Heterogeneity of mature oligodendrocytes in the central nervous system.

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system. Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons. Despite the recognition of potential heterogeneity in mature oligodendrocyte function, a comprehensive summary of mature oligodendrocyte diversity is lacking. We delve into early 20 th -century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes. Indeed, recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences. Furthermore, modern molecular investigations, employing techniques such as single cell/nucleus RNA sequencing, consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region. Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis, Alzheimer's disease, and psychiatric disorders. Nevertheless, caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations. Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity. Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species, sex, central nervous system region, age, and disease, hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Epididymal mRNA expression profiles for the protein disulfide isomerase gene family: Modulation by development and androgens.

BACKGROUND: The endoplasmic reticulum (ER) is the central hub for protein quality control, where the protein disulfide isomerases (PDIs), encoded by at least 21 genes, play a pivotal role. These multifunctional proteins contribute to disulfide bond formation, proper folding, and protein modifications, and may act as hormone-binding proteins (e.g., steroids), influencing hormone biology. The interplay between ER proteostasis, PDIs, and epididymis-a crucial site for sperm maturation-remains largely understudied. OBJECTIVES: This study characterizes transcriptional signatures of Pdi genes in the epididymis. MATERIAL AND METHODS: Transcriptional profiles of selected Pdi genes were assessed in adult Wistar rat tissues, and epididymis under different experimental conditions (developmental stages, surgical castration, and efferent ductules ligation [EDL]). In silico bioinformatic analyses identified expression trends of this gene family in human epididymal segments. RESULTS: P4hb, Pdia3, Pdia5, Pdia6, Erp44, Erp29, and Casq1 transcripts were detected in both reproductive and non-reproductive tissues, while Casq2 exhibited higher abundance in vas deferens, prostate, and heart. Pdilt, highly expressed in testis, and Pdia2, highly expressed in heart, showed minimal mRNA levels in the epididymis. In the mesonephric duct, epididymal embryonic precursor, P4hb, Pdia3, Pdia5, Pdia6, and Erp29 mRNAs were found at gestational day (GD) 17.5. Except for Erp29, which remained stable, these Pdi transcript levels increased from GD17.5 to GD20.5, when epididymal morphogenesis occurs, and were maintained to varying degrees in the epididymis during postnatal development. Surgical castration downregulated P4hb, Pdia3, Pdia5, Pdia6, Pdilt and Erp29 transcripts, an effect reversed by testosterone replacement. Conversely, transcript levels remained unaffected by EDL, except P4hb, which was reduced in caput epididymis. All 21 PDI genes exhibited diverse transcriptional profiles across the human epididymis. DISCUSSION AND CONCLUSION: The findings lay the foundations to explore Pdi genes in epididymal biology. As a considerable proportion of male infertility cases are idiopathic, targeting hormonal regulation of protein quality control in epididymis represents a route to address male infertility and advance therapeutic interventions in this domain.

Robust data-driven segmentation of pulsatile cerebral vessels using functional magnetic resonance imaging.

Functional magnetic resonance imaging (fMRI) captures rich physiological and neuronal information that can offer insights into neurofluid dynamics, vascular health, and waste clearance function. The availability of cerebral vessel segmentation could facilitate fluid dynamics research in fMRI. However, without magnetic resonance angiography scans, cerebral vessel segmentation is challenging and time-consuming. This study leverages cardiac-induced pulsatile fMRI signal to develop a data-driven, automatic segmentation of large cerebral arteries and the superior sagittal sinus (SSS). The method was validated in a local dataset by comparing it to ground truth cerebral artery and SSS segmentations. Using the Human Connectome Project (HCP) aging dataset, the method's reproducibility was tested on 422 participants aged 36 to 100 years, each with four repeated fMRI scans. The method demonstrated high reproducibility, with an intraclass correlation coefficient > 0.7 in both cerebral artery and SSS segmentation volumes. This study demonstrates that the large cerebral arteries and SSS can be reproducibly and automatically segmented in fMRI datasets, facilitating the investigation of fluid dynamics in these regions.

Developments and applications of the OPTIMADE API for materials discovery, design, and data exchange.

