Miracle-dz/UniFAR-FTUs huggingface dataset:
Oral fingolimod rescues the functional deficits of synapses in experimental autoimmune encephalomyelitis

BACKGROUND AND PURPOSE Alterations of glutamate‐mediated synaptic transmission occur early during neuroinflammatory insults, and lead to degenerative neuronal damage in multiple sclerosis (MS) and also in experimental autoimmune encephalomyelitis (EAE), which is a murine model of MS. Fingolimod is an effective orally active agent for the treatment of MS, affecting lymphocyte invasion of the brain. However, it is still unclear if fingolimod can be neuroprotective in this disorder.
Intervertebral Disc Facet Joints Dysfunction Normal Muscular sprain Small annular tears Facet synovitis Annular tears Capsular laxity Capsular tears

Address Correspondence: Laxmaiah Manchikanti, M.D., Pain Management Center of Paducah, 2831 Lone Oak Road, Paducah, KY 42003 Chronic neck pain, headache, and arm pain are some of the most common patient complaints confronting today’s health care provider. Chronic neck pain is reported to be a frequency symptom in 34% of the general population with 14% of the general population reporting neck pain that lasted for more than 6 months. The magnitude of the problem is demonstrated by increase of cervical spine surgery by 45% and cervical fusion by 70% over a ten year period from 1979 through 1988. Therapeutic effectiveness of a large variety of interventions in managing chronic neck pain is inconclusive. Pain and dysfunction have been attributed to a number of structure in the neck which have a potential for producing a pain pattern in the neck, head, and upper extremity which include intervertebral disc, nerve roots, facet joints, and ligamentous and muscular structures.
Preoperative evaluation of bile duct cancer: MRI combined with MR cholangiopancreatography versus MDCT with direct cholangiography.

OBJECTIVE The purpose of this study was to compare the performance of MRI combined with MR cholangiopancreatography (MRCP) with that of MDCT combined with direct cholangiography in the evaluation of the tumor extent and resectability of bile duct cancer with surgical and pathologic findings as the reference standard. MATERIALS AND METHODS From January 2003 to March 2006, 27 patients (18 men, nine women; mean age, 60.8 years; range, 43-80 years) with surgically proven hilar cholangiocarcinoma or common bile duct (CBD) cancer who had undergone preoperative 2D and 3D MRCP with gadolinium-enhanced MRI and triple-phase MDCT with direct cholangiography (ERCP or percutaneous transhepatic cholangiography) were included in this retrospective study. Two experienced radiologists independently reviewed the two image sets. These readers evaluated the longitudinal extent of the tumor for involvement of the secondary confluence of both intrahepatic ducts and the intrapancreatic CBD, vascular involvement of the tumor, lymph node metastasis, and tumor resectability. The radiologists' performance was evaluated by calculation of sensitivity, specificity, and overall accuracy. Correlation was made with the resected specimens or findings at surgical exploration. RESULTS For each reviewer, the overall accuracy rates for predicting involvement of the bilateral secondary biliary confluences and the intrapancreatic CBD were 90.7% and 87.0% for MRI with MRCP and 85.1% and 87.0% for MDCT with direct cholangiography. The differences were not statistically significant for either image set for either reviewer (p > 0.05). In the assessment of vascular involvement, lymph node metastasis, and tumor resectability, the readers' diagnostic performance using MRI with MRCP was similar to that with MDCT with direct cholangiography (p > 0.05). CONCLUSION In the diagnosis of bile duct cancer with a noninvasive procedure, the information regarding tumor extent and resectability obtained with contrast-enhanced MRI combined with MRCP is comparable with that obtained with MDCT with direct cholangiography.
Central and peripheral mechanisms involved in hypertension induced by chronic inhibition of nitric oxide synthase in rats.

OBJECTIVE To study the possible central and peripheral mechanisms involved in hypertension induced by chronic inhibition of nitric oxide synthase. METHODS We evaluated neurohormonal and renal responses of Wistar rats to chronic oral administration of 20 and 100 mg/kg per day NG-nitro-L-arginine methyl ester (L-NAME). Effects of intracerebroventricular and intravenous injections of NO donors (NOC-18 and FK-409) and an angiotensin II type 1 receptor antagonist CV-11974, and intravenous injection of alpha-adrenergic receptor antagonist phentolamine after chronic treatment with 100 mg/kg per day L-NAME were also studied. RESULTS The chronic treatment with L-NAME induced a sustained dose-dependent hypertension with a decrease in heart rate. Urinary levels of norepinephrine and epinephrine decreased with no changes in plasma catecholamine levels, renin activity, and vasopressin level. Serum nitrate/nitrite levels in the rats treated with the high dose of L-NAME decreased. The intracerebroventricular and intravenous injections of the NO donors reduced arterial pressure in L-NAME-treated rats to a significantly greater extent than they did that in control rats. The intravenous but not intracerebroventricular injection of CV-11974 produced a sustained decrease in arterial pressure of L-NAME-treated rats. The depressor responses to intravenous injection of phentolamine of L-NAME-treated and control rats were similar. CONCLUSIONS Results indicate that L-NAME-induced hypertension is associated with a deficiency of nitric oxide, both peripherally and centrally. Circulating angiotensin II could contribute to the maintenance of hypertension via angiotensin II type 1 receptor while the sympathetic nervous system seems to be suppressed.
Lung Collapse and Gas Exchange during General Anesthesia: Effects of Spontaneous Breathing, Muscle Paralysis, and Positive End‐expiratory Pressure

Lung densities (atelectasis) and pulmonary gas exchange were studied in 13 supine patients with no apparent lung disease, the former by transverse computerized tomography (CT) and the latter by a multiple inert gas elimination technique for assessment of the distribution of ventilation/perfusion ratios. In the awake state no patient had clear signs of atelectasis on the CT scan. Lung ventilation and perfusion were well matched in most of the patients. Three patients had shunts corresponding to 2–5% of cardiac output, and in one patient there was low perfusion of poorly ventilated regions. CT scans after 15 min of halothane anesthesia and mechanical ventilation showed densities in dependent lung regions in 11 patients. A shunt was present in all patients, ranging from 1% in two patients (unchanged from the awake state) to 17%. Ventilation of poorly perfused regions was noted in nine patients, ranging from 1–19% of total ventilation. The magnitude of the shunt significantly correlated to the size of dependent densities (r = 0.84, P < 0.001). Five patients studied during spontaneous breathing under anesthesia displayed both densities in dependent regions and a shunt, although of fairly small magnitude (1.8% and 3.7%, respectively). Both the density area and the shunt increased after muscle paralysis. PEEP reduced the density area in all patients but did not consistently alter the shunt. It is concluded that the development of atelectasis in dependent lung regions is a major cause of gas exchange impairment during halothane anesthesia, during both spontaneous breathing and mechanical ventilation, and that PEEP diminishes the atelectasis, but not necessarily the shunt.
The long land grab: market-assisted enclosure on the China-Lao rubber frontier

ABSTRACT The rise in transnational land deals has brought nationally inflected concerns about foreign land acquisition into uneasy tension with longstanding scholarly and popular concerns about dispossession. Using the case of Chinese rubber plantation promotion projects in northern Laos, we examine the intersection of these two processes during the boom decade of the 2000s, as well as the aftermath during the 2010s, when global rubber prices have fallen. We describe a ‘long’ land grab from upland communities in northern Laos that cannot be blamed on either ‘the Chinese’ (whether private, state or both) or Lao government policy, which has long mobilized political and legal authority to enclose smallholder lands for national development. Rather, what is significant is the interaction of regulatory politics and market dynamics under conditions of both unequal international relations and internally competing policy agendas on both sides of the border. Examining a case where the initial regulatory impulse from the host government was for the protection of smallholder land tenure, the paper demonstrates the need to examine the interaction of local land governance and international relations in a way that treats the latter as the product of internal struggles rather than coherent national strategy.
Shadow Economy Worsens Income distribution

