social parameters to obesity outcome in French children and adults with PWS. Method (1) Cross-sectional comparison of BMI of 40 French adults, 38 Belgian adults, 46 British adults and 292 North American adults; (2) Construction of growth curves for French children aged 2-20 years from longitudinal data for 150 individuals with PWS, and comparison with published growth curves from Germany and the USA; and (3) Longitudinal regression analysis of 141 French children and adults to determine the factors contributing to obesity outcome. Results A total of 82.5% French adults with PWS have BMI > 30 compared with 65.8% in Belgium (n.s.), 58.2% in the USA (P < 0.005), and 54.3% in the UK (P < 0.01). Higher rates of obesity in females vs. males were found in the USA sample (P < 0.001) but not in the other samples. In contrast to adults, growth curves for French children with PWS show similar rates of growth compared with children with PWS in Germany and the USA. The principal determining factors of BMI status in the French PWS population are age (P < 0.0001), cohort (born within the last 15 years vs. born over 15 years ago, P < 0.0002) and growth hormone replacement therapy (P < 0.0002). Significant subsidiary effects include domestic situation (P < 0.0001), genetic diagnosis (P < 0.0001) and age of diagnosis (P < 0.0001). Conclusions French adults with PWS have significantly higher rates of obesity than adults in the UK and the USA, but growth in French children with PWS is similar to the USA and Germany. Clinical management has a greater impact on obesity outcome in PWS than cultural factors.

Inhibition and recovery of maternal and foetal cholinesterase enzymes following fenitrothion administration in CD rats.

The purpose of this study was to characterize tissue esterase activity and blood fenitrothion concentrations in the rat dam and foetus following in-utero exposure to the organophosphate insecticide fenitrothion. Time-mated, 8-week-old rats were gavaged on gestation day 19 with 0, 5, or 25 mg fenitrothion kg-1. Fenitrothion was absorbed rapidly from the gastrointestinal tract, with peak maternal and foetal blood levels observed 0.5-1.0 h after dosing. Fenitrothion concentrations in maternal and foetal blood were virtually identical and demonstrated a non-linear dose-response relationship. Acetylcholinesterase and carboxylesterase activities in maternal liver and blood and in foetal liver and brain decreased within 30-60 min of fenitrothion exposure. Esterase inhibition occurred at a fenitrothion dose (5 mg kg-1) that has not been previously associated with reproductive toxicity, suggesting that esterase inhibition should be considered as the critical effect in risk assessments for this pesticide.

Changes in intracellular pH play a secondary role in hydrogen sulfide-induced nasal cytotoxicity.

Hydrogen sulfide (H(2)S) is a naturally occurring gas that is also associated with several industries. The potential for widespread human inhalation exposure to this toxic gas is recognized as a public health concern. The nasal epithelium is particularly susceptible to H(2)S-induced pathology. Cytochrome oxidase inhibition is postulated as one mechanism of H(2)S toxicity. Another mechanism by which the weak acid H(2)S could cause nasal injury is intracellular acidification and cytotoxicity. To further understand the mechanism by which H(2)S damages the nasal epithelium, nasal respiratory and olfactory epithelial cell isolates and explants from naive rats were loaded with the pH-sensitive intracellular chromophore SNARF-1 and exposed to air or 10, 80, 200, or 400 ppm H(2)S for 90 min. Intracellular pH was measured using flow cytometry or confocal microscopy. Cell lysates were used to quantify total protein and cytochrome oxidase activity. A modest but statistically significant decrease in intracellular pH occurred following exposure of respiratory and olfactory epithelium to 400 ppm H(2)S. Decreased cytochrome oxidase activity was observed following exposure to >10 ppm H(2)S in both respiratory and olfactory epithelia. None of the treatments resulted in cytotoxicity. The intracellular acidification of nasal epithelial cells by high-dose H(2)S exposure and the inhibition of cytochrome oxidase at much lower H(2)S concentrations suggest that changes in intracellular pH play a secondary role in H(2)S-induced nasal injury.

Nontarget arthropod abundance in areawide-managed corn habitats treated with semiochemical-based bait insecticide for corn rootworm (Coleoptera: Chrysomelidae) control.

