Evaluating the safety, tolerability, pharmacokinetics and efficacy of clofazimine in cryptosporidiosis (CRYPTOFAZ): study protocol for a randomized controlled trial.

Background: Cryptosporidium infection and diarrhea (cryptosporidiosis) is a life-threatening infection in persons with HIV and also in children of 6-18 months of age in the developing world. To date, only nitazoxanide is licensed for treatment of cryptosporidiosis, and only in persons after the first year of life and with healthy immune systems. Clofazimine (CFZ: Lamprene®), an established drug that has been used for leprosy for more than 50 years, recently has been described as effective against Cryptosporidium in vitro and in mouse infections.

Topological remodeling of cortical perineuronal nets in focal cerebral ischemia and mild hypoperfusion.

Despite the crucial role of perineuronal nets (PNNs) in neural plasticity and neurological disorders, their ultrastructural organization remains largely unresolved. We have developed a novel approach combining superresolution structured illumination microscopy (SR-SIM) and mathematical reconstruction that allows for quantitative analysis of PNN topology. Since perineuronal matrix is capable to restrict neural plasticity but at the same time is necessary to maintain synapses, we hypothesized that a beneficial post stroke recovery requires a reversible loosening of PNNs.

Immunological and non-immunological effects of stem cell-derived extracellular vesicles on the ischaemic brain.

Following the implementation of thrombolysis and endovascular recanalization strategies, stroke therapy has profoundly changed in recent years. In spite of these advancements, a considerable proportion of stroke patients still exhibit functional impairment in the long run, increasing the need for adjuvant therapies that promote neurological recovery. Stem cell therapies have initially attracted great interest in the stroke field, since there were hopes that transplanted cells may allow for the replacement of lost cells.

Glutamate concentration in the anterior cingulate cortex in alcohol dependence: association with alcohol withdrawal and exploration of contribution from glutamatergic candidate genes.

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Implications of polymorphonuclear neutrophils for ischemic stroke and intracerebral hemorrhage: Predictive value, pathophysiological consequences and utility as therapeutic target.

Polymorphonuclear neutrophil granulocytes (PMN) orchestrate the removal of cell debris in ischemic stroke and intracerebral hemorrhage. In both pathologies, high neutrophil to lymphocyte ratios in peripheral blood are predictive of poor outcome in human stroke patients. Following earlier studies indicating that the cerebral microvasculature forms an efficient barrier that impedes neutrophil brain entry, intravital microscopy and immunohistochemistry in the meantime unequivocally revealed the accumulation of PMN in the ischemic and hemorrhagic brain parenchyma.

Defining mechanisms of neural plasticity after brainstem ischemia in rats.

Objective: Neurological recovery after stroke mainly depends on the location of the lesion. A substantial portion of strokes affects the brainstem. However, patterns of neural plasticity following brainstem ischemia are almost unknown.

Towards Bridging Translational Gap in Cardiotoxicity Prediction: an Application of Progressive Cardiac Risk Assessment Strategy in TdP Risk Assessment of Moxifloxacin.

Drug-induced cardiac arrhythmia, especially occurrence of torsade de pointes (TdP), has been a leading cause of attrition and post-approval re-labeling and withdrawal of many drugs. TdP is a multifactorial event, reflecting more than just drug-induced cardiac ion channel inhibition and QT interval prolongation. This presents a translational gap in extrapolating pre-clinical and clinical cardiac safety assessment to estimate TdP risk reliably, especially when the drug of interest is used in combination with other QT-prolonging drugs for treatment of diseases such as tuberculosis.

Quantitative approach for cardiac risk assessment and interpretation in tuberculosis drug development.

Cardiotoxicity is among the top drug safety concerns, and is of specific interest in tuberculosis, where this is a known or potential adverse event of current and emerging treatment regimens. As there is a need for a tool, beyond the QT interval, to quantify cardiotoxicity early in drug development, an empirical decision tree based classifier was developed to predict the risk of Torsades de pointes (TdP). The cardiac risk algorithm was developed using pseudo-electrocardiogram (ECG) outputs derived from cardiac myocyte electromechanical model simulations of increasing concentrations of 96 reference compounds which represented a range of clinical TdP risk.

Higher levels of kallikrein-8 in female brain may increase the risk for Alzheimer's disease.

Women seem to have a higher vulnerability to Alzheimer's disease (AD), but the underlying mechanisms of this sex dichotomy are not well understood. Here, we first determined the influence of sex on various aspects of Alzheimer's pathology in transgenic CRND8 mice. We demonstrate that beta-amyloid (Aβ) plaque burden starts to be more severe around P180 (moderate disease stage) in female transgenics when compared to males and that aging aggravates this sex-specific difference.

The Role of the Physician in Patient Perceptions of Barriers to Primary Adherence With Acne Medications.

Importance: Primary nonadherence with acne medications is high but commonly underreported to prescribing physicians.

Objectives: To describe patient experiences with primary nonadherence to medications for acne and to identify physician-level factors that may improve adherence in this population.

Design, Setting, And Participants: A qualitative analysis was conducted from structured interviews with patients reporting nonadherence with acne medications at a large academic health system in the Philadelphia, Pennsylvania, area.

High-density lipoprotein (HDL) promotes angiogenesis via S1P3-dependent VEGFR2 activation.

High-density lipoprotein (HDL) has previously been shown to promote angiogenesis. However, the mechanisms by which HDL enhances the formation of blood vessels remain to be defined. To address this, the effects of HDL on the proliferation, transwell migration and tube formation of human umbilical vein endothelial cells were investigated.

Breaking paradigms in severe epistaxis: the importance of looking for the S-point.

