Miracle-dz/UniFAR-FTUs huggingface dataset:
Cocoa flavonoids protect hepatic cells against high-glucose-induced oxidative stress: relevance of MAPKs.

SCOPE Oxidative stress plays a main role in the pathogenesis of type 2 diabetes mellitus. Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in type 2 diabetes mellitus because of their protective effects against oxidative stress and insulin-like properties. In this study, the protective effect of EC and a cocoa phenolic extract (CPE) against oxidative stress induced by a high-glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells. METHODS AND RESULTS Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs), nuclear factor E2 related factor 2 (Nrf2) and p-(Ser)-IRS-1 expression, and glucose uptake were evaluated. EC and CPE regulated antioxidant enzymes and activated extracellular-regulated kinase and Nrf2. EC and CPE pre-treatment prevented high-glucose-induced antioxidant defences and p-MAPKs, and maintained Nrf2 stimulation. The presence of selective MAPK inhibitors induced changes in redox status, glucose uptake, p-(Ser)- and total IRS-1 levels that were observed in CPE-mediated protection. CONCLUSION EC and CPE recovered redox status of insulin-resistant HepG2 cells, suggesting that the functionality in EC- and CPE-treated cells was protected against high-glucose-induced oxidative insult. CPE beneficial effects on redox balance and insulin resistance were mediated by targeting MAPKs.
Liposome-encapsulated MTP-PE: a novel biologic agent for cancer therapy.

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), a new biologic response modifier, was designed to target the immunomodulator to monocytes and macrophages. Human monocytes/macrophages phagocytize L-MTP-PE, with subsequent upregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and monocyte chemotactic and activating factor genes and with the production and secretion of these cytokines in vitro. L-MTP-PE-activated macrophages kill tumor but not normal cells in vitro. Following i.v. infusion of L-MTP-PE into cancer patients, its uptake was demonstrated in liver, spleen, lung, and in and around metastases to lung. We also investigated whether L-MTP-PE therapy administered in a neoadjuvant setting could improve the disease-free interval in relapsed osteosarcoma patients with lung metastasis. Patients received either a 12- or 24-week course of L-MTP-PE after surgical removal of all metastases. Following L-MTP-PE infusion, induction of circulating TNF-alpha, IL-6, neopterin, and C-reactive protein was demonstrated. Disease-free intervals were calculated from the day of surgery to the day of relapse in each group and were compared with the disease-free interval for a historical control group. Those patients receiving 24 weeks of L-MTP-PE showed a significant (p < 0.03) prolongation in time to relapse. These data indicate that L-MTP-PE is an active agent against osteosarcoma and warrants further investigation in an adjuvant setting.
Monocyte 1α‐hydroxylase regulation: induction by inflammatory cytokines and suppression by dexamethasone and uremia toxin

Abstract: Alveolar macrophages acquire lα‐hydroxylase activity in inflammation, and thereby metabolize 25 hydroxyvitamin D3 (25 D3) to the active metabolite, la,25‐dihydroxyvitamin D3 (1,25 D3, calcitriol). Cal‐ citriol is a potent differentiation agent that modulates mononuclear phagocyte activation and effector functions. The mediators that induce macrophage lα‐hydroxylase activity are not well delineated. Furthermore, it is unclear whether calcitriol is a product only of terminally differentiated macrophages or whether less mature mononuclear phagocytes can produce it as well. The ability of newly recruited monocytes to produce calcitriol as an autocrine differentiation agent is particularly important in inflammation, as it may substantially expand the functional repertoire of these cells. To assess the effects of cytokines on lα‐hydroxylase activity, blood monocytes were cultured in the presence and absence of human recombinant tumor necrosis factor a (TNF‐α), interferon‐7 (IFN‐γ), and interleukins 1 and 2 and then incubated with 25 D3 substrate. The conditioned media were assayed for calcitriol by high‐performance liquid chromatography and competitive receptor binding assay. No detectable calcitriol was produced by unstimulated monocytes. However, all the cytokines markedly increased monocyte calcitriol production (range 133‐151 pg/mg protein; in all cases P < .001). We then determined whether calcitriol production was suppressed by preincubation with either dexamethasone or the putative uremia toxin guanidinosuccinic acid (GSA). Dexamethasone pretreatment significantly inhibited subsequent cytokine‐induced calcitriol production by monocytes, as did GSA (average 69 and 63% of control, respectively).
News and Financial Intermediation in Aggregate Fluctuations

Abstract An important disconnect in the news view of fluctuations is the lack of consistent evidence suggestive of significant macroeconomic effects of news shocks. Findings from estimated DSGE models that in theory allow news shocks to matter quantitatively suggest that they do not. This disconnect can be resolved once we augment a DSGE model with a financial channel that provides amplification to news shocks. Our results suggest that news shocks to the future growth prospects of the economy are significant drivers of U.S. fluctuations, explaining as much as 50% and 37% of the variance in hours worked and output, respectively, in cyclical frequencies.
The relationship between clients’ cognitive functioning and the therapeutic working alliance in post-acute brain injury rehabilitation

Objective: To examine the impact of brain-injured patients’ cognitive abilities on their working alliance (WA) with their therapist in post-acute rehabilitation. Design: Cognitive tests were administered to brain-injured individuals at the beginning of post-acute, holistic brain-injury rehabilitation. Clients as well as their primary therapists rated their mutual WA at four time points throughout a 14-week rehabilitation programme. Subjects consisted of 86 clients as well as their primary therapists. Clients had suffered a traumatic brain injury (n = 27), a cerebrovascular accident (n = 49) or another neurological insult (n = 10). Measures: (1) Neuropsychological tests of attention, memory and higher cognitive functions; (2) the Working Alliance Inventory, client and therapist short form. Results: Overall, the relationships between cognitive tests and WA ratings were weak. The tests of attention, memory and higher cortical functions were differentially related to clients’ and therapists’ view of their mutual WA at the different stages of their collaborative work. Discussion and conclusion: Clients’ cognitive profile affects clients’ and therapists’ view of their WA in different ways. The weakness of the correlations between cognitive tests and WA ratings may indicate that a good WA is achievable also with clients with severe cognitive difficulties.
Melt Granulation and Heat Treatment for Wax Matrix-Controlled Drug Release

Abstract The purpose of this study was to evaluate sustained drug release after melt granulation and heat treatment. Theophylline (anhydrous) and phenylpropanolamine hydrochloride (PPA) were used as model drugs. Compritol® 888 ATO (Glyceryl Behenate NF) was incorporated as the wax matrix material. Formulations with drug:wax in 3:1 and 1:1 ratios were evaluated. Tablets were made by dry blending or melt granulation; some of the tablets were heat treated at 80°C for 30 min. Tablets with or without heat treatment were tested for drug release using in vitro drug dissolution. The results showed that melt granulation gave slower drug release than dry blending. Heat treatment further retarded drug release for both dry blending and melt granulation. The drug release rates for theophylline were slower than for PPA at the same wax level and processing method. The drug release profiles were linear using a square root of time scale. In conclusion, melt granulation and heat treatment slowed drug release for the wax matrix-controlled release tablets. Heat treatment of the tablets made by melt granulation further retarded drug release. Heat treatment redistributed the wax, forming a new matrix system with higher tortuosity. The application of melt granulation or heat treatment can successfully retard drug release.
Role of lung apolipoprotein A-I in idiopathic pulmonary fibrosis: antiinflammatory and antifibrotic effect on experimental lung injury and fibrosis.