The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the v1.2 release, and has underpinned multiple scientific studies. In this work, we highlight the latest features of the API format, accompanying software tools, and provide an update on the implementation of OPTIMADE in contributing materials databases. We end by providing several use cases that demonstrate the utility of the OPTIMADE API in materials research that continue to drive its ongoing development.

Diatom abundance in the polar oceans is predicted by genome size.

A principal goal in ecology is to identify the determinants of species abundances in nature. Body size has emerged as a fundamental and repeatable predictor of abundance, with smaller organisms occurring in greater numbers than larger ones. A biogeographic component, known as Bergmann's rule, describes the preponderance, across taxonomic groups, of larger-bodied organisms in colder areas. Although undeniably important, the extent to which body size is the key trait underlying these patterns is unclear. We explored these questions in diatoms, unicellular algae of global importance for their roles in carbon fixation and energy flow through marine food webs. Using a phylogenomic dataset from a single lineage with worldwide distribution, we found that body size (cell volume) was strongly correlated with genome size, which varied by 50-fold across species and was driven by differences in the amount of repetitive DNA. However, directional models identified temperature and genome size, not cell size, as having the greatest influence on maximum population growth rate. A global metabarcoding dataset further identified genome size as a strong predictor of species abundance in the ocean, but only in colder regions at high and low latitudes where diatoms with large genomes dominated, a pattern consistent with Bergmann's rule. Although species abundances are shaped by myriad interacting abiotic and biotic factors, genome size alone was a remarkably strong predictor of abundance. Taken together, these results highlight the cascading cellular and ecological consequences of macroevolutionary changes in an emergent trait, genome size, one of the most fundamental and irreducible properties of an organism.

Barcoded overexpression screens in gut Bacteroidales identify genes with roles in carbon utilization and stress resistance.

A mechanistic understanding of host-microbe interactions in the gut microbiome is hindered by poorly annotated bacterial genomes. While functional genomics can generate large gene-to-phenotype datasets to accelerate functional discovery, their applications to study gut anaerobes have been limited. For instance, most gain-of-function screens of gut-derived genes have been performed in Escherichia coli and assayed in a small number of conditions. To address these challenges, we develop Barcoded Overexpression BActerial shotgun library sequencing (Boba-seq). We demonstrate the power of this approach by assaying genes from diverse gut Bacteroidales overexpressed in Bacteroides thetaiotaomicron. From hundreds of experiments, we identify new functions and phenotypes for 29 genes important for carbohydrate metabolism or tolerance to antibiotics or bile salts. Highlights include the discovery of a D-glucosamine kinase, a raffinose transporter, and several routes that increase tolerance to ceftriaxone and bile salts through lipid biosynthesis. This approach can be readily applied to develop screens in other strains and additional phenotypic assays.

Phylogenetic distribution of DNA topoisomerase VI and its distinction from SPO11.

DNA topoisomerases (topos) are major targets for antimicrobial and chemotherapeutic drugs due to their fundamental roles in regulating DNA topology. Type II topos are essential for chromosome segregation and relaxing positive DNA supercoils, and are exemplified by topo II in eukaryotes, topo IV and DNA gyrase in bacteria, and topo VI in archaea. Topo VI occurs ubiquitously in plants and sporadically in bacteria, algae, and other protists and is highly homologous to Spo11, which initiates eukaryotic homologous recombination. This homology makes the two complexes difficult to distinguish by sequence and leads to discrepancies such as the identity of the putative topo VI in malarial Plasmodium species. A lack of understanding of the role and distribution of topo VI outside of archaea hampers its pursuit as a potential drug target, and the present study addresses this with an up-to-date and extensive phylogenetic analysis. We show that the A and B subunits of topo VI and Spo11 can be distinguished using phylogenetics and structural modelling, and that topo VI is not present in Plasmodium nor other members of the phylum Apicomplexa. These findings provide insights into the evolutionary relationships between topo VI and Spo11, and their adoption alongside other type II topos.

Molecular mechanisms and environmental adaptations of flagellar loss and biofilm growth of Rhodanobacter under environmental stress.

