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Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions.

Organophosphates (OPs) are routinely used as pesticides in agriculture and as insecticides within the household. Our prior work on Reelin and APOE delineated a gene-environment interactive model of autism pathogenesis, whereby genetically vulnerable individuals prenatally exposed to OPs during critical periods in neurodevelopment could undergo altered neuronal migration, resulting in an autistic syndrome. Since household use of OPs is far greater in the USA than in Italy, this model was predicted to hold validity in North America, but not in Europe. Here, we indirectly test this hypothesis by assessing linkage/association between autism and variants of the paraoxonase gene (PON1) encoding paraoxonase, the enzyme responsible for OP detoxification. Three functional single nucleotide polymorphisms, PON1 C-108T, L55M, and Q192R, were assessed in 177 Italian and 107 Caucasian-American complete trios with primary autistic probands. As predicted, Caucasian-American and not Italian families display a significant association between autism and PON1 variants less active in vitro on the OP diazinon (R192), according to case-control contrasts (Q192R: chi2=6.33, 1 df, P<0.025), transmission/disequilibrium tests (Q192R: TDT chi2=5.26, 1 df, P<0.025), family-based association tests (Q192R and L55M: FBAT Z=2.291 and 2.435 respectively, P<0.025), and haplotype-based association tests (L55/R192: HBAT Z=2.430, P<0.025). These results are consistent with our model and provide further support for the hypothesis that concurrent genetic vulnerability and environmental OP exposure may possibly contribute to autism pathogenesis in a sizable subgroup of North American individuals.

Aryldialkylphosphatase↗

Subcontinental-scale crustal velocity changes along the Pacific-North America plate boundary.

Transient tectonic deformation has long been noted within approximately 100 km of plate boundary fault zones and within active volcanic regions, but it is unknown whether transient motions also occur at larger scales within plates. Relatively localized transients are known to occur as both seismic and episodic aseismic events, and are generally ascribed to motions of magma bodies, aseismic creep on faults, or elastic or viscoelastic effects associated with earthquakes. However, triggering phenomena and systematic patterns of seismic strain release at subcontinental (approximately 1,000 km) scale along diffuse plate boundaries have long suggested that energy transfer occurs at larger scale. Such transfer appears to occur by the interaction of stresses induced by surface wave propagation and magma or groundwater in the crust, or from large-scale stress diffusion within the oceanic mantle in the decades following clusters of great earthquakes. Here we report geodetic evidence for a coherent, subcontinental-scale change in tectonic velocity along a diffuse approximately 1,000-km-wide deformation zone. Our observations are derived from continuous GPS (Global Positioning System) data collected over the past decade across the Basin and Range province, which absorbs approximately 25 per cent of Pacific-North America relative plate motion. The observed changes in site velocity define a sharp boundary near the centre of the province oriented roughly parallel to the north-northwest relative plate motion vector. We show that sites to the west of this boundary slowed relative to sites east of it by approximately 1 mm yr(-1) starting in late 1999.

Letter↗

[Appropriate antibiotic prophylaxis and treatment in surgery--comparison of concepts in North America and Japan].

Three principles must be followed to maximize the benefits of antimicrobial prophylaxis (AMP): 1) use an AMP agent that is bactericidal with a spectrum that covers the most probable intraoperative contaminants; 2) the initial dose of AMP agents should be given no more than 30 min before the skin is incised: and 3) maintain effective levels of antibiotics throughout the surgery and until at most a few hours after the incision is closed in the operating room. These recommendations have become standardized in North America and Europe. A few controversies, however, persist in Japan, especially concerning the duration of AMP. Most practitioners recommend that prophylaxis be continued until postoperative day 3 to 4. However, some authors reported that the administration of AMP agents for 3 to 4 days causes the development of resistant strains. It is thus necessary to formulate national guidelines for appropriate AMP which are validated by the results of randomized, controlled trials conducted in Japan. In the treatment of postoperative infections, Gram-stain-based antibiotic selection is necessary and full knowledge of the interrelationships between pharmacokinetics and pharmacodynamics is important for determining effective regimens. The time that serum levels exceed the minimum inhibitory concentration is the most significant parameter determining the efficacy of beta-lactams, whereas the log area under the curve and peak serum level are the major parameters for aminoglycosides and new quinolones, respectively. Careful application of these concepts should allow surgeons to use more optimal dosing regimens in Japan.

Anti-Bacterial Agents↗

Annual rotavirus epidemic patterns in North America. Results of a 5-year retrospective survey of 88 centers in Canada, Mexico, and the United States. Rotavirus Study Group.

Rotavirus is the major cause of severe diarrhea in children. A recent study of hospitalizations for diarrhea in the United States suggested that the annual rotavirus epidemic may follow a regional sequence from west to east. As part of a program to establish active surveillance of rotavirus prior to the introduction of vaccines, we obtained 5 years of retrospective data on rotavirus detections from 88 centers throughout North America. Analysis of 34,644 detections indicates that the peak of the annual rotavirus epidemic occurs first in Mexico and the Southwest of the United States in late fall, goes systematically across the continent in the winter, and ends in the Northeast United States and the Maritime Provinces of Canada in the spring. When detections are grouped by region, onset of the epidemic follows the same regional sequence as the peak. To our knowledge, this is the only description of a repetitive geographic sequence for the seasonal epidemic activity of a viral agent. Further studies are indicated to determine whether climate, features of the virus itself, or other factors are responsible for this apparently unique pattern. A system of active surveillance can use this pattern to detect natural alterations in the epidemic behavior of rotavirus and to assess the impact of vaccines.

