Dendritic-Cell (DC)-Based Immunotherapy: Tumor Endothelial Marker 8 (TEM8) Gene Expression of DC Vaccines Correlates with Clinical Outcome

ABSTRACT\ud Previous studies have shown that tumor-endothelial markers (TEMs) are upregulated in immunosuppressive, pro-angiogenic dendritic cells (DCs) found in tumor microenvironments. \ud We reported that pro-angiogenic monocyte-derived DCs (Mo-DCs), utilized for therapeutic vaccination of cancer patients upon maturation, markedly differ in their ability to up-regulate tumor-endothelial marker 8 (TEM8) gene\ud expression. A DC vaccination trial of 17 advanced cancer patients (13 melanoma and 4 renal cell carcinoma), carried out at the Cancer Institute of Romagna (I.R.S.T.) in Meldola, highlighted a significant correlation between delayed-type hypersensitivity test (DTH) and overall survival (OS). In the study, relative TEM8 mRNA and protein expression levels (mature (m) vs. immature (i) DCs), in DCs obtained for therapeutic vaccines were evaluated by quantitative real-time RT-PCR and cytofluorimetric analysis, respectively. mDCs from six healthy donors were included for comparison purposes. Eight non-progressing patients, all DTH-positive, had a mean fold increase\ud (mfi) of 1.97 in TEM8 expression. Similarly, a TEM8 mRNA mfi = 2.7 was found in healthy donor mDCs. Conversely, mDCs from nine progressing patients, all but one with negative DTH, had a TEM8 mRNA mfi of 12.88. Thus, mDC TEM8 expression levels would seem to identify (p = 0.0018) patients who could benefit from DC therapeutic vaccination

Do Recommendations for the Management of Hypertension Improve Cardiovascular Outcome? The Canadian Experience

The Canadian Hypertension Education Program (CHEP) was established in 1999 as a response to the result of a national survey that showed that a high percentage of Canadians were unaware of having hypertension with only 13% of those treated for hypertension having their blood pressure controlled. The CHEP formulates yearly recommendations based on published evidence. A repeat survey in 2006 showed that the percentage of treated hypertensive patients with the blood pressure controlled had risen to 65.7%. Over the first decade of the existence of the CHEP, the number of prescriptions for antihypertensive medications had increased by 84.4% associated with a significant greater decline in the yearly mortality from stroke, heart failure and myocardial infarction and a significant decrease in the hospitalization for stroke and heart failure. Therefore, the introduction of the CHEP and the yearly issue of updated recommendations resulted in a significant increase in the awareness, diagnosis and treatment of hypertension and in a significant reduction in stroke and cardiovascular morbidity and mortality. The CHEP model could serve as a template for its adoption to other regions or countries

A grammar of Tadaksahak a northern Songhay language of Mali

This dissertation is a descriptive grammar of the language Tadaksahak spoken by about 30,000 people living in the most eastern part of Mali. The four chapters of the book give 1. Information about the background of the group. 2. The phonological features of the language with the inventory of the phonemes and the observed sound rules. 3. The description of the morphology. It is shown that verbal derivation pulls on unrelated Tamasheq for causative, reciprocal and middle as well as passive. In addition, any verb root that is of Songhay origin is suppleted when derived and a semantic equivalent of Tamasheq origin takes its place. Another non-Songhay feature concerns inflection where the subject pronoun cliticizes to the verb and is always present even when a noun phrase holds the subject slot. The nominalization strategy used depends on the etymology of the term, a feature paralleled in the formation of adjectives. 4. Basic syntax. Noun phrases, simple clauses, focalization and topicalization, question words with their syntax, complement clauses and the two possible relativization strategies as well as subordinate clauses are described. The appendixes provide texts with glosses, lists of verb roots with their suppletions when derived, and two differently organized wordlists.LEI Universiteit LeidenNWO (Netherlands Organization for Scientific Research) research project “Tuareg and the Central Sahelian Languages, A History of Language Contact”Language Use in Past and Presen

Zn–al layered double hydroxides synthesized on aluminum foams for fluoride removal from water

Fluoride excess in water represents an environmental issue and a risk for human health since it can cause several diseases, such as fluorosis, osteoporosis, and damage of the nervous system. Layered double hydroxides (LDHs) can be exploited to remove this contaminant from water by taking advantage of their high ion-exchange capability. LDHs are generally mixed with polluted water in the form of powders, which then cause the problem of uneasy separation of the contaminated LDH sludge from the purified liquid. In this work, Zn–Al LDH films were directly grown in situ on aluminum foams that acted both as the reactant and substrate. This method enabled the removal of fluoride ions by simple immersion, with ensuing withdrawal of the foam from the de-contaminated water. Different LDH synthesis methods and aluminum foam types were investigated to improve the adsorption process. The contact time, initial fluoride concentration, adsorbent dosage, and pH were studied as the parameters that affect the fluoride adsorption capacity and efficiency. The highest absorption efficiency of approximately 70% was obtained by using two separate growth methods after four hours, and it effectively reduced the fluoride concentration from 3 mg/L to 1.1 mg/L, which is below the threshold value set by WHO for drinking water