Biofilms aid bacterial adhesion to surfaces via direct and indirect mechanisms, and formation of biofilms is considered as an important strategy for adaptation and survival in sub-optimal environmental conditions. However, the molecular underpinnings of biofilm formation in subsurface sediment/groundwater ecosystems where microorganisms often experience fluctuations in nutrient input, pH, nitrate or metal concentrations is underexplored. We examined biofilm formation under different nutrient, pH, metal, and nitrate regimes of 16 Rhodanobacter strains isolated from subsurface groundwater wells spanning diverse pH (3.5 to 5) and nitrate levels (13.7 to 146 mM). Eight Rhodanobacter strains demonstrated significant biofilm growth under low pH, suggesting adaptation to survive and grow at low pH. Biofilms intensified under aluminum stress, particularly in strains possessing fewer genetic traits associated with biofilm formation warranting further investigation. Through RB-TnSeq, proteomics, use of specific mutants and transmission electron microscopy analysis, we discovered flagellar loss under aluminum stress, indicating a potential relationship between motility, metal tolerance, and biofilm growth. Comparative genomic analyses revealed absence of flagella and chemotaxis genes, and presence of putative Type VI secretion system in the high biofilm-forming strain FW021-MT20. This study identifies genetic determinants associated with biofilm growth in a predominant environmental genus, Rhodanobacter, under metal stress and identifies traits aiding survival and adaptation to contaminated subsurface environments.

Perioperative Management of Antiplatelet and Anticoagulant Therapy in Patients Undergoing Interventional Techniques: 2024 Updated Guidelines from the American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: The frequency of performance of interventional techniques in chronic pain patients receiving anticoagulant and antiplatelet therapy continues to increase. Understanding the importance of continuing chronic anticoagulant therapy, the need for interventional techniques, and determining the duration and discontinuation or temporary suspension of anticoagulation is crucial to avoiding devastating complications, primarily when neuraxial procedures are performed. Anticoagulants and antiplatelets target the clotting system, increasing the bleeding risk. However, discontinuation of anticoagulant or antiplatelet drugs exposes patients to thrombosis risk, which can lead to significant morbidity and mortality, especially in those with coronary artery or cerebrovascular disease. These guidelines summarize the current peer reviewed literature and develop consensus-based guidelines based on the best evidence synthesis for patients receiving anticoagulant and antiplatelet therapy during interventional procedures. STUDY DESIGN: Review of the literature and development of guidelines based on best evidence synthesis. OBJECTIVES: To provide a current and concise appraisal of the literature regarding the assessment of bleeding and thrombosis risk during interventional techniques for patients taking anticoagulant and/or antiplatelet medications. METHODS: Development of consensus guidelines based on best evidence synthesis included review of the literature on bleeding risks during interventional pain procedures, practice patterns, and perioperative management of anticoagulant and antiplatelet therapy. A multidisciplinary panel of experts developed methodology, risk stratification based on best evidence synthesis, and management of anticoagulant and antiplatelet therapy. It also included risk of cessation of anticoagulant and antiplatelet therapy based on a multitude of factors. Multiple data sources on bleeding risk, practice patterns, risk of thrombosis, and perioperative management of anticoagulant and antiplatelet therapy were identified. The relevant literature was identified through searches of multiple databases from 1966 through 2023. In the development of consensus statements and guidelines, we used a modified Delphi technique, which has been described to minimize bias related to group interactions. Panelists without a primary conflict of interest voted on approving specific guideline statements. Each panelist could suggest edits to the guideline statement wording and could suggest additional qualifying remarks or comments as to the implementation of the guideline in clinical practice to achieve consensus and for inclusion in the final guidelines, each guideline statement required at least 80% agreement among eligible panel members without primary conflict of interest. RESULTS: A total of 34 authors participated in the development of these guidelines. Of these, 29 participated in the voting process. A total of 20 recommendations were developed. Overall, 100% acceptance was obtained for 16 of 20 items. Total items were reduced to 18 with second and third round voting. The final results were 100% acceptance for 16 items (89%). There was disagreement for 2 statements (statements 6 and 7) and recommendations by 3 authors. These remaining 2 items had an acceptance of 94% and 89%. The disagreement and dissent were by Byron J. Schneider, MD, with recommendation that all transforaminals be classified into low risk, whereas Sanjeeva Gupta, MD, desired all transforaminals to be in intermediate risk. The second disagreement was related to Vivekanand A. Manocha, MD, recommending that cervical and thoracic transforaminal to be high risk procedures.Thus, with appropriate literature review, consensus-based statements were developed for the perioperative management of patients receiving anticoagulants and antiplatelets These included the following: estimation of the thromboembolic risk, estimation of bleeding risk, and determination of the timing of restarting of anticoagulant or antiplatelet therapy.Risk stratification was provided classifying the interventional techniques into three categories of low risk, moderate or intermediate risk, and high risk. Further, on multiple occasions in low risk and moderate or intermediate risk categories, recommendations were provided against cessation of anticoagulant or antiplatelet therapy. LIMITATIONS: The continued paucity of literature with discordant recommendations. CONCLUSION: Based on the review of available literature, published clinical guidelines, and recommendations, a multidisciplinary panel of experts presented guidelines in managing interventional techniques in patients on anticoagulant or antiplatelet therapy in the perioperative period. These guidelines provide a comprehensive assessment of classification of risk, appropriate recommendations, and recommendations based on the best available evidence.

