Cross-fostering does not alter the differential sensitivity of Fischer and Lewis rats to central neurotensin-induced locomotion and hypothermia

A cross-fostering paradigm was used to determine whether the differential locomotor and hypothermic responses to neurotensin (NT) in Fischer (F344) and Lewis (LEW) rats are mediated by the post-natal environment. From post-natal day (PD) 1 to PD 21, male pups from each strain were assigned to a same-strain dam (in-fostered) or were cross-fostered, and at adulthood were implanted with a guide cannula over the lateral ventricle. They were then tested for locomotion and hypothermia following injection of vehicle, 0.18, 1.8 or 18nmol of NT or D-Tyr([11])NT. In-fostered LEW, but not F344, displayed a strong dose-orderly hypothermic response to NT and to D-Tyr([11])NT while in-fostered F344, but not LEW, rats displayed strong locomotor responses to D-Tyr([11])NT. Cross-fostering had no effect on D-Tyr([11])NT-induced locomotor responses in either strain; it had no effect also on NT- and D-Tyr([11])NT-induced hypothermia in F344 rats while it slightly increased the sensitivity to NT in LEW rats. The results show that these NT-mediated actions are not influenced by cross-fostering or the pre-weaning environment.     

Intrinsic membrane properties of central vestibular neurons in rodents

Numerous studies in rodents have shown that the functional efficacy of several neurotransmitter receptors and the intrinsic membrane excitability of central vestibular neurons, as well as the organization of synaptic connections within and between vestibular nuclei can be modified during postnatal development, after a lesion of peripheral vestibular organs or in vestibular-deficient mutant animals. This review mainly focuses on the intrinsic membrane properties of neurons of the medial vestibular nuclei of rodents, their postnatal maturation, and changes following experimental or congenital alterations in vestibular inputs. It also presents the concomitant modifications in the distribution of these neurons into different neuron types, which has been based on their membrane properties in relation to their anatomical, biochemical, or functional properties. The main points discussed in this review are that (1) the intrinsic membrane properties can be used to distinguish between two dominant types of neurons, (2) the system remains plastic throughout the whole life of the animal, and finally, (3) the intracellular calcium concentration has a major effect on the intrinsic membrane properties of central vestibular neurons.     

Reduction in Ventral Midbrain NMDA Receptors Reveals Two Opposite Modulatory Roles for Glutamate on Reward

Glutamate is a major component of the reward circuitry and recent clinical studies suggest that new molecules that would target glutamate neurotransmission are most likely to constitute more effective medications for mood disorders. It is well known that activation of N-methyl-D-aspartate glutamate receptors (NMDARs) initiates dopamine burst firing, a mode associated with reward signaling; but NMDARs also contribute to the maintenance of an inhibitory drive to dopamine neurons. Such opposite modulatory functions imply that different subtypes of NMDARs are expressed on different ventral midbrain (VM) neurons and/or afferent inputs to dopamine neurons. By using the small interfering RNA (siRNA) technique, we studied the effects of VM downregulation of NMDAR subunits GluN1, GluN2A, and GluN2D on reward induced by dorsal raphe electrical stimulation. Reward thresholds were measured before and 24 h after each of three consecutive daily bilateral microinjections of siRNA for the targeted receptor subunit(s) or non-active RNA sequence. After the last measurement, reward thresholds were reassessed following a bilateral microinjection of the preferred GluN2A-NMDA antagonist, (2R,4S)-4-(3-Phosphopropyl)-2-piperidinecarboxylic acid (PPPA). Western-blot analysis showed that siRNAs reduced GluN1- and GluN2A-containing receptors whereas behavioral tests showed that only a reduction in GluN1 produced reward attenuation. Despite NMDAR reduction, reward-enhancing effect of PPPA remained unchanged. We conclude that VM glutamate relays the reward signal initiated by dorsal raphe electrical stimulation by acting on NMDARs devoid of GluN2A/2D subunits and exerts an inhibition on this reward signal by acting on GluN2A-containing NMDARs most likely located on afferent terminals.     

Preventing falls: the use of machine learning for the prediction of future falls in individuals without history of fall

Journal of Neurology - Nowadays, it becomes of paramount societal importance to support many frail-prone groups in our society (elderly, patients with neurodegenerative diseases, etc.) to remain...     

