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Sodium diclofenac (50 mg) together with [14 C]-PEG as a non-absorbable marker were dissolved in 400 ml of water (A), phosphate buffer pH 7.5 (B) or a homogenized meal (C). Each of these was ingested in random order by six volunteers on 3 consecutive days. Some gastric absorption of the drug was established with C but the plasma drug concentration- time profiles mainly reflected the process of gastric emptying. [ABSTRACT FROM AUTHOR]

Most organisms on earth, humans included, have developed strategies to cope with environmental day-night and seasonal cycles to survive. For most of them, their physiological and behavioral functions, including the reproductive function, are synchronized with the annual changes of day length, to ensure winter survival and subsequent reproductive success in the following spring. Sheep are sensitive to photoperiod, which also regulates natural adult neurogenesis in their hypothalamus. We postulate that the ovine model represents a good alternative to study the functional and metabolic changes occurring in response to photoperiodic changes in hypothalamic structures of the brain. Here, the impact of the photoperiod on the neurovascular coupling and the metabolism of the hypothalamic structures was investigated at 3T using BOLD fMRI, perfusion-MRI and proton magnetic resonance spectroscopy ( 1 H-MRS). A longitudinal study involving 8 ewes was conducted during long days (LD) and short days (SD) revealing significant BOLD, rCBV and metabolic changes in hypothalamic structures of the ewe brain between LD and SD. More specifically, the transition between LD and SD revealed negative BOLD responses to hypercapnia at the beginning of SD period followed by significant increases in BOLD, rCBV, Glx and tNAA concentrations towards the end of the SD period. These observations suggest longitudinal mechanisms promoting the proliferation and differentiation of neural stem cells within the hypothalamic niche of breeding ewes. We conclude that multiparametric MRI studies including 1 H-MRS could be promising non-invasive translational techniques to investigate the existence of natural adult neurogenesis in-vivo in gyrencephalic brains., (Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.)

Recent studies have reported the presence of adult neurogenesis in the arcuate nucleus periventricular space (pvARH) and in the median eminence (ME), two structures involved in reproductive function. In sheep, a seasonal mammal, decreasing daylight in autumn induces a higher neurogenic activity in these two structures. However, the different types of neural stem and progenitor cells (NSCs/NPCs) that populate the arcuate nucleus and median eminence, as well as their location, have not been evaluated. Here, using semi-automatic image analyzing processes, we identified and quantified the different populations of NSCs/NPCs, showing that, during short days, higher densities of [SOX2 +] cells are found in pvARH and ME. In the pvARH, higher densities of astrocytic and oligodendrocitic progenitors mainly contribute to these variations. The different populations of NSCs/NPCs were mapped according to their position relative to the third ventricle and their proximity to the vasculature. We showed that [SOX2 +] cells extended deeper into the hypothalamic parenchyma during short days. Similarly, [SOX2 +] cells were found further from the vasculature in the pvARH and the ME, at this time of year, indicating the existence of migratory signals. The expression levels of neuregulin transcripts (NRGs), whose proteins are known to stimulate proliferation and adult neurogenesis and to regulate progenitor migration, as well as the expression levels of ERBB mRNAs, cognate receptors for NRGs, were assessed. We showed that mRNA expression changed seasonally in pvARH and ME, suggesting that the ErbB-NRG system is potentially involved in the photoperiodic regulation of neurogenesis in seasonal adult mammals., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sheep, like most seasonal mammals, exhibit a cyclic adaptive reproductive physiology that allows ewes to give birth to their progeny during the spring when environmental conditions are favorable to their survival. This process relies on the detection of day length (or photoperiod) and is associated with profound changes in cellular plasticity and gene expression in the hypothalamic-pituitary-gonadal axis, mechanisms that are suggested to participate in the seasonal adaptation of neuroendocrine circuits. Recently, pituitary vascular growth has been proposed as a seasonally regulated process in which the vascular endothelial growth factor A (VEGFA), a well-known angiogenic cytokine, is suspected to play a crucial role. However, whether this mechanism is restricted to the pituitary gland or also occurs in the mediobasal hypothalamus (MBH), a crucial contributor to the control of the reproductive function, remains unexplored. Using newly developed image analysis tools, we showed that the arcuate nucleus (ARH) of the MBH exhibits an enhanced vascular density during the long photoperiod or non-breeding season, associated with higher expression of VEGFA. In the median eminence (ME), a structure connecting the MBH to the pituitary gland, higher VEGFA, kinase insert domain receptor (KDR/VEGFR2) and plasmalemma vesicle-associated protein (PLVAP) gene expressions were detected during the long photoperiod. We also found that VEGFA and its receptor, VEGFR2, are expressed by neurons and tanycytes in both the ARH and ME. Altogether, these data show variations in the MBH vasculature according to seasons potentially through a VEGFA-dependent pathway, paving the way for future studies aiming to decipher the role of these changes in the hypothalamic control of seasonal reproduction., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: About 25% of patients experience adverse drug events (ADE) in primary care, but few events are reported by the patients themselves. One solution to improve the detection and management of ADEs in primary care is for patients to report them to their general practitioner. The study aimed to assess the effect of a booklet designed to improve communication and interaction between patients treated with anti-hypertensive drugs and general practitioners on the reporting of ADEs., Methods: A cluster randomized controlled cross-sectional stepped wedge open trial (five periods of 3 months) was conducted. A cluster was a group of general practitioners working in ambulatory offices in France. Adults consulting their general practitioner to initiate, modify, or renew an antihypertensive prescription were included. A booklet including information on cardiovascular risks, antihypertensive treatments, and ADE report forms was delivered by the general practitioner to the patient in the intervention group. The primary outcome was the reporting of at least one ADE by the patient to his general practitioner during the three-month period after enrolment. Two clusters were randomised by sequence for a total of 8 to receive the intervention. An intention-to-treat analysis was conducted. A logistic mixed model with random intercept was used., Results: Sixty general practitioners included 1095 patients (median: 14 per general practitioner; range: 1-103). More patients reported at least one ADE to their general practitioner in the intervention condition compared to the control condition (aOR = 3.5, IC 95 [1.2-10.1], p = 0.02). The modification and initiation of an antihypertensive treatment were also significantly associated with the reporting of ADEs (aOR = 4.4, CI 95 [1.9-10.0], p <  0.001 and aOR = 11.0, CI 95 [4.6-26.4], p <  0.001, respectively). The booklet delivery also improved patient satisfaction on general practitioner communication and high blood pressure management., Conclusion: A booklet can improve patient self-reporting of ADEs to their general practitioners. Future research should assess whether it can improve general practitioner management of ADEs and patient's health status., Trial Registration: Trial registry identifier NCT01610817 (2012/05/30)., (© 2021. The Author(s).)

Melatonin (MLT) is a biological modulator of circadian and seasonal rhythms and reproduction. The photoperiodic information is detected by retinal photoreceptors and transmitted through nerve transmissions to the pineal gland, where MLT is synthesized and secreted at night into the blood. MLT interacts with two G protein-coupled receptors, MT1 and MT2. The aim of our work was to provide evidence for the presence of MLT receptors in the ovine pineal gland and define their involvement on melatonin secretion. For the first time, we identified the expression of MLT receptors with the specific 2-[125I]-MLT agonistic radioligand in ovin pinealocytes. The values of Kd and Bmax are 2.24 ± 1.1 nM and 20 ± 6.8 fmol/mg. MLT receptors are functional and inhibit cAMP production and activate ERK1/2 through pertussis toxin-sensitive Gi/o proteins. The MLT receptor antagonist/ inverse agonist luzindole increased cAMP production (189 ± 30%) and MLT secretion (866 ± 13%). The effect of luzindole on MLT secretion was additive with the effect of well-described activators of this pathway such as the β-adrenergic agonist isoproterenol and the α-adrenergic agonist phenylephrine. Co-incubation of all three compounds increased MLT secretion by 1236 ± 199%. These results suggest that MLT receptors are involved in the negative regulation of the synthesis of its own ligand in pinealocytes. While adrenergic receptors promote MLT secretion, MLT receptors mitigate this effect to limit the quantity of MLT secreted by the pineal gland., Competing Interests: The authors have declared that no competing interests exist.

The ovine model could be an effective translational model but remains underexplored. Here, Blood Oxygen Level dependent functional MRI during visual stimulation and resting-state perfusion MRI were explored. We aimed at investigating the impact of isoflurane anesthesia during visual stimulation and evaluate resting cerebral blood flow and cerebral blood volume parameters in the lamb and adult sheep brain. BOLD fMRI and perfusion MRI after a bolus of DOTAREM were conducted in 4 lambs and 6 adult ewes at 3 T. A visual stimulation paradigm was delivered during fMRI at increasing isoflurane doses (1-3%). Robust but weak BOLD responses (0.21 ± 0.08%) were found in the lateral geniculate nucleus (LGN) up to 3% isoflurane anaesthesia. No significant differences were found beween BOLD responses in the range 1 to 3% ISO (p > 0.05). However, LGN cluster size decreased and functional localization became less reliable at high ISO doses (2.5-3% ISO). BOLD responses were weaker in adult sheep than in lambs (4.6 ± 1.5 versus 13.6 ± 8.5; p = 0.08). Relative cerebral blood volumes (rCBV) and relative cerebral blood flows (rCBF) were significantly higher (p < 0.0001) in lambs than in adult sheep for both gray and white matter. The impact of volatile anesthesia was explored for the first time on BOLD responses demonstrating increased reliability of functional localization of brain activity at low doses. Perfusion MRI was conducted for the first time in both lambs and adult ewes. Assessment of baseline cerebrovascular values are of interest for future studies of brain diseases allowing an improved interpretation of BOLD responses., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Unlike mammals, the role of adipokines and more particularly of chemerin in the regulation of food intake is totally unknown in avian species. Here we investigated the effect of chemerin on the food and water consumption and on the body weight in chicken. We studied the effects on the plasma glucose and insulin concentrations and the hypothalamic neuropeptides and AMPK signaling pathway. Female broiler chickens were intraperitoneally injected, daily for 13 days with either vehicle (saline; n = 25) or chemerin (8 μg/kg; n = 25 and 16 μg/kg; n = 25). Food and water intakes were recorded 24 h after each administration. Overnight fasted animals were sacrificed at day 13 (D13), 24 h after the last injection and hypothalamus and left cerebral hemispheres were collected. Chemerin and its receptors protein levels were determined by western-blot. Gene expression of neuropeptide Y (Npy), agouti-related peptide (Agrp), corticotrophin releasing hormone (Crh), pro-opiomelanocortin (Pomc), cocaine and amphetamine-regulated transcript (Cart) and Taste 1 Receptor Member 1 (Tas1r1) were evaluated by RT-qPCR. In chicken, we found that the protein amount of chemerin, CCRL2 and GPR1 was similar in left cerebral hemisphere and hypothalamus whereas CMKLR1 was higher in hypothalamus. Chemerin administration (8 and 16 μg/kg) decreased both food intake and body weight compared to vehicle without affecting water intake and the size or volume of different brain subdivisions as determined by magnetic resonance imaging. It also increased plasma insulin levels whereas glucose levels were decreased. These data were associated with an increase in Npy and Agrp expressions and a decrease in Crh, Tas1r1 mRNA expression within the hypothalamus. Furthermore, chemerin decreased hypothalamic CMKLR1 protein expression and AMPK activation. Taken together, these results support that chemerin could be a peripheral appetite-regulating signal through modulation of hypothalamic peptides expression in chicken., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of this trial was to study the effects of dietary protein content during the rearing period on the performance of mule ducks, according to age at overfeeding (O). Ducks (n = 612) were divided into four groups differing in the protein content in the diet offered during the starting period (S, 0-20 days; S l vs. S h : 150 vs. 175 g/kg crude protein (CP)) and growing-finishing period (GF; 21-67 or 81 days, depending on age at O; GF l vs. GF h : 133 vs. 152 g/kg CP). The relative weight of pectoral muscle was lower when ducks were fed a low protein diet during S (-5%, P < 0.01) or GF period (-6%, P < 0.001) at 68 days and higher in ducks of the S l GF h group (+6%; P < 0.05) at 82 days. Both foie gras and magret weights fell when ducks were fed S l or GF l (P < 0.05 and < 0.01). Mortality during the O period was higher in ducks fed the S l diet and overfed at late age (7.4% vs. 0%; P < 0.01). In conclusion, a reduction in the dietary protein supply should be recommended only during the GF period for ducks overfed at a late age., (© 2017 Japanese Society of Animal Science.)

Purpose  The purpose of this paper is to validate a Spanish version of patient-rated wrist evaluation (PRWE) and evaluate its psychometric attributes in a population of patients with distal radius fracture. Material and Methods  A translation and cross-cultural adaptation of the PRWE to Spanish (PRWE-S) was performed according to standardized guidelines. A total of 50 patients with a distal radius fracture were included during the different steps of the study. The reliability of the new instrument was assessed in terms of construct validity with the Quick DASH (Disability of the Arm, Shoulder, and Hand). Internal consistency and test-retest stability were also examined. Results  The Spearman's correlation test for analysis of the criterion validity (0.75) indicates a strong positive correlation between the PRWE-S and the Quick DASH. The internal consistency according to Cronbach's α was 0.96, and the intraclass correlation coefficient was moderate (0.46). Conclusion  A Spanish version of the PRWE indicated good validity and reliability in distal radius fracture patients. This valuable tool can be used in Spanish-speaking countries to evaluate various aspects as pain and function in patients with injuries of the wrist.

In small ungulates such as sheep or goats, the introduction of a male among a group of anovulatory females during the anestrus season leads to the reactivation of the gonadotrope axis and ovulation, a phenomenon known as the 'male effect'. In goats, our previous studies have demonstrated the importance of male sexual activity for an efficient reactivation of the gonadotrope axis assessed through ovulation and blood LH pulsatility. In the present experiment, we assessed whether the level of male sexual activity would also induce differential activation of two brain regions of key importance for the reactivation of GnRH activity, namely the medial preoptic area and the hypothalamic arcuate nucleus. In both structures, we observed a differential activation of Fos in females, depending on the level of buck sexual activity. Indeed, goats unexposed to males showed low levels of expression of Fos while those exposed to sexually inactive bucks showed an intermediate level of Fos expression. Finally, the highest level of Fos expression was found in females exposed to sexually active males. However, and contrary to our initial hypothesis, we were not able to find any specific activation of kisspeptin cells in the arcuate nucleus following the introduction of highly sexually active males. As a whole, these results demonstrate that the level of male sexual activity is a key factor to stimulate brain regions involved in the control of the gonadotrope axis in the context of the male effect in goats., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of this trial was to study the effects of replacing yellow corn (C) with condensed tannin-free sorghum (S) during the finishing period (F period; age 53 to 79 d) and/or overfeeding period (O period; age 80 to 91 d) on the performance of overfed mule ducks. 192 ducks were divided into 4 groups (48 in each) differing in the cereal (yellow corn or sorghum) included in the diet given during the F and/or the O periods, using a 2 × 2 factorial arrangement of treatments : SS, SC, CS, CC. At the end of the O period, the birds were slaughtered after 10 h of fasting to measure foie gras and magret qualities. Mortality (1%; P > 0.05) and weight gain (2,030 g; P > 0.05) during the O period were similar in the 4 groups. At the end of the O period, birds overfed with sorghum had foie gras that was heavier (723 vs. 694 g in CS+SS vs. CC+SC, respectively; P < 0.05) and less yellow (24.40 vs. 38.59 for b* in CS+SS vs. CC+SC, respectively; P < 0.001) than birds overfed with corn. Fat loss during foie gras cooking was similar in the 4 groups (18%; P > 0.05), but the foie gras was less yellow in birds overfed with sorghum (14.84 vs. 26.01 for b* in CS+SS vs. CC+SC, respectively; P < 0.001). Weight of magret was similar in the 4 groups (491 g, P > 0.05) but the color of the breast muscle and skin of magret was less yellow in birds overfed with sorghum compared with corn (12.26 vs. 12.92 and 13.84 vs. 18.30 in CS+SS vs. CC+SC, respectively; P < 0.001). In conclusion, the replacement of yellow corn with sorghum during finishing and/or overfeeding is possible and useful in a mule duck foie gras production system because it increases foie gras weight without decreasing the weight of magret However, it changes the quality of the products, mainly their color., (© 2016 Poultry Science Association Inc.)

The aim of this work was to study the effects of incorporating sugar beet pulp (SBP) into the diet on the development of the crop and performance of geese. A total of 480 1-day-old ganders were divided into three groups differing in the composition and mode of distribution of the diet offered from day 56 to 89. The following two diets were used: a standard diet (nitrogen-corrected apparent metabolizable energy, AMEn 11.44 MJ/kg; 160 g/kg CP) or a diet containing 10% of SBP (SBP diet; AMEn 11.47 MJ/kg; 160 g/kg CP). The swelling capacity (SC) hydration was higher for SBP than for the standard diet (3.62 v. 2.72 ml of H2O/g of dry matter at 60 min; P<0.05). In the Control group, birds were fed with a controlled time of access to a standard diet. Other birds were fed the SBP diet with a controlled time of access (SBPt group) or a controlled quantity offered (SBPq). From day 90 to 104, 88 birds/group were overfed with a mixture containing mainly corn. Body traits including volume of the crop were measured at day 89. Fatty liver weight and commercial grading were measured at d 104. Feed intake from day 56 to 89 was higher in the Control group than in the SBPt group (8097 v. 7545 g; P<0.05), feed intake in the SBPq group being intermediate (7801 g); however, live weights (LW) of the birds were similar in the three groups measured at day 89 (5746 g; P>0.05). At day 89, the volume of the crop tended to be higher in the SBPt compared with the Control group (52.8 v. 48.8 ml/kg of LW; P=0.101). After overfeeding, feed intake (12 922 g), weight gain (2412 g), LW (8170 g), fatty liver weight (875 g) and commercial grading of the fatty liver were similar (P>0.1) for all the three groups. Therefore, SBP could help adapt the digestive tract of waterfowl to high feed intake through an increase in the crop volume, but its method of use - that is, level of incorporation and mode of distribution - should continue to be investigated.

The aim of this trial was to study the influence of choice feeding and cereal type (corn or triticale) during the finishing period on performance of ducks. In total, 624 one-day-old male mule ducks (Cairina moschata × Anas platyrhynchos) were divided into 3 groups differing in the diet they received between 56 and 84 d of age: a commercial complete pelleted diet (control group; AMEn 12.1 MJ/kg, CP 15%), or corn whole seeds (AMEn 14.4 MJ/kg, CP 7.3%) and protein-rich pellets (AMEn 9.9 MJ/kg, CP 22.7%) in 2 separated feeders [choice feeding with corn (CFC) group]; or triticale whole seeds (AMEn 13.0 MJ/kg, CP 10.5%) and protein-rich pellets (AMEn 11.2 MJ/kg, CP 19.5%) in 2 separated feeders [choice feeding with triticale (CFT) group]. From 85 to 96 d, 96 birds/group were overfed with corn. Feed intake (complete pellets or cereal and protein-rich pellets) per pen was measured at 60, 62, 65, 69, 78, and 84 d of age. Body weight and body traits were measured at 56 to 84 d of age. Over the entire period, from 56 to 84 d, the feed intake of the CFC group was 7% lower than the control group, and 5% lower than that in the CFT group (P = 0.002). Whatever the diet tested, at 56 and 84 d of age, the BW (4,099 and 4,779 g, P = 0.42 and P = 0.35, respectively) and the carcass traits (P > 0.05) of ducks were similar in the 3 groups. During and after overfeeding, the performances of the ducks were also similar (P > 0.05). The present results suggest that CFC during the finishing period is a solution to reduce the cost of diet destined to ducks. Indeed, using locally grown grains could reduce the economic and environmental impacts of duck feeding, reducing the transportation and crushing processes., (© 2014 Poultry Science Association Inc.)

The aim of this trial was to study the effects of substitution of yellow corn with sorghum during the growing-finishing (G period), overfeeding (O period), or both periods on magret and foie gras quality in geese. In total, 260 ganders were divided into 4 groups (65 birds in each) differing in the cereal (yellow corn or sorghum) included in the diet given during the G and the O periods, using a 2 × 2 factorial arrangement of treatments. The groups differed in the nature of the cereal in the diet offered to birds between 44 and 104 d of age (G period: a diet containing 500 g of sorghum/kg (SS and SC groups) or a diet containing 500 g of yellow corn/kg (CS and CC groups). The groups differed also in the diet offered to birds between 105 and 120 d of age (O period): 967 g of yellow corn/kg (SC and CC groups) or 965 g of sorghum/kg (SS and CS groups). At the end of the O period, the birds were slaughtered after 10 h of fasting to measure foie gras and breast muscle weight, color, and chemical composition. The mortality in the SC group was higher (P < 0.05) than in the other 3 groups (14.29 vs. 3.58%, average of the 3 groups). After overfeeding, birds fed with sorghum had foie gras that were heavier 984 vs. 885 g, in CS+SS vs. CC+SC groups, respectively; P < 0.001) and less yellow (18.03 vs. 23.97 for b*, in CS+SS vs. CC+SC groups, respectively, P < 0.001) than birds fed with corn. The substitution of yellow corn with sorghum during the G and O periods (SS group) increased the weight of the foie gras, but altered its color to a paler yellow. In contrast, a substitution during the G period only (SC group) resulted in increased mortality during the O period.

Background: Adverse drug events could often be prevented. One of their main causes is that patients rarely know how to detect them. Another cause is inadequate communication between patients and physicians. If patients were to be effectively trained in detecting and reporting adverse drug events, this should help to prevent their occurrence and subsequent complications. Our purpose is to present the protocol of the InPAct trial, which aims to evaluate an interactive program that encourages patients to report adverse drug events in primary care., Methods/design: We will conduct a cluster randomised controlled stepped wedge trial, with eight clusters of 10 general practitioners each. The physicians will suggest to all of their antihypertensive-treated patients that they take part in this study. The InPAct program will be implemented in the clusters in random order along five successive three-month periods. Two new clusters will be trained in implementing the program at each step. The program features: an interactive patient booklet including informative paragraphs, several care plans and adverse drug event report forms; and standardised training of physicians in how to present the booklet to the patient. The primary outcome will be the reporting of adverse drug events by patients to their physician within three months. We assume that the number of patients reporting at least one adverse drug event will increase from 3% before program implementation to 7.5% afterward (coefficient of variation = 0.5, α = 0.05, β = 0.2), which means that 1,200 patients must be included. The effect of the intervention on the main outcome will be quantified and tested using a mixed logistic model to integrate cluster and time effects., Discussion: Our choice of a stepped wedge design is particularly appropriate for evaluating the implementation of a patient safety program within the constraints of general practice. We describe the InPAct intervention, which is an original program that is intended to improve communication between patients and physicians. Indeed, none of the previously published intervention studies has combined a patient education program and a patient reporting system for adverse drug events with the aim of improving patient safety in primary care., Trial Registration: This study is registered in ClinicalTrials.gov NCT01610817.

The aim of this trial was to study the influence of loose-mix feeding on behavior, feed intake, and BW of growing geese. In total, 252 one-day-old geese (Anser anser) were divided into 2 groups differing in the form of diet they received between 42 and 98 d of age (AMEn 11.55 MJ/kg, CP 16%): a complete pelleted diet containing 500 g of sorghum/kg (control group) or a mixture containing 500 g of protein-rich pellets and 500 g of sorghum whole seeds/kg (mixed group). Feed intake was measured daily from 42 to 48 d and every 3 d from 49 to 98 d. Individual BW was measured weekly from 42 to 98 d. Goose behavior was monitored by the scan sampling method throughout the experiment, which was divided into 5 periods according to the timing of access to feed: period 1 from 42 to 55 d (ad libitum feeding access), period 2 from 56 to 62 d (2 + 2 h feeding access), period 3 from 63 to 70 d (2 h feeding access), period 4 from 71 to 94 d (1 h feeding access), and period 5 from 95 to 97 d (3 h feeding access). Over the whole period, the feed intake (13,968 and 14,480 g) and the feed conversion ratio (8.53 and 8.15) were similar in both groups (P = 0.112 and P = 0.168; respectively). Body weight was similar in both groups from 42 to 91 d of age, but at 98 d of age, BW was 3.7% lower in the control than in the mixed group (P = 0.006). Goose behavior was influenced by period, because the percentage of birds feeding increased when the daily access time to the feed decreased (P < 0.001), but not by group (P > 0.05). The results suggest that a loose-mix feeding could be recommended in feeding of growing geese because it weakly influences their feed behavior but slightly increases their weight at the end of the growing period.

In France, there is a discrepancy between perceptions and practices related to vaccination, the causes of which are poorly understood. The purpose of this study was to examine and compare patients' and physicians' social representations of vaccination. A qualitative study based on hierarchized evocation was conducted on a sample of 30 patients and 30 general practitioners. The participants were asked to write down seven words or word groups (word associations) induced by the concept of "vaccination" and to rank them in order of importance. The associations were grouped by theme and sub-theme. Their frequency, connotations and importance were compared between the two groups. The results show that, overall, the physicians had a positive view of vaccination, while the patients had a more neutral view (polarity index: + 0.38 vs + 0.07, p &lt; 0.01). Among both patients and general practitioners, vaccination tends to be perceived as a form of medical care mainly targeting children and aimed at prevention, and its effectiveness is considered to be implicit. However, the patients appeared to be more concerned about the potential side effects of certain vaccinations, while the GPs emphasized the harmlessness of vaccination. The participating GPs also tended to take a collective view of vaccination, while some patients criticized the lack of targeted vaccinations. Better communication on these key aspects of representations may help to increase confidence in vaccination and to close the gap between perception and practice.

The aim of this trial was to study the influence of feed form on the performance, gizzard development and carcass traits of growing geese. Between 42 and 98 days of age, 360 geese (type Maxipalm(®)) were fed a diet containing 500 g sorghum/kg (nitrogen-corrected apparent metabolizable energy 12.6 MJ/kg, 15.1 g/kg CP). Birds were divided into three groups differing in feed form: complete pellets (Control group, n = 120); a coarse-ground meal (CG group, n = 120); or a mixture containing protein-rich pellets and sorghum whole grains (M group, n = 120). Feed intake per pen (40 birds/pen) was measured weekly between 42 and 98 days of age, and individual live weight (LW) was measured every 2 weeks. At 84 and 98 days of age, 12 birds were slaughtered in each group to measure the gizzard development and body traits. Irrespective of the goose sex, LW at 98 days was lower for the CG group than for the Control group (5555 v. 5888 g, P < 0.05 for males and 5039 v. 5215 g, P < 0.05 for females). The feed intake over the entire period was 5.5% higher in the M group (P < 0.05) than in the Control and CG groups but the feed conversion ratio (6.91, P > 0.05) was similar in the three groups. The gizzard development (as % of LW) was higher in birds of the CG group than those of the Control and M groups at 84 days of age (+13.98% and +13.51%, respectively; P < 0.05) but was similar in all three groups at 98 days of age (4.01%, P > 0.05). The relative liver development was lower in the birds of the CG group than those of the other two groups at 84 and 98 days of age (-20%, P < 0.001 and -10%, P < 0.05, respectively). The other body traits were similar in the three groups at both 84 and 98 days of age. The present results suggest that a simplified diet presented in the form of a mixture of sorghum whole grains and protein-rich pellets did not reduce the performance of growing geese.

The aim of this trial was to study the effects of cereal (corn or sorghum) and of the presentation of the diet (pelleted diet or a mixture with cereal) on the performance of geese. In total, 480 one-day-old geese were divided into 4 groups differing in the diet they received between 52 and 102 d of age: a pelleted diet containing 500 g of sorghum/kg (CS group; AMEn 11.29 MJ/kg, CP 16.70%); a mixture containing 500 g of protein-rich pellets and 500 g of sorghum whole seeds/kg (MS group; AMEn 11.61 MJ/kg, CP 14.30%); a pelleted diet containing 500 g of corn/kg (group CC; AMEn 11.33 MJ/kg, CP 16.40%); and a mixture containing 500 g of protein-rich pellets and 500 g of corn mash/kg (group MC; AMEn 11.48 MJ/kg, CP 14.50%). From 102 to 117 d, 33 birds/sex/group were force-fed with corn. Between 52 and 102 d of age, individual BW and collective feed intake (40 birds/pen) were measured weekly. Body traits were measured at 69, 96, and 117 d and the volume of the crop was measured at 102 d of age. The cereal had no significant effect on total feed intake (15,028 g, NS) or BW (5,811 g, NS) but the breast development at 102 d was less in birds fed sorghum compared with corn (-4.9%; P<0.05). Feed intake (+8.4% between 69 and 102 d; P<0.001), BW (+3.9%; P<0.001) and gut development (+9.3%; P<0.001) were higher when the diet was offered as a mixture compared with a complete pelleted diet. The birds fed the complete pelleted diets had a larger crop (+10.1%; P<0.05) than others. The cereal and the presentation of the diet had no effect on the body traits at the end of the force feeding. The results suggest that the use of sorghum whole seeds is interesting for feeding geese.

Background: Infantile colics or excessive crying represent a source of stress for parents and a frequent reason for encounter in primary care., Objective: To assess the effectiveness of treatments of this syndrome from a systematic review., Information Sources: Medline, Cochrane and Embase databases., Selection of Studies: We used the following inclusion criteria: therapeutic assessment of infant colics or excessive crying, randomized controlled trials or meta-analyses, published in English or French language. Thirty-one randomized controlled trials and one meta-analysis have been included., Results: Allopathic drugs have not proved effectiveness (simethicone, lactase) and some of them can cause potentially serious adverse reactions (dicyclomine). Protein hydrolysate or soy formulas seem to be effective, but soy milk can induce allergies. Sucrose solutions provide some benefit in studies with low level of evidence. Effectiveness is likely for a probiotics (Lactobacillus reuteri) and for herbal mixtures containing fennel extracts. Evidence is lacking for manual (osteopathy, acupuncture) and behavioural therapies (decreased stimulations, reassurance of parents)., Limitations: The definition of infantile colics and the methods used for crying measurement changed across trials. The included trials were of variable quality, especially with no double-blind procedure in 17 trials., Conclusion: The most validated treatments for infantile colics are the substitution of cows' milk by a hydrolysed formula, the use of L. reuteri and of fennel extracts., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Algol and Comptage de Photons Nouvelle Génération (CPNG) are new generation photon counting cameras developed for high angular resolution in the visible by means of optical aperture synthesis and speckle interferometry and for photon noise limited fast imaging of biological targets. They are intensified CCDs. They have been built to benefit from improvements in photonic commercial components, sensitivity, and personal computer workstations processing power. We present how we achieve optimal performances (sensitivity and spatiotemporal resolution) by the combination of proper optical and electronics design, and real-time elaborated data processing. The number of pixels is 532 x 516 and 1024(2) read at a frame rate of 262 and 100 Hz for CPNG and Algol, respectively. The dark current is very low: 5.5 x 10(-4) e(-) .pixel(-1). s(-1). The saturation flux is approximately 7 photon events /pixel/s. Quantum efficiencies reach up to 36% and 26% in the visible with the GaAsP photocathodes and in the red with the GaAs ones, respectively, thanks to the sensitivity of the photocathodes and to the photon centroiding algorithm; they are likely the highest values reported for intensified CCDs.

Venus has thick clouds of H2SO4 aerosol particles extending from altitudes of 40 to 60 km. The 60-100 km region (the mesosphere) is a transition region between the 4 day retrograde superrotation at the top of the thick clouds and the solar-antisolar circulation in the thermosphere (above 100 km), which has upwelling over the subsolar point and transport to the nightside. The mesosphere has a light haze of variable optical thickness, with CO, SO2, HCl, HF, H2O and HDO as the most important minor gaseous constituents, but the vertical distribution of the haze and molecules is poorly known because previous descent probes began their measurements at or below 60 km. Here we report the detection of an extensive layer of warm air at altitudes 90-120 km on the night side that we interpret as the result of adiabatic heating during air subsidence. Such a strong temperature inversion was not expected, because the night side of Venus was otherwise so cold that it was named the 'cryosphere' above 100 km. We also measured the mesospheric distributions of HF, HCl, H2O and HDO. HCl is less abundant than reported 40 years ago. HDO/H2O is enhanced by a factor of approximately 2.5 with respect to the lower atmosphere, and there is a general depletion of H2O around 80-90 km for which we have no explanation.

The provision of care for patients with end-stage chronic renal failure is an important medical and economic challenge for the Health Insurance. Previous studies have shown a lower cost for home dialysis. More recently, studies have confirmed identical short-term survival rates between haemodialysis and peritoneal dialysis. Notwithstanding, home dialysis techniques utilization remains weak in France. This work aims at: determining the average annual cost of dialysis, per patient and per technique of dialysis, and assessing the global annual cost of dialysis in France, from the Health Insurance perspective. Methodologically, this article provides a static estimation of the cost of dialysis. Costs related to co-morbidities of end-stage chronic renal failure have not been considered. Standard patient care schemes have been outlined by a multidisciplinary expert committee, for each dialysis technique, and have been valorised using publicly available data and tariffs recorded in 2005. Our result show that home dialysis techniques are the less costly, with an average annual cost per patient of 49.9, 49.7 and 50.0 k euro respectively for home haemodialysis, automated peritoneal dialysis, and continuous ambulatory peritoneal dialysis. Autodialysis, autonomous in-center haemodialysis and in-center haemodialysis respectively cost 59.5, 62.3 and 81.5 k euro per patient and per annum. The total 2005 cost of dialysis for the Health Insurance is estimated at 2.1 billion euro. Therefore, the development of alternative techniques to in-center haemodialysis, such as home dialysis or autonomous in-center haemodialysis, autodialysis being already well developed, could generate savings for the Health Insurance. From the patient's perspective, it could also allow the enlightened choice of the best customized technique, less guided by local offer than by medical or social criteria, as well as by the patient's own opinion.

A new compact spaceborne high-resolution spectrometer developed for the European Space Agency's Venus Express spacecraft is described. It operates in the IR wavelength range of 2.2 to 4.3 microm and measures absorption spectra of minor constituents in the Venusian atmosphere. It uses a novel echelle grating with a groove density of 4 lines/mm in a Littrow configuration in combination with an IR acousto-optic tunable filter for order sorting and an actively cooled HgCdTe focal plane array of 256 by 320 pixels. It is designed to obtain an instrument line profile of 0.2 cm(-1). First results on optical and spectral properties are reported.

Treatment of renal insufficiency is, in it principle, covered by "hospital law" and its decrees of application: however the regulations for these methods of treatment only concern hemodialysis centers. CAPD is only subjected to a memorandum from the "Caisse Nationale d'Assurance Maladie" (National Medical Insurance) dated November 26, 1979, which fixes a weekly price. The text only concerns CAPD with single bag and does not deal the new methods. These new techniques are very expensive and well above the current weekly fixed price. According to a survey of the cost, carried out by AURA (Paris), during the first six months in 1992, the price of such techniques involves an average additional cost of 45% when double bags were used and 80% when APD was operated. In the long term, these techniques will result in substantial savings for the National Medical insurance scheme by reducing the risk of peritonitis and by facilitating patients' social and professional activity. However, the absence of adequate reimbursement causes running deficits and curbs development. Public Service Authorities should consider all these factors and should not forget that PD is generally cheaper than hemodialysis.

The topsoil of a 14.5 km(2) region of the Swiss Jura has been surveyed to identify the distributions of trace metals in it. The soil was sampled at 366 sites selected by combining a square grid and nesting. Concentrations of seven potentially toxic metals, namely Cd, Co, Cr, Cu, Ni, Pb and Zn, were measured. Land use and geology (stratigraphy) were also recorded. Variograms were bounded in the range from 110 m to 1500 m with contributions to the variance at all distances exceeding 6 m. The variograms of Cd, Cr, Cu and Pb are dominated by short range correlation, those of Co and Ni by correlation of long range, and Zn is intermediate. The concentrations were estimated at the nodes of a fine grid by ordinary block kriging and then contoured to produce maps. The maps of Co and Ni have a coarse patchy pattern similar to that of the geology, suggesting that these metals derive from the bedrock. This is supported by analysing the variance by geology. Copper and Pb have finer patterns of distribution, and are more likely to have been added with fertilizer or manure or domestic waste. Cadmium could originate from human activities, such as smelters or fertilizer spreading, or from specific geological deposits, such as moraine.

The concentrations of cadralazine in plasma were studied in 101 hypertensive patients treated with oral doses of 10, 15, or 20 mg of cadralazine once daily. Most of the patients received additionally a beta-blocking drug (n = 87) and a diuretic (n = 52). Few blood samples were collected in each patient on several occasions during the treatment, which usually lasted for more than 6 months. No accumulation of cadralazine in plasma occurred in any of the patients and the maximum concentrations were similar to those recorded in a small sample of healthy volunteers. The terminal half-life of elimination (3.6 h) was longer than that observed in healthy subjects (approximately 2.5 h). Conversely, the total clearance (197 ml/min) was lower (285 ml/min in healthy). The half-life and the total clearance in plasma were not dose dependent. In the patients treated for more than 6 months, no change in the pharmacokinetics of cadralazine was detected. The description of the distribution of concentrations showed that one-half of the patients behaved similarly to healthy subjects concerning half-life and total clearance. The other half presented a slower elimination of the drug (t 1/2 = 4.4 h and ClT = 130 ml/min) and these patients were significantly older (p = 0.01) than the former. This suggests that special attention should be paid to old hypertensive patients when a dose higher than 15 mg once daily is prescribed. Though concentrations were proportional to the dose, the body weight was not found to be a determining factor for dose adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)

Pirprofen (100 or 200 mg; Rengasil) was administered to experimental groups of children (children with juvenile chronic arthritis, JCA) and to a control group of children (children without JCA) as a single dose or as repeated doses. The pharmacokinetics of pirprofen in these children were compared to the pharmacokinetic parameter values obtained in healthy volunteers and in elderly arthritic adults receiving 400 mg of pirprofen. The children were examined regularly and laboratory values were determined in order to detect possible side effects. The results demonstrated that the pharmacokinetics of pirprofen were similar for children and adults when taking into account the dose and the body weight. There was no drug accumulation after repeated administration of pirprofen. As already observed in rheumatic adults, pirprofen remains in synovial fluid longer than in plasma.

An overview of methods for the determination of benzodiazepines in biological media, based on the application of chromatographic techniques, is presented. A general discussion of the techniques in terms of stability, selectivity, validation, standardization, detection and sensitivity is given. No single technique can be claimed as the method of choice for benzodiazepines. Gas chromatography with electron-capture detection has some strong claims and shows generally good sensitivity and reproducibility. High-performance liquid chromatographic equipment is readily available in most laboratories. The ultimate choice of an assay method for benzodiazepines will be determined by the clinical application (routine monitoring, pharmacokinetics, overdose, forensic medicine) and by the characteristics of the benzodiazepine, the expertise of the analyst, the equipment available, the desired sensitivity and specificity and the time involved in method development or adaptation and validation.

The pharmacokinetics of oxiracetam in patients with renal impairment were investigated after administration of a 800 mg single oral dose of oxiracetam. The renal insufficiency was estimated on the basis of the creatinine clearance (CLcr) which ranged from 9 to 95 ml/min among the 20 patients. In plasma, the terminal elimination half-life (T1/2) ranged from 10.6 to 68.1 h, the highest T1/2 corresponding to the patients with a high degree of renal impairment. In urine, the amounts of oxiracetam excreted during the 48 h postdosing represented 8.3 to 82.6% of the dose. They were lower in patients with a high degree of renal impairment. The correlations between the total clearance of oxiracetam, the renal clearance, the terminal apparent elimination rate constant in plasma, and CLcr were estimated by linear regression analysis. The correlation coefficients were 0.916, 0.985 and 0.803 respectively. The apparent volume of distribution of the central compartment V(1) and the total volume of distribution at the steady-state V(SS) were not dependent on the degree of renal impairment. The mean values +/- SD were 25.9 +/- 13.0 litres and 48.3 +/- 21.5 litres respectively. Oxiracetam concentrations in plasma of patients were estimated for repeated administration of 800 mg of oxiracetam.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacokinetics of oxiracetam have been studied in eighteen elderly patients and in six healthy non-geriatric adults. A 800 mg single oral dose was administered in the morning of the first day and repeatedly, every 12 h, from day 2 evening to day 10 morning, to the elderly patients. The healthy non-geriatric adults were given a 800 mg single oral dose of oxiracetam. In healthy non-geriatric subjects after a single oral administration of 800 mg, the normalized plasma levels of oxiracetam for 1 mg/kg dose were similar to those already recorded after a 2000 mg single dose of oxiracetam. Therefore, there was no tendency towards non-linear pharmacokinetics of oxiracetam between 800 and 2000 mg single doses in healthy subjects. After the single oral dose, the mean area under the plasma concentration-time curve of oxiracetam in elderly patients was increased by a factor of two as compared to that observed in non-geriatric healthy subjects whereas the maximum concentration (Cmax) was almost not modified and slightly delayed. This can be explained by a slower absorption and elimination in the elderly patients. The highest oxiracetam levels were predominantly recorded in the oldest patients. The slower elimination (mean T1/2 = 12.3 h in elderly and 7.7 h in healthy subjects) could be attributed to a physiological decrease of the renal function. The volume of distribution was not significantly modified in the elderly patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Two healthy male volunteers received 10 mg carbamazepine (CBZ) as a 2-h constant-rate intravenous (i.v.) infusion and 100 mg 15N-labeled CBZ as a 2% oral suspension, concomitantly. The two compounds have identical pharmacokinetics. Their respective concentrations in plasma were determined by gas chromatography-mass spectrometry (GC-MS) for 168 h. The comparison of the areas under the plasma curves (AUC) obtained by the two routes of administration, showed the systemic availability of CBZ given as an oral suspension to be equal to its availability when given intravenously. A two-compartment model was estimated: The apparent volume of distribution of CBZ at the steady-state (Vss) was approximately 1 L/kg.

