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This study investigated 2 hypotheses about genotype-phenotype relationships for the efflux transporter, P-glycoprotein: (1) the presence of a synonymous C3435T variant in exon 26 of the MDR1 gene correlates to higher plasma concentrations of a P-glycoprotein substrate, dicloxacillin, and (2) the effects of genotypic differences decrease under conditions of P-glycoprotein induction by rifampin. Eighteen healthy volunteers received two 1-g doses of dicloxacillin, one on the 1st study day and the other on the 11th day of rifampin dosing (600 mg daily). Dicloxacillin and its 5-hydroxymethyl metabolite were analyzed using liquid chromatography/tandem mass spectrometry. Mean dicloxacillin C(max) measurements were 30.5 +/- 13.5, 33.3 +/- 4.7, and 31.1 +/- 12.8 mug/mL in individuals with the CC, CT, and TT genotype at position 3435 in exon 26 of the MDR1 gene. Following rifampin dosing, the mean dicloxacillin C(max) across genotypes decreased from 31.4 +/- 10.8 to 22.9 +/- 7.0 microg/mL (P < .05), whereas the mean oral clearance increased from 235 +/- 82 to 297 +/- 71 mL/min (P < .001), and the mean absorption time increased from 0.71 +/- 0.55 to 1.34 +/- 0.77 h (P < .05). Rifampin treatment increased the formation clearance, C(max), and AUC of the 5-hydroxymethyl metabolite by 135%, 119%, and 59%, respectively. The C3435T variant had no effect on dicloxacillin pharmacokinetics. The data suggested that rifampin induced intestinal P-glycoprotein and increased dicloxacillin metabolism. [ABSTRACT FROM AUTHOR]

In a prospective, explorative study, the donor-source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft-versus-host disease (GVHD) in HF-HCT patients (49%, 7%, and 16% for HF-, MS- and UD-HCT respectively; p < 0.001). A quarter of acute GVHD cases observed in HF-HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri-engraftment acute GVHD was not observed in MS-HCT or UD-HCT patients. Additionally, a significantly higher proportion of HF-HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF-, MS- and UD-HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non-relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG-containing conditioning, stronger donor-patient alloreactivity was observed in HF-HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Objective:   To replicate a previously reported association between pollen counts and county suicide rates in the continental United States, across space and time., Method:   The authors evaluated the relationship between airborne pollen counts and suicide rates in 42 counties of the continental United States, containing a pollen-counting station participating in the Aeroallergen Monitoring Network in the United States (N = 120,076 suicides), considering years' quarter, age group, sex, race, rural/urban location, number of local psychiatrists, and median household income, from 1999 to 2002. The county-level effects were broken into between-county and within-county., Results:   No within-county effects were found. Between-county effects for grass and ragweed pollen on suicide rates lost statistical significance after adjustment for median income, number of psychiatrists, and urban vs. rural location., Conclusion:   Future research is necessary to reappraise the previously reported relationship between pollen levels and suicide rates that may have been driven by socioeconomic confounders., (© 2011 John Wiley & Sons A/S.)

Statement of Problem: A recent study reported a decrease in dentin fracture toughness after the application of peroxide bleaching products to dentin in vitro., Purpose: The objective of the present study was to investigate this in vitro decrease in fracture toughness further by evaluating the effect of different peroxide application times on dentin fracture toughness., Materials and Methods: Compact test fracture toughness specimens were prepared from coronal human. These were divided into five groups (N = 12) and subjected to either bleach (10% carbamide peroxide) and/or placebo gel for a total of 336 consecutive hours (0 and 336, 84 and 252, 168 and 168, 252 and 84, 336 and 0 hours of bleach and placebo application time, respectively). The gel materials were changed every 6 hours. Fracture toughness testing was done 24 hours after the end of bleaching using tensile loading at 10 mm/min. Results were analyzed by analysis of variance and linear regression (p < 0.05)., Results: Dentin fracture toughness after 252 and 336 hours was significantly reduced compared to the 0- and 84-hour bleach times. An association between fracture toughness and bleach time (r(2) = 0.82) with an inverse linear regression line (K(1C) = -0.0032 [hour] + 3.386) was found., Conclusions: A significant correlation was found between bleach time and dentin fracture toughness. Dentin fracture toughness was reduced over time during the 336-hour course of in vitro bleaching., Clinical Significance: The results suggest that it would be prudent to minimize the length of time for clinical bleaching procedures when dentin is directly exposed to bleach.