Lupin (Lupinus spp.) seeds exert anthelmintic activity associated with their alkaloid content.

The growing range of drug resistant parasitic nematode populations threatens the sustainability of ruminant farming worldwide. In this context, nutraceuticals, animal feed that provides necessary dietary requirements while ensuring parasite control, could contribute to increase farming sustainability in developed and low resource settings. In this study, we evaluated the anthelmintic potential of lupin seed extracts against the major ruminant trichostrongylids, Haemonchus contortus and Teladorsagia circumcincta. In vitro observations showed that seed extracts from commercially available lupin varieties could significantly but moderately inhibit larval migration. This anthelmintic effect was mediated by the seed alkaloid content and was potent against both fully susceptible and multidrug resistant H. contortus isolates as well as a susceptible T. circumcincta isolate. Analytical chemistry revealed a set of four lupanine and sparteine-derivatives with anthelmintic activity, and electrophysiology assays on recombinant nematode acetylcholine receptors suggested an antagonistic mode of action for lupin alkaloids. An in vivo trial in H. contortus infected lupin-fed ewes and goats failed to demonstrate any direct anthelmintic effect of crude lupin seeds but infected lupin-fed goats suffered significantly less parasite-mediated blood losses. Altogether, our findings suggest that the anthelmintic potential of lupin remains limited. However, the potent alkaloids identified could lead to the development of novel drugs or may be used in combination with current anthelmintics to improve their efficacy.

Balneotherapy Together with a Psychoeducation Program for Benzodiazepine Withdrawal: A Feasibility Study.

Benzodiazepines should be prescribed on a short-term basis, but a significant proportion of patients (%) use them for more than 6 months, constituting a serious public health issue. Indeed, few strategies are effective in helping patients to discontinue long-term benzodiazepine treatments. The aim of this study was to assess the feasibility and the impact of a program including cognitive behavioural therapy, psychoeducation, and balneotherapy in a spa resort to facilitate long-term discontinuation of benzodiazepines. We conducted a prospective multicentre cohort study. Patients with long-term benzodiazepine use were recruited with the aim of anxiolytic withdrawal by means of a psychoeducational program and daily balneotherapy during 3 weeks. The primary efficacy outcome measure was benzodiazepine use 6 months after the program, compared to use at baseline. A total of 70 subjects were enrolled. At 6 months, overall benzodiazepine intake had decreased by 75.3%, with 41.4% of patients completely stopping benzodiazepine use. The results also suggest a significantly greater improvement in anxiety and depression symptoms among patients who discontinued benzodiazepines compared to patients who only reduced their use. Our findings suggest that balneotherapy in association with a psychoeducative program is efficient in subjects with benzodiazepine addiction.

Pre- and post-partum mild underfeeding influences gene expression in the reproductive tract of cyclic dairy cows.

Undernutrition before and after calving has a detrimental effect on the fertility of dairy cows. The effect of nutritional stress was previously reported to influence gene expression in key tissues for metabolic health and reproduction such as the liver and the genital tract early after calving, but not at breeding, that is, between 70 and 90 days post-partum. This study investigated the effects of pre- and post-partum mild underfeeding on global gene expression in the oviduct, endometrium and corpus luteum of eight multiparous Holstein cows during the early and middle phases of an induced cycle 80 days post-partum. Four control cows received 100% of energy and protein requirements during the dry period and after calving, while four underfed received 80% of control diet. Oestrous synchronization treatment was used to induce ovulation on D80 post-partum. Oviducts, ovaries and the anterior part of each uterine horn were recovered surgically 4, 8, 12 and 15 days after ovulation. Corpora lutea were dissected from the ovaries, and the endometrium was separated from the stroma and myometrium in each uterine horn. The oviduct segments were comprised of ampulla and isthmus. RNAs from ipsi- and contralateral samples were pooled on an equal weight basis. In each tissue, gene expression was assessed on a custom bovine 10K array. No differentially expressed gene (DEG) in the corpus luteum was identified between underfed and control, conversely to 293 DEGs in the oviduct vs 1 in the endometrium under a false discovery rate (FDR) < 0.10 and 1370 DEGs vs 3, respectively, under FDR < 0.15. Additionally, we used dedicated statistics (regularized canonical correlation analysis) to correlate the post-partum patterns of six plasma metabolites and hormones related to energy metabolism measured weekly between calving and D80 with gene expression. High correlations were observed between post-partum patterns of IGF-1, insulin, ß-hydroxybutyrate and the expression in the oviduct of genes related to reproductive system disease, connective tissue disorders and metabolic disease. Moreover, we found special interest in the literature to retinoic acid-related genes (e.g. FABP5/CRABP2) that might indicate abnormalities in post-partum tissue repair mechanisms. In conclusion, this experiment highlights relationships between underfeeding and gene expression in the oviduct and endometrium after ovulation in cyclic Holstein cows. This might help to explain the effect of mild undernutrition on fertilization failure and early embryonic mortality in post-partum dairy cows.

