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1.
J Chem Phys ; 158(5): 054501, 2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36754828

ABSTRACT

Multiple-step nucleation pathways have been observed during mineral formation in both inorganic and biomineral systems. These pathways can involve precursor aqueous species, amorphous intermediates, or metastable phases. Despite the widespread occurrence of these processes, elucidating the precise nucleation steps and the transformation mechanisms between each step remains a challenging task. Using a suite of potentiometric, microscopic, and spectroscopic tools, we studied the nucleation pathway of SrSO4 as a function of the physico-chemical solution parameters. Our observations reveal that below a threshold supersaturation, nucleation is driven by bound species, akin to the prenucleation cluster model, which directly leads to the formation of the stable phase celestine, SrSO4. At higher supersaturations, this situation is altered, with nucleation dominated by the consumption of free ions. Importantly, this change in nucleation mechanism is coupled to the formation of a hemihydrate metastable phase, SrSO4 · 1/2H2O, which eventually transforms into celestine, adhering to Ostwald's rule of stages. This transformation is a solution-mediated process, also occurring in the presence of a fluid film and is controlled by the physico-chemical parameters of the surrounding environment. It proceeds through the dissolution of the metastable phase and the de novo crystallization of the final phase. Overall, our results reveal that ion association taking place during the prenucleation stage dictates whether the nucleation pathway goes through an intermediate phase or not. This also underlines that although Ostwald's rule of stages is a common process, it is not a prerequisite for mineral formation-even in systems where it can occur.

2.
Faraday Discuss ; 235(0): 95-108, 2022 Jul 14.
Article in English | MEDLINE | ID: mdl-35389401

ABSTRACT

In this work we link experimental results of SrSO4 precipitation with a nucleation model based on mesoscopic nucleation theory (MeNT) to stride towards a cohesive view of the nucleation process that integrates both classical and non-classical views. When SrCl2 and Na2SO4 are co-titrated at slow dosing rates, time-resolved turbidity, conductivity and ion-specific data reveal that the initial stage of the nucleation process is driven by neutral species, i.e. ion-pairs or larger, akin to the prenucleation cluster model. However, when co-titrations are conducted at higher rates, the onset of nucleation is dominated by the consumption of free ions, akin to the explanation provided by classical nucleation theory (CNT). The occurrence of both mechanisms for the same system is explained by a toy model that includes both the thermodynamics (consisting of a single energy barrier) and kinetics of cluster formation formally obtained from MeNT. This gives rise to an effective energy barrier exhibiting a local intermediate minimum, which does not originate from a minimum in the thermodynamic free energy. Rather, it is associated with an increased probability of observing a specific class (in terms of size/density) of precursor clusters due to their slower kinetics. At high supersaturations this minimum in the kinetics of cluster formation becomes less pronounced and the effective barrier is also significantly lowered. Consequently, the probability of observing an intermediate state is blurred and we recover a nucleation pathway more closely following the one envisaged by the classical model. Thus, our model is capable of capturing both single and multistep nucleation mechanisms observed experimentally considering only a single energy barrier.

3.
J Food Prot ; 85(5): 755-772, 2022 05 01.
Article in English | MEDLINE | ID: mdl-35259246

ABSTRACT

ABSTRACT: This multiagency report developed by the Interagency Collaboration for Genomics for Food and Feed Safety provides an overview of the use of and transition to whole genome sequencing (WGS) technology for detection and characterization of pathogens transmitted commonly by food and for identification of their sources. We describe foodborne pathogen analysis, investigation, and harmonization efforts among the following federal agencies: National Institutes of Health; Department of Health and Human Services, Centers for Disease Control and Prevention (CDC) and U.S. Food and Drug Administration (FDA); and the U.S. Department of Agriculture, Food Safety and Inspection Service, Agricultural Research Service, and Animal and Plant Health Inspection Service. We describe single nucleotide polymorphism, core-genome, and whole genome multilocus sequence typing data analysis methods as used in the PulseNet (CDC) and GenomeTrakr (FDA) networks, underscoring the complementary nature of the results for linking genetically related foodborne pathogens during outbreak investigations while allowing flexibility to meet the specific needs of Interagency Collaboration partners. We highlight how we apply WGS to pathogen characterization (virulence and antimicrobial resistance profiles) and source attribution efforts and increase transparency by making the sequences and other data publicly available through the National Center for Biotechnology Information. We also highlight the impact of current trends in the use of culture-independent diagnostic tests for human diagnostic testing on analytical approaches related to food safety and what is next for the use of WGS in the area of food safety.


