Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of hyaluronate sodium on pain and physical functioning in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND Intra-articular hyaluronate sodium is a relatively new therapy for the treatment of osteoarthritis of the knee. This randomized, double-blind clinical trial was conducted at a large primary care medical center to determine the impact of hyaluronate sodium vs conventional therapy on measures of pain, stiffness, and disability at rest and following functionally relevant walking and stepping activities. METHODS A total of 120 patients (mean age, 67 years) with unilateral grades 1 to 3 medial compartment knee osteoarthritis were randomized to 1 of 4 treatment groups: group 1, 2 mL of hyaluronate sodium at a concentration of 10 mg/mL and placebo (100 mg of lactose); group 2, nonsteroidal anti-inflammatory drugs (NSAIDs) (75 mg of diclofenac and 200 microg of misoprostol) and hyaluronate sodium; group 3, NSAIDs and placebo (2 mL of isotonic sodium chloride solution [saline]); and group 4, placebo (lactose and saline). Intra-articular hyaluronate sodium or saline (2 mL) was administered once weekly over 3 weeks while NSAIDs or lactose were administered twice daily over 12 weeks. MAIN OUTCOME MEASURES (1) Western Ontario McMaster Universities Index (WOMAC) global measure of pain, stiffness, and disability; (2) visual analog scale (VAS) scores for pain at rest and following functional walking and stepping activities (self-paced walking and stepping); and (3) functional performance (exercise time, heart rate, and predicted maximum oxygen uptake) at baseline and weeks 4 and 12. RESULTS At week 4, significant improvement in WOMAC scores for pain and disability and VAS score for resting pain was observed in groups 1 to 3 compared with baseline measures. Groups 1 and 2 showed significantly lower self-paced stepping pain, while no change was observed in group 4. At week 12, groups 1 to 3 showed significantly greater improvement in WOMAC pain subscale score and VAS score for resting pain; however, these differences did not vary from week 4. Following self-paced walking and stepping, groups 1 and 2 reported significantly less activity pain, while group 1 showed significantly faster self-paced walking and stepping test results. Groups 1 to 3 improved self-paced walking and stepping time at week 12 compared with baseline measures, while predicted maximum oxygen uptake was significantly higher in the hyaluronate sodium groups 1 and 2 at weeks 4 and 12 compared with baseline measures. CONCLUSIONS For resting pain relief, hyaluronate sodium seems to be as effective as NSAIDs. Further, for pain with physical activity and functional performance, hyaluronate sodium may be superior to placebo alone or NSAIDs alone.
Phenotype Correction in Murine Mucopolysaccharidosis Type VII by Transplantation of Human Amniotic Epithelial Cells after Adenovirus-Mediated Gene Transfer

Cell therapy with human amniotic epithelial (HAE) cells was developed as an alternative method for enzyme replacement therapy in congenital lysosomal storage disorders, but only limited therapeutic efficacy has been reported. A major drawback is insufficient production and secretion of lysosomal enzymes from HAE cells. In this study, we infected HAE cells with an E1-deleted adenoviral vector expressing human β-glucuronidase (GUSB), and generated cells overexpressing GUSB by a hundred times as much as endogenous GUSB in untreated HAE cells. GUSB secreted from the gene-transferred HAE cells were efficiently transported to murine fibroblasts with endocytosis mediated by mannose-6-phosphate receptors. The cells were administered into the spleen of the mice with the lysosomal storage disease mucopolysaccharidosis type VII (B6/MPSVII). Approximately 10–15% of the normal GUSB activity was detected in both liver and spleen 7 days after the cell administration. Histopathological examination showed that lysosomal enlargement in tissue macrophages in the liver and the spleen had disappeared by day 14. These results suggest that transplantation of the HAE cells transduced with adenoviral vectors can be employed for the treatment of congenital lysosomal storage disorders.
Immediate Effects of Aerobic Exercise on Plasma/Serum Zinc Levels: A Meta-analysis.

