Plasma levels of DDE/DDT and liver function in malaria control personnel 6 months after indoor residual spraying with DDT in northern Uganda, 2008

Objective. We investigated the relationship between plasma levels of dichlorodiphenyltrichloroethane (DDT) and liver function in malaria control personnel 6 months after one round of DDT indoor residual spraying (IRS).Method. This was a cross-sectional study in the districts of Apac and Oyam of Lango, northern Uganda. Volunteers were clinically examined, and 5 ml samples of venous blood were taken in heparinised tubes for a 6-month post-spray screening for DDT and plasma markers of liver function and internal organ disease. DDE/DDT was assayed using ELISA kits (Abraxis, USA); plasma enzyme activity concentrationsof amylase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transpeptidase(GGT) were analysed using routine clinical chemistryautomatedmethods (Konelab, Vantaa, Finland).Results. All 96 plasma samples analysed for xenobiotics contained DDE/DDT in the empirical range of 24.00 - 128.00 parts per billion (ppb) with a mean (SD) of 77.00 (±26.00) ppb. All 119 plasma samples studied for the markers exhibited enzyme activity concentration values within the population reference ranges, with empirical means (SD) of amylase 71.86 (34.07), AST 23.83 (12.71), ALT 7.84 (10.01) and GGT 58.37 (62.68) ìg/l.Conclusion. Six months after IRS with DDT, the spray team had an average concentration of plasma DDE/DDT of 77 ppb. This had no deleterious effect on liver function. We recommend continued use of DDT for IRS disease control in Uganda until better practical alternatives are available

Evolutionary selection of alleles in the melanophilin gene that impacts on prostate organ function and cancer risk.

BACKGROUND AND OBJECTIVES: Several hundred inherited genetic variants or SNPs that alter the risk of cancer have been identified through genome-wide association studies. In populations of European ancestry, these variants are mostly present at relatively high frequencies. To gain insight into evolutionary origins, we screened a series of genes and SNPs linked to breast or prostate cancer for signatures of historical positive selection. METHODOLOGY: We took advantage of the availability of the 1000 genome data and we performed genomic scans for positive selection in five different Caucasian populations as well as one African reference population. We then used prostate organoid cultures to provide a possible functional explanation for the interplay between the action of evolutionary forces and the disease risk association. RESULTS: Variants in only one gene showed genomic signatures of positive, evolutionary selection within Caucasian populations melanophilin (MLPH). Functional depletion of MLPH in prostate organoids, by CRISPR/Cas9 mutation, impacted lineage commitment of progenitor cells promoting luminal versus basal cell differentiation and on resistance to androgen deprivation. CONCLUSIONS AND IMPLICATIONS: The MLPH variants influencing prostate cancer risk may have been historically selected for their adaptive benefit on skin pigmentation but MLPH is highly expressed in the prostate and the derivative, positively selected, alleles decrease the risk of prostate cancer. Our study suggests a potential functional mechanism via which MLPH and its genetic variants could influence risk of prostate cancer, as a serendipitous consequence of prior evolutionary benefits to another tissue. LAY SUMMARY: We screened a limited series of genomic variants associated with breast and prostate cancer risk for signatures of historical positive selection. Variants within the melanophilin (MLPH) gene fell into this category. Depletion of MLPH in prostate organoid cultures, suggested a potential functional mechanism for impacting on cancer risk, as a serendipitous consequence of prior evolutionary benefits to another tissue

Cardiac Calcitropes, Myotropes, and Mitotropes: JACC Review Topic of the Week.

The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes

Nesiritide: Harmful or Harmless?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90328/1/phco.26.10.1465.pd

Effects of hydroxyapatite and PDGF concentrations on osteoblast growth in a nanohydroxyapatite-polylactic acid composite for guided tissue regeneration

