Valproate Use Is Associated With Posterior Cortical Thinning and Ventricular Enlargement in Epilepsy Patients

Valproate is a drug widely used to treat epilepsy, bipolar disorder, and occasionally to prevent migraine headache. Despite its clinical efficacy, prenatal exposure to valproate is associated with neurodevelopmental impairments and its use in children and adults was associated with rare cases of reversible brain atrophy and ventricular enlargement. To determine whether valproate use is related with structural brain changes we examined through a cross-sectional study cortical and subcortical structures in a group of 152 people with epilepsy and a normal clinical brain MRI. Patients were grouped into those currently using valproate (n = 54), those taking drugs other than valproate (n = 47), and drug-naïve patients (n = 51) at the time of MRI, irrespectively of their epilepsy syndrome. Cortical thickness and subcortical volumes were analyzed using Freesurfer, version 5.0. Subjects exposed to valproate (either in mono- or polytherapy) showed reduced cortical thickness in the occipital lobe, more precisely in the cuneus bilaterally, in the left lingual gyrus, and in left and right pericalcarine gyri when compared to patients who used other antiepileptic drugs, to drug-naïve epilepsy patients, and to healthy controls. Considering the subgroup of patients using valproate monotherapy (n = 25), both comparisons with healthy controls and drug-naïve groups confirmed occipital lobe cortical thickness reduction. Moreover, patients using valproate showed increased left and right lateral ventricle volume compared to all other groups. Notably, subjects who were non-valproate users at the time of MRI, but who had valproate exposure in the past (n = 27) did not show these cortical or subcortical brain changes. Cortical changes in the posterior cortex, particularly in the visual cortex, and ventricular enlargement, are present in people with epilepsy using valproate, independently from clinical and demographical variables. These findings are relevant both for the efficacy and adverse events profile of valproate use in people with epilepsy

Eliciting Implicit Awareness in Alzheimer’s Disease and Mild Cognitive Impairment: A Task-Based Functional MRI Study

Background: Recent models of anosognosia in dementia have suggested the existence of an implicit component of self-awareness about one’s cognitive impairment that may remain preserved and continue to regulate behavioral, affective, and cognitive responses even in people who do not show an explicit awareness of their difficulties. Behavioral studies have used different strategies to demonstrate implicit awareness in patients with anosognosia, but no neuroimaging studies have yet investigated its neural bases. Methods: Patients with amnestic mild cognitive impairment and dementia due to Alzheimer’s disease underwent functional magnetic resonance imaging (fMRI) during the execution of a color-naming task in which they were presented with neutral, negative, and dementia-related words (Dementia-Related Emotional Stroop). Results: Twenty-one patients were recruited: 12 were classified as aware and 9 as unaware according to anosognosia scales (based on clinical judgment and patient-caregiver discrepancy). Behavioral results showed that aware patients took the longest time to process dementia-related words, although differences between word types were not significant, limiting interpretation of behavioral results. Imaging results showed that patients with preserved explicit awareness had a small positive differential activation of the posterior cingulate cortex (PCC) for the dementia-related words condition compared to the negative words, suggesting attribution of emotional valence to both conditions. PCC differential activation was instead negative in unaware patients, i.e., lower for dementia-related words relative to negative-words. In addition, the more negative the differential activation, the lower was the Stroop effect measuring implicit awareness. Conclusion: Posterior cingulate cortex preserved response to dementia-related stimuli may be a marker of preserved implicit self-awareness

Indicators Affecting the Urban Resilience with a Scenario Approach in Tehran Metropolis

