Treatment of combat-related traumatic chronic osteomyelitis with tigecycline: a case series

Objective: To evaluate the efficacy of tigecycline treatment in Combat-Related Traumatic Chronic Osteomyelitis (CRTCO). Methods: A retrospective study evaluated tigecycline in the treatment of CRTCO. Cases were reviewed for patients who were treated for the period 2011 - June 2012. During the tigecycline treatment period, orthopedic surgeon taking care of patients started tigecycline treatment upon their discretion, not knowing about the pending study Results: Ten cases were included (one female), mean age 45.5 years. Most common involved bones with CRTCO were femur followed by tibia. Microbiological diagnoses were obtained mostly from bone biopsies and bone swabs. Microorganisms isolated were Acinetobacter spp. (6), Klebsiella pneumoniae (6), Escherichia coli (5), Pseudomonas aeruginosa (4), Enterococcus spp. (3), Staphylococcus aureus (1). Tigecycline mean duration of treatment was 35.7 days (range 21 - 91). Patients were treated with other antimicrobials earlier to tigecycline for a mean duration of 467.37 days (range 2 - 1825). Reasons for switching to tigecycline were: Clinical failure in all patients, in addition to side effects and microbiological failure of previous regimen. Paired difference of the ESR for eight available patients’ pair was not significant (p = 0.055), the same was for CRP (p = 0.9). Clinically improved patients were seven cases (70%). Conclusion: CRTCO is a polymicrobial infection mostly caused by gram-negative bacilli. The outcome of treating these infections with tigecycline is promising

Why honey is effective as a medicine. 1. Its use in modern medicine

Honey has been used as a medicine for thousands of years and its curative properties are well documented. However, modern medicine turned its back on honey and it is only now, with the advent of multi-resistant bacteria, that the antibiotic properties of honey are being rediscovered

Quantum dynamics in strong fluctuating fields

A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. Herein, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis the influence of nonequilibrium fluctuations and periodic electrical fields on quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres

Publisher Correction: Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma.

The original version of this Article omitted Suzana A. Kahn, Siddhartha S. Mitra & Samuel H. Cheshier as jointly supervising authors. This has now been corrected in both the PDF and HTML versions of the Article

Synthesis of 2D Germanane (GeH):a New, Fast, and Facile Approach

Germanane (GeH), a germanium analogue of graphane, has recently attracted considerable interest because its remarkable combination of properties makes it an extremely suitable candidate to be used as 2D material for field effect devices, photovoltaics, and photocatalysis. Up to now, the synthesis of GeH has been conducted by substituting Ca by H in a beta-CaGe2 layered Zintl phase through topochemical deintercalation in aqueous HCl. This reaction is generally slow and takes place over 6 to 14 days. The new and facile protocol presented here allows to synthesize GeH at room temperature in a significantly shorter time (a few minutes), which renders this method highly attractive for technological applications. The GeH produced with this method is highly pure and has a band gap (E-g) close to 1.4 eV, a lower value than that reported for germanane synthesized using HCl, which is promising for incorporation of GeH in solar cells

Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE−/−) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p < 0.0001). Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted. Keywords: Non-alcoholic fatty liver disease, Glyoxalase, Methylglyoxal, Proteomics, iTRA

Pathway and network analysis of more than 2500 whole cancer genomes

The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments