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The influence of the composition of calcium (Ca(2+)), magnesium (Mg(2+)), and iron (Fe(3+)) ions in two concentration levels (low-500 mg/L of CaCl2, 125 mg/L of MgCl2, and 10 mg/L of FeCl3 and high-2,500 mg/L of CaCl2, 625 mg/L of MgCl2, and 50 mg/L of FeCl3) contained in water on the pharmacokinetics (PK) of oxytetracycline (OTC) was determined. OTC hydrochloride was administered at a dose of 25 mg/kg of body weight to broiler chickens divided into four groups of nine birds each, including 3 oral groups (in deionized water -control, in water with low ion concentration, and in water with high ion concentration) and 1 intravenous group. OTC concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry, after which non-compartmental pharmacokinetic analysis was conducted.The absolute bioavailability of OTC in the group of birds exposed to higher ions concentration was reduced (8.68% ± 2.56) as compared to the control (13.71% ± 2.60). Additionally, in this group, decrease in PK parameters such as: area under the concentration-time curve from 0 to infinity (15.36 μg × h/mL ± 4.36), from 0 to t (14.78 μg × h/mL ± 4.37), area under the first moment of curve from 0 to t (107.54 μg × h/mL ± 36.48), and maximum plasma concentration (2.13 μg/mL ± 0.32) were also observed. It is noteworthy, all mentioned parameters demonstrated a downward trend with high correlation coefficient (P = 0.004, P = 0.002, P = 0.005, P = 0.004, P = 0.011, respectively), reflecting the influence of increasing concentrations of Ca(2+), Mg(2+), and Fe(3+) ions on the decreasing absorption rate of OTC.Based on the current research results, it can be assumed that high concentrations of several ions applied concomitantly are able to decrease the absorption of OTC from gastrointestinal tract in broiler chickens. This occurrence might impair the drug's clinical efficacy toward some pathogenic microorganisms. It implies that using OTC on a farm may require administration of higher doses than the routine one when infections are caused by less sensitive pathogens., (© 2016 Poultry Science Association Inc.)

Based on comprehensive testing and educational history, children in grades 4-9 (on average 12 years) were diagnosed with dysgraphia (persisting handwriting impairment) or dyslexia (persisting word spelling/reading impairment) or as typical writers and readers (controls). The dysgraphia group (n = 14) and dyslexia group (n = 17) were each compared to the control group (n = 9) and to each other in separate analyses. Four brain region seed points (left occipital temporal gyrus, supramarginal gyrus, precuneus, and inferior frontal gyrus) were used in these analyses which were shown in a metaanalysis to be related to written word production on four indicators of white matter integrity and fMRI functional connectivity for four tasks (self-guided mind wandering during resting state, writing letter that follows a visually displayed letter in alphabet, writing missing letter to create a correctly spelled real word, and planning for composing after scanning on topic specified by researcher). For those DTI indicators on which the dysgraphic group or dyslexic group differed from the control group (fractional anisotropy, relative anisotropy, axial diffusivity but not radial diffusivity), correlations were computed between the DTI parameter and fMRI functional connectivity for the two writing tasks (alphabet and spelling) by seed points. Analyses, controlled for multiple comparisons, showed that (a) the control group exhibited more white matter integrity than either the dysgraphic or dyslexic group; (b) the dysgraphic and dyslexic groups showed more functional connectivity than the control group but differed in patterns of functional connectivity for task and seed point; and (c) the dysgraphic and dyslexic groups showed different patterns of significant DTI-fMRI connectivity correlations for specific seed points and written language tasks. Thus, dysgraphia and dyslexia differ in white matter integrity, fMRI functional connectivity, and white matter-gray matter correlations. Of clinical relevance, brain differences were observed in dysgraphia and dyslexia on written language tasks yoked to their defining behavioral impairments in handwriting and/or in word spelling and on the cognitive mind wandering rest condition and composition planning.