Harmonized connectome resampling for variance in voxel sizes.

To date, there has been no comprehensive study characterizing the effect of diffusion-weighted magnetic resonance imaging voxel resolution on the resulting connectome for high resolution subject data. Similarity in results improved with higher resolution, even after initial down-sampling. To ensure robust tractography and connectomes, resample data to 1 mm isotropic resolution.

The Ruminant Telomere-to-Telomere (RT2T) Consortium.

Telomere-to-telomere (T2T) assemblies reveal new insights into the structure and function of the previously 'invisible' parts of the genome and allow comparative analyses of complete genomes across entire clades. We present here an open collaborative effort, termed the 'Ruminant T2T Consortium' (RT2T), that aims to generate complete diploid assemblies for numerous species of the Artiodactyla suborder Ruminantia to examine chromosomal evolution in the context of natural selection and domestication of species used as livestock.

Outpatient surgery for tibial plateau fractures.

PURPOSE: The purpose of this study was to determine the rates of compartment syndrome and other early complications following outpatient open reduction and internal fixation (ORIF) of tibial plateau fractures. METHODS: This was a retrospective cohort at a single US level I academic trauma centre of patients with tibial plateau fractures managed operatively. Inpatients received their definitive ORIF during their index hospital stay and were admitted post-operatively following ORIF. Outpatients were scheduled for ambulatory surgery during definitive ORIF. Exclusion criteria for outpatient surgery included compartment syndrome, polytrauma, open types IIIb/IIIc, and patients who received any internal fixation during index presentation. The primary outcome measure was post-operative compartment syndrome. Secondary outcomes were return to the 90-day return to the ED, 90-day readmission, surgical wound infection, thromboembolism, and 90-day mortality. An intention-to-treat (ITT) and as-treated (AT) analyses were performed. RESULTS: Totally, 71 inpatients and 47 outpatients were included. There were no cases of post-operative compartment syndrome. In the ITT analysis, there were no differences for inpatients vs outpatients for 90-day re-admission (22.5% vs 12.8%, p = 0.275), 90-day return to the ED (35.2% vs 17.0%, p = 0.052), infection (12.7% vs 2.1%, p = 0.094), DVT (7% vs 4.3%, p = 0.819), or PE 1.4% vs 0.0%, p = 1.000). The AT analysis showed a significantly higher 90-day re-admission (26.9% vs 2.5%, p = 0.003) and 90-day ED visit (38.5% vs 7.5%, p = 0.001) rate in the inpatient group. CONCLUSIONS: Appropriately selected patients with isolated tibial plateau fractures can have non-inferior rates of compartment syndrome and post-operative complications when compared to inpatients.

Neuroimaging correlates of Alzheimer's disease biomarker concentrations in a racially diverse high-risk cohort of middle-aged adults.

