Anxiety-provoking and painful emergency department procedures such as laceration repair are made more tolerable to the pediatric patient and easier for the practitioner through the judicious use of ...pharmacologic agents for conscious sedation and analgesia. Both the American Academy of Pediatrics and the American College of Emergency Physicians have published documents that guide the physician in the use of these agents in the care of children. Most new information concerns the evaluation of new drugs for use in the pediatric emergency department, adverse effects of familiar products, and evaluation of sedative and analgesic antagonist medications that may increase a practitioner's control when conscious sedation is used. Large controlled trials of protocols and drugs are necessary to establish safe, appropriate standards for conscious sedation in the pediatric emergency department.
ABSTRACT
The gene (
dctA
) encoding the aerobic C
4
-dicarboxylate transporter (DctA) of
Escherichia coli
was previously mapped to the 79-min region of the linkage map. The nucleotide sequence of ...this region reveals two candidates for the
dctA
gene:
f428
at 79.3 min and the
o157a-o424-o328
(or
orfQMP
) operon at 79.9 min. The
f428
gene encodes a homologue of the
Sinorhizobium meliloti
and
Rhizobium leguminosarum
H
+
/C
4
-dicarboxylate symporter, DctA, whereas the
orfQMP
operon encodes homologues of the aerobic periplasmic-binding protein- dependent C
4
-dicarboxylate transport system (DctQ, DctM, and DctP) of
Rhodobacter capsulatus
. To determine which, if either, of these loci specify the
E. coli
DctA system, the chromosomal
f428
and
orfM
genes were inactivated by inserting Sp
r
or Ap
r
cassettes, respectively. The resulting
f428
mutant was unable to grow aerobically with fumarate or malate as the sole carbon source and grew poorly with succinate. Furthermore, fumarate uptake was abolished in the
f428
mutant and succinate transport was ∼10-fold lower than that of the wild type. The growth and fumarate transport deficiencies of the
f428
mutant were complemented by transformation with an
f428
-containing plasmid. No growth defect was found for the
orfM
mutant. In combination, the above findings confirm that
f428
corresponds to the
dctA
gene and indicate that the
orfQMP
products play no role in C
4
-dicarboxylate transport. Regulation studies with a
dctA-lacZ
(
f428-lacZ
) transcriptional fusion showed that
dctA
is subject to cyclic AMP receptor protein (CRP)-dependent catabolite repression and ArcA-mediated anaerobic repression and is weakly induced by the DcuS-DcuR system in response to C
4
-dicarboxylates and citrate. Interestingly, in a
dctA
mutant, expression of
dctA
is constitutive with respect to C
4
-dicarboxylate induction, suggesting that DctA regulates its own synthesis. Northern blot analysis revealed a single, monocistronic
dctA
transcript and confirmed that
dctA
is subject to regulation by catabolite repression and CRP. Reverse transcriptase-mediated primer extension indicated a single transcriptional start site centered 81 bp downstream of a strongly predicted CRP-binding site.
A kinetic scheme is presented for Lactobacillus casei dihydrofolate reductase that predicts steady-state kinetic parameters. This scheme was derived from measuring association and dissociation rate ...constants and pre-steady-state transients by using stopped-flow fluorescence and absorbance spectroscopy. Two major features of this kinetic scheme are the following: (i) product dissociation is the rate-limiting step for steady-state turnover at low pH and follows a specific, preferred pathway in which tetrahydrofolate (H4F) dissociation occurs after NADPH replaces NADP+ in the ternary complex; (ii) the rate constant for hydride transfer from NADPH to dihydrofolate (H2F) is rapid (khyd = 430 s-1), favorable (Keq = 290), and pH dependent (pKa = 6.0), reflecting ionization of a single group. Not only is this scheme identical in form with the Escherichia coli kinetic scheme Fierke et al. (1987) Biochemistry 26, 4085 but moreover none of the rate constants vary by more than 40-fold despite there being less than 30% amino acid homology between the two enzymes. This similarity is consistent with their overall structural congruence. The role of Trp-21 of L. casei dihydrofolate reductase in binding and catalysis was probed by amino acid substitution. Trp-21, a strictly conserved residue near both the folate and coenzyme binding sites, was replaced by leucine. Two major effects of this substitution are on (i) the rate constant for hydride transfer which decreases 100-fold, becoming the rate-limiting step in steady-state turnover, and (ii) the affinities for NADPH and NADP+ which decrease by approximately 3.5 and approximately 0.5 kcal mol-1, respectively.
To determine the sensitivity, specificity, and charges associated with single-specimen bile cytologic study in patients with obstructive jaundice.
Eighty consecutive patients with presumed malignant ...biliary strictures underwent percutaneous biliary drainage (PBD). Cytologic evaluation was performed on a single bile specimen from each patient collected at the time of the PBD. Final diagnoses were obtained from either percutaneous (n = 14) or surgical (n = 66) histologic specimens (gold standard). Both data sets were then compared to determine the sensitivity and specificity of bile cytology. The charges associated with bile cytodiagnosis were compared to those for other biopsy procedures utilized in the same setting.
Eighty bile specimens were obtained with a mean of 14 mL (range, 3-65 mL) per patient with 79 (99%) specimens adequate for cytologic processing. Eleven (13%) specimens were acellular. The overall sensitivity was 15% and specificity was 100%; these values were not dependent on the volume of the bile specimen (P > .10) or type of malignancy (P = .10). For bile cytodiagnosis, the mean charge was $160 and the successful biopsy rate (true-positive plus true-negative results/total number procedures) was 27%.
Single-specimen bile cytology has a low sensitivity; however, because of its convenience, simplicity, atraumatic nature, and low relative charge versus comparable procedures, it may be useful as an adjunct to PBD in patients with suspected malignant biliary disease.
Background. Protamine administration can cause left ventricular (LV) dysfunction, which may have clinical significance in the setting of congestive heart failure (CHF). Protamine variants have ...recently been constructed with heparin reversal capacity similar to protamine. The purpose of this study was to examine the potential differential effects of these protamine variants on isolated myocyte contractile function in normal myocytes and in myocytes after the development of CHF.
Methods. Contractile function was measured by means of computer-aided videomicroscopy in myocytes from five normal pigs and five pigs with CHF induced by rapid pacing (240 beats/min for 3 weeks). Myocyte contractility was examined in the presence of 40 μg/ml native protamine or one of three protamine variants: (1) reduced charge (+18) and lysine substituted for arginine; (2) lysine-substituted variant with glutamic acid substituted for the initial proline; or (3) arginine-rich peptide with a terminal arginine-glycine-aspartic acid (RGD) amino acid sequence.
Results. In the presence of native protamine, myocyte percent shortening fell from baseline in both the normal (2.86 ± 0.15 versus 4.58 ± 0.08, p < 0.05) and the CHF groups (1.01 ± 0.06 versus 2.07 ± 0.05, p < 0.05). With both of the lysine-substituted protamine variants, percent shortening fell from baseline in the normal group (3.42 ± 0.20 for arginine and 3.74 ± 0.20 for glutamic acid versus 4.58 ± 0.08, p < 0.05), and was unchanged in the CHF group (1.94 ± 0.13 versus 2.07 ± 0.05, p = 0.34 for arginine; and 1.96 ± 0.10 versus 2.07 ± 0.05, p = 0.31, for glutamic acid). However, with the arginine/RGD variant, percent shortening fell from baseline in both the normal (2.86 ± 0.23 versus 4.58 ± 0.08, p < 0.05) and the CHF groups (1.32 ± 0.10 versus 2.07 ± 0.05, p < 0.05).
Conclusions. Specific changes in the primary and secondary structures of protamine had different effects on myocyte contractile function. Furthermore, the negative effects of ly sine-substituted protamine variants on myocyte contractility were less pronounced in both CHF and normal myocytes. Thus protamine variants may be of clinical use, particularly in the setting of preexisting LV dysfunction.
Supernova (SN) 2018oh (ASASSN-18bt) is the first spectroscopically-confirmed
type Ia supernova (SN Ia) observed in the $Kepler$ field. The $Kepler$ data
revealed an excess emission in its early light ...curve, allowing to place
interesting constraints on its progenitor system (Dimitriadis et al. 2018,
Shappee et al. 2018b). Here, we present extensive optical, ultraviolet, and
near-infrared photometry, as well as dense sampling of optical spectra, for
this object. SN 2018oh is relatively normal in its photometric evolution, with
a rise time of 18.3$\pm$0.3 days and $\Delta$m$_{15}(B)=0.96\pm$0.03 mag, but
it seems to have bluer $B - V$ colors. We construct the "uvoir" bolometric
light curve having peak luminosity as 1.49$\times$10$^{43}$erg s$^{-1}$, from
which we derive a nickel mass as 0.55$\pm$0.04M$_{\odot}$ by fitting radiation
diffusion models powered by centrally located $^{56}$Ni. Note that the moment
when nickel-powered luminosity starts to emerge is +3.85 days after the first
light in the Kepler data, suggesting other origins of the early-time emission,
e.g., mixing of $^{56}$Ni to outer layers of the ejecta or interaction between
the ejecta and nearby circumstellar material or a non-degenerate companion
star. The spectral evolution of SN 2018oh is similar to that of a normal SN Ia,
but is characterized by prominent and persistent carbon absorption features.
The C II features can be detected from the early phases to about 3 weeks after
the maximum light, representing the latest detection of carbon ever recorded in
a SN Ia. This indicates that a considerable amount of unburned carbon exists in
the ejecta of SN 2018oh and may mix into deeper layers.
TWI biaxial test program: 1984–1994 Phaal, R.; Andrews, R.M.; Garwood, S.J.
International journal of pressure vessels and piping,
1995, 1995-1-00, 19950101, Letnik:
64, Številka:
3
Journal Article, Conference Proceeding
Recenzirano
The majority of welded structures experience complex loading. For example girth and seam welds in pressure vessels are subject to biaxial stress fields. However, the integrity of such structures is ...routinely assessed using fracture assessment methods such as BSI PD6493:1991, which takes no account of biaxial loading. A series of test programmes investigating the effects of biaxial loading on the fracture behaviour of A533B pressure vessel steel commenced at The Welding Institute (TWI) in 1984, funded by the UK Nuclear Installations Inspectorate (NII). A complementary program of work was carried out with the same material for the former Central Electricity Generating Board (CEGB). The influence of biaxiality on the upper shelf (+70 deg C), lower shelf (-130 to -160 deg C) and the ductile-to-brittle transition (-100 deg to -70 deg C) has been investigated using a purpose built wide plate rig which applies biaxial loading of up to 12.5 MN. All wide plate tests have been assessed to R6/PD6493 procedures to evaluate the conservatism of the procedures for assessing A533B under the action of a biaxial stress field. In addition the effect of biaxiality has been investigated using nonlinear finite element analysis, indicating that constraint due to biaxiality may be an important consideration when assessing leak-before-break conditions for pressure vessels.
Previously we demonstrated that, in low-income NYC communities, where cat ownership is less common than in suburban communities, cat ownership increased risk for developing sensitization but, ...surprisingly, not for asthma symptoms.
NYC Neighborhood Asthma and Allergy case-control study recruited MIDDLE-INCOME children from the same employer-based health insurance who lived in low (LAPN) (Group A) and high (HAPN) (Group B) ...asthma prevalence neighborhoods.