Subject(s)
Foodborne Diseases , Animals , Disease Outbreaks/prevention & control , Food Safety , Foodborne Diseases/epidemiology , Foodborne Diseases/prevention & control , Genomics , United States , Whole Genome Sequencing
4.
Genomics ; 113(5): 3152-3162, 2021 09.
Article in English | MEDLINE | ID: mdl-34242711

ABSTRACT

Species and subspecies within the Salmonella genus have been defined for public health purposes by biochemical properties; however, reference laboratories have increasingly adopted sequence-based, and especially whole genome sequence (WGS), methods for surveillance and routine identification. This leads to potential disparities in subspecies definitions, routine typing, and the ability to detect novel subspecies. A large-scale analysis of WGS data from the routine sequencing of clinical isolates was employed to define and characterise Salmonella subspecies population structure, demonstrating that the Salmonella species and subspecies were genetically distinct, including those previously identified through phylogenetic approaches, namely: S. enterica subspecies londinensis (VII), subspecies brasiliensis (VIII), subspecies hibernicus (IX) and subspecies essexiensis (X). The analysis also identified an additional novel subspecies, reptilium (XI). Further, these analyses indicated that S. enterica subspecies arizonae (IIIa) isolates were divergent from the other S. enterica subspecies, which clustered together and, on the basis of ANI analysis, subspecies IIIa was sufficiently distinct to be classified as a separate species, S. arizonae. Multiple phylogenetic and statistical approaches generated congruent results, suggesting that the proposed species and subspecies structure was sufficiently biologically robust for routine application. Biochemical analyses demonstrated that not all subspecies were distinguishable by these means and that biochemical approaches did not capture the genomic diversity of the genus. We recommend the adoption of standardised genomic definitions of species and subspecies and a genome sequence-based approach to routine typing for the identification and definition of novel subspecies.


Subject(s)
Salmonella enterica , Genome, Bacterial , Phylogeny , Salmonella/genetics , Salmonella enterica/genetics , Serogroup
5.
Int J Cosmet Sci ; 42(5): 421-428, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32390187

ABSTRACT

In 2017, Cosmetics Europe performed a double-blinded ring test of 24 emulsion-type sunscreen products, across 3 in vivo test laboratories and 3 in vitro test laboratories, using a new candidate in vitro SPF test method. Based on the results of this work, an article was published showing how data derived from a new lead candidate method conform to new International Standards (ISO) acceptance criteria for alternative SPF test methods (Any alternative method should consider the matrix effect and if required, specify the matrix applicability of the method; Criterion 1a: Systematic differences between methods should be negligible: 95% of all individual results of an alternative method are within the range of ±2× reproducibility standard deviation of the in vivo method, that is overall bias must be below 0.5× reproducibility standard deviation of the in vivo method; Criterion 1b: Measurement uncertainty of an alternative method should be below the measurement uncertainty of the in vivo method. Candidate method predicted values must fall within the full 'funnel' (SPF 6-50+) limits proposed by Cosmetics Europe (derived from the same minimum test design, that is using the ISO24444 Method to measure at least 24 products across at least 3 laboratories using at least 5 test subjects/laboratory, in a blinded fashion).). Of the 24 sunscreen products tested, the majority of emulsions were of the oil-in-water (O/W) type, whereas only one was water-in-oil (W/O) and there were no products with a mineral-only sun filter system. In order to confirm the scope of this method, therefore, a new study was conducted that included 73 W/O (12 mineral + organic, 44 mineral only and 17 organic only) and 3 O/W mineral-only, emulsion-type sunscreen products (a total of 76 new sunscreen products). When combined with the previous 24 products (tested in 3 different laboratories), this yielded a new data set comprising a total of 100 emulsion-type sunscreen products, with SPF values ranging from 6 to 50+ (with a total of 148 data points). These products were tested using the double-plate in vitro SPF test method and compared with the ISO TC217/WG7 acceptance criteria for alternative SPF test methods. Over 95% of paired in vitro: in vivo SPF values lay within the upper and lower limits of the ISO acceptance criteria funnel, with no bias. This new in vitro SPF test method, therefore, meets the minimum requirements for an alternative SPF test method to ISO24444:2010, for emulsion-type sunscreen products (which make up the majority of marketed sunscreen products).


