Molecular characteristics of extended-spectrum beta-lactamase-producing Escherichia coli from Rio de Janeiro, Brazil

Twenty-five extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli clinical isolates from Rio de Janeiro, Brazil were characterized by isoelectric focusing, PCR and sequencing of bla(ESBL) genes, plasmid-mediated quinolone resistance determinants, phylogenetic groups, replicon typing, pulsed-field electrophoresis, and multilocus sequencing typing. Twenty-three (92%) ESBL-producing E. coli isolates were positive for bla(CTX-M) genes, aac(6`)-lb-cr, and qnrB. Genetic relatedness of ESBL producers clustered seven (28%) CTX-M-15-producing isolates as sequence type (ST) 410, clonal complex (CC) 23, and two (8%) as clone O25-ST131. Our results illustrate the predominance of phylo-group A (52%), ST410 (CC 23) and CTX-M-15 among ESBL-producing E. coli isolates from hospitals in Rio de Janeiro.

Effects of gonadotropin-releasing hormone at initiation of the 5-d timed artificial insemination (AI) program and timing of induction of ovulation relative to AI on ovarian dynamics and fertility of dairy heifers

Two experiments evaluated the effects of the first GnRH injection of the 5-d timed artificial insemination (AI) program on ovarian responses and pregnancy per AT (P/AI), and the effect of timing of the final GnRH to induce ovulation relative to AT on P/AI. In experiment 1, 605 Holstein heifers were synchronized for their second insemination and assigned randomly to receive GnRH on study d 0 (n = 298) or to remain as untreated controls (n = 307). Ovaries were scanned on study d 0 and 5. All heifers received a controlled internal drug-release (CIDR) insert containing progesterone on d 0, a single injection of PGF(2 alpha),, and removal of the CIDR on d 5, and GnRH concurrent with timed AT on d 8. Blood was analyzed for progesterone at AI. Pregnancy was diagnosed on d 32 and 60 after AI. Ovulation on study d 0 was greater for GnRH than control (35.4 vs. 10.6%). Presence of a new corpus luteum (CL) at PGF(2 alpha),, injection was greater for GnRH than for control (43.1 vs. 20.8%), although the proportion of heifers with a CL at PGF(2 alpha) did not differ between treatments and averaged 87.1%. Progesterone on the day of AT was greater for GaRH than control (0.50 +/- 0.07 vs. 0.28 +/- 0.07 ng/mL). The proportion of heifers at AI with progesterone <0.5 ng/mL was less for GURH than for control (73.8 vs. 88.2%). The proportion of heifers in estrus at AI did not differ between treatments and averaged 66.8%. Pregnancy per AI was not affected by treatment at d 32 or 60 (GnRH = 52.5 and 49.8% vs. control = 54.1 and 50.0%), and pregnancy loss averaged 6.0%. Responses to GnRH were not influenced by ovarian status on study d 0. In experiment 2, 1,295 heifers were synchronized for their first insemination and assigned randomly to receive a CIDR on d 0, PGF(2 alpha) and removal of the CIDR on d 5, and either GnRH 56 h after PGF(2 alpha) and AI 16 h later (OVS56, n = 644) or GnRH concurrent with AI 72 h after PGF(2 alpha) (COS72; n = 651). Estrus at AI was greater for COS72 than for OVS56 (61.4 vs. 47.5). Treatment did not affect P/AI on d 32 in heifers displaying signs of estrus at AI, but COS72 improved P/AI compared with OVS56 (55.0 vs. 47.6%) in those not in estrus at AI. Similarly, P/AI on d 60 did not differ between treatments for heifers displaying estrus, but COS72 improved P/AI compared with OVS56 (53.0 vs. 44.7%) in those not in estrus at AI. Administration of GnRH on the first day of the 5-d timed AI program resulted in low ovulation rate and no improvement in P/AI when heifers received a single PGF(2 alpha) injection 5 d later. Moreover, extending the proestrus by delaying the finAI GnRH from 56 to 72 h concurrent with AI benefited fertility of dairy heifers that did not display signs of estrus at insemination following the 5-d timed AI protocol.

Absolute and relative abundance estimates of Australian east cost humpback whales (Megaptera novaeangliae)

The humpback whales that migrate along the east coast of Australia were hunted to near-extinction in the 1950s and early 1960s. Two independent series of land-based surveys conducted over the last 25 years during the whales’ northward migration along the Australian coastline have demonstrated a rapid increase in the size of the population. In 2004 we conducted a survey of the migratory population as a continuation of these series of surveys. Two methods of data analysis were used in line with the previous surveys, both for calculation of absolute and relative abundance. We consider the best estimates for 2004 to be 7,090 ± 660 (95% CI) whales with an annual rate of increase of 10.6 ± 0.5% (95% CI) for 1987 – 2004. The rate of increase agrees with those previously obtained for this population and demonstrates the continuation of a strong post-exploitation recovery. While there are still some uncertainties concerning the absolute abundance estimate and structure of this population, the rate of annual increase should be independent of these and highly robust.

