Miracle-dz/UniFAR-FTUs huggingface dataset:
Oral available agents in the treatment of relapsing remitting multiple sclerosis: an overview of merits and culprits

Multiple sclerosis (MS) is a chronic immunological disease of the central nervous system characterized by early inflammatory demyelination and subsequent neurodegeneration. Major therapeutic progress has occurred during the past decade, in particular since the introduction of immunomodulatory agents, however, MS is still an incurable disease. In addition, parenteral application of the currently licensed drugs is associated with injection-related adverse events (AEs) and low patient compliance. Thus, there remains an unmet need for the development of more effective and well tolerated oral therapies for the treatment of MS. A number of new orally administered agents including fingolimod, laquinimod, teriflunomide, cladribine, and BG-12 have been licensed recently or are currently under investigation in relapsing remitting MS patients. In multi-center, randomized, placebo-controlled phase III clinical studies, all of these agents have already shown their efficacy on both clinical disease parameters and magnetic resonance imaging-based measures of disease activity in patients with relapsing remitting MS. However, there are essential differences concerning their clinical efficacy and side-effect profiles. Additionally, the mechanisms by which these substances exert clinical efficacy have not been fully elucidated. In this article, we review the pharmaceutical properties of fingolimod, laquinimod, teriflunomide, cladribine, and BG-12; and their suggested mechanisms of action, clinical efficacy, and side-effect profiles.
Associations of Phthalates and Phthalate Replacements With CRH and Other Hormones Among Pregnant Women in Puerto Rico

Abstract Context Phthalates are endocrine-disrupting chemicals that may be associated with adverse birth outcomes. Dysregulation of maternal endocrine homeostasis could be a possible biological pathway between phthalates and birth outcomes. Objective Examine associations between 19 maternal urinary phthalate or phthalate replacement metabolites and 9 serum hormones measured over two time points during pregnancy. Design Longitudinal study conducted in the PROTECT pregnancy cohort. Setting Puerto Rico. Patients Six hundred seventy-seven women in the first trimester of pregnancy. Main Outcome Measures Serum CRH, estriol, SHBG, progesterone, TSH, total T3, free T4, total T4, and testosterone. Results T3 was significantly associated with most metabolites. CRH was inversely associated with mono carboxyisononyl phthalate [MCNP; percent change (%Δ), −4.08; 95% CI, −7.24, −0.804], mono-3-carboxypropyl phthalate (MCPP; %Δ, −5.25; 95% CI, −8.26, −2.14), mono-2-ethyl-5-carboxypentyl phthalate (MECPP; %Δ, −18.4; 95% CI, −30.4, −4.37), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; %Δ, −13.4; 95% CI, −22.7, −2.92), and mono-2-ethyl-5-oxohexyl phthalate (MEOHP; %Δ, −12.7; 95% CI, −22.2, −2.20). Positive associations were found between numerous phthalate metabolites and free T4, T4, and the T3/T4 ratio. Testosterone was positively associated with mono hydroxybutyl phthalate (MHBP; %Δ, 4.71; 95% CI, 0.27, 9.35) and inversely associated with monoethyl phthalate (MEP; %Δ, −14.5; 95% CI, −24.3, −3.42), and relationships with MCNP and mono carboxyisooctyl phthalate (MCOP) were significantly modified by study visit. Finally, an inverse association was found between mono-2-ethyl-5-hydrohexyl terephthalate (MEHHTP), a terephthalate metabolite, and progesterone at visit 3 only (%Δ, −13.1; 95% CI, −22.3, −2.75). Conclusions These results indicate that exposure to phthalates may differentially impact the maternal endocrine system at different points during pregnancy, and that exposures to phthalate replacement chemicals may be particularly important to consider in future human health studies.
Magnetic Properties of Fe Doped, Co Doped, and Fe+Co Co-Doped ZnO

