Lead exposure assessment among pregnant women, newborns, and children: case study from Karachi, Pakistan.

Lead (Pb) in petrol has been banned in developed countries. Despite the control of Pb in petrol since 2001, high levels were reported in the blood of pregnant women and children in Pakistan. However, the identification of sources of Pb has been elusive due to its pervasiveness. In this study, we assessed the lead intake of pregnant women and one- to three-year-old children from food, water, house dust, respirable dust, and soil. In addition, we completed the fingerprinting of the Pb isotopic ratios (LIR) of petrol and secondary sources (food, house-dust, respirable dust, soil, surma (eye cosmetics)) of exposure within the blood of pregnant women, newborns, and children. Eight families, with high (~50 μg/dL), medium (~20 μg/dL), and low blood levels (~10 μg/dL), were selected from 60 families. The main sources of exposure to lead for children were food and house-dust, and those for pregnant women were soil, respirable dust, and food. LIR was determined by inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) with a two sigma uncertainty of ±0.03%. The LIR of mothers and newborns was similar. In contrast, surma, and to a larger extent petrol, exhibited a negligible contribution to both the child’s and mother’s blood Pb. Household wet-mopping could be effective in reducing Pb exposure. This intake assessment could be replicated for other developing countries to identify sources of lead and the burden of lead exposure in the population

TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP

Transient receptor potential V3 (TRPV3) and TRPV4 are heat-activated cation channels expressed in keratinocytes. It has been proposed that heat-activation of TRPV3 and/or TRPV4 in the skin may release diffusible molecules which would then activate termini of neighboring dorsal root ganglion (DRG) neurons. Here we show that adenosine triphosphate (ATP) is such a candidate molecule released from keratinocytes upon heating in the co-culture systems. Using TRPV1-deficient DRG neurons, we found that increase in cytosolic Ca(2+)-concentration in DRG neurons upon heating was observed only when neurons were co-cultured with keratinocytes, and this increase was blocked by P2 purinoreceptor antagonists, PPADS and suramin. In a co-culture of keratinocytes with HEK293 cells (transfected with P2X(2) cDNA to serve as a bio-sensor), we observed that heat-activated keratinocytes secretes ATP, and that ATP release is compromised in keratinocytes from TRPV3-deficient mice. This study provides evidence that ATP is a messenger molecule for mainly TRPV3-mediated thermotransduction in skin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00424-009-0703-x) contains supplementary material, which is available to authorized users

Shortened cataract surgery by standardisation of the perioperative protocol according to the Joint Commission International accreditation: a retrospective observational study

OBJECTIVES: To investigate the impact of standardisation of the perioperative protocol based on the Joint Commission International (JCI) accreditation guidelines for operating time in cataract surgery. DESIGN: Retrospective observational study. SETTING: Single centre in Japan. PARTICIPANTS: Between March 2014 and June 2016, 3127 patients underwent cataract surgery under topical anaesthesia including 2581 and 546 patients before and after JCI accreditation, respectively. PRIMARY AND SECONDARY OUTCOMES: We compared three time periods, comprising the preprocedure/surgery time (pre-PT), PT and post-PT, and total PT (TPT) of cataract surgery between patients before and after JCI accreditation, by regression analysis adjusted for age, sex and cataract surgery-associated confounders. RESULTS: The main outcomes were pre-PT, PT, post-PT and TPT. Pre-PT (19.8+/-10.5 vs 13.9+/-8.5 min, p \u3c 0.001) and post-PT (3.5+/-4.6 vs 2.6+/-2.1 min, p \u3c 0.001) significantly decreased after JCI accreditation, while PT did not significantly change (16.8+/-6.7 vs 16.2+/-6.3 min, p=0.065). Consequently, TPT decreased on average by 7.3 min per person after JCI accreditation (40.1+/-13.4 vs 32.8+/-10.9 min, p \u3c 0.001). After adjusting for confounders, pre-PT (beta=-5.82 min, 95% CI -6.75 to -4.88), PT (beta=-0.76 min, 95% CI -1.34 to -1.71), post-PT (beta=-0.85 min, 95% CI -1.24 to -0.45) and TPT (beta=-7.43 min, 95% CI -8.61 to -6.24) were significantly shortened after JCI accreditation. CONCLUSION: Perioperative protocol standardisation, based on JCI accreditation, shortened TPT in cataract surgery under local anaesthesia

Opn5L1 is a retinal receptor that behaves as a reverse and self-regenerating photoreceptor

Most opsins are G protein-coupled receptors that utilize retinal both as a ligand and as a chromophore. Opsins’ main established mechanism is light-triggered activation through retinal 11-cis-to-all-trans photoisomerization. Here we report a vertebrate non-visual opsin that functions as a Gi-coupled retinal receptor that is deactivated by light and can thermally self-regenerate. This opsin, Opn5L1, binds exclusively to all-trans-retinal. More interestingly, the light-induced deactivation through retinal trans-to-cis isomerization is followed by formation of a covalent adduct between retinal and a nearby cysteine, which breaks the retinal-conjugated double bond system, probably at the C11 position, resulting in thermal re-isomerization to all-trans-retinal. Thus, Opn5L1 acts as a reverse photoreceptor. We conclude that, like vertebrate rhodopsin, Opn5L1 is a unidirectional optical switch optimized from an ancestral bidirectional optical switch, such as invertebrate rhodopsin, to increase the S/N ratio of the signal transduction, although the direction of optimization is opposite to that of vertebrate rhodopsin

ZMYND10 functions in a chaperone relay during axonemal dynein assembly

Molecular chaperones promote the folding and macromolecular assembly of a diverse set of ‘client’ proteins. How ubiquitous chaperone machineries direct their activities towards specific sets of substrates is unclear. Through the use of mouse genetics, imaging and quantitative proteomics we uncover that ZMYND10 is a novel co-chaperone that confers specificity for the FKBP8-HSP90 chaperone complex towards axonemal dynein clients required for cilia motility. Loss of ZMYND10 perturbs the chaperoning of axonemal dynein heavy chains, triggering broader degradation of dynein motor subunits. We show that pharmacological inhibition of FKBP8 phenocopies dynein motor instability associated with the loss of ZMYND10 in airway cells and that human disease-causing variants of ZMYND10 disrupt its ability to act as an FKBP8-HSP90 co-chaperone. Our study indicates that primary ciliary dyskinesia (PCD), caused by mutations in dynein assembly factors disrupting cytoplasmic pre-assembly of axonemal dynein motors, should be considered a cell-type specific protein-misfolding disease

Influence of Temperature on the Anti-allergic Activity of Fucoidan Extracted from Saccharina japonica

It has been ascertained in our laboratory that fucoidan, a polysaccharide contained in Saccharina japonica, shows anti-allergic activity through galectin 9 secretion in blood. A crude fucoidan fraction was chromatographically fractionated into three fractions using a Toyopearl-DEAE 650 M column in stepwise elusion with 0, 0.5 and 1.0 M NaCl in 0.05 M Tris-HCl buffer (pH 7.4). Each fraction was assessed using the passive cutaneous anaphylaxis (PCA) reaction. The non-absorbed fraction of the three fractions suppressed PCA, whereas the fractions eluted with 0.5 M and 1.0 M NaCl did not. Moreover, it was discovered that heat treatment of fucoidan at 50 °C for 10 min abolished its anti-allergic activity in the PCA reaction. Using DEAE chromatography, it was demonstrated that heat-treatment of the crude fucoidan fraction decreased the non-absorbed fraction, which possessed the anti-allergic activity, and increased the two fractions eluted with 0.5 M and 1.0 M NaCl. This clearly revealed the importance of temperature in maintaining the anti-allergic activity of fucoidan