Search

We evaluate how regional characteristics of weather, population, and background pollution might impact the selection of optimal model resolution when calculating the human health impacts of changes to air quality. Using an approach consistent with air quality policy evaluation, we use a regional chemical transport model (CAMx) and a health benefits mapping program (BenMAP) to calculate the human health impacts associated with changes in ozone and fine particulate matter resulting from an emissions reduction scenario. We evaluate this same scenario at 36, 12 and 4 km resolution for nine regions in the Eastern US representing varied characteristics. We find that the human health benefits associated with changes in ozone concentrations are sensitive to resolution, especially in urban areas where we estimate that benefits calculated using coarse resolution results are on average two times greater than benefits calculated using finer scale results. In three urban areas we analyzed, results calculated using 36 km resolution modeling fell outside the uncertainty range of results calculated using finer scale modeling. In rural areas the influence of resolution is less pronounced with only an 8% increase in the estimated health impacts when using 36 km resolution over finer scales. In contrast, health benefits associated with changes in PM2.5 concentrations were not sensitive to resolution and did not follow a pattern based on any regional characteristics evaluated. The largest difference between the health impacts estimated using 36 km modeling results and either 12 or 4 km results was at most ± 10% in any region. Several regions showed increases in estimated benefits as resolution increased (opposite the impact seen with ozone modeling) due to a higher contribution of primary PM in those regions, while some regions showed decreases in estimated benefits as resolution increased due to a higher contribution of secondary PM. Given that changes in PM2.5 dominate the human health impacts we conclude that human health benefits associated with decreases in ozone plus PM2.5, when calculated at 36 km resolution are indistinguishable from the benefits calculated using fine (12 km or finer) resolution modeling in the context of policy decisions. [ABSTRACT FROM AUTHOR]

Presents a case study of a family in which two spontaneous miscarriages were followed by the births of two children with trisomy-G Down's syndrome. Purpose of the study; Facts about the mother's miscarriages and birth of the children with Down's syndrome; Analysis of mitotic and meiotic chromosome; Histological preparations of the father's testicular tissue; Explanations for the serial occurrence of two miscarriages and two mongol children.

