The efficacy of lamotrigine in bipolar disorder: A systematic review and meta-analysis.

OBJECTIVE: To provide up-to-date clinical guidance on the efficacy of lamotrigine in bipolar disorder (BD). METHODS: Eligible studies were identified during a systematic literature search according to PRISMA-guidelines. We included randomized controlled trials (RCTs) and cohort studies that quantitatively assessed lamotrigine's efficacy in BD. We divided the included studies into three groups: 1. acute treatment of depression, 2. acute treatment of mania and hypomania, and 3. maintenance treatment. Analyses were stratified by control group (placebo vs active comparator) and treatment strategy (monotherapy vs add-on treatment). RESULTS: We included 20 RCTs (n = 1166 lamotrigine users) and 20 cohort studies (n = 11,141 lamotrigine users). Twenty-four of these studies were included in meta-analyses. During depressive episodes, greater decreases in depressive symptomatology were associated with initiation of lamotrigine as add-on treatment than with placebo (SMD -0.30 [95% CI = -0.51, -0.10], df = 3, p = 0.004). Decreases in depressive symptomatology did not differ significantly between lamotrigine and the active comparator (SMD -0.28 [95% CI = -1.06, 0.50], df = 3, p = 0.488). As a maintenance treatment, lamotrigine was associated with a significantly lower relapse/recurrence rate than placebo (risk ratio (RR) 0.84 [95% CI = 0.71, 0.99], df = 2, p = 0.037). Relapse/recurrence rates did not differ significantly between lamotrigine and lithium (RR 1.06 [95% CI = 0.89, 1.25], df = 2, p = 0.513). A qualitative assessment of high-quality register-based studies found that lamotrigine was associated with lower hospital admission rates than other commonly used treatment regimes. CONCLUSIONS: There is substantial evidence for the efficacy of lamotrigine in BD, specifically as add-on treatment during acute depressive episodes and as maintenance treatment for preventing relapse and recurrence.

Memory recall: New behavioral protocols for examining distinct forms of context specific recall in animals.

This study outlines two novel protocols for examining context specific recall in animals prior to embarking on neurobiological studies. The approach is distinct from and contrasts with studies investigating associative familiarity that depend upon procedural variations of the widely used novel object recognition task. It uses an event arena in which animals are trained across numerous sessions to search for, find and dig up reward from sandwells during sample and choice trials - a prominent spatial event for a rodent. The arena could be laid out as either of two highly distinct contexts with which the animals became fully familiar throughout training. In one protocol, the location of the correct sandwell in each context remained stable across days, whereas in the other, the correct digging location varied in a counterbalanced manner across each successive session. Thus, context-specific recall of the spatial location of successful digging during choice trials was either from a stable long-term memory or could reflect context specific spatial recency of the location where reward had been available that session. Both protocols revealed effective memory recall in choice and probe tests which, at the point of test, were procedurally identical in both cases.

Distinct differences in gut microbial composition and functional potential from lean to morbidly obese subjects.

INTRODUCTION: The gut microbiome may contribute to the development of obesity. So far, the extent of microbiome variation in people with obesity has not been determined in large cohorts and for a wide range of body mass index (BMI). Here, we aimed to investigate whether the faecal microbial metagenome can explain the variance in several clinical phenotypes associated with morbid obesity. METHODS: Caucasian subjects were recruited at our hospital. Blood pressure and anthropometric measurements were taken. Dietary intake was determined using questionnaires. Shotgun metagenomic sequencing was performed on faecal samples from 177 subjects. RESULTS: Subjects without obesity (n = 82, BMI 24.7 ± 2.9 kg m-2 ) and subjects with obesity (n = 95, BMI 38.6 ± 5.1 kg m-2 ) could be clearly distinguished based on microbial composition and microbial metabolic pathways. A total number of 52 bacterial species differed significantly in people with and without obesity. Independent of dietary intake, we found that microbial pathways involved in biosynthesis of amino acids were enriched in subjects with obesity, whereas pathways involved in the degradation of amino acids were depleted. Machine learning models showed that more than half of the variance in body fat composition followed by BMI could be explained by the gut microbiome, composition and microbial metabolic pathways, compared with 6% of variation explained in triglycerides and 9% in HDL. CONCLUSION: Based on the faecal microbiota composition, we were able to separate subjects with and without obesity. In addition, we found strong associations between gut microbial amino acid metabolism and specific microbial species in relation to clinical features of obesity.

Myogenic tone is impaired at low arterial pressure in mice deficient in the low-voltage-activated CaV 3.1 T-type Ca(2+) channel.