[Needs and expectations of Alzheimer's disease family caregivers]. / Attentes et besoins des aidants de personnes souffrant de maladie d'Alzheimer.

BACKGROUND: Family members of people suffering from Alzheimer's disease play a major role in providing daily life care for their relatives. Compared to non-caregivers, they present increased risks of mortality as well as psychological and physical co-morbidity. Altered relationships between caregivers and medical staff and dissatisfaction with the quality of help provided tend to increase the risk of depression and anxiety disorders among caregivers. The present study aimed at exploring the needs and expectations of family caregivers of patients with Alzheimer's disease who request medical assistance for their relatives. METHODS: The present analysis is an ancillary study of a large multicentric controlled randomized study designed to assess the efficacy of three non-pharmacological treatments in Alzheimer's disease, in which 645 mild-to-moderate Alzheimer patients were enrolled. Needs and expectations of the caregivers were assessed with a French scale of patient expectations for medical consultation, the échelle d'attentes en matière de consultations (EAC), completed by caregivers during the inclusion visit. This scale consists in a self-administered 28-item questionnaire concerning four main needs: learning skills to improve daily life management of their relatives; information regarding the disease; improving caregivers' self-confidence; support to improve communication with their relatives. RESULTS: The ten items for which more than 40% of caregivers reported high or very high expectations referred to two main needs: information regarding the disease (treatment, prognosis…) and learning skills in order to improve daily life management of their relative. The predominance of such needs was observed whatever the relationship between the caregiver and the cared relative but seemed to be more pronounced in female spouses and children of patients with Alzheimer's disease. CONCLUSIONS: Needs and expectations of Alzheimer's disease family caregivers involve two major aspects: first, information regarding the disease (treatment, prognosis…) and second, learning skills for improving daily life management of their relative. These results suggest that among the various available family caregivers support programs, programs providing information, education, and practical advice to improve daily life assistance seem to be adequate.

Lysophosphatidic acid receptors in ovine uterus during estrous cycle and early pregnancy and their regulation by progesterone.

In the present study, we examined the lysophosphatidic acid (LPA) pathway in the ovine uterus during the estrous cycle and early pregnancy. With the use of quantitative reverse transcription PCR, expression of LPAR1 and LPAR3 was analyzed. Both receptors were present in the ovine uterus. Immunolocalization showed that LPAR1 was mainly present in the stroma of the ovine endometrium, whereas LPAR3 was mostly restricted to epithelial compartments. In luminal and glandular epithelia, LPAR1 and LPAR3 levels were affected by pregnancy status, day, or the day-by-status interaction, whereas in stroma the receptors were not modified. Analysis of the whole endometrium from ovariectomized ewes showed that the expression of LPAR3 but not LPAR1 was regulated by the administration of progesterone. However, the examination of receptors at cellular levels showed that progesterone increases LPAR1 and LPAR3 in glandular epithelium and, in a minor extent, in endometrial stroma. Emerging evidence suggests that LPA is an essential component in the estrous cycle and early pregnancy regulation. We demonstrated that LPA induced stress fiber formation in ovine uterine epithelial cells, suggesting that LPA may be involved in cytoskeleton reorganization occurring cyclically in ovine uterus.

Balneotherapy, prevention of cognitive decline and care the Alzheimer patient and his family: outcome of a multidisciplinary workgroup.