RATIONALE Idiopathic pulmonary fibrosis (IPF) is caused by alterations in expression of proteins involved in multiple pathways, including matrix deposition, inflammation, injury, and repair. OBJECTIVES To understand the pathogenic changes in lung protein expression in IPF and to evaluate apolipoprotein (Apo) A-I as a candidate therapeutic molecule. METHODS Two-dimensional electrophoresis was adopted for differential display proteomics. Reverse-transcriptase polymerase chain reaction, Western blotting, immunohistochemical staining, and ELISA were performed for identification and quantitative measurement of Apo A-I in bronchoalveolar lavage fluids from subjects with IPF and experimental bleomycin-induced mice. MEASUREMENTS AND MAIN RESULTS Sixteen protein spots showed differences in relative intensity between IPF (n = 14) and healthy control subjects (n = 8). Nano liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed increase of haptoglobulin and decrease of alpha(1)-antitrypsin, alpha(1)-antichymotrypsin, macrophage capping protein, angiotensinogen, hemoglobin chain B, Apo A-I, clusterin, protein disulfide isomerase A3, immunoglobulin, and complement C4A in IPF compared with normal control subjects (P = 0.006-0.044). Apo A-I concentrations were lower in bronchoalveolar lavage fluids from subjects with IPF (n = 28) than in normal control subjects (n = 18; P < 0.01). In bleomycin-treated mice, Apo A-I protein in BALF was lower than that in sham-treated control animals. Immunohistochemical analysis showed positive staining on intraalveolar macrophages and epithelial cells of the lungs. Intranasal treatment with Apo A-I protein reduced the bleomycin-induced increases in number of inflammatory cells and collagen deposition in sham-treated mice in a dose-dependent manner. CONCLUSIONS Alterations of several inflammatory and antiinflammatory proteins in the lungs may be related to the pathogenesis of IPF, and local treatment with Apo A-I is very effective against the development of experimental lung injury and fibrosis.
Non‐invasive bioluminescent detection of prostate cancer growth and metastasis in a bigenic transgenic mouse model

We previously established a bioluminescent transgenic mouse model, sPSA‐Luc, with luciferase gene expression restricted to the prostate under the control of the supra prostate‐specific antigen (sPSA) promoter. We now assess the feasibility of generating bigenic mice, TRAMP‐Luc, with the sPSA‐Luc as the founder strain crossbred with TRAMP (transgenic adenocarcinoma mouse prostate) mice, to evaluate non‐invasively the metastatic potential of prostate tumors.
ANALYSIS OF THE INFLUENCE OF DISTANCE ON DATA ACQUISITION INTENSITY FORESTRY TARGETS BY A LIDAR TECHNIQUE WITH TERRESTRIAL LASER SCANNER

The forest sciences as well as other areas of knowledge benefit from technological advances to develop their working methods and increase their knowledge of their specific field of study. New equipment and methods are continually developed to support these applications. In the last decade, laser scanning and profiling systems have been consolidated as one of the most effective technologies for geospatial data acquisition. Based on the time-of-flight and with an electromagnetic spectrum that ranges into the mid-infrared, 1535 nm, the terrestrial laser systems are appropriate for correlating the intensity data with physicochemical properties. Thus, the main objective of this study was to evaluate the influence of the distance to the target in the data acquisition intensity targets forest in order to support future studies of correlation between this variable and the physicochemical characteristics of the targets. In this study we used the Terrestrial Laser Scanner 3D Ilris with Optech operating principle based on flight time and wavelength of 1535 nm spectral range from infrared magnetic medium. The data acquisition targets intensity was assessed at distances (1 m a 50 m) by using a target reference of 99% reflectance. The results were analysed and showed that the distance interferes with the return of intensity. From the results of this research recommend that the intensity data are calibrated in relation to distance before using them as a source for study of the physical-chemical characteristics of the targets.
Local treatment of chronic wounds: in patients with peripheral vascular disease, chronic venous insufficiency, and diabetes.

BACKGROUND A chronic wound is defined as an area where the skin is not intact that fails to heal within eight weeks. Such wounds usually develop on the lower limbs as a complication of diabetes, venous insufficiency, or inadequate arterial perfusion. Most of the roughly 45,000 limb amputations performed in Germany each year are necessitated by non-healing chronic wounds. METHODS In the development of this S3 guideline, a systematic search was performed that yielded 4998 references including 38 randomized, controlled trials and 26 systematic reviews, which were used as the basis for the recommendations and statements made in the guideline. Twelve member societies of the umbrella Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF), as well as the German Association of Nursing Science (Deutsche Gesellschaft für Pflegewissenschaft, and patient representatives participated in the consensus rounds in which the guideline's recommendations and statements were agreed upon. RESULTS This guideline contains seven evidence-based recommendations and 30 good clinical practice (GCP) recommendations. Evidence-based recommendations are given in favor of hydrogel, hyperbaric oxygenation, and integrated care, and against the use of medicinal honey and growth factors. Terms are defined precisely in order to ease communication and to specify what is meant by "wound debridement" (a procedure performed by a physician) as opposed to cleansing a wound. Under the premise of preventing pain, exudation, and maceration, local therapeutic agents can be chosen on the basis of the scientific evidence, the patient's preference, the physician's experience, and the wound situation. Costs should also be considered. CONCLUSION Scant evidence is available to answer many of the relevant questions about chronic wounds. There are valid data in support of hyperbaric oxygen and integrated care. More research is needed.
Individual Differences in Sensitivity to Interaural Differences in Time and Level 1

Previous research had indicated the existence of two groups—people more sensitive to interaural time differences than to interaural level (intensity) differences and people more sensitive to level differences than to time differences. A population of undergraduates was surveyed in an attempt to estimate the relative proportions of people in the two groups. Two characteristics possessed by previous Ss classified as time-sensitive or level-sensitive were used as the basis for classification of the present Ss. The psychophysical method was single-interval forced-choice, and Ss' task was to lateralize an auditory image. Usable data were obtained from 73 out of 76 Ss. Of those that met the criterion for classification into one of the two groups, about 25% were more sensitive to time differences than to level differences.
Cancer-associated thrombosis.

Thrombosis was identified as a complication of cancer by Trousseau in 1865, and the combination of the two conditions is still often called Trousseau's syndrome. Arterial and, more commonly, venous thrombosis is a frequent complication of cancer and sometimes a harbinger of occult cancer. Moreover, the use of new and aggressive therapy for cancer increases the risk of thrombosis. There are many causes of thrombosis in cancer. Cancer itself is often the underlying mechanism. When cells of the monocyte or macrophage lineage interact with malignant cells, they release tumor necrosis factor, interleukin-1, and interleukin-6, causing endothelial damage and sloughing of .
The chromosomes of Moniliformis dubius (Acanthocephala).

Squashes of testes and ovarian masses of Moniliformis dubius contained some gonial cells with mitotic metaphase configurations which are described and figured. The diploid chromosome number is eight in females and seven in males. An XO sex-determining mechanism is proposed, with the male heterogametic. During the first meiotic division of spermatocytes, the single X chromosome begins polar migration before the autosomes move away from the equator of the spindle. Meiosis in oocytes takes place after sperm penetration. The two X chromosomes move to opposite poles of the spindle before separation of the autosomes in Meiosis I. The differences in chromosome number and behavior between M. dubius and Macracanthorhynchus hirudinaceus are noted. Apart from the studies of Jones and Ward (1950) and Robinson (1964) on the chromosomes of Macracanthorhynchus hirudinaceus, the author is not aware of any published work on karyotype analysis of archiacanthocephalans. In M. hirudinaceus there is a diploid chromosome number of six and an XY sex-determining mechanism, the male being heterogametic. Another archiacanthocephalan, Moniliformis dubius Meyer, 1933, is currently being studied in this laboratory. We are particularly interested in the cytology and development of the parasite together with the nature and extent of cytological and morphological changes which follow X-irradiation. One aspect of the project has been the determination of the chromosome number and the morphology and behavior of the chromosomes during mitosis and meiosis. This was done in order to provide a description of the karyotype of this species which could be used as a basis for comparison of the chromosome complements and sex-determining mechanisms in Mon. dubius and Macr. hirudinaceus. Also, a knowledge of normal chromosome morphology and behavior is necessary before the effects of X-irradiation on the chromosomes can be satisfactorily described. MATERIALS AND METHODS Specimens of Periplaneta americana infected with cystacanths of M. dubius, and laboratory rats infected with adults were kindly provided early in 1963 by Dr. W. L. Nicholas, Zoology Department, The Australian National University, Canberra. From these initial infections, the parasite has been maintained in cockroaches and rats in this laboratory. More recently, cockroaches natReceived for publication 21 November 1964. u ally infected with cystacanths were found in the Sydney area, and from this material additional laboratory infections have been established. Male and female white Wistar rats were killed about 21 days after infection with 10 to 15 cystacanths. Infection rates varied considerably, but seldom fell below 50%. After removal from the host, the worms were washed in physiological saline and squashes of testes or ovarian masses were prepared in the way described earlier (Robinson, 1964). All preparations were examined and all photographs were taken with a Zeiss photomicroscope. Adox KB14 film and Adox E10 film developer were used.
Establishing auditory stimulus control over an eight-member equivalence class via conditional discrimination procedures.

