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1.
Proc Biol Sci ; 288(1944): 20202770, 2021 02 10.
Article in English | MEDLINE | ID: mdl-33563118

ABSTRACT

Studies increasingly show that social connectedness plays a key role in determining survival, in addition to natural and anthropogenic environmental factors. Few studies, however, integrated social, non-social and demographic data to elucidate what components of an animal's socio-ecological environment are most important to their survival. Female giraffes (Giraffa camelopardalis) form structured societies with highly dynamic group membership but stable long-term associations. We examined the relative contributions of sociability (relationship strength, gregariousness and betweenness), together with those of the natural (food sources and vegetation types) and anthropogenic environment (distance from human settlements), to adult female giraffe survival. We tested predictions about the influence of sociability and natural and human factors at two social levels: the individual and the social community. Survival was primarily driven by individual- rather than community-level social factors. Gregariousness (the number of other females each individual was observed with on average) was most important in explaining variation in female adult survival, more than other social traits and any natural or anthropogenic environmental factors. For adult female giraffes, grouping with more other females, even as group membership frequently changes, is correlated with better survival, and this sociability appears to be more important than several attributes of their non-social environment.


Subject(s)
Giraffes , Animals , Environment , Female , Food , Sociological Factors
2.
Mediators Inflamm ; 2020: 9501617, 2020.
Article in English | MEDLINE | ID: mdl-32508528

ABSTRACT

BACKGROUND: Sarcoidosis and hypersensitivity pneumonitis (HP) are immunologically mediated processes caused by hypersensitivity reaction accompanied by similar features including lymphocytic alveolitis and granuloma formation. Recent studies describe the role of TREM receptors in T cell activation, differentiation, and granuloma formation. Alveolar macrophages activation via TREM receptors may be the key factor mediating subsequent immune response. The aim of the study was to analyse TREM-1 and TREM-2 expression to identify further molecular mechanisms participating in the immunopathogenesis of sarcoidosis and HP. METHODS: Flow cytometry was performed to analyse TREM-1 and TREM-2 expression on CD14+ cells in bronchoalveolar lavage fluid from patients having sarcoidosis or HP and a control group. RESULTS: The study proved increased TREM-1 expression on alveolar macrophages in pulmonary sarcoidosis and diminished TREM-1 expression in HP-Sarcoidosis: median: 76.7; HP: median: 29.9; control: median: 53.3, (sarcoidosis versus HP: p < 0.001; sarcoidosis versus control: p < 0.05). TREM-2 expression was increased in both, sarcoidosis and HP-sarcoidosis: median: 34.79; HP: median: 36.00; control: median: 12.98, (sarcoidosis versus control: p < 0.05; HP versus control: p < 0.05). Correlation analysis showed negative correlation between TREM-1 and total number of CD8+ cytotoxic T cells. In sarcoidosis TREM-1 expression decreased with changes of HRCT image, decrease in CD4/CD8 ratio and decrease in DLCO. CONCLUSIONS: Differences in TREM receptor expression in sarcoidosis (increase in TREM-1 and TREM-2) and HP (increase in TREM-2) and correlation analysis suggests that activation via TREM may participate in typical immunological characteristics of sarcoidosis and HP.


Subject(s)
Bronchoalveolar Lavage Fluid , Lipopolysaccharide Receptors/metabolism , Membrane Glycoproteins/metabolism , Receptors, Immunologic/metabolism , Sarcoidosis, Pulmonary/metabolism , T-Lymphocytes/immunology , Triggering Receptor Expressed on Myeloid Cells-1/metabolism , Adult , Aged , Brain Neoplasms/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Glioma/metabolism , Humans , Immune System , Inflammation , Interleukin-10/metabolism , Interleukin-6/metabolism , Male , Middle Aged , Monocytes/metabolism , Proportional Hazards Models
3.
J Synchrotron Radiat ; 27(Pt 1): 60-66, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-31868737

ABSTRACT

A new Rococo 2 X-ray fluorescence detector was implemented into the cryogenic sample environment at the Hard X-ray Micro/Nano-Probe beamline P06 at PETRA III, DESY, Hamburg, Germany. A four sensor-field cloverleaf design is optimized for the investigation of planar samples and operates in a backscattering geometry resulting in a large solid angle of up to 1.1 steradian. The detector, coupled with the Xspress 3 pulse processor, enables measurements at high count rates of up to 106 counts per second per sensor. The measured energy resolution of ∼129 eV (Mn Kα at 10000 counts s-1) is only minimally impaired at the highest count rates. The resulting high detection sensitivity allows for an accurate determination of trace element distributions such as in thin frozen hydrated biological specimens. First proof-of-principle measurements using continuous-movement 2D scans of frozen hydrated HeLa cells as a model system are reported to demonstrate the potential of the new detection system.


