Miracle-dz/UniFAR-FTUs huggingface dataset:
Preparation and Characterization of Demeclocycline Liposomal Formulations and Assessment of their Intraocular Pressure-Lowering Effects

ABSTRACT The objective of the present study is to enhance the ocular permeability and to study the ocular disposition of demeclocycline (DEM), liposomal topical formulation for treatment of elevated intraocular pressure using Male New Zealand albino rabbits as an animal model. Methods: Different liposomal formulations of the DEM were prepared and characterized for their drug entrapment, drug-liposome affinity and the in vivo distribution of DEM in various ocular tissues. Liposomal formulations of promising drug distribution within the various ocular tissues have been scaled up for the in vivo intraocular pressure (IOP) measurements by Pneuma-tonometer using different dosing regimens. Results: The amounts of drug entrapped in the charged liposomal formulations were comparable and lower than that entrapped with neutral ones. DEM was found to be more concentrated (69–95%) in the lipid phase of the liposome. The concentrations of DEM in the cornea, aqueous humor, and conjunctiva were 4.76, 2.18, and 23.32 µg/g of tissue, respectively. Test formulations have shown significant reductions in the IOP on using different treatment protocols. Conclusion: Preparation of liposomal formulations of DEM has substantially enhanced its transcorneal transport. Furthermore, the test formulations have shown promising and long-lasting intraocular pressure-lowering effect comparable with that of pilocarpine formulation as a control.
Benchmark of AC and DC active power decoupling circuits for second-order harmonic mitigation in kW-scale single-phase inverters

This paper presents the benchmark study of ac and dc active power decoupling circuits for second-order harmonic mitigation in kW-scale single-phase inverters. First of all, the best solutions of active power decoupling to achieve high efficiency and power density are identified and comprehensively studied, where the commercially available film capacitors, circuit topologies, and control strategies for active power decoupling are all taken into account. Then, an adaptive decoupling voltage control method is proposed to further improve the performance of dc decoupling in terms of efficiency and reliability. The feasibility and superiority of the identified solution for active power decoupling together with the proposed adaptive decoupling voltage control method are finally verified by both the experimental results obtained on a 2 kW single-phase inverter.
The similarity of protein expression in trabecular meshwork and lamina cribrosa: implications for glaucoma.

The purpose of the present investigation was to compare protein expression in various ocular cells and tissues including the human trabecular meshwork (TM) and the lamina cribrosa (LC). To conduct the comparisons, we primarily utilized autofluorography of one-dimensional (1D) and high resolution, two-dimensional (2D) polyacrylamide gels of proteins from radiolabelled tissues and cultured cells. Results from the investigations indicated that patterns of protein expression from TM and LC were the most similar among the ocular cells and tissues compared.Specifically, these autofluorographic ' fingerprints' indicated that proteins in TM and LC cultured cells and tissue were exceptionally similar (a) in band position and intensity (1D gels) and (b) in spot congruence (2D gels) as compared to other ocular cells and tissues. We conclude that the TM and the LC, two ocular tissues intimately linked to the pathogenesis of primary open-angle glaucoma, display remarkable similarity in protein expression. This finding may have implications for the molecular etiology of glaucoma.
MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine

Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2–6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann‐grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1776–1783, 2015.
Time to death and health expenditure: an improved model for the impact of demographic change on health care costs.

BACKGROUND Obtaining well-founded estimates of the effect of demographic change on future health expenditures is a pressing issue in all developed countries. Thus far, expenditure projections have examined the effect of age on health care costs, but fail to account for the influence of remaining life expectancy on costs. OBJECTIVE This paper seeks to create a more accurate projection model that considers the concentration of costs towards the end of life, and to compare this model with the more traditional approach that holds age- and sex-specific per capita expenditures constant. METHODS We used a longitudinal hospital dataset which followed 90 929 patients aged 65 and older from 1970 to death, to create an economic model of hospital costs based on patient age and time remaining to death. We then applied the model to England population projections to predict the effect of demographic changes on hospital expenditures from 2002 to 2026. RESULTS The decline in age-specific mortality rates over time postpones death to later ages, pushing back death-related costs. Accounting for this in expenditure projections gave a predicted annual growth rate of 0.40%-half of the rate predicted with a traditional method. CONCLUSIONS Using richer data and more refined methods than have hitherto been employed, this study strongly confirms that the pressure of population increases and ageing demographic structure on hospital expenditures will be partially countered by the postponement of death-related hospital costs to later in life-a finding consistent with emerging epidemiological evidence, and heartening for policy makers and physicians alike.
Low frequency dynamics of water in reverse micelle sugar solutions

In this paper, we explore the use of reverse micelle systems to investigate the terahertz absorption of varying water trehalose solutions. Fourier Transform Infra-Red (FTIR) spectroscopy and molecular dynamic simulations were used to determine the absorption at each concentration. Both sets of results showed increasingly sterically hindered waters with increasing trehalose concentration.
CHARACTERIZATION AND LARGE-SCALE EXPRESSION OF THE RECOMBINANT CYSTEINE PROTEINASE FROM ADULT CLONORCHIS SINENSIS

Cysteine proteinases play important roles in the pathogenesis of several parasitic infections and have been proposed as targets for the structure-based approach of drug design. As the first step toward applying this strategy to design inhibitors as antiparasitic agents for Clonorchis sinensis, we overexpressed and characterized the 24-kDa cysteine proteinase from adult worms. First, the partial cysteine proteinase gene from C. sinensis was cloned by performing reverse transcription polymerase chain reaction (RT-PCR) with degenerate oligonucleotide primers derived from conserved cysteine proteinase sequences. The 5′ and the 3′ regions of the cysteine proteinase gene were amplified using the PCR protocol for the rapid amplification of cDNA ends–polymerase chain reaction (RACE-PCR). The cDNA has an open reading frame of 981 bp, and the deduced amino acid sequence shares similarity with the cathepsin L–like cysteine proteinases from Schistosoma mansoni, Paragonimus westermani metacercaria, Fasciola hepatica, and human cathepsin L by 52%, 47%, 34%, and 29%, respectively. The cysteine proteinase was then overexpressed in the yeast Pichia pastoris as an active enzyme on a large-scale basis (19.7 mg/L). The active recombinant enzyme was purified from culture media using a Ni2+–NTA–agarose affinity column and gel filtration chromatography. This 24-kDa recombinant protein exhibited a substrate preference for Z-Phe-Arg-AMC (benzyloxycarbonyl-l-phenylalanyl-l-arginine-7-amino-4-methyl-coumarin) compared with Z-Arg-Arg-AMC, and the activity was inhibited by E-64 (l-trans-epoxysuccinylleucylamido(4-quanidino)butane).
Composición corporal y condición nutricional en estudiantes de ballet cubanos

El objetivo del presente trabajo fue evaluar y comparar por sexos la composicion corporal y la condicion nutricional de estudiantes de ballet frente a un grupo control no practicante de la danza. La muestra consistio en 304 alumnos de uno y otro sexo de la Escuela Elemental de Ballet Alejo Carpentier de Cuba, y con edades comprendidas entre 10 y 14 anos. El grupo control, de las mismas edades, incluyo 340 escolares asistentes a escuelas de Primaria y Secundaria de la Ciudad de la Habana. Se midieron la estatura, el peso, los perimetros del brazo, cintura y cadera y los pliegues bicipital, tricipital, subescapular y suprailiaco. Se estimararon los indice de conicidad (IC), cintura/cadera (C/C), masa corporal (IMC) y sumatorio de pliegues. Como variables de composicion corporal el porcentaje de grasa (G%) y peso magro (PM) aplicando ecuaciones de Durnin y Wormerseley (1974) y Siri (1961). Respecto a la serie control, las bailarinas, excepto para la estatura, presentaron promedios significativamente inferiores, tanto para las medidas directas como para los indices y los parametros de composicion corporal. Los bailarines tuvieron niveles de adiposidad total y relativa significativamente inferior, menor IC e IMC y un peso magro proporcionalmente mas elevado. El 38% de las ninas y el 13,5 % de los ninos estudiantes de ballet, presentaron deficit ponderal respecto a las referencias internacionales para el IMC propuestas por Cole et al. (2000; 2007). En el grupo de bailarines se estimaron ecuaciones para el calculo del peso magro y el porcentaje de grasa a partir del peso, el perimetro del brazo y los pliegues subcutaneos
[Study on construction of a plasmid vector carrying human hepatocyte growth factor gene and activity of its expression product].

AIM To construct a plasmid carrying hepatocyte growth factor gene and investigate its effects in vitro. METHODS A complementary DNA (cDNA) clone for human HGF was isolated from human placental cDNA, then subcloned into pUDK vector, which was constructed by ourselves, to form the pUDKH plasmid. The transfection efficiency and the expression level of HGF and VEGF were evaluated by transfecting pUDK or pUDKH into primary rat skeletal muscle cells. The biological effects of HGF-expressing product at different doses on endothelial cells were investigated in vitro, and assessed by MTT. RESULTS The primary rat skeletal muscle cells could be transfected efficiently with pUDKH (0.057%), and secreted HGF(16 -18 ng/4 x 10(5) cells) and VEGF proteins. The expressing product could significantly stimulate proliferation of human umbilical vein endothelial cells, in a dose-dependent manner (P < 0.05). CONCLUSION pUDKH has the potential application in vivo to treat ischemic diseases.
Social-Network Analysis for Pain Medications: Influential physicians may not be high-volume prescribers

According to the Institute of Medicine of the National Academies, more than 100 million Americans suffer from chronic pain related to diabetes, heart disease, and cancer combined. Adoption of pain medications and safe healthcare practices is a major global policy concern. This adoption process is highly influenced by the interpersonal network of physicians prescribing medications to treat pain. However, existing research into physician networks have been hospital-specific, applied to a smaller number of physicians, and dependent upon physicians’ self-reports. In this paper, using big-data and data-mining, we overcome these limitations: By using a case of 30+ hospitals spanning across 2000+ physicians, we create a social network containing physicians’ prescription data and adoption behavior of pain medications. The social network assumes that connected physicians work in the same hospital and belong to the same specialty or specialty group. Then, using the centrality measures, degree and eigenvector centrality, we analyze prescription volumes and proportion of adopters of pain medications. We also analyze gender effects. Results revealed that the most influential physicians were not the high-volume prescribers. Male physicians were more influential compared to female physicians; however, females prescribed more volume compared to males. Our results help us identify critical physicians from certain core specialties and specialty groups who may be approached by patients seeking pain relief.
MatArray: a Matlab toolbox for microarray data

The microarray technology allows the high-throughput quantification of the mRNA level of thousands of genes under dozens of conditions, generating a wealth of data which must be analyzed using some form of computational means. A popular framework for such analysis is Matlab, a powerful computing language for which many functions have been written. However, although complex topics like neural networks or principal component analysis are freely available in Matlab, functions to perform more basic tasks like data normalization or hierarchical clustering in an efficient manner are not. The MatArray toolbox aims at filling this gap by offering efficient implementations of the most needed functions for microarray analysis. The functions in the toolbox are command-line only, since it is geared toward seasoned Matlab users.
Carotid plaque echogenicity and types of silent CT-brain infarcts. Is there an association in patients with asymptomatic carotid stenosis?

BACKGROUND The aim of this study was to identify the differences in echogenicity and the degree of stenosis of asymptomatic carotid plaques associated with different types of ipsilateral silent CT-brain infarcts. METHODS Some 273 asymptomatic carotid plaques (218 patients) causing 50 to 99% stenosis were studied with high-resolution ultrasound. B-mode images were digitised and normalised by assigning certain grey values to blood and adventitia. The grey scale median (GSM) of the plaque in the normalised image was used to quantify echogenicity. Every patient had a CT-brain scan which an independent neuroradiologist read. The presence of 1) non-lacunar and 2) lacunar silent CT-brain infarcts ipsilateral to the carotid plaque was noted. RESULTS The mean GSM of plaques associated with non-lacunar silent CT-brain infarcts was 19.6, of plaques associated with lacunar infarcts was 35.5 and of those associated with no infarcts was 32 (p=0.008, ANOVA). The mean degree of stenosis was 79%, 72% and 73% respectively (p = 0.1, ANOVA). Plaque echogenicity (p = 0.007) and not the degree of stenosis (p = 0.07) predicted the presence of non-lacunar silent CT-brain infarcts (logistic regression). CONCLUSIONS Carotid bifurcation plaques, which are associated with non-lacunar silent CT-brain infarcts, are significantly more hypoechoic than those associated with lacunar or no infarcts. Plaques associated with lacunar silent infarcts and no infarcts have the same echogenicity and degree of stenosis. These findings suggest an embologenic mechanism of non-lacunar silent CT-brain infarcts that may have prognostic implications in patients with asymptomatic carotid stenosis. Prospective studies of asymptomatic carotid stenosis should assess the significance of 1) plaque echogenicity and 2) the presence of different types of silent CT-brain infarcts and atheroembolic stroke.
Sigma-2 Receptors Play a Role in Cellular Metabolism: Stimulation of Glycolytic Hallmarks by CM764 in Human SK-N-SH Neuroblastoma

Sigma-2 receptors are attractive antineoplastic targets due to their ability to induce apoptosis and their upregulation in rapidly proliferating cancer cells compared with healthy tissue. However, this role is inconsistent with overexpression in cancer, which is typically associated with upregulation of prosurvival factors. Here, we report a novel metabolic regulatory function for sigma-2 receptors. CM764 [6-acetyl-3-(4-(4-(2-amino-4-fluorophenyl)piperazin-1-yl)butyl)benzo[d]oxazol-2(3H)-one] binds with Ki values of 86.6 ± 2.8 and 3.5 ± 0.9 nM at the sigma-1 and sigma-2 receptors, respectively. CM764 increased reduction of MTT [3-[4,5 dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide] in human SK-N-SH neuroblastoma compared with untreated cells, an effect not due to proliferation. This effect was attenuated by five different sigma antagonists, including CM572 [3-(4-(4-(4-fluorophenyl)piperazin-1-yl)butyl)-6-isothiocyanatobenzo[d]oxazol-2(3H)-one], which has no significant affinity for sigma-1 receptors. This effect was also observed in MG-63 osteosarcoma and HEK293T cells, indicating that this function is not exclusive to neuroblastoma or to cancer cells. CM764 produced an immediate, robust, and transient increase in cytosolic calcium, consistent with sigma-2 receptor activation. Additionally, we observed an increase in the total NAD+/NADH level and the ATP level in CM764-treated SK-N-SH cells compared with untreated cells. After only 4 hours of treatment, basal levels of reactive oxygen species were reduced by 90% in cells treated with CM764 over untreated cells, and HIF1α and VEGF levels were increased after 3–24 hours of treatment. These data indicate that sigma-2 receptors may play a role in induction of glycolysis, representing a possible prosurvival function for the sigma-2 receptor that is consistent with its upregulation in cancer cells compared with healthy tissue.
Visual processing of straight lines in dyslexic and normal children.

Summary. Separation thresholds for groups of 26 dyslexic and normal children attending the first year of secondary school were obtained with pairs of identically-oriented and spatially-overlapping straight lines presented at orientations varying from zero to 90 degrees. The dyslexics as a group had about 10 to 15 msec longer separation times than normals. In a second experiment single straight line contours were preceded by an homogeneous light mask. Dyslexics required longer stimulus exposures for detection than controls. It is suggested that the present results are compatible with the view of a developmental lag in the visual information processing of dyslexics.
Albuminuria and Endothelial Dysfunction in Patients with Non-Diabetic Chronic Kidney Disease

Background Albuminuria has been associated with cardiovascular events, but whether such an association can be explained by endothelial dysfunction is not fully understood. In this study, we examined the relationship between the urine albumin-to-creatinine ratio (UACR) and biomarkers of endothelial function in patients with chronic kidney disease (CKD). Material/Methods The cross-sectional associations of renal dysfunction and UACR with procoagulant and inflammatory factors were evaluated for 151 consecutive CKD (stage 3–5) patients. Subjects were grouped by UACR (≤300 mg/g or >300 mg/g) and estimated glomerular filtration rate (eGFR) (30≤ eGFR <60, 15≤ eGFR <30, or eGFR <15 ml/min per 1.73 m2). Results A higher UACR level was associated with an increase in von Willebrand factor antigen (vWF: Ag) levels, vWF activity, factor VIII, interleukin-2, and log (interleukin-6), even after adjustment for risk factors. Linear regression analysis indicated that for every 88.5 mg/g increase in UACR, the vWF activity and factor VIII were elevated by 8.3% and 6.3%, respectively. The factorial design ANOVA data showed no statistically significant interaction between UACR and CKD stage with procoagulant and inflammatory factors. Conclusions Our study shows an eGFR-independent association of higher UACR with elevations in markers of endothelial dysfunction and inflammatory factors in CKD patients.
Inefficacy of ultrasound-guided local injections of autologous conditioned plasma for recent epicondylitis: results of a double-blind placebo-controlled randomized clinical trial with one-year follow-up.

OBJECTIVES The aim was to assess the efficacy of two intra-tendinous injections of platelet-rich plasma (PRP) on epicondylitis of recent evolution (≤3 months). METHODS Our study was a double-blind placebo-controlled randomized trial. Two US-guided injections of either PRP (autologous conditioned plasma) or saline solution were performed with an interval of 4 weeks. The exclusion criterion was previous CS infiltration. Patients were monitored by an independent evaluator blinded to treatment at baseline and 1, 3, 6 and 12 months of follow-up. The primary evaluation criterion was the relative improvement from baseline to 6 months in pain score on visual analog scale (0-10). Secondary criteria were the Roles-Maudsley score and the assessment of pain on isometric contraction of extensor carpi radialis brevis and extensor digitorum communis. RESULTS Twenty-five patients were randomly assigned to each group. Three patients in each arm dropped out before 6 months. In both groups, the pain score [mean (s.d.)] decreased significantly between two consecutive visits from 6.8 (0.8) (PRP) and 7 (1) (saline) at baseline to 2.5 (1.6) and 1.6 (1.5) (PRP) and to 2.1 (1.6) and 1.8 (2.1) (saline) at 6 and 12 months, respectively. At 6 months, no statistically significant difference was found between groups for relative improvement in pain score [autologous conditioned plasma: -63.2 (22.4%); saline: -69.7 (25.1%); P = 0.24]. No significant difference was found for the secondary criteria. CONCLUSION Two US-guided PRP injections for epicondylitis of recent evolution were not more efficacious than saline injections, until 6- and 12-months follow-up. TRIAL REGISTRATION ClinicalTrials.gov; https://clinicaltrials.gov/; NCT02378285.