En 2017, Cosmetics Europe a réalisé un ring test en double aveugle de 24 produits de protection solaire de type émulsion, dans 3 laboratoires de test in vivo et 3 laboratoires de test in vitro, en utilisant une nouvelle méthode de test SPF in vitro. Sur la base des résultats de ces travaux, un article a été publié montrant comment les données dérivées de cette nouvelle méthode sont conformes aux nouveaux critères d'acceptation des normes internationales (ISO) pour les méthodes de test SPF alternatives. Sur les 24 produits de protection solaire testés, la majorité des émulsions étaient du type huile dans l'eau (H / E), tandis qu'un seul était de l'eau dans l'huile (E / H) et il n'y avait aucun produit contenant uniquement des minéraux. Afin de confirmer cette méthode, une nouvelle étude a donc été menée comprenant 73 produits E/ H (12 produits contenant des filtres minéraux + organiques, 44 produits contenant des filtres minéraux uniquement et 17 produits contenant des filtres organiques uniquement) et 3 produits H / E contenant des filtres minéraux uniquement, tous de type émulsion (donc un un total de 76 nouveaux produits de protection solaire). Combiné aux 24 produits précédents (testés dans 3 laboratoires différents), cela a donné un nouvel ensemble de données comprenant un total de 100 produits de protection solaire de type émulsion, avec des valeurs SPF allant de 6 à 50+ (avec un total de 148 points de données) . Ces produits ont été testés à l'aide de la méthode de test SPF in vitro double approche et comparés aux critères d'acceptation de l'ISO TC217 / WG7 pour les méthodes alternatives du SPF in vivo. Plus de 95% des valeurs de SPF appariées in vitro: in vivo se situent dans les limites supérieure et inférieure de l'entonnoir des critères d'acceptation ISO, sans biais. Cette nouvelle méthode de test SPF in vitro, par conséquent, répond aux exigences minimales d'une méthode de test SPF alternative à ISO24444: 2010, pour les produits de protection solaire de type émulsion (qui constituent la majorité des produits de protection solaire commercialisés).


Subject(s)
Emulsions , Radiation-Protective Agents , Sun Protection Factor , Sunscreening Agents , In Vitro Techniques
6.
Appl Environ Microbiol ; 85(23)2019 12 01.
Article in English | MEDLINE | ID: mdl-31540993