Subject(s)
Spectrometry, X-Ray Emission/instrumentation , Synchrotrons , Calcium/analysis , Chlorides/analysis , Cryopreservation , Electrodes , Equipment Design , HeLa Cells/chemistry , Humans , Phosphorus/analysis , Potassium/analysis , Silicon Compounds , Spectrometry, X-Ray Emission/methods , Sulfur/analysis , X-Rays
4.
Arch Oral Biol ; 104: 133-140, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31202148

ABSTRACT

OBJECTIVES: The present study aimed to investigate if bovine milk or milk protein isolates, respectively, alter the ultrastructure of thein situ pellicle and might therefore have an influence on oral health. METHODS: In situ pellicle samples were formed on bovine enamel slabs exposed in the oral cavity of three subjects for 6, 30, 60 or 120 min. After 3 min of pellicle formation, mouthrinses were performed for 3 min with (non-)homogenized UHT- or fresh milk (0.3% or 3.8% fat), 30% UHT-treated cream or different types of casein- or milk protein isolates containing preparations. The specimens were removed after the exposure times and transmission electron microscopy (TEM) was performed. Native pellicle samples served as controls. RESULTS: Topical ultrastructural pellicle modifications were detected after mouthrinses with all types of homogenized UHT- or fresh milk and after the application of a 3% native casein micelles containing experimental solution. Atypical globular protein structures, identified as casein micelles, were temporarily adsorbed onto the pellicle. They were closely associated with lipid droplets. Furthermore, the mouthrinses occasionally affected the morphology of salivary bacteria. However, no notable ultrastructural alterations remained after 120 min of pellicle formation. CONCLUSION: For the first time, bovine milk- and micellar casein-induced pellicle modifications were revealed by TEM. The adsorption of micellar casein is possibly due to its molecular interactions. CLINICAL SIGNIFICANCE: Bovine milk or micellar caseins provide some potential for the development of preventive strategies against bacterial biofilm formation or erosive processes at the tooth surface.


Subject(s)
Biofilms , Dental Pellicle , Milk Proteins , Milk , Tooth Erosion , Animals , Cattle , Dental Enamel/microbiology , Dental Pellicle/drug effects , Humans , Mouth/microbiology
5.
Sci Rep ; 9(1): 5336, 2019 03 29.
Article in English | MEDLINE | ID: mdl-30926846

ABSTRACT

The particular feature of this study is the investigation of effects of pure fluoride- or stannous ions based mouthrinses on the erosion protective properties and the ultrastructure of the in situ pellicle (12 volunteers). Experimental solutions were prepared either from 500 ppm NaF, SMFP, AmF or SnF2 or 1563 ppm SnCl2, respectively. After 1 min of in situ pellicle formation on bovine enamel slabs, rinses with one of the preparations were performed for 1 min and intraoral specimens' exposure was continued for 28 min. Native enamel slabs and rinses with bidestilled water served as controls. After oral exposure, slabs were incubated in HCl (pH 2; 2.3; 3) for 120 s and kinetics of calcium- and phosphate release were measured photometrically; representative samples were analysed by TEM and EDX. All mouthrinses reduced mineral loss compared to the native 30-min pellicle. The effect was pH-dependent and significant at all pH values only for the tin-containing mouthrinses. No significant differences were observed between the SnF2- and the SnCl2-containing solutions. TEM/EDX confirmed ultrastructural pellicle modifications. SnF2 appears to be the most effective type of fluoride to prevent erosive enamel demineralisation. The observed effects primarily have to be attributed to the stannous ions' content.