Elucidating the brain basis for psychological processes and behavior is a fundamental aim of cognitive neuroscience. The lesion method, using voxel-based statistical analysis, is an important approach to this goal, identifying neural structures that are necessary for the support of specific mental operations, and complementing the strengths of functional imaging techniques. Lesion coverage in a population is by nature spatially heterogeneous and biased, systematically affecting the ability of lesion-deficit correlation methods to detect and localize functional associations. We have developed a simulator that allows investigators to model parameters in a lesion-deficit study and characterize the statistical bias in lesion deficit detection coverage that will result from specific assumptions. We used the simulator to assess the signal detection properties and localization accuracy of standard lesion-deficit correlation methods, under a simple truth model - that a critical region of interest (CR), when damaged, gives rise to a deficit. We considered voxel-based lesion-symptom mapping (VLSM) and proportional MAP-3 (PM3). Using regression analysis, we examined if the pattern of outcome statistics can be explained by simulation parameters, factors that are inherent to anatomic parcels, and lesion coverage of the population, which consisted of a representative sample of 351 subjects drawn from the Iowa Patient Registry. We examined the effect of using nonparametric versus parametric statistics to obtain thresholded maps and the effect of correcting for multiple comparisons using false discovery rate or cluster-based correction. Our results, which are derived from samples of realistic lesions, indicate that even a simple truth model yields localization errors that are systematic and pervasive, averaging 2 cm in the standard anatomic space, and tending to be directed towards areas of greater anatomic coverage. This displacement positions the center of mass of the detected region in a different anatomical region 87% of the time. This basic result is not affected by the choice of PM3 vs VLSM as the fundamental approach, nor is localization error ameliorated by incorporation of lesion size as a covariate in the VLSM approach, or by data distribution-driven approaches to controlling multiple spatial comparisons (false discovery rate or cluster-based correction approaches). Our simulations offer a quantitative basis for interpreting lesion studies in cognitive neuroscience. We suggest ways in which lesion simulation and analysis frameworks could be productively extended.

Guidelines published by the European Union Regulatory Authority, regarding the planning of bioequivalence studies, are the primary source of knowledge about the study design optimization. The goal of this paper is to compare the key elements (27 points) of bioequivalence study optimization based on a comparison of the two European Medicines Agency guidelines relating to medicines used for humans (HB) and to veterinary drugs (AB). In case of the latter, one can get the impression that the issues of species differences in relation to the physiology and anatomy have been completely ignored. Many details that the AB guideline omits are included in the new HB guideline and were present in many other guidelines from the last 20 years. Most have not been adopted by the AB document, even though they are the product of many years of work of many teams and specialists from various agencies in the regulatory affairs field., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Neuronal processes that underlie the subjective experience of satiety after a meal are not well defined., Objective: We investigated how satiety alters the perception of and neural response to visual food cues., Design: Normal-weight participants (10 men, 13 women) underwent 2 fMRI scans while viewing images of high-calorie food that was previously rated as incompatible with weight loss and "fattening" and low-calorie, "nonfattening" food. After a fasting fMRI scan, participants ate a standardized breakfast and underwent reimaging at a randomly assigned time 15-300 min after breakfast to vary the degree of satiety. Measures of subjective appetite, food appeal, and ad libitum food intake (measured after the second fMRI scan) were correlated with activation by "fattening" (compared with "nonfattening") food cues in a priori regions of interest., Results: Greater hunger correlated with higher appeal ratings of "fattening" (r = 0.46, P = 0.03) but not "nonfattening" (r = -0.20, P = 0.37) foods. Fasting amygdalar activation was negatively associated with fullness (left: r = -0.52; right: r = -0.58; both P ≤ 0.01), whereas postbreakfast fullness was positively correlated with activation in the dorsal striatum (right: r = 0.44; left: r = 0.45; both P < 0.05). After breakfast, participants with greater activation in 4 regions-medial orbital frontal cortex (r = 0.49, P < 0.05), left amygdala (r = 0.49, P < 0.05), left insula (r = 0.47, P < 0.05), and nucleus accumbens (right: r = 0.57, P < 0.01; left: r = 0.43, P < 0.05)-chose buffet foods with higher fat content., Conclusions: Postmeal satiety is shown in regional brain activation by images of high-calorie foods. Regions including the amygdala, nucleus accumbens, and dorsal striatum may alter perception of, and reduce motivation to consume, energy-rich foods, ultimately driving food choice. This trial was registered at clinicaltrials.gov as NCT01631045.

