Synthetic Pathways to Non-Psychotropic Phytocannabinoids as Promising Molecules to Develop Novel Antibiotics: A Review.
Due to the rapid emergence of multi drug resistant (MDR) pathogens against which current antibiotics are no longer functioning, severe infections are becoming practically untreatable. Consequently, the discovery of new classes of effective antimicrobial agents with novel mechanism of action is becoming increasingly urgent. The bioactivity of Cannabis sativa, an herbaceous plant used for millennia for medicinal and recreational purposes, is mainly due to its content in phytocannabinoids (PCs). Among the 180 PCs detected, cannabidiol (CBD), Δ8 and Δ9-tetrahydrocannabinols (Δ8-THC and Δ9-THC), cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN) and some of their acidic precursors have demonstrated from moderate to potent antibacterial effects against Gram-positive bacteria (MICs 0.5-8 µg/mL), including methicillin-resistant Staphylococcus aureus (MRSA), epidemic MRSA (EMRSA), as well as fluoroquinolone and tetracycline-resistant strains. Particularly, the non-psychotropic CBG was also capable to inhibit MRSA biofilm formation, to eradicate even mature biofilms, and to rapidly eliminate MRSA persiter cells. In this scenario, CBG, as well as other minor non-psychotropic PCs, such as CBD, and CBC could represent promising compounds for developing novel antibiotics with high therapeutic potential. Anyway, further studies are necessary, needing abundant quantities of such PCs, scarcely provided naturally by Cannabis plants. Here, after an extensive overture on cannabinoids including their reported antimicrobial effects, aiming at easing the synthetic production of the necessary amounts of CBG, CBC and CBD for further studies, we have, for the first time, systematically reviewed the synthetic pathways utilized for their synthesis, reporting both reaction schemes and experimental details.


Comparison of optical microscopy and optical coherence tomography as quality assurance methods for evaluating lubricious hydrophilic coatings surrounding catheter shafts.
Cardiac catheters are a vital tool in medicine due to their widespread use in many minimally invasive procedures. To aid in advancing the catheter within the patient's vasculature, many catheters are coated with a lubricious hydrophilic coating (HPC). Although HPCs benefit patients, their delamination during use is a serious safety concern. Adverse health effects associated with HPC delamination include pulmonary and myocardial embolism, embolic stroke, infarction, and death. In order to improve patient outcomes, more consistent manufacturing methods and improved quality assurance techniques are needed to evaluate HPC medical devices. The present work investigates the efficacy of two novel methods to image and evaluate HPCs post-manufacturing, relative to industry-standard scanning electron microscopy (SEM)-based methods. We have shown that novel evaluation approaches based on optical microscopy (OM) and optical coherence tomography (OCT) are capable of imaging HPC layers and quantifying HPC thickness, saving hours of time relative to SEM sample preparation and imaging. Additionally, the nondestructive nature of OCT avoids damage and alteration to the HPC prior to imaging, leading to more reliable HPC thickness measurements. Overall, the work demonstrated the feasibility and advantages of using OM and OCT to image and measure HPC thickness relative to industry-standard SEM methods.


An experimental analysis of the origins of somatostatin-like immunoreactivity in the dentate gyrus of the rat.
In previous studies, fibers demonstrating somatostatin-like immunoreactivity were observed in the outer half of the molecular layer of the dentate gyrus in the rat and monkey. They occupy the same region as those of the perforant pathway that originates in the entorhinal cortex. Numerous somatostatin immunoreactive neuronal cell bodies were also observed in the hilar region, though stained axonal profiles could not be followed from these cells into the molecular layer. In the present study, several experimental procedures were employed to determine the origin of the somatostatin-positive fibers in the molecular layer. Transection of the perforant path fibers resulted in such characteristic changes as shrinkage of the molecular layer and sprouting of AChE-positive fibers. There was no apparent decrease, however, in the density of somatostatin-positive fibers. In fact, since the stained fibers occupied a narrower band in the shrunken molecular layer, their density appeared greater. Injections of kainic acid into the hilar region produced a lesion of hilar neurons, including those positive for somatostatin. In the region of cell loss, there was a marked reduction of somatostatin-immunoreactive fibers in the ipsilateral molecular layer, with no detectable changes in the homotopic contralateral molecular layer. The distribution of AChE fibers, which presumably have an extrinsic origin, was not altered by the treatment. In a final series of experiments, the retrograde tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the hilar region and sections were prepared for the simultaneous demonstration of the tracer and of somatostatin-like immunoreactivity. Somatostatin-positive neurons demonstrating WGA-HRP reaction product were observed primarily in the ipsilateral hilar region, but a few double-labeled cells were also seen in the same area of the contralateral side. These studies indicate that a population of intrinsic neurons located in the polymorphic layer of the dentate gyrus projects to the outer half of the ipsilateral molecular layer. A similar, but very much smaller, projection also extends to the contralateral dentate gyrus. Taken together, these projections appear to account for much of the somatostatin-like immunoreactivity in the molecular layer of the dentate gyrus.


Long segment detection of HTLV-1 genome based on the fluorescence quenching technique.
Detecting fluorescence changes due to energy transfer between a quencher and fluorophore is a common method used for the fluorescence-based biosensors. In the present report, a new biosensor for long segment detection of the human T cell-lymphotropic virus 1 genome was constructed based on the fluorescence quenching of graphene oxide by gold nanoparticles. The fluorescence signal of unmodified graphene oxide was measured before and after hybridization of target and probes functionalized with gold nanoparticles. The limit of detection of the biosensor was determined to be around 10 pg/mL. The specific design for long segment of target assures the selectivity of biosensor. Our results proposed that further development may be useful to detect other viruses.


Analysis of rotaviral gastroenteritis in Tbilisi.
Electrophoretypes of 107 rotaviral isolates collected in Tbilisi for 18 months revealed seven patterns from which 4 were "long" and 3 "short". The "long" electrophoretypes represented 74.8% of total number of the isolates analysed. One of the "long" electrophoretypes dominated for the whole investigation period. Differences in the seasonal distribution of the isolates with various electrophoretypes were demonstrated and appearance of rotaviral isolates was registered with a "short" electrophoretype which had never been detected before.


Paranasal sinus disease and sputum eosinophilia in prednisone-dependent asthma.
to investigate the extent and characteristics of paranasal sinus abnormalities (anatomic and mucosal) on computed tomographic (CT) sinus scans and to determine whether there is a relationship between these findings and eosinophilic airway inflammation in patients with prednisone-dependent asthma. we conducted an observational survey of 15 prednisone-dependent asthmatic patients with respect to measures of airway inflammation and CT sinus scans. The pathologic changes on the CT scans were scored using the Lund-Mackay and JAMA staging systems, and several paranasal bony anatomic variations were recorded. Correlations between CT sinus measures and sputum eosinophil count as well as prednisone dose requirement to control sputum eosinophilia were examined. the JAMA and Lund-Mackay staging systems showed that greater sphenoidal mucosal disease was associated with increased prednisone dose requirements (OR 1.7, p = .05; OR 1.6, p = .021). Generally, both staging systems showed that specific sinus site involvement correlated with higher levels of sputum eosinophils. Mucosal thickening in the sphenoid sinus correlated most closely with sputum eosinophilia, followed by the maxillary and ethmoid sinuses and osteomeatal complex. Finally, there appeared to be a limited role for sinus anatomy as a predictive factor for the dose of prednisone required to control sputum eosinophilia. sinomucosal thickening, but not sinus anatomy, appears to be an important predictor of prednisone requirement and severity of eosinophilic bronchitis in severe asthma.


When does behavior follow intent? Relationships between trait level dietary restraint and daily eating behaviors.
The relationship between self-report trait level restriction and daily engagement in restriction behaviors is not well understood, and as a result the usefulness of such trait level measures is unclear. The present study aimed both to examine the validity of self-reported trait dietary restraint behaviors, and to examine the respective relationships among self-reported trait dietary restraint intentions and behaviors and both restrained and disinhibited eating at the daily level. A sample of 109 women (Mage = 24.72, SD = 4.15) completed a self-report trait level measure of dietary restraint before providing EMA data on their daily engagement in dietary restraint and disinhibited eating behaviors, as well as mood, over a period of 7 days. Multilevel hurdle models were used to test the relationship between trait levels of dietary restraint, and daily level reports of restraint and disinhibited eating behaviors. Trait restraint behavior was a consistent predictor of daily presence and frequency of restraint behaviors. In contrast, trait restraint intentions was not a predictor of daily restraint behaviors, however it did predict daily frequency of overeating. In addition, daily negative affect emerged as a predictor of comfort eating, but was not predictive of restraint behaviors. Findings confirm the usefulness of assessments of self-reported trait dietary restraint behaviors as a method of capturing dieting behaviors. In contrast, trait level dietary restraint intentions was a poor predictor of eating outcomes and more research on the way that restraint intentions affect eating behaviors is warranted.


[Evolution of patient safety culture in a medium-stay hospital: monitoring indicators].
Patient safety is a challenge for health care. The aim of this study is to identify the dimensions with the greatest impact on patient safety culture of healthcare staff in a medium-stay hospital; to asses its evolution over time and to check the sensitivity of monitoring indicators. Two cross-sectional studies (2013 to 2015) were conducted. The safety culture assessment tool used was the Spanish version of the "Hospital Survey on Patient Safety" (AHRQ). Outcome variable is high perception of safety (score = 75th percentile). socio-demographic characteristics and perceptions of the evaluated dimensions. The association between variables was quantified by Odds Ratio. The mean of perceived safety was similar in both studies: (7.81 and 7.48, N2013= 66; N2015=92). The best aspects evaluated were: "Supervisor actions" and "Teamwork within unit"; the worst evaluated were: "Staffing", "Management support" and "Teamwork across units". Socio-demographic variables had little significance, while a positive perception in some of the considered dimensions was associated with high perceived safety. The most strongly associated aspects were: "Supervisor actions", "Communication openness" and "Problems in transitions". In the comparative study, indicators based on individual dimensions detected changes better than the assessment of the degree of perceived safety. The regular assessment of Patient Safety Culture makes it possible to know the status and evolution of professionals' perceptions. The choice of appropriate indicators optimises the information obtained through these surveys.


