[Contribution of mindfulness meditation in cognitive behavioral therapy for insomnia]. / Apport de la pleine conscience dans les thérapies cognitives et comportementales de l'insomnie.

INTRODUCTION: Insomnia is considered to be a serious public health issue affecting approximately 10% of adults. Chronic insomnia may increase the risk of health problem, psychological vulnerability and proneness to accidents. Cognitive behavioral therapy for insomnia (CBT-I) is recommended as the first line of treatment. Even though CBT-I is widely considered as an effective therapy, 20 to 30% of patients do not respond to this treatment. Mindfulness therapy, known to reduce rumination and stress, could be an interesting complement to enhance CBT-I. The aim of this study is to evaluate the efficacy of therapy combining mindfulness meditation and CBT-I for the treatment of chronic insomnia. METHODS: Thirty-three patients, diagnosed with chronic insomnia, aged 18 to 75 years (51±15 years) were recruited between October 2015 and June 2016 at the Sleep Center of Marseille. The patients were then divided into two groups according to their psychotherapy method: group CBT-I alone (17 patients) or a group therapy combining CBT-I and Mindfulness (16 patients). All participants were given five sessions of standard CBT during eight weeks. The patient-reported outcome measures were sleep onset latency, wake after sleep onset (WASO), total wake time, total sleep time, time in bed, sleep efficiency and number of awakening from sleep diaries before treatment (T0) and six weeks later (T1). Assessments were done using Pittsburgh Sleep quality index (PSQI), Insomnia severity Index (ISI), the Epworth sleepiness scale, the hospital anxiety and depression scale (HAD), the dysfunctional beliefs and attitude about sleep (DBAS-16); further, the use of sleeping pills was also recorded at T0 and T1. RESULTS: Out of the 33 participants who began the treatment, 29 completed all sessions and were included in the analyses (4 dropouts in the group CBT-I alone). The data shows that each treatment yielded significant improvements over time in sleep variables from the diary, PSQI, ISI, anxiety (P=0.004), DBAS 16, sleeping pill use and vitality measured by SF36 health survey (P=0.004). Comparing the results of the two therapy groups, the meditation associated to CBT-I shows significantly greater rates of reduction in WASO relative to CBT-I group (P=0.009). CONCLUSIONS: This study confirms the beneficial effects of CBT for patients suffering from insomnia on sleep parameters, anxiety symptoms and quality of life. Furthermore, this study suggests, for the first time, that combining CBT and mindfulness is a superior approach compared to that of only conventional CBT-I in improving sleep.

Establishment of ruminal bacterial community in dairy calves from birth to weaning is sequential.

AIM: Establishment of ruminal bacterial community in dairy calves. METHODS AND RESULTS: Rumen bacterial community was analysed on 6 calves bred according to commercial practices from day one to weaning at day 83 of age, using 454 16S rRNA-based pyrosequencing. Samples taken at day 1 did not produce amplicons. Analysis of data revealed a three-stage implantation process with a progressive but important shift of composition. At day 2, the bacterial community was mainly composed of Proteobacteria (70%) and Bacteroidetes (14%), and Pasteurellaceae was the dominant family (58%). The bacterial community abruptly changed between days 2 and 3, and until day 12, dominant genera were Bacteroides (21%), Prevotella (11%), Fusobacterium (5%) and Streptococcus (4%). From 15 to 83 days, when solid food intake rapidly increased, Prevotella became dominant (42%) and many genera strongly decreased or were no longer detected. A limited number of bacteria genera correlated with feed intake, rumen volatile fatty acids and enzymatic activities. CONCLUSION: The ruminal bacterial community is established before intake of solid food, but solid food arrival in turn shapes this community. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides insight into the establishment of calves' rumen bacterial community and suggests a strong effect of diet.