6.
Org Biomol Chem ; 17(9): 2467-2478, 2019 02 27.
Article in English | MEDLINE | ID: mdl-30747188

ABSTRACT

The neuropeptide Y (NPY) Y4 receptor is a G protein coupled receptor, which is targeted by pancreatic polypeptide, a homologue of NPY. Selective Y4R agonists were suggested as potential therapeutics for the treatment of obesity. Highly potent dimeric peptidic Y4R agonists, constituting two pentapeptide moieties connected through an aliphatic linker, represent an interesting class of Y4R ligands. Based on this compound class, photoresponsive Y4R ligands, containing an azobenzene, azopyrazole, diethienylethene or a fulgimide chromophore were prepared to explore structural requirements of such Y4R agonists on Y4R binding. The synthesized Y4R ligands, containing a non-aliphatic rigid photochromic linker, switch reversibly in aqueous buffer and exhibited high Y4R affinity throughout. This demonstrated that the replacement of the highly flexible aliphatic linker by a considerably less flexible photochromic linker was well tolerated with respect to Y4R binding. Differences in Y4R affinity and activity between the individual photoisomers (varying in spatial orientation and flexibility) were marginal suggesting that the linking element in the dimeric ligands is less critical for the adaptation of high-affinity binding modes at the receptor.


Subject(s)
Chromogenic Compounds/chemistry , Chromogenic Compounds/pharmacology , Oligopeptides/chemistry , Oligopeptides/pharmacology , Receptors, Neuropeptide Y/metabolism , Animals , Azo Compounds/chemistry , Azo Compounds/pharmacology , CHO Cells , Cricetulus , Humans , Ligands , Protein Binding , Receptors, Neuropeptide Y/agonists , Structure-Activity Relationship
7.
Epidemiol Infect ; 147: e58, 2018 Dec 03.
Article in English | MEDLINE | ID: mdl-30501684

ABSTRACT

Although the impact of diarrhoeal disease on paediatric health in Nigeria has decreased in recent years, it remains an important cause of morbidity and mortality in children under 5 years. Rotavirus is recognised as an important aetiological agent, but information on the contribution of intestinal protozoa to watery diarrhoea in this age group in Nigeria is scarce. In this cross-sectional study, faecal samples from children admitted to healthcare centres in Abakaliki, Nigeria with acute watery diarrhoea (N = 199) and faecal samples from age-matched controls (N = 37) were examined for Cryptosporidium and Giardia using immunofluorescent antibody testing and molecular methods. Cryptosporidium was identified in 13 case samples (6.5%) and no control samples. For three samples, molecular characterisation indicated C. hominis, GP60 subtypes IaA30R3, IaA14R3 and IdA11. Giardia was not detected in any samples. This contrast in prevalence between the two intestinal protozoa may reflect their variable epidemiologies and probably differing routes of infection. Given that these two parasitic infections are often bracketed together, it is key to realise that they not only have differing clinical spectra but also that the importance of each parasite is not the same in different age groups and/or settings.

8.
Br J Dermatol ; 179(6): 1358-1367, 2018 12.
Article in English | MEDLINE | ID: mdl-30192389

ABSTRACT

BACKGROUND: To prevent infections that arise from the skin surface it is necessary to decolonize human skin prior to any proposed treatment or surgical intervention. Photodynamic inactivation of bacteria (PIB) uses cationic photosensitizers that attach to the surface of bacteria, generate reactive oxygen species on light irradiation and thereby kill bacteria via oxidative mechanisms. OBJECTIVES: To evaluate the potential and the safety of PIB for decolonization of bacteria from skin. METHODS: PIB with the new photosensitizer SAPYR [2-((4-pyridinyl)methyl)-1H-phenalen-1-one chloride] was initially tested against different bacterial species in vitro. Then, ex vivo porcine skin samples were used as a model for decolonization of different bacteria species. The numbers of viable bacteria were quantified and the mitochondrial activity of skin cells was histologically analysed (using nitroblue tetrazolium chloride, NBTC). The same procedure was performed for human skin and meticillin-resistant Staphylococcus aureus (MRSA). RESULTS: The in vitro studies showed a 5 log10 reduction of all tested bacterial species. On ex vivo porcine skin samples, PIB reduced the viability of all tested bacterial species by at least 3 log10 steps. On human skin samples ex vivo, PIB reduced the number of viable MRSA by maximal 4·4 log10 steps (1000 µmol L-1 SAPYR, incubation time 10 min, 60 J cm-2 ). NBTC staining showed normal mitochondrial activity in skin cells after all PIB modalities. CONCLUSIONS: The results of this study show that PIB can effectively and safely kill bacteria like MRSA on the skin surface and might have the potential of skin decolonization in vivo.


Subject(s)
Disinfection/methods , Methicillin-Resistant Staphylococcus aureus/radiation effects , Photochemotherapy/methods , Photosensitizing Agents/administration & dosage , Skin/microbiology , Administration, Cutaneous , Animals , Colony Count, Microbial , Humans , Methicillin Resistance/drug effects , Methicillin Resistance/radiation effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Mitochondria/drug effects , Mitochondria/radiation effects , Photochemotherapy/adverse effects , Photosensitizing Agents/adverse effects , Skin/cytology , Skin/radiation effects , Staphylococcal Infections/microbiology , Staphylococcal Infections/prevention & control , Swine
9.
Photochem Photobiol Sci ; 17(8): 1056-1067, 2018 Aug 08.
Article in English | MEDLINE | ID: mdl-29915828

ABSTRACT

We report the synthesis and the spectroscopic and electrochemical properties of six mononuclear iridium(iii) and ruthenium(ii) complexes bearing S,S'-extended phenanthroline ligands. Starting from 5,6-dibromide-1,10-phenanthroline, the dithiine derivatives N,N'-1,10-phenanthrolinedithiino[2,3-b]quinoxaline and N,N'-1,10-phenanthrolinedithiino[2,3-b]benzene were prepared by primary N,N'-complexation of the dibromo derivative and subsequent nucleophilic substitution at the complex. The photoluminescence of the phenanthroline-dithiine containing complexes shows distinctively increased lifetimes for all Ir(iii) and Ru(ii) complexes. The activity of the series of Ir(iii) and Ru(ii) complexes as photosensitizers in visible-light photocatalytic water reduction is demonstrated by dihydrogen evolution with a [Fe3(CO)12] catalyst and triethylamine as a sacrificial donor.

10.
Pregnancy Hypertens ; 12: 136-143, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29858106

ABSTRACT

OBJECTIVE: Soluble Fms-like tyrosine kinase-1 (sFlt-1) is thought to be causative in the pathogenesis of preeclampsia (PE) and specific removal of sFlt-1 via dextran sulfate cellulose (DSC)-apheresis was suggested as cure to allow prolongation of pregnancy in preterm PE. However, in addition a deranged lipoprotein metabolism may impact endothelial and placental function in PE. Lipoprotein-apheresis by heparin-mediated extracorporeal LDL-precipitation (H.E.L.P.) was previously applied and has been shown to alleviate symptoms in PE. This clinical trial reevaluates the clinical efficacy of H.E.L.P.-apheresis in PE considering sFlt-1. STUDY DESIGN: Open pilot study assessing the prolongation by H.E.L.P.-apheresis in 6 women (30-41 years) with very preterm PE (24+4 to 27+0 gestational weeks (GW)) (NCT01967355) compared to a historic control-group matched for GW at admission (<28 GW; n = 6). Clinical outcome of mothers and babies, and pre- and post H.E.L.P.-apheresis levels of sFlt-1 and PlGF were monitored. MAIN OUTCOME MEASURES: In apheresis patients (2-6 treatments), average time from admission to birth was 15.0 days (6.3 days in controls; p = 0.027). Lung maturation was induced in all treated cases, and all children were released in healthy condition. Apheresis reduced triglycerides and LDL-cholesterol by more than 40%. Although H.E.L.P.-apheresis induced a transient peak baseline levels did not change and rather stabilized sFlt-1 levels at pre-apheresis levels throughout treatments, with sFlt-1/PLGF ratio remaining unaffected. CONCLUSIONS: H.E.L.P.-apheresis proved again to be safe and prolongs pregnancies in PE. However, without changing sFlt-1 levels below baseline lowering lipids or other yet undefined factors appear to be of more relevance than reducing sFlt-1.


Subject(s)
Anticoagulants/administration & dosage , Blood Component Removal/methods , Cholesterol, LDL/blood , Heparin/administration & dosage , Pre-Eclampsia/therapy , Premature Birth/prevention & control , Vascular Endothelial Growth Factor Receptor-1/blood , Adult , Anticoagulants/adverse effects , Biomarkers/blood , Blood Component Removal/adverse effects , Case-Control Studies , Female , Germany , Gestational Age , Heparin/adverse effects , Humans , Pilot Projects , Placenta Growth Factor/blood , Pre-Eclampsia/blood , Pre-Eclampsia/diagnosis , Pre-Eclampsia/physiopathology , Pregnancy , Premature Birth/etiology , Time Factors , Treatment Outcome , Triglycerides/blood , Young Adult
11.
Sci Rep ; 7(1): 16584, 2017 11 29.
Article in English | MEDLINE | ID: mdl-29185495

ABSTRACT

This study investigated the impact of customary fluoride based mouthrinses on the ultrastructure and the functional properties of the in situ pellicle, considering the prevention of erosion (8 volunteers) and initial biofilm formation (12 volunteers). Bovine enamel slabs were carried intraorally. After 1 min of pellicle formation, the subjects rinsed with elmex Kariesschutz (A), Dontodent Med Care (B), meridol (C) or elmex Zahnschmelzschutz Professional (D) for 1 min. In situ pellicle formation was continued up to 30 min/8 h before processing the slabs in vitro. Erosion was simulated by incubating the specimens in HCl (pH 3.0, 2.3, 2.0) for 120 s, measuring the kinetics of calcium/phosphate release photometrically; representative samples were evaluated by TEM and EDX. Bacterial adhesion was visualized fluorescence microscopically (DAPI/BacLight). Native enamel slabs or physiological pellicle samples served as controls. All investigated mouthrinses enhanced the erosion preventive pellicle effect in dependence of the pH-value. A significant decrease of Ca/P release at all pH values was achieved after rinsing with D; TEM/EDX confirmed ultrastructural pellicle modifications. All mouthrinses tendentially reduced bacterial adherence, however not significantly. The mouthrinse containing NaF/AmF/SnCl2 (D) offers an effective oral hygiene supplement to prevent caries and erosion.

12.
Acta Psychiatr Scand ; 136(6): 571-582, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28722128

ABSTRACT

OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.


Subject(s)
Bipolar Disorder/epidemiology , Electromagnetic Radiation , Internationality , Seasons , Adolescent , Adult , Africa/epidemiology , Age of Onset , Asia/epidemiology , Australia/epidemiology , Europe/epidemiology , Female , Humans , Male , Middle Aged , North America/epidemiology , Solar System , South America/epidemiology , Sunlight , Young Adult
13.
Eur J Clin Microbiol Infect Dis ; 36(10): 1955-1964, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28560472

ABSTRACT

Coagulase-negative staphylococci (CoNS) are the most prevalent pathogens causing late-onset sepsis in neonates. The question is whether neonates acquire endemic hospital-adapted clones or incidentally occurring CoNS strains after birth during their hospital stay. Therefore, a prospective study was performed on the prevalence of CoNS in the stool of babies (born vaginally or by cesarean section) during their first days of life. Their clonal relatedness and potential to induce invasive disease were characterized. CoNS were analyzed from the stool samples of newborns with a load of CoNS above 103 colony-forming units (CFU)/mL. The identification of CoNS was performed phenotypically and genotypically. For typing, repetitive polymerase chain reaction (PCR), pulsed-field gel electrophoresis, and multilocus sequence typing were used. Resistance profiles, biofilm production, the presence of icaAD and of IS256 were determined as well. From a total of 207 stool samples (56 newborns), CoNS were detected in 41% of the newborns, mostly on day 3 for the first time (62.5%). Staphylococcus epidermidis was isolated in 85.7% of cases, harbored no IS256 element, and mostly expressed no biofilm. The isolates were separated into four main clusters by repetitive sequence-based PCR. 24% of the strains showed no antimicrobial resistance. 20% were resistant against four antibiotics of two different antibiotic classes. The remaining strains were resistant only against one antimicrobial substance class. Thus, it can be concluded that newborns do not acquire hospital-adapted endemic, multidrug-resistant S. epidermidis isolates during their first days of life. Yet, the results support the thesis that, during hospital stay, environmental parameters may convert sensible/noninvasive S. epidermidis strains into multidrug-resistant strains with characteristics of invasiveness.