The effect of lithium iodide (LiI) on the mechanical strength, properties, and molecular orientation of poly(vinyl alcohol) (PVA) fibers spun by wet spinning and then heat-stretched was studied. The stretchability of LiI-PVA fibers was improved, and the rupture during stretching was suppressed compared to PVA fibers. In addition, the tensile strength and elastic modulus of the thermally stretched fibers have been significantly improved. It was also found that the addition of LiI improves the molecular orientation of PVA. This was achieved because LiI reduced the hydrogen bonds between the molecular chains of PVA, resulting in reduced crystallinity. Most of the LiI in the fiber could be removed by a coagulation bath and washing during the spinning process. This means that LiI is eventually removed, and the heat-treatment strengthens the hydrogen bonds, resulting in excellent mechanical strength., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig-to-primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti-inflammatory agents on pro-inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients. Baboons received an artery patch (Group1, n=8) or heart (Group2, n=4) from genetically engineered pigs. All baboons received lymphodepletion with thymoglobulin (ATG) and costimulation blockade-based immunosuppression (anti-CD40 and/or CTLA4Ig). In Group1, baboons received either (i) no anti-inflammatory agents (n=2), (ii) cobra venom factor (CVF, n=2), (iii) α1-antitrypsin (AAT, n=2), or (iv) interleukin (IL)-6 receptor antagonist (IL-6RA, n=2). In Group2, all baboon received corticosteroids, either without (n=2) or with (n=2) IL-6RA. Serum IFN-γ, TNF-α, IL-1β, IL-17, IL-6, IL-8, MCP-1, and sCD40L levels were measured by Luminex. Fibrinogen, D-dimers, and C-reactive protein (C-RP) were also measured. Recipient baboon T cell proliferation was evaluated by mixed lymphocyte reaction (MLR) before and after transplantation. Pig and baboon tissue factor (TF) mRNA levels in heart xenografts were measured by RT-PCR. In no recipient was a marked increase in T cell response to pig cells observed after transplantation. In Groups 1 and 2, post-transplantation levels of IFN-γ, TNF-α, IL-1β, and IL-17 remained comparable to or lower than pre-transplant levels, except in one heart recipient that succumbed to CMV infection. In Group1, when no anti-inflammatory agent was administered, post-transplant levels of IL-6, IL-8, and MCP-1 were elevated. After CVF, IL-6, IL-8, and MCP-1 remained low. After IL-6RA, IL-6 and MCP-1 were elevated. After AAT, IL-8 was elevated. sCD40L became elevated intermittently in most recipients irrespective of the administered anti-inflammatory agent. In Group2, IL-6 was transiently elevated, particularly after IL-6RA administration. MCP-1 gradually increased by 2 months in Group2 recipients. sCD40L generally remained low except in one recipient. In Group1 and Group2 recipients, C-RP levels were elevated except after IL-6RA administration, while D-dimers were elevated regardless of administration of anti-inflammatory agent. In Group2, pig TF mRNA levels were increased in heart xenografts compared to naive pig hearts, irrespective of IL-6 receptor antagonist administration. Additionally, baboon TF mRNA levels were detectable in heart xenografts, but not in naive pig hearts. Some pro-inflammatory cytokines and chemokines are elevated in xenograft recipients, even with efficient T cell-directed immunosuppressive therapy. Persistent elevation of D-dimers, and individual cytokines and chemokines suggest a continuous inflammatory response, despite administration of anti-inflammatory agents. Systemic administration of combined anti-inflammatory agents as well as complement regulation may be essential to prevent SIXR after xenotransplantation., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The National School-Based Health Survey 2012 was a nationwide school health survey of students in Standard 4 to Form 5 (10-17 years of age), who were schooling in government schools in Malaysia during the period of data collection. The survey comprised 3 subsurveys: the Global School Health Survey (GSHS), the Mental Health Survey, and the National School-Based Nutrition Survey. The aim of the survey was to provide data on the health status of adolescents in Malaysia toward strengthening the adolescent health program in the country. The design of the survey was created to fulfill the requirements of the 3 subsurveys. A 2-stage stratified sampling method was adopted in the sampling. The methods for data collection were via questionnaire and physical examination. The National School-Based Health Survey 2012 adopted an appropriate methodology for a school-based survey to ensure valid and reliable findings., (© 2014 APJPH.)

This study is a secondary data analysis from the National Health Morbidity Survey III, a population-based study conducted in 2006. A total of 7,749 children between 7 and 12 years old were recruited into the study. This study seeks to report the prevalence of overweight (including obesity) children in Malaysia using international cut-off point and identify its associated key social determinants. The results show that the overall prevalence of overweight children in Malaysia was 19.9%. The urban residents, males, Chinese, those who are wealthy, have overweight or educated guardians showed higher prevalence of overweight. In multivariable analysis, higher likelihood of being overweight was observed among those with advancing age (OR=1.15), urban residents (OR=1.16, 95% CI: 1.01-1.36), the Chinese (OR=1.45, 95% CI: 1.19-1.77), boys (OR=1.23, 95% CI: 1.08-1.41), and those who came from higher income family. In conclusion, one out of five of 7-12 year-old-children in Malaysia were overweight. Locality of residence, ethnicity, gender, guardian education, and overweight guardian were likely to be the predictors of this alarming issue. Societal and public health efforts are needed in order to reduce the burden of disease associated with obesity.

Quinoline, isoquinoline, quinoxaline, and quinazoline derivatives were synthesized using microwave-assisted synthesis and their CB1/CB2 receptor activities were determined using the [³⁵S]GTPγS binding assay. Most of the prepared quinoline, isoquinoline, and quinoxalinyl phenyl amines showed low-potency partial CB2 receptor agonists activity. The most potent CB2 ligand was the 4-morpholinylmethanone derivative (compound 40e) (-log EC₅₀ = 7.8; E(max) = 75%). The isoquinolin-1-yl(3-trifluoromethyl-phenyl)amine (compound 26c) was a high efficacy CB2 agonist (-log EC₅₀ = 5.8; E(max) = 128%). No significant CB1 receptor activation or inactivation was shown in these studies, except 40e, which showed weak CB1 agonist activity (CB1 -log EC₅₀ = 5.0). These ligands serve as novel templates for the development of selective CB2 receptor agonist., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