INTRODUCTION: In this study, we investigated biomarkers in a midlife, racially diverse, at-risk cohort to facilitate early identification and intervention. We examined neuroimaging measures, including resting state functional magnetic resonance imaging (fMRI), white matter hyperintensity vo (WMH), and hippocampal volumes, alongside cerebrospinal fluid (CSF) markers. METHODS: Our data set included 76 cognitively unimpaired, middle-aged, Black Americans (N = 29, F/M = 17/12) and Non-Hispanic White (N = 47, F/M = 27/20) individuals. We compared cerebrospinal fluid phosphorylated tau141 and amyloid beta (Aß)42 to fMRI default mode network (DMN) subnetwork connectivity, WMH volumes, and hippocampal volumes. RESULTS: Results revealed a significant race × Aß42 interaction in Black Americans: lower Aß42 was associated with reduced DMN connectivity and increased WMH volumes regions but not in non-Hispanic White individuals. DISCUSSION: Our findings suggest that precuneus DMN connectivity and temporal WMHs may be linked to Alzheimer's disease risk pathology during middle age, particularly in Black Americans. HIGHLIGHTS: Cerebrospinal fluid (CSF) amyloid beta (Aß)42 relates to precuneus functional connectivity in Black, but not White, Americans. Higher white matter hyperintensity volume relates to lower CSF Aß42 in Black Americans. Precuneus may be a hub for early Alzheimer's disease pathology changes detected by functional connectivity.

Pediatric glioma immune profiling identifies TIM3 as a therapeutic target in BRAF-Fusion pilocytic astrocytoma.

Despite being the leading cause of childhood mortality, pediatric gliomas have been relatively understudied, and the repurposing of immunotherapies has not been successful. Whole transcriptome sequencing, single-cell sequencing, and sequential multiplex immunofluorescence were used to identify an immunotherapy strategy evaluated in multiple preclinical glioma models. MAPK-driven pediatric gliomas have a higher interferon signature relative to other molecular subgroups. Single-cell sequencing identified an activated and cytotoxic microglia population designated MG-Act in BRAF-fused MAPK-activated pilocytic astrocytoma (PA), but not in high-grade gliomas or normal brain. TIM3 is expressed on MG-Act and on the myeloid cells lining the tumor vasculature but not normal brain. TIM3 expression becomes upregulated on immune cells in the PA microenvironment and anti-TIM3 reprograms ex vivo immune cells from human PAs to a pro-inflammatory cytotoxic phenotype. In a genetically engineered murine model of MAPK-driven low-grade gliomas, anti-TIM3 treatment increased median survival over IgG and anti-PD1 treated mice. ScRNA sequencing data during the therapeutic window of anti-TIM3 demonstrates enrichment of the MG-Act population. The therapeutic activity of anti-TIM3 is abrogated in the CX3CR1 microglia knockout background. These data support the use of anti-TIM3 in clinical trials of pediatric low-grade MAPK-driven gliomas.

ModDotPlot-rapid and interactive visualization of tandem repeats.

MOTIVATION: A common method for analyzing genomic repeats is to produce a sequence similarity matrix visualized via a dot plot. Innovative approaches such as StainedGlass have improved upon this classic visualization by rendering dot plots as a heatmap of sequence identity, enabling researchers to better visualize multi-megabase tandem repeat arrays within centromeres and other heterochromatic regions of the genome. However, computing the similarity estimates for heatmaps requires high computational overhead and can suffer from decreasing accuracy. RESULTS: In this work, we introduce ModDotPlot, an interactive and alignment-free dot plot viewer. By approximating average nucleotide identity via a k-mer-based containment index, ModDotPlot produces accurate plots orders of magnitude faster than StainedGlass. We accomplish this through the use of a hierarchical modimizer scheme that can visualize the full 128 Mb genome of Arabidopsis thaliana in under 5 min on a laptop. ModDotPlot is bundled with a graphical user interface supporting real-time interactive navigation of entire chromosomes. AVAILABILITY AND IMPLEMENTATION: ModDotPlot is available at https://github.com/marbl/ModDotPlot.

Radiotelemetry reveals the dependence of inland tern breeding and foraging habitats on ADCP-identified sediment aggradation reaches in lowland rivers.

The largest rivers in developed countries have usually been turned into waterways by straightening them and removing large bedforms hampering navigation. For river restoration and their sustainable management it is important to know how large bedforms support biodiversity, whether they could be protected and what potential conflicts in river management they can pose. We have addressed these questions by studying the role of large bedforms in supporting populations of two inland tern species Sternula albifrons and Sterna hirundo. We spatially analysed the behaviour of these two species with reference to the bedform structure mapped over a long semi-natural reach of the River Wisla (Vistula) (S. Poland). The results show that radiotagged terns breed on islands within the aggradation reaches, foraging in the adjacent shallows inhabited by populations of small fish. For Little Terns, the more complex the water line of emergent forms, the greater their foraging intensity. The islands do not pose any flood risk to human settlements. The whole geofeature forms an integral habitat for fish and birds; it is maintained by its geographic settings and so is stable over long periods of time (over 200 years). Protection of such habitats is thus feasible.

Para-Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models.

Para-hydroxycinnamic acid (pHCA) is one of the most abundant naturally occurring hydroxycinnamic acids, a class of chemistries known for their antioxidant properties. In this study, we evaluated the impact of pHCA on different parameters of skin aging in in vitro skin models after H2O2 and UV exposure. These parameters include keratinocyte senescence and differentiation, inflammation, and energy metabolism, as well as the underlying molecular mechanisms. Here we demonstrate that pHCA prevents oxidative stress-induced premature senescence of human primary keratinocytes in both 2D and 3D skin models, while improving clonogenicity in 2D. As aging is linked to inflammation, referred to as inflammaging, we analyzed the release of IL-6, IL-8, and PGE2, known to be associated with senescence. All of them were downregulated by pHCA in both normal and oxidative stress conditions. Mechanistically, DNA damage induced by oxidative stress is prevented by pHCA, while pHCA also exerts a positive effect on the mitochondrial and glycolytic functions under stress. Altogether, these results highlight the protective effects of pHCA against inflammaging, and importantly, help to elucidate its potential mechanisms of action.

Community-Based Participatory Research with Sexual and Gender Minority Trauma Survivors: Challenges, Solutions, and Recommendations for Future Research.

Research on sexual and gender minority (SGM) and domestic violence/sexual assault (DV/SA) is needed given that SGM people are at elevated risk of experiencing DV/SA and accessing inclusive and affirming services from DV/SA community agencies poses challenges for SGM survivors. Community-based participatory research (CBPR) is emerging as a valuable methodological tool in this area, yet few CBPR studies focus on DV/SA among SGM people. In the current paper, we present a case study of a CBPR study conducted in collaboration with SGM survivors of DV/SA, as well as community stakeholders (i.e., DV/SA agency staff and providers). More specifically, we make six recommendations to address CBPR study challenges specifically focused on SGM DV/SA, including (a) integrating positionality throughout every step of the research process, (b) establishing rapport with community partners early in the process, (c) engaging external experts in conducting research related to SGM DV/SA to enhance community-research partnerships, (d) ensuring diverse identities are represented within the study team, (e) developing clear, co-defined feedback and communication guidelines with a Survivor Advisory Board (SAB), and (f) implementing an SAB engagement/retention plan. We also provide concrete examples from our CBPR case study to illustrate each recommendation. These recommendations may enhance the impact of conducting CBPR that seeks to promote recovery from DV/SA among SGM via practices for sustainable community partnerships and linkage-to-care efforts for SGM survivors.

Emerging Treatments and Therapies for Autism Spectrum Disorder: A Narrative Review.

The prevalence of autism spectrum disorder (ASD) has increased over the last decade. In this regard, many emerging therapies have been described as ASD therapies. Although ASD does not have a cure, there are several management options available that can help reduce symptom severity. ASD is highly variable and, therefore, standard treatment protocols and studies are challenging to perform. Many of these therapies also address comorbidities for which patients with ASD have an increased risk. These concurrent diagnoses can include psychiatric and neurological disorders, including attention deficit and hyperactivity disorder, anxiety disorders, and epilepsy, as well as gastrointestinal symptoms such as chronic constipation and diarrhea. Both the extensive list of ASD-associated disorders and adverse effects from commonly prescribed medications for patients with ASD can impact presenting symptomatology. It is important to keep these potential interactions in mind when considering additional drug treatments or complementary therapies. This review addresses current literature involving novel pharmacological treatments such as oxytocin, bumetanide, acetylcholinesterase inhibitors, and memantine. It also discusses additional therapies such as diet intervention, acupuncture, music therapy, melatonin, and the use of technology to aid education. Notably, several of these therapies require more long-term research to determine efficacy in specific ASD groups within this patient population.