Coercion in psychiatric care: systematic review of correlates and themes.
This study systematically examined the empirical literature on the themes and correlates of coercion as defined by the subjective experience of patients in psychiatric care. The study was a systematic review of the literature on coercion as covered in MEDLINE, PsycINFO, and CINAHL. From qualitative studies, themes that the authors identified were extracted. From quantitative studies, correlational and outcome data were extracted. The final analysis included 27 articles. Themes related to perceived coercion were almost all negative. Correlation and outcome data were insufficiently homogeneous to allow meaningful combined statistical analysis. There was no strong quantitative evidence that the experience of coercion is negatively or positively associated with psychopathology or general well-being. Coercion was commonly felt by patients as dehumanizing. Compulsory actions likely to increase perceived coercion had mixed correlates, and it was therefore difficult to predict who is at greatest risk of experiencing coercion as a "side effect" of intervention. Clinicians should routinely consider that all patients have the potential to experience an intervention as coercive.


The effects of low-, medium-, and high-oil distillers dried grains with solubles on growth performance, nutrient digestibility, and fat quality in finishing pigs.
A total of 1,480 pigs were used in 3 experiments to determine the effects of corn distillers dried grains with solubles (DDGS) varying in oil content on growth performance, carcass traits, and nutrient digestibility in finishing pigs. In Exp. 1, 1,198 pigs (PIC Line 337 × 1050; initially 46.1 kg) were allotted to a corn-soybean meal-based diet or diets with 20 or 40% of a 5.4% oil DDGS (29.5% CP, 8.9% ADF, and 21.8% NDF; as-fed basis) or a 9.6% oil DDGS (29.6% CP, 15.3% ADF, and 28.6% NDF; as-fed basis). From d 0 to 82, ADG was unaffected by DDGS source or level. However, increasing 5.4% oil DDGS decreased (linear, P < 0.01) G:F, whereas G:F did not change among pigs fed 9.6% oil DDGS (DDGS source × level interaction; P < 0.01). Regardless of DDGS source, carcass yield and HCW decreased (linear, P < 0.04) with increasing DDGS. Increasing DDGS increased jowl iodine value (IV), but the magnitude was greater in pigs fed the 9.6% oil DDGS compared with those fed 5.4% oil DDGS (DDGS source × level interaction; P < 0.01). In Exp. 2, 270 pigs (PIC Line 327 × 1050; initially 46.5 kg) were allotted a corn-soybean meal-based diet or diets with 20 or 40% of a 9.4% oil DDGS (29.4% CP, 19.6% ADF, and 34.5% NDF; as-fed basis) or a 12.1% oil DDGS (28.5% CP, 17.6% ADF, and 31.4% NDF; as-fed basis). From d 0 to 75, ADG increased and then decreased for pigs fed 9.4% oil DDGS but was unchanged for pigs fed 12.1% oil DDGS (quadratic interaction, P < 0.02). Increasing DDGS increased (linear, P < 0.01) jowl IV and tended (linear, P < 0.07) to increase G:F. Regardless of source, HCW and carcass yield decreased (linear, P < 0.05) as DDGS increased. In Exp. 3, nutrient digestibility of the 4 DDGS sources was determined using pigs fed either a corn-based basal diet (96.6% corn and 3.4% vitamins and minerals) or a DDGS diet with 50% basal diet and 50% DDGS. On an as-fed basis, corn contained 3,871 and 3,515 kcal/kg GE and DE, respectively. The 5.4, 9.6, 9.4, and 12.1% oil DDGS contained 4,347, 4,648, 4,723, and 4,904 kcal/kg (as-fed basis) GE and 3,417, 3,690, 3,838, and 3,734 kcal/kg DE, respectively (as-fed basis). Stepwise regression indicated that the oil (ether extract) content was the only significant variable to explain differences in energy content. The equations generated to predict DE and NE as a function of oil content on an as-fed basis were DE (kcal/kg) = 62.347 × ether extract (%) + 3,058.13 (n = 5, adjusted R(2) = 0.41) and NE (kcal/kg) = 115.011 × ether extract (%) + 1,501.01 (n = 5, adjusted R(2) = 0.86).


Gene-Level, but Not Chromosome-Wide, Divergence between a Very Young House Fly Proto-Y Chromosome and Its Homologous Proto-X Chromosome.
X and Y chromosomes are usually derived from a pair of homologous autosomes, which then diverge from each other over time. Although Y-specific features have been characterized in sex chromosomes of various ages, the earliest stages of Y chromosome evolution remain elusive. In particular, we do not know whether early stages of Y chromosome evolution consist of changes to individual genes or happen via chromosome-scale divergence from the X. To address this question, we quantified divergence between young proto-X and proto-Y chromosomes in the house fly, Musca domestica. We compared proto-sex chromosome sequence and gene expression between genotypic (XY) and sex-reversed (XX) males. We find evidence for sequence divergence between genes on the proto-X and proto-Y, including five genes with mitochondrial functions. There is also an excess of genes with divergent expression between the proto-X and proto-Y, but the number of genes is small. This suggests that individual proto-Y genes, but not the entire proto-Y chromosome, have diverged from the proto-X. We identified one gene, encoding an axonemal dynein assembly factor (which functions in sperm motility), that has higher expression in XY males than XX males because of a disproportionate contribution of the proto-Y allele to gene expression. The upregulation of the proto-Y allele may be favored in males because of this gene's function in spermatogenesis. The evolutionary divergence between proto-X and proto-Y copies of this gene, as well as the mitochondrial genes, is consistent with selection in males affecting the evolution of individual genes during early Y chromosome evolution.


[Treatment of prostatitis with a new laser probe with optic fiber].
The present treatment of the subacute abatteric prostatitis, prostatodinia, prostatosis (the most common prostatic flogistic diseases) is represented by the transrectal applications of infrared Laser. The concrete opportunity of applying such an energy directly to the prostate in cases of flogistic diseases--a very frequent pathology treated in many different and controversial ways--is a stimulating therapeutical method which we tested and that we presently use in our clinics. The thanks to the realization of an high technology equipment, easy to handle, cheap, safe, perfectly suitable, formed by a new infrared Laser probe, transrectal, atermical, made by a optical fibre, which we present. Micturition, ejaculation, fertility may draw a relevant improvement, provided that the same treatment is performed after a specific medical diagnosis and following a strict protocol.


Clonality, genetic diversity and support for the diversifying selection hypothesis in natural populations of a flower-living yeast.
Vast amounts of effort have been devoted to investigate patterns of genetic diversity and structuring in plants and animals, but similar information is scarce for organisms of other kingdoms. The study of the genetic structure of natural populations of wild yeasts can provide insights into the ecological and genetic correlates of clonality, and into the generality of recent hypotheses postulating that microbial populations lack the potential for genetic divergence and allopatric speciation. Ninety-one isolates of the flower-living yeast Metschnikowia gruessii from southeastern Spain were DNA fingerprinted using amplified fragment length polymorphism (AFLP) markers. Genetic diversity and structuring was investigated with band-based methods and model- and nonmodel-based clustering. Linkage disequilibrium tests were used to assess reproduction mode. Microsite-dependent, diversifying selection was tested by comparing genetic characteristics of isolates from bumble bee vectors and different floral microsites. AFLP polymorphism (91%) and genotypic diversity were very high. Genetic diversity was spatially structured, as shown by amova (Φ(st) = 0.155) and clustering. The null hypothesis of random mating was rejected, clonality seeming the prevailing reproductive mode in the populations studied. Genetic diversity of isolates declined from bumble bee mouthparts to floral microsites, and frequency of five AFLP markers varied significantly across floral microsites, thus supporting the hypothesis of diversifying selection on clonal lineages. Wild populations of clonal fungal microbes can exhibit levels of genetic diversity and spatial structuring that are not singularly different from those shown by sexually reproducing plants or animals. Microsite-dependent, divergent selection can maintain high local and regional genetic diversity in microbial populations despite extensive clonality.


Role of eosinophils in inflammatory bowel and gastrointestinal diseases.
Inflammatory bowel diseases (IBD) are characterized by the invasion of leukocytes into the intestinal mucosa. However, a mixed inflammatory picture is observed that includes neutrophils, lymphocytes, monocytes, and eosinophils. To this day, the role of eosinophils in health and in disease remains unclear. Investigations into their function stem primarily from allergic diseases, asthma, and parasitic infections. This makes it even more difficult to discern a role for the fascinating eosinophil in IBDs because, unlike the lung or the skin, eosinophils reside in normal intestinal mucosa and increase in disease states; consequently, an intricate system must regulate their migration and numbers. These granulocytes are equipped with the machinery to participate in gastrointestinal (GI) inflammation and in the susceptible microenvironment, they may initiate or perpetuate an inflammatory response. A significant body of literature characterizes eosinophils present in the GI microenvironment where they have the potential to interact with other resident cells, thus promoting intestinal remodeling, mucus production, epithelial barrier, cytokine production, angiogenesis, and neuropeptide release. A number of lines of evidence support both potential beneficial and deleterious roles of eosinophils in the gut. Although studies from the gut and other mucosal organs suggest eosinophils affect mucosal GI inflammation, definitive roles for eosinophils in IBDs await discovery.