Shadow economy has many repercussions affecting most sectors of the economy. Our research question is how shadow economy affects income distribution. The contribution of the present paper is that if is found that shadow economy worsens income distribution. Our sample includes the following countries Austria, Belgium, Cyprus, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Sweden and UK. It becomes evident that, international accounting standards and international standards of auditing should be adopted by EU members to eliminate shadow economy, and thus promote not only economic growth but also political stability. The structure of this paper has as follows. Literature review will be presented in sector1. In sector 2 the econometric model will be analyzed and finally conclusions will be discussed in sector 3.
On Comparing Learning Disabled and Regular Classroom Children

Forty-seven studies, which compared normal and learning disabled children, were reviewed with a focus on the variability of performance within groups and the degree of overlap between LD and normal groups. The amount of variability of performance within LD and normal groups was similar and was approximately 75% of the variability of a randomly selected national sample. The average difference between the means of normal and LD groups was less than . 75 SD, or about one sixth the range of performance which existed within either group. Assuming normal distributions, this means that more than 23% of the LD children scored above the mean of the normal group in most of the studies reviewed. On the basis of this data, it was asserted that categorical claims about the etiology or education of LD children were unwarranted and that combining LD and regular classroom groups has a relatively small effect on the range of ability in the classroom.
Setting Expected Rates of Return on Pension Plan Assets: New Evidence on the Influence of Audit Committee Accounting Experts

This study examines whether having accounting experts on audit committees can mitigate the upward bias of expected rates of return (ERR) on pension plan assets documented in prior research. ERRs are found to be lower in firms with accounting expertise on their audit committees. These results are robust after controlling for variables from extant governance and pension research, and they suggest that audit committee accounting experts can help deter managers from setting higher ERRs on pension assets. While extant studies find that opportunistic setting of pension assumptions can be controlled through regulation, this paper provides new evidence on the influence of audit committee accounting experts on critical pension estimates. This newfound governance effect is different from and incremental to the regulation effect previously documented in the pension accounting literature.
Program Evaluation and the Venture Development Program at the University of Calgary: A Research Note

This study was designed to evaluate the programs offered by the Venture Development Group of the University of Calgary and to discuss the manner in which program evaluations are conducted. Results show that clients of the program have (1) grown faster than the average business in Alberta, (2) perceive that the program has added value to their ventures, (3) believe the programs have met most of their expectations, and (4) often implement the advice received. Discussion of program evaluation indicates that issues of causality, generalization, control measures, nonresponse bias, and evaluator bias are among the most pressing issues that must be addressed in designing more effective impact studies.
Cerebrolysin prevents deficits in social behavior, repetitive conduct, and synaptic inhibition in a rat model of autism

Autism spectrum disorder (ASD) is a syndrome of diverse neuropsychiatric diseases of growing incidence characterized by repetitive conduct and impaired social behavior and communication for which effective pharmacological treatment is still unavailable. While the mechanisms and etiology of ASD are still unknown, a consensus is emerging about the synaptic nature of the syndrome, suggesting a possible avenue for pharmacological treatment with synaptogenic compounds. The peptidic mixture cerebrolysin (CBL) has been successfully used during the last three decades in the treatment of stroke and neurodegenerative disease. Animal experiments indicate that at least one possible mechanism of action of CBL is through neuroprotection and/or synaptogenesis. In the present study, we tested the effect of CBL treatment (daily injection of 2.5 mL/Kg i.p. during 15 days) on a rat model of ASD. This was based on the offspring (43 male and 51 female pups) of a pregnant female rat injected with valproic acid (VPA, 600 mg/Kg) at the embryonic day 12.5, which previous work has shown to display extensive behavioral, as well as synaptic impairment. Comparison between saline vs. CBL‐injected VPA animals shows that CBL treatment improves behavioral as well as synaptic impairments, measured by behavioral performance (social interaction, Y‐maze, plus‐maze), maximal response of inhibitory γ‐amino butyric acid type A receptor (GABAAR)‐mediated synaptic currents, as well as their kinetic properties and adrenergic and muscarinic modulation. We speculate that CBL might be a viable and effective candidate for pharmacological treatment or co‐treatment of ASD patients. © 2017 Wiley Periodicals, Inc.
What does a diagnostic label of ‘polycystic ovary syndrome’ really mean in adolescence? a review of current practice recommendations

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, with many women initially presenting during adolescence. Diagnosis during this period is particularly challenging, yet many emphasize the importance of an early diagnosis given the long‐term metabolic and reproductive health consequences associated with the syndrome. The objective of this study was to review the current literature to determine whether the diagnostic label ‘PCOS’ is necessary to effectively manage adolescent girls presenting with features of the syndrome. A literature search was conducted (PubMed, Medline, Informit Health and the Cochrane Database of Systematic Reviews) identifying papers addressing the diagnosis and management of PCOS during adolescence. Articles were selected based on date of publication, relevance of material and the quality of evidence presented. A total of 427 papers were screened, with 40 of these selected from the initial search. A subsequent 154 were included from manual review of reference lists from key papers identified in the initial search. Current guidelines recommend treating the individual manifestations of PCOS. In doing so, there is good evidence identifying that this approach adequately targets the underlying metabolic and reproductive changes associated with the syndrome. This suggests that providing a diagnostic label of PCOS is not actually necessary to effectively manage adolescent girls with features of this syndrome.
Pharmacologic Inhibition of Phosphoinositide 3-Kinase Gamma (PI3Kγ) Promotes Infarct Resorption and Prevents Adverse Cardiac Remodeling After Myocardial Infarction in Mice

Background: Phosphoinositide 3-kinase gamma is upregulated in the heart during acute myocardial infarction (AMI) potentially contributing to the development and maintenance of heart failure. Methods: CD-1 male mice were randomly assigned to pharmacologic inhibition of phosphoinositide 3-kinase gamma using AS-605240 (10 mg/kg/day intraperitoneally) or vehicle (NaCl 0.9% + DMSO 25% solution) for 14 days after experimental AMI induced by surgical coronary artery ligation. Echocardiography was performed at baseline and 1, 7, 14, and 28 days after surgery to measure left ventricular dimensions and function. Infarct size was also measured at weekly intervals to evaluate for infarct resorption. Results: When compared with vehicle-treated mice over the 4-week period, animals treated with AS-605240 showed a smaller increase in left ventricular cavitary dimensions, a smaller decrease in left ventricular systolic function (P < 0.05), and a significant increase in posterior wall diastolic and systolic thickness reflective of compensatory hypertrophy (P < 0.05). Initial infarct size (measured at 24 hours) was not different comparing AS-605240 (29% ± 4%) and vehicle-treated mice (31% ± 1%, P = nonsignificant). At 4 weeks after AMI, infarct size was significantly smaller in the AS-605240-treated mice (14% ± 2%) compared with vehicle-treated mice (28% ± 3%, P < 0.001), reflecting greater infarct resorption. Conclusions: Phosphoinositide 3-kinase gamma inhibition with AS-605240 after AMI leads to enhanced infarct resorption, greater compensatory hypertrophy of the nonischemic myocardium, and more favorable cardiac remodeling and function.
Nitric oxide mediates stretch-induced Ca2+ oscillation in smooth muscle

ABSTRACT The stretching of smooth muscle tissue modulates contraction through augmentation of Ca2+ transients, but the mechanism underlying stretch-induced Ca2+ transients is still unknown. We found that mechanical stretching and maintenance of mouse urinary bladder smooth muscle strips and single myocytes at 30% and 18% beyond the initial length, respectively, resulted in Ca2+ oscillations. Experiments indicated that mechanical stretching remarkably increased the production of nitric oxide (NO) as well as the amplitude and duration of muscle contraction. Stretch-induced Ca2+ oscillations and contractility increases were completely abolished by the NO inhibitor L-NAME or eNOS (also known as NOS3) gene inactivation. Moreover, exposure of eNOS-knockout myocytes to exogenous NO donor induced Ca2+ oscillations. The stretch-induced Ca2+ oscillations were greatly inhibited by the selective inositol 1,4,5-trisphosphate receptor (IP3R) inhibitor xestospongin C and partially inhibited by ryanodine. Moreover, the stretch-induced Ca2+ oscillations were also suppressed by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002, but not by the soluble guanylyl cyclase (sGC) inhibitor ODQ. These results suggest that stretching myocyte and maintenance at a certain length results in Ca2+ oscillations that are NO dependent , and sGC and cGMP independent, and results from the activation of PI3K in smooth muscle. Summary: Stretching of myocytes and maintenance at the stretched length results in a Ca2+ oscillation that is dependent on NO, but not on soluble guanylyl cyclase (sGC) or cGMP. This results from the activation of PI3K.
Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors.

BACKGROUND The idiotypic determinants of the surface immunoglobulin of a B-cell lymphoma can serve as a clonal tumor-specific marker, which may have implications for immunotherapy. We sought to determine whether idiotype-specific immune responses against this autologous antigen could be induced in patients with B-cell lymphoma. METHODS Nine patients were selected who had minimal residual disease or a complete remission after chemotherapy. Each received a series of subcutaneous injections of the immunoglobulin derived from his or her tumor cells (immunoglobulin-idiotype protein), which had been conjugated to a protein carrier and mixed with an immunologic adjuvant. RESULTS In seven of the nine patients the injections induced sustained idiotype-specific immunologic responses of the humoral type (two patients), the cell-mediated type (four patients), or both (one patient). The use of an adjuvant was essential for these immune responses. The induced antibodies bound specifically to autologous immunoglobulin idiotype, inhibited the binding of murine monoclonal antiidiotype antibodies, and bound autologous tumor cells. Cell-mediated responses were demonstrated by the specific proliferation of immune peripheral-blood mononuclear cells to the soluble immunoglobulin-idiotype protein in vitro. The tumors of both of the patients with measurable disease regressed completely. Toxicity associated with the vaccine was minimal and consisted only of mild reactions at the site of intramuscular injection. CONCLUSIONS These results demonstrate that autologous immunoglobulin idiotype can be formulated into an immunogenic, tumor-specific antigen in humans with B-cell lymphoma, and they provide the background for large-scale trials of active specific immunotherapy of this disease.
Chemoprevention of rat mammary carcinogenesis by black tea polyphenols: Modulation of xenobiotic‐metabolizing enzymes, oxidative stress, cell proliferation, apoptosis, and angiogenesis

Chemoprevention of dietary constituents has emerged as a cost‐effective approach to control the incidence of breast cancer. The present study was therefore designed to evaluate the chemopreventive efficacy of black tea polyphenols (Polyphenon‐B) during the preinitiation phase of 7,12‐dimethylbenz[a]anthracene (DMBA) induced mammary carcinogenesis using xenobiotic‐metabolizing enzymes, cellular redox status, cell proliferation, apoptosis, and angiogenesis as biomarkers of chemoprevention. Intragastric administration of DMBA induced adenocarcinomas that showed enhanced activities of phase I carcinogen activation and phase II detoxification enzymes with increased lipid and protein oxidation and decrease in antioxidant status. This was associated with increased cell proliferation, angiogenesis, and evasion of apoptosis as revealed by upregulation of proliferating cell nuclear antigen (PCNA), Bcl‐2, and vascular endothelial growth factor (VEGF), and downregulation of Bax, caspase 3, and poly(ADP‐ribose) polymerase (PARP). Dietary administration of Polyphenon‐B effectively suppressed the incidence of mammary tumors as evidenced by modulation of xenobiotic‐metabolizing enzymes and oxidant–antioxidant status, inhibition of cell proliferation and angiogenesis, and induction of apoptosis. The present study provides evidence that Polyphenon‐B exerts multifunctional inhibitory effects on DMBA‐induced mammary carcinogenesis and suggests that it can be developed as a potential chemopreventive agent. © 2007 Wiley‐Liss, Inc.