Introduction: Since the introduction of nasal endoscopy into the field of Otorhinolaryngology, the treatment paradigm for cases of severe epistaxis has shifted toward early and precise identification of the bleeding site. Although severe epistaxis is usually considered to arise from posterior bleeding, an arterial vascular pedicle in the superior portion of the nasal septum, around the axilla projection of the middle turbinate, posterior to the septal body, frequently has been observed. That vascular pedicle was named the Stamm's S-point.

Identification of the histone lysine demethylase KDM4A/JMJD2A as a novel epigenetic target in M1 macrophage polarization induced by oxidized LDL.

Oxidized low density lipoprotein (oxLDL) induces macrophage activation, an event essential for atherosclerosis. Emerging evidence supports that epigenetic regulation plays important roles in macrophage activation and function. However, it remains unclear which epigenetic modulator is responsible for oxLDL-induced macrophage activation.

Identification of hospitalized elderly patients at risk for adverse in-hospital outcomes in a university orthopedics and trauma surgery environment.

Background: As a consequence of demographic changes, hospitals are confronted with increasing numbers of elderly patients, who are at high risk of adverse events during hospitalization. Geriatric risk screening followed by comprehensive geriatric assessment (CGA) and treatment has been requested by geriatric societies and task forces to identify patients at risk. Since empirical evidence on factors predisposing to adverse hospital events is scarce, we now prospectively evaluated implications of geriatric risk screening followed by CGA in a university hospital department of orthopedics and trauma surgery.

Age and personal values: Similar value circles with shifting priorities.

This study examined the relationship of personal values to age using data from two representative surveys. We hypothesized that individuals organize personal values, regardless of their age, as a circle with the same order of values on this circle but that older persons are closer to conservation and more remote from openness to change and closer to self-transcendence and more distant from self-enhancement. The structural stability of the value circle over age was largely confirmed across and within individuals.

Concise Review: Extracellular Vesicles Overcoming Limitations of Cell Therapies in Ischemic Stroke.

Despite recent advances in stroke therapy, current therapeutic concepts are still limited. Thus, additional therapeutic strategies are in order. In this sense, the transplantation of stem cells has appeared to be an attractive adjuvant tool to help boost the endogenous regenerative capacities of the brain.

Gastric Ulcer Complications after the Introduction of Proton Pump Inhibitors into Clinical Routine: 20-Year Experience.

Background: The aim of this study was to analyze the admissions and the management of peptic ulcer disease (PUD) in a tertiary care surgical center.

Methods: We evaluated the medical records of all patients admitted to the University Hospital of Tübingen, Germany, for treatment of PUD during 1989-2008. Patients were included into the study if the diagnosis was verified endoscopically or surgically.

[How Active is the Catholic Church in the Prevention of Sexual Abuse? Preliminary Results of the MHG-Study].

Objective: A subproject of the study "Sexual abuse of minors by Catholic priests and deacons in the authority of the German Bishops' conference" deals with aspects of prevention.

Method: Structured questions were used to record objective data on preventive work. The questionnaire was completed in all 27 dioceses of Germany.

Photoswitchable nanoporous films by loading azobenzene in metal-organic frameworks of type HKUST-1.

Photoswitchable metal-organic frameworks (MOFs) enable the dynamic remote control of their key properties. Here, a readily producible approach is presented where photochromic molecules, i.e.

Developmental Competence and Epigenetic Profile of Porcine Embryos Produced by Two Different Cloning Methods.

The "Dolly" based cloning (classical nuclear transfer, [CNT]) and the handmade cloning (HMC) are methods that are nowadays routinely used for somatic cloning of large domestic species. Both cloning protocols share several similarities, but differ with regard to the required in vitro culture, which in turn results in different time intervals until embryo transfer. It is not yet known whether the differences between cloned embryos from the two protocols are due to the cloning methods themselves or the in vitro culture, as some studies have shown detrimental effects of in vitro culture on conventionally produced embryos.

Biochemical markers in vascular cognitive impairment associated with subcortical small vessel disease - A consensus report.

Background: Vascular cognitive impairment (VCI) is a heterogeneous entity with multiple aetiologies, all linked to underlying vascular disease. Among these, VCI related to subcortical small vessel disease (SSVD) is emerging as a major homogeneous subtype. Its progressive course raises the need for biomarker identification and/or development for adequate therapeutic interventions to be tested.

Vesicular glutamate transporters play a role in neuronal differentiation of cultured SVZ-derived neural precursor cells.

The role of glutamate in the regulation of neurogenesis is well-established, but the role of vesicular glutamate transporters (VGLUTs) and excitatory amino acid transporters (EAATs) in controlling adult neurogenesis is unknown. Here we investigated the implication of VGLUTs in the differentiation of subventricular zone (SVZ)-derived neural precursor cells (NPCs). Our results show that NPCs express VGLUT1-3 and EAAT1-3 both at the mRNA and protein level.

Sexual abuse of minors within the Catholic Church and other institutions : A literature review.

Sexual violence against children remains a global public health problem. The health sector has an opportunity and responsibility to be part of the multisector collaboration to prevent and respond to sexual abuse of minors. The following article presents a critical analysis of hitherto published empirical studies that examine the extent and variety of sexual abuse of minors within the Catholic Church and other institutions.

3D visualization and quantification of microvessels in the whole ischemic mouse brain using solvent-based clearing and light sheet microscopy.

The visualization of cerebral microvessels is essential for understanding brain remodeling after stroke. Injection of dyes allows for the evaluation of perfused vessels, but has limitations related either to incomplete microvascular filling or leakage. In conventional histochemistry, the analysis of microvessels is limited to 2D structures, with apparent limitations regarding the interpretation of vascular circuits.