Epidemiologic relationship between fluoroquinolone-resistant Salmonella enterica Serovar Choleraesuis strains isolated from humans and pigs in Taiwan (1997 to 2002)

The emergence of ciprofloxacin-resistant Salmonella enterica serovar Choleraesuis in recent years has become an important public health issue in Taiwan. The resistant strains that cause human infections are considered to be from pigs. In this study, we characterized 157 swine and 42 human Salmonella serovar Choleraesuis isolates by pulsed-field gel electrophoresis (PFGE) and drug susceptibility testing to investigate the epidemiologic relationship among the isolates. By PFGE analyses, two major clusters (clusters GA and GB) were identified. Isolates in cluster GA were of both human and swine origins, while those in cluster GB were from pigs only. Among the various genotypes identified, genotype gt-1a was the most prevalent, which was found in 71% (30 of 42) and 48% (76 of 157) of human and swine isolates, respectively. The susceptibility tests for the 106 gt-1a isolates identified 44 susceptibility profiles and showed that 73% of human isolates and 34% of swine isolates were resistant to three fluoroquinolones (ciprofloxacin, enrofloxacin, and norfloxacin). Our findings indicate that a clonal group of Salmonella serovar Choleraesuis may have been circulating in human and swine populations in Taiwan for years and that the fluoroquinolone-resistant Salmonella serovar Choleraesuis strains most likely evolved from a gt-1a clone that emerged in 2000 and that then caused widespread infections in humans and pigs. Nevertheless, it is still debatable whether those Salmonella infections in humans are caused by isolates derived from pigs, on the basis of the higher fluoroquinolone and other antimicrobial resistance percentages in human isolates than in pig isolates.     

Using a photon phase-space source for convolution/superposition dose calculations in radiation therapy

For a given linac design, the dosimetric characteristics of a photon beam are determined uniquely by the energy and radial distributions of the electron beam striking the x-ray target. However, in the usual commissioning of a beam from measured data, a large number of variables can be independently tuned, making it difficult to derive a unique and self-consistent beam model. For example, the measured dosimetric penumbra in water may be attributed in various proportions to the lateral secondary electron range, the focal spot size and the transmission through the tips of a non-divergent collimator; the head-scatter component in the tails of the transverse profiles may not be easy to resolve from phantom scatter and head leakage; and the head-scatter tails corresponding to a certain extra-focal source model may not agree self-consistently with in-air output factors measured on the central axis. To reduce the number of adjustable variables in beam modelling, we replace the focal and extra-focal sources with a single phase-space plane scored just above the highest adjustable collimator in a EGS/BEAM simulation of the linac. The phase-space plane is then used as photon source in a stochastic convolution/superposition dose engine. A photon sampled from the uncollimated phase-space plane is first propagated through an arbitrary collimator arrangement and then interacted in the simulation phantom. Energy deposition kernel rays are then randomly issued from the interaction points and dose is deposited along these rays. The electrons in the phase-space file are used to account for electron contamination. 6 MV and 18 MV photon beams from an Elekta SL linac are used as representative examples. Except for small corrections for monitor backscatter and collimator forward scatter for large field sizes (<0.5% with <20 x 20 cm2 field size), we found that the use of a single phase-space photon source provides accurate and self-consistent results for both relative and absolute dose calculations.     

Effect of enterohepatic circulation on the pharmacokinetics of diflunisal in rats

The purpose of this study was to examine the effect of enterohepatic circulation on the pharmacokinetics of diflunisal in rats. The "linked animals" experiments provided evidence that diflunisal exhibits an enterohepatic circulation. Within 26 hr after iv administration of diflunisal (10 mg/kg) to rats, excretion was as follows: 42.2% of the dose, bile; 2.3%, unchanged drug; 27.8%, ester glucuronide; and 12.1%, ether glucuronide. On the average, approximately 65% of the amount of the drug and its glucuronides excreted in bile was reabsorbed from the gut. Biliary excretion and plasma data showed that biotransformation of diflunisal to its glucuronides is the rate-limiting step in their elimination. A concentration-dependent decrease in the partial formation clearance to ester glucuronide was observed with decreased concentration of diflunisal. These concentration-dependent kinetics can be at least partly explained by the nonlinear protein binding of diflunisal.     

Molecular modification of anticholinergics as probes for muscarinic receptors. 2. Amino esters of alpha-methyltropic acid

As a continuation of our goals to study molecular probes for muscarinic cholinergic receptors, a series of 3-substituted 2-methyl-2-phenylpropanoates with the general structure of C6H5C(CH2X)(CH3)COOCH2CH2NEt2 where X = OH, OTs, F, Cl, Br, I, and OAc were prepared and their antispasmodic activities examined on isolated rat ileum preparations. Structure-activity relationship studies with these compounds provide further evidence suggesting that binding of an aromatic moiety in a specific location within the hydrophobic region of the receptor is important for anticholinergic potency. A nucleophilic displacement of chloride by "naked" fluoride under mild conditions is also reported.     

Necessity of ascorbic acid in the radioligand binding assay for [3H]5-hydroxytryptamine

Evidence is presented to suggest that ascorbic acid is required in the radioligand binding assay for [3H]5-hydroxytryptamine ([3H]5-HT, [3H]serotonin). In the absence of ascorbic acid, oxidation of [3H]5-HT occurred if the radioligand solution was left on ice for 1 or 3 hr. The oxidative products were detectable by thin-layer chromatography. They increased the binding significantly, although there was only slight oxidation (less than 1%) of the [3H]5-HT. When ascorbic acid was not used in the radioligand binding assay for [3H]5-HT, even though [3H]5-HT was prepared immediately before incubating with the membranes from the cortex of the rat, the binding also increased. The increased binding of [3H]5-HT had a low affinity (Kd = 14 nM) and high B max (1180 fmol/mg protein), compared to that in the presence of ascorbic acid (Kd = 5 nM; B max = 210 fmol/mg protein). However, the increased binding was not receptor-related because the additional radioactivity was not displaceable by excess of unlabelled 5-HT (10 microM) or d-LSD (d-lysergic acid iethylamide) and anomalous "specific binding" occurred in boiled membranes from cortex, in which the binding sites for 5-HT were destroyed. These results suggest that oxidation of [3H]5-HT may occur during the incubation with membranes and that ascorbic acid is therefore required as an antioxidant.     

Clinical benefits of routine examination and synchronous repair of occult inguinal hernia during laparoscopic peritoneal dialysis catheter insertion: a single-center experience

Hernia - Occult inguinal hernias (IH) predispose peritoneal dialysis (PD) patients to the symptomatic IH formation after starting PD, which may cause complications. We conducted a retrospective...     

Viral transmission and evolution dynamics of SARS-CoV-2 in shipboard quarantine

ObjectiveTo examine transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in shipboard quarantine of the Diamond Princess cruise ship.MethodsWe obtained the full SARS-CoV-2 genome sequences of 28 samples from the Global Initiative on Sharing All Influenza Data database. The samples were collected between 10 and 25 February 2020 and came for individuals who had been tested for SARS-CoV-2 during the quarantine on the cruise ship. These samples were later sequenced in either Japan or the United States of America. We analysed evolution dynamics of SARS-CoV-2 using computational tools of phylogenetics, natural selection pressure and genetic linkage.FindingsThe SARS-CoV-2 outbreak in the cruise most likely originated from either a single person infected with a virus variant identical to the WIV04 isolates, or simultaneously with another primary case infected with a virus containing the 11083G > T mutation. We identified a total of 24 new viral mutations across 64.2% (18/28) of samples, and the virus evolved into at least five subgroups. Increased positive selection of SARS-CoV-2 were statistically significant during the quarantine (Tajima’s D: −2.03, P < 0.01; Fu and Li’s D: −2.66, P < 0.01; and Zeng’s E: −2.37, P < 0.01). Linkage disequilibrium analysis confirmed that ribonucleic acid (RNA) recombination with the11083G > T mutation also contributed to the increase of mutations among the viral progeny.ConclusionThe findings indicate that the 11083G > T mutation of SARS-CoV-2 spread during shipboard quarantine and arose through de novo RNA recombination under positive selection pressure.     

Distinguishing depression and negative symptoms in unmedicated patients with schizophrenia

Depression can occur in schizophrenia but can be difficult to distinguish from negative symptoms of the illness. To evaluate whether concurrent use of the Hamilton Rating Scale for Depression (HRSD) and the Brief Psychiatric Rating Scale (BPRS) could successfully separate depression and negative symptoms, we examined ratings on 69 unmedicated schizophrenic inpatients. A classical BPRS depression subscale score correlated highly (rho = 0.80) with the HRSD total score. The classical BPRS "negative symptom" subscale score was unrelated to both the BPRS and HRSD depression summary measures. Among individual HRSD items, negative symptoms correlated only with work/activities and retardation. The findings suggest that negative and depressive symptoms may be assessed independently.