ABSTRACT

SeqSero, launched in 2015, is a software tool for Salmonella serotype determination from whole-genome sequencing (WGS) data. Despite its routine use in public health and food safety laboratories in the United States and other countries, the original SeqSero pipeline is relatively slow (minutes per genome using sequencing reads), is not optimized for draft genome assemblies, and may assign multiple serotypes for a strain. Here, we present SeqSero2 (github.com/denglab/SeqSero2; denglab.info/SeqSero2), an algorithmic transformation and functional update of the original SeqSero. Major improvements include (i) additional sequence markers for identification of Salmonella species and subspecies and certain serotypes, (ii) a k-mer based algorithm for rapid serotype prediction from raw reads (seconds per genome) and improved serotype prediction from assemblies, and (iii) a targeted assembly approach for specific retrieval of serotype determinants from WGS for serotype prediction, new allele discovery, and prediction troubleshooting. Evaluated using 5,794 genomes representing 364 common U.S. serotypes, including 2,280 human isolates of 117 serotypes from the National Antimicrobial Resistance Monitoring System, SeqSero2 is up to 50 times faster than the original SeqSero while maintaining equivalent accuracy for raw reads and substantially improving accuracy for assemblies. SeqSero2 further suggested that 3% of the tested genomes contained reads from multiple serotypes, indicating a use for contamination detection. In addition to short reads, SeqSero2 demonstrated potential for accurate and rapid serotype prediction directly from long nanopore reads despite base call errors. Testing of 40 nanopore-sequenced genomes of 17 serotypes yielded a single H antigen misidentification.IMPORTANCE Serotyping is the basis of public health surveillance of Salmonella It remains a first-line subtyping method even as surveillance continues to be transformed by whole-genome sequencing. SeqSero allows the integration of Salmonella serotyping into a whole-genome-sequencing-based laboratory workflow while maintaining continuity with the classic serotyping scheme. SeqSero2, informed by extensive testing and application of SeqSero in the United States and other countries, incorporates important improvements and updates that further strengthen its application in routine and large-scale surveillance of Salmonella by whole-genome sequencing.


Subject(s)
Genome, Bacterial , Salmonella/genetics , Serotyping/methods , Whole Genome Sequencing , Serogroup , Serotyping/instrumentation , Software
8.
AJNR Am J Neuroradiol ; 39(7): 1273-1279, 2018 07.
Article in English | MEDLINE | ID: mdl-29748200

ABSTRACT

BACKGROUND AND PURPOSE: Chronic hemodynamic impairment in high-grade carotid occlusive disease is thought to cause microstructural abnormalities that might be subclinical or lead to subtle symptoms including cognitive impairment. Quantitative MR imaging allows assessing pathologic structural changes beyond macroscopically visible tissue damage. In this study, high-resolution quantitative T2 mapping combined with DSC-based PWI was used to investigate quantitative T2 changes as a potential marker of microstructural damage in relation to hemodynamic impairment in patients with unilateral high-grade carotid occlusive disease. MATERIALS AND METHODS: Eighteen patients with unilateral high-grade ICA or MCA stenosis/occlusion were included in the study. T2 values and deconvolved perfusion parameters, including relative CBF, relative CBV, and the relative CBF/relative CBV ratio as a potential indicator of local cerebral perfusion pressure, were determined within areas with delayed TTP and compared with values from contralateral unaffected areas after segmentation of normal-appearing hypoperfused WM and cortical regions. Hemispheric asymmetry indices were calculated for all parameters. RESULTS: Quantitative T2 was significantly prolonged (P < .01) in hypoperfused tissue and correlated significantly (P < .01) with TTP delay and relative CBF/relative CBV reduction in WM. Significant correlations (P < .001) between TTP delay and the relative CBF/relative CBV ratio were found both in WM and in cortical areas. CONCLUSIONS: Quantitative T2 can be used as a marker of microstructural tissue damage even in normal-appearing GM and WM within a vascular territory affected by high-grade carotid occlusive disease. Furthermore, the extent of damage correlates with the degree of hemodynamic failure measured by DSC perfusion parameters.


Subject(s)
Brain/diagnostic imaging , Brain/pathology , Carotid Stenosis/complications , Hemodynamics/physiology , Magnetic Resonance Imaging/methods , Adult , Aged , Brain/blood supply , Cerebrovascular Circulation/physiology , Female , Humans , Male , Middle Aged
9.
Phys Rev Lett ; 120(12): 122503, 2018 Mar 23.
Article in English | MEDLINE | ID: mdl-29694087

ABSTRACT

A beam containing a substantial component of both the J^{π}=5^{+}, T_{1/2}=162 ns isomeric state of ^{18}F and its 1^{+}, 109.77-min ground state is utilized to study members of the ground-state rotational band in ^{19}F through the neutron transfer reaction (d,p) in inverse kinematics. The resulting spectroscopic strengths confirm the single-particle nature of the 13/2^{+} band-terminating state. The agreement between shell-model calculations using an interaction constructed within the sd shell, and our experimental results reinforces the idea of a single-particle-collective duality in the descriptions of the structure of atomic nuclei.

10.
Int J Cosmet Sci ; 2018 Apr 20.
Article in English | MEDLINE | ID: mdl-29676800

ABSTRACT

OBJECTIVE: The objective of this work was to investigate the utility of a new in vitro SPF test method in blinded ring-testing, against new ISO acceptance criteria. METHODS: Twenty four blinded, commercial, emulsion-type, primary sunscreen products, covering the full range of labelled SPF in Europe (SPF6 - 50+), were tested by three test institutes using the current ISO24444:2010 In Vivo SPF Test Method and simultaneously by three separate test laboratories using a new candidate in vitro SPF test method, developed under the leadership of Cosmetics Europe (CE). The resulting relationship between in vitro SPF and in vivo SPF values was then compared with acceptance criteria developed recently by the International Standards (ISO) TC217/WG7 Sun Protection Test Methods Working Group. RESULTS: Analysis of the mean inter-laboratory in vitro and mean inter-institute in vivo SPF values revealed a strong correlation between in vitro and in vivo values, with a Pearson correlation coefficient of r2  = 0.88 (P < 0.0001), a slope of 1.01 and a non-significant intercept (-1.48; P = 0.62). When these data were compared to the new ISO WG7 acceptance criteria, method bias was found to be extremely low and over 95% of the coupled data lay within the model 'funnel' (defined by upper and lower confidence intervals). CONCLUSION: In conclusion, the results of blinded ring testing and comparison to new ISO WG7 acceptance criteria indicate that a new in vitro SPF test method meets (and exceeds) these minimum criteria and is an interesting candidate for possible deployment as an industry test methodology.

11.
Cardiovasc Intervent Radiol ; 41(5): 699-705, 2018 May.
Article in English | MEDLINE | ID: mdl-29468288

ABSTRACT

PURPOSE: Intra-arterial therapy of acute ischemic stroke has developed rapidly in recent years. Due to proven efficacy in randomized trials, stent retrievers were replacing first-generation thrombectomy devices and have been defined as method of choice. However, aspiration catheters or a combination of several techniques have shown promising rates of successful recanalizations. To create a basis for comparison of the new approaches according to real-world data, we determined the first pass recanalization rate of an evidence-based standard technique with the use of a stent retriever in combination with a balloon-guiding catheter. The assessment was based on the number of required passages and reperfusion rate, but not on clinical results. METHODS: Patients from our institution with anterior circulation occlusions and mechanical thrombectomy by using stent retrievers in combination with balloon-guiding catheters were analyzed retrospectively. Reperfusion was graded with the "thrombolysis in cerebral infarction" (TICI) classification on post-interventional angiograms. Additionally, the number of passes and the duration of the recanalization procedure were recorded. RESULTS: Between 2014 and July 2017, 201 patients met the inclusion criteria. Successful recanalization, defined as a TICI scale 2b/3, was 91% (TICI 2b was achieved in 44% and TICI 3 in 47%) after the procedure. After the first passage, successful recanalization was achieved in 65% of the patients. Mean number of passes was 1.4 (1-5 passes) for all patients. Median duration of the procedure was 49 min (0:11-2:35 h). CONCLUSIONS: Even a standard thrombectomy technique with the use of a stent retriever together with a balloon-guiding catheter provides reasonable recanalization rates with only one passage. The results can be taken as benchmark for alternative and more complex techniques.