Subject(s)
Genotype , Staphylococcal Infections/microbiology , Staphylococcus epidermidis/classification , Staphylococcus epidermidis/isolation & purification , Virulence Factors/analysis , Bacterial Load , Bacterial Typing Techniques , Feces/microbiology , Humans , Infant, Newborn , Microbial Sensitivity Tests , Molecular Typing , Prevalence , Prospective Studies , Staphylococcus epidermidis/pathogenicity
14.
Org Biomol Chem ; 15(22): 4882-4896, 2017 Jun 07.
Article in English | MEDLINE | ID: mdl-28537315

ABSTRACT

Histone deacetylases (HDACs) play a crucial role in numerous biological processes and therefore are targeted in anticancer research and in the field of epigenetics. Dithienylethenes (DTEs) and fulgimides were functionalized with hydroxamic acids, which is a known moiety binding to zinc dependent HDACs, to gain photoswitchable HDAC inhibitors. The new DTE based inhibitors showed moderate photochromic properties in polar solvents and the inhibitory activity changes up to a factor of four. The photochromic performance of the prepared fulgimide inhibitors was very good, even in aqueous buffer. They achieved a maximum three-fold difference in inhibitory activity. Docking experiments using the crystal structures of the tested enzymes gave a rationale for the observed moderate differences in the activities of the inhibitors.


Subject(s)
Ethylenes/pharmacology , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/metabolism , Indoles/pharmacology , Succinimides/pharmacology , Thiophenes/pharmacology , Dose-Response Relationship, Drug , Ethylenes/chemical synthesis , Ethylenes/chemistry , Histone Deacetylase Inhibitors/chemical synthesis , Histone Deacetylase Inhibitors/chemistry , Humans , Indoles/chemical synthesis , Indoles/chemistry , Molecular Structure , Photochemical Processes , Structure-Activity Relationship , Succinimides/chemical synthesis , Succinimides/chemistry , Thiophenes/chemical synthesis , Thiophenes/chemistry
15.
J Viral Hepat ; 24(10): 840-849, 2017 10.
Article in English | MEDLINE | ID: mdl-28342229

ABSTRACT

Real-world studies are relevant to complement clinical trials on novel antiviral therapies against chronic hepatitis C; however, clinical practice data are currently limited. This study investigated effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r)±dasabuvir (DSV)±ribavirin (RBV) for treatment of HCV genotype (GT) 1 and GT4 infection in a large real-world cohort. The German Hepatitis C Registry is an observational cohort study prospectively collecting clinical practice data on direct-acting antiviral therapies. Patients with GT1/4 infection treated with OBV/PTV/r±DSV±RBV were analysed. Effectiveness was assessed by sustained virologic response in 558 patients who reached post-treatment week 12 (SVR12). Safety is reported in 1017 patients who initiated treatment. Of the patients, 892 (88%) had GT1 and 125 (12%) had GT4 infection. Prior treatment experience and cirrhosis were reported in 598 (59%) and 228 (22%) patients, respectively. Overall, SVR12 (mITT) was 96% (486/505) in GT1- and 100% (53/53) in GT4 patients. SVR12 rates were high across subgroups including patients with cirrhosis (95%, 123/129), patients with moderate to severe renal impairment (100%, 34/34), and subgroups excluded from registrational trials like patients ≥70 years (96%, 64/67) and failures to prior protease inhibitor treatment (96%, 46/48). Adverse events (AEs) and serious AEs were reported in 52% (525/1017) and 2% (21/1017) of patients, respectively, and led to treatment discontinuation in 1.5% (15/1017) of patients. OBV/PTV/r±DSV±RBV was effective and generally well tolerated for treatment of HCV infection in clinical practice.


Subject(s)
Anilides/administration & dosage , Carbamates/administration & dosage , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Macrocyclic Compounds/administration & dosage , Ritonavir/administration & dosage , Sulfonamides/administration & dosage , Uracil/analogs & derivatives , 2-Naphthylamine , Adult , Aged , Anilides/adverse effects , Carbamates/adverse effects , Cohort Studies , Cyclopropanes , Drug Therapy, Combination , Female , Genotype , Germany , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/diagnosis , Humans , Lactams, Macrocyclic , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Macrocyclic Compounds/adverse effects , Male , Middle Aged , Proline/analogs & derivatives , Ritonavir/adverse effects , Severity of Illness Index , Sulfonamides/adverse effects , Treatment Outcome , Uracil/administration & dosage , Uracil/adverse effects , Valine , Viral Load
16.
Z Orthop Unfall ; 155(1): 67-71, 2017 Feb.
Article in German | MEDLINE | ID: mdl-27612314

ABSTRACT

Introduction: Pelvic ring injuries occur in 3-8 % of patients with fractures. They are rare, with an annual incidence of only 19-37 per 100,000 people annually. There have been publications on the generation of these injuries, as well as their diagnosis and treatment concepts, but there is little information on how these injuries impact the ability to work. Patients: The study covered all hospitalised patients between January 2003 and December 2011 with a pelvic ring injury, who had already been included in the data collection of the AG Becken III and who had had a work-related accident. Data acquisition was completed 12 months after the first cover letter. Data collection was supported by the statutory accident insurance institutions. Responses to the following questions were collected: Results: During the time period, 835 patients were admitted to our hospital with an injury to the pelvic ring or acetabulum. 632 patients (75.7 %) had a pelvic ring injury. 95 patients had a work-related accident, for which 67 records (70.5 %) could be evaluated. Seven patients were in retirement at the time. The average age was 48 years. In the patient population, we identified 9 type A, 16 type B and 42 type C injuries. The mean duration of incapacity for work was 9.5 months. 36 patients were able to return to their old work again, 22 patients did not. For two of these patients, this was due to cerebral haemorrhage. The mean reduction in earning capacity at the 1st and 2nd pension reports was 28 %. The individual rating of the degree of trauma lay between 0 % (B2.1) to 60 % (C1.2). Subgroup analysis was not performed, due to the small number of patients and their lack of homogeneity. As only hospitalised patients were included in the study group, there was excessive accumulation of pelvic B and C fractures in the patient group. The study shows that pelvic ring injuries can have a significant impact on the duration of the incapacity and the ability to work.


Subject(s)
Fractures, Bone/economics , Occupational Injuries/economics , Pelvic Bones/injuries , Return to Work/economics , Salaries and Fringe Benefits/economics , Adult , Age Distribution , Aged , Disability Evaluation , Disabled Persons/statistics & numerical data , Female , Fractures, Bone/epidemiology , Fractures, Bone/therapy , Germany/epidemiology , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Occupational Injuries/epidemiology , Salaries and Fringe Benefits/statistics & numerical data , Sex Distribution , Work Capacity Evaluation , Workload/economics
17.
Z Orthop Unfall ; 154(5): 488-492, 2016 Oct.
Article in German | MEDLINE | ID: mdl-27366952

ABSTRACT

Introduction: There have been significant increases in the number of acetabular fractures in elderly patients with primarily ventral pathology and medial protrusion of the femoral head. We have developed the "acetabulum wing plate", which is designed to facilitate repositioning, with its anatomically precontoured structure, and which offers full support of the quadrilateral surface, thus counteracting the force of the femoral head pushing inwards. Conventional plate osteosynthesis only provides insufficient support to the medial surface. After a successful series of biomechanical tests, we now report a clinical case series. Material and Methods: Between April 2012 and August 2013, a total of twelve patients underwent plate osteosynthesis using the precontoured plate described above. The patients (ten male, two female) were aged between 45 and 87 years, the average age being 62.5 years. We were able to perform all osteosynthesis with the modified Stoppa approach, in combination with the first window of the ilioinguinal approach (according to Letournel). In most patients, the plate was applied without complications, In some patients, it even supported repositioning. In six patients, the fractures were of the anterior collum and six fractures were fractures of both colla. The mean time span of follow-up was 13.1 months, the minimum being 4.5 and the maximum 23 months. Results: In most patients, the intra- and postoperative computed tomographic scans showed anatomically correct placement of the plate, thus confirming the correct repositioning of the bone. Routine follow-ups are part of the hospital's postsurgical care system for acetabular fractures; these revealed no secondary dislocation or loosening of the plate. The radiological examination showed consolidation of the fractures after a mean period of twelve weeks. A full year after the initial procedure, no implant-specific complications were observed. Revision surgery was necessary in one patient due to bleeding five days after surgery. In another patient, necrosis of the femoral head necessitated total hip replacement ten weeks after the first surgical intervention. In summary, the concept of the plate proved to be successful in its first case series. Summary: In spite of increasing surgical expertise and the refinements of standard approaches, there is a recognisable shift in acetabular fractures from mainly posterior fracture patterns to fractures of the anterior column. The new acetabulum wing plate takes these factors into account and is an implant designed to address the anterior aspects of the acetabulum. The outcome of the first application is promising and the acetabulum wing plate produces satisfactory results in our patients.