Canada↗

Preparation of mercury emissions inventory for eastern North America.

Point and area inventories of anthropogenic mercury emissions documented by US and Canadian environmental agencies have been aggregated into a single archive for analysis and air pollution modeling work. For 5341 point sources and 1634 aggregated area sources, mercury emissions are apportioned among elemental gaseous [Hg(0)], reactive gaseous[Hg(II)], and particulate [Hg(p)] emissions using speciation factors derived from available monitoring measurements. According to this inventory, 4.82 x 10(5) mol of mercury were emitted in calendar year 1996 in the latitude range 24-51 degrees north, and longitude range 64-91 degrees west, which covers most of North America east of the Mississippi River. Using speciation factors consistent with past emission source studies, we find the relative emission proportions among Hg(0):Hg(II):Hg(p) species are 47:35:18. Maps of the various mercury species' emissions patterns are presented. Gridded emission patterns show local mercury emission extremes associated with individual cement production and municipal incineration facilities, and in contrast to past inventories, population centers do not stand out. Considerable uncertainties are still present in estimating emissions from large point sources, as are methods of apportioning emissions among various mercury species.

Air Pollutants↗

A comparison of blood lead levels in bald eagles from two regions on the great plains of North America.

The connection between bald eagles (Haliaeetus leucocephalus) and the consumption of waterfowl, lead shotshell pellet ingestion, and subsequent lead exposure is well documented in the United States and is presumed also to be widespread in Canada. We compared blood lead concentrations in samples from bald eagles ranging in age from 0.5- to 1.5-yr-old at Galloway Bay, Saskatchewan, Canada (n = 97) during October-November, 1992-95 and Hauser Lake, Montana, USA (n = 81) during October-December, 1990-94, within the Great Plains region of North America. Abundant prey are available in the form of hunter-injured waterfowl in Saskatchewan and spawning salmon in Montana; both areas attract large numbers of mid-continent bald eagles during fall migration. Blood lead concentrations suggestive of recent lead exposure (> 0.201 microgram/ml) were found in 32% and 8% of eagles at Hauser Lake and Galloway Bay, respectively, when samples from each study area were analyzed independently at two laboratories. To determine if this difference was an artifact of interlaboratory variation, we determined a correction factor by reanalyzing 14 Saskatchewan blood samples at each laboratory and predicted blood lead concentrations from Hauser Lake had the samples been analyzed at the Canadian laboratory. Adjusted blood lead concentrations of samples from Hauser Lake indicated that 21% of eagles were recently exposed to lead, a proportion not significantly different from the proportion of the same exposure category at Galloway Bay. Our data do not support the supposition that a large proportion of bald eagles feeding on waterfowl in areas of high hunting pressure will be exposed to lead via consumption of lead shotshell pellets in waterfowl.

Animals↗

Strains of JC virus in Amerind-speakers of North America (Salish) and South America (Guaraní), Na-Dene-speakers of New Mexico (Navajo), and modern Japanese suggest links through an ancestral Asian population.

Previously we showed that strains of human polyoma virus JC among the Navajo in New Mexico, speakers of an Athapaskan language in the Na-Dene language phylum, and among the Salish people in Montana, speakers of a language of the Salishan group in the Amerind family, were mainly of a northeast Asian genotype found in Japan (type 2A). We now report partial VP1-gene, regulatory region, and complete genome sequences of JC virus (JCV) from the Guaraní Indians of Argentina. The Tupí-Guaraní language represents the Equatorial branch of the Amerind language family proposed by Greenberg ([1987] Language in the Americas, Stanford: Stanford University Press). The partial VP1 gene sequences of the Guaraní revealed several variants of strains found in northeast Asia (Japan), as did the Salish. In contrast, the strains in the Navajo largely conformed to the prototype type 2A sequence (MY). Phylogenetic reconstruction with both the neighbor-joining and maximum parsimony methods utilized three complete Guaraní JCV genome sequences, three genomes from the Salish people, and 27 other complete JCV genomes, including three from the Navajo and three from Japan. Both trees showed that all type 2A JCV strains from the North and South Americans are closely related phylogenetically to strains in present-day Japan. However, variant sites in the coding regions, the T-antigen intron, and the regulatory region link the type 2A strains in Amerind groups (Guaraní and Salish), but differentiate them from those in a Na-Dene-speaking (Navajo) population. The data suggest separation from a population ancestral to modern Japanese, followed by a second division within the ancestral group that led to Amerind- and Na-Dene-speaking groups. The data cannot, however, localize the latter split to the Asian mainland (two migrations) or to North America (one migration).

Adult↗