A column-switching high-performance liquid chromatographic method was developed for the determination of oxiracetam in plasma and urine. A sample of plasma (250 microliters) or urine (10 microliters) is mixed with the internal standard solution, 4.2 ml of acetonitrile-water (1000:4, v/v) and 0.8 ml of dichloromethane, and 1 ml of the clear solution is injected onto a first column filled with Li-Chrosorb NH2. The sample is eluted with acetonitrile-water (95:5, v/v). The portion of the eluate (heart-cutting) from this column containing the compounds of interest is selected and loaded on a Nucleosil NH2 column and eluted with acetonitrile-water (90:10, v/v). During this chromatography the first column (LiChrosorb NH2) is rinsed with acetonitrile-water (50:50, v/v). Ultraviolet detection at 200 nm is used for quantitation. The limit of quantitation of oxiracetam is ca. 1.5 microM (240 ng/ml) in plasma and 76 microM (12 micrograms/ml) in urine. Oxiracetam was stable in plasma and urine samples kept frozen at -20 degrees C for nine months and one year, respectively.

A high-performance liquid chromatographic (HPLC) method was developed to determine the (+)- and (-)-enantiomers of pirprofen, an anti-inflammatory drug. After addition of an internal standard, the plasma sample was brought onto a glass column pre-packed with silica and eluted with dichloromethane. The extracts were derivatized with 1,1'-carbonyldiimidazole and R (+)-1-methylbenzylamine to form the two diastereomeric amides. The diastereoisomers were separated on a chiral column by HPLC with ultraviolet detection at 272 nm using n-hexane-dichloromethane (64:36, v/v) as the mobile phase. The limit of quantitation was 0.992 mumol/l (0.25 microgram/ml) for each enantiomer.

In view of the considerable variations in contour shapes noted in transverse sections of myelinated axons from dental pulps a morphometric method involving image analysis (TAS Leitz) was used to calculate directly the surfaces of the nerves in sections of human root pulp using the Bodian stain. The sample studies consisted of 26 patients aged 10.5 to 72 years. The variation in numbers of myelinated pulpal nerves was analysed by age. Of 3606 myelinated fibres measured, 95% had a diameter less than 5 microns (A delta fibres) and about 0.5% had a diameter greater that 7 microns (A beta fibres). The mean diameter of these myelinated fibres was 2.90 microns. The statistical analysis clearly showed a difference in distribution between these fibres in young and very old subjects. The total number of pulpar myelinated fibres decreased with age particularly at the expense of a A delta fibres. The A beta fibres remained constant. This decrease of A delta fibres with age may be related to a reduced sensitivity to the perception of dental pain transmitted by these fast-conducting A delta fibres.

The pharmacokinetics of clofazimine was evaluated in 12 healthy male volunteers following single and multiple oral doses of clofazimine. Six volunteers received a single dose of 200 mg together with food. A 200-mg dose was administered to three volunteers either with or without food. In a multiple-dose experiment, three volunteers were repeatedly dosed with 50 mg per day together with food for 8 days. Following a single oral dose of 200 mg, the mean peak plasma concentration of clofazimine was 861 +/- 289 pmol/g (+/- S.D., N = 6) after 8 hr (median). The mean terminal half-life was 10.6 +/- 4.0 days. Comparison of the bioavailability of clofazimine administered with or without food revealed a 60% higher mean area under the curve (AUC) value and a 30% higher mean maximum concentration (Cmax) value with food (N = 3). The median of times to peak (Tmax) was 8 hr with food and 12 hr without food. In the multiple-dose study, good agreement was found between the mean experimental plasma concentration values and the plasma concentration profile predicted from the single-dose pharmacokinetics. The elimination half-life calculated from the terminal phase of the individual profiles after the last dose was 8.8 +/- 1.0 days (+/- S.D., N = 3). The half-life obtained from the fitted mean multiple-dose profile was 10.5 days. The slow elimination of clofazimine has its implications for the treatment regimen in patients. To avoid the long-lasting accumulation toward the steady state, higher daily loading doses are recommended at the beginning of therapy followed by a daily maintenance dose.

The metabolism of hydralazine (1-hydrazinophthalazine hydrochloride, Apresoline) was investigated in 17 hypertensive patients of known acetylator status who were chronically treated with oral doses of 50 mg b.i.d. or 100 mg b.i.d. hydralazine. The acetylator status was assessed either by the monoacetyldapsone/dapsone ratio or by the isoniazide plasma half-life. In each patient the tests were performed on two different days of treatment and they included the analyses of four hydralazine metabolites (NAc-HPZ, 3OH-MTP, MTP and TP), as well as apparent hydrazine in urine and also the determination of plasma concentrations of apparent hydralazine. All data of the two experiments performed within an interval of at least five days were in good agreement, thus indicating that the patients were in pharmacokinetic steady states. No correlation was detectable between any of the determined amounts of metabolites of hydralazine and the assigned acetylator status of the patients. On the other hand the rank order of the urinary yields of the two main metabolites NAc-HPZ and 3OH-MTP suggest to be a representative scale for the patients' status in respect to the biotransformation of the drug itself. The urinary yield of apparent hydrazine is dependent on the pH applied during the analyses and is not correlated with any of the other data recorded. The findings of the present study support the assumption that measuring a relevant prominent metabolite of the drug itself may lead to a more reliable assessment of the particular metabolic status of the patients than by classification through a non treatment related foreign compound.(ABSTRACT TRUNCATED AT 250 WORDS)

A sensitive and enantiospecific gas chromatographic method for the determination of the S(+)- and R(-)-enantiomers of baclofen (I and II) in plasma and urine has been developed and validated. The method is based on the complete resolution of the derivatized enantiomers on a chiral fused-silica capillary column. The hydrochloride salt of a (-)-fluoro analogue of baclofen (III.HCl) was used as the internal standard in plasma, the hydrochloride salt of a (+)-fluoro analogue of baclofen (IV.HCl) as the internal standard in urine. Rapid and convenient isolation of the compounds was achieved using reversed-phase Bond-Elut C18 columns. After elution, the compounds were converted into isobutyl esters and purified by base-specific solvent extraction. The isobutyl esters were then N-acylated with heptafluorobutyric anhydride. The derivatives were quantitated after separation on the chiral column using electron-capture detection. The analysis of spiked plasma and urine samples demonstrated the good accuracy and precision of the method, with limits of quantitation of 25 nmol/l for I and II in plasma and of 2 mumol/l for I and II in urine. The method appears to be suitable for use in pharmacokinetic studies of the enantiomers in plasma and urine from animals and man after administration of the racemic baclofen.