Urban resilience refers to the capacity of an urban system to fully recover from unforeseen calamities. This study aims to assess the physical resilience indicators used to measure urban resilience in Tehran, the political and economic capital of Iran, and to pinpoint the most significant direct and indirect influences on urban resilience. The research process divided into two parts. The environmental scanning approach (reviewing papers and published sources, interviewing specialists, and monitoring conferences) and the literature review were employed in the first part to compile a database of the key information on the elements impacting physical resilience. The most significant factors impacting physical resilience over the next ten years were requested to be identified by specialists and intellectuals in the second part. Finally, the MicMac program was used to analyze the data after 29 variables were specified in Delphi. In light of the trace-analysis-dependence diagram, which depicts the instability of the influential factors and the persistence of their impact on other variables, the results demonstrate that Tehran’s physical resilience is in an unstable condition. According to the results, the factors that have the maximum impact on other variables are granularity drivers, emergency evacuation capacity, rescue and security spaces (emergency, fire station, and police station), impermeability, rate of the amendment and retrofitting measures in the buildings of each zone, building age, and the compatibility of land uses. The variables that are most susceptible to change from other variables include the distribution status of dangerous land uses, the quality of the buildings, the rate of historically vulnerable buildings, the vulnerability of internal and external roads, the rate of improvements and retrofitting measures in buildings in each zone, as well as historically vulnerable historical buildings

Non-operatively managed small to medium-sized subscapularis tendon tears: MRI evaluation with a minimum of 5 years follow-up

Background Isolated or combined subscapularis (SSC) tendon tears are frequently found in patients with shoulder pain. The purpose of this study was to evaluate the structural changes associated with SSC tear in a consecutive series of patients with nonoperatively treated small size to midsize SSC tendon tears using magnetic resonance imaging (MRI). Methods In this retrospective case series, all patients with an isolated or combined SSC tendon tear treated nonoperatively between 1999 and 2019 were identified from our MRI and clinical databases. Twenty-one patients with a mean age of 52.6 years (range 26.6-64.8, standard deviation 9.3) with a second MRI scan at a minimum of 5 years of follow-up were enrolled. The mean follow-up was 8.6 years (range 5.6-12.6, standard deviation 1.8). Initial and last follow-up MRI scans were used to determine concomitant cuff lesions, size of the SSC tear, fatty infiltration of the SSC muscle, and biceps pathology. Results Five patients had an isolated SSC lesion; 7 patients had a concomitant tear of the supraspinatus, and 9 patients had a supraspinatus and anterior infraspinatus tendon tear. At diagnosis, 14 patients had a type 1 SSC lesion as classified by Lafosse et al, 4 patients had type 2, and 3 patients had type 3 lesions. Nineteen patients (90%) were found to have an SSC tear progression of at least one Lafosse grade (P < .001); however, no tear had progressed to an irreparable type lesion (defined as Lafosse type 5). In addition, the size of SSC tendon tears increased significantly from 75 mm2 to 228 mm2 (P < .001). At the final MRI scan, the grading of fatty infiltration increased by 1 grade in 4 cases and by 2 grades in 4 cases (P = .042). At the final follow-up, in eight patients, the condition of the long head of biceps tendon was unchanged from the initial MRI; in nine patients, there was a newly subluxated biceps tendon, and in 6 patients, there was a newly ruptured long head of biceps tendon (P < .001). Conclusion After a mean of 8.6 years, almost all nonoperatively treated SSC tendon tears had increased in size, but only one-third showed additional progression of muscle fatty degeneration on MRI scan. None of the SSC lesions became irreparable during the observation period

Effect of the nud gene on grain yield in barley

Naked barleys are less yielding than the hulled ones while the reason for this difference has not beendefinitely clarified. To investigate the effect of the nud gene on yield, a barley doubled haploid (DH, Proctor 7Nudinka) population was initially tested in three environments and a QTL study was run on the entire populationas well as on two nud/NUD DH subpopulations. Among the agronomic traits studied, a QTL effect was found atnud locus on chromosome 7H only for yield and thousand grain weight (TGW), while a second QTL was found on6H, although contributed by the naked parent. Other QTLs for TGW were identified on 2H, 3H and 5H. Most QTLsfound in the entire population were confirmed by the study on the two groups. No interaction was observed betweenQTLs. To provide a more accurate evaluation of the effects of the nud gene upon grain yield, its components andother agronomic traits, sixteen naked advanced backcross (AB) BC5F2 lines in the hulled background of cultivarArda were prepared and evaluated in a replicated yield trial for two years. The only differences found betweenAB lines and Arda in grain yield and TGW were due to hull weight (11.97% of kernel weight). No differences wereobserved in other traits such as grains/m2, grains per spike, plant height, heading date and mildew resistance. Inconclusion, we think to have clarified that the effect of the nud gene on yield is due to hulls, and we did not findany pleiotropic effect of nud on other traits. This suggests, together with the finding of a QTL contributed by thenaked parent, that there is a great potential to improve naked barley up to the yield levels of hulled barley