Subject(s)
Balloon Embolectomy/instrumentation , Catheters , Device Removal/instrumentation , Stents , Stroke/surgery , Thrombectomy/instrumentation , Aged , Balloon Embolectomy/methods , Device Removal/methods , Female , Humans , Male , Retrospective Studies , Thrombectomy/methods , Treatment Outcome
12.
Unfallchirurg ; 120(4): 350-354, 2017 Apr.
Article in German | MEDLINE | ID: mdl-27770168

ABSTRACT

Traumatic hip dislocations in children are not frequent but constitute true emergencies. They require urgent reduction because of the risk of consecutive avascular necrosis of the femoral head. We report a 6-year-old boy with traumatic posterior hip dislocation on a vacation abroad. After closed reduction the day of the accident, a hip spica cast was applied and the patient was transferred home. Once home, X­ray and CT diagnostics were completed by MRI. In future, long-term clinical and radiological investigations for avascular necrosis and growth disorders, as well as thoroughly informing the parents, should be mandatory.


Subject(s)
Closed Fracture Reduction/methods , Fracture Dislocation/therapy , Hip Dislocation/therapy , Immobilization/methods , Child , Combined Modality Therapy/methods , Fracture Dislocation/complications , Fracture Dislocation/diagnostic imaging , Hip Dislocation/diagnostic imaging , Hip Dislocation/etiology , Hip Fractures , Humans , Male , Recovery of Function , Treatment Outcome
13.
Oral Dis ; 22(5): 438-44, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26988924

ABSTRACT

BACKGROUND: This study was conducted to assess whether statin intake is associated with clinical parameters of periodontitis and matrix metalloproteinase (MMP) levels in gingival crevicular fluid (GCF) of non-diabetic and diabetic patients. METHODS: We first determined the effect of simvastatin on MMP expression in mononuclear cells. We then recruited 117 non-diabetic and diabetic patients, who all had periodontitis and took or did not take statin, and measured periodontal probing depth (PPD) and clinical attachment level (CAL), and collected gingival crevicular fluid (GCF) to quantify MMPs. RESULTS: The in vitro studies showed that simvastatin potently inhibited the expression of MMP-1, MMP-8, and MMP-9 upregulated by lipopolysaccharide (LPS) and high glucose in mononuclear cells. The patient study showed that, after adjusting for age and smoking status, PPD in diabetic patients on statin was significantly less than that in diabetic patients not on statin. MMP-1 level in GCF of non-diabetic and diabetic patients on statin was lower than that of non-diabetic and diabetic patients not on statin, respectively. No difference was found for MMP-8 and -9 levels in GCF. CONCLUSION: Statin intake is associated with reduced PPD in diabetic patients and MMP-1 level in GCF in either non-diabetic or diabetic patients.


Subject(s)
Gingival Crevicular Fluid/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacokinetics , Matrix Metalloproteinase 1/metabolism , Periodontitis/metabolism , Adult , Aged , Blood Glucose/metabolism , Collagenases/genetics , Collagenases/metabolism , Diabetes Complications/drug therapy , Diabetes Complications/metabolism , Diabetes Mellitus/drug therapy , Female , Gingival Crevicular Fluid/drug effects , Humans , Lipopolysaccharides/pharmacology , Male , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 8/genetics , Matrix Metalloproteinase 8/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Middle Aged , Periodontal Attachment Loss , Periodontitis/genetics , Simvastatin/pharmacology , Up-Regulation
14.
Rev Sci Instrum ; 86(10): 103113, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26520946

ABSTRACT

The Pixel Imaging Mass Spectrometry (PImMS) camera is used in proof-of-principle three-dimensional imaging experiments on the photodissociation of carbonyl sulfide and ethyl iodide at wavelengths around 230 nm and 245 nm, respectively. Coupling the PImMS camera with DC-sliced velocity-map imaging allows the complete three-dimensional Newton sphere of photofragment ions to be recorded on each laser pump-probe cycle with a timing precision of 12.5 ns, yielding velocity resolutions along the time-of-flight axis of around 6%-9% in the applications presented.