Impacts of semiochemical-based insecticidal bait applications on beneficial arthropod groups common to field corn, Zea mays L., habitats were assessed in areawide-managed field sites in South Dakota and Iowa during 1997 and 1998. Slam, a commercial bait formulation comprised of 87% cucurbitacin and 13% carbaryl insecticide, was used for management of adult rootworm, Diabrotica spp., and controls consisted of cornfield habitats without bait applications. Effects on beneficial organisms were variable, and negative impacts were infrequent. Coccinellidae, Staphylinidae, and Anthocoridae were usually more abundant in bait-treated plots than in controls that received at-plant soil insecticides, especially by 4 wk postapplication. Carabid beetle activity also had increased in bait-treated corn by proportionally greater rates than in control plots at 4 wk postapplication in two of the four site by year combinations in this study. Impacts of semiochemical-based adulticide applications on Formicidae were not consistently negative or positive. The relative lack of consistent negative impacts on nontarget arthropods suggests that other biotic and abiotic factors leading to natural population fluxes may have more influence on these groups of beneficial organisms than applications of semiochemical-based bait containing carbaryl. Overall, it seems that areawide applications of these baits for managing rootworm populations in corn are not likely to impose deleterious effects on the nontarget faunal groups we surveyed, especially in comparison with the at-plant applications of soil insecticides used as experimental controls in this study.

Abundance of Coleomegilla maculata (Coleoptera: Coccinellidae) in corn rootworm-resistant Cry3Bb1 maize.

Lady beetles (Coleoptera: Coccinellidae) are important polyphagous predators in maize, Zea mays L., fields. Transgenic Cry3Bb1 maize hybrids express a coleopteran-specific insecticidal protein derived from Bacillus thuringiensis (Berliner) subsp. kumamotoensis that is targeted at corn rootworm larvae. This study evaluated impacts of Cry3Bb1 protein-expressing maize, tefluthrin-treated maize, and untreated controls on lady beetle abundance at preanthesis, anthesis, and postanthesis maize-developmental periods near Brookings in eastern South Dakota during 2001 and 2002. The dominant lady beetle species captured on Pherocon AM sticky traps was Coleomegilla maculata De Geer. It comprised 73.5 and 69.9% of all adult Coccinellidae caught in 2001 and 2002, respectively. Numbers of C. maculata captured in Cry3Bb1 maize were not significantly different from those in untreated plots during preanthesis, and adults were more abundant in Cry3Bb1 maize than in tefluthrin-treated and untreated plots during anthesis and postanthesis. Whole-plant sampling confirmed C. maculata predominance with the species representing 89.2 and 91.4% of all adult lady beetles observed in 2001 and 2002, respectively. Whole-plant sampling also indicated a lack of negative effects from Cry3Bb1 maize on abundance of lady beetle eggs, larvae, pupae, or adults. Overall, these findings indicate that Cry3Bb1-expressing hybrids are not likely to impose harmful effects on C. maculata, a species common to maize production systems in the northern Great Plains. This research further suggests that Cry3Bb1 maize has the potential for conservation of these beneficial coccinellids in maize production systems.

Seventeen-point dermal ultrasound scoring system--a reliable measure of skin thickness in patients with systemic sclerosis.

OBJECTIVE: Our objective was to develop a 17-site ultrasound method of measuring skin thickness in patients with systemic sclerosis (SSc) and to assess its inter- and intra-observer variability. METHODS: Dermal thickness (using a 22 MHz ultrasound probe) was measured at 17 sites (corresponding to those assessed in the modified Rodnan skin score) in 39 patients with SSc (26 limited cutaneous, 13 diffuse) and 34 healthy controls. The sum of the thicknesses (at the 17 sites) and the maximal thickness were also documented. Because skin thickness varies between sites, each measurement was converted to a z-score. Inter- and intra-observer variability were assessed in 35 patients/33 controls, and 20 patients/15 controls respectively. RESULTS: Measurement precision was good for the dermal measurements-intraclass correlation coefficients at the 17 sites ranged from 0.65 to 0.94 for the inter-observer variability (0.86 for maximum thickness) and from 0.55 to 0.96 for the intra-observer variability (0.92 for maximum thickness). CONCLUSION: Our results suggest that the 17-point dermal ultrasound scoring system is extremely reliable and may therefore be a useful measure of outcome, including in clinical trials.