[Fixed drug combinations in hypertension: a budget impact analysis for the Spanish Health System on the marketing of a fixed combination of olmesartan/amlodipine]. / Las combinaciones fijas en hipertensión: análisis de impacto presupuestario para el Sistema Nacional de Salud Español de la comercialización de la combinación fija de olmesartan/amlodipino.

OBJECTIVE: To carry out a budget impact analysis (BIA) of olmesartan/amlodipine (20/5, 40/5 and 40/10mg) marketed as a fixed combination (FC) in its approved indication for the National Health System (NHS). DESIG: We developed a decision tree model in order to estimate usual hypertension treatment algorithm in Spanish clinical practice. SETTINGS: The BIA has been developed from the perspective of the NHS for a period of 3 years (years 2010-2012). PARTICIPANTS: Spanish hypertensive population ≥ 35 years old. INTERVENTIONS: Introduction into the market of a fixed combination (FC) olmesartan/amlodipine in Spain. PRIMARY MEASURES: Expected costs to be assumed by the Spanish NHS (RRP-VAT) for hypertensive population able to be treated with the FC versus currently assumed costs by the NHS with free combination olmesartan and amlodipine. RESULTS: Estimated pharmaceutical costs in hypertensive population treated with olmesartan and amlodipine (2 pills) would be €25.2M (1(st) year), €26.4M (2011), €27.6M (2012), with a total 3-year period of €79.2M. According to patient tree model, the population able to be treated with FC would be 71,283 patients (2010), with a growth rate of 4.8% in the successive years, which supposes an annual cost of €21.2M (2010), €21.8M (2011) and €22.4M (2012), with a total 3-year period of €65.4M. The BIA shows savings of €13.8M in a total 3-year period. CONCLUSION: The BIA of FC olmesartan/amlodipine could generate net savings of €13.8M for the NHS in the period ranging from years 2010 to 2012.

Tratamento da Alopecia Areata / Treatment of alopecia areata

Alopecia Areata é uma enfermidade relacionada á perda nao cicatricial de cabelos. É difícil de ser tratada devido a sua natureza inflamatória crónica. Apresenta algumas variáveis (inicio, duraçao, extensao) e uma evoluc;ao imprevisível, o que torna dificil o planejamento e a comparaçao dos estudos. Os autores revisa m o trata mento da alopecia areata

Alopecia Areata is a nonscarring hair loss condition. It is difficult to treat because of its chronic, inflammatory nature. It presents some variables (onset, duration, extent) and an unpredictable evolution that make elinical trials difficult to plan and to compare. The authors review the treatment of alopecia areata

Serial topoisomerase II expression in primary breast cancer and response to neoadjuvant anthracycline-based chemotherapy.

OBJECTIVE: We analyzed the value of topoisomerase IIalpha (Topo II) in predicting the clinical response to anthracycline-based neoadjuvant chemotherapy in breast cancers and the potential changes in Topo II after chemotherapy. In parallel, HER2, which is commonly coexpressed with Topo II, and p53, a modulator of chemotherapy activity, were also analyzed. METHODS: Forty-one patients with primary breast cancer and treated with neoadjuvant anthracycline-based chemotherapy (FAC or FEC) were included for the present study. Topo II, HER2 and p53 expression were measured by immunohistochemistry in pre and post chemotherapy (at the time of surgery), tumor specimens and the results were correlated with the clinical response. RESULTS: Topo II was overexpressed in 16 of 41 (31%) tumors before treatment, and this overexpression was significantly associated with clinical response (p = 0.03). HER2 and p53 were unrelated to response. Notably, Topo II overexpression, but not HER2 or p53, was lost in specimens after chemotherapy (p = 0.01). CONCLUSION: The observed link between Topo II and the clinical response to neoadjuvant anthracycline-based chemotherapy, together with its loss after chemotherapy, implies that Topo II deserves further testing in a prospective setting as a predictive marker.

[Gamma knife radiosurgery for the treatment of severe epilepsy]. / Rôle de la radiochirurgie Gamma Knife dans le traitement des épilepsies sévères.

The Gamma Knife radiosurgery is a neurosurgical approach having now demonstrated well its efficiency, its low morbidity and its comfort in the treatment of numerous neurosurgical disorders. These advantages of this type of intervention make it a method of great interest in functional neurosurgery and quite particularly in surgery of epilepsy. French experience is a pionner one in this domain. If for several years the positive evolution of the epilepsy associated to brain lesions had been noticed after the Gamma Knife radiosurgical treatment, the use of this approach in surgery of the epilepsy is systematically estimated since 1993. Data are today available concerning the surgical treatment of the epilepsies originating in temporomesiale area without occupying process, epilepsies associated to hypothalamic hamartomas and epilepsies associated to cavernous angiomas or to low grade gliomas. The quality of the epileptological result obtained in these various indications associated to a very reduced morbidity lets suppose that the Gamma Knife radiosurgery could indeed have tomorrow a place within the sample group of surgical approaches dedicated to the treatment of severe epilepsies. However, a larger number of treated patients and a more prolonged follow-up remains necessary to estimate in a more definitive way this approach.

Complete nucleotide sequence and host range of South African cassava mosaic virus: further evidence for recombination amongst begomoviruses.

Complete nucleotide sequences of the DNA-A (2800 nt) and DNA-B (2760 nt) components of a novel cassava-infecting begomovirus, South African cassava mosaic virus (SACMV), were determined and compared with various New World and Old World begomoviruses. SACMV is most closely related to East African cassava mosaic virus (EACMV) in both its DNA-A (85% with EACMV-MH and -MK) and -B (90% with EACMV-UG2-Mld and EACMV-UG3-Svr) components; however, percentage sequence similarities of less than 90% in the DNA-A component allowed SACMV to be considered a distinct virus. One significant recombination event spanning the entire AC4 open reading frame was identified; however, there was no evidence of recombination in the DNA-B component. Infectivity of the cloned SACMV genome was demonstrated by successful agroinoculation of cassava and three other plant species (Phaseolus vulgaris, Malva parviflora and Nicotiana benthamiana). This is the first description of successful infection of cassava with a geminivirus using Agrobacterium tumefaciens.

The catR gene encoding a catalase from Aspergillus niger: primary structure and elevated expression through increased gene copy number and use of a strong promoter.

Synthetic oligonucleotide probes based on amino acid sequence data were used to identify and clone cDNA sequences encoding a catalase (catalase-R) of Aspergillus niger. One cDNA clone was subsequently used to isolate the corresponding genomic DNA sequences (designated catR). Nucleotide sequence analysis of both genomic and cDNA clones suggested that the catR coding region consists of five exons interrupted by four small introns. The deduced amino acid sequence of catalase-R spans 730 residues which show significant homology to both prokaryotic and eukaryotic catalases, particularly in regions involved in catalytic activity and binding of the haem prosthetic group. Increased expression of the catR gene was obtained by transformation of an A. niger host strain with an integrative vector carrying the cloned genomic DNA segment. Several of these transformants produced three- to fivefold higher levels of catalase than the untransformed parent strain. Hybridization analyses indicated that these strains contained multiple copies of catR integrated into the genome. A second expression vector was constructed in which the catR coding region was functionally joined to the promoter and terminator elements of the A. niger glucoamylase (glaA) gene. A. niger transformants containing this vector produced from three- to 10-fold higher levels of catalase-R than the untransformed parent strain.

Primate supplementary eye field. II. Comparative aspects of connections with the thalamus, corpus striatum, and related forebrain nuclei.

The supplementary eye field (SEF) was defined electrophysiologically in behaving monkeys to study its connections with the diencephalon and corpus striatum. The specificity of SEF pathways was determined with horseradish peroxidase (HRP) histochemistry to compare its connections with those of the arcuate frontal eye field (FEF), contiguous dorsocaudal area 6 (6DC), and primary motor cortex (M1, arm/hand region). Results indicate that patterns of SEF connectivity were similar to the FEF and markedly different from areas 6DC and M1. Primary reciprocal thalamic pathways of the SEF were with the magnocellular ventral anterior (VA) nucleus, medial parvicellular VA, medial area X, and paralaminar medialis dorsalis (multiformis and parvicellularis). FEF showed similar connections but its most robust pathway was with MD rather than VA. In contrast, area 6DC showed the most extensive reciprocal connections with lateral VApc and lateral area X with only sparse connections with paralaminar MD. Area 6DC also exhibited reciprocal connections with the ventral lateral (VL) complex and the ventral posterior lateral nucleus, pars oralis (VPLo). M1 showed dense bidirectional connections with VPLo, and to a lesser extent, with VL. M1 pathways with the medial dorsal nucleus were negligible. All areas exhibited connections with the paracentral and central lateral nuclei and only M1 lacked connections with the central superior lateral nucleus. SEF and FEF exhibited similar efferent projections to the caudate and putamen. In the caudate, terminal fields were restricted to a central longitudinal core while those from area 6DC were more widely distributed. Eye field efferents were restricted to the putamen's face region while 6DC projections were more exuberant. The arm/hand region of M1 projected to the arm/hand region of the putamen. Pathways are discussed with respect to their significance in oculomotor control.

Interactions between natural and electrically evoked saccades. II. At what time is eye position sampled as a reference for the localization of a target?

Electrical microstimulation was applied at brain sites (thalamic internal medullary lamina complex and superficial layers of superior colliculus) of alert, trained monkeys to evoke fixed-vector saccades. When the stimulation was timed to occur during or after an eye movement, the evoked saccade had a modified trajectory, compensating for, at least, the last portion of the ongoing eye movement. The hypothesis proposed to explain this compensatory effect (Schlag-Rey et al. 1989) is that the electrical stimulation produces a saccade by generating a signal, equivalent to a retinal error, specifying the saccade goal at a fixed location with respect to some eye position (called reference eye position). If the eyes are moving at the time of stimulation, the reference eye position lies somewhere along the trajectory of the ongoing movement. In the present study, we tried to determine this reference eye position, and deduce from it the instant at which the goal was specified. A significant timing difference was observed between thalamic and collicular stimulations. The goal appeared to be referred to an eye position existing at stimulation onset in superior colliculus (SC), and 35-65 ms before stimulation onset in central thalamus. In the latter case, the results suggest that the evoked saccade was aimed at the spatial location that the brain computed by summing a retinal error signal (evoked by stimulation) with the eye position at the time such a signal would have been elicited by a real target. In contrast, the collicular results suggest that the evoked saccade was directed to the retinal location specified by the retinal error signal. The findings imply that if the eyes are not steady while the target position is calculated, signals conveyed in the superficial layers of SC (in contrast to the thalamus) cannot direct the eyes correctly to a visual target.

Does microstimulation evoke fixed-vector saccades by generating their vector or by specifying their goal?

Electrical stimulation was performed at several sites of the monkey's forebrain producing fixed-vector saccades when the eyes were steady. When the same stimulation was applied during or immediately after a spontaneous eye movement, the saccade trajectory was considerably modified: the eyes were driven, from wherever they were deviated by the spontaneous movement, to the point where the fixed-vector saccade would have brought them if the spontaneous movement had not occurred. This finding implies first, that saccades evoked from these sites are directed toward a goal and, a second, that the goal is defined with respect to an eye position sampled long in advance (before the spontaneous eye movement). This is consistent with the hypothesis that the electrical stimulation evoked the retinotopic representation of a target whose spatial coordinates were then computed at further stages to produce a saccade. Using the present paradigm, it may be possible to distinguish brain sites processing retinal error (at the visual stage) from those processing motor error (at the motor stage).