Resistance of European spring 2-row barley cultivars to Pyrenophora graminea and detection of associated loci

Pyrenophora graminea is the seed-borne pathogen causal agent of barley leaf stripe disease. In this work, we screened a collection of 206 spring two-row barley cultivars from Europe for their resistance to the fungal pathogen. Artificial inoculation with the highly virulent isolate Dg2 revealed a continuous variation for the incidence of infection, with few highly resistant or highly susceptible genotypes. On average, old cultivars showed higher resistance than the more modern ones. Genome- Wide Association Scan was performed by exploiting available molecular data for >4000 SNP markers and revealed a single, highly significant association on the short arm of chromosome 6H, in a genomic position where quantitative trait loci (QTL) for barley resistance to P. graminea were not detected before. Based on the last version of the reference barley genome, genes encoding for proteins with a kinase domain were suggested as candidates for the locus

Genome-Wide Association Study Using Genotyping by Sequencing for Bacterial Leaf Blight Resistance Loci in Local Thai Indica Rice

Bacterial leaf blight (BLB) is a devastating disease caused by Xanthomonas oryzae pv. oryzae (Xoo), which poses a significant threat to global rice production. In this study, a genomewide association study (GWAS) was conducted using the genotyping-by-sequencing (GBS) approach to identify candidate single nucleotide polymorphisms (SNPs) associated with BLB resistance genes. The study utilized 200 indica rice accessions inoculated with seven distinct Xoo isolates and filtered highly significant SNPs using a minor allele frequency (MAF) of >5% and a call rate of 75%. Four statistical models were used to explore potential SNPs associated with BLB resistance, resulting in the identification of 32 significant SNPs on chromosomes 1–8 and 12 in the rice genome. Additionally, 179 genes were located within 100 kb of the SNP region, of which 49 were selected as candidate genes based on their known functions in plant defense mechanisms. Several candidate genes were identified, including two genes in the same linkage disequilibrium (LD) decay as the well-known BLB resistance gene (Xa1). These findings represent a valuable resource for conducting further functional studies and developing novel breeding strategies to enhance the crop’s resistance to this disease

A possible role of the trehalose/trehalose-6-phosphate/SnRK1 system in rice response to salt stress

Among the abiotic stresses exacerbated by climate change, soil salinity is one of the most harmful for crops. Rice (Oryza sativa L.) is a very salt-sensitive cereal, with particular regard to the cultivars belonging to the subspecies japonica. In order to identify genomic traits conferring salt tolerance, a collection of 277 rice accessions (ssp. japonica) has been phenotypized under mild-salinity considering germination kinetic parameters and seedling emergence rate. Genotyping By Sequencing (GBS) followed by a Genome Wide Association Study (GWASs) were carried out. A total of 31.421 SNPs were used for the analysis. Significant genotypic-phenotypic associations were observed and a few Marker-Trait Associations (MTAs) were identified. By alignment with the rice reference genome (Os-Nipponbare-Reference-IRGSP-1.0), some of the genes putatively involved in salt stress were highlighted. Among them, our interest has been focused on OsTPP7 (chromosome 9) and OsTPP10 (chromosome 7), genes that belong to the OsTPP gene family encoding for Trehalose-6-Phosphate Phosphatase (TPP) enzymes catalyzing the dephosphorylation of Trehalose-6-Phosphate (T6P) to Trehalose (Tre). The level of T6P plays a central role in abiotic stress tolerance, acting as a signal in the cascade of events regulating sugar metabolism (sucrose) during seed germination and seedling growth. This activity is mediated by Snf1-Related protein Kinase-1 (SnRK1), a metabolic sensor fundamental in maintaining carbon homeostasis under stress condition. Biochemical and molecular analyses were performed on two rice accessions showing opposite behavior under salt stress (Olcenengo, tolerant, and SR113, sensitive). Results concerning T6P, Tre and sucrose levels in growing embryos, the evaluation of the time course of \u3b1-amylase enzyme (target of the SnRK1 system) activity and of OsTPP10-OsTPP7 gene expression appear to allow us to define a picture coherent with the different effects of salt stress in Olcenengo and SR113. Functional characterization of OsTPP10 gene and its allele mining analysis within the 277 rice accessions are in progress

