Highlights • Pharmacy compounding is an integral part of the modern health care system. • Pharmacy compounding legislation requires harmonization among European countries. • Quality assurance and ...standards for pharmacy compounding have to be defined.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We evaluated whether anserine, a methylated analog of the dipeptide carnosine, is present in the cardiac and skeletal muscles of humans and whether the CARNMT1 gene, which encodes the anserine ...synthesizing enzyme carnosine‐N‐methyltransferase, is expressed in human skeletal muscle. We found that anserine is present at low concentrations (low micromolar range) in both cardiac and skeletal muscles, and that anserine content in skeletal muscle is ~15 times higher than in cardiac muscle (cardiac muscle: 10.1 ± 13.4 μmol·kg−1 of dry muscle, n = 12; skeletal muscle: 158.1 ± 68.5 μmol·kg−1 of dry muscle, n = 11, p < 0.0001). Anserine content in the heart was highly variable between individuals, ranging from 1.4 to 45.4 μmol·kg−1 of dry muscle, but anserine content was not associated with sex, age, or body mass. We also showed that CARNMT1 gene is poorly expressed in skeletal muscle (n = 10). This is the first study to demonstrate that anserine is present in the ventricle of the human heart. The presence of anserine in human heart and the confirmation of its expression in human skeletal muscle open new avenues of investigation on the specific and differential physiological functions of histidine dipeptides in striated muscles.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Leishmania (L.) infantum is one of the main causative agents of animal and human leishmaniasis across many endemic areas in South America, Europe, North Africa, and Asia. Despite its clinical ...significance, little is known about the genetic diversity of L. infantum circulating in a given endemic area. Here, we investigate this important open question by applying a comparative genomics approach to seven L. infantum isolates from different hosts and Italian regions, including the northern part of the country (Emilia-Romagna, RER), Sicily, and Sardinia, as an initial attempt to explore the breadth of parasite genetic heterogeneity in Italy. Additionally, microsatellite analysis was carried out to compare the isolates from RER with other 70 L. infantum strains from the same region as well as 65 strains belonging to the L. donovani complex from other countries. We revealed important karyotypic instability and identified strain-specific changes in gene dosage, which affected important virulence factors such as amastins and surface antigen-like proteins. Single nucleotide polymorphism-based clustering analysis of these genomes together with over 80 publicly available L. infantum and L. donovani genomes placed the Italian isolates into three geographically distinct clusters within the Mediterranean basin and uncovered three isolates clustering with putative L. infantum/L. donovani hybrids isolated in Cyprus. As judged by microsatellite profiling, these hybrid isolates are representative of a sub-population of parasites circulating in northern Italy that preferentially infect humans but not dogs. Our results place Italy at the crossroads of L. infantum infection in the Mediterranean and call attention to the public health risk represented by the introduction of non-European Leishmania species.IMPORTANCEThis study closes important knowledge gaps with respect to Leishmania (L.) infantum genetic heterogeneity in a given endemic country, as exemplified here for Italy, and reveals genetic hybridization as a main cause for re-emerging human leishmaniasis in northern Italy. The observed high diversity of Leishmania parasites on the Italian peninsula suggests different geographical origins, with genomic adaptation to various ecologies affecting both pathogenicity and transmission potential. This is documented by the discovery of a putative L. infantum/L. donovani hybrid strain, which has been shown to preferentially infect humans but not dogs. Our results provide important information to health authorities, which need to consider the public health risk represented by the introduction of new Leishmania species into EU countries due to population displacement or travel from countries where exotic/allochthonous parasite species are endemic.
The
in vitro passive diffusion of
S-ibuprofen (
S-IB) and
RS-ibuprofen (
RS-IB) through human epidermis was determined to study the effects of drug chirality.
S-IB has a lower melting point (
T
m
=
...54
°C) than
RS-IB (
T
m
=
77
°C) and, therefore, a greater solubility (
S-IB: 127
±
1
μg/mL;
RS-IB: 81
±
1
μg/mL). Supersaturated plasters were prepared by using a poly(dimethylsiloxane) adhesive and Eugragit
® RL and propylene glycol as antinucleant agents. The
in vitro skin permeation profiles were determined by Franz cells and human epidermis obtained from three different donors. The permeation profiles of
S-IB from saturated solutions resulted statistically higher than those of
RS-IB (
p
<
0.002). When plasters were used, no differences were noticeable between the enantiomer and racemate (
p
>
0.17). The latter unexpected results could be explained considering that the
RS-IB or
S-IB
in vitro release rate constants, determined using 3% w/w or 6% w/w loaded plasters, were not statistically different, suggesting that the drug diffusivity within the adhesive matrix represented the rate limiting step to the skin absorption.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In response to rapid alkali delivery during hemodialysis, hydrogen ions (H+) are mobilized from body buffers and from stimulation of organic acid production in amounts sufficient to convert most of ...the delivered bicarbonate to CO2 and water. Release of H+ from nonbicarbonate buffers serves to back‐titrate them to a more alkaline state, readying them to buffer acids that accumulate in the interval between treatments. By contrast, stimulation of organic acid production only serves to remove added bicarbonate (HCO3−) from the body; the organic anions produced by this process are lost into the dialysate, irreversibly acidifying the patient as well as diverting metabolic activity from normal homeostasis. We have developed an analytic tool to quantify these acid‐base events, which has shown that almost two‐thirds of the H+ mobilized during hemodialysis comes from organic acid production when bath bicarbonate concentration (HCO3−) is 32 mEq/L or higher. Using data from the hemodialysis patients we studied with our analytical model, we have simulated the effect of changing bath solute on estimated organic acid production. Our simulations demonstrate that reducing bath HCO3− should decrease organic acid production, a change we propose as beneficial to the patient. They also highlight the differential effects of variations in bath acetate concentration, as compared to HCO3−, on the amount and rate of alkali delivery. Our results suggest that transferring HCO3− delivery from direct influx to acetate influx and metabolism provides a more stable and predictable rate of HCO3− addition to the patient receiving bicarbonate‐based hemodialysis. Our simulations provide the groundwork for the clinical studies needed to verify these conclusions.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The objective was to compare L4/5 range of motions of fusion constructs using anchored cages. Twelve human cadaveric spine were tested in intact condition, and divided into TLIF and PLIF groups. ...Testing consisted in applying pure moments in flexion-extension, lateral bending and axial rotation. The computation of intersegmental motion was assessed using 3 D biplanar radiographs. In TLIF group, the addition of contralateral transfacet decreased flexion-extension motion (39%; p = 0.036) but without difference with the ipsilateral pedicle screw construction (53%; p = 0.2). In PLIF group, the addition of interspinous anchor reduced flexion-extension motion (12%; p = 0.036) but without difference with the bilateral pedicle screw construction (17%; p = 0.8).