The technique of guided tissue regeneration (GTR) has evolved over recent years in an attempt to achieve periodontal tissue regeneration by the use of a barrier membrane. However, there are significant limitations in the currently available membranes and overall outcomes may be limited. A degradable composite material was investigated as a potential GTR membrane material. Polylactic acid (PLA) and nanohydroxyapatite (nHA) composite was analysed, its bioactive potential and suitability as a carrier system for growth factors were assessed. The effect of nHA concentrations and the addition of platelet derived growth factor (PDGF) on osteoblast proliferation and differentiation was investigated. The bioactivity was dependent on the nHA concentration in the films, with more apatite deposited on films containing higher nHA content. Osteoblasts proliferated well on samples containing low nHA content and differentiated on films with higher nHA content. The composite films were able to deliver PDGF and cell proliferation increased on samples that were pre absorbed with the growth factor. nHA–PLA composite films are able to deliver active PDGF. In addition the bioactivity and cell differentiation was higher on films containing more nHA. The use of a nHA–PLA composite material containing a high concentration of nHA may be a useful material for GTR membrane as it will not only act as a barrier, but may also be able to enhance bone regeneration by delivery of biologically active molecules

Linear-T resistivity and change in Fermi surface at the pseudogap critical point of a high-Tc superconductor

A fundamental question of high-temperature superconductors is the nature of the pseudogap phase which lies between the Mott insulator at zero doping and the Fermi liquid at high doping p. Here we report on the behaviour of charge carriers near the zero-temperature onset of that phase, namely at the critical doping p* where the pseudogap temperature T* goes to zero, accessed by investigating a material in which superconductivity can be fully suppressed by a steady magnetic field. Just below p*, the normal-state resistivity and Hall coefficient of La1.6-xNd0.4SrxCuO4 are found to rise simultaneously as the temperature drops below T*, revealing a change in the Fermi surface with a large associated drop in conductivity. At p*, the resistivity shows a linear temperature dependence as T goes to zero, a typical signature of a quantum critical point. These findings impose new constraints on the mechanisms responsible for inelastic scattering and Fermi surface transformation in theories of the pseudogap phase.Comment: 24 pages, 6 figures. Published in Nature Physics. Online at http://www.nature.com/nphys/journal/vaop/ncurrent/full/nphys1109.htm

Visual recovery in a patient with total hyphema, neovascular glaucoma, long-standing retinal detachment and no light perception vision: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report the case of a patient with total hyphema, neovascular glaucoma, long-standing retinal detachment and no light perception vision, who regained counting fingers vision with complete regression of neovascularization following anterior chamber washout, intravitreal bevacizumab, pars plana vitrectomy, and silicone oil placement. This represents a rare case in which a patient with no light perception vision was able to regain functional vision.</p> <p>Case presentation</p> <p>A 63-year-old Caucasian man with a 55-year history of long-standing retinal detachment after trauma presented to our facility with pain and redness, a total hyphema, no light perception vision and an intraocular pressure of 60 mmHg (right eye). He had a history of diabetes mellitus and coronary artery disease. Following anterior chamber washout, he was found to have neovascular glaucoma, for which intravitreal bevacizumab was administered. After washout and intraocular pressure control, his visual acuity improved to light perception. He subsequently underwent vitrectomy, membrane peeling, endolaser and silicone oil placement to reattach his retina, and then a second retinal reattachment procedure. Following these procedures, he had visual recovery to counting fingers vision in his right eye at five metres, complete regression of neovascularization, and intraocular pressure of 10 to 12 mmHg on one antiglaucoma medication.</p> <p>Conclusion</p> <p>Functional vision can be regained despite long-standing retinal detachment.</p

The role of parental achievement goals in predicting autonomy-supportive and controlling parenting

Although autonomy-supportive and controlling parenting are linked to numerous positive and negative child outcomes respectively, fewer studies have focused on their determinants. Drawing on achievement goal theory and self-determination theory, we propose that parental achievement goals (i.e., achievement goals that parents have for their children) can be mastery, performance-approach or performance-avoidance oriented and that types of goals predict mothers' tendency to adopt autonomy-supportive and controlling behaviors. A total of 67 mothers (aged 30-53 years) reported their goals for their adolescent (aged 13-16 years; 19.4 % girls), while their adolescent evaluated their mothers' behaviors. Hierarchical regression analyses showed that parental performance-approach goals predict more controlling parenting and prevent acknowledgement of feelings, one autonomy-supportive behavior. In addition, mothers who have mastery goals and who endorse performance-avoidance goals are less likely to use guilt-inducing criticisms. These findings were observed while controlling for the effect of maternal anxiety

Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted β-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of KATP channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, α-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance