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Due to their variable phenotypes, mitochondrial disorders (MDs) can be difficult to diagnose. The absolute load lactate stress test (LSTA) and the relative load lactate stress test (LSTR) have been shown to be useful screening tools for the detection of MDs. In this study, we aimed to perform a meta-analysis to evaluate the diagnostic accuracy of these tests in detecting MDs. The study protocol was registered with PROSPERO (no. CRD42022331710). We performed a comprehensive search of PubMed, Web of Science and Scopus from January 10th, 2022 to July 27th, 2022 and included case-control and cohort diagnostic studies that targeted participants with MDs and used LSTA and/or LSTR as index tests. Two reviewers worked separately to compile information from selected articles. Risk of bias and applicability were assessed using the QUADAS-2 tool. Sensitivity and specificity, as well as diagnostic odds ratios (DORs) and area under the curve (AUC) were calculated using Meta-DiSc 2.0 and Stata software. The analysis included 14 studies with a total of 1064 participants, divided into six studies with 793 participants for LSTA and eight studies with 271 participants for LSTR. For LSTA the meta-analysis gave a pooled sensitivity of 0.67 (95 % CI 0.62, 0.72), a specificity of 0.93 (95 % CI 0.85, 0.97), DOR of 26.63 (95 % CI 10.99, 64.52), and AUC of 0.70 (95 % CI 0.66, 0.74). For LSTR, the pooled sensitivity was 0.52 (95 % CI 0.33, 0.70), specificity 0.94 (95 % CI 0.79, 0.99), DOR 18.14 (95 % CI 2.99, 109.85), and the AUC 0.80 (95 % CI 0.76, 0.83). LSTA and LSTR showed as screening tests moderate sensitivity and high specificity for MD diagnosis, particularly for LSTR. The choice of test may depend on the patient's individual aerobic capacity and motor skills and the availability of equipment.

The objective of this work is to establish the existence of entropy solutions to degenerate nonlinear elliptic problems for L1-data f with a Hardy potential, in weighted Sobolev spaces with variable exponent, which are represented as follows where is a Leray-Lions operator from into its dual, is a non-linearity term that only meets the growth condition, and ρ > 0 is a constant.

Le syndrome de Fahr est une entité anatomoclinique rare dont la principale étiologie est l'hypoparathyroïdie primitive ou postopératoire. Il est caractérisé par des calcifications intracérébrales bilatérales et symétriques, localisées dans les noyaux gris centraux, le plus souvent associées à des troubles du métabolisme phosphocalcique. Les auteurs rapportent le cas d'un patient âgé de 54 ans suivi depuis 20 ans pour hypoparathyroïdie primaire, qui a présenté des troubles amnésiques révélant un syndrome de Fahr secondaire à l'hypoparathyroïdie.

A Computational Fluid Dynamics (CFD) and response surface-based multiobjective design optimization were performed for six different 2D airfoil profiles, and the Pareto optimal front of each airfoil is presented. FLUENT, which is a commercial CFD simulation code, was used to determine the relevant aerodynamic loads. The Lift Coefficient (CL) and Drag Coefficient (CD) data at a range of 0° to 12° angles of attack (α) and at three different Reynolds numbers (Re=68,459, 479, 210, and 958, 422) for all the six airfoils were obtained. Realizable k-ε turbulence model with a second-order upwind solution method was used in the simulations. The standard least square method was used to generate response surface by the statistical code JMP. Elitist Non-dominated Sorting Genetic Algorithm (NSGA-II) was used to determine the Pareto optimal set based on the response surfaces. Each Pareto optimal solution represents a different compromise between design objectives. This gives the designer a choice to select a design compromise that best suits the requirements from a set of optimal solutions. The Pareto solution set is presented in the form of a Pareto optimal front.

Bipolaris cynodontis was isolated for the fi rst time from Oryza sativa leaves in northwestern Morocco. The pathogenicity of three isolates of B. cynodontis was compared by inoculating the isolates on the leaves of three rice varieties. All the isolates developed similar foliar lesions that differed from those caused by other species of Bipolaris pathogenic on rice.

Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants. To define the phenotypic effects of RBL2 mutations in detail, we identified and clinically characterized a cohort of 35 patients from 20 families carrying pLOF variants in RBL2, including fifteen new variants that substantially broaden the molecular spectrum. The clinical presentation of affected individuals is characterized by a range of neurological and developmental abnormalities. Global developmental delay and intellectual disability were uniformly observed, ranging from moderate to profound and involving lack of acquisition of key motor and speech milestones in most patients. Disrupted sleep was also evident in some patients. Frequent features included postnatal microcephaly, infantile hypotonia, aggressive behaviour, stereotypic movements, seizures, and non-specific dysmorphic features. Neuroimaging features included cerebral atrophy, white matter volume loss, corpus callosum hypoplasia and cerebellar atrophy. In parallel, we used the fruit fly, Drosophila melanogaster, to investigate how disruption of the conserved RBL2 orthologue Rbf impacts nervous system function and development. We found that Drosophila Rbf LOF mutants recapitulate several features of patients harbouring RBL2 variants, including developmental delay, alterations in head and brain morphology, locomotor defects, and perturbed sleep. Surprisingly, in addition to its known role in controlling tissue growth during development, we found that continued Rbf expression is also required in fully differentiated post-mitotic neurons for normal locomotion in Drosophila, and that adult-stage neuronal re-expression of Rbf is sufficient to rescue Rbf mutant locomotor defects. Taken together, our study provides a clinical and experimental basis to understand genotype-phenotype correlations in an RBL2-linked neurodevelopmental disorder, and suggests that restoring RBL2 expression through gene therapy approaches may ameliorate some symptoms caused by RBL2 pLOF., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)