BACKGROUND Zinc is involved in numerous metabolic roles, including energy metabolism, immunity, and antioxidative effects. Zinc losses during exercise, in particular through sweat, are well documented. However, conflicting results have been reported for changes in circulating and tissue zinc concentration as a result of exercise. The purpose of this article is to quantify the immediate effect of aerobic exercise on plasma or serum zinc levels, in healthy participants. METHODS We conducted a systematic review of peer-reviewed articles published up to December 20, 2014, to identify studies that investigated the acute effects of exercise on selected indices of zinc status. Meta-analyses were conducted to determine the change in serum zinc concentration immediately after a bout of aerobic exercise. RESULTS Forty-five studies were included in the systematic literature review. Of the included studies, sufficient data were available from 34 studies (providing 46 comparisons) to quantify the change in serum zinc concentration after exercise. Serum zinc concentration was significantly higher immediately after exercise (0.45 ± 0.12 μmol·L(-1), P < 0.001; mean ± SE). Secondary analyses showed greater increase in serum zinc for untrained individuals and exercise sessions that involved running or maximal intensity. Insufficient data were available to determine the effects of exercise on urinary, sweat, and erythrocyte zinc. CONCLUSIONS The present systematic review and meta-analysis indicated significant increase in serum zinc concentration immediately after an aerobic exercise session, suggesting acute perturbations in zinc homeostasis. Further research is required to ascertain the long-term effects of exercise on zinc metabolism and potential consequences for dietary zinc requirement for physically active populations.
[Periventricular and intraventricular hemorrhage in the premature infants].

OBJECTIVE To review intracranial hemorrhage originated in the subependymal germinal matrix region. DEVELOPMENT Incidence rates of germinal matrix-intraventricular hemorrhage (GMH) range from 20 to 40% of infants born before 32 weeks gestational age or with birth weight less than 1,500 g. Because the GMH is usually diagnosed during the first 72 postnatal hours, that is the optimal time to perform ultrasound scans. The pathogenesis of GMH is multifactorial and related to vascular, intravascular and extravascular factors. The grading system relies on the detection of blood in the germinal matrix region and into the ventricular system. Ultrasound scans are the diagnostic method of choice, once it is easy to perform and has low costs. In a prospective study of 146 preterm infants (< 2,200 g), the incidence of GMH in those weighing less than 1,501 g, was 36%. GMH occurred mainly in the first week of life (65%) and in 70% of cases was classified as grade I. Risk factors found to be related to the GMH were: general anesthesia for cesarean section, Apgar score below 4 in the first minute or below 8 in the fifth minute, low birth weight, the presence of respiratory distress, patent ductus arteriosus, anemia, repeated arterial functions and umbilical arterial catheterization. Mean gestational age, systolic and diastolic pressure in the first 24 hours of life and hematocrit were lower in patients with GMH. CONCLUSIONS GMH is frequent in the preterm infant, and occurs mainly in the first week of life. Ultrasound scans are the method of choice for the diagnosis and follow-up. Risk factors associated were hypoxia and excessive handling.
Neuroprotective effects of melatonin administered alone or in combination with topiramate in neonatal hypoxic-ischemic rat model.

PURPOSE The objective of this study was to compare the effects of two neuroprotective agents; melatonin, a free radical scavenger and topiramate, AMPA/kainate receptor antagonist, administered alone or in combination in neonatal hypoxic-ischemic model. METHODS After being anesthetized, 7-day-old pups underwent ischemia followed by exposure to hypoxia. The pups were divided into 4 groups in order to receive the vehicle, melatonin, topiramate and combination of topiramate and melatonin. These were administered intraperitoneally for three times; the first before ischemia, the second after hypoxia and the third 24 hours after the second dose. After sacrification, infarct volume and apoptosis were evaluated. RESULTS Percent infarcted brain volume was significantly reduced in rats which received drugs compared with those which received the vehicle. The number of TUNEL positive cells per unit area in hippocampus and cortex were markedly reduced in drug treated groups compared with control group. No significant differences were found regarding percent infarcted brain volume and number of TUNEL positive cells among drug-treated groups. CONCLUSIONS Melatonin and topiramate, administered either alone or in combination significantly reduced the percent infarcted brain volume and number of TUNEL positive cells suggesting that these agents may confer benefit in treatment of infants with hypoxic-ischemic encephalopathy.
Cognitive Processing Speed, Working Memory, and the Intelligibility of Hearing Aid-Processed Speech in Persons with Hearing Impairment

Previous studies have demonstrated that successful listening with advanced signal processing in digital hearing aids is associated with individual cognitive capacity, particularly working memory capacity (WMC). This study aimed to examine the relationship between cognitive abilities (cognitive processing speed and WMC) and individual listeners’ responses to digital signal processing settings in adverse listening conditions. A total of 194 native Swedish speakers (83 women and 111 men), aged 33–80 years (mean = 60.75 years, SD = 8.89), with bilateral, symmetrical mild to moderate sensorineural hearing loss who had completed a lexical decision speed test (measuring cognitive processing speed) and semantic word-pair span test (SWPST, capturing WMC) participated in this study. The Hagerman test (capturing speech recognition in noise) was conducted using an experimental hearing aid with three digital signal processing settings: (1) linear amplification without noise reduction (NoP), (2) linear amplification with noise reduction (NR), and (3) non-linear amplification without NR (“fast-acting compression”). The results showed that cognitive processing speed was a better predictor of speech intelligibility in noise, regardless of the types of signal processing algorithms used. That is, there was a stronger association between cognitive processing speed and NR outcomes and fast-acting compression outcomes (in steady state noise). We observed a weaker relationship between working memory and NR, but WMC did not relate to fast-acting compression. WMC was a relatively weaker predictor of speech intelligibility in noise. These findings might have been different if the participants had been provided with training and or allowed to acclimatize to binary masking noise reduction or fast-acting compression.
Cyclic AMP Selectively Uncouples Mitogen-Activated Protein Kinase Cascades from Activating Signals

ABSTRACT Cells integrate signals to select the appropriate response from an array of possible outcomes. Signal integration causes the reorganization of signaling pathways by undescribed events. To analyze the molecular changes in signaling pathways that elicit different responses, we focused on the interaction between cyclic AMP (cAMP) and growth factors. We show that the activation of extracellular signal-regulated kinase 5 (ERK5), but not ERK1/2, by growth factors is disrupted by cAMP through cAMP-dependent protein kinase (PKA). Activation of MEKK2, a mitogen-activated protein (MAP) kinase kinase kinase upstream of ERK5 that is required for growth factor activation of ERK5, is also disrupted by PKA. Transcription of c-Jun is induced by ERK5, and like ERK5, c-Jun induction is also blocked by cAMP. Transcription from the serum response element, like activation of ERK1/2, is not blocked by cAMP. Collectively, these results support a model in which cAMP shapes the growth factor-induced cellular response through PKA-dependent uncoupling of selected MAP kinase cascades from activating signals.
Nerve Growth Factor, Epidermal Growth Factor, and Insulin Differentially Potentiate ATP‐Induced [Ca2+]i Rise and Dopamine Secretion in PC12 Cells

Abstract: To study how growth factors affect stimulus‐secretion coupling pathways, we examined the effects of nerve growth factor (NGF), epidermal growth factor (EGF), and insulin on ATP‐induced [Ca2+]i rise and dopamine secretion in PC12 cells. After a 4‐day incubation of cells, all three factors increased ATP‐induced dopamine secretion significantly. We then examined which step of ATP‐induced secretion was affected by the growth factors. Cellular levels of dopamine‐β‐hydroxylase and catecholamines were increased by NGF treatment but were not affected by EGF or insulin. The ATP‐induced [Ca2+]i rise was also enhanced after growth factor treatment. The EC50 of ATP for inducing [Ca2+]i rise and dopamine secretion was increased by NGF treatment but not by treatment with EGF or insulin. Accordingly, the dependence on [Ca2+]i of dopamine secretion was increased significantly only in NGF‐treated cells. Our results suggest that for EGF‐ and insulin‐treated PC12 cells, the increase in secretion is mainly due to increased potency of ATP in inducing [Ca2+]i rise. NGF treatment not only increased the potency of ATP but also decreased the Ca2+ sensitivity of the secretory pathway, which as a result becomes more tightly regulated by changes in [Ca2+]i.
E46K Human α-Synuclein Transgenic Mice Develop Lewy-like and Tau Pathology Associated with Age-dependent, Detrimental Motor Impairment*