15.
Drugs Today (Barc) ; 50(12): 779-90, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25588083

ABSTRACT

In the last decade, intravitreal medications targeted to vascular endothelial growth factor (VEGF) such as pegaptanib, ranibizumab and bevacizumab have revolutionized the treatment and significantly improved visual acuity outcomes in patients with retinal vascular diseases such as age-related macular degeneration (AMD), diabetic macula edema (DME) and retinal vein occlusion (RVO). In recent years, aflibercept, an anti-VEGF drug that targets all isoforms of VEGF as well as placenta growth factor, has shown similar effectiveness in recent clinical trials. Aflibercept has firmly joined ranibizumab and bevacizu-mab as an important therapeutic option in the management of neovascular AMD. More recently, aflibercept appears to be contending with ranibizumab and bevacizumab as an important therapeutic option in the management of DME and RVO.


Subject(s)
Macular Degeneration/drug therapy , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Retinal Vein Occlusion/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Clinical Trials as Topic , Humans , Intravitreal Injections , Visual Acuity
16.
Neuroscience ; 250: 181-8, 2013 Oct 10.
Article in English | MEDLINE | ID: mdl-23856067

ABSTRACT

Recombinant tissue-type plasminogen activator (rt-PA) is the mainstay of acute stroke treatment and the only approved medical therapy so far. Because of its fibrinolytic action, it is presumed to aggravate intracerebral hemorrhage (ICH). Since clinical features do not discriminate between ischemic stroke and ICH, brain imaging is strictly required before the initiation of thrombolysis. A recent study has shown that rt-PA does not worsen (primary) ICH in two different experimental mouse models. Here, we further explored this surprising finding and examined hematoma expansion and long-term outcome after rt-PA treatment in a murine model of ICH. We induced ICH by collagenase injection into the right basal ganglia of C57BL/6 mice. At 30 min, 90 min or 4h after ICH induction, respectively, mice were treated with vehicle or 10mg/kg rt-PA. In parallel, we administered the vascular tracer Evans Blue (EB) and sacrificed the mice 2h after injection to assess EB extravasation as a marker of ongoing bleeding and rt-PA induced rebleeding. Additionally, we observed mice which were treated with vehicle or rt-PA 30 min after ICH induction for 72 h and quantified functional outcome and hematoma volume. EB extravasation was highest in the groups that were treated after 30 min and decreased thereafter according to a cessation of active bleeding. At all three time points covering the early phase of ICH, treatment with rt-PA did not increase EB extravasation. In the 72 h observation, there was also no difference in functional outcome and hematoma volume. In our experimental study, we were not able to demonstrate that peracute rt-PA treatment in (primary) ICH has detrimental effects on hematoma expansion, hematoma volume or functional outcome. This finding needs careful consideration in future translational studies.


Subject(s)
Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/pathology , Fibrinolytic Agents/therapeutic use , Hematoma/drug therapy , Hematoma/pathology , Tissue Plasminogen Activator/therapeutic use , Animals , Cerebral Hemorrhage/chemically induced , Collagenases , Data Interpretation, Statistical , Evans Blue , Fluorescent Dyes , Hematoma/chemically induced , Male , Mice , Mice, Inbred C57BL , Nervous System Diseases/etiology , Nervous System Diseases/physiopathology , Recombinant Proteins/therapeutic use , Treatment Outcome
17.
Rev Sci Instrum ; 83(11): 114101, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23206074

ABSTRACT

Imaging mass spectrometry is a powerful technique that allows chemical information to be correlated to a spatial coordinate on a sample. By using stigmatic ion microscopy, in conjunction with fast cameras, multiple ion masses can be imaged within a single experimental cycle. This means that fewer laser shots and acquisition cycles are required to obtain a full data set, and samples suffer less degradation as overall collection time is reduced. We present the first spatial imaging mass spectrometry results obtained with a new time-stamping detector, named the pixel imaging mass spectrometry (PImMS) sensor. The sensor is capable of storing multiple time stamps in each pixel for each time-of-flight cycle, which gives it multi-mass imaging capabilities within each pixel. A standard velocity-map ion imaging apparatus was modified to allow for microscope mode spatial imaging of a large sample area (approximately 5 × 5 mm(2)). A variety of samples were imaged using PImMS and a conventional camera to determine the specifications and possible applications of the spectrometer and the PImMS camera.