Anosognosia in Early- and Late-Onset Dementia and Its Association With Neuropsychiatric Symptoms

Background: The symptom anosognosia or unawareness of disease in dementia has mainly been studied in patients with late-onset dementia (LOD, ≥65 years), whereas little is known on whether it is also present in patients with early-onset dementia (EOD, &lt;65 years). We aimed at investigating differences in anosognosia between LOD and EOD, by also studying its association with different clinical variants of EOD and the presence of neuropsychiatric symptoms. Methods: A total of 148 patients, 91 EOD and 57 LOD, were recruited and underwent extended clinical assessment and caregiver interview that included questionnaires aimed at measuring anosognosia and neuropsychiatric symptoms. Differences in anosognosia between EOD and LOD and between subgroups with different clinical variants were investigated, as well as correlation between anosognosia and neuropsychiatric symptoms. A regression analysis was applied to explore the association between anosognosia and development of neuropsychiatric symptoms during disease progression. Results: Median levels of anosognosia were not significantly different between EOD and LOD. Anosognosia increased overtime with disease progression and was higher in frontotemporal dementia patients or, more precisely, in frontotemporal dementia and Alzheimer's disease variants associated with involvement of the frontal lobes. Higher levels of early anosognosia were associated with higher frequency and severity of subsequent neuropsychiatric symptoms, in particular apathy, later in the course of the disease. Conclusion: Anosognosia is a frequent symptom of EOD, occurring in 94.5% of all-cause EOD, and it is associated with higher risk of developing neuropsychiatric symptoms during disease progression. Recognising anosognosia may be helpful for clinicians and families to reduce diagnostic delay and improve disease managment

Determinants of barley grain yield in drought-prone Mediterranean environments

The determinants of barley grain yield in drought-prone Mediterranean environments have been studied in the Nure x Tremois (NT) population. A large set of yield and other morpho-physiological data were recorded in 118 doubled haploid (DH) lines of the population, in multi-environment field trials (18 site-year combination). Agrometeorological variables have been recorded and calculated at each site too. Four main periods of barley development were considered, vegetative, reproductive early and late grain filling phases, to dissect the effect on yield traits of the growth phases. Relationships between agrometeorological variables, grain yield (GY) and its main components (GN and GW) were also investigated by correlation. Results firstly gave a clear indication of the involvement of water consumption in determining GY and GW (r2=0.616, P=0.007 and r2=0.703, P=0.005, respectively) calculated from sowing to the early grain filling period, while GN showed its highest correlation with the total photothermal quotient (PQ) calculated for the same period (r2=0.646, P=0.013). With the only exception of total PQ calculated during the vegetative period, all significant correlations with GY were associated to water-dependent agrometeorological parameters. As a second result, the NT segregating population allowed us to weight the amount of interaction due to genotypes over environments or to environments in relation to genotypes by a GGE analysis; 47.67% of G+GE sum of squares was explained by the first two principal components. Then, the introduction of genomic information at major barley genes regulating the length of growth cycle allowed us to explain patterns of adaptation of different groups of NT lines according to the variants (alleles) harbored at venalization (Vrn-H1) in combination with earliness (Eam6) genes. The superiority of the lines carrying the Nure allele at Eam6 was confirmed by factorial ANOVA testing the four possible haplotypes obtained combining alternative alleles at Eam6 and Vrn-H1. Maximum yield potential and differentials among the NT genotypes was finally explored through Finlay-Wilkinson model to interpret grain yield of NT genotypes together with yield adaptability (Ya), as the regression coefficient bi; Ya ranged from 0.71 for NT77 to 1.20 for NT19. Lines simply harboring the Nure variants at the two genes behaved as highest yielding (3.04 t ha-1), and showed the highest yield adaptability (bi=1.05). The present study constitutes a starting point towards the introduction of genomic variables in agronomic models for barley grain yield in Mediterranean environments