Neurobehavioral performance in preschool children from agricultural and non-agricultural communities in Oregon and North Carolina

Organophosphate (OP) pesticides produce acute toxic effects but little is known about low-level chronic exposures. Latino children of agricultural workers have a high risk of exposure to pesticides because of the close proximity of their homes to fields where pesticides are applied and from take-home exposure. Neurobehavioral performance of preschool children from agricultural (AG) communities was compared to performance of those from non-agricultural (Non-AG) communities in Oregon and North Carolina. Seventy-eight children aged 48-71 months completed a battery of neurobehavioral tests two times, approximately 1 month apart. Multiple regression revealed that the AG children performed poorer on measures of response speed (Finger Tapping) and latency (Match-to-Sample) compared to the Non-AG children. These results demonstrate modest differences in AG children compared to Non-AG children that are consistent with functional effects seen in adults exposed to low concentrations of OP pesticides. Just as was the case following early research on adults poisoned by pesticides, this study points to the need for additional investigations to test the hypothesis that low-concentration OP exposures affect acquisition of test performance, response speed and latency in children of agricultural workers.     

In vitro and in vivo activities of C-terminally truncated PTH peptides reveal a disconnect between cAMP signaling and functional activity

There is considerable evidence implicating the cAMP-signaling pathway in the anabolic action of PTH; and to date, all PTH and PTHrp peptides that stimulate cyclic AMP are active in animal models of osteogenesis. We have tested two C-terminally truncated peptides, PTH(1–29) and a modified PTH(1–21) (MPTH(1–21)), in in vitro and in vivo assays of PTH action. Each of the C-terminally truncated peptides was of low nanomolar potency in assays of receptor binding and cAMP stimulation. However, when we tested these peptides for functional response in Saos-2 cells stably transfected with a cyclic AMP response element (CRE) reporter, the C-terminally truncated peptides were two to four times less potent than would be expected from their binding and cAMP-stimulating properties. Furthermore, PTH(1–29), although active, was approximately 20-fold less potent than PTH(1–34) in a rat model of osteogenesis while MPTH(1–21) was inactive. The relative lack of activity of these peptides in vivo suggests that while activation of the cAMP pathway may be important for the anabolic effect of PTH fragments, it is not, of itself, predictive of their in vivo activity.     

Dementia Deficits Scale. Rating self-awareness of deficits

Impaired deficit awareness is important to detect because of its clinical implications; for example, patients with impaired awareness are more likely to engage in potentially dangerous activities, such as operating the stove. This study evaluated the reliability and validity of the Dementia Deficits Scale (DDS), a new multidimensional instrument for the assessment of self-awareness of cognitive, emotional, and functional deficits associated with dementia. Three parallel forms of the DDS were independently completed by the patient, clinician, and informant. The DDS yields two measures of deficit awareness: the discrepancy between clinician and patient assessments of the patient's deficits, and the discrepancy between informant and patient assessments. The DDS demonstrated adequate reliability and good divergent and convergent validity. Clinician and informant reports each added unique information, highlighting the importance of including both perspectives in the awareness assessment process. The DDS is recommended as a reliable and valid tool for the clinical and empirical assessment of deficit awareness in patients with dementia.     

Pragmatic controlled clinical trials in primary care: the struggle between external and internal validity

Background  

Controlled clinical trials of health care interventions are either explanatory or pragmatic. Explanatory trials test whether an intervention is efficacious; that is, whether it can have a beneficial effect in an ideal situation. Pragmatic trials measure effectiveness; they measure the degree of beneficial effect in real clinical practice. In pragmatic trials, a balance between external validity (generalizability of the results) and internal validity (reliability or accuracy of the results) needs to be achieved. The explanatory trial seeks to maximize the internal validity by assuring rigorous control of all variables other than the intervention. The pragmatic trial seeks to maximize external validity to ensure that the results can be generalized. However the danger of pragmatic trials is that internal validity may be overly compromised in the effort to ensure generalizability. We are conducting two pragmatic randomized controlled trials on interventions in the management of hypertension in primary care. We describe the design of the trials and the steps taken to deal with the competing demands of external and internal validity.     