[reaction: see text] A versatile, efficient, and simple method for the preparation of various 1-chloroethyl phosphates and phosphoramidates is described. The protected chlorophosphates or phosphoramidates are synthesized to the vinyl derivative under mild conditions, followed by conversion to the chloroethylidene phosphate or phosphoramidate by dry HCl gas, resulting in good to excellent yields. 1-Chloroethyl phosphates and phosphoramidates are excellent building blocks for the synthesis of novel ethylidene-linked phosphate prodrugs.

TfdA is a non-heme iron enzyme which catalyzes the first step in the oxidative degradation of the widely used herbicide (2, 4-dichlorophenoxy)acetate (2,4-D). Like other alpha-keto acid-dependent enzymes, TfdA utilizes a mononuclear Fe(II) center to activate O(2) and oxidize substrate concomitant with the oxidative decarboxylation of alpha-ketoglutarate (alpha-KG). Spectroscopic analyses of various Cu(II)-substituted and Fe(II)-reconstituted TfdA complexes via electron paramagnetic resonance (EPR), electron spin-echo envelope modulation (ESEEM), and UV-vis spectroscopies have greatly expanded our knowledge of the enzyme's active site. The metal center is coordinated to two histidine residues as indicated by the presence of a five-line pattern in the Cu(II) EPR signal, for which superhyperfine splitting is attributed to two equivalent nitrogen donor atoms from two imidazoles. Furthermore, a comparison of the ESEEM spectra obtained in H(2)O and D(2)O demonstrates that the metal maintains several solvent-accessible sites, a conclusion corroborated by the increase in multiplicity in the EPR superhyperfine splitting observed in the presence of imidazole. Addition of alpha-KG to the Cu-containing enzyme leads to displacement of an equatorial water on copper, as determined by ESEEM analysis. Subsequent addition of 2,4-D leads to the loss of a second water molecule, with retention of a third, axially bound water. In contrast to these results, in Fe(II)-reconstituted TfdA, the cosubstrate alpha-KG chelates to the metal via a C-1 carboxylate oxygen and the alpha-keto oxygen as revealed by characteristic absorption features in the optical spectrum of Fe-TfdA. This binding mode is maintained in the presence of substrate, although the addition of 2,4-D does alter the metal coordination environment, perhaps by creating an O(2)-binding site via solvent displacement. Indeed, loss of solvent to generate an open binding site upon the addition of substrate has also been suggested for the alpha-keto acid-dependent enzyme clavaminate synthase 2 [Zhou et al. (1998) J. Am. Chem. Soc. 120, 13539-13540]. Nitrosyl adducts of various Fe-TfdA complexes have also been investigated by optical and EPR spectroscopy. Of special interest is the tightly bound NO complex of Fe-TfdA.(alpha-KG).(2,4-D), which may represent an accurate model of the initial oxygen-bound species.

The first step in the degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) by Ralstonia eutropha JMP134 is catalyzed by the alpha-ketoglutarate (alpha-KG)-dependent dioxygenase TfdA. Previously, EPR and ESEEM studies on inactive Cu(II)-substituted TfdA suggested a mixture of nitrogen/oxygen coordination with two imidazole-like ligands. Differences between the spectra for Cu TfdA and alpha-KG- and 2,4-D-treated samples were interpreted as a rearrangement of the g-tensor principal axis system. Herein, we report the use of X-ray absorption spectroscopy (XAS) to further characterize the metal coordination environment of Cu TfdA as well as that in the active, wild-type Fe(II) enzyme. The EXAFS data are interpreted in terms of four N/O ligands (two imidazole-like) in the Cu TfdA sample and six N/O ligands (one or two imidazole-like) in the Fe TfdA sample. Addition of alpha-KG results in no significant structural change in coordination for Cu or Fe TfdA. However, addition of 2,4-D results in a decrease in the number of imidazole ligands in both Cu and Fe TfdA. Since this change is seen both in the Fe and Cu EXAFS, loss of one histidine ligand upon 2,4-D addition best describes the phenomenon. These XAS data clearly demonstrate that changes occur in the atomic environment of the metallocenter upon substrate binding.