Visuomotor functions of central thalamus in monkey. I. Unit activity related to spontaneous eye movements.

The region in and around the thalamic internal medullary lamina (IML) in the cat recently has been shown to contain neurons active with ocular saccades and responding to visual stimuli. In the present study, single-unit microelectrode recordings were made in the corresponding thalamic region of the alert monkey in order to determine whether neurons with similar properties existed. Our objective was to specify the functional characteristics of these thalamic cells in the monkey, since 1) cell populations in the central thalamus form an important link between brain stem structures, such as superior colliculus and paramedian pontine reticular formation, and cortical areas, such as frontal eye field and inferior parietal lobule; and 2) most neurophysiological information on these structures with regard to gaze mechanisms has been obtained in primates. In this first part of the study we report observations on 164 thalamic units whose activity was related to the performance of spontaneous eye movements, head fixed. The animals had been trained on a visual discrimination task but photic stimuli were used only for calibrating the eye-position recording and for inducing small saccades and smooth pursuit. The experiments were performed in dim red light and in total darkness. Three types of units were found: 67 saccadic burst units, 58 saccade pause-rebound units, and 39 eye-position units. Sixty-two of the burst units had a directional preference. Most of the on-directions were contraversive, and it was in such units that the lead time of firing before saccades was the longest (up to at least 400 ms). Some of the burst units had a movement field, others fired more intensively and with a longer lead time, depending on the eccentricity of the eye position reached in orbit. The five units with no directional preference were the ones showing the best relation of burst duration with saccade duration. Three types of pause-rebound units were distinguished, depending on whether the saccadic pause or the postsaccadic burst was the most conspicuous event or the pause occurred after saccade offset. The three types were called, respectively, omnipausers, omnirebound cells, and late pausers. Omnipausers and omnirebound cells had no directional preference but their typical firing patterns occurred very consistently with all saccades, even less than 2 degrees. In a few units, the rebound progressively faded away in total darkness. The relation of firing rate of eye-position units with eccentricity of the eyes in orbit was analyzed. Fluctuations in time and a hysteresis effect were found to affect this relation.(ABSTRACT TRUNCATED AT 400 WORDS)

Visuomotor functions of central thalamus in monkey. II. Unit activity related to visual events, targeting, and fixation.

In alert monkeys, single-unit responses to visual stimuli were recorded in the central thalamic region where eye movement-related activity has been observed (33). Usually, the stimuli were 1 degree annulus patterns of dim light presented at unpredictable locations on a tangent screen. The animals were trained on two tasks: one in which they delivered the stimulus themselves by pressing a panel that they had to release immediately when the stimulus shape changed to a square, and another one in which the stimulus was turned on by the experimenter and the monkeys were rewarded for fixating this target for a predetermined length of time. In both tasks, continuous stimulus fixation was required. Receptive fields were tested with and without a fixation point. Retinal coordinates of stimuli were obtained by subtracting eye-position coordinates from stimulus coordinates in space, the monkey's head being fixed. Unit responses in the cases where targeting occurred or did not occur were analyzed separately. Transient responses were observed in 63 units and sustained responses in 44 units. Among the 63 units responding transiently, 42 did so irrespective of targeting. Their receptive fields were very large, generally including the fovea, and predominantly contralateral when the fields were asymmetric. The responses of the other 21 units depended on the occurrence of targeting. They were called visually triggered eye movement-related responses (VTEM). VTEM units were further subdivided in 9 units active only with targeting and 12 units showing the classical phenomenon of "response enhancement" under this condition. VTEM units were contrasted to six units that were both passively visually responsive and bursting with saccades, either spontaneous or visually triggered. The latencies of passive visual and VTEM responses to stimulus onset were comprised between 77 and 135 ms in 80% of the units. VTEM units also fired prior to retargeting saccades. Presaccadic units active with spontaneous saccades also discharged with visually elicited saccades. The earliest sign of activation after stimulus onset eliciting a saccade appeared between 80 and 100 ms, that is, in the same range of latencies as passive visual and VTEM units. Sustained visual responses consisted of activation in 18 units and inactivation in 26 units. The occurrence of these patterns of firing was related to stimulus fixation. In the majority of cases, the changes in discharge frequency started before fixation was achieved by a targeting saccade. They terminated before fixation was broken by a saccade away from the stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of 41-CRF antiserum on the secretion of ACTH, B-endorphin and alpha-MSH in the rat.