Patient-level meta-analysis of the EDITION 1, 2 and 3 studies : glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes

AimsTo conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively. MethodsThe EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249). ResultsNo significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each -1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) -0.08 to 0.07)%]. Annualized rates of confirmed (3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with 1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low ( ConclusionGla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia.Peer reviewe

Cr segregation and impact fracture in a martensitic stainless steel

The fracture surfaces of a 10.5 wt.% Cr martensitic stainless steel broken in Charpy tests have been investigated through X-ray photoelectron spectroscopy (XPS). The specimens have been examined in two different conditions: as-quenched and heat treated for 10 h at 700°C. The trends of Fe/Cr ratio vs. test temperature are similar to the sigmoidal curves of absorbed energy and, after both ductile and quasi-cleavage brittle fractures, such ratio is always significantly lower than the nominal value of the steel chemical composition. Cr segregation does not occur on a macroscopic scale but takes place in microscopic zones which represent weaker spots in the steel matrix and a preferred path for moving cracks. Small area (diameter 300 μm) XPS measurements evidenced a higher density of such microscopic zones in the inner part of probes; this is explained by the different diffusion length of Cr atoms in the external and inner parts during quenching from austenitic field which has been calculated through FEM simulations. No significant differences of Cr concentration were observed in fracture surfaces of probes with and without heat treatment. The results highlight how Cr segregation plays a role not only in the intergranular mode of fracture but also in the quasi-cleavage and ductile ones

Calcium antagonist induced vasodilation in peripheral, coronary and cerebral vasculature as important factors in the treatment of elderly hypertensives

Increased arteriolar tone is the pathophysiological hallmark of essential hypertension and is determined by the intracellular free calcium concentration in the vascular smooth muscle cell. Calcium influx is an important determinant of vasoconstriction and excess calcium influx-dependent vasoconstriction has been shown by plethysmographical studies in patients with essential hypertension. Calcium antagonists acutely lower BP by reducing calcium influx, calcium concentration and peripheral resistance. The degree of the attendant sympathetic nerve reflex activation and counter-regulatory mechanisms determines the antihypertensive response of the individual. Chronic monotherapy with a calcium antagonist results in an antihypertensive response, which is directly related to the patient's age and pretreatment BP and indirectly related to plasma renin levels. The resulting reduction in after-load neither leads to reduced cerebral blood flow in hypertensive patients, nor aggravates congestive heart failure. Calcium antagonists are a useful alternative to diuretics, primarily in older patients with low renin levels, either alone or combined with any other antihypertensive drug, and provide effective and safe control of blood pressur

Two different acid oxidation syntheses to open C60 fullerene for heavy metal detection

Graphene oxide quantum dots (GOQDs) can be synthesized through a large variety of synthesis methods starting from different carbon allotropes such as nanotubes, graphite, C60 and exploiting various synthesis and reactions. These different approaches have great influence on the properties of the obtained materials, and, consequently, on the potential applications. In this work, Buckminster C60 fullerene has been used to prepare unfolded fullerene nanoparticles (UFNPs) via two distinct synthesis methods namely: Hummer and H2 SO4 + HNO3 solution. The different characteristics of the final materials and the different response in the presence of heavy metal ions have been investigated in view of sensing applications of water contamination

Morning administration of 0.4 U/kg/day insulin glargine 300 U/mL provides less fluctuating 24-hour pharmacodynamics and more even pharmacokinetic profiles compared with insulin degludec 100 U/mL in type 1 diabetes

Abstract Aim To compare steady state pharmacodynamic and pharmacokinetic profiles of insulin glargine 300U/mL (Gla-300) with insulin degludec 100U/mL (Deg-100) in people with type 1 diabetes. Methods This single-centre, randomized, double-blind crossover euglycaemic clamp study included two parallel cohorts with fixed once-daily morning dose regimens. For both insulins participants received 0.4 ( n =24) or 0.6U/kg/day ( n =24), before breakfast, for 8 days prior to the clamp. The main endpoint was within-day variability (fluctuation) of the smoothed glucose infusion rate (GIR) over 24 hours (GIR-smFL 0–24 ). Results Gla-300 provided 20% less fluctuation of steady state glucose infusion rate profiles than Deg-100 over 24 hours at 0.4U/kg/day (GIR-smFL 0–24 treatment ratio 0.80 [90% confidence interval: 0.66 to 0.96], P =0.047), while at the dose of 0.6U/kg/day the difference between insulins was not statistically significant (treatment ratio 0.96 [0.83 to 1.11], P =0.603). Serum insulin concentrations appeared more evenly distributed with both dose levels of Gla-300 versus the same doses of Deg-100, as assessed by relative 6-hour fractions of the area under the curve within 24 hours. Both insulins provided exposure and activity until 30 hours (end of clamp). Conclusion Gla-300 provides less fluctuating steady state pharmacodynamic profiles (i.e. lower within-day variability) and more evenly distributed pharmacokinetic profiles, compared with Deg-100 in a once-daily morning dosing regimen of 0.4U/kg/day