Early outcomes of migraine after erenumab discontinuation: data from a real-life setting

Neurological Sciences - Monoclonal antibodies targeting the calcitonin gene-related peptide, including erenumab, are migraine-specific preventive treatments, whose long-term effectiveness has still...     

Prospective Comparison of Infective Endocarditis in Khon Kaen,Thailand and Rennes,France

Prospectively collected, contemporary data are lacking on how the features of infective endocarditis (IE) vary according to region. We, therefore, compared IE in Rennes, France and Khon Kaen, Thailand. Fifty-eight patients with confirmed IE were enrolled at each site during 2011 and 2012 using a common protocol. Compared with French patients, Thais had a lower median age (47 versus 70 years old; P < 0.001) and reported more animal contact (86% versus 21%; P < 0.001). There were more zoonotic infections among Thai than France patients (6 and 1 cases; P = 0.017) and fewer staphylococcal infections (4 versus 15 cases; P = 0.011). Underlying rheumatic heart disease was more prevalent in Thai than in French patients (31% and 4%; P = 0.001), whereas prosthetic heart valves were less prevalent (9% and 35%; P = 0.001). Our data strengthen previous observations that IE in the tropics has distinctive demographic characteristics, risk factors, and etiologies and underscore the need for improved prevention and control strategies.     

Transgene-mediated cosuppression and RNA interference enhance germ-line apoptosis in Caenorhabditis elegans

Introduction of multiple copies of a germ-line-expressed gene elicits silencing of the corresponding endogenous gene during Caenorhabditis elegans oogenesis; this process is referred to as germ-line cosuppression. Transformed plasmids assemble into extrachromosomal arrays resembling extra minichromosomes with repetitive structures. Loss of the transgene extrachromosomal array leads to reversion of the silencing phenomenon. Cosuppression and RNAi depend upon some of the same genes. In the C. elegans germ line, about half the cells undergo a physiological programmed cell death that shares most genetic requirements with somatic apoptosis. In addition, apoptosis is stimulated by DNA damage and synaptic failure mediated through different apoptotic checkpoints. We found that both germ-line cosuppression and RNAi of germ-line-expressed genes enhance apoptosis during C. elegans oogenesis. In contrast, apoptosis is not enhanced by extrachromosomal arrays carrying genes not driven by germ-line-specific promoters that thus do not elicit transgene-mediated cosuppression/silencing. Similarly, introduction of doubled-stranded RNA that shares no homology with endogenous genes has no effect on apoptosis. "Silencing-induced apoptosis" is dependent upon sir-2.1 and cep-1 (the worm p53 ortholog), and is accompanied by a rise in RAD-51 foci, a marker for ongoing DNA repair, indicating induction of DNA double-strand breaks. This finding suggests that the DNA damage-response pathway is involved. RNAi and cosuppression have been postulated as defense mechanisms against genomic intruders. We speculate that the mechanism here described may trigger the elimination of germ cells that have undergone viral infection or transposon activation.     

Cortical evolution in mammals: the bane and beauty of phenotypic variability

Evolution by natural selection, the unifying theory of all biological sciences, provides a basis for understanding how phenotypic variability is generated at all levels of organization from genes to behavior. However, it is important to distinguish what is the target of selection vs. what is transmitted across generations. Physical traits, behaviors, and the extended phenotype are all selected features of an individual, but genes that covary with different aspects of the targets of selection are inherited. Here we review the variability in cortical organization, morphology, and behavior that have been observed across species and describe similar types of variability within species. We examine sources of variability and the constraints that limit the types of changes that evolution has and can produce. Finally, we underscore the importance of how genes and genetic regulatory networks are deployed and interact within an individual, and their relationship to external, physical forces within the environment that shape the ultimate phenotype.     

Olfactory identification deficits and associated response inhibition in obsessive-compulsive disorder: On the scent of the orbitofronto–striatal model

Olfactory identification ability implicates the integrity of the orbitofrontal cortex (OFC). The fronto–striatal circuits including the OFC have been involved in the neuropathology of Obsessive Compulsive Disorder (OCD). However, only a few studies have examined olfactory function in patients with OCD. The Brief Smell Identification Test (B-SIT) and tests from the Cambridge Neuropsychological Automated Battery (CANTAB) were administered to 25 patients with OCD and to 21 healthy matched controls. OCD patients showed a significant impairment in olfactory identification ability as well as widely distributed cognitive deficits in visual memory, executive functions, attention, and response inhibition. The degree of behavioural impairment on motor impulsivity (prolonged response inhibition Stop-Signal Reaction Time) strongly correlated with the B-SIT score. Our study is the first to indicate a shared OFC pathological neural substrate underlying olfactory identification impairment, impulsivity, and OCD. Deficits in visual memory, executive functions and attention further indicate that regions outside of the orbitofronto–striatal loop may be involved in this disorder. Such results may help delineate the clinical complexity of OCD and support more targeted investigations and interventions. In this regard, research on the potential diagnostic utility of olfactory identification deficits in the assessment of OCD would certainly be useful.     

The effect of summer vacation on bilingual preschoolers' language development

The purpose of the investigation was to examine the developmental trajectories of bilingual preschoolers' comprehension of Spanish and English and to determine whether a lengthy summer vacation impacted children's development during the preschool years. Participants included 83 bilingual children who were followed over a 2‐year period during which time children attended a federally funded preschool programme for children from low‐income homes living in the US. Children were divided into two groups based on whether their scores on receptive language measures increased or decreased during their first year of Head Start. Results revealed that children whose scores increased experienced positive growth in their language comprehension in Spanish and English over the 2‐year period, whereas children whose scores decreased during the first year continued to experience a negative developmental trajectory in their second year. Additionally, it was found that a lengthy summer vacation had a differential effect on children's development. Summer vacation had a negative effect on the developmental trajectories of children who experienced gains in their comprehension of English and Spanish and a positive impact on children whose scores declined during the school year. Clinical implications suggest that children may require differential support during the school year and summer vacation depending upon their developmental trajectories during the first year in preschool.     

Proton MR spectroscopy in the breast: Technical innovations and clinical applications

Proton magnetic resonance spectroscopy (MRS) is a promising noninvasive diagnostic technique for investigation of breast cancer metabolism. Spectroscopic imaging data may be obtained following contrast‐enhanced MRI by applying the point‐resolved spectroscopy sequence (PRESS) or the stimulated echo acquisition mode (STEAM) sequence from the MR voxel encompassing the breast lesion. Total choline signal (tCho) measured in vivo using either a qualitative or quantitative approach has been used as a diagnostic test in the workup of malignant breast lesions. In addition to tCho metabolites, other relevant metabolites, including multiple lipids, can be detected and monitored. MRS has been heavily investigated as an adjunct to morphologic and dynamic MRI to improve diagnostic accuracy in breast cancer, obviating unnecessary benign biopsies. Besides its use in the staging of breast cancer, other promising applications have been recently investigated, including the assessment of treatment response and therapy monitoring. This review provides guidance on spectroscopic acquisition and quantification methods and highlights current and evolving clinical applications of proton MRS. Level of Evidence 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.