Two eight-member equivalence classes of visual stimuli were established during three phases of a training program. In Phase 1, two training arrangements were compared. In one, 3 subjects were taught on different trials to select from a single pair of comparison stimuli (A1, A2) in response to eight sample stimuli that were trained in pairs (B1, B2; C1, C2; D1, D2; E1, E2). In the second arrangement, subjects were taught to select from four pairs of comparisons (B1, B2; C1, C2; D3, D2; E2, E2) in response to two samples (A1, A2). Training with the single pair of comparison stimuli resulted in the development of equivalence relations (B1C1, B2C2, D1B1, D2B2, B1E1, B2E2, C1D1, C2D2, C1E1, C2E2, D1E1, D2E2, and their reciprocals) between the sample stimuli without direct training of these relations. In the other training arrangement, these relations among the comparison stimuli developed in the performance of 1 subject only. In Phase 2, three new pairs of stimuli (F1, F2; G1, G2; H1, H2) were substituted for three of the original pairs (B1, B2; C1, C2; D1, D2) and the training arrangements for the groups were reversed. Following training, the performances that showed equivalence relations on the probes in the first phase also showed equivalence relations in the second phase. If such relations did not develop in the first phase, they did not do so in the second phase. In Phase 3, relations between stimuli across the two previous phases (e.g., B1F1, B2F2, B1G1, B2H2, C1F1, etc.) were investigated. The 4 subjects whose performances showed the development of these relations were taught to select one stimulus from each class (E1 and E2) in response to a verbal label (I1 and I2) and then were tested to see if the verbal label controlled responding to the remaining members of the class (e.g., I1A1, I2A2, I1B1, I2B2, etc.). For 3 subjects, this generalized control occurred; for the 4th, generalization occurred only after verbal training with a second pair of visual stimuli (F1 and F2). In retests several months later, these auditory-visual relations were found to be intact or, if not, were recovered without direct training.
Clinical use of FFP: results of a retrospective process and outcome audit

An audit has been carried out on the usage of 216 units of fresh frozen plasma (FFP) issued to 41 patients. This involved the systems of FFP issue, the appropriateness of prescription as well as the recorded benefits. Sixty‐six per cent of the initial requests for FFP appeared to satisfy criteria for appropriate use. Review of the case notes resulted in some changes to earlier decisions and a slight increase to 73% of those accepted as valid. Only 94% of the FFP issued could be proved to have been given to identified patients and only 88% of case notes showed the reason for treatment.
Myoclonic Seizures in Down's Syndrome

Three children with Down's syndrome are reported with spontaneously occurring myoclonic seizures. Electroencephalograms were markedly abnormal, but improved after medication in two cases. Seizures were controlled with drugs in two of the children, but are not well controlled in the third, despite attempts with several types of medication. The aetiology of these myoclonic seizures remains unclear.