New treatment options in the management of fibromyalgia: role of pregabalin

Fibromyalgia (FM) is a common, chronic pain disorder with unknown etiology, characterized by widespread musculoskeletal pain and tenderness, and accompanied by several other symptoms such as sleep disturbance, fatigue, and mood disorders. Pregabalin is the first drug approved for the treatment of FM. Pregabalin has analgesic, anticonvulsant, and anxiolytic activity and has earlier demonstrated efficacy in the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and as adjuvant therapy for adult patients with partial onset seizures. Pregabalin, a lipophilic gamma-aminobutyric acid (GABA) analog, is α2δ-1 ligand that binds to, and modulates, voltage-gated calcium channels. This modulation is characterized by a reduction of the excessive neurotransmitter release that is observed in certain neurological and psychotic disorders. Several randomized, double-blind, placebo-controlled studies have demonstrated that pregabalin has been effective in pain management, improving sleep quality and fatigue, as well as in several domains of health related quality of life. Because of mild to moderate adverse effects it can be considered a well-tolerated therapy for FM

Microglial ‘fat shaming’ in development and disease

Neuronal-immune interactions are known to play crucial roles in brain development and homoeostasis. Of great relevance in this context are microglia, brain macrophages that phagocytose neurons that die during development, and many neurological disorders. Single-cell RNA sequencing methods have significantly advanced our understanding of microglial heterogeneity and transcriptional response to environmental changes. Here, we review recent work showing how microglia adopt a similar molecular signature during development and disease characterised by the expression of genes linked to phagocytosis and lipid uptake and metabolism. These studies show that in many neurodegenerative conditions, microglia accumulate cholesterols and lipid-rich debris, pointing to lipid processing and transport as promising targets for developing new therapeutical treatments against neurodegenerative disorders

Representations of isotropic Gaussian random fields with homogeneous increments

We present series expansions and moving average representations of isotropic Gaussian random fields with homogeneous increments, making use of concepts of the theory of vibrating strings. We illustrate our results using the example of Lévy’s fractional Brownian motion on R N. Copyright © 2006 Kacha Dzhaparidze et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1

Influence of age and cognitive performance on resting-state functional connectivity of dopaminergic and noradrenergic centers

Aging is associated with structural and functional changes in the brain, with a decline in cognitive functions observed as its inevitable concomitant. The body of literature suggests dopamine and noradrenaline as prominent candidate neuromodulators to mediate these effects; however, knowledge regarding the underlying mechanisms is scarce. To fill this gap, we compared resting-state functional connectivity (FC) patterns of ventral tegmental area (VTA), substantia nigra pars compacta (SNc) and locus coeruleus (LC) in healthy young (20–35 years; N = 37) and older adults (55–80 years; N = 27). Additionally, we sought FC patterns of these structures associated with performance in tasks probing executive, attentional and reward functioning, and we compared the functional coupling of the bilateral SNc. The results showed that individual SNc had stronger coupling with ipsilateral cortical and subcortical areas along with the contralateral cerebellum in the whole sample, and that the strength of connections of this structure with angular gyrus and lateral orbitofrontal cortex predicted visuomotor search abilities. In turn, older age was associated with greater local synchronization within VTA, its lower FC with caudate, mediodorsal thalamus, and SNc, as well as higher FC of both midbrain dopaminergic seeds with red nuclei. LC functional coupling showed no differences between the groups and was not associated with any of the behavioral functions. To the best of our knowledge, this work is the first to report the age-related effects on VTA local synchronization and its connectivity with key recipients of dopaminergic innervation, such as striatum and mediodorsal thalamus

Развојне тенденције у савременом пољском језику

Приказ социолингвистичких услова у Пољској током последњих шездесетак година (у периоду поделе пољске територије између три државе, тзн. до 1918. год., од ослобођења до 1939, год., и, најзад, у току II светског рата све до 1945. год. и до данас). Посебно су наглашене битне ванјезичке промене после 1945. године: велике миграције становништва, индустријализација и урбанизација, ширење просвете и културе и сл. Размотрен је утицај наведених социјалних фактора на језик, који води ка следећим резултатима: а, формирање нових пољских мешовитих дијалеката, б. ширење пољског књижевног језика, в. нивелација односно нестанак дијалеката, г. утицај дијалеката на књижевни језик, д. слабљење стандарда у књижевном језику. Карактеристика важнијих језичких промена у свим подсистемима: фонологији и фонетици (пре свега деназализација и ширење особина дијалекатског изговора), у промени (тенденција ка губитку промене код од ређених категорија, описна компарација придева), у творби речи (различите појаве скраћивања, мултивербизација), синтакси (промене у рекцији), најзад, посебно изразите промене у области лексике (позајмице, лексички неологизми, неосемантизми), такође у односу на лична имена. Закључци показују динамику и диференцијацију промена у појединим подсистемима, утицај административних фактора и масовних медија на језик, а такође зависност тих промена од развоја самог језика. На крају - покушај опште оцене промена и развојних тенденција у савременом пољском језику