According to the latest forecasts of the INSEE - Institut National de la Statistique et des Etudes Economiques (National Statistics and Economic Studies Institute), ageing of the French population will increase between 2005 and 2050: whereas 20.8% of the population living in continental France reached the age of 60 years or more in 2005, this proportion would be of 30.6% in 2035 and 31.9% in 2050. In 2050, 22.3 million persons will have reached the age of 60 years or more compared to 12.6 million in 2005, increasing by 80% in a 45-year period. In line with the actual age pyramid, ageing is unavoidable, as those who will reach 60 years of age in 2050 are already born (in 1989 or before). This expansion will be most important between 2006 and 2035, when the numerous "baby-boom" generations born between 1946 and 1975, will reach these ages. In future years, lifespan improvement will only emphasize this increase. Even if life expectancy stabilizes at the 2005 level, the number of seniors reaching 60 years or more would still increase to 50% between 2005 and 2050. This issue is identical in all countries of the European Union. Ageing is a major risk factor for dementia that will considerably worsen in the next years, if no curative therapies are found. Today, 25 million persons in the world suffer from Alzheimer's disease (AD). In France, it is estimated that 860,000 persons are affected and that 225,000 news cases are annually diagnosed. After 75 years of age, more than 20% of women and 13% of men are concerned. Forecasts for the coming years are frightening. Considering ageing of the population, the number of Alzheimer's disease cases should raise to 1.3 million in 2020 (20 patients for 1000 inhabitants) ant 2.1 million in 2040 (30 patients for 1000 inhabitants).

Developmental regulation of prostacyclin synthase and prostacyclin receptors in the ovine uterus and conceptus during the peri-implantation period.

This study documents the expression of prostacyclin (PGI2) synthase (PTGIS) and PGI2 receptors in the trophoblast and uterus of the ewe at the time of maternal recognition of pregnancy (i.e. days 7, 9, 12, 14 and 17). The membrane receptor for PGI2 (PTGIR) and the nuclear receptors, i.e. peroxisome proliferator-activated receptors (PPAR) and their heterodimer partners the retinoid X receptors (RXR), were analysed. In the endometrium, PTGIS transcript and protein were expressed at day 9 of pregnancy and levels declined from days 12 to 17. Immunohistochemistry and in situ hybridization indicated that PTGIS was mainly located in the luminal epithelium of the endometrium. Endometrial PTGIR, PPARA, PPARG and RXRG expression was regulated during the peri-implantation period whereas PPARD, RXRA and RXRB were consistently expressed. In the trophoblast, PTGIS transcript levels rose as development progressed and peaked at day 17. PTGIR and PPARA transcripts peaked before day 12 and then declined and became nearly undetectable by day 17, whereas PPARD and PPARG transcript levels rose steadily from days 12 to 17. Because the PPARs and the RXRs display different expression profiles, we suggest that different heterodimers may form and support distinct functions as development proceeds. Our results also underline the importance of PTGIS and PPARD in the trophoblast and PTGIR in the uterus, suggesting that PGI2 is of both uterine and trophoblastic origin and is involved in a complex signalling pathway at around the time of implantation in the ewe.

Identification of differentially regulated genes during elongation and early implantation in the ovine trophoblast using complementary DNA array screening.

Following hatching, pre-elongated conceptuses undergo elongation by intense proliferation, until implantation. We investigated the changes in gene expression associated with these physiological events using human cDNA arrays containing 2370 known genes. Comparison of pre-elongated, elongated, and implanting trophoblasts allowed the determination of 313 expressed genes, 63 of which were differentially regulated. These were classified into four functional families. Pre-elongated trophoblasts were characterized by preferential expression of genes involved in protein trafficking, whereas only latter developmental stages expressed cell signaling genes and receptors. Among the 63 developmentally regulated genes, four exhibited the highest levels of expression (TMSB10, CTNNA1, NMP1, and CX3CL1). Each of these also represents a functional family and display a specific expression pattern. One of them, CX3CL1 (CX3C chemokine, also known as fractalkine), is a chemokine that seems to have potential importance in trophoblast development, and which deserves further clarification of its role in implantation.

