Systematic review and meta-analysis on the association between chronic low back pain and cognitive function

This study aimed to identify and assess the evidence on the association between idiopathic chronic low back pain (LBP) and cognitive function in individuals with LBP. A secondary aim was to explore whether changes in cognitive function are associated with pain characteristics and psychological factors (eg, catastrophizing and fear of movement). Eleven studies were included in this systematic review, and four meta-analyses were conducted. Low to very low-quality evidence suggests impaired cognitive function in individuals with LBP compared to asymptomatic controls for problem solving (k = 5; d = 0.33; CI = 0.16–0.50; z = 3.85 p = 0.0001), speed of information processing (k = 5; d = 0.44; CI = 0.22–0.65; z = 4.02 p < 0.0001), working memory (k = 6; d = 0.50; CI = 0.34–0.66; z = 6.09 p < 0.0001), and delayed memory (k = 3; d = 0.34; CI = 0.07–0.6, z = 2.49 p = 0.02). The association between LBP intensity and psychological factors and cognitive function was inconclusive. More studies are needed to explore these associations and improve evidence in this field. The results of this study suggest that cognitive aspects should be considered during the rehabilitation process of patients with LBP and raise further questions, including whether individuals with LBP are at a greater risk of developing dementia or whether targeting cognitive function will increase the probability of success of LBP treatment. These questions should, also, be considered in future studies.This work was supported by the National Funds through FCT – Fundação para a Ciência e a Tecnologia, I.P., within CINTESIS, R&D Unit (reference DFA/BD/8869/2020)

Predicting cortical bone adaptation to axial loading in the mouse tibia

The development of predictive mathematical models can contribute to a deeper understanding of the specific stages of bone mechanobiology and the process by which bone adapts to mechanical forces. The objective of this work was to predict, with spatial accuracy, cortical bone adaptation to mechanical load, in order to better understand the mechanical cues that might be driving adaptation. The axial tibial loading model was used to trigger cortical bone adaptation in C57BL/6 mice and provide relevant biological and biomechanical information. A method for mapping cortical thickness in the mouse tibia diaphysis was developed, allowing for a thorough spatial description of where bone adaptation occurs. Poroelastic finite-element (FE) models were used to determine the structural response of the tibia upon axial loading and interstitial fluid velocity as the mechanical stimulus. FE models were coupled with mechanobiological governing equations, which accounted for non-static loads and assumed that bone responds instantly to local mechanical cues in an on–off manner. The presented formulation was able to simulate the areas of adaptation and accurately reproduce the distributions of cortical thickening observed in the experimental data with a statistically significant positive correlation (Kendall's τ rank coefficient τ = 0.51, p < 0.001). This work demonstrates that computational models can spatially predict cortical bone mechanoadaptation to a time variant stimulus. Such models could be used in the design of more efficient loading protocols and drug therapies that target the relevant physiological mechanisms

Epileptic Spasms in Congenital Disorders of Glycosylation

Congenital disorders of glycosylation (CDG) are a group of rare metabolic diseases, characterized by impaired glycosylation. Multisystemic involvement is common and neurological impairment is notably severe and disabling, concerning the central and peripheral nervous system. Epilepsy is frequent, but detailed electroclinical description is rare. We describe, retrospectively, the electroclinical features in five children with CDG and epileptic spasms. Epileptic spasms were observed in patients with ALG1-, ALG6, ALG11-CDG and CDG-Ix, and occurred at an early age, before 6 months in all cases, except one who had spasms that started at 18 months. In this patient, spasms had an unusual aspect; they did not occur in clusters and were immediately preceded by a myoclonus. All but one child also presented rare myoclonias. On EEG, background activity was poorly organized with abundant posterior spike and fast rhythm activity, but without hypsarrhythmia. At the last evaluation (age range: 6-12 years), two patients still presented epileptic spasms and subcortical myoclonias, one showed rare generalized tonic-clonic seizures, and two were seizure-free. CDG disorders can be associated with epileptic spasms showing particular features, such as absence of hypsarrhythmia, posterior EEG anomalies, and an unusual combination of epileptic spasms with myoclonus. These features, associated with pre-existing developmental delay and subcortical myoclonias, may shift toward CDG screening. [Published with video sequence and supplemental EEG plates on www.epilepticdisorders.com].info:eu-repo/semantics/publishedVersio

