Prospective evaluation of rapid antimicrobial susceptibility testing by disk diffusion on Mueller-Hinton rapid-SIR directly on blood cultures

Background

With the worldwide spread of antibiotic resistance, delivering antibiotic susceptibility test (AST) results in a timely manner represents a major challenge. In cases of sepsis, rapid AST may facilitate early optimization of empiric antibiotic therapy. Disc diffusion is a well-standardized AST method, however 16 to 24?h are required to achieve an overall AST profile according to antimicrobial societies.

IL-7 Is the Limiting Homeostatic Factor that Constrains Homeostatic Proliferation of CD8+ T Cells after Allogeneic Stem Cell Transplantation and Graft-versus-Host Disease

Immune reconstitution after allogeneic hematopoietic stem cell transplantation relies primarily on homeostatic proliferation (HP) of mature T lymphocytes, but this process is typically impaired during graft-versus-host disease (GVHD). We previously showed that low IL-7 levels combined with lack of dendritic cell (DC) regeneration constrain CD4⁺ T cell HP during GVHD. However, it is not clear whether these alterations to the peripheral CD4⁺ T cell niche also contribute to impair CD8⁺ T cell regeneration during GVHD. We found that IL-7 therapy was sufficient for restoring CD8⁺ T cell HP in GVHD hosts while forcing DC regeneration with Flt3-L had only a modest effect on CD8⁺ T cell HP in IL-7 treated mice. Using bone marrow chimeras, we showed that HP of naïve CD8⁺ T cells is primarily regulated by MHC class I on radio-resistant stromal cells, yet optimal recovery of CD8⁺ T cell counts still requires expression of MHC class I on both radio-resistant and radio-sensitive hematopoietic cells. Thus, IL-7 level is the primary limiting factor that constrains naïve CD8⁺ T cell HP during GVHD, and accessibility of MHC class I on stromal cells explains how IL-7 therapy, as a single agent, can induce robust CD8 ⁺ T cell HP in the absence of DCs.     

Urinary metal concentrations among mothers and children in a Mexico City birth cohort study

Personal care product use is a potential source of metals exposure among children, but studies have been limited. We measured urinary concentrations of 10 metals (aluminum, arsenic [As], barium [Ba], cadmium, cobalt [Co], lead [Pb], manganese [Mn], molybdenum [Mo], nickel, and zinc [Zn]) in third trimester pregnant women (n?=?212) and their children at 8–14 years of age (n?=?250). Demographic factors (child sex, age, socioeconomic status, and maternal education), body mass index (BMI) z-score, and child personal care product use in the 24?h prior to urine collection were examined as predictors of urinary metal concentrations. Metals were detected in 80–100% of urine samples, with significant differences in maternal versus childhood levels. However, metal concentrations were not strongly correlated within or between time points. In linear regression models including all demographic characteristics, BMI z-score, and specific gravity, age was associated with higher Co (6% [95% CI: 2, 10]), while BMI z-score was associated with lower Mo (-6% [95% CI: -11, -1). In addition, significantly higher metal concentrations were observed among users of colored cosmetics (Mo: 42% [95% CI: 1, 99]), deodorant (Ba: 28% [3, 58]), hair spray/hair gel (Mn: 22% [3, 45]), and other toiletries (As: 50% [9, 108]), as well as with an increasing number of personal care products used (As: 7% [3, 11]) after adjustment for child sex, age, total number of products used, and specific gravity. However, significantly lower metal concentrations were noted for users of hair cream (As and Zn: -20% [-36, -2] and -21% [-35, -2], respectively), shampoo (Pb: -40% [-62, -7]), and other hair products (Pb: -44% [-65, -9]). We found that personal care product use may be a predictor of exposure to multiple metals among children. Further research is recommended to inform product-specific exposure source identification and related child health risk assessment efforts.     

The sinus lift with phycogenic bone substitute. A histomorphometric study

OBJECTIVES: The aim of this histomorphometric prospective study was to ascertain the efficacy of phycogenic bone substitute in an augmented sinus. The process of graft healing, bone remodeling, and biomaterial replacement was examined. MATERIAL AND METHODS: The phycogenic material (fluorohydroxyapatite) made from calcium-encrusted sea algae was used for the sinus lifts. Twenty-four procedures were carried out (one-stage and two-stage equally) and 45 titanium stepped-screw implants were placed. The patients were followed for 12-23 months. In intervals of 6, 9, 12, or 15 months after the sinus lift, 24 graft specimens were taken with a trephine bur. These specimens were examined histomorphometrically. RESULTS: The grafting material was gradually resorbed and replaced by newly formed bone. Between the sixth and 15th month after the sinus lift, the percentage of newly formed bone grew linearly (from 15.5+/-9.6% to 40.8+/-15.3%) and the percentage of bone substitute decreased linearly (from 34.5+/-8.6% to 13+/-9.6%). After 15 months, the density of trabeculae in grafted bone corresponded to cancellous bone of good quality; however, the bone substitute was not completely resorbed during this period. No significant difference between the quality of the newly formed bone in the cases of the one- and two-stage sinus lifts was found. CONCLUSION: Sinus lift carried out with phycogenic bone substitute was shown to be an effective method with limited invasiveness and a high survival rate of implants (97.8%).     

A IIIman protein is involved in the transport of glucose,mannose and fructose by oral streptococci

We show in this article that the transport of glucose, mannose and fructose by the phosphoenolpyruvate: mannose phosphotransferase system of oral streptococci requires the participation of a protein component that we have called III_man. This protein was purified from Streptococcus salivarius by chromatography on DEAE-cellulose, DEAE-TSK, hydroxyapatite, and Dyematrex Green A. The purified protein migrated as a 38,900 molecular weight protein on a sodium dodecyl sulfate polyacrylamide gel. However, electrophoretic analysis of phosphoproteins and Western blot experiments indicated the presence in membrane-free cellular extracts of S. salivarius of 2 different forms of III_man having molecular weights of 38,900 and 35,200. The presence of the high-molecular-weight form of III_man was observed by immunodiffusion. Western blot and phosphorylation by [³²]PEP in S. salivarius, Streptococcus mutans, Streptococcus sobrinus, and Streptococcus lactis but not in Streptococcus faecium, Staphylococcus aureus, Bacillus subtilis and Lactobacillus casei. Antibodies directed against the III_man of S. salivarius did not react with the III_man of Escherichia coli.     

Alveolar bone regeneration for immediate implant placement using an injectable bone substitute: an experimental study in dogs

BACKGROUND: The aim of the present study was to assess the efficacy of a ready-to-use injectable bone substitute for bone regeneration around dental implants placed into fresh extraction sockets. METHODS: Third and fourth mandibular premolars were extracted from three beagle dogs and the interradicular septa were surgically reduced to induce a mesial bone defect. Thereafter, titanium implants were immediately placed. On the left side of the jaw, mesial bone defects were filled with an injectable bone substitute (IBS), obtained by combining a polymer and biphasic calcium phosphate ceramic granules. The right defects were left unfilled as controls. After 3 months of healing, specimens were prepared for histological and histomorphometric evaluations. RESULTS: No post-surgical complications were observed during the healing period. In all experimental conditions, histological observations revealed a lamellar bone formation in contact with the implant. Histomorphometric analysis showed that IBS triggers a significant (P<0.05) increase in terms of the number of threads in contact with bone, bone-to-implant contact, and peri-implant bone density of approximately 8.6%, 11.0%, and 14.7%, respectively. In addition, no significant difference was observed when number of threads, bone-to-implant contact, and bone density in the filled defects were compared to the no-defect sites. CONCLUSION: It is concluded that an injectable bone substitute composed of a polymeric carrier and calcium phosphate significantly increases bone regeneration around immediately placed implants.     

Long-Term Pooled Safety Analysis of Palbociclib in Combination with Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Updated Analysis with up to 5 Years of Follow-Up

BackgroundPrevious studies demonstrated the tolerability of palbociclib plus endocrine therapy (ET). This analysis evaluated safety based on more recent cutoff dates and a longer palbociclib treatment exposure.Patients and MethodsData were pooled from three randomized studies of patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative (HR+/HER2−) advanced breast cancer (ABC), including postmenopausal women who had not received prior systemic treatment for advanced disease (PALOMA‐1/‐2) and pre‐ and postmenopausal women who had progressed on prior ET (PALOMA‐3).ResultsUpdated cutoff dates were December 21, 2017 (PALOMA‐1), May 31, 2017 (PALOMA‐2), and April 13, 2018 (PALOMA‐3). Total person‐years of treatment exposure were 1,421.6 with palbociclib plus ET (n = 872) and 528.4 with ET (n = 471). Any‐grade neutropenia and infections were more frequent with palbociclib plus ET (82.1% and 59.2%, respectively) than with ET (5.1% and 39.5%). The hazard ratios were 1.6 (p = .0995) for grade 3/4 infections, 1.8 (p = .4358) for grade 3/4 viral infections, 1.4 (p = .0001) for infections, and 30.8 (p < .0001) for neutropenia. Febrile neutropenia was reported in 1.4% of patients receiving palbociclib plus ET. Cumulative incidence of all‐grade hematologic adverse events in both arms peaked during the first year of treatment and plateaued over the 5 subsequent years. Interstitial lung disease was reported in 13 patients receiving palbociclib plus ET and 3 receiving ET.ConclusionThis 5‐year, long‐term analysis demonstrated that palbociclib plus ET has a consistent and stable safety profile and is a safe treatment for patients with HR+/HER2− ABC.Implications for PracticeSeveral treatments for patients with breast cancer are associated with long‐term or latent adverse events. This long‐term, 5‐year analysis demonstrated that palbociclib plus endocrine therapy has a consistent and stable safety profile without cumulative or delayed toxicities. These results further support palbociclib plus endocrine therapy as a safe and manageable treatment in clinical practice for patients with hormone receptor‐positive/human epidermal growth factor receptor 2‐negative advanced breast cancer.     

Bayesian algorithm using spatial priors for multiexponential T(2) relaxometry from multiecho spin echo MRI

Multiexponential T₂ relaxometry is a powerful research tool for detecting brain structural changes due to demyelinating diseases such as multiple sclerosis. However, because of unusually high signal‐to‐noise ratio requirement compared with other MR modalities and ill‐posedness of the underlying inverse problem, the T₂ distributions obtained with conventional approaches are frequently prone to noise effects. In this article, a novel multivoxel Bayesian algorithm using spatial prior information is proposed. This prior takes into account the expectation that volume fractions and T₂ relaxation times of tissue compartments change smoothly within coherent brain regions. Three‐dimensional multiecho spin echo MRI data were collected from five healthy volunteers at 1.5 T and myelin water fraction maps were obtained using the conventional and proposed algorithms. Compared with the conventional method, the proposed method provides myelin water fraction maps with improved depiction of brain structures and significantly lower coefficients of variance in white matter. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.