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
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•Thermal activated reaction after milling of β-LiAlSi2O6 and solid-NaOH was studied.•Li2CO3 and NaAlSi2O6 phases were observed after heating up to 300 °C.•Over 500 °C ...non-stoichiometric sodium aluminosilicates were identified.•Lithium recovery process gives 91.2 wt% of Li2CO3 in the solid residue.
Li2CO3 was obtained by the solid-state reaction between β-LiAlSi2O6 (β-spodumene) and NaOH under dynamic and static thermal conditions in the temperature range between 300 °C and 800 °C followed by washing and drying stages. Prior to the reaction, the reagents have been mixed by mechanical milling 1 h under air atmosphere at room temperature. The ball-milled mixture of β-LiAlSi2O6:NaOH has been studied after heating to determine its morphological, microstructural, structural and thermal stability characteristics. The results indicate that sodium from NaOH replaces lithium in the aluminosilicate structure by heating under air. Different crystalline phases have been observed depending on temperature: NaAlSi2O6 near 300 °C and non-stoichiometric sodium aluminosilicates over 500 °C. The only lithium-containing product formed has been Li2CO3 obtained at 350 °C and 300 °C under dynamic and static heating conditions, respectively. Additional experiments at different β-LiAlSi2O6:NaOH molar ratios have shown that a major amount of NaAlSi2O6 phase is obtained for the 1:1 M ratio. Lithium recovery experiments (as Li2CO3) combining washing and drying stages have given 91.2 wt% of Li2CO3 in the recovered solid residue.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To evaluate the effect of different first-line chemotherapy durations in patients with metastatic breast cancer (MBC) on overall survival (OS) and progression-free survival (PFS).
We searched ...literature databases to identify randomized controlled trials that compared different chemotherapy durations in the first-line treatment of MBC. Only trials with unconfounded comparisons of additional cycles of chemotherapy were included. The main outcome measures for this analysis were OS and PFS. Published data from retrieved studies were analyzed according to standard meta-analytic techniques.
We found 11 randomized clinical trials including 2,269 patients. Longer first-line chemotherapy duration resulted into a significantly improved OS (hazard ratio HR, 0.91; 95% CI, 0.84 to 0.99; P = .046) and PFS (HR, 0.64; 95% CI, 0.55 to 0.76; P < .001). There were no differences in effects on either OS or PFS between subgroups defined by time of random assignment, study design, number of chemotherapy cycles in the control arm or concomitant endocrine therapy.
Longer first-line chemotherapy duration is associated with marginally longer OS and a substantially longer PFS.
Since the late 1950s, an effect of electrical current in addition to joule heating on the deformation of metals called the Electroplastic Effect (EPE) has been known. It is used nowadays in the ...so-called Electrically Assisted Forming (EAF) processes, but the understanding of the phenomenon is not very clear yet. It has been found that EPE increases the formability of high stacking fault energy (SFE) materials, while low SFE materials reach fracture prematurely. Since Duplex Stainless Steels (DSSs) possess a microstructure consisting of two phases with very different SFE (low SFE austenite and high SFE ferrite) and they are widely used in industry, we investigated EPE on those alloys. Tensile tests at 5 A/mm
, 10 A/mm
and 15 A/mm
current densities along with thermal counterparts were conducted on UNS S32101, UNS S32205, UNS S32304 and UNS S32750. The DSS grades were characterized by means of optical microscopy, X-ray diffraction and their mechanical properties (ultimate tensile strength, total elongation, uniform elongation and yield stress). An increase in uniform elongation for the electrical tests compared to the thermal counterparts as well as an increase in total elongation was found. No differences were observed on the yield stress and on the ultimate tensile strength. Un uneven distribution of the current because of the different resistivity and work hardening of the two phases has been hypothesized as the explanation for the positive effect of EPE.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Primary school curricula teach children conversation norms for promoting positive social interactions, such as turn-taking and turn reserving, while curricula discourage other aspects of ...conversations, such as overlapping in turns. However such norms are abstract and difficult to master. Recently, interactive tangible solutions (briefly, tangibles) have been used to sustain the scaffolding of conversation norms. This paper continues this line of investigation. It discusses how meta-design and action research complement each other and tackle trade-offs in designing tangibles for conversations in primary schools. It reports on the emergence and genesis of tangibles for class conversation, named ClassTalk. Then it focusses on usages and actions with ClassTalk in 2018 in primary school classes, and it discusses them in relation to children's and teachers' engagement and usages of tangibles. It concludes by reflecting on the entire experience, and considers trade-offs and lessons learnt for meta-design and action research, as well as for the design of such tangibles per se.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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