Purpose: To investigate the pharmacokinetics and pharmacodynamics of ciprofloxacin in critically ill patients after the first intravenous administration of 400 mg., Material/methods: Plasma concentrations were measured in 20 critically ill patients (mean [SD]; age, 55.5 [16.5] years; weight, 80.3 [16.9] kg; and creatinine clearance, 110.0 [71.5] mL/min). Four blood samples were drawn at the following time points 0, 0.5, 6 , 8 hours after infusion. Ciprofloxacin concentrations were determined by high-performance liquid chromatography., Results: In the cases where ciprofloxacin was applied in targeted antibiotic therapy the minimum inhibitory concentrations (MIC) were ≤0.5 mg/l. The maximum and minimum plasma concentrations of ciprofloxacin were 1.74 (0.58-7.90) and 0.45 (0.16-2.96) mg/l, respectively. The main pharmacokinetic parameters for ciprofloxacin in the analyzed patients were as follows: k(el), 0.21 h-1; t(1/2kel), 3.37 h; AUC(0-inf), 10.10 mg×h/l; AUMC(0-last), 15.36 mg×h(2)/l; MRT, 1.71 h; V(d), 214.8 l; Cl, 39.70 l/h. Considering the maximum value of MIC (0.5 mg/l) only 30% and 25% of analyzed patients had desired values of the PK/PD indexes AUIC>125 and C(max) /MIC>10, respectively., Conclusions: The target plasma concentrations after the first dose of ciprofloxacin were reached only in a few critically ill patients. Considerable inter-subject variability for PK/PD parameters in ICU patients requires systematic monitoring.

Coordination polymers [Ag(L(1,3))](n) (L(1)=hydantoin, L(3)=5,5-dimethylhydantoin), {[Ag(L(2))](.)0.5H(2)O}(n) (L(2)=1-methylhydantoin) and [Ag(NH(3))(L(4))](n) (L(4)=allantoin) were prepared and characterized by elemental analysis, spectroscopic (IR, FTIR and NMR), thermal and mass spectrometry methods. The crystal structure of {[Ag(1-methylhydantoin)]·0,5H(2)O}(n) was determined and analyzed. Three 1-methylhydantoinate ligands create a T-shape (CN=3) coordination sphere around the Ag(+) ion. Additionally, a short Ag⋯Ag distance of 2.997Å was found in the structure resulting in the expanded [3+2] environment of a distorted square shape. The [Ag(L(2))] entities are bound to each other by the bridging organic ligands. Thus a two-dimensional coordination polymer is created with water molecules located between the layers. In contrast to hydantoins, the allantoin complex contains an additional ammonia molecule in the coordination sphere. Moreover, in the Ag-alla complex the M-organic ligand binding site is shifted to the N-atom of the ureid chain. Free ligands are cytotoxically inactive against human MCF-7 and A549 cancer cell lines and mouse fibroblasts Balb/3T3. The silver hydantoin complexes exhibit a very strong activity against these lines. (The introduction of the methyl groups to the ring slightly increases resistance only against the A549 cell line.) In contrast, the silver complex of allantoin shows only a weak activity which may be related to the presence of the cytotoxic ammonia group in the composition of the compound and/or the different binding site of the ligand. Calculated in silico physiochemical parameters are promising for the future application of the complexes as drugs., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Two complexes of calcium ions containing monodeprotonated caffeate ligands were synthesized and physicochemically (IR, FIR, NMR, thermal analysis) and theoretically (DFT and pharmacokinetical parameters) characterized. [Ca(C(9)H(7)O(4))(2)].2H(2)O 1a and [Ca(C(9)H(7)O(4))(2)].2H(2)O KNO(3)1b are compounds with unusual four coordinate calcium ion containing the ligand coordinated to the metal ion through two carboxylic groups arranged with tetrahedrally-like mode (CaO(4)). Two water molecules are outside the first coordination sphere bound non-equivalently to the ligand through a net of hydrogen bonding. The compounds were found to be cytotoxically inactive. Finally, in silico parameters predict the potential application of the compound as a supplement and/or drug.

Four calcium compounds containing uronic acids (D(+)-galacturonic and D(+)-glucuronic) in L:M ratio = 2 and 3 were isolated by applying novel (except for one complex) synthetic procedures. The compounds were characterized by elemental analysis, spectroscopic methods (diffuse reflectance and absorption UV-visible, IR, FIR), mass spectrometry, fast atom bombardment (FAB), thermal decomposition, thermogravimetry/derivative thermogravimetry (TG/DTG) data and differential scanning calorimetric studies (DSC). Two modes of water binding in the complexes, i.e., hydration and coordination-like, were established. Computer-aided analysis has shown that further investigations are needed in order to determine the applicability of calcium uronates as calcium carriers.

Using both the lesion method and functional imaging (positron emission tomography) in large cohorts of subjects investigated with the same experimental tasks, we tested the following hypotheses: (A) that the retrieval of words which denote concrete entities belonging to distinct conceptual categories depends upon partially segregated regions in higher-order cortices of the left temporal lobe; and (B) that the retrieval of conceptual knowledge pertaining to the same concrete entities also depends on partially segregated regions; however, those regions will be different from those postulated in hypothesis A, and located predominantly in the right hemisphere (the second hypothesis tested only with the lesion method). The analyses provide support for hypothesis A in that several regions outside the classical Broca and Wernicke language areas are involved in name retrieval of concrete entities, and that there is a partial segregation in the temporal lobe with respect to the conceptual category to which the entities belong, and partial support for hypothesis B in that retrieval of conceptual knowledge is partially segregated from name retrieval in the lesion study. Those regions identified here are seen as parts of flexible, multi-component systems serving concept and word retrieval for concrete entities belonging to different conceptual categories. By comparing different approaches the article also addresses a number of method issues that have surfaced in recent studies in this field.

Positron emission tomography was used to investigate whether the motor-iconic basis of certain forms in American Sign Language (ASL) partially alters the neural systems engaged during lexical retrieval. Most ASL nouns denoting tools and ASL verbs referring to tool-based actions are produced with a handshape representing the human hand holding a tool and with an iconic movement depicting canonical tool use, whereas the visual iconicity of animal signs is more idiosyncratic and inconsistent across signs. We investigated whether the motor-iconic relation between a sign and its referent alters the neural substrate for lexical retrieval in ASL. Ten deaf native ASL signers viewed photographs of tools/utensils or of actions performed with or without an implement and were asked to overtly produce the ASL sign for each object or action. The control task required subjects to judge the orientation of unknown faces. Compared to the control task, naming tools engaged left inferior and middle frontal gyri, bilateral parietal lobe, and posterior inferotemporal cortex. Naming actions performed with or without a tool engaged left inferior frontal gyrus, bilateral parietal lobe, and posterior middle temporal gyrus at the temporo-occipital junction (area MT). When motor-iconic verbs were compared with non-iconic verbs, no differences in neural activation were found. Overall, the results indicate that even when the form of a sign is indistinguishable from a pantomimic gesture, the neural systems underlying its production mirror those engaged when hearing speakers name tools or tool-based actions with speech.