Subject(s)
Acetabulum/injuries , Acetabulum/surgery , Bone Plates , Fracture Fixation, Internal/instrumentation , Fractures, Bone/surgery , Acetabuloplasty/instrumentation , Aged , Aged, 80 and over , Equipment Failure Analysis , Female , Fractures, Bone/diagnostic imaging , Humans , Male , Middle Aged , Prosthesis Design , Treatment Outcome
18.
Org Biomol Chem ; 13(40): 10198-204, 2015 Oct 28.
Article in English | MEDLINE | ID: mdl-26303394

ABSTRACT

Flavin derivatives with an extended π-conjugation were synthesized in moderate to good yields from aryl bromides via a Buchwald-Hartwig palladium catalyzed amination protocol, followed by condensation of the corresponding aromatic amines with violuric acid. The electronic properties of the new compounds were investigated by absorption and emission spectroscopy, cyclic voltammetry, density functional theory (DFT) and time dependent density functional theory (TDDFT). The compounds absorb up to 550 nm and show strong luminescence. The photoluminescence quantum yields ϕPL measured in dichloromethane reach 80% and in PMMA (poly(methyl methacrylate)) 77%, respectively, at ambient temperature. The electrochemical redox behaviour of π-extended flavins follows the mechanism previously described for the parent flavin.


Subject(s)
Flavins/chemistry , Flavins/chemical synthesis , Electrons , Molecular Structure , Oxidation-Reduction , Quantum Theory
19.
Chem Commun (Camb) ; 51(30): 6568-71, 2015 Apr 18.
Article in English | MEDLINE | ID: mdl-25772087

ABSTRACT

Highly oxidizing nitrate radicals (NO3˙) are easily accessed from readily available nitrate salts by visible light photoredox catalysis using a purely organic dye as the catalyst and oxygen as the terminal oxidant. The interaction of the excited catalyst and nitrate anions was studied by spectroscopic methods to elucidate the mechanism, and the method was applied to the NO3˙ induced oxidation of alkynes and alcohols.


Subject(s)
Light , Nitrates/chemistry , Photochemical Processes , Catalysis , Free Radicals/chemistry , Oxidation-Reduction
20.
J Hosp Infect ; 89(3): 179-85, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25623204

ABSTRACT

BACKGROUND: Multi-drug-resistant Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae are an increasing cause of healthcare-associated infections worldwide. AIMS: To investigate the impact of clinical infection on mortality, and examine the effect of use of KPC-2-specific polymerase chain reaction (PCR) on the time to contact isolation during an outbreak. METHODS: Cases were defined as patients clinically infected or colonized with KPC-2-producing K. pneumoniae between June 2010 and July 2012. Cases were described by demographic and health characteristics, and the association between infection and mortality, adjusted for comorbidities and demographic characteristics, was determined using Poisson regression with robust standard errors. A comparison was made between the time to contact isolation with a culture-based method and PCR using Wilcoxon's rank sum test. FINDINGS: Of 72 cases detected, 17 (24%) had undergone transplantation and 21 (29%) had a malignancy. Overall, 35 (49%) cases were clinically infected, with pneumonia and sepsis being the most common infections. Infection was an independent risk factor for mortality (risk ratio 1.67, 95% confidence interval 0.99-2.82). The median time to contact isolation was 1.5 days (range 0-21 days) using PCR and 5.0 days (range 0-39 days) using culture-based methods (P = 0.003). Intermittent negative tests were observed in 48% (14/29) of cases tested using culture-based methods. CONCLUSION: KPC-2-producing K. pneumoniae mainly affect severely ill patients. Half of the cases developed clinical infection, associated with increased risk of death. As PCR accelerates isolation and provides the opportunity for preventive measures in colonized cases, its use should be implemented promptly during outbreaks. Further studies are needed to enhance knowledge about KPC detection patterns and to adjust screening guidelines.


Subject(s)
Cross Infection/epidemiology , Cross Infection/microbiology , Disease Outbreaks , Klebsiella Infections/epidemiology , Klebsiella Infections/microbiology , beta-Lactamases/isolation & purification , Adult , Aged , Aged, 80 and over , Female , Greece/epidemiology , Hospitals/statistics & numerical data , Humans , Length of Stay , Male , Middle Aged , Polymerase Chain Reaction/methods , Retrospective Studies , beta-Lactamases/genetics
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