This paper aims at providing a link between fiber orientation and the properties of FRC, the structure to be built and its respective production process. Since the proposed framework is to a large ...extent new, the main components are described in the beginning. Then, two major subjects are approached from a theoretical perspective: fiber orientation in 3-D and the wall-effects of fibers in anisotropic conditions. Finally, in the last part, the main steps of the proposed framework are analyzed in detail and validated with experimental results. This comprehensive and straightforward model has shown to be capable of estimating the average orientation of fibers with very good accuracy. Thereby, this paper is a meaningful contribution to create an engineering toolbox for the prediction of fiber orientation in practical applications of fiber reinforced concrete.
The orientation of fibers has a pronounced influence on the tensile behavior of steel fiber reinforced concrete (SFRC) and, consequently, this aspect should be considered in modeling the material ...constitutive law. Previous works have shown that the tensile strength of SFRC is directly related to the average orientation of the fibers. However, few studies have investigated the correlation between the variation of distribution of fiber orientation and material strength. This paper introduces a new concept of orientation profile in order to characterize fiber orientation through an unambiguous method. From the investigation on experimental data it could be observed that fiber orientation follows a Gaussian law and that the distribution and average values of single fiber orientations are correlated with each other. Conclusions from this paper are particularly relevant for the development of micromechanical models for SFRC.
Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has ...proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients.
Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018.
Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome.
This study describes the natural history of classic galactosemia based on the hitherto largest data set.
Background
Ex vivo confocal laser scanning microscopy (CLSM) is a novel diagnostic tool for the fast examination of native tissue. However, CLSM produces black/white/green images, depending on the ...refraction indices of the tissue structures, complemented by nuclear fluorescence staining, which the vast majority of Mohs surgeons and dermatopathologists are not trained to interpret. Digital staining is applicable to ex vivo CLSM investigations to simulate the images of conventional slides stained with haematoxylin and eosin (H&E).
Objectives
The aim of our study was to evaluate in detail the appearance of human skin structures using digitally stained ex vivo CLSM images and compare the results to that of conventional H&E slides of the same specimen.
Methods
After providing informed consent, 26 patients donated their Burow's triangles (healthy skin) that resulted from plastic reconstruction after the R0 excision of skin tumours. After being investigated by ex vivo CLSM, including automated digital staining (VivaScope 2500M‐4G, MAVIG GmbH), the specimens were fixed in formalin, embedded in paraffin and stained with H&E.
Results
Almost all skin structures in the digitally stained ex vivo CLSM images morphologically resembled the structures in the histopathological images acquired from H&E slides. Due to the high refraction index of melanin, the hair shafts appeared bright pink, and the melanocytes and melanophages were poorly imaged, resulting in a strong pink appearance that vastly differed from the appearance of conventional H&E‐stained histopathology.
Conclusions
Digital staining of ex vivo CLSM images is an easy and highly useful tool to facilitate the interpretation of black‐field images generated by confocal laser scanning microscopy for dermatopathologists and Mohs surgeons who are familiar with H&E staining. Unlike the pigmented structures, the cutaneous and subcutaneous structures had excellent visualization with only minimal differences from their appearance on H&E slides.
What happens to the unsuccessful spermatozoa? Engel, K. M.; Springsguth, C. H.; Grunewald, S.
Andrology (Oxford),
March 2018, 2018-Mar, 2018-03-00, 20180301, Letnik:
6, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Summary
To study apoptosis as a functional pathway in mature spermatozoa and apoptosis correlated to the acrosome reaction via the intracellular calcium concentration, semen samples from 27 healthy ...human donors were treated with inducers of apoptosis (betulinic acid, thapsigargin), inducers of the acrosome reaction (thapsigargin, calcium ionophore) or hydrogen peroxide to produce reactive oxygen species with and without prior incubation with a calcium chelator. Computer‐assisted sperm analysis, flow cytometry, and transmission electron microscopy were performed to analyze changes in the acrosomal status and in apoptotic features. Betulinic acid, thapsigargin, and the calcium ionophore treatment resulted in an increased number of sperm cells with caspase 9 and caspase 3 activation, disrupted mitochondrial membrane potential, and a reacted acrosome. Sperm motility was decreased in all cases. Transmission electron analyses showed ultra‐morphological changes, such as membrane integrity, membrane blebbing, the formation of head vacuoles, defects of the nuclear envelope, nuclear fragmentation, and the acrosome reaction. Acrosome reaction and apoptotic features decreased due to the reduction in intracellular calcium by the calcium chelator NP‐EGTA, AM. Therefore, apoptotic cell death in acrosome‐reacted sperm cells mediated by high intracellular calcium levels is possible.
Inhibin B is an important serum marker of spermatogenesis, whereas sensitivity and predicting power for the spermatogenic situation at several ages are under debate. We performed a retrospective ...analysis of data from 2448 men who attended our University-based male infertility clinic to evaluate inhibin B in relation to age and semen sample qualities in comparison with FSH. Moreover, the range of inhibin B in 82 nonobstructive azoospermic patients was correlated with the sperm retrieval in testicular sperm extraction procedures. Inhibin B correlated with FSH (Spearman rank correlation (R)=-0.50; P<0.00001). Inhibin B and inhibin B/FSH ratio (IFR) showed an inverse U-shaped dependence on age, whereas FSH showed a U-shaped dependence on age (optimum 20-40 years). However, in men with normal spermiograms inhibin B concentrations did not differ between age groups. Their levels of inhibin B amounted to 130.5, 54.5-247 ng/l (median, 10th-90th precentile), and of IFR to 38.3, 12.5-104.8 (median, 10th-90th percentile), which might be taken as the reference range. Using the 10th percentile of IFR, correct classification in normal or pathological semen groups was achieved in 99.1%. The percentage of aniline blue-negative spermatozoa, i.e. mature spermatozoa with protamines, did not correlate with FSH (P>0.05) but with inhibin B (R=0.15, P<0.001). The probability of retrieving testicular spermatozoa decreased with declining inhibin B: <20 ng/l sperm could never be found. Our results from a large group of men with a wide spectrum of semen qualities allow estimating reference values for inhibin B and IFR. Inhibin B and especially the IFR are more sensitive markers of male infertility than FSH alone.
Background
Enzyme replacement therapy (ERT) for infantile-onset Pompe disease has been commercially available for almost 10 years. We report the experience of its use in a cohort treated at three ...specialist lysosomal treatment centres in the UK.
Methods
A retrospective case-note review was performed, with additional data being gathered from two national audits on all such patients treated with ERT. The impact on the outcome of various characteristics, measured just prior to the initiation of ERT (baseline), was evaluated using logistic regression.
Results
Thirty-three patients were identified; 13/29 (45 %) were cross-reactive immunological material (CRIM) negative, and nine were immunomodulated. At baseline assessment, 79 % were in heart failure, 66 % had failure to thrive and 70 % had radiological signs of focal pulmonary collapse. The overall survival rate was 60 %, ventilation-free survival was 40 % and 30 % of patients were ambulatory. Median follow-up of survivors was 4 years, 1.5 months (range 6 months to 13.5 years). As with previous studies, the CRIM status impacted on all outcome measures. However, in this cohort, baseline failure to thrive was related to death and lack of ambulation, and left ventricular dilatation was a risk factor for non-ventilator-free survival.
Conclusion
The outcome of treated patients remains heterogeneous despite attempts at immunomodulation. Failure to thrive at baseline and left ventricular dilation appear to be associated with poorer outcomes.
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