Long-term outcome of open or endovascular repair of abdominal aortic aneurysm.
For patients with large abdominal aortic aneurysms, randomized trials have shown an initial overall survival benefit for elective endovascular repair over conventional open repair. This survival difference, however, was no longer significant in the second year after the procedure. Information regarding the comparative outcome more than 2 years after surgery is important for clinical decision making. We conducted a long-term, multicenter, randomized, controlled trial comparing open repair with endovascular repair in 351 patients with an abdominal aortic aneurysm of at least 5 cm in diameter who were considered suitable candidates for both techniques. The primary outcomes were rates of death from any cause and reintervention. Survival was calculated with the use of Kaplan-Meier methods on an intention-to-treat basis. We randomly assigned 178 patients to undergo open repair and 173 to undergo endovascular repair. Six years after randomization, the cumulative survival rates were 69.9% for open repair and 68.9% for endovascular repair (difference, 1.0 percentage point; 95% confidence interval [CI], -8.8 to 10.8; P=0.97). The cumulative rates of freedom from secondary interventions were 81.9% for open repair and 70.4% for endovascular repair (difference, 11.5 percentage points; 95% CI, 2.0 to 21.0; P=0.03). Six years after randomization, endovascular and open repair of abdominal aortic aneurysm resulted in similar rates of survival. The rate of secondary interventions was significantly higher for endovascular repair. (ClinicalTrials.gov number, NCT00421330.)


Promising antimicrobial and antibiofilm activities of reduced graphene oxide-metal oxide (RGO-NiO, RGO-AgO, and RGO-ZnO) nanocomposites.
Microbial infections are considered one of the most dangerous infections in humans due to their resistance to most antimicrobial agents. In this study, nanocomposites based on reduced graphene oxide (RGO) and metal oxides (NiO, AgO, and ZnO) were fabricated. The graphite precursor and RGO were characterized by XRD, Raman spectroscopy, SEM, and HRTEM, while SEM, XRD, and EDX mapping analysis validated the synthesized nanocomposites. In addition, ZOI and MIC were employed to test the antimicrobial potential, while their antibiofilm activity and the effect of UV illumination were also investigated. Finally, reaction mechanism determination was performed using SEM analysis. The results revealed that all the synthesized nanocomposites (RGO-NiO, RGO-AgO, and RGO-ZnO) had outstanding antimicrobial activity against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), unicellular fungi (Candida albicans and Cryptococcus neoformans) and multicellular fungi (Aspergillus niger, A. terreus, A. flavus and A. fumigatus). Moreover, the synthesized RGO-NiO nanocomposite exhibited antibiofilm activity (following 10.0 µg mL-1 RGO-NiO), with an inhibition percentage of 94.60% for B. subtilis, 91.74% for P. aeruginosa, and 98.03% for C. neoformans. The maximum percentage inhibition under UV illumination toward P. aeruginosa, B. subtilis and C. neoformans at the end of the experiment using RGO-NiO were 83.21%, 88.54%, and 91.15%, respectively, while the values of RGO-AgO were 64.85%, 68.0%, and 80.15%, respectively, and those of RGO-ZnO were 72.95%, 82.15%, and 79.25%, respectively. The SEM analysis of C. neoformans in the absence of the RGO-NiO nanocomposite showed the development of unicellular fungal cells by regular budding. In contrast, after RGO-NiO treatment, noticeable morphological differences were identified in C. neoformans, including the lysis of the outer surface with deformations of the fungal cells. In conclusion, the prepared nanocomposites are promising antimicrobial and antibiofilm agents and can be used to treat the pathogenic microbes at low concentrations and represent a new strategy for managing infectious diseases caused by pathogenic microorganisms.


Differences in Importance Attached to Drug Effects Between Patients With Type 2 Diabetes From the Netherlands and Turkey: A Preference Study.
Objective: The aim of this study was to compare the importance that patients with type 2 diabetes mellitus from the Netherlands and Turkey attach to certain drug effects of oral anti-diabetic drugs. Methods: Data were collected through a cross-sectional survey containing demographic questions and a discrete choice experiment assessing preferences for oral anti-diabetic drugs. Adults from the Netherlands and Turkey were included if they had type 2 diabetes mellitus and had received a prescription of an oral anti-diabetic drug in the last 4 months. The oral anti-diabetic drugs in the discrete choice experiment were described in terms of six attributes: effects on HbA1c, cardiovascular diseases, weight change, gastrointestinal adverse drug events hypoglycemic events, and bladder cancer. Multinomial logit models with country as an interaction factor were fitted. Results: In total, 381 patients were included, 199 from the Netherlands and 182 from Turkey. Patients' preferences toward drug effects varied between the countries. Turkish patients attached the highest importance to reducing the risk of cardiovascular diseases (relative weight: 0.51, 95% CI 0.45-0.55), followed by reducing hypoglycemic events (relative weight: 0.16, 95% CI 0.11-0.22), and reducing gastrointestinal adverse drug events (relative weight: 0.11, 95% CI 0.07-0.18). Patients from the Netherlands attached the highest importance to gastrointestinal ADEs (relative weight: 0.22, 95% CI 0.14-0.39), followed by reducing hypoglycemic events (relative weight: 0.22, 95% CI 0.16-0.25), and reducing the risk of cardiovascular diseases (relative weight: 0.20, 95% CI 0.13-0.23). Conclusion: Patient preferences may differ across countries. Such differences should be acknowledged in regulatory decisions and clinical practice.


Evaluation and unification of some methods for estimating reflectance spectra from RGB images.
The problem of estimating spectral reflectances from the responses of a digital camera has received considerable attention recently. This problem can be cast as a regularized regression problem or as a statistical inversion problem. We discuss some previously suggested estimation methods based on critically undersampled RGB measurements and describe some relations between them. We concentrate mainly on those models that are using a priori information in the form of high-resolution measurements. We use the "kernel machine" framework in our evaluations and concentrate on the use of multiple illuminations and on the investigation of the performance of global and locally adapted estimation methods. We also introduce a nonlinear transformation of reflectance values to ensure that the estimated reflection spectra fulfill physically motivated boundary conditions. The reported experimental results are derived from measured and simulated camera responses from the Munsell Matte, NCS, and Pantone data sets.


[Pachydermatodactyly associated with plantar pachydermy].
Pachydermodactyly is a superficial fibromatosis located on the proximal portion of fingers'phalanges and interphalangeal joints. Several types of this disease have been described depending on topography, etiology and pathological associations. We report a typical observation of pachydermodactyly associated with a plantar pachydermy. A 19 year-old man was followed for a psychotic disease, associated with mental retardation. On clinical examination, he showed a typical pachydermodactyly, predominantly located on the second, third and fourth fingers of both hands, associated with recent acrocyanosis. A pachydermic aspect was also observed on the external part of the feet sole. Histopathological analysis was identical on digital and plantar lesions with collagen swelling. These lesions extended into the subcutaneous fat only in the feet. This observation is compatible with the most classical form of pachydermodactyly which involves several fingers of both hands, usually in men. Furthermore, the association with a psychiatric disorder and the notion of repeated traumatisms have been frequently reported in the literature. However, acrocyanosis and the important disability observed in our case are unusual. Association with plantar pachydermy has never been reported. The identical histological aspect on finger and feet sole suggests that pachydermatodactyly should be integrated in framework of acral pachydermy.


Coherent backscattering in biological media: measurement and estimation of optical properties.
We measured the coherent backscattering of light from milk solutions and biological tissues by using a He-Ne laser (633 nm) and a CCD array as a detector. A coherent peak from the milk solutions could bemeasured with a single exposure. However, ensemble averaging was required for coherent peaks to be produced from solid media such as tissue samples. By fitting experimental data to an existing model numerically, effective scattering and absorption coefficients were estimated. They were compared with those computed from integrating sphere measurements. Effective scattering coefficients computed by the two different methods were in good agreement for high-scattering media. However, higher absorption was estimated by the coherent peak method.


Fear of heights: cognitive performance and postural control.
Fear of heights, or acrophobia, is one of the most frequent subtypes of specific phobia frequently associated to depression and other anxiety disorders. Previous evidence suggests a correlation between acrophobia and abnormalities in balance control, particularly involving the use of visual information to keep postural stability. This study investigates the hypotheses that (1) abnormalities in balance control are more frequent in individuals with acrophobia even when not exposed to heights, that (2) acrophobic symptoms are associated to abnormalities in visual perception of movement; and that (3) individuals with acrophobia are more sensitive to balance-cognition interactions. Thirty-one individuals with specific phobia of heights and thirty one non-phobic controls were compared using dynamic posturography and a manual tracking task. Acrophobics had poorer performance in both tasks, especially when carried out simultaneously. Previously described interference between posture control and cognitive activity seems to play a major role in these individuals. The presence of physiologic abnormalities is compatible with the hypothesis of a non-associative acquisition of fear of heights, i.e., not associated to previous traumatic events or other learning experiences. Clinically, this preliminary study corroborates the hypothesis that vestibular physical therapy can be particularly useful in treating individuals with fear of heights.


The discovery and early validation of novel plasma biomarkers in mild-to-moderate Alzheimer's disease patients responding to treatment with rosiglitazone.
Recent advances in clinical, pathological and neuroscience studies have identified disease-modifying therapeutic approaches for Alzheimer's disease that are now in clinical trials. This has highlighted the need for reliable and convenient biomarkers for both early disease diagnosis and a rapid signal of drug efficacy. We describe the identification and assessment of a number of candidate biomarkers in patients with Alzheimer's disease and the correlation of those biomarkers with rosiglitazone therapeutic efficacy, as represented by a change in the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Plasma from 41 patients with Alzheimer's disease were analysed by open platform proteomics at baseline and after receiving 8 mg rosiglitazone for 24 weeks. From a comparison of protein expression following treatment with rosiglitazone, 97 proteins were observed to be differentially expressed with a p-value<0.01. From this analysis and comparison to recently published data from our laboratory, a prioritized list of 10 proteins were analysed by immunoassay and/or functional assay in a wider set of samples from the same clinical study, representing a rosiglitazone dose response, in order to verify the changes observed. A number of these proteins appeared to show a correlation with change in ADAS-Cog at the higher treatment doses compared with the placebo. Alpha-2-macroglobulin, complement C1 inhibitor, complement factor H and apolipoprotein E expression showed a correlation with ADAS-Cog score at the higher doses (4 mg and 8 mg). These results are discussed in light of the pathology and other recently published data.


The N2pc component reliably captures attentional bias in social anxiety.
We systematically compared different measures of attentional bias (i.e., reaction times, the N2pc component in the EEG, and explicit stimulus ratings) on their ability to reveal attentional engagement to threatening versus neutral facial stimuli in a Dot Probe Task and tested their relation to trait measures of general and social anxiety. We found that the N2pc component reflects a bias toward angry faces with excellent internal consistency. Similar results were obtained for explicit ratings. Reaction time (RT) differences, however, were not indicative of attentional biases and showed zero odd-even reliability. We further found that both higher (i.e., more negative) N2pc amplitudes and earlier peak latencies were associated with more severe symptoms of social anxiety even when controlling for general trait anxiety. The explicit rating biases were also specifically associated with social anxiety. Conversely, the RT bias was not related to social anxiety levels but to general trait anxiety. This highlights the importance of valid and reliable outcome measures for interventions such as attentional bias modification protocols. Mutual exclusivity of different bias operationalizations is discussed.


Matronized nursing service at Mobile City Hospital in the mid-19th century: a paradigm of altruism and indigent patient care.
Influences upon the development and evolution of nursing groups and the profession have been multifactorial: cultural, economic, political, and social. Although monastic and chivalric orders throughout antiquity provided the beginnings with hierarchical organizations and a sense of voluntarism and vocation, it was not until the mid-19th century that the concept of a nursing service became codified and more hospital-oriented. The inception of a matronized nursing service in the Mobile City Hospital under the tutelage of the Superintendent, Dr. Willis Roberts, antedated the rapid expansion of nursing education and service recommended and instituted by Florence Nightingale. The former served as a paradigm of altruism as "women attendants" became formally associated with a hospital-based "nursing service," initially under the directorship of a lay matron, Mrs. Sarah Dubois, and subsequently under a succession of Sisters of the Roman Catholic Order of the Sisters of Charity (America). Although ostensibly instituted to render care to "female paupers," the matronized nursing service was readily expanded, and subsequently delivered care to the entire, predominantly indigent patient population. The paradigm was worthily perpetuated during the latter half of the 19th century in vitually all hospitals as nursing education and services continued to become more secularized and technologically sophisticated.


Analysis and processing of heart rate variability by time-frequency representation: quantification of the pedaling frequency modulation.
It has been shown that a pedaling frequency component can be extracted from the heart rate variability (HRV) signal using a time-varying filter. It is shown that this filter can be implemented directly in the time-frequency plane with different approaches. The need of resampling the data is also discussed with regard to the artifacts produced when the shanon condition is not fulfilled. In order to interpret the similar amplitude profiles of the pedaling component for untrained and trained subjects, an attempt for the model parameters setting is proposed. Consistent results on a large data set illustrate the feasibility of such processing.


Benthic foraminifera assemblages as elemental pollution bioindicator in marine sediments around fish farm (Vrgada Island, Central Adriatic, Croatia).
Effects on sediments of fish farming activity near Vrgada Island was analysed through living and total foraminiferal assemblages and concentration of major, minor and trace elements from three sediment cores. Elemental concentrations of sediments are in accordance with carbonate characteristics of the surrounding area and show mostly natural element variations between sampling locations and throughout the cores, with no significant increases due to fish farming activity. Only phosphorus concentration shows elevate values below the fish cage, assigned to fish pellets. Foraminiferal communities are dominated by epifaunal and stress tolerant species, while diversity indices point to normal marine conditions. The type of substrate and phosphorus content in sediments principally influence foraminiferal community composition, while other elemental concentrations have no perceptible effect on the assemblages. Some foraminiferal species Ammoniatepida, Ammoniabeccarii, Elphidiumcrispum, Elphidiummacellum and genus Haynesina are confirmed to be tolerant to elevated nutrient (phosphorus) content, while Ammonia parkinsoniana shows sensitivity to pollution. Postmortem processes cause decrease of foraminiferal density and species richness with core depth. All results point to negligible influence of fish farming and relatively stable environmental conditions at all sampling locations.


Effects of Mannheimia haemolytica leukotoxin on apoptosis and oncosis of bovine neutrophils.
To investigate the concentration-dependent effects of Mannheimia haemolytica (formerly Pasteurella haemolytica) leukotoxin (LKT) on apoptosis and oncosis in bovine neutrophils and to examine the role of calcium ions (Ca2+) in LKT-induced apoptosis. Neutrophils isolated from blood samples obtained from healthy calves. Neutrophil suspensions were exposed to lytic or sublytic dilutions of LKT and then examined by use of transmission electron microscopy (TEM) or gel electrophoresis. Contribution of extracellular Ca2+ to LKT-induced apoptosis was investigated by incubating neutrophils with LKT or control solutions in buffer containing 1 mM CaCl2 or in Ca2+-free buffer containing 1 mM ethylene glycol-bis (b-aminoethyl ether)-N,N-tetraacetic acid (EGTA) prior to diphenyl amine analysis. Examination by TEM revealed that bovine neutrophils exposed to lytic dilutions of LKT had changes consistent with oncosis, whereas neutrophils exposed to sublytic dilutions of LKT and staurosporin, an inducer of apoptosis, had changes consistent with apoptosis. Effects of sublytic dilutions of LKT on apoptosis were confirmed by gel electrophoresis. Replacement of extracellular Ca2+ with EGTA, a Ca2+ chelator, reduced apoptosis attributable to the calcium ionophore A23187, but it did not have significant effects on apoptosis induced by LKT or staurosporin. The ability of LKT to cause apoptosis instead of oncosis is concentration-dependent, suggesting that both processes of cell death contribute to an ineffective host-defense response, depending on the LKT concentration in pneumonic lesions. Furthermore, although Ca2+ promotes A23187-induced apoptosis, it is apparently not an essential second messenger for LKT-induced apoptosis.


Nongenetic origins of cell-to-cell variability in B lymphocyte proliferation.
Rapid antibody production in response to invading pathogens requires the dramatic expansion of pathogen-derived antigen-specific B lymphocyte populations. Whether B cell population dynamics are based on stochastic competition between competing cell fates, as in the development of competence by the bacterium Bacillus subtilis, or on deterministic cell fate decisions that execute a predictable program, as during the development of the worm Caenorhabditis elegans, remains unclear. Here, we developed long-term live-cell microscopy of B cell population expansion and multiscale mechanistic computational modeling to characterize the role of molecular noise in determining phenotype heterogeneity. We show that the cell lineage trees underlying B cell population dynamics are mediated by a largely predictable decision-making process where the heterogeneity of cell proliferation and death decisions at any given timepoint largely derives from nongenetic heterogeneity in the founder cells. This means that contrary to previous models, only a minority of genetically identical founder cells contribute the majority to the population response. We computationally predict and experimentally confirm nongenetic molecular determinants that are predictive of founder cells' proliferative capacity. While founder cell heterogeneity may arise from different exposure histories, we show that it may also be due to the gradual accumulation of small amounts of intrinsic noise during the lineage differentiation process of hematopoietic stem cells to mature B cells. Our finding of the largely deterministic nature of B lymphocyte responses may provide opportunities for diagnostic and therapeutic development.


Neural entrainment to the rhythmic structure of music.
The neural resonance theory of musical meter explains musical beat tracking as the result of entrainment of neural oscillations to the beat frequency and its higher harmonics. This theory has gained empirical support from experiments using simple, abstract stimuli. However, to date there has been no empirical evidence for a role of neural entrainment in the perception of the beat of ecologically valid music. Here we presented participants with a single pop song with a superimposed bassoon sound. This stimulus was either lined up with the beat of the music or shifted away from the beat by 25% of the average interbeat interval. Both conditions elicited a neural response at the beat frequency. However, although the on-the-beat condition elicited a clear response at the first harmonic of the beat, this frequency was absent in the neural response to the off-the-beat condition. These results support a role for neural entrainment in tracking the metrical structure of real music and show that neural meter tracking can be disrupted by the presentation of contradictory rhythmic cues.


Maintaining rigor in research: flaws in a recent study and a reanalysis of the relationship between state abortion laws and maternal mortality in Mexico.
A recent publication [Koch E, Chireau M, Pliego F, Stanford J, Haddad S, Calhoun B, Aracena P, Bravo M, Gatica S, Thorp J. Abortion legislation, maternal healthcare, fertility, female literacy, sanitation, violence against women and maternal deaths: a natural experiment in 32 Mexican states. BMJ Open 2015;5(2):e006013] claimed that Mexican states with more restrictive abortion laws had lower levels of maternal mortality. Our objectives are to replicate the analysis, reanalyze the data and offer a critique of the key flaws of the Koch study. We used corrected maternal mortality data (2006-2013), live births, and state-level indicators of poverty. We replicate the published analysis. We then reclassified state-level exposure to abortion on demand based on actual availability of abortion (Mexico City versus the other 31 states) and test the association of abortion access and the maternal mortality ratio (MMR) using descriptives over time, pooled chi-square tests and regression models. We included 256 state-year observations. We did not find significant differences in MMR between Mexico City (MMR=49.1) and the 31 states (MMR=44.6; p=.44). Using Koch's classification of states, we replicated published differences of higher MMR where abortion is more available. We found a significant, negative association between MMR and availability of abortion in the same multivariable models as Koch, but using our state classification (beta=-22.49, 95% CI=-38.9; -5.99). State-level poverty remains highly correlated with MMR. Koch makes errors in methodology and interpretation, making false causal claims about abortion law and MMR. MMR is falling most rapidly in Mexico City, but our main study limitation is an inability to draw causal inference about abortion law or access and maternal mortality. We need rigorous evidence about the health impacts of increasing access to safe abortion worldwide. Transparency and integrity in research is crucial, as well as perhaps even more in politically contested topics such as abortion. Rigorous evidence about the health impacts of increasing access to safe abortion worldwide is needed.