The first step in catabolism of the broadleaf herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is catalyzed by 2,4-D/alpha-ketoglutarate (alpha-KG)-dioxygenase (TfdA) in Ralstonia eutropha (formerly Alcaligenes eutrophus) JMP134. This oxygen- and ferrous-ion-dependent enzyme couples the oxidative decarboxylation of alpha-KG (yielding CO2 and succinate) with the oxidation of 2,4-D to produce 2,4-dichlorophenol and glyoxylate. TfdA was shown to utilize thiophenoxyacetic acid (TPAA) to produce thiophenol, allowing the development of a continuous spectrophotometric assay for the enzyme using the thiol-reactive reagent 4,4'-dithiodipyridine. In contrast to the reaction with 2,4-D, however, the kinetics of TPAA oxidation were nonlinear and ascorbic acid was found to be required for and consumed during TPAA oxidation. The ascorbic acid was needed to reduce a reversibly oxidized inactive state that was formed by reaction of the ferrous enzyme with oxygen, either in the absence of substrate or in the presence of TPAA. The dependency on this reductant was not due to an uncoupling of alpha-KG decarboxylation from substrate hydroxylation, as has been reported for several other alpha-KG-dependent hydroxylases. Significantly, the rate of formation of this reversibly oxidized species was much lower when the enzyme was turning over 2,4-D. Evidence also was obtained for the generation of an inactive enzyme species that could not be reversed by ascorbate. The latter species, not associated with protein fragmentation, arose from an oxidative reaction that is likely to involve hydroxyl radical reactions. On the basis of initial rate studies, the kcat and Km values for TPAA were estimated to be 20-fold lower and 80-fold higher than the corresponding values for 2,4-D. The results are incorporated into a model of TfdA reactivity involving both catalytic and inactivating events.

We studied characteristics of ocular inflammation in Reiter's disease after Salmonella enteritis in eight patients. After an acute onset with diarrhea, fever in six patients, and headache in three patients, all patients developed arthritis; six patients had myalgia; six patients, urethritis; and one patient, carditis. Sacroiliitis was found in four patients. All patients had HLA-B28 antigen. Conjunctivitis occurred in seven patients. It was mostly mild with no chemosis, follicles, or keratitis, and resolved in ten days. In one case palpebral edema, chemosis in the conjunctiva, and purulent exudate were seen. One patient had transient episodes of keratitis and corneal erosion for two months and episodes of conjunctivitis for 11 months. Three patients developed unilateral acute anterior uveitis with aqueous flare, cells, fine keratic precipitates, and fibrinous exudation from three to four years after the onset of the illness. One of these patients had vitritis and macular and papillary edema.

We studied characteristics of ocular inflammation associated with Yersinia infection in 23 patients. After an acute onset with fever, diarrhea, and abdominal pain, 22 patients developed arthritis, 11 patients developed myalgia, 11 patients developed Reiter's syndrome, 17 patients developed acute anterior uveitis, and nine patients developed conjunctivitis. Sacroiliitis was found in 12 patients. The patients had high erythrocyte sedimentation rates, leukocytosis, and lack of antinuclear antibodies and rheumatoid factor. All 17 patients tested had HLA-B27 antigen. The patients with acute anterior uveitis showed aqueous flare, cells, fine keratic precipitates, and often exudates, posterior synechiae, vitritis, and macular edema. Acute anterior uveitis was mostly unilateral and resolved during corticosteroids on the average during the first six weeks; recurrences were seen in about half of the cases. Conjunctivitis was generally mild with no chemosis, follicles, or keratitis; and it resolved in one week without treatment. Our results indicate that in HLA-B27 positive patients infective agents can trigger acute anterior uveitis or conjunctivitis, which often occur together with rheumatic diseases.