Before and after a disease outbreak: Tracking a keystone species recovery from a mass mortality event.

Mass mortality events involving marine taxa are increasing worldwide. The long-spined sea urchin Diadema africanum is considered a keystone herbivore species in the northeastern Atlantic due to its control over the abundance and distribution of algae. After a first registered mass mortality in 2009, another event off the coasts of Madeira archipelago affected this ecologically important species in summer 2018. This study documented the 2018 D. africanum mass mortality event, and the progress of its populations on the southern coast of Madeira island. A citizen science survey was designed targeting marine stakeholders to understand the extent and intensity of the event around the archipelago. Underwater surveys on population density prior, during and after the mass mortality, permitted an evaluation of the severity and magnitude of the event as well as urchin population recovery. A preliminary assessment of causative agents of the mortality was performed. The event was reported in the principal islands of the archipelago reducing the populations up to 90%. However, a fast recovery was registered during the following months, suggesting that the reproductive success was not compromised. Microbiological analyses in symptomatic and asymptomatic individuals, during and after the event, was not conclusive. Nevertheless, the bacteria Aeromonas salmonicida, or the gram-negative bacteria, or the interaction of different types of bacteria may be responsible for the disease outbreak. Further studies are needed to assess the role of pathogens in sea urchin mass mortalities and the compound effects that sea urchins have in local habitats and ecological functioning of coastal marine ecosystems.

Dynamic behavior of different quantities of osteoblasts during formation of micromass cultures.

Implantation of micromass cultures of osteoblastic cells offers the possibility of scaffold free tissue engineering for example, regeneration of bone defects. However, the details of cell dynamics during the formation of these micromasses are still not well understood. This study aims to investigate and clarify the extent to which cell quantity influences the dynamics of micromass formation of osteoblastic cell cultures. For this purpose, the migration and aggregation during this process are investigated by optical inspection employing image processing software that allows for automated tracking of cell groups using digital image correlation. An exponential time behavior is observed with respect to the velocity of the cells and the distance of the cells to their common center of gravity. Characteristic time constants are derived as quantitative measures of the cell dynamics. The results indicate that the time constants strongly depend on the quantity of cells, that is, will decrease with increasing cell quantity. © 2018 International Society for Advancement of Cytometry.

Quantitative analysis of dynamic behavior of osteoblasts during in vitro formation of micro-mass cell cultures.

Improvements in bone tissue engineering require an understanding of cellular and tissue level behavior of osteoblast-like cells. Experiments indicate that in the absence of an anchoring material, intercellular adhesion may be based on signals that promote cell activity resulting in the formation of a spheroid cell-matrix. The aim of the present study is to investigate the formation of scaffold-free three-dimensional micro-mass cell spheroids in vitro, and to characterize quantitatively the cell movement. A new correlation based automated tracking method is evaluated in order to optimize the processing parameters and to identify statistical parameters that characterize the cell behavior. Results suggest that the temporal development of the mean distance of the cells to the center of gravity may be described by an exponential function, thus providing a characteristic time constant as a quantitative measure of cell dynamics. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

Bone marrow biopsies of patients with hematopoietic and lymphoid disorders - epidemiology, chromosomal aberrations and molecular pathology.

Bone marrow biopsy of the iliac crest is the first and most important step in the diagnostics of hematopoietic disorders. The biopsies of the years 2006 and 2007 from the Institute of Pathology of the Jena University Hospital were retrospectively analyzed for clinicopathological parameters. In addition, the Mitelman database was retrieved for chromosomal aberrations. The analysis of 2820 reports from 1185 patients revealed that lymphomas, plasma cell myeloma and acute leukemia were most frequent. Males predominated in myeloproliferative neoplasms and lymphoma subtypes, particularly CLL, except for plasma cell myeloma and acute leukemia. A peak incidence was seen between 61 and 70 years of age with a varying pattern for single entities. The database search revealed that ALL, AML, CLL and CML were mainly diploid while Hodgkin lymphoma, mature B-cell lymphoma and multiple myeloma mostly carried hyperdiploid chromosome numbers. Numerical aberrations like chromosome 8 gains in hyperdiploid CML were prominent in specific subgroups. Molecular testing is exemplified in CML, plasma cell myeloma and hairy cell leukemia. The study highlights typical clinicopathological characteristics and new genetic findings in hematopoietic and lymphoid neoplasms with relevance for the new WHO classification and beyond. We hope that it may help in the differential diagnosis of bone marrow biopsies.

Platinum nanoparticles on gallium nitride surfaces: effect of semiconductor doping on nanoparticle reactivity.