Modifiable risk factors associated with clearance of type-specific cervical human papillomavirus infections in a cohort of university students.

BACKGROUND: Previous findings regarding risk factors for human papillomavirus (HPV) persistence, other than viral determinants, identified from prospective cohort studies have been inconsistent in part because study designs have differed with respect to differing HPV detection methods and varying lengths of follow-up time. Therefore, the objectives of this study were to continue the search for epidemiologic risk factors of persistent cervical HPV infections and determine what behaviors differed between those women with transient HPV infections and those women who cannot clear their type-specific HPV infections. METHODS: Female university students (n = 621) in Montreal were followed for 24 months at 6-month intervals. At each visit, a cervical cell specimen was collected. HPV DNA was detected using the MY09/MY11 PCR protocol and 27 HPV genotypes were identified by the line blot assay (Roche Molecular Systems, Inc., Alameda, CA). Proportional hazards regression was used to estimate the crude and adjusted hazard ratios of clearing a type-specific high-risk (n = 222) or low-risk (n = 105) HPV infection over time according to specific baseline and time-dependent covariates. RESULTS: Daily consumption of vegetables seemed to increase the rate of HPV clearance independent of type. The use of tampons was associated with a reduced rate of high-risk HPV clearance, whereas regular condom use was associated with an increased rate of low-risk HPV clearance only. CONCLUSION: Some proactive measures can be taken to increase the rate of HPV clearance, and there may be some differences between the sets of predictors of low-risk and high-risk HPV clearance.     

Vestibular compensation: the neuro-otologist’s best friend

Why vestibular compensation (VC) after an acute unilateral vestibular loss is the neuro-otologist’s best friend is the question at the heart of this paper. The different plasticity mechanisms underlying VC are first reviewed, and the authors present thereafter the dual concept of vestibulo-centric versus distributed learning processes to explain the compensation of deficits resulting from the static versus dynamic vestibular imbalance. The main challenges for the plastic events occurring in the vestibular nuclei (VN) during a post-lesion critical period are neural protection, structural reorganization and rebalance of VN activity on both sides. Data from animal models show that modulation of the ipsilesional VN activity by the contralateral drive substitutes for the normal push–pull mechanism. On the other hand, sensory and behavioural substitutions are the main mechanisms implicated in the recovery of the dynamic functions. These newly elaborated sensorimotor reorganizations are vicarious idiosyncratic strategies implicating the VN and multisensory brain regions. Imaging studies in unilateral vestibular loss patients show the implication of a large neuronal network (VN, commissural pathways, vestibulo-cerebellum, thalamus, temporoparietal cortex, hippocampus, somatosensory and visual cortical areas). Changes in gray matter volume in these multisensory brain regions are structural changes supporting the sensory substitution mechanisms of VC. Finally, the authors summarize the two ways to improve VC in humans (neuropharmacology and vestibular rehabilitation therapy), and they conclude that VC would follow a “top-down” strategy in patients with acute vestibular lesions. Future challenges to understand VC are proposed.     

The Oxford unicompartmental knee prosthesis: an independent 10-year survival analysis

One hundred forty-nine medial prostheses were implanted in 140 patients between 1988 and 1996. After a mean of 67 months 28 patients had died, without the need for revision. Seventeen prostheses were lost to follow-up. Revision surgery using a total knee prosthesis was performed in 16 cases. In four others, a lateral prosthesis was implanted subsequently to a medial one. One of these four was revised to a total knee prosthesis 6 years later. In another four cases, late complications of the meniscal bearing were treated with replacement of this bearing. The surviving prostheses were seen back after a mean of 126 months. The cumulative survival rate at 10 years was 82% for the whole population and 84% when knees with a previous high tibial osteotomy were excluded. Since these results compare poorly to the survival of total knee arthroplasty, this prosthesis is not the first-choice implant. Because it preserves a maximum of bone stock and is revised to a total prosthesis almost without difficulty, it is the first-choice implant for medial unicompartmental osteoarthritis in patients younger than 65. Further research is mandatory to confirm that this prosthesis very rarely needs revision in patients older than 75. It should not be used in osteotomized knees.