Rigorous decimation-based construction of ground pure states for spin-glass models on random lattices.

A constructive scheme for determining pure states at very low temperature in the 3-spins glass model on a random lattice is provided, in full agreement with Parisi's one step replica symmetry breaking (RSB) scheme. Proof is based on the analysis of a partial decimation procedure and of the statistical properties of its output, i.e., a reduced Hamiltonian acting on a subset of the initial spins. The number of ground states (GS) in each state, the number of states, and the distances between GS are calculated and correspond to RSB predictions.

[Computerized obstetrical record of the North Pas-de-Calais region]. / Dossier obstétrical informatisé de la région Nord - Pas-de-Calais.

The computerized obstetrical record of the North-Pas-de-Calais region proceeds from the desire of a number of people from the Regional Health Observatory, to dispose of a prospective epidemiologic tool in the field of perinatology. The objective is a better knowledge of the cause of perinatal death, analyzing the modalities of prenatal monitoring, delivery conditions, transfer of the newborns, as well as socio-economical conditions. The program manages the computerization of a usual obstetrical file, in the region, including approximately 200 items and allowing every possible comparison with the well-known CCIM record. The program permits local treatment of the data (statistical calculations) in each maternity hospital: rapid transmission of information between maternity and correspondents (computerized personalized mail), a base of agreement between the different protagonists: midwives, pediatricians, specialists, an easier collaboration with the protection agencies and, especially, the Regional Direction of Sanitary and Social Affairs, with automatic response to hundreds of questions of the yearly questionnaire, which saves a great deal of time and an extreme reliability of the information. This program is compatible with any IBM PC microcomputer and includes a hard disk of 10 or 20 mega-octets. The current price (microcomputer with hard disk, monitor, keyboard, letter-quality printer, management program) make all these performances available at a relatively low expense, under 25,000 francs (not including the tax).

[Variations in birth weight as a function of various fetal and maternal characteristics. The application to the diagnosis of hypotrophy]. / Variations du poids de naissance en fonction de diverses caractéristiques foetales et maternelles. Application au diagnostic d'hypotrophie.

The known variations in weight for gestational age as well as compounding maternal and/or fetal factors, puts into question the usual definition of small for gestational age (SGA) which is based on gestational age alone. On the basis of more than 20,000 births studied in 4 maternity hospitals from 3 separate regions in France, the authors propose a new definition for growth retardation in full-term babies, taking into account 4 factors: gestational age, sex, birth rank, height and usual weight of mothers. This definition allows constitutionally SGA newborns to be considered normal, while some babies previously classified as normal would now lead one to suspect intra-uterine growth retardation (IUGR). This approach tries to take constitutional and environmental risk factors into account in fetal growth hopefully allowing for help better detection of IUGR.

[Transfer of neonates in northern france. Factors of mortality (author's transl)]. / Transferts des nouveau-nés dans la région Nord. Facteurs de risque de mortalité des enfants de moins de 2 000 grammes.

An extensive study was undertaken in northern France from January 1st to May 31st 1978, concerning the transfer of neonates from maternity hospitals to specialized units. Analysis of 250 children whose birth weight was below 2,000 gm showed that several risk factors could be taken into account to reduce neonatal mortality in this area. Prematurity (22% children weighing less than 1,500 gm in those discharged alive, 54% in the dead), neonatal distress (36% versus 61% of resuscitation) hypothermia (7% versus 23% with temperature below 34 degrees 6 at the time of admission), the need for an other transfer (1% vs. 12%) seem to be features highly related with poor prognosis. This stresses the importance of the prevention of prematurity, of proper management of the babies in the maternity hospital, of the conditions of transport and of the choice of the neonatal unit.

New concepts for a microprocessor oriented long term intelligent monitoring of newborns.

This paper is based on the utilization of the very elementary principle of linear regression used in a recursive way. This technique tested on electrophysiological signals readily leads to the conception of a monitoring system built on a biprocessor unit. In a clinical context, the use of microprocessors leads then to the design of very compact devices including the capability of distributed processing which embrances the concept of intelligent monitoring. Finally, a proposal is given for the realization of a complete monitoring control desk (MCD) devoted to the survey of eight patients.