Background: Synucleinopathies are a group of neurodegenerative disorders associated with the formation of amyloid inclusions composed of the normally soluble presynaptic protein α-synuclein. Results: We describe transgenic mice expressing E46K human α-synuclein. Conclusion: These E46K α-synuclein transgenic mice accumulate age-dependent intracytoplasmic neuronal α-synuclein inclusions and motor impairments. Significance: Our findings provide novel insights into the mechanisms of formation and consequence of α-synuclein inclusions. Synucleinopathies are a group of neurodegenerative disorders associated with the formation of aberrant amyloid inclusions composed of the normally soluble presynaptic protein α-synuclein (α-syn). Parkinson disease is the most well known of these disorders because it bears α-syn pathological inclusions known as Lewy bodies (LBs). Mutations in the gene for α-syn, including the E46K missense mutation, are sufficient to cause Parkinson disease as well as other synucleinopathies like dementia with LBs. Herein, we describe transgenic mice expressing E46K human α-syn in CNS neurons that develop detrimental age-dependent motor impairments. These animals accumulate age-dependent intracytoplasmic neuronal α-syn inclusions that parallel disease and recapitulate the biochemical, histological, and morphological properties of LBs. Surprisingly, the morphology of α-syn inclusions in E46K human α-syn transgenic mice more closely resemble LBs than the previously described transgenic mice (line M83) that express neuronal A53T human α-syn. E46K human α-syn mice also develop abundant neuronal tau inclusions that resemble neurofibrillary tangles. Subsequent studies on the ability of E46K α-syn to induce tau inclusions in cellular models suggest that both direct and indirect mechanisms of protein aggregation are probably involved in the formation of the tau inclusions observed here in vivo. Re-evaluation of presymptomatic transgenic mice expressing A53T human α-syn reveals that the formation of α-syn inclusions in mice must be synchronized; however, inclusion formation is diffuse within affected areas of the neuroaxis such that there was no clustering of inclusions. Collectively, these findings provide insights in the mechanisms of formation of these aberrant proteinaceous inclusions and support the notion that α-syn aggregates are involved in the pathogenesis of human diseases.
Selling to the Socially Interactive Consumer: Order More or Less?

This paper studies the newsvendor problem in the presence of consumer behavior, specifically, social interaction. We show that deterministic consumer valuation on products derived from social interaction can be an advantage for firms. This paper examines the implications of random consumer product valuation and a lower threshold number of subscribers to the proposed deal. Several implications have been yielded.
In vitro differentiation of embryonic stem cells: Immunophenotypic analysis of cultured embryoid bodies

The process of in vitro embryonic stem cell differentiation and embryoid body development was monitored using a panel of antibodies against surface markers traditionally associated with embryonic tissue (Forssman, SSEA‐1) and hematopoietic progenitor cells (Fall‐3, HSA, Sca‐1, Thy‐1.2, ER‐MP12, CD45, AA4.1, and c‐kit). All markers with the exception of CD45 and AA4.1 were initially detected in cultures of undifferentiated ES cells. During the first 11 days of differentiation, distinct and reproducible patterns of surface expression were observed for each marker. Using the kinetic display of surface markers as a gauge of differentiation, perturbations in embryoid body development were detected in cultures supplemented with interleukin‐11, a gp130‐activating cytokine thought to affect embryonic stem cell differentiation. In the absence of exogenous cytokines, microbead immunoselected day 7 c‐kit, ER‐MP12, and CD45‐positive embryoid body cells were enriched for hematopoietic progenitors as detected by methylcellulose colony assays, while no significant enrichment of hematopoietic progenitors was observed with Sca‐1, Thy‐1.2, Fall‐3, and Forssman‐immunoselected cells. These results indicate that the process of early embryoid body development is associated with a programmed sequence of cell surface marker display, concomitant with the development of phenotypically definable embryonic cell lineages. J. Cell. Physiol. 171:104–115, 1997. © 1997 Wiley‐Liss, Inc.
Optimal Power Allocation Scheme for NOMA with Adaptive Rates and alpha-Fairness