Physiology of folic acid in health and disease.
Folates are important cofactors in the transfer and utilization of one-carbon-groups and play a key role in the remethylation of methionine thus providing essential methyl groups for numerous biological reactions. Furthermore, folates donate one-carbon units in the process of DNA-biosynthesis with implications for the regulation of gene expression, transcription, chromatine structure, genomic repair and genomic stability. As the role of folate deficiency in atherosclerotic cardiovascular disease, neurological and neuropsychiatric disorders, in congenital defects and carcinogenesis has become better understood, folate has been recognized as having great potential to prevent these many disorders through folate supplementation for the general population. Folate acts directly to produce antioxidant effects, interactions with enzyme endothelial NO synthase (eNOS) and effects on cofactor bioavailability of NO. Folate acts indirectly to lower homocysteine levels and insure optimal functioning of the methylation cycle. Folate metabolism provides an interesting example of gene-environmental interaction. A great part of the population, especially subgroups with higher demand, appears to have suboptimal folate intake, as determined through more sensitive parameters now widely determined. The available data strongly suggest that criteria for "folate deficiency" may have to be redefined.


[Current concepts in the genetics of hereditary and sporadic colorectal cancer and the role of genetics in patient management. Hereditary colorectal cancers].
Colorectal cancer (CRC) is the second leading cause of mortality of malignant diseases in Hungary and according to the incidence and prevalence of CRC Hungary is second among European countries. Hence, it is of outstanding interest to know the current concepts on pathogenesis and genetical background of CRC, as well as incorporate this knowledge in the everyday practice. In the first part of the review authors address the genetic background of hereditary colorectal cancer syndromes. In fact, a positive family history may be found in 20-30% and genetically defined trait (e.g. familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and Peutz-Jeghers-syndrome (PJS)) is responsible for 3-5% of all colon cancers. Germline mutations of tumor suppressor gene, APC (5q21) are found in 70-90% of the cases. Until now more than 300 mutations were identified. Though a typical mutation was not found, the location of the mutation is associated to the clinical phenotype and prognosis. Of note, beside APC mutations, biallelic mutations of the MYH gene may be found in a subset of individuals with FAP. The diagnosis of HNPCC is based on family history and the presence of Amsterdam I-Il or Bethesda criteria. The genetic background and clinical phenotype of the syndrome is heterogeneous. Mutations of different mismatch repair genes (mainly hMLH1 or hMSH2) may be identified in most cases. Genetic testing is advised in first degree relatives of FAP patients, if genetic testing is not available colonoscopic surveillance should be done starting at the age of 10-12 years. Due to the high number of mutation genetic testing is difficult in HNPCC families and colonoscopic screening should be advised to affected families.


Functional improvement of mutant keratin cells on addition of desmin: an alternative approach to gene therapy for dominant diseases.
A major challenge to the concept of gene therapy for dominant disorders is the silencing or repairing of the mutant allele. Supplementation therapy is an alternative approach that aims to bypass the defective gene by inducing the expression of another gene, with similar function but not susceptible to the disrupting effect of the mutant one. Epidermolysis bullosa simplex (EBS) is a genetic skin fragility disorder caused by mutations in the genes for keratins K5 or K14, the intermediate filaments present in the basal cells of the epidermis. Keratin diseases are nearly all dominant in their inheritance. In cultured keratinocytes, mutant keratin renders cells more sensitive to a variety of stress stimuli such as osmotic shock, heat shock or scratch wounding. Using a 'severe' disease cell culture model system, we demonstrate reversion towards wild-type responses to stress after transfection with human desmin, an intermediate filament protein normally expressed in muscle cells. Such a supplementation therapy approach could be widely applicable to patients with related individual mutations and would avoid some of the financial obstacles to gene therapy for rare diseases.


Laminin 5 promotes activation and apoptosis of the T cells expressing alpha3beta1 integrin.
By introducing an alpha3 gene-containing plasmid into a human T cell line Jurkat, we prepared the T cells, which express a high level of the alpha3beta1 integrin, to assess the role of laminin 5 in the skin immune system. The alpha3beta1-expressing T cells adhered to laminin 5 and exhibited spreading. These adhered T cells showed a significant tyrosine phosphorylation of intracellular proteins including p59(fyn) upon T-cell receptor (TCR) stimulation. Six hours after cross-linking TCR, these cells on laminin 5 secreted a three times higher level of IL-2 than those on a BSA-coated plate. Twenty hours after the stimulation, 48% of the alpha3beta1-expressing T cells on laminin 5 caused apoptosis. The protein level of cyclin D3 and E decreased, while that of p53 increased in these T cells. These data suggest that laminin 5 may play at least two regulatory roles for T cell functions: augmentation of IL-2 production by antigen-stimulated T cells and induction of apoptosis in these T cells.


Cigarette smoke condensate enhances respiratory syncytial virus-induced chemokine release by modulating NF-kappa B and interferon regulatory factor activation.
Exposure to cigarette smoke is a risk factor contributing to the severity of respiratory tract infections associated with respiratory syncytial virus (RSV). Stimulation of airway epithelial cells by either RSV or cigarette smoke condensate (CSC) has been shown to induce secretion of the proinflammatory chemokines. However, the effect of coexposure of airway epithelial cells to CSC and RSV on inducible chemokine production has not been previously investigated. The results of this study indicate that CSC costimulation significantly increased RSV-induced interleukin-8 (IL-8) and monocyte chemoattactant protein-1 gene and protein expression when compared with each stimulus alone. Promoter deletion studies identified the interferon stimulatory response element (ISRE) of the IL-8 promoter as a critical region responsible for the synergistic increase of IL-8 gene transcription during mixed exposure. CSC costimulation enhanced RSV-induced activation of interferon regulatory factor (IRF)-1 and IRF-7, which bind to the ISRE site. CSC also furthered RSV-induced activation of the transcription factor nuclear factor kappa B (NF-kappaB), as shown by increased NF-kappaB DNA binding to its specific site of the IL-8 promoter and increased NF-kappaB-driven gene transcription. Therefore, our data demonstrate that a combined exposure to CSC and RSV synergistically increases chemokine expression in airway epithelial cells, suggesting that CSC contributes to an exuberant immune response to RSV by stimulating overlapping signal transduction pathways.


Cleaving mercury-alkyl bonds: a functional model for mercury detoxification by MerB.
The extreme toxicity of organomercury compounds that are found in the environment has focused attention on the mechanisms of action of bacterial remediating enzymes. We describe facile room-temperature protolytic cleavage by a thiol of the Hg-C bond in mercury-alkyl compounds that emulate the structure and function of the organomercurial lyase MerB. Specifically, the tris(2-mercapto-1-t-butylimidazolyl)hydroborato ligand [Tm(Bu(t))], which features three sulfur donors, has been used to synthesize [Tm(Bu(t))]HgR alkyl compounds (R = methyl or ethyl) that react with phenylthiol (PhSH) to yield [Tm(Bu(t))]HgSPh and RH. Although [Tm(Bu(t))]HgR compounds exist as linear two-coordinate complexes in the solid state, 1H nuclear magnetic resonance spectroscopy indicates that the complexes exist in rapid equilibrium with their higher-coordinate [kappa2-Tm(Bu(t))]HgR and [kappa3-Tm(Bu(t))]HgR isomers in solution. Facile access to a higher-coordinate species is proposed to account for the exceptional reactivity of [Tm(Bu(t))]HgR relative to that of other two-coordinate mercury-alkyl compounds.


Diagnosis and differentiation of congenital diaphragmatic hernia from other noncardiac thoracic fetal masses.
This retrospective study was designed to evaluate individual sonographic parameters that might help differentiate congenital diaphragmatic hernia (CDH) from other noncardiac thoracic masses such as cystic adenomatoid malformation of the lung (CAML) and congenital lobar emphysema (CLE) prenatally. Twenty-four cases of CDH, CAML, and CLE detected during prenatal ultrasound and documented postnatally (with surgical, autopsy, or radiological proof) were identified through extensive chart and record review. The hard copy gray-scale images were retrospectively reviewed for imaging characteristics that may differentiate the three entities. Additionally, the prospective diagnosis during prenatal ultrasound was also compared with the postnatal diagnosis. The most reliable indicators in our retrospective review included confident visualization of a diaphragmatic defect (92.3/100.0 PPV/NPV, p< or =0.002) and/or localization of the stomach within the chest as well as the presence of severe cardiac deviation (both 92.3/62.5 PPV/NPV, p< or =0.01). Other sonographic indicators (including the presence of cystic areas, side and size of the lesion and the presence of polyhydramnios) offered lower levels of sensitivity and specificity. Prospective diagnosis during real-time assessment was also integral, offering >80% sensitivity and specificity (p< or =0.001). Accurate prenatal diagnosis of CDH is difficult despite the relative frequency of this lesion. The classic triad of a thoracic mass accompanying a displaced heart, absence of a normally positioned fluid-filled stomach and polyhydramnios, although seen with CDH, may not adequately differentiate this entity from other noncardiac fetal thoracic masses. Realtime assessment remains integral to the appropriate diagnosis.


[Physical education, science, and health: notes on the holdings of the Center for Sports Memory (UFRGS)].
The article offers a brief inventory of the holdings of the Center for Sports Memory and its main collections. It underscores their relevance to research on the historiography of body and sporting practices and their relation to health, education, and leisure. The structuring of physical education in Brazil dates to the early twentieth century, a time when scientific knowledge was important, especially in terms of the ties between this field and eugenics and hygienism. Physical activities were identified as part of a national project that could be felt at various levels and that made it evident that physical education would only display consistency if anchored in scientific knowledge, primarily biomedical.


Dietary fluoride supplements for Indiana's children: the role of the physician.
Fluoride supplements for Indiana children are necessary for caries reduction where communal and well water tests show deficient levels of fluoride. The role of the physician in providing optimum preventive dental care to young patients is discussed. Also, the proper dental protocol for fluoride supplements is provided.