18.
Drugs Today (Barc) ; 48(5): 317-29, 2012 May.
Article in English | MEDLINE | ID: mdl-22645720

ABSTRACT

Age-related macular degeneration (AMD) can have devastating effects on vision, especially in its neovascular form. In the last decade, the use of intravitreal pharmacotherapy targeted to vascular endothelial growth factor (VEGF) has significantly improved the visual outcomes in patients with neovascular AMD. Although we have become accustomed to these unprecedented improvement outcomes, maintaining good visual results with anti-VEGF therapy requires tremendous effort, time and cost, typically involving monthly clinic visits and intravitreal injections. The introduction of aflibercept, an anti-VEGF drug that targets all isoforms of VEGF as well as placenta growth factor, has shown promise throughout recent clinical trials as an equally effective treatment for neovascular AMD that requires less frequent dosing than either ranibizumab or bevacizumab. Based on clinical trial results, the U.S. Food and Drug Administration approved aflibercept in November 2011 for use in neovascular AMD, giving patients the hope of alleviating some of the burden associated with treatment.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Choroidal Neovascularization/drug therapy , Macular Degeneration/drug therapy , Recombinant Fusion Proteins/therapeutic use , Vascular Endothelial Growth Factors/antagonists & inhibitors , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/pharmacokinetics , Angiogenesis Inhibitors/pharmacology , Animals , Diabetes Complications/drug therapy , Humans , Intravitreal Injections , Macular Edema/drug therapy , Randomized Controlled Trials as Topic , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/pharmacokinetics , Recombinant Fusion Proteins/pharmacology
20.
Article in German | MEDLINE | ID: mdl-19756338

ABSTRACT

The rate of healthcare-associated infections can be regarded as an important outcome parameter of the hygienic quality of care in nursing homes. Our study aimed to evaluate the applicability of repeated prevalence investigations as a tool for surveillance of healthcare-associated infections in nursing homes. From December 2006 to September 2007 a total of five prevalence investigations were conducted in four nursing homes each (n=2,369 residents). Initially, defined structural and procedural parameters of the hygienic quality of the four nursing homes were evaluated based on a detailed inspection and a checklist including 40 parameters. The results showed a uniformly high level of the hygienic quality with only minor variation (mean 84%, range 75%-93% of parameters fulfilled). In total, the prevalence of healthcare-associated infections was 6.8%, with a marked increase with higher categories of dependency (3.5%, 4.0%, 8.5%, and 12.3%, respectively, in the categories 0, I, II, and III of the German grading of skilled nursing care). Respiratory tract (4.1%), skin/soft tissue (1.5%), and urinary tract infections were the most prevalent healthcare-associated infections. Respiratory tract infections showed a marked seasonal pattern. During the second prevalence investigation (February 2007), an outbreak of upper respiratory tract infections occurred in one of the nursing homes (attack rate, 17%). The crude prevalence rates showed considerable differences between the four nursing homes; however, after adjusting for the different categories of dependency, the standardized infection rates (SIR) were largely comparable (excluding the outbreak). After inclusion of the outbreak, the SIR of the specific nursing home was significantly higher compared to all other nursing homes. In conclusion, our study shows that repeated prevalence investigations can be an easy to use tool for surveillance of healthcare-associated infections as a surrogate parameter of the hygienic quality in nursing homes. This implies a knowledge of the seasonality of specific infections and a risk adjustment according to the categories of dependency. The primary intention of surveillance should be the identification of hygienic problems. However, the resources should preferentially be focused on hygienic structures and processes.


Subject(s)
Cross Infection/epidemiology , Homes for the Aged/statistics & numerical data , Homes for the Aged/standards , Hygiene/standards , Nursing Homes/statistics & numerical data , Nursing Homes/standards , Population Surveillance/methods , Aged , Aged, 80 and over , Cross Infection/prevention & control , Cross-Sectional Studies , Disability Evaluation , Germany , Humans , Quality Assurance, Health Care/standards , Risk Factors , Sanitation/standards
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