The protist Trichomonas vaginalis harbors multiple lineages of transcriptionally active Mutator-like elements

<p>Abstract</p> <p>Background</p> <p>For three decades the <it>Mutator </it>system was thought to be exclusive of plants, until the first homolog representatives were characterized in fungi and in early-diverging amoebas earlier in this decade.</p> <p>Results</p> <p>Here, we describe and characterize four families of <it>Mutator</it>-like elements in a new eukaryotic group, the Parabasalids. These <b><it>T</it></b><it>richomonas </it><b><it>v</it></b><it>aginalis </it><it><b>Mu</b>tator- <b>l</b>ike </it><it><b>e</b>lements</it>, or <it>TvMULEs</it>, are active in <it>T. vaginalis </it>and patchily distributed among 12 trichomonad species and isolates. Despite their relatively distinctive amino acid composition, the inclusion of the repeats <it>TvMULE1</it>, <it>TvMULE2</it>, <it>TvMULE3 </it>and <it>TvMULE4 </it>into the <it>Mutator </it>superfamily is justified by sequence, structural and phylogenetic analyses. In addition, we identified three new <it>TvMULE</it>-related sequences in the genome sequence of <it>Candida albicans</it>. While <it>TvMULE1 </it>is a member of the <it>MuDR </it>clade, predominantly from plants, the other three <it>TvMULEs</it>, together with the <it>C. albicans </it>elements, represent a new and quite distinct <it>Mutator </it>lineage, which we named <it>TvCaMULEs</it>. The finding of <it>TvMULE1 </it>sequence inserted into other putative repeat suggests the occurrence a novel TE family not yet described.</p> <p>Conclusion</p> <p>These findings expand the taxonomic distribution and the range of functional motif of <it>MULEs </it>among eukaryotes. The characterization of the dynamics of <it>TvMULEs </it>and other transposons in this organism is of particular interest because it is atypical for an asexual species to have such an extreme level of TE activity; this genetic landscape makes an interesting case study for causes and consequences of such activity. Finally, the extreme repetitiveness of the <it>T. vaginalis </it>genome and the remarkable degree of sequence identity within its repeat families highlights this species as an ideal system to characterize new transposable elements.</p

Cupin: A candidate molecular structure for the Nep1-like protein family

<p>Abstract</p> <p>Background</p> <p>NEP1-like proteins (NLPs) are a novel family of microbial elicitors of plant necrosis. Some NLPs induce a hypersensitive-like response in dicot plants though the basis for this response remains unclear. In addition, the spatial structure and the role of these highly conserved proteins are not known.</p> <p>Results</p> <p>We predict a <it>3d</it>-structure for the <it>β</it>-rich section of the NLPs based on alignments, prediction tools and molecular dynamics. We calculated a consensus sequence from 42 NLPs proteins, predicted its secondary structure and obtained a high quality alignment of this structure and conserved residues with the two Cupin superfamily motifs. The conserved sequence GHRHDWE and several common residues, especially some conserved histidines, in NLPs match closely the two cupin motifs. Besides other common residues shared by dicot Auxin-Binding Proteins (ABPs) and NLPs, an additional conserved histidine found in all dicot ABPs was also found in all NLPs at the same position.</p> <p>Conclusion</p> <p>We propose that the necrosis inducing protein class belongs to the Cupin superfamily. Based on the <it>3d</it>-structure, we are proposing some possible functions for the NLPs.</p

Benefícios dos Ativadores Seletivos dos Recetores de Vitamina D em Doentes Transplantados Renais