The fate and function of oligodendrocyte progenitor cells after traumatic spinal cord injury.
Oligodendrocyte progenitor cells (OPCs) are the most proliferative and dispersed population of progenitor cells in the adult central nervous system, which allows these cells to rapidly respond to damage. Oligodendrocytes and myelin are lost after traumatic spinal cord injury (SCI), compromising efficient conduction and, potentially, the long-term health of axons. In response, OPCs proliferate and then differentiate into new oligodendrocytes and Schwann cells to remyelinate axons. This culminates in highly efficient remyelination following experimental SCI in which nearly all intact demyelinated axons are remyelinated in rodent models. However, myelin regeneration comprises only one role of OPCs following SCI. OPCs contribute to scar formation after SCI and restrict the regeneration of injured axons. Moreover, OPCs alter their gene expression following demyelination, express cytokines and perpetuate the immune response. Here, we review the functional contribution of myelin regeneration and other recently uncovered roles of OPCs and their progeny to repair following SCI.


A low-cost, accurate method of producing large quantities of digitally filtered images.
We demonstrate how to produce complex image transformations of bitmap files for vision experiments using the Cogimatic Vision Starter Kit (VSK) library of mathematical routines along with Visual Basic, C++, or the Delphi Pascal compiler. Implementing this system on an IBM-compatible PC running Windows 95, 98, or NT4 enables researchers to quickly and economically manipulate images for vision research. The VSK includes a simple stand-alone image-processing application. In addition, VSK has the ability to automate image transformations and to fully integrate image processing into new experimental software on the PC platform.


Health workforce needs: projections complicated by practice and technology changes.
As population growth and the aging of the overall population increase demand for health care, policymakers and analysts posit whether sufficient health care providers will be able to meet that demand. Some argue there are too few providers already; others say our current supply-demand problems lie with efficiency. But suppose both are correct? Perhaps the real challenge is to understand how physician practices are changing in response to market forces such as payment changes, provider distributions, and technology innovations. This issue brief reviews what is known about evolving practice organizations, professional mixes, information technology support, and the implications of these and other factors for public workforce policies.


Microarray-based method for screening of immunogenic proteins from bacteria.
Detection of immunogenic proteins remains an important task for life sciences as it nourishes the understanding of pathogenicity, illuminates new potential vaccine candidates and broadens the spectrum of biomarkers applicable in diagnostic tools. Traditionally, immunoscreenings of expression libraries via polyclonal sera on nitrocellulose membranes or screenings of whole proteome lysates in 2-D gel electrophoresis are performed. However, these methods feature some rather inconvenient disadvantages. Screening of expression libraries to expose novel antigens from bacteria often lead to an abundance of false positive signals owing to the high cross reactivity of polyclonal antibodies towards the proteins of the expression host. A method is presented that overcomes many disadvantages of the old procedures. Four proteins that have previously been described as immunogenic have successfully been assessed immunogenic abilities with our method. One protein with no known immunogenic behaviour before suggested potential immunogenicity.We incorporated a fusion tag prior to our genes of interest and attached the expressed fusion proteins covalently on microarrays. This enhances the specific binding of the proteins compared to nitrocellulose. Thus, it helps to reduce the number of false positives significantly. It enables us to screen for immunogenic proteins in a shorter time, with more samples and statistical reliability. We validated our method by employing several known genes from Campylobacter jejuni NCTC 11168. The method presented offers a new approach for screening of bacterial expression libraries to illuminate novel proteins with immunogenic features. It could provide a powerful and attractive alternative to existing methods and help to detect and identify vaccine candidates, biomarkers and potential virulence-associated factors with immunogenic behaviour furthering the knowledge of virulence and pathogenicity of studied bacteria.


Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.
The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the existence of pre-existing heterosubtypic immunity may dampen the impact a future influenza pandemic may have.


Acute vascular rejection of the coronary arteries in human heart transplantation: pathology and correlations with immunosuppression and cytomegalovirus infection.
Prior studies of vascular rejection in transplanted human hearts have stressed the importance of accelerated coronary arteriosclerosis (chronic vascular rejection). We, however, have had four patients with sudden onset of acute heart failure within 90 days of transplantation who have died without significant myocardial interstitial rejection or the concentric intimal thickening with dense collagen that is typical of chronic vascular rejection. In contrast, the coronary arteries in our patients had a prominent lymphocytic infiltrate, a loosely organized intimal thickening composed of smooth muscle cells, and extensive endothelial injury. We believe that these changes define acute vascular rejection of the coronary artery. In 14 transplanted hearts obtained consecutively, at autopsy or at a second transplant procedure, graft failure was caused by acute coronary vascular rejection in six cases and by chronic coronary vascular rejection in one case. The remaining seven patients showed no evidence of vascular rejection and died primarily of sepsis. Cytomegalovirus (CMV) disease was present in 6 of 7 patients with vascular rejection, of which 43% were CMV-negative recipients of hearts from CMV-positive donors. The adoption of a triple-drug protocol, in which azathioprine was added to cyclosporine and prednisone, reduced the incidence of acute vascular rejection from 27% to 8%. We conclude that acute coronary vascular rejection may be initially seen as global cardiac ischemia in the absence of significant interstitial myocardial rejection. Further, acute vascular rejection should be pathologically distinguished from chronic vascular rejection, although both are probably stages in the natural history of immune-mediated vascular injury.


Identification and characterization of a novel de novo mutation (L346V) in the thyroid hormone receptor beta gene in a family with generalized thyroid hormone resistance.
We have investigated an Italian family with generalized resistance to thyroid hormone (RTH), consisting of two individuals with elevated serum thyroid hormones (TH) and a non-suppressed TSH, together with unaffected family members, for a mutation in the thyroid hormone receptor beta gene (hTR beta). We have identified a single nucleotide substitution (1321 CTT to GTT) corresponding to a leucine to valine substitution at codon 346 (L346V) in the predicted protein. The index case and her affected child are heterozygous for the receptor defect, with normal sequence in unaffected family members. Furthermore, both parents of the index case were unaffected, suggesting that the mutation had arisen de novo. When expressed in vitro, the L346V mutant receptor showed a marked reduction in its affinity for tri-iodothyronine (T3), impaired ligand-dependent transactivation and potent dominant negative activity. Its functional impairment could not be alleviated, even at supraphysiological concentrations of T3, suggesting that the mutation might interfere with the intrinsic ligand-dependent transactivation function (AF-2) located in the hormone binding domain of hTR beta. Finally, the presence of the L346V mutation in the son of the propositus, who died from complications associated with congenital heart disease, raises the possibility that RTH might have contributed to the pathogenesis or severity of the latter.


Nuclear import of protein kinase C occurs by a mechanism distinct from the mechanism used by proteins with a classical nuclear localization signal.
Protein kinase C does not have any known nuclear localization signal but, nevertheless, is redistributed from the cytoplasm to the nucleus upon various stimuli. In NIH 3T3 fibroblasts stimulation with phorbol ester leads to a translocation of protein kinase C alpha to the plasma membrane and into the cell nucleus. We compared the mechanism of protein kinase C alpha's transport into the nucleus with the transport mechanism of a protein with a classical nuclear localization signal at several steps. To this end, we co-microinjected fluorescently labeled bovine serum albumin to which a nuclear localization signal peptide was coupled, together with substances interfering with conventional nuclear protein import. Thereafter, the distribution of both the nuclear localization signal-bearing reporter protein and protein kinase C alpha was analyzed in the same cells. We can show that, in contrast to the nuclear localization signal-dependent transport, the phorbol ester-induced transport of protein kinase C alpha is not affected by microinjection of antibodies against the nuclear import factor p97/importin/karyopherin beta or microinjection of non-hydrolyzable GTP-analogs. This suggests that nuclear import of protein kinase C alpha is independent of p97/importin/karyopherin beta and independent of GTP. At the nuclear pore there are differences between the mechanisms too, since nuclear transport of protein kinase C alpha cannot be inhibited by wheat germ agglutinin or an antibody against nuclear pore complex proteins. Together these findings demonstrate that the nuclear import of protein kinase C alpha occurs by a mechanism distinct from the one used by classical nuclear localization signal-bearing proteins at several stages.


Two methods for determining plasma IL-6 in humans at rest and following exercise.
We compared two methods to determine IL-6 at rest and following exercise. On two occasions, plasma IL-6 was determined in 10 men and 13 women before and immediately following 90 min of cycling at 65% V(O)(2max) using a cytometric bead array (CBA) and an ELISA. The CBA detected IL-6 in 63% of pre-exercise samples and 84% of post-exercise samples; the ELISA detected IL-6 in all samples. In samples with detectable IL-6, resting values were comparable between the CBA and ELISA (2.3 +/- 1.0 and 2.4 +/- 1.2 pg/mL, respectively; p = 0.99); the IL-6 response to exercise was underestimated (p = 0.0003) by the CBA by ~45%, compared with the ELISA. CBA- and ELISA-determined IL-6 values were moderately correlated (r = 0.66, p < 0.0001), but exhibited poor agreement (mean bias +/- 1SD = -1.4 +/- 2.1 pg/mL). The CBA provided concordant IL-6 concentrations at rest, when detected, but underestimated exercise-induced increases in IL-6 versus the ELISA method.


Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation.
The influence of extracellular matrix configuration on the tissue-specific function of cultured hepatocytes was investigated. Adult rat hepatocytes sandwiched between two layers of collagen gel were compared to cells cultured on a single layer of collagen gel for differences in the total RNA content, the level of albumin-specific mRNA, the rate of albumin gene transcription, and the rate of albumin mRNA translation. Adult hepatocytes in the sandwich system maintained the level of albumin mRNA similar to that found in the normal liver for at least six weeks, whereas the level of albumin mRNA declined rapidly in the single gel system. After one week of culture, hepatocytes in the single gel system could be induced to recover the high level of albumin mRNA and albumin production when a second layer of collagen gel was overlaid at that time. Furthermore, sandwiched hepatocytes maintained significantly higher transcriptional activity compared to cells in the single gel system. In addition to transcriptional control, the ultimate rate of albumin production was shown to depend on the rate of translation, which increased with culture time and reached a plateau in one to two weeks. This increase in translational activity over time in culture was observed in both the sandwich and the single gel systems and, thus, appeared to be independent of the configuration of extracellular matrix.


Acupuncture combined with moxibustion for insomnia after stroke: A protocol for systematic review and meta analysis.
Stroke is the main cause of death and disability in the world and insomnia is a common complication of stroke patients. Insomnia will not only seriously affect the prognosis and quality of life of patients with stroke, but even cause the recurrence of stroke. Many studies have proved that acupuncture and moxibustion can effectively improve insomnia symptoms. This study will systematically evaluate the effectiveness and safety of acupuncture combined with moxibustion in treating insomnia after stroke. The following 8 databases will be searched from the inception to October 31, 2020, including China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journal Database (VIP database), China Biomedical Literature Database (CBM), Wanfang Data Chinese Database, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Allied and Alternative Medicine Database (AMED), Excerpt Medica Database (Embase). We will also search for ongoing trials from the World Health Organization International Clinical Trial Registration Platform search portal, Chinese Clinical Trial Register, Clinical trials.gov. In addition, the reference lists of studies meeting the inclusion criteria will also be searched for achieving the comprehensive retrieval to the maximum. All randomized controlled trials of acupuncture and moxibustion in treating insomnia after stroke will be included. Two reviewers will conduct literature screening, data extraction, and quality evaluation respectively. The main outcome is the Pittsburgh sleep quality index (PSQI), and the secondary outcomes include clinical efficacy, quality of life, and safety. RevMan V.5.4.1 will be used for meta-analysis. We will express the results as risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous data and mean difference (MD) or standard mean difference (SMD) 95% CIs for continuous data. This study will provide a comprehensive review of the available evidence of acupuncture combined with moxibustion in treating insomnia after stroke. The conclusion of our study will provide the updated evidence to judge the effectiveness and safety of acupuncture combined with moxibustion for the treatment of insomnia after stroke. PROSPERO CRD42020216720.


Phonemic fluency quantity and quality: Comparing patients with PSP, Parkinson's disease and focal frontal and subcortical lesions.
Progressive supranuclear palsy (PSP) can be difficult to distinguish from Parkinson's disease (PD), but has a much graver prognosis. PSP is characterised severely reduced output on measures of phonemic fluency, suggesting that it may be a specific marker of PSP. However, reduced phonemic fluency has also been noted in PD, and very few studies have actually compared phonemic fluency in PSP and PD. Although anecdotal reports suggest that phonemic fluency output in PSP may have specific characteristics, with more low-frequency words and perseverative errors, no study to date has formally explored this. Further investigation into phonemic fluency output and its cognitive and neuroanatomical correlates is now critical for improving our understanding of the verbal fluency in PSP. In this study, we compared phonemic fluency characteristics (including quantity, frequency and error rates) in patients with PSP, PD and focal frontal or subcortical lesions, and age- and education-matched healthy controls. We then compared these characteristics with performance on extensive neuropsychological testing. We found that PSP patients generated significantly fewer words than patients with PD and patients with right frontal focal lesions, and healthy controls. Phonemic fluency was also significantly reduced in patients with left frontal and subcortical focal lesions. However, there were no significant group differences in word frequency or error rates. Phonemic fluency was best predicted by performance on the Vocabulary and Hayling neuropsychological tests. We argue that these findings provide important evidence that reduced phonemic fluency is a hallmark of PSP and argue that the specificity of this impairment betrays an underlying impairment in energization, reflecting dysfunction of left frontal and subcortical networks.


Clinical trials with new oral anticoagulants. Additive value of indirect comparisons also named network meta-analyses.
To compare the efficacy and safety of the new oral anticoagulants (NOAC), ideally head-to-head clinical trials should be performed. Given the expense of such an undertaking, it is highly unlikely that such a comparison would be performed. Therefore, there is a need for an unbiased comparative assessment of the benefits and risks of the NOACs, based on the available trial data. Indirect or mixed treatment comparisons may be an useful tool to overcome these limitations also known as network meta-analysis (NMA). The aim of this paper is to give an overview on published NMAs for dabigatran, rivaroxaban and apixaban, each assessed against warfarin in patients with atrial fibrillation, and against enoxaparin in patients undergoing total knee and total hip replacement surgery, in order to obtain insights into the comparability of the adopted methodological techniques.


Counting niches: Abundance-by-trait patterns reveal niche partitioning in a Neotropical forest.
Tropical forests challenge us to understand biodiversity, as numerous seemingly similar species persist on only a handful of shared resources. Recent ecological theory posits that biodiversity is sustained by a combination of species differences reducing interspecific competition and species similarities increasing time to competitive exclusion. Together, these mechanisms counterintuitively predict that competing species should cluster by traits, in contrast with traditional expectations of trait overdispersion. Here, we show for the first time that trees in a tropical forest exhibit a clustering pattern. In a 50-ha plot on Barro Colorado Island in Panama, species abundances exhibit clusters in two traits connected to light capture strategy, suggesting that competition for light structures community composition. Notably, we find four clusters by maximum height, quantitatively supporting the classical grouping of Neotropical woody plants into shrubs, understory, midstory, and canopy layers.


Role of low-molecular-weight heparins in the management of patients with unstable angina pectoris and non-Q-wave acute myocardial infarction.
The development of effective approaches to the management of the unstable coronary syndromes has resulted from an improved understanding of interactions between the vascular wall, platelets, and coagulation factors, and of their response to pharmacologic and mechanical interventions. Furthermore, the occurrence of frequent adverse events after discharge in patients with unstable coronary artery disease (CAD) treated with these therapies alone would argue that, for many of these patients, such stabilization is not the end of the therapeutic pathway; rather, these therapies are for many a preparation for ultimate revascularization, to preserve myocardium and minimize periprocedural complications. The low-molecular-weight heparins with their unique pharmacology offer a new option in the therapy of patients with unstable CAD. There is now extensive experience in the use of several of the low-molecular-weight heparins, particularly dalteparin and enoxaparin, in the management of patients with unstable angina. Several trials have investigated the questions raised by these observations, taking advantage of the unique pharmacologic properties of the low-molecular-weight heparins for both acute inpatient use and prolonged outpatient administration. Although differences in study design preclude direct comparison between the available low-molecular-weight heparins, in these trials low-molecular-weight heparins have been shown to be effective alternatives to conventional heparin for the management of patients with unstable angina and non-Q-wave infarction. These include several small-scale trials and the larger FRagmin during InStability in Coronary artery disease (FRISC), Fragmin in Unstable Coronary Artery Disease (FRIC), Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE), FRISC II, and Thrombolysis in Myocardial Infarction (TIMI)-11B trials. Thus, the low-molecular-weight heparins appear to be a superior alternative to traditionally administered intravenous unfractionated heparin. They are more predictable in action, do not require frequent activated partial thromboplastin time (aPTT) measurements and dosage adjustments, are easier to administer, and are potentially more efficacious. With their proven efficacy, predictability of action, and convenience of administration and dosing, there are very good reasons for selecting them as first-line therapies for patients presenting with unstable angina and non-Q-wave myocardial infarction.


[Retroperitoneal recurrence of non-seminomatous testicular tumors: computerized tomography findings before retroperitoneal lymph node excision].
In relapsing testicular cancer, additional chemotherapy is followed by abdominal CT. If residual lesions are found, retroperitoneal lymphadenectomy is considered. We studied retrospectively whether morphological criteria can help in selected cases in deciding about lymphadenectomy by distinguishing between vital tumor, scarring and mature teratoma. In 26 patients who had been treated by salvage chemotherapy and retroperitoneal lymphadenectomy for non-seminomatous testicular cancer between 1990 and 1997, abdominal computed tomography and histology were correlated. Histological examination found scarring in 10 patients, vital tumor in 6, mature teratoma in 4, and simultaneous teratoma and vital tumor in 6. A single CT criterion for distinguishing between these histologies was not identified. In two patients with large masses which were partly cystic and partly solid vital tumor and teratoma were verified. Scarrings may be expected in cystic lesions at the level of the renal hilus which are lined by a thin and smooth wall. Size did not matter. Accurate differentiation between vital tumor and necrosis was not possible. Before lymphadenectomy CT, however, localised lesions.


Putting artificial intelligence (AI) on the spot: machine learning evaluation of pulmonary nodules.
Lung cancer remains the leading cause of cancer related death world-wide despite advances in treatment. This largely relates to the fact that many of these patients already have advanced diseases at the time of initial diagnosis. As most lung cancers present as nodules initially, an accurate classification of pulmonary nodules as early lung cancers is critical to reducing lung cancer morbidity and mortality. There have been significant recent advances in artificial intelligence (AI) for lung nodule evaluation. Deep learning (DL) and convolutional neural networks (CNNs) have shown promising results in pulmonary nodule detection and have also excelled in segmentation and classification of pulmonary nodules. This review aims to provide an overview of progress that has been made in AI recently for pulmonary nodule detection and characterization with the ultimate goal of lung cancer prediction and classification while outlining some of the pitfalls and challenges that remain to bring such advancements to routine clinical use.


