Role of the Sibling Relationship to Reduce the Negative Impact of Adverse Childhood Experiences (ACEs) on Wellbeing in Adulthood.

Over the past two decades, public health research has demonstrated that Adverse Childhood Experiences (ACEs) are associated with significant and prolonged physical and mental health problems, demanding investigation into the factors that may mitigate the poor outcomes. One potential factor that may attenuate the negative impact of ACEs on individuals' health is social support. An important source of social support, both during and after adverse childhood experiences, is sibling relationships. Consequently, the purpose of the current study was to examine if two components of sibling relationships-perceived warmth and conflict-affect the relationship between ACEs and wellbeing in adulthood. A total of 439 participants (Mage = 35.06, SD = 11.19) completed self-report measures of their ACEs, their perceived warmth and conflict with a living sibling, and their wellbeing. Results revealed that sibling relationships characterized by higher perceived warmth-and, interestingly, higher perceived conflict-attenuated the negative impact of ACEs on wellbeing in adulthood. Findings from the current study provide valuable information about how psychologist, social workers, and other health professionals may use siblings as a source of social support to mitigate the negative effects of ACEs on wellbeing in adulthood.

Identification and Characterization of Mitogen-Activated Protein Kinase (MAPK) Genes in Sunflower (Helianthus annuus L.).

Mitogen-Activated Protein Kinase (MAPK) genes encode proteins that regulate biotic and abiotic stresses in plants through signaling cascades comprised of three major subfamilies: MAP Kinase (MPK), MAPK Kinase (MKK), and MAPKK Kinase (MKKK). The main objectives of this research were to conduct genome-wide identification of MAPK genes in Helianthus annuus and examine functional divergence of these genes in relation to those in nine other plant species (Amborella trichopoda, Aquilegia coerulea, Arabidopsis thaliana, Daucus carota, Glycine max, Oryza sativa, Solanum lycopersicum, Sphagnum fallax, and Vitis vinifera), representing diverse taxonomic groups of the Plant Kingdom. A Hidden Markov Model (HMM) profile of the MAPK genes utilized reference sequences from A. thaliana and G. max, yielding a total of 96 MPKs and 37 MKKs in the genomes of A. trichopoda, A. coerulea, C. reinhardtii, D. carota, H. annuus, S. lycopersicum, and S. fallax. Among them, 28 MPKs and eight MKKs were confirmed in H. annuus. Phylogenetic analyses revealed four clades within each subfamily. Transcriptomic analyses showed that at least 19 HaMPK and seven HaMKK genes were induced in response to salicylic acid (SA), sodium chloride (NaCl), and polyethylene glycol (Peg) in leaves and roots. Of the seven published sunflower microRNAs, five microRNA families are involved in targeting eight MPKs. Additionally, we discussed the need for using MAP Kinase nomenclature guidelines across plant species. Our identification and characterization of MAP Kinase genes would have implications in sunflower crop improvement, and in advancing our knowledge of the diversity and evolution of MAPK genes in the Plant Kingdom.

Evaluation of the potential for pharmacokinetic interaction between fenofibrate and ezetimibe: A phase I, open-label, multiple-dose, three-period crossover study in healthy subjects.

OBJECTIVE: This study was conducted to evaluate the potential for pharmacokinetic interaction between fenofibrate and ezetimibe in healthy subjects. METHODS: This was a Phase I, open-label, multiple-dose,3-period crossover study conducted in healthy adult men and women. Subjects received fenofibrate 145 mg alone, fenofibrate 145 mg with ezetimibe 10 mg, and ezetimibe 10 mg alone for 10 consecutive days, in an order determined by computerized randomization schedule. Blood samples were collected for up to 24 hours after dosing on study day 1 and up to 120 hours after dosing on study day 10 for determination of plasma concentrations of fenofibric acid, unconjugated (free) ezetimibe, and total (conjugated and unconjugated) ezetimibe using validated high-performance liquid chromatography methods with mass-spectrometric detection. Ezetimibe glucuronide concentrations were estimated by subtracting free ezetimibe concentrations from total ezetimibe concentrations. RESULTS: Eighteen healthy adults (12 men, 6 women; 17 white, 1 black) were enrolled in the study. Their mean age was 43.4 years (range, 27-55 years), their mean weight 78.7 kg (range, 60-98 kg), and their mean height 174.9 cm (range, 156-194 cm). Coadministration of multiple doses of fenofibrate and ezetimibe produced no statistically significant effect on the pharmacokinetics of fenofibric acid but significantly increased exposures to total ezetimibe and ezetimibe glucuronide (P < 0.05). Using point estimates, co-administration of fenofibrate and ezetimibe increased AUC central values for total ezetimibe and ezetimibe glucuronide by 43% (90% CI, 29-59) and 49% (90% CI, 34-65), respectively. CONCLUSION: In these healthy volunteers, coadministration of multiple doses of fenofibrate and ezetimibe had no statistically significant effect on the pharmacokinetics of fenofibric acid but was associated with a significant increase in exposure to total ezetimibe and its metabolite ezetimibe glucuronide.

The effects of multiple doses of fenofibrate on the pharmacokinetics of pravastatin and its 3alpha-hydroxy isomeric metabolite.

Published data indicate that coadministration of multiple doses of the fibrate drug, gemfibrozil, led to a 202% increase in pravastatin systemic exposure (area under the plasma concentration-time curve, AUC). To evaluate the effects of another fibrate drug, fenofibrate, on the pharmacokinetics of pravastatin, 24 healthy subjects took pravastatin (40 mg once daily) on study days 1 to 15 and fenofibrate (160 mg once daily) on study days 6 to 15. Blood samples were collected for 24 hours after dosing on days 5, 6, and 15. Plasma concentrations of pravastatin and its active metabolite, 3alpha-hydroxy-iso-pravastatin, were measured, and pharmacokinetics was assessed. Safety assessments were based on adverse events, physical examinations, electrocardiogram results, vital signs, and clinical laboratory testing. Safety results were unremarkable. Coadministration of fenofibrate had modest effects on pravastatin and 3alpha-hydroxy-iso-pravastatin systemic exposures (AUC). Increases in pravastatin systemic exposures (19%-28%, on average) and 3alpha-hydroxy-iso-pravastatin systemic exposures (24%-39%, on average) were observed upon coadministration, but individual changes were variable. Pravastatin and 3alpha-hydroxy-iso-pravastatin systemic exposures were not statistically significantly different following the 1st and 10th doses of fenofibrate.

The effects of occupational exposure to chlorpyrifos on the neurologic examination of central nervous system function: a prospective cohort study.

Questions persist about adverse effects such as impaired cognition and attention, incoordination, spasticity, or parkinsonism from chronic, low-level exposures to organophosphate (OP) compounds. In a prospective cohort study, we evaluated chlorpyrifos-manufacturing workers and a referent group on 2 occasions, 1 year apart, to determine whether occupational exposure to chlorpyrifos produced clinically evident central nervous system (CNS) dysfunction. Chlorpyrifos subjects had significantly higher TCP excretion and lower average BuChE activity than referents in a range in which physiological effects on B-esterases exist. Few subjects had neurologic symptoms or signs, and there were no significant group differences in terms of signs at baseline or second examinations. Chronic chlorpyrifos exposure produced no clinical evidence of cortical, pyramidal tract, extrapyramidal, or other CNS dysfunction among chlorpyrifos subjects compared with referents, either at baseline or after 1 year of additional chlorpyrifos exposure.

Absence of sensory neuropathy among workers with occupational exposure to chlorpyrifos.

Several studies have reported the occurrence of sensory neuropathy with exposure to chlorpyrifos and other organophosphorus insecticides, at levels not associated with overt toxicity. We evaluated 113 chemical workers, including 53 of 66 (80%) eligible chlorpyrifos workers and 60 of 74 (81%) randomly selected referent workers, to identify evidence of sensory neuropathy or subclinical neuropathy. Compared to referents, chlorpyrifos subjects had significantly longer duration of work in chlorpyrifos-exposed areas (9.72 vs. 0.01 years; P < 0.0001), greater cumulative chlorpyrifos exposure (64.16 vs. 0.69 mg/m(3). day; P < 0.0001), higher urine 3,5,6-trichloro-2-pyridinol (TCP) excretion (108.6 vs. 4.3 microg/g creatinine; P < 0.0001), and lower plasma butyrylcholinesterase (BuChE) activity (7281 vs. 8176 mU/ml; P = 0.003). Despite exposures among chlorpyrifos subjects to levels at which well-described physiological effects on B-esterases exist, the frequency of symptoms or signs of neuropathy did not differ significantly between groups, and the only 2 subjects fulfilling criteria for confirmed neuropathy were both in the referent group. Mean nerve conduction study results were comparable to established control values and did not differ significantly between groups. We found no evidence of sensory neuropathy or isolated peripheral abnormalities among subjects with long-term chlorpyrifos exposure at levels known to be associated with the manufacturing process.

Cancer mortality in a Texas county with prior uranium mining and milling activities, 1950-2001.

Uranium was discovered in Karnes County, Texas, in 1954 and the first uranium mill began operating in 1961 near Falls City. Uranium milling and surface and in situ mining continued in Karnes County until the early 1990s. Remediation of uranium tailings ponds was completed in the 1990s. There were three mills and over 40 mines operating in Karnes County over these years and potential exposure to the population was from possible environmental releases into the air and ground water. From time to time concerns have been raised in Karnes County about potential increased cancer risk from these uranium mining and milling activities. To evaluate the possibility of increased cancer deaths associated with these uranium operations, a mortality survey was conducted. The numbers and rates of cancer deaths were determined for Karnes County and for comparison for four 'control' counties in the same region with similar age, race, urbanisation and socioeconomic distributions reported in the 1990 US Census. Comparisons were also made with US and Texas general population rates. Following similar methods to those used by the National Cancer Institute, standardised mortality ratios (SMRs) were computed as the ratio of observed numbers of cancers in the study and control counties compared to the expected number derived from general population rates for the United States. Relative risks (RRs) were computed as the ratios of the SMRs for the study and the control counties. Overall, 1223 cancer deaths occurred in the population residing in Karnes County from 1950 to 2001 compared with 1392 expected based on general population rates for the US. There were 3857 cancer deaths in the four control counties during the same 52 year period compared with 4389 expected. There was no difference between the total cancer mortality rates in Karnes County and those in the control counties (RR = 1.0; 95% confidence interval 0.9-1.1). There were no significant increases in Karnes County for any cancer when comparisons were made with either the US population, the State of Texas or the control counties. In particular, deaths due to cancers of the lung, bone, liver and kidney were not more frequent in Karnes County than in the control counties. These are the cancers of a priori interest given that uranium might be expected to concentrate more in these tissues than in others. Further, any radium intake would deposit primarily in the bone and radon progeny primarily in the lung. Deaths from all cancers combined also were not increased in Karnes County and the RRs of cancer mortality in Karnes County before and in the early years of operations (1950-64), shortly after the uranium activities began (1965-79) and in two later time periods (1980-89, 1990-2001) were similar, 1.0, 0.9, 1.1 and 1.0, respectively. No unusual patterns of cancer mortality could be seen in Karnes County over a period of 50 years, suggesting that the uranium mining and milling operations had not increased cancer rates among residents.

A cohort mortality study among titanium dioxide manufacturing workers in the United States.

Although titanium dioxide (TiO2) is generally regarded as a nontoxic mild pulmonary irritant, some laboratory studies have reported lung adenomas in rats exposed to high levels of TiO2. Limited data on health effects among humans exist. A retrospective cohort mortality study was conducted among 4241 TiO2 workers who were employed for at least 6 months, on or after January 1, 1960, at four TiO2 plants in the United States. Exposure categories, defined by plant, job title, and calendar years in the job, were created to examine mortality patterns in those jobs where the potential for TiO2 exposure is greatest. Standardized mortality ratios (SMRs) and their 95% confidence intervals (CI) were calculated to compare the mortality pattern of the workers with the general background population. Relative risks were estimated and trend tests were conducted to examine risk of disease among different exposure level groups in internal analyses. Workers experienced a significantly low overall mortality (SMR = 0.8; 95% CI = 0.8-0.9). No significantly increased SMRs were found for any specific cause of death. Deaths from lung cancer were as expected, and SMRs for this cancer did not increase with increasing TiO2 levels. Workers in jobs with greatest TiO2 exposure had significantly fewer than expected total deaths (SMR = 0.7; 95% CI = 0.6-0.9). Internal analyses revealed no significant trends or exposure-risk associations for total cancers, lung cancer, or other causes of death. Results from our study indicate that the exposures at these United States plants are not associated with increases in the risk of death from cancer or other diseases. Moreover, workers with likely higher levels of TiO2 exposure had similar mortality patterns to those with less exposure, as internal analyses among workers revealed no increase in mortality by level of TiO2 exposure.

Conversion of stable renal allograft recipients to a bioequivalent cyclosporine formulation.

BACKGROUND: Gengraf capsule, an AB-rated generic cyclosporine for Neoral, has been shown to be bioequivalent in previous studies. The purpose of this pharmacokinetic study performed in stable renal transplant recipients was to evaluate interchangeability of Gengraf and Neoral. METHODS: Using an open-label, three-period design, 50 renal transplant recipients taking stable doses of Neoral completed a multicenter study. Subjects continued their Neoral regimen during period I (days 1-14). Subjects then switched from Neoral on a milligram-for-milligram basis to Gengraf during period II (days 15-28), followed by conversion to the same milligram-for-milligram dosing regimen of Neoral during period III (days 29-35). Twelve-hour pharmacokinetic evaluations (maximum observed blood concentration [C(max) ], concentration before dosing [C(trough) ], time to maximum observed concentration [T(max) ], and area under the blood concentration-vs.-time curve [AUC]) occurred on days 1, 14, 15, 28, and 29. Additional predose samples (C (trough)) were evaluated on days 7, 21, and 35. Laboratory and safety parameters were also evaluated. RESULTS: The pharmacokinetics of Gengraf (C(max), T(max), C(trough), and AUC) were indistinguishable from the Neoral values in stable renal allograft recipients. The bioequivalent capsules were interchangeable with respect to C(max), C(trough), and AUC at steady state and also on conversion from one capsule formulation to the other. The 90% confidence intervals (CI) for the Gengraf versus Neoral comparison at steady state (day 28 vs. day 14) were 0.95 to 1.03 for AUC and 0.92 to 1.04 for C(max). Trough concentrations remained consistent throughout the study, with no need for dosage adjustment in any of the subjects. Gengraf is well tolerated, with an excellent safety profile, comparable to the safety profile of Neoral. CONCLUSIONS The pharmacokinetics of Gengraf are equivalent and indistinguishable from those of Neoral. Gengraf is well tolerated and interchangeable with Neoral in stable renal transplant recipients.

Epidemiology of latex sensitization and allergies in health care workers.

Although it is often claimed that health care workers are at increased risk of latex sensitization and type I allergies, there has been no systematic analysis of the epidemiologic studies that are relevant to this conclusion. A systematic analysis of the epidemiologic literature found that, in the past 14 years, there have been 48 epidemiologic studies of type I latex allergy among health care workers. Of these, 2 cohort studies estimated the incidence of latex sensitization by skin prick testing at between 1% and 2.5% per year. Neither compared the risk to that in the general population. The prevalence of sensitization in health care workers varied between 0% and 30%, yet this large variation was unexplained. Increased risk of sensitization was not clearly associated with the duration of work in health care, the time spent wearing latex gloves, the frequency of exposure, the specific job categories, the use of powdered versus nonpowdered latex gloves, the use of latex versus nonlatex gloves, or any measurements of ambient exposure to latex proteins. The epidemiologic studies do not support a conclusion that health care workers are at clearly increased risk of latex sensitization or type I allergies compared to other occupations in the United States. The role of latex gloves in causing latex sensitization and type I allergic symptoms remains poorly defined because of the inconsistent results across studies. Future epidemiologic studies are needed that include measured exposures to latex antigens, that compare health care workers to appropriate referent groups, and that address confounding by atopy, age, sex, and race.