Algebraic Bethe ansatz for integrable extended Hubbard models arising from supersymmetric group solutions

Integrable extended Hubbard models arising from symmetric group solutions are examined in the framework of the graded quantum inverse scattering method. The Bethe ansatz equations for all these models are derived by using the algebraic Bethe ansatz method.

Integrable extended hubbard models with boundary Kondo impurities

Three kinds of integrable Kondo impurity additions to one-dimensional q-deformed extended Hubbard models are studied by means of the boundary Z(2)-graded quantum inverse scattering method. The boundary K matrices depending on the local magnetic moments of the impurities are presented as nontrivial realisations of the reflection equation algebras in an impurity Hilbert space. The models are solved by using the algebraic Bethe ansatz method, and the Bethe ansatz equations are obtained.

On single laws for varieties of quasigroups associated with extended cycle systems

It has been previously shown by Lindner and Rodger that quasigroups associated with 2-perfect extended m-cycle systems can be equationally defined if and only if m is an element of {3, 5, 7}. In this paper we present a single identity for each such m which is equivalent to the identities given for these varieties.

Closure of the Challinor Centre II: An extended report on 95 individuals after 12 months of community living

As part of an institutional closure programme, 95 individuals with an intellectual disability were relocated to community-based group homes. Each individual was assessed 6 months prior to the relocation and then again after 1, 6, and 12 months of community living. Assessments involved ratings of adaptive and maladaptive behaviour, choice-making, and life circumstances. The group means comparing institution to community ratings showed improvements in adaptive functioning but no significant change in maladaptive behaviour. There were also improvements in life circumstances and increased opportunities for choice-making following relocation to the community. These outcomes suggest that relocation to the community was associated with a more active and normalised lifestyle than experienced in the institutional setting.

Mutation analysis of the CDKN2A promoter in Australian melanoma families

Approximately 50% of all melanoma families worldwide show linkage to 9p21-22, but only about half of these have been shown to contain germ line CDKN2A mutations. It has been hypothesized that a proportion of these families carry mutations in the noncoding regions of CDKN2A. Several Canadian families have been reported to carry a mutation in the 5' UTR, at position -34 relative to the start site, which gives rise to a novel AUG translation initiation codon that markedly decreases translation from the wild-type AUG (Liu et al., 1999). Haplotype sharing in these Canadian families suggested that this mutation is of British origin. We sequenced 1,327 base pairs (bp) of CDKN2A, making up 1,116 bp of the 5' UTR and promoter, all of exon 1, and 61 bp of intron 1, in at least one melanoma case from 110 Australian families with three or more affected members known not to carry mutations within the p16 coding region. In addition, 431 bp upstream of the start codon was sequenced in an additional 253 affected probands from two-case melanoma families for which the CDKN2A mutation status was unknown. Several known polymorphisms at positions -33, -191, -493, and -735 were detected, in addition to four novel variants at positions 120, -252, -347, and -981 relative to the start codon. One of the probands from a two-case family was found to have the previously reported Q50R mutation. No family member was found to carry the mutation at position -34 or any other disease-associated mutation. For further investigation of noncoding CDKN2A mutations that may affect transcription, allele-specific expression analysis was carried out in 31 of the families with at least three affected members who showed either complete or indeterminate 9p haplotype sharing without CDKN2A exonic mutations. Reverse transcription polymerase chain reaction and automated sequencing showed expression of both CDKN2A alleles in all family members tested. The lack of CDKN2A promoter mutations and the absence of transcriptional silencing in the germ line of this cohort of families suggest that mutations in the promoter and 5' UTR play a very limited role in melanoma predisposition. (C) 2001 Wiley-Liss, Inc.

Emmetropization in chicks uses optical vergence and relative distance cues to decode defocus

When visual information is confined to one object plane, the emmetropization end-point is adjusted in accord with the corresponding incident optical vergence at the eye [Proceedings of the 7th International Conference on Myopia (2000) 113]. We now report the effect of adding extra visual information beyond the target plane. Visual conditions were controlled using a cone-lens system: black Maltese cross targets on white opaque backgrounds (OMX) were attached to the open faces of 2.5 cm translucent cones fitted with either 0, +25 or +40 D imaging lenses. An alternative target (TMX) was made by substituting the opaque target background for a transparent background, which allowed access to visual information beyond the target plane. The imaging devices were applied to 7-day-old chicks and worn for 4 days. Prior to this treatment, on day 2, some chicks underwent ciliary nerve section (CNS) to preclude accommodation. All treatments were monocular. Refractive errors and axial ocular dimensions were measured using retinoscopy and A-scan ultrasonography under halothane anesthesia. Treatment effects were specified as mean ( +/-S.D.) interocular differences. Eyes with the OMX/ + 40 D lens combination remained emmetropic ( +0.73 +/-3.57 D), consistent with the target plane being approximately conjugate with the retina. Switching to the TMX caused a hyperopic shift in refractive error ( + 3.78 +/- 3.41 D). This relative shift towards hyperopia in switching from the OMX to the TMX target also occurred for the other two lens powers. Thus, the OMX/ + 25 D lens induced myopia ( - 7.00 +/-5.88 D), corresponding to the imposed hyperopic defocus (target plane now imaged behind the retina), and switching to the TMX resulted in a reduction in myopia (-1.73 +/-5.36 D), The OMX/0 D lens combination produced the largest myopic shift, and here, switching to the TMX condition almost eliminated the myopic response (-15.50 +/-6.62 D cf. -0.56 +/-1.24 D). This relative hyperopic shift associated with switching from the OMX to the TMX target was eliminated by CNS surgery. Thus, the two CNS/TMX groups were both more myopic than the equivalent no CNS/TMX groups ( + 40 D lens: -2.66 +/-2.34 D; +25 D lens: -7.97 +/-6.87 D). When the visual information is restricted to one plane, incident optical vergence appears to direct emmetropization. Adding Visual information at other distances produces a shift in the end-point of ernmetropization in the direction of the added information. That these effects are dependent on the integrity of the accommodation system implies that accommodation plays a role in emmetropization and represents the first reported evidence of this kind. Published by Elsevier Science Ltd.

Macrocycles mimic the extended peptide conformation recognized by aspartic, serine, cysteine and metallo proteases

It has been previously demonstrated that aspartic, serine, metallo and cysteine proteases bind to their inhibitors and substrate analogues in a single conformation, the saw-tooth or extended beta-strand. Consequently a generic approach to the development of protease inhibitors is the use of constraints that conformationally restrict putative inhibitor molecules to an extended form. In this way the inhibitor is pre-organized for binding to a protease and does not need to rearrange its structure. One constraining device that has proven to be effective for such pre-organization is macrocyclization. This article illustrates the general principle that macrocycles, especially those composed of 3-4 amino acids and usually 13-17 ring atoms, can effectively mimic the extended conformation of short peptide sequences. Such structure-stabilising macrocycles are stable to degradation by proteases, valuable components of potent protease inhibitors, and in many cases they are also bioavailable.

An extended interval dosing method for gentamicin in neonates

Traditional gentamicin dosing every 8–24 h depending on age and weight in neonates does not provide the ideal concentration–time profile to both optimize the concentration-dependent killing by aminoglycosides and minimize toxicity. Fifty-three neonates were audited prospectively while receiving gentamicin 2.5 mg/kg every 8–24 h, aiming for peak concentrations (Cmax) of 6–10 mg/L and trough concentrations (Cmin) 10 mg/L after the first dose. The mean area under the concentration versus time curve AUC0–24 was 93 mg•h/L (target = 100 mg•h/L). The extended interval dosing achieved higher Cmax values while ensuring that overall exposure per 24 h was acceptable. Prospective testing of the method demonstrated good predictive ability.

Outcomes of cephalosporin treatment for serious infection due to apparently susceptible organisms producing extended-spectrum b-Lactamases: Implications for the clinical microbiology laboratory

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs, We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range, Thus, it is clinically important to detect ESBL production by klebsiellae or E, coli even when cephalosporin MICs are in the susceptible range (less than or equal to 8 mug/ml) and to report ESBL-producing organisms as resistant to aztreonam and all cephalosporins (with the exception of cephamycins).

The human melanocortin-1 receptor locus: analysis of transcription unit, locus polymorphism and haplotype evolution

The complete sequence of the MCIR locus has been assembled, the coding region of the gene is intronless and placed within a 12 kb region flanked by the NULP1 and TUBB4 genes. The immediate promoter region has an E-box site with homology to the M-box consensus known to bind the microphthalmia transcription factor (MITF), however, promoter deletion analysis and transactivation studies have failed to show activation through this element by MITF. Polymorphism within the coding region, immediate 5' promoter region and a variable number tandem repeat (VNTR) minisatellite within the locus have been examined in a collection of Caucasian families and African individuals. Haplotype analysis shows linkage disequilibrium between the VNTR and MCIR coding region red hair variant alleles which can be used to estimate the age of these missense changes. Assuming a mean VNTR mutation rate of 1% and a star phylogeny, we estimate the Arg151Cys variant arose 7500 years before the present day, suggesting these variants may have arisen in the Caucasian population more recently than previously thought. (C) 2001 Published by Elsevier Science B.V.