Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.

Exploring the Potential of Nanoporous Materials for Advancing Ophthalmic Treatments.

The landscape of ophthalmology is undergoing significant transformations, driven by technological advancements and innovations in materials science. One of the advancements in this evolution is the application of nanoporous materials, endowed with unique physicochemical properties ideal for a variety of ophthalmological applications. Characterized by their high surface area, tunable porosity, and functional versatility, these materials have the potential to improve drug delivery systems and ocular devices. This review, anchored by a comprehensive literature focusing on studies published within the last five years, examines the applications of nanoporous materials in ocular drug delivery systems (DDS), contact lenses, and intraocular lenses. By consolidating the most current research, this review aims to serve as a resource for clinicians, researchers, and material scientists engaged in the rapidly evolving field of ophthalmology.

Costs and Benefits of Undergraduates Revealing Depression to Online Science Instructors.

Depression is one of the leading mental health concerns among science undergraduates, and rates of student depression increased during the COVID-19 pandemic. Revealing one's depression in an academic science environment can be helpful, because it can result in increased support from others. However, depression is considered a concealable stigmatized identity, meaning that it can be kept hidden and may carry a stigma. A national pivot to online learning owing to COVID-19 not only increased the need to bolster student mental health, but also presented a novel learning environment. However, it is unclear to what extent students revealed their depression in science courses and why. We surveyed 1179 undergraduates with depression at a research-intensive institution about whether they had revealed their depression to an online college science instructor. Very few undergraduates (5.9%) had revealed their depression to online science instructors; students who identify as LGBTQ+, have lower grade point averages, or experience more severe depression were more likely to reveal their depression to an instructor. Undergraduates reported potential benefits from doing so, including building a connection with the instructor and receiving accommodations. This work provides insight into steps science instructors can take to foster inclusive course environments for students with depression.

Metabolomic Signatures of Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is associated with many variations in metabolism, but the ex-act correlates of these metabolic disturbances with behavior and development and their links to other core metabolic disruptions are understudied. In this study, large-scale targeted LC-MS/MS metabolomic analysis was conducted on fasting morning plasma samples from 57 children with ASD (29 with neurodevelopmental regression, NDR) and 37 healthy controls of similar age and gender. Linear model determined the metabolic signatures of ASD with and without NDR, measures of behavior and neurodevelopment, as well as markers of oxidative stress, inflammation, redox, methylation, and mitochondrial metabolism. MetaboAnalyst ver 5.0 (the Wishart Research Group at the University of Alberta, Edmonton, Canada) identified the pathways associated with altered metabolic signatures. Differences in histidine and glutathione metabolism as well as aromatic amino acid (AAA) biosynthesis differentiated ASD from controls. NDR was associated with disruption in nicotinamide and energy metabolism. Sleep and neurodevelopment were associated with energy metabolism while neurodevelopment was also associated with purine metabolism and aminoacyl-tRNA biosynthesis. While behavior was as-sociated with some of the same pathways as neurodevelopment, it was also associated with alternations in neurotransmitter metabolism. Alterations in methylation was associated with aminoacyl-tRNA biosynthesis and branched chain amino acid (BCAA) and nicotinamide metabolism. Alterations in glutathione metabolism was associated with changes in glycine, serine and threonine, BCAA and AAA metabolism. Markers of oxidative stress and inflammation were as-sociated with energy metabolism and aminoacyl-tRNA biosynthesis. Alterations in mitochondrial metabolism was associated with alterations in energy metabolism and L-glutamine. Using behavioral and biochemical markers, this study finds convergent disturbances in specific metabolic pathways with ASD, particularly changes in energy, nicotinamide, neurotransmitters, and BCAA, as well as aminoacyl-tRNA biosynthesis.

Central Nervous System Metabolism in Autism, Epilepsy and Developmental Delays: A Cerebrospinal Fluid Analysis.

Neurodevelopmental disorders are associated with metabolic pathway imbalances; however, most metabolic measurements are made peripherally, leaving central metabolic disturbances under-investigated. Cerebrospinal fluid obtained intraoperatively from children with autism spectrum disorder (ASD, n = 34), developmental delays (DD, n = 20), and those without known DD/ASD (n = 34) was analyzed using large-scale targeted mass spectrometry. Eighteen also had epilepsy (EPI). Metabolites significantly related to ASD, DD and EPI were identified by linear models and entered into metabolite-metabolite network pathway analysis. Common disrupted pathways were analyzed for each group of interest. Central metabolites most involved in metabolic pathways were L-cysteine, adenine, and dodecanoic acid for ASD; nicotinamide adenine dinucleotide phosphate, L-aspartic acid, and glycine for EPI; and adenosine triphosphate, L-glutamine, ornithine, L-arginine, L-lysine, citrulline, and L-homoserine for DD. Amino acid and energy metabolism pathways were most disrupted in all disorders, but the source of the disruption was different for each disorder. Disruption in vitamin and one-carbon metabolism was associated with DD and EPI, lipid pathway disruption was associated with EPI and redox metabolism disruption was related to ASD. Two microbiome metabolites were also detected in the CSF: shikimic and cis-cis-muconic acid. Overall, this study provides increased insight into unique metabolic disruptions in distinct but overlapping neurodevelopmental disorders.

Aspects of Large-Enrollment Online College Science Courses That Exacerbate and Alleviate Student Anxiety.

Anxiety is the top mental health concern for undergraduates. While researchers have identified ways that in-person science courses can affect anxiety, little is known about how online science courses affect anxiety. In this study, 2111 undergraduates at a large research-intensive institution completed survey questions about their anxiety in large-enrollment online science courses. Specifically, we assessed students' anxiety in the context of online science courses and asked what aspects of online science courses increase and decrease their anxiety. Students also identified what instructors can do to lessen anxiety in online classrooms. We used open coding and logistic regression to analyze student responses. More than 50% of students reported at least moderate anxiety in the context of online college science courses. Students commonly reported that the potential for personal technology issues (69.8%) and proctored exams (68.0%) increased their anxiety, while being able to access content at a later time (79.0%) and attending class from where they want (74.2%) decreased their anxiety. The most common ways that students suggested that instructors could decrease student anxiety is to increase test-taking flexibility (25.0%) and be understanding (23.1%). This study provides insight into how instructors can create more inclusive online learning environments for students with anxiety.

Complete Genome Sequence of Microbacterium Bacteriophage Erla.

We characterized the complete genome sequence of Siphoviridae bacteriophage Erla, an obligatory lytic subcluster EA1 bacteriophage infecting Microbacterium foliorum NRRL B-24224, with a capsid width of 65 nm and a tail length of 112 nm. The 41.5-kb genome, encompassing 62 predicted protein-coding genes, is highly similar (99.52% identity) to that of bacteriophage Calix.