Risedronate Pharmacokinetics and Intra- and Inter-Subject Variability Upon Single-Dose Intravenous and Oral Administration

Purpose. To determine the pharmacokinetics and absolute bioavailability of risedronate after single-dose oral administration of 30 mg risedronate as a tablet and an aqueous solution, and 0.3 mg risedronate as an intravenous infusion. Methods. This study was a randomized, three-treatment, four-period, partial replicate crossover study involving 33 healthy volunteers. Treatments were administered 7 weeks apart, and the third treatment was repeated during the fourth period. Serum and urine were collected over 72 hours and 672 hours, respectively. Results. Following intravenous administration, renal clearance accounted for 87% of total clearance, with 65% of the dose excreted within 24 hours and 85% of the dose excreted within four weeks. The absolute bioavailability was approximately 0.62% after both oral formulations, and the relative bioavailability of the tablet compared with the oral solution was 104%. The rate and extent of absorption from the two formulations were bioequivalent based on the range proposed for highly variable drugs. Intrasubject variability following oral administration was 50-80%, and was primarily associated with absorption. Conclusion. The majority of the total clearance after intravenous administration of risedronate was renal clearance, indicating that only a small percentage of a systemic dose is potentially incorporated, or cleared, into bone. The absolute bioavailability of orally administered risedronate is 0.6%, and is independent of formulation. Variability in the pharmacokinetics following oral administration is primarily associated with intrasubject variability in absorption.     

Negotiating risky bodies: childbirth and constructions of risk

Policy makers, practitioners and researchers have identified risk as a key concept in relation to maternity care and childbirth. There is however a lack of research exploring women’s discursive constructions of risk and childbirth in relation to sociological risk theories. In this article we explore pregnant women’s everyday negotiations of risk in relation to the self-chosen plan to birth either at home or via an elective Caesarean section. We use sociocultural risk theories to contextualise our findings. This article draws on data from a study conducted in 2005–2006 in which we interviewed 24 pregnant middle-class South African women who were planning a home birth or elective Caesarean section and used social constructionist discourse analysis to analyse the data. We found that women’s risk constructions were related to three different conceptions of birthing embodiment: technocratic bodies, vulnerable bodies and knowing bodies. Women who planned Caesarean sections were committed to biomedical constructions of risk and birth. Woman who planned home births shifted between endorsing and subverting biomedical models of risk. They also resisted definitions of birthing bodies as inherently abject (unclean, polluting, unruly) and constructed the process of giving birth as risky in medicalised settings. In such settings, the birthing body was constructed as vulnerable to objectification, loss of dignity and shaming. Women who planned to give birth at home constructed an alternative approach to birth which emphasised embodied ways of knowing, relational connection and empowerment over normative and medicalised risk constructions. In the process, biomedical risk definitions were destabilised.     

Prevalence of a history of prior varicella/herpes zoster infection in multiple sclerosis

Varicella zoster virus (VZV) infection has been implicated in multiple sclerosis (MS), but direct causal involvement has been disputed. Nevertheless, knowledge of VZV exposure is important, given the risk of serious complications of first exposure while undergoing immunosuppressive treatment, in particular with fingolimod. We distributed questionnaires to MS clinic patients, requesting information about history of chickenpox, sibling/household/occupational exposure, history of zoster (shingles), and disease-modifying treatment. A random, proportionally representative sample of 51 patients that included patients with positive, negative, and unknown chickenpox history were selected for determination of VZV IgG by ELISA. Of 1206 distributed questionnaires, 605 were returned (50% response rate). Of these, 86% reported history of chickenpox, 5.6% gave negative history, and 8.5% did not know. Of 594 who answered the zoster question, 78% gave a negative response, 4% did not know, and 104 (17%) answered yes. Of these, 83 reported 1 episode; 12 had 2; 5 had 3; and 1 each reported 5, 6, and 15 episodes. Of 51 patients tested for VZV IgG (44 “yes,” 4 “no,” and 3 “I don’t know” answers to the question of whether they had chickenpox), 48 were seropositive; the 3 seronegative all had reported having had chickenpox. The high rate of MS patients reporting prior chickenpox infection is comparable with previous reports. A substantial proportion of MS patients, estimated to be higher than an age-matched general population, report single or multiple episodes of zoster. These data are useful for consideration of immunosuppressive treatments and/or VZV and zoster vaccination.