Ceftriaxone for the Treatment of Chronic Bacterial Prostatitis:A Case Series and Literature Review

Chronic bacterial prostatitis is increasingly difficult to treat due to rising antimicrobial resistance limiting oral treatment options. In this case series, 11 men with CBP (including patients with urological comorbidities) due to multi-resistant E. coli were treated with once-daily ceftriaxone intravenously for 6 weeks. Nine patients were clinically cured at 3 months follow up. No early withdrawal of medication due to side effects occurred. A literature review was conducted to describe the prostate pharmacokinetics of ceftriaxone and its use in prostatic infection. In conclusion, ceftriaxone can be considered an appropriate treatment of chronic bacterial prostatitis

Immune checkpoint inhibition combined with targeted therapy using a novel virus-like drug conjugate induces complete responses in a murine model of local and distant tumors

Metastases remain the leading cause of cancer-related death worldwide. Therefore, improving the treatment efficacy against such tumors is essential to enhance patient survival. AU-011 (belzupacap sarotalocan) is a new virus-like drug conjugate which is currently in clinical development for the treatment of small choroidal melanoma and high-risk indeterminate lesions in the eye. Upon light activation, AU-011 induces rapid necrotic cell death which is pro-inflammatory and pro-immunogenic, resulting in an anti-tumor immune response. As AU-011 is known to induce systemic anti-tumor immune responses, we investigated whether this combination therapy would also be effective against distant, untreated tumors, as a model for treating local and distant tumors by abscopal immune effects. We compared the efficacy of combining AU-011 with several different checkpoint blockade antibodies to identify optimal treatment regimens in an in vivo tumor model. We show that AU-011 induces immunogenic cell death through the release and exposure of damage-associated molecular patterns (DAMPs), resulting in the maturation of dendritic cells in vitro. Furthermore, we show that AU-011 accumulates in MC38 tumors over time and that ICI enhances the efficacy of AU-011 against established tumors in mice, resulting in complete responses for specific combinations in all treated animals bearing a single MC38 tumor. Finally, we show that AU-011 and anti-PD-L1/anti-LAG-3 antibody treatment was an optimal combination in an abscopal model, inducing complete responses in approximately 75% of animals. Our data show the feasibility of combining AU-011 with PD-L1 and LAG-3 antibodies for the treatment of primary and distant tumors.Ophthalmic researc

Predicting vasovagal reactions to needles with anticipatory facial temperature profiles

Around one-third of adults are scared of needles, which can result in adverse emotional and physical responses such as dizziness and fainting (e.g. vasovagal reactions; VVR) and consequently, avoidance of healthcare, treatments, and immunizations. Unfortunately, most people are not aware of vasovagal reactions until they escalate, at which time it is too late to intervene. This study aims to investigate whether facial temperature profiles measured in the waiting room, prior to a blood donation, can be used to classify who will and will not experience VVR during the donation. Average temperature profiles from six facial regions were extracted from pre-donation recordings of 193 blood donors, and machine learning was used to classify whether a donor would experience low or high levels of VVR during the donation. An XGBoost classifier was able to classify vasovagal groups from an adverse reaction during a blood donation based on this early facial temperature data, with a sensitivity of 0.87, specificity of 0.84, F1 score of 0.86, and PR-AUC of 0.93. Temperature fluctuations in the area under the nose, chin and forehead have the highest predictive value. This study is the first to demonstrate that it is possible to classify vasovagal responses during a blood donation using temperature profiles

Modification of Cu surface with picosecond laser pulses

High purity, mirror-polished polycrystalline Cu surface was treated with single picosecond laser pulses at fluence levels close to the single-pulse modification threshold. The induced surface topography and sub-surface changes were examined with scanning and transmission electron microscopy, respectively. The analysis showed an increased absorption of laser energy on the microscopic surface topography inhomogeneities, even at a fluence level below the modification threshold. Many features, like spikes, bubbles, spheres, as well as small periodic ripples at the bottom of scratches, reveal a significant influence of melting and eruptive relaxation of the absorbed laser energy on the final appearance of the surface. Further, it was found that thermal stresses result in twinning to a depth of few tens of nanometers under the surface. Voids at this depth have been observed as well. The results of the observations provide new insights into the early stages of the picosecond laser pulse modification of metals, especially metals witha weak electron-phonon coupling. (C) 2014 Elsevier B.V. All rights reserved

Intervention mapping for the development of a strategy to implement the insurance medicine guidelines for depression

<p>Abstract</p> <p>Background</p> <p>This article describes the development of a strategy to implement the insurance medicine guidelines for depression. Use of the guidelines is intended to result in more transparent and uniform assessment of claimants with depressive symptoms.</p> <p>Methods</p> <p>The implementation strategy was developed using the Intervention Mapping (IM) method for alignment with insurance-medical practice. The ASE behavioural explanation model (Attitude, Social Influence and Self-Efficacy) was used as theoretical basis for the development work. A literature study of implementation strategies and interviews with insurance physicians were performed to develop instruments for use with the guideline. These instruments were designed to match the needs and the working circumstances of insurance physicians. Performance indicators to measure the quality of the assessment and the adherence to the guidelines were defined with input from insurance physicians.</p> <p>Results</p> <p>This study resulted in the development of a training course to teach insurance physicians how to apply the guidelines for depression, using the aforementioned instruments. The efficacy of this training course will be evaluated in a Randomized Controlled Trial.</p> <p>Conclusions</p> <p>The use of IM made it possible to develop guideline support instruments tailored to insurance medical practice.</p

Kinase and Phosphatase Cross-Talk at the Kinetochore

Multiple kinases and phosphatases act on the kinetochore to control chromosome segregation: Aurora B, Mps1, Bub1, Plk1, Cdk1, PP1, and PP2A-B56, have all been shown to regulate both kinetochore-microtubule attachments and the spindle assembly checkpoint. Given that so many kinases and phosphatases converge onto two key mitotic processes, it is perhaps not surprising to learn that they are, quite literally, entangled in cross-talk. Inhibition of any one of these enzymes produces secondary effects on all the others, which results in a complicated picture that is very difficult to interpret. This review aims to clarify this picture by first collating the direct effects of each enzyme into one overarching schematic of regulation at the Knl1/Mis12/Ndc80 (KMN) network (a major signaling hub at the outer kinetochore). This schematic will then be used to discuss the implications of the cross-talk that connects these enzymes; both in terms of why it may be needed to produce the right type of kinetochore signals and why it nevertheless complicates our interpretations about which enzymes control what processes. Finally, some general experimental approaches will be discussed that could help to characterize kinetochore signaling by dissociating the direct from indirect effect of kinase or phosphatase inhibition in vivo. Together, this review should provide a framework to help understand how a network of kinases and phosphatases cooperate to regulate two key mitotic processes