Diverse Applications of the Anti-Diabetic Drug Metformin in Treating Human Disease.

Metformin is a commonly used drug for treating type 2 diabetes. Metformin is an inexpensive drug with low/no side effects and is well tolerated in human patients of different ages. Recent therapeutic strategies for human disease have considered the benefits of drug repurposing.

Genomic Epidemiologic Investigation of a Multispecies Hospital Outbreak of NDM-5-Producing Enterobacterales Infections.

Background: New Delhi metallo-β-lactamase (NDM) represents an emergent mechanism of carbapenem resistance associated with high mortality and limited antimicrobial treatment options. Because the resistance gene is often carried on plasmids, traditional infection prevention and control (IP&C) surveillance methods like speciation, antimicrobial resistance testing, and reactive whole genome sequencing (WGS) may not detect plasmid transfer in multispecies outbreaks.

Methods: Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance, which was performed weekly using the Illumina platform.

Transmission visualizations of healthcare infection clusters: A scoping review.

Objective: To evaluate infectious pathogen transmission data visualizations in outbreak publications.

Design: Scoping review.

Methods: Medline was searched for outbreak investigations of infectious diseases within healthcare facilities that included ≥1 data visualization of transmission using data observable by an infection preventionist showing temporal and/or spatial relationships.

High-detectivity optical heterodyne method for wideband carrier-envelope phase noise analysis of laser oscillators.

Broadband characterization of the carrier-envelope phase (CEP) noise spectral density of free-running mode-locked lasers is essential for advanced low-noise optical frequency comb designs. Here we present a direct method that utilizes an optical heterodyne beat between a pair of repetition-rate-locked mode-locked lasers for CEP noise characterization, without requiring an f-2f interferometer or nonlinear optical conversion steps. A proof-of-principle experiment in a femtosecond Yb-fiber laser achieves CEP noise spectral density characterization with >270  dB dynamic range over a Fourier frequency range from 5 mHz to 8 MHz.

Role of Intrapulse Coherence in Carrier-Envelope Phase Stabilization.

The concept of coherence is of fundamental importance for describing the physical characteristics of light and for evaluating the suitability for experimental application. In the case of pulsed laser sources, the pulse-to-pulse coherence is usually considered for a judgment of the compressibility of the pulse train. This type of coherence is often lost during propagation through a highly nonlinear medium, and pulses prove incompressible despite multioctave spectral coverage.

Excess carrier-envelope phase noise generation in saturable absorbers.

Attosecond spectroscopy and precision frequency metrology depend on the stabilization of the carrier-envelope phase (CEP) of mode-locked lasers. Unfortunately, the phase of only a few types of lasers can be stabilized to jitters in the few-hundred millirad range. In a comparative experimental study, we analyze a femtosecond Ti:sapphire laser and three mode-locked fiber lasers.

[Evaluation of family doctor-centred health care in Germany based on AOK Rheinland/Hamburg claims data].

Background: Health insurance funds in Germany are obliged to offer family doctor-centred health care models (Hausarztzentrierte Versorgung, "HzV"). The participation is voluntary for the insured persons. Participants agree to utilise outpatient specialist care only if their family doctor or general practitioner ("gatekeeper") refers them to a specialist.

Intracavity measurement of the electro-optic Kerr effect via carrier-envelope phase demodulation.

Placing a sinusoidally driven air capacitor in the intracavity beam path of a mode-locked few-cycle Ti:sapphire oscillator, we measure the influence of the electro-optical Kerr effect on the carrier-envelope phase of the laser pulses. Using a capacitor length of only 8 cm at atmospheric pressure, we observe a Kerr-induced frequency modulation of the carrier-envelope beat note. From the measured frequency excursion, we determine a Kerr constant of the order of 10  m/V, which is found to agree with theoretically computed hyperpolarizabilities of the nitrogen and oxygen molecules.

[The Willingness to Consent to the Linkage of Primary and Secondary Data: An Analysis Based on a Survey of Patients with Primary Breast Cancer in Northrhine Westfalia].

By linking data it is possible to merge, for example, survey data with routine data from statutory health insurance (GKV), to gain benefit from the advantages of both. As personal data is involved, it is necessary to obtain consent. Previous studies show that willingness to release this kind of data for scientific research is limited.

Combined Preclinical Magnetic Particle Imaging and Magnetic Resonance Imaging: Initial Results in Mice.

Purpose: Magnetic particle imaging (MPI) is a new radiologic imaging modality. For the first time, a commercial preclinical scanner is installed. The goal of this study was to establish a workflow between MPI and magnetic resonance imaging (MRI) scanners for a complete in vivo examination of a mouse and to generate the first co-registered in vivo MR-MP images.

Low-dose-rate brachytherapy for low-grade prostate cancer.

Background: Prostate cancer is a radiosensitive type of cancer for which radiotherapy is used for both curative and palliative purposes. Low-dose-rate brachytherapy is an internal radiotherapy technique which allows high doses of radiation to be delivered to a tumour at short range and with a high degree of precision. We have conducted a systematic review of the evidence base for this treatment.

Determination of liver-specific r2 * of a highly monodisperse USPIO by (59) Fe iron core-labeling in mice at 3 T MRI.

Accurate determination of tissue concentration of ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) using T2 * MR relaxometry is still challenging. We present a reliable quantification method for local USPIO amount with the estimation of the liver specific relaxivity r2 * using monodisperse (59) Fe-core-labeled USPIO ((59) FeUSPIO). Dynamic and relaxometric in vivo characteristics of unlabeled monodisperse USPIO were determined in MRI at 3 T.

Imaging of the murine biliopancreatic tract at 7 Tesla: technique and results in a model of primary sclerosing cholangitis.

Purpose: To assess the feasibility of a 7 Tesla (T) MR cholangiopancreatography (MRCP) protocol to image the morphology and detect and intraindividually monitor pathological changes of the biliopancreatic tract in a mouse model of primary sclerosing cholangitis (PSC).

Materials And Methods: Six female Mdr2(Abcb)(-/-) mice, a well-established model of PSC, were imaged five times during weeks 10-19. Three wild-type controls were imaged at age 15 weeks.

Superparamagnetic iron oxide nanoparticles in biomedicine: applications and developments in diagnostics and therapy.

Superparamagnetic iron oxide nanoparticles (SPIO) can be used to image physiological processes and anatomical, cellular and molecular changes in diseases. The clinical applications range from the imaging of tumors and metastases in the liver, spleen and bone marrow, the imaging of lymph nodes and the CNS, MRA and perfusion imaging to atherosclerotic plaque and thrombosis imaging. New experimental approaches in molecular imaging describe undirected SPIO trapping (passive targeting) in inflammation, tumors and associated macrophages as well as the directed accumulation of SPIO ligands (active targeting) in tumor endothelia and tumor cells, areas of apoptosis, infarction, inflammation and degeneration in cardiovascular and neurological diseases, in atherosclerotic plaques or thrombi.

Effective inhibition of metastases and primary tumor growth with CTCE-9908 in esophageal cancer.

Background: In spite of multimodular treatment, the therapeutic options for esophageal carcinoma are limited, and metastases remain the leading cause of tumor-related mortality. Expression of the chemokine receptor CXCR4 significantly correlates with poor survival rates in patients with esophageal carcinoma and is associated with lymph node and bone marrow metastases. The aim of this study was to evaluate the effect of the CXCR4 antagonist CTCE-9908 on metastatic homing and primary tumor growth in vitro and in vivo in an orthotopic xenograft model of esophageal cancer.

A simple and widely applicable method to 59Fe-radiolabel monodisperse superparamagnetic iron oxide nanoparticles for in vivo quantification studies.

A simple, fast, efficient, and widely applicable method to radiolabel the cores of monodisperse superparamagnetic iron oxide nanoparticles (SPIOs) with (59)Fe was developed. These cores can be used as precursors for a variety of functionalized nanodevices. A quality control using filtration techniques, size-exclusion chromatography, chemical degradation methods, transmission electron microscopy, and magnetic resonance imaging showed that the nanoparticles were stably labeled with (59)Fe.

Implementation of high-dose-rate brachytherapy and androgen deprivation in patients with prostate cancer.

Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims.

Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy × 25) combined with HDR-BT (iridium 192; prostate 10 Gy × 2) with long-term androgen deprivation therapy (ADT).

Results: After a median observation time of 44.

[High dose rate brachytherapy in prostate cancer in Norway].

Background: A correlation exists between applied dose to the prostate and local tumour control. External radiotherapy of the prostate implies administering curative doses near the upper limit of normal tissue tolerance. Brachytherapy with a high dose rate permits an escalation of dose within the prostate without increasing the risk of side effects to the surrounding rectum and bladder.

[Treatment of hormone-resistant prostate cancer].

Hormone-resistant prostate cancer is defined by disease progression despite of castration levels of serum testosterone. Due to a good palliative effect and low toxicity, radiotherapy is the cornerstone in treatment of painful bone metastases, the most frequent symptom of advanced hormone-resistant prostate cancer. Patients presenting with spinal cord compression should be assessed for decompressive surgery before radiotherapy.

Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients.

Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 x 10(7) transfected DCs either intranodally or intradermally.