Platinum nanoparticles supported on n- and p-type gallium nitride (GaN) are investigated as novel hybrid systems for the electronic control of catalytic activity via electronic interactions with the semiconductor support. In situ oxidation and reduction were studied with high pressure photoemission spectroscopy. The experiments revealed that the underlying wide-band-gap semiconductor has a large influence on the chemical composition and oxygen affinity of supported nanoparticles under X-ray irradiation. For as-deposited Pt cuboctahedra supported on n-type GaN, a higher fraction of oxidized surface atoms was observed compared to cuboctahedral particles supported on p-type GaN. Under an oxygen atmosphere, immediate oxidation was recorded for nanoparticles on n-type GaN, whereas little oxidation was observed for nanoparticles on p-type GaN. Together, these results indicate that changes in the Pt chemical state under X-ray irradiation depend on the type of GaN doping. The strong interaction between the nanoparticles and the support is consistent with charge transfer of X-ray photogenerated free carriers at the semiconductor-nanoparticle interface and suggests that GaN is a promising wide-band-gap support material for photocatalysis and electronic control of catalysis.

Use of OROS® hydromorphone in the treatment of osteoarthritis and osteoporosis: A pooled analysis of three non-interventional studies focusing on different starting doses.

OBJECTIVE: To determine the effect of a lower starting dose of OROS® hydromorphone compared with a higher starting dose. DESIGN: Data from the first 15 days of treatment were compared in a combined analysis of three prospective, non-interventional studies. SETTING: Non-interventional, carried out in daily routine settings. PATIENTS: Patients had chronic severe pain due to osteoarthritis or from fragility fractures related to osteoporosis. INTERVENTIONS: OROS-ANA-4001 and OROS-ANA-4002 had a daily starting dose of 8 mg of OROS® hydromorphone; OROS-ANA-4003 had a daily starting dose of 4 mg. MAIN OUTCOME MEASURE(S): A post-hoc analysis to assess the effect of a low starting dose of OROS® hydromorphone on tolerability, pain control, and treatment satisfaction overall and for subgroups of opioid-naïve patients versus patients previously treated with opioids, and patients aged >65 years versus patients aged ≤65 years. RESULTS: Treatment satisfaction and pain control improved in all studies; treatment satisfaction improved in a higher percentage of patients in the lower starting dose group. Gastrointestinal disorders were the most frequent treatment-emergent adverse events. Incidence of nausea was comparable between studies. Incidence of constipation, vomiting, fatigue, and pruritus was less frequent with the lower starting dose. In elderly and opioid-naïve patients, a lower starting dose was associated with lower overall incidence of adverse events, treatment-related adverse events, and those leading to discontinuation. CONCLUSIONS: A lower starting dose was associated with better tolerability and a lower number of treatment terminations at a comparable level of pain control with high treatment satisfaction.

Non-invasive pulmonary perfusion assessment in young patients with cystic fibrosis using an arterial spin labeling MR technique at 1.5 T.

OBJECT: To assess lung perfusion in young patients with cystic fibrosis (CF) using an arterial spin labeling (ASL) technique. MATERIALS AND METHODS: Perfusion imaging was performed in 5 healthy volunteers and 33 pediatric patients (13 ± 5 years) with CF using an ASL technique. Image quality was evaluated on a five-point scale (1 = excellent). Quantitative perfusion maps were calculated based on the modified Bloch equations. Perfusion differences between volunteers and CF patients and regional differences between lobes were analyzed using Student's t test. The association of perfusion values and forced expiratory volume in 1 s (FEV1) was analyzed using univariate regression analysis. RESULTS: Mean lung perfusion was 698 ± 67 ml/100g/min (range: 593-777 ml/100g/min) in volunteers and 526 ± 113 ml/100g/min (range: 346-724 ml/100g/min) in CF patients. Median image quality was 2 in volunteers and 3 in CF patients. In CF patients, significantly lower perfusion was observed in the upper lobes compared to healthy volunteers. Mean perfusion values significantly correlated with FEV1 (r = 0.84, P < 0.0001). CONCLUSION: ASL perfusion imaging provides lung perfusion assessment in young CF patients. This non-invasive functional imaging technique is worth being evaluated in the clinical monitoring of CF patients.

Combined TPRx, in situ GISAXS and GIXAS studies of model semiconductor-supported platinum catalysts in the hydrogenation of ethene.

The preparation, characterization and catalytic reactivity of a GaN supported Pt catalyst in the hydrogenation of ethene are presented in this feature article, highlighting the use of in situ characterization of the material properties during sample handling and catalysis by combining temperature programmed reaction with in situ grazing incidence small-angle X-ray scattering and X-ray absorption spectroscopy. The catalysts are found to be sintering resistant at elevated temperatures as well as during reduction and hydrogenation reactions. In contrast to Pt particles of approximately 7 nm diameter, smaller particles of 1.8 nm in size are found to dynamically adapt their shape and oxidation state to the changes in the reaction environment. These smaller Pt particles also showed an initial deactivation in ethene hydrogenation, which is paralleled by the change in the particle shape. The subtle temperature-dependent X-ray absorbance of the 1.8 nm sized Pt particles indicates that subtle variations in the electronic structure induced by the state of reduction by electron tunnelling over the Schottky barrier between the Pt particles and the GaN support can be monitored.

Topiramate for migraine prevention in a naturalistic setting: results from an open label, flexible dose study.

BACKGROUND: Headaches are one of the most common neurological symptoms and migraines are the most common primary headache disorder. The global prevalence of migraines is around 10% and the condition is associated with a high burden of disease. Despite an abundance of good quality evidence, only 1 in 5 of patients who fulfill the criteria for preventive migraine therapy are appropriately treated. Data on patient outcomes with preventive medication derive mostly from specialized academic centers, which contrasts with normal clinical practice where the majority of patients are treated outside tertiary care centers. OBJECTIVE: To explore tolerability, safety and efficacy outcomes of patients receiving topiramate for migraine prevention in a naturalistic setting. METHODS: After a 4-week prospective baseline, patients with a diagnosis of migraine according to International Headache Society criteria and eligible for migraine prevention were treated with flexible dosing of topiramate for 24 weeks (core phase), and optionally for a total of 48 weeks. The primary safety analysis included adverse events (AEs) during the core phase. For the main efficacy measures, the absolute changes from baseline to end of core phase as well as last follow-up visit were calculated for migraine days per 4 weeks, migraine attacks per 4 weeks, mean maximum visual analogue scale of migraine headache per 4 weeks and mean maximum pain intensity of migraine headache (4-point scale) per 4 weeks. In addition, changes in individual quality of life aspects were captured. RESULTS: The intention-to-treat population (ITT) consisted of 161 patients (90.7% female, mean age 45.7 +/- 11.1 years). Topiramate median dose was 45.7 mg/day at endpoint. Some 74.1% of patients reported treatment emergent AEs, most frequently paresthesias (18.4%) and nausea (12.4%). Some 20.0% of patients withdrew from the study due to AEs. The mean number of migraine days per 4 week decreased from 6.2 +/- 3.9 days at baseline to 3.9 +/- 3.5 days at last core visit (P < .001). Mean maximum pain intensity per 4 week changed from 7.0 +/- 2.3 at baseline to 4.7 +/- 3.2 at last visit core phase (P < .001). Consumption of triptans and analgesics reduced during the course of the core phase (P < .005). Fifty-one percent of all patients experienced at least a 50% reduction in migraine days during the core phase. CONCLUSION: Topiramate used for migraine prevention in non-academic institutions is generally safe, well tolerated and results in good control of migraine headaches and improvement in several aspects of quality of life.

Microcontact printing of proteins for neuronal cell guidance.

The growth of neurons into networks of controlled geometry is of great interest in the field of cell-based biosensors, neuroelectronic circuits, neurological implants, pharmaceutical testing as well as fundamental biological questions about neuronal interactions. The precise control of the network architecture can be achieved by defined engineering of the surface material properties: this process is called neuronal cell patterning. Different techniques can be used to produce such surface patterns. We have chosen microcontact printing (µCP), because it is a comparatively simple and universal method for patterning biomolecules.

Reduced hemoglobin after heart transplantation is no independent risk factor for survival but is associated closely with impaired renal function.

BACKGROUND: Reduced hemoglobin (Hb) levels after heart transplantation (HTX) are common; however, there are only limited data on the association of posttransplant anemia with survival. METHODS: In the present study, the effect of Hb levels determined 7 to 12 months after HTX on survival was investigated in 156 heart transplant recipients (129 men and 27 women; age at transplantation, 51.3+/-10.45 years; follow-up, 6.77+/-3.6 years) by univariate and multivariate analyses including a broad range of clinical and demographic patient characteristics. RESULTS: Anemia by standard definition was found in 141 of 156 (91.6%) patients. According to Hb levels above or below the gender-specific median (men, 12.07 g/dL; women, 11.69 g/dL), patients were separated into a high- or low-Hb group, respectively. Kaplan-Meier analysis demonstrated significantly worse survival in the low-Hb group (P =0.033). Those patients showed significantly lower body weight, higher serum creatinine levels, and lower calculated creatinine clearance; the association of creatinine clearance and Hb levels was highly significant (P <0.0001). No differences were demonstrated between groups for age, preoperative cardiac diagnosis, diabetes, azathioprine, steroid or angiotensin-converting enzyme inhibitor medication, leukocyte and thrombocyte levels, rejection index, or cytomegalovirus (CMV) infection or serostatus. Multivariate Cox stepwise regression analysis demonstrated that CMV infection, diabetes, and female donor gender were significant risk factors for post-HTX survival. An Hb level below the median was, however, completely lost as a risk factor (P =0.44); instead, a strong trend for reduced creatinine clearance could be demonstrated (P =0.09). Subsequently, a significant association was demonstrated between low calculated creatinine clearance and impaired survival by separate Kaplan-Meier analysis (P =0.02). CONCLUSIONS: Low Hb levels after HTX do not represent an independent risk factor for reduced survival, but the demonstrated correlation appears to be primarily caused by concomitant functional renal impairment. Further studies will be required to investigate the role of post-HTX anemia as a sensitive indicator of functional renal impairment and the effects of anemia treatment on long-term survival.