The structural, electronic, and magnetic properties of Zn0.95Co0. 05O, Zn0.95Fe0. 05O, and Zn0.90Fe0. 05Co0.05O nanoparticles prepared by a sol-gel method are presented and discussed. X-ray diffraction and optical analysis indicated that high spin Co2+ ions substitute for the Zn2+ ions in tetrahedral sites. 57Fe Mossbauer spectroscopy showed the presence of isolated paramagnetic Fe3+ ions in both Fe doped and Fe+Co co-doped ZnO, however, no evidence of ferromagnetically ordered Fe3+ ions is observed. In the Zn0.95Fe0. 05O sample, weak presence of ZnFe2O4 was detected as an impurity phase, whereas Zn0.90Fe0. 05Co0.05O was impurity-free within detection limit in all those measurements. Results of these studies suggest that Fe and Co ions in the Fe+Co co-doped sample has a strong synergistic effect because they eliminated the presence of impurities and gave the strongest ferromagnetic signal. Possible role of charge transfer ferromagnetism involving mixed valence ions is considered as a potential mechanism in the.
Malnutrition-Wasting Conditions in Older Dialysis Patients: An Individualized Approach.

BACKGROUND The dialysis population is growing and aging worldwide. The aging dialysis population exhibits specific conditions, including sarcopenia, protein-energy wasting, and frailty, that are associated with worse outcomes. Thus, strategies to address these conditions are indispensable to improving prognosis, quality of life, and ability to perform activities of daily living in older patients. SUMMARY Several strategies have been employed to manage these conditions. The two major approaches are nutritional therapy and exercise training. These correlate strongly with each other and each is necessary to maintain the health of patients. Ensuring adequate protein and energy intake is the mainstay of nutritional therapy. However, older dialysis patients often have reduced appetite, and appropriate nutritional therapy can enhance appetite. Conversely, nutritional therapy without an appropriate exercise training system will fail to enhance physical function. Thus, the focus of attention has been on exercise training both during dialysis treatment and while at home. The Japanese Society of Renal Rehabilitation has issued a guideline for exercise training in patients with kidney disease. It encourages using the time during dialysis treatment for performing both nutritional intake measures and exercise training. Nutritional care in dialysis patients has previously focused on restriction of dietary intake. However, patients with these malnutrition-wasting conditions should be encouraged to improve their dietary intake and physical activity. Older dialysis patients have heterogenic characteristics in terms of frailty, so their nutritional and exercise plans should be individualized. Key Messages: Individualized management should be used in the heterogeneous older dialysis population, with special considerations for malnutrition-wasting conditions.
Maslinic Acid-Enriched Diet Decreases Intestinal Tumorigenesis in ApcMin/+ Mice through Transcriptomic and Metabolomic Reprogramming

Chemoprevention is a pragmatic approach to reduce the risk of colorectal cancer, one of the leading causes of cancer-related death in western countries. In this regard, maslinic acid (MA), a pentacyclic triterpene extracted from wax-like coatings of olives, is known to inhibit proliferation and induce apoptosis in colon cancer cell lines without affecting normal intestinal cells. The present study evaluated the chemopreventive efficacy and associated mechanisms of maslinic acid treatment on spontaneous intestinal tumorigenesis in ApcMin/+ mice. Twenty-two mice were randomized into 2 groups: control group and MA group, fed with a maslinic acid–supplemented diet for six weeks. MA treatment reduced total intestinal polyp formation by 45% (P<0.01). Putative molecular mechanisms associated with suppressing intestinal polyposis in ApcMin/+ mice were investigated by comparing microarray expression profiles of MA-treated and control mice and by analyzing the serum metabolic profile using NMR techniques. The different expression phenotype induced by MA suggested that it exerts its chemopreventive action mainly by inhibiting cell-survival signaling and inflammation. These changes eventually induce G1-phase cell cycle arrest and apoptosis. Moreover, the metabolic changes induced by MA treatment were associated with a protective profile against intestinal tumorigenesis. These results show the efficacy and underlying mechanisms of MA against intestinal tumor development in the ApcMin/+ mice model, suggesting its chemopreventive potential against colorectal cancer.
Experimental Abdominal Aortic Aneurysms in Mice Lacking Expression of Inducible Nitric Oxide Synthase

To determine if nitric oxide synthase (NOS) contributes to the pathophysiology of abdominal aortic aneurysms (AAAs), C57BL/6J mice underwent transient aortic injury to induce a chronic inflammatory response. Wild-type mice developed a significant increase in aortic diameter within 14 days of elastase perfusion (115±16%, 40% incidence of AAAs), along with intense and widespread staining for nitrotyrosine, mononuclear inflammation, and delayed destruction of the elastic lamellae. Expression of both endothelial and neuronal forms of NOS was substantially decreased within AAAs, whereas inducible NOS (iNOS) mRNA was increased 360%, and the enzyme was localized to infiltrating inflammatory cells. By using mice with targeted deletion of iNOS to evaluate the functional importance of this enzyme, male iNOS−/− mice developed the same extent of aneurysmal dilatation as congenic controls (121±22%, 40% incidence of AAAs) and exhibited similar structural features except for diminished nitrotyrosine staining. Aneurysmal dilatation was actually enhanced in female iNOS−/− mice (141±16%, 80% incidence of AAAs;P <0.05), but this effect was reversed by previous oophorectomy. Although extensive protein nitration and increased expression of iNOS accompany the development of elastase-induced experimental AAAs, iNOS is not required in this process and its absence may be deleterious.
The sensitivity of the premature infant pain profile - PIPP to measure pain in hospitalized neonates.

AIM The present study uses an Icelandic translation of the original version of the Premature Infant Pain Profile (PIPP) in order to assess its accuracy and sensitivity to the measure of pain in hospitalized neonates in Iceland. The PIPP is a composite tool developed to assess acute pain in preterm and term neonates. METHODS A crossover design, with a sample of 24 neonates, was used on three, routinely occurring events in the neonatal intensive care unit, where neonates were their own controls. The three events were baseline, non-pain and pain event. Neonates were independently assessed for their pain, using the Icelandic translation of the PIPP, at the bedside. RESULTS Repeated measures analysis yielded a statistically significant main effect for the three events (pain, non-pain and baseline), thus differentiating pain from non-pain and baseline events (F = 57.11; P < 0.0001). Pair-wise comparisons were subsequently carried out and the results show that PIPP scores at the pain event (11.72) were significantly lower (P < 0.0001) than that at the non-pain event (6.04) and that at the baseline event (3.54; P < 0.0001). The PIPP scores at the non-pain event were also significantly higher than that at the baseline event (P < 0.0001). These results suggest that the PIPP measure is sensitive to a painful event and differentiates between stress and pain in a clinical context across linguistic barriers. The findings also revealed almost a complete correlation between the PIPP scores of the two independent nurse raters at all events (P < 0.0001). CONCLUSION Therefore the authors conclude that the Icelandic translation of the PIPP qualifies as a satisfying measure of pain responses in Icelandic neonates and can be recommended for use by clinicians and researchers. More research is, however, needed to further the accuracy and validity of the PIPP measure in general to assess pain in neonates in comparison to other pain measures.
Systemic Autoimmune Diseases: Not So Rare in Black Africans

Conventional beliefs and some publications, had in the past, asserted that systemic auto - immune diseases such as inflammatory arthritis, connective tissue diseases and vasculitis are rare. Many of such reports had been hospital based and were not based on the ACR criteria. Rheumatoid arthritis was reported as being rare, especially among West Africans; so also Systemic Lupus Erythematosus, Scleroderma and Inflammatory myopathies. Even rarer are the Vasculitis. However, increasing reportage of these conditions may indicate that these conditions do occur, although under reported. As efforts are being made to overcome acute and chronic infections such as Malaria, Tuberculosis, chronic debilitating diseases such as arthritis and cancers may rear their head
Intravenous delivery of the toll-like receptor 7 agonist SC1 confers tumor control by inducing a CD8+ T cell response

ABSTRACT TLR7 agonists are considered promising drugs for cancer therapy. The currently available compounds are not well tolerated when administered intravenously and therefore are restricted to disease settings amenable for topical application. Here we present the preclinical characterization of SC1, a novel synthetic agonist with exquisite specificity for TLR7. We found that intravenously administered SC1 mediates systemic release of type I interferon, but not of proinflammatory cytokines such as TNFα and IL6, and results in activation of circulating immune cells. Tumors of SC1-treated mice have brisk immune cell infiltrates and are polarized towards a Th1 type signature. Intratumoral CD8+ T cells and CD11b+ conventional dendritic cells (cDCs) are significantly increased, plasmacytoid dendritic cells (pDCs) are strongly activated and macrophages are M1 phenotype polarized, whereas myeloid-derived suppressor cells (MDSCs) are decreased. We further show that treatment of mice with SC1 profoundly inhibits the growth of established syngeneic tumors and results in significantly prolonged survival. Mice, which are tumor-free after SC1 treatment are protected from subsequent tumor rechallenge. The antitumor effect of SC1 depends on antigen-specific CD8+ T cells, which we found to be strongly enriched in the tumors of SC1-treated mice. In conclusion, this study shows that systemically administered SC1 mobilizes innate and adaptive immunity and is highly potent as single agent in mice and thereby provides a rationale for clinical testing of this compound.
Cardiovascular effects of 2, 5-dimethoxy-4-methylamphetamine (DOM, STP).

A single dose of 2,5-dimethoxy-4-methylamphetamine (DOM) (246 µg/kg) produced a pressor response in vagotomized dogs. There was also an increase in pulse pressure. Tachyphylaxis developed rapidly after repeated doses of DOM. Responses to tyramine were not diminished after tachyphylaxis to DOM developed. DOM also enhanced pressor responses to norepinephrine, epinephrine and tyramine. In perfused dog fore limb DOM produced a vasodilation followed by a vasoconstriction. The vasoconstriction produced by DOM was not blocked by phentolamine but was antagonized by methysergide. In isolated superfused vascular strips of dog dorsal metatarsal vein, DOM elicited a muscle contraction which was not blocked by phentolamine or cocaine but was antagonized by cinanserin. It was concluded that DOM had a direct stimulatory effect on serotonin receptors. The vasodilation in the perfused fore limb of the dog induced by DOM was not antagonized by propranolol, atropine, pyrilamine or bulbocapnine. In isolated guinea-pig atria, DOM exhibited an antiicotine action and also blocked the inhibitory effect induced by vagus nerve stimulation.
On the Accuracy of the GN-Model and on Analytical Correction Terms to Improve It

The GN-model has been proposed as an approximate but sufficiently accurate tool for predicting uncompensated optical coherent transmission system performance, in realistic scenarios. For this specific use, the GN-model has enjoyed substantial validation, both simulative and experimental. Recently, however, it has been pointed out that its predictions, when used to obtain a detailed picture of non-linear interference (NLI) noise accumulation along a link, may be affected by a substantial NLI overestimation error, especially in the first spans of the link. In this paper we analyze in detail the GN-model errors. We discuss recently proposed formulas for correcting such errors and show that they neglect several contributions to NLI, so that they may substantially underestimate NLI in specific situations, especially over low-dispersion fibers. We derive a complete set of formulas accounting for all single, cross, and multi-channel effects, this set constitutes what we have called the enhanced GN-model (EGN-model). We extensively validate the EGN model by comparison with accurate simulations in several different system scenarios. The overall EGN model accuracy is found to be very good when assessing detailed span-by-span NLI accumulation and excellent when estimating realistic system maximum reach. The computational complexity vs. accuracy trade-offs of the various versions of the GN and EGN models are extensively discussed.
Advanced gastric cancer in jordan from 2004 to 2008: a study of epidemiology and outcomes.

BACKGROUND WE REPORT THE EPIDEMIOLOGIC FEATURES AND THE TREATMENT EXPERIENCE OF ADVANCED GASTRIC CANCER (GC) AT KING HUSSEIN CANCER CENTER (KHCC) IN JORDAN, AND WE RETROSPECTIVELY COMPARE OUTCOMES OF TWO DIFFERENT REGIMENS: DCF (docetaxel/cisplatin/5-fluorouracil) vs. ECF (epirubicin/cisplatin/5-fluorouracil). METHODS Charts of 162 patients with inoperable GC treated between January 2004 and December 2008 were reviewed. A total 143 patients received chemotherapy (ECF = 113; DCF = 30). Choice of regimen was changed from ECF to DCF on January 2008 according to KHCC guidelines. RESULTS The median patient age was 59 years, with a male:female ratio of 1.8:1. Lymph nodes (67.9%) and liver (49.4%) were the most common sites of metastasis. Primary disease site was stomach in 78.4%, gastroesophageal junction in 16.7%, lower esophagus in 4.9%. Poorly differentiated histology was predominant (46.9%). Anemia (53.7%), pain (48.1%), and reflux (44.4%) were the most common presenting symptoms. Helicobacter pylori infection was present in 79%. Average time between initial symptom and diagnosis was 6.0 months. The overall response rate (ORR) was 59.3% with DCF and 32.6% with ECF (P = .01). Time to tumor progression (TTP) was 6.9 months with DCF and 5.9 months with ECF (P = .005). Median survival was 11.0 months with DCF and 10.2 months with ECF (P = .17). CONCLUSION Some epidemiologic features of GC in Jordan mimic those of high-risk areas. Our outcomes of chemotherapy are comparable to internationally reported data and suggest superiority of DCF over ECF in terms of ORR and TTP.
Adult Epiglottitis in a Canadian Setting

The objective of this study was to determine stable estimates of the incidence, case fatality, and epidemiologic features of adult epiglottitis, and risk factors for intubation. The authors designed a retrospective cohort combined with a nested casecontrol study, followed by detailed analysis of cases from two tertiary care institutions. Among 813 cases, the incidence was 2.02 cases/105 population per year. Ten recorded deaths constituted a case fatality rate of 1.2% (95% confidence interval [CI]: 0.5% to 1.9%). The eight fully documented deaths indicated no sudden episodes of catastrophic upper airway obstructions without previous dyspnea. A detailed review of 51 cases revealed that 18% of patients underwent expeditious intubation. Patients managed without initially requiring intubation did not need emergency airway interventions. Only the presence of dyspnea (noted in 29% of patients) at the time of admission ( P < 0.001) predicted the need for intubation. A low case fatality rate in a conservatively managed cohort and the absence of sudden upper airway catastrophes in patients without dyspnea suggest that prophylactic intubation and intensive care unit monitoring is not warranted in all patients. An early complaint of dyspnea may safely discriminate between patients requiring invasive airway management and close observation.
Corticosterone rapidly increases thorns of CA3 neurons via synaptic/extranuclear glucocorticoid receptor in rat hippocampus

Modulation of synapses under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. We tried to test whether rapid CORT effects involve activation of essential kinases as non-genomic processes. We demonstrated rapid effects (~1 h) of CORT on the density of thorns, by imaging Lucifer Yellow-injected neurons in adult male rat hippocampal slices. Thorns of thorny excrescences of CA3 hippocampal neurons are post-synaptic regions whose presynaptic partners are mossy fiber terminals. The application of CORT at 100, 500, and 1000 nM induced a rapid increase in the density of thorns in the stratum lucidum of CA3 pyramidal neurons. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, including MAPK, PKA, or PKC, suppressed CORT-induced enhancement of thorn-genesis. On the other hand, GSK-3β was not involved in the signaling of thorn-genesis. Blocking AMPA receptors suppressed the CORT effect. Expression of CA3 synaptic/extranuclear GR was demonstrated by immunogold electron microscopic analysis. From these results, stress levels of CORT (100–1000 nM) might drive the rapid thorn-genesis via synaptic/extranuclear GR and multiple kinase pathways, although a role of nuclear GRs cannot be completely excluded.
Optoelectronic Capillary Sensors in Microfluidic and Point-of-Care Instrumentation

This paper presents a review, based on the published literature and on the authors’ own research, of the current state of the art of fiber-optic capillary sensors and related instrumentation as well as their applications, with special emphasis on point-of-care chemical and biochemical sensors, systematizing the various types of sensors from the point of view of the principles of their construction and operation. Unlike classical fiber-optic sensors which rely on changes in light propagation inside the fiber as affected by outside conditions, optical capillary sensors rely on changes of light transmission in capillaries filled with the analyzed liquid, which opens the possibility of interesting new applications, while raising specific issues relating to the construction, materials and instrumentation of those sensors.