AIM: Using mice deficient in the CaV 3.1 T-type Ca(2+) channel, the aim of the present study was to elucidate the molecular identity of non-L-type channels involved in vascular tone regulation in mesenteric arteries and arterioles. METHODS: We used immunofluorescence microscopy to localize CaV 3.1 channels, patch clamp electrophysiology to test the effects of a putative T-type channel blocker NNC 55-0396 on whole-cell Ca(2+) currents, pressure myography and Ca(2+) imaging to test diameter and Ca(2+) responses of the applied vasoconstrictors, and Q-PCR to check mRNA expression levels of several Ca(2+) handling proteins in wild-type and CaV 3.1(-/-) mice. RESULTS: Our data indicated that CaV 3.1 channels are important for the maintenance of myogenic tone at low pressures (40-80 mm Hg), whereas they are not involved in high-voltage-activated Ca(2+) currents, Ca(2+) entry or vasoconstriction to high KCl in mesenteric arteries and arterioles. Furthermore, we show that NNC 55-0396 is not a specific T-type channel inhibitor, as it potently blocks L-type and non-L-type high-voltage-activated Ca(2+) currents in mouse mesenteric vascular smooth muscle cell. CONCLUSION: Our data using mice deficient in the CaV 3.1 T-type channel represent new evidence for the involvement of non-L-type channels in arteriolar tone regulation. We showed that CaV 3.1 channels are important for the myogenic tone at low arterial pressure, which is potentially relevant under resting conditions in vivo. Moreover, CaV 3.1 channels are not involved in Ca(2+) entry and vasoconstriction to large depolarization with, for example, high KCl. Finally, we caution against using NNC 55-0396 as a specific T-type channel blocker in native cells expressing high-voltage-activated Ca(2+) channels.

[The potentials and outlook for the surgical treatment of complicated injuries and tumors of the spine by total vertebrectomy]. / Vozmozhnosti i perspektivy khirurgicheskogo lecheniia oslozhnennykh povrezhdenii i opukholei pozvonochnika posredstvom total'noi vertebréktomii.

The use of vertebrectomy in 9 patients with long-standing complicated dislocation fractures of vertebrae and defects of tissues of the spinal cord from 1 up to 12 cm has shown that the operation of removal of up to 3 vertebrae is technically quite realizable. Clinical results however are yet minimum, which requires further search for methods of stimulation of regenerative processes in the zone of connection of the spinal cord stumps. The use of the method for treatment of 4 patients with tumors of the vertebrae has revealed a number of problems requiring a somewhat different approach both to the performance of the operation and to the following fixation of the backbone. Possible variants to settle the problems are proposed. Good prospects of this trend are noted.

[The possibilities and outlook for the surgical treatment of complicated injuries and tumors of the spine by total vertebrectomy]. / Vozmozhnosti i perspektivy khirurgicheskogo lecheniia oslozhnennykh povrezhdenii i opukholei pozvonochnika total'noi vertebréktomiei.

On the basis of experimental and clinical investigations the authors consider the removal of the vertebra body as the whole block to be the optimal variant. Shortening of the vertebral column is permissible for the approximation of ends of the spinal cord or its roots for suturing without intention. The use of vertebrectomy in 9 patients with long-standing dislocation fractures and defects of the spinal cord tissues from 1 to 12 cm and in 4 patient without tumors of the vertebrae has shown that the operation with removal of as many as 3 vertebrae is quite realizable technically. However, positive clinical results are minimal for the present which requires further researches by stimulation of regenerative processes.

[Lumbar spondylarthrosis]. / Poiasnichnyi spondiloartroz.

The results are presented of pathomorphological studies and clinical examinations of 572 patients with lumbar zygo-apophyseal joint arthrosis using arthrography, intraarticular treatment- and- diagnostic blockades, intracutaneous joint denervation and surgical treatment of arthrogenous lumbar canal stenosis. Based on the data obtained, the pathogenetic classification of lumbar spondyloarthrosis has been elaborated and presented in the given paper.

[Single-stage total removal of the cervical vertebrae in plasmacytoma]. / Odnoétapnaia total'naia vertebrektomiia Cv pri plazmotsitome.

The article includes the description of successful case of surgical treatment of a patient (53 years old) with VC plasmocytoma, complicated with upper paraparesis, tetanoid paraplegia and pelvic disturbances. The patient has been subjected to complete removal of VC in one stage of 2 accesses. The patient's spine has been fixed by means of implant, made of corundum porous ceramic, metal plate and lavsan band. A year after the operation--no tumor recurrence, the patient walks without additional support. In the process of discussion of the given observation the authors suggest that the technical difficulties of the operation are quite surmountable and its expediency is obvious.

[Arthrographic changes in the lumbar intervertebral joints in osteochondrosis]. / Izmeneniia dugootrostchatykh sustavov poiasnichnogo otdela pozvonochnika i ikh artrografiia pri osteokhondroze.

The data of pathomorphologic investigations of intervertebral ++ joints of the lumbar++ part of spine in case of osteochondrosis and in connection with age are presented in the article. 32 arthrograms of ++ intervertebral++ joint, taken in the patients' lifetime, have been analyzed. The special features of morphologic changes have been revealed and their connection with the clinical signs of osteochondrosis has been determined.

[The effect of the group and individual characteristics of the vertebrae on their strength in experimental compression fractures]. / Vliianie gruppovykh i individual'nykh osobennostei pozvonkov na ikh prochnost' pri kompressionnykh perelomakh v éksperimente.

The authors give an account of their investigation into the strength characteristics of the vertebrae preparations depending on a number of geometric characteristics of the vertebral bodies, the biological state of the bone tissue (osteoporosis, degenerative and dystrophic changes) and their group belonging. A number of factors has been revealed in some parameters of which it is possible to determine the dynamics of the state of the support function of the injured segment in the modelling of compressive fractures of the vertebral bodies. The results obtained by the authors allow to specify the literature data concerning the strength properties of the compressed vertebral body.