In order to elucidate the physiological role of the 41 amino-acid residue corticotropin-releasing factor (41-CRF) on the secretion of ACTH, B-Endorphin and alpha-MSH, plasma levels of these peptides were measured by radioimmunoassay in intact and adrenalectomized rats, two hours after the injection of either 41-CRF antiserum (CRF-AS) or normal rabbit serum for controls. The administration of CRF-AS strikingly lowered the plasma ACTH levels in both intact and adrenalectomized rats. A statistically significant reduction of plasma levels of B-Endorphin was also observed in the same rats. However, the effect of CRF-AS on B-Endorphin release was less pronounced than the effect on ACTH release. No changes in plasma alpha-MSH levels were observed after passive immunization with CRF-AS. We conclude that, in the rat, 41-CRF plays a physiological role in the regulation of ACTH and B-Endorphin secretion, but is not involved in the regulation of alpha-MSH release from the pituitary gland.

Thalamic units firing upon refixation may be responsible for plasticity in visual cortex.

In alert cat and monkey, a unit type recorded in the region of the thalamic internal medullary lamina seems to provide the extraretinal signal postulated by Singer (1982) to explain the development of mature receptive field properties in cortical visual neurons. These thalamic units are silent (or silenced) during saccades in all directions; they discharge as soon as the eyes assume a new position. The abolition of this discharge by thalamic lesion, or conversely, its elicitation by electrical stimulation could respectively prevent or facilitate plastic changes in visual cortical areas of kittens.

Visual responses of thalamic neurons depending on the direction of gaze and the position of targets in space.

Visual receptive field properties of neurons in the region of the thalamic internal medullary lamina were studied in alert cats while they fixated in various directions. In slightly more than 50% of the cells, the responsiveness of the cells was found to depend on the location of the stimulus with respect to the head-body axis (stimulus absolute position). A cell could ignore a stimulus outside its absolute field even if it was well placed within its receptive field. Three types of neurons were distinguished. Neurons with small central receptive fields were tonically activated when the animal fixated the stimulus in one half of the screen (usually contralateral). The firing rate of these cells was related to the stimulus absolute position measured along a preferred axis. Similarly, neurons with large receptive fields fired as a function of stimulus absolute position but stimulus fixation was not required. Neurons with eccentric fields responded to stimuli located in a target area defined in head-body coordinates. Such cells gave presaccadic bursts with eye movements terminating in the target area. The conclusion proposed is that neurons exist which code visual spatial information in a non-retinal frame of reference. This coding takes place at the time of stimulus presentation. Its role may be seen in the initiation of visually guided movements.

Estudio fitoquímico del Agave fourcroydes (henequén). Parte I / A phytochemical study of Agave fourcroydes (Mexican agave). Part I

Se estudia la composición del crudo de sapogeninas del jugo de henequén, así como la evaluación de sus componentes principales: tigogenina y hecogenina, mediante el método de cromatografía gaseosa. Además de las dos sapogeninas principales, fueron detectadas, mediante CCD, otras cuatro manchas bien definidas: una de ellas correspondió, por comparación con patrones, a las 9-11 dehidrohecogenina dada a conocer por primera vez en el Agave fourcroydes que crece en Cuba. Se establecieron las condiciones para separar cualitativamente, por cromatografía gaseosa, la 9-11 dehidrohecogenina de la hecogenina(AU)