Cefpodoxime proxetil suspension compared with cefaclor suspension for treatment of acute otitis media in paediatric patients.
A multicentre open-label, randomised trial was performed to compare the efficacy and safety of cefpodoxime proxetil bd and cefaclor tds in the treatment of acute otitis media in children. A total of 167 children aged from 1 month to 11 years were enrolled in five centres: 78 treated with cefpodoxime and 83 treated with cefaclor, were evaluated in the ITT analysis. After tympanocentesis and culture of middle ear fluid, a pathogen was isolated from 85 (53%) of the 161 evaluable patients for the ITT analysis. The organisms isolated were as follows: Streptococcus pneumoniae: (n = 33, 37.5%); Haemophilus influenzae: (n = 22, 25%); Staphylococcus aureus: (n = 15, 17.1%); Streptococcus pyogenes: (n = 8, 9.1%); Moraxella catarrhalis: (n = 2, 2.3%); others (n = 6, 6.8%). Success (defined as a satisfactory clinical outcome, either cure or improvement) was achieved at the end of treatment, in 93.6% of ther patients in the cefpodoxime group and 91.6% of the patients in the cefaclor group (P> 0.05). Clinical recurrence was identified at the follow-up visit (30 days after inclusion), in 6.4% of the cefpodoxime-treated patients and 7.2% of the cefaclor-treated patients (P> 0.05). The drugs were well tolerated by 78/79 (99%) of patients in the cefpodoxime-treated group and 80/85 (94%) in the cefaclor-treated group. The incidence of adverse effects was higher in the cefaclor group than in the cefpodoxime group, but this was not statistically significant (P > 0.05). IN conclusion, cefpodaxime proxetil administered bd is as effective as cefaclor administered tds in the treatment of acute otitis media in children. The less frequent dosing schedule of cefpodoxime (bd) compared with cefaclor (tds) appears to be more convenient for the treatment of the infections in children.


Memory, attention and fluency deficits in COPD may be a specific form of cognitive impairment.
There is increasing evidence demonstrating an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. We present a narrative review of published studies on the subject and a cross-sectional study investigating domain-specific cognitive impairment in people with COPD compared to people with known Alzheimer's dementia, and controls without known COPD or cognitive impairment. The aim of the study was to compare prevalence and pattern of cognitive impairment between the three groups using the Addenbrooke's Cognitive Examination (ACE)-III tool. A total of 89 participants were recruited (44 with COPD, 17 with Alzheimer's and 28 controls). Patients with COPD had significantly lower total ACE-III scores than controls (p<0.001). When comparing the COPD group to the known Alzheimer's dementia group, overall ACE-III scores were significantly lower in the Alzheimer's dementia group than the COPD group (p=0.019). The domain-specific scores for attention (p<0.004), memory (p<0.004) and fluency (p<0.001) were significantly lower in the Alzheimer's dementia group than the COPD group. Our result suggest that the COPD group were significantly more likely to have cognitive impairment than the healthy control group. This was supported by the results of a narrative review of the published literature. Our results show that the pattern of impairment in the COPD group is different to the pattern of impairment shown in the known Alzheimer's dementia group, with significant differences in the cognitive domains affected. These results are in keeping with the findings of other previously published studies included in the narrative review.


Mediator analysis: an overview of recent research on carers supporting people with intellectual disability and challenging behavior.
Families and front-line care staff are often key agents in helping deliver behavioural interventions to people with intellectual disability and challenging behaviour. The present paper reviews factors which may impact on the effectiveness of such interventions. Both PsychLit and MedLine were used to conduct an automated literature search which included the terms 'learning disability', 'mental handicap', 'mental retardation', 'intellectual disability', 'challenging behaviour', 'families' and 'staff. This search was substantially augmented by additional citations obtained from books and journal articles. The impact of attitudes, beliefs and emotional states as setting conditions for interventions was highlighted. A variety of more general setting conditions related to intervention effectiveness were also identified. Implications for both clinical practice and future research were discussed.


Testing cryopreserved European eel sperm for hybridization (A. japonica × A. anguilla).
The objective of this study was to assess impact of cryopreserved European eel sperm and Japanese eel native sperm on early fertilization, hatch, survival, and malformation rates of larvae, as well as develop molecular techniques to distinguish different eel species. Eggs from Japanese eel females (Anguilla japonica) were artificially fertilized with sperm of Japanese eel males and cryopreserved sperm from European eel (A. anguilla, extender was modified Tanaka solution and methanol as cryoprotectant). There were no statistical differences (p > 0.05) among the measured parameters such as fertilization, hatch and survival after 10 days post-hatch rates due to large individual differences. The malformation rate of larvae compared to the hatching rate was higher in cryopreserved groups than in the control indicating that the methodology needs further refinement. Genetic analyses (PCR-RFLP, PCR-HRM) proved a clear result in the detection of paternal contribution in hybridization between the Japanese and the European eel and applied PCR-HRM method is a quick and cost effective tool to identify illegally imported A. anguilla at the glass eel stage, which can be transported from Europe to Asia.


Sensory receptor sensitivity in autistic children: response times to proximal and distal stimulation.
On the basis of behavioral observation, it has been postulated that autistic children prefer proximal (touch, taste) to distal (sight, hearing) sensory modalities. To assess this systematically, autistic children's simple response times were measured with auditory, visual, and tactile stimulation. Children were studied for up to 25 sessions of 40 trials with each modality. Response times were significantly related to mental age. Autistic children's responses were significantly slower than normal children's. However, autistic children and normal children had the same pattern, fastest responding to auditory stimuli and slowest responding to tactile stimulation. Autistic children's preference for proximal stimuli probably reflects a continuation of immature behavior rather than a basic disturbance in sensory receptor sensitivity.


Real-time observation of the vibration of a single adsorbed molecule.
The newly developed femtosecond field emission camera was used to observe the time dependence of field emission through a single copper phthalocyanine molecule adsorbed on a tungsten tip. In many of the individual 212-picosecond-long recordings, the field emission was found to oscillate with a frequency between 5 x 10(10) and 20 x 10(10) hertz. The oscillations, which were not observed from a bare tip, are believed to arise from the vibration of a single molecule with respect to the surface. Numerical simulations confirmed the statistical significance of the data.


The cerebrovascular response to norepinephrine: A scoping systematic review of the animal and human literature.
Intravenous norepinephrine (NE) is utilized commonly in critical care for cardiovascular support. NE's impact on cerebrovasculature is unclear and may carry important implications during states of critical neurological illness. The aim of the study was to perform a scoping review of the literature on the cerebrovascular/cerebral blood flow (CBF) effects of NE. A search of MEDLINE, BIOSIS, EMBASE, Global Health, SCOPUS, and Cochrane Library from inception to December 2019 was performed. All manuscripts pertaining to the administration of NE, in which the impact on CBF/cerebral vasculature was recorded, were included. We identified 62 animal studies and 26 human studies. Overall, there was a trend to a direct vasoconstriction effect of NE on the cerebral vasculature, with conflicting studies having demonstrated both increases and decreases in regional CBF (rCBF) or global CBF. Healthy animals and those undergoing cardiopulmonary resuscitation demonstrated a dose-dependent increase in CBF with NE administration. However, animal models and human patients with acquired brain injury had varied responses in CBF to NE administration. The animal models indicate an increase in cerebral vasoconstriction with NE administration through the alpha receptors in vessels. Global and rCBF during the injection of NE displays a wide variation depending on treatment and model/patient.


Adoption and Use of a Mobile Health Application in Older Adults for Cognitive Stimulation.
Serious games could be used to improve cognitive functions in the elderly. We evaluated the adoption of a new tablet application dedicated to cognitive stimulation in the elderly. The Stim'Art application offers various serious games to work different cognitive functions (memory, attention, concentration, etc.). The usage of fifteen older adults was followed for six months. The type of the game, the number of launches for each game, the time spent on each game, the difficulty level, the success rate and perceived well-being of users have been studied and compared at the end of the first and the sixth months. The participants have played half an hour per day on average. The average time of playing per day in the sixth month was significantly higher than the average time of playing during the first month (p value < 7 * 10(-4)). The same result was found for the average number of game launches per day (p value < 7 * 10(-4)). However, older people seem not to launch more difficult levels in the last month. The success rate at sixth months was significantly higher than the success rate at the end of the first month (p value < 6.4 * 1010(-4)). Generally, seniors have had an improvement in their wellbeing score judged by themselves. Our study showed that the mobile application receives a good admission from users. The results are promising and can pave the way for improving cognitive function in the elderly patients. The use of tablets and the constitution of serious games in close cooperation with health professionals and elderly patients (the end user), are likely to provide satisfactory results to improve healthcare provided for elderly patients suffering from cognitive disorders.


Primary carcinoma of the fallopian tube.
The present report of 16 new cases of fallopian tube carcinoma also includes 2 new cases of adenoacanthoma, an exceedingly rare tumor. The histologic evaluation of tubal carcinoma is discussed. A meticulous search at surgery for occult disease is urged, because penetration of the tubal serosa seems to be the most important determinant of prognosis. Suggestions are made for adjunctive therapy, although the authors believe the time has come for a multicentered attempt to evaluate treatment protocols randomly.


[Control and usefulness of a capillary-wall switch mechanism in blood microcirculation. Recent results of oxygen multistep therapy research].
The measurement of the O2 status of the human organism, the knowledge of factors which influence it and the using and development, respectively, of measures for its permanent improvement are of great importance for the prevention diagnosis, prophylaxis and therapy. The O2-intake in rest of the organism is regarded as absolute characteristic of the oxygen status. In investigations of the dynamics of the status it is in most cases sufficient to use the arteriovenous Hb-O2 saturation difference as relative distinctive mark, the representative determination of which from routine measurements of pO2 in rest is discussed. From such measurements the strong dynamics of the O2 status was found. Apart from the deterioration with growing age the deterioration by stressor influences of different kind, in hyposthenias and the minima in the 24-hour-cycle were established. Improvements were measured after perseverance training and after treatments with processes of the oxygen multistep therapy. After discussion of the three basic steps of this therapy the 36-h-O2-multistep process and the 15-min-O2-multistep rapid process are mentioned as standard variants which are to be used ambulatorily. The rapid process is entered more in detail and the practice of its performance as well as the results of measurements of the typical pO2 in rest before and after these processes are discussed. Surprising is the existence of the increase effected of the arterial pO2 in rest and of the decrease of the venous pO2 in rest for weeks, months up to years.(ABSTRACT TRUNCATED AT 250 WORDS)