In this paper, the optimal power allocation scheme is investigated for sum rate maximization of non- orthogonal multiple access (NOMA) with adaptive rates and α-fairness. Compared to the existing fairness NOMA models, α-fairness can only utilize a single scalar to achieve different user fairness levels. Specifically, the power allocation problem is first formulated to maximize the instantaneous sum rate with α-fairness, where user rates are adapted according to the instantaneous channel state information (CSI). Then, a simple alternate algorithm is proposed to solve the Karush-Kuhn Tucker (KKT) conditions of the formulated power allocation problem. Analytical results demonstrate that the proposed algorithm converges and yields the optimal solution. Numerical results reveal that, at the same fairness level, NOMA significantly outperforms the conventional orthogonal multiple access (MA).
Diabetes mellitus in patients with thalassemia major

Diabetes mellitus is a major endocrinopathy for patients with thalassemia major. Although diabetes mellitus is multifactorial, iron loading is its primary cause and its management poses a clinical challenge. Detecting the pre‐diabetes stage is critical because clinical diabetes can potentially be reversed or prevented.
Mitogenic activity of neu differentiation factor/heregulin mimics that of epidermal growth factor and insulin‐like growth factor‐I in human mammary epithelial cells

Recently, a family of growth factors has been described that activates erbB‐2 receptors. These factors, known as the neu differentiation factors (NDF) or heregulins (HRG), induce tyrosine phosphorylation of erbB‐2 receptors as a result of their direct interaction with either erbB‐3 or erbB‐4 receptors. Although it is known that expression of erbB‐2 receptors has relevance in human breast cancer progression, how erbB‐2, ‐3 and ‐4 receptors regulate mammary epithelial cell proliferation is not known. Therefore, experiments were carried out to study the mitogenic activity of NDF/HRG on the human mammary epithelial cell line MCF‐10A which can be cultured continuously under serum‐free conditions. MCF‐10A cells, like primary cultures of normal human mammary epithelial cells, express an absolute requirement for exogenous epidermal growth factor (EGF) and insulin‐like growth factor I (IGF‐I) for growth. The results of these experiments indicate that NDF/HRG can induce tyrosine phosphorylation of p185erbB‐2 in MCF‐10A cells and is mitogenic for these cells. This is consistent with the coexpression of erbB‐2 and erbB‐3 mRNA that we have observed in MCF‐10A cells. In addition, we found that NDF/HRG can substitute for either EGF or IGF‐I to stimulate proliferation of these cells. The ability to substitute for both EGF and IGF‐I is a unique property of NDF/HRG and is not shared by other members of the EGF or IGF family of growth factors, nor by other factors that we have studied. A striking isoform specificity was also observed which indicated that the β‐isoforms of NDF/HRG were greater than ten times more mitogenic than the α‐isoforms. We also examined the mitogenic activity of NDF/HRG on MCF‐10A cells that overexpress the erbB‐2 receptor as a result of infection with a retroviral vector containing the human c‐erbB‐2 gene (MCF‐10AerbB‐2 cells). These studies indicated that MCF‐10AerbB‐2 cells have increased sensitivity to the mitogenic effects of NDF/HRG and that these cells are responsive to the α‐isoforms of NDF/HRG at physiological concentrations. Thus, NDF/HRG is a dual specificity growth factor for human mammary epithelial cells, and the responsiveness of the cells to NDF/HRG is influenced by the level of expression of erbB‐2 receptors. © 1995 Wiley‐Liss, Inc.