Severe chronic kidney disease may lead to disturbances, such as hyperphosphatemia, increased secretion of fibroblast growth factor -23 (FGF -23) and vitamin D deficiency. These may increase plasmatic levels of parathyroid hormone, and decrease plasmatic levels of calcium. Altogether, these may contribute to the development of secondary hyperparathyroidism, and to abnormalities in mineral metabolism. Kidney transplantation is the best option to improve longevity and quality of life in end -stage chronic kidney disease patients. Vitamin D deficiency has been associated with cardiovascular disease, which is the leading cause of death in chronic kidney disease. Therefore, diagnosing this deficiency may be pivotal for minimizing mortality in chronic kidney disease, because pharmacological treatments for this deficiency may be prescribed. Calcitriol is indicated for the treatment of vitamin D deficiency, both in chronic kidney disease and in kidney transplanted patients. However, calcitriol may increase the plasmatic levels of calcium and phosphorous, which can lead to vascular calcifications, that have been associated with cardiovascular mortality. Selective vitamin D receptor activators are indicated for the treatment of vitamin D deficiency in chronic kidney disease. These have the advantage of being associated with lower increases of plasmatic levels of calcium and phosphorous. These drugs also seem to have additional effects that may minimise patient morbidity and mortality, especially due to potentially reducing cardiovascular events. Unfortunately, there are few studies about the use of these drugs in kidney transplanted patients. Here we present a review about the physiology of vitamin D, the consequences of its deficiency in chronic kidney disease and in kidney transplanted patients, and about the diagnosis and treatment of this deficiency. Finally, we discuss the new line of research about the efficacy and safety of selective vitamin D receptor activators in kidney transplanted patients

Trochlear Nerve Palsy Associated with Claude Bernard-Horner Syndrome after Brainstem Stroke

The association of unilateral trochlear nerve palsy with Claude Bernard-Horner syndrome represents a rare clinical condition. We present the case of a patient with this unusual presentation. The investigation performed implicated cerebrovascular disease as the underlying cause of the condition in this patient

Optical sideband generation up to room temperature with mid-infrared quantum cascade lasers

Room temperature sideband generation on an optical carrier is demonstrated using midinfrared quantum cascade lasers. This is achieved via an enhancement of the nonlinear susceptibility via resonant interband and intersubband excitations, compensating the large phase-mismatch

CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

<p>Abstract</p> <p>Background</p> <p>Recent studies have reported the clinical importance of <it>CYP2C19 </it>and <it>ABCB1 </it>polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of <it>CYP2C19 </it>and <it>ABCB1 </it>polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population.</p> <p>Methods</p> <p>One hundred and eighty-three Amerindians and 1,029 subjects of the general population of 4 regions of the country were included. Genotypes for the <it>ABCB1</it>c.C3435T (rs1045642), <it>CYP2C19*2 </it>(rs4244285), <it>CYP2C19*3 </it>(rs4986893), <it>CYP2C19*4 </it>(rs28399504), <it>CYP2C19*5 </it>(rs56337013), and <it>CYP2C19*17 </it>(rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The <it>CYP2C19*3</it>, <it>CYP2C19*4 </it>and <it>CYP2C19*5 </it>variants were genotyped in a subsample of subjects (300 samples randomly selected).</p> <p>Results</p> <p>The <it>CYP2C19*3 </it>and <it>CYP2C19*5 </it>variant alleles were not detected and the <it>CYP2C19*4 </it>variant allele presented a frequency of 0.3%. The allelic frequencies for the <it>ABCB1</it>c.C3435T, <it>CYP2C19*2 </it>and <it>CYP2C19*17 </it>polymorphisms were differently distributed according to ethnicity: Amerindian (51.4%, 10.4%, 15.8%); Caucasian descent (43.2%, 16.9%, 18.0%); Mulatto (35.9%, 16.5%, 21.3%); and African descent (32.8%, 20.2%, 26.3%) individuals, respectively. As a result, self-referred ethnicity was able to predict significantly different clopidogrel-predicted metabolic phenotypes prevalence even for a highly admixtured population.</p> <p>Conclusion</p> <p>Our findings indicate the existence of inter-ethnic differences in the <it>ABCB1 </it>and <it>CYP2C19 </it>variant allele frequencies in the Brazilian general population plus Amerindians. This information could help in stratifying individuals from this population regarding clopidogrel-predicted metabolic phenotypes and design more cost-effective programs towards individualization of clopidogrel therapy.</p

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation