An Update on Psychopharmacological Treatment of Autism Spectrum Disorder

While behavioral interventions remain the mainstay of treatment of autism spectrum disorder (ASD), several potential targeted treatments addressing the underlying neurophysiology of ASD have emerged in the last few years. These are promising for the potential to, in future, become part of the mainstay treatment in addressing the core symptoms of ASD. Although it is likely that the development of future targeted treatments will be influenced by the underlying heterogeneity in etiology, associated genetic mechanisms influencing ASD are likely to be the first targets of treatments and even gene therapy in the future for ASD. In this article, we provide a review of current psychopharmacological treatment in ASD including those used to address common comorbidities of the condition and upcoming new targeted approaches in autism management. Medications including metformin, arbaclofen, cannabidiol, oxytocin, bumetanide, lovastatin, trofinetide, and dietary supplements including sulforophane and N-acetylcysteine are discussed. Commonly used medications to address the comorbidities associated with ASD including atypical antipsychotics, serotoninergic agents, alpha-2 agonists, and stimulant medications are also reviewed. Targeted treatments in Fragile X syndrome (FXS), the most common genetic disorder leading to ASD, provide a model for new treatments that may be helpful for other forms of ASD.

Usher Syndrome

Usher syndrome (USH) is the most common genetic condition responsible for combined loss of hearing and vision. Balance disorders and bilateral vestibular areflexia are also observed in some cases. The syndrome was first described by Albrecht von Graefe in 1858, but later named by Charles Usher, who presented a large number of cases with hearing loss and retinopathy in 1914. USH has been grouped into three main clinical types: 1, 2, and 3, which are caused by mutations in different genes and are further divided into different subtypes. To date, nine causative genes have been identified and confirmed as responsible for the syndrome when mutated: MYO7A, USH1C, CDH23, PCDH15, and USH1G (SANS) for Usher type 1; USH2A, ADGRV1, and WHRN for Usher type 2; CLRN1 for Usher type 3. USH is inherited in an autosomal recessive pattern. Digenic, bi-allelic, and polygenic forms have also been reported, in addition to dominant or nonsyndromic forms of genetic mutations. This narrative review reports the causative forms, diagnosis, prognosis, epidemiology, rehabilitation, research, and new treatments of USH.

Polyelectrolyte Complexes of Ciprofloxacin and Lidocaine Improve Wound Healing in Deep Second Degree Burns and Reduce in Vitro Ciprofloxacin Cytotoxicity in Fibroblasts

The development of new treatments capable of controlling infections and pain related to burns continues to be a challenge. Antimicrobials are necessary tools, but these can be cytotoxic for regenerating cells.In this study, antibiotic-anesthetic smart systems obtained by ionic complexation of polyelectrolytes with ciprofloxacin and lidocaine were obtained as film and hydrogel. The complexation of ciprofloxacin with natural polyelectrolytes efficiently contributed to increasing biocompatibility in a primary culture of isolated fibroblasts. In addition, the relative levels of the proteins integrin β1 and p-FAK involved in cell migration were increased with no modifications in cell mobility. Their evaluation in a deep second-degree burn model revealed fast reepithelization, with appendage conservation and complete dermis organization. Encouragingly, we found that both the film and the hydrogel showed a significantly superior performance compared to the reference treatment of silver sulfadiazine cream. This work highlights the great potential of this smart system as an attractive dressing for burns, which surpasses currently available treatments.

A Short History of Bernard Fisher’s Contributions to Randomized Clinical Trials

Dr. Bernard Fisher (1918-2019) was an early proponent of evidence-based medicine using the mechanism of prospective, multicenter, randomized clinical trials to test biological and clinical hypotheses. In this article, I trace how his early scientific work in striving to understand the nature of cancer metastasis through animal experiments led to a new, testable, clinical hypothesis: that surgery to remove only the tumor and a small amount of tissue around it was as effective as the more disfiguring operations that were then the standard treatment. Fisher’s work with the National Surgical Adjuvant Breast and Bowel Project (NSABP) using large, randomized clinical trials to demonstrate the veracity of this hypothesis led to a new paradigm in which the emphasis was placed on how systemic therapies used at an early stage of disease could effectively eradicate breast cancer for many patients. This new therapeutic approach led to the successful development of new treatments, many of which are widely used today. Ultimately, the new paradigm led to successfully preventing breast cancer in women who were at high risk for the disease but who had not yet been diagnosed with the disease. Throughout his entire career, Fisher championed the use of large prospective, randomized clinical trials despite criticism from many in the medical community who strongly criticized his use of randomization as a mechanism for testing clinical hypotheses. The approach he and the NSABP employed is still considered to be the highest standard of evidence in conducting clinical studies.

Identification of Potential Key Genes and Molecular Mechanisms of Medulloblastoma Based on Integrated Bioinformatics Approach

Background. Medulloblastoma (MB) is the most occurring brain cancer that mostly happens in childhood age. This cancer starts in the cerebellum part of the brain. This study is designed to screen novel and significant biomarkers, which may perform as potential prognostic biomarkers and therapeutic targets in MB. Methods. A total of 103 MB-related samples from three gene expression profiles of GSE22139, GSE37418, and GSE86574 were downloaded from the Gene Expression Omnibus (GEO). Applying the limma package, all three datasets were analyzed, and 1065 mutual DEGs were identified including 408 overexpressed and 657 underexpressed with the minimum cut-off criteria of ∣ log fold change ∣ > 1 and P < 0.05 . The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and WikiPathways enrichment analyses were executed to discover the internal functions of the mutual DEGs. The outcomes of enrichment analysis showed that the common DEGs were significantly connected with MB progression and development. The Search Tool for Retrieval of Interacting Genes (STRING) database was used to construct the interaction network, and the network was displayed using the Cytoscape tool and applying connectivity and stress value methods of cytoHubba plugin 35 hub genes were identified from the whole network. Results. Four key clusters were identified using the PEWCC 1.0 method. Additionally, the survival analysis of hub genes was brought out based on clinical information of 612 MB patients. This bioinformatics analysis may help to define the pathogenesis and originate new treatments for MB.

Pyroptosis-Mediated Cell Death as an Approach for Novel Cancer Treatment

Cancer is the leading cause of death in the world, which makes understanding its biology and creating new treatments to save lives vitally important. To understand the pathways through which cancer evades apoptosis and how death can be induced upon cancerous cells, apoptosis has been extensively researched, but we propose the benefits of investigating another form of mediated cell death--pyroptosis--to understand alternative ways that cancer can be treated and how utilizing pyroptosis may be a more effective alternative than apoptosis. We also review one of the most controversial usages of bacteria-mediated treatment for cancer, as well as advise future researchers hoping to implement pyroptosis-based treatment to investigate the necessity of the situation before resorting to bacteria-mediated onco-treatments.

Characterization of antibiotic resistance in clinical isolates of Klebsiella pneumoniae in Denmark

Klebsiella pneumoniae (KP) is a major global health problem as it leads to hospital outbreaks all over the world and is becoming more difficult to treat due to its increasing antimicrobial resistance (AMR). Optimization and development of new treatments of KP requires understanding of its population structure and AMR properties. Therefore, in this study, we collected and sequenced 491 KP strains from four major Danish microbiology departments covering 51% of the Danish population. The isolates were whole genome sequenced (WGS), phenotypically characterized and compared with 2,124 KP strains from 13 different countries (PATRIC strains). We found that while genomic content varies significantly across the Danish strains, they also differ significantly from strains from other countries, due to the lack of certain AMR sequence types (e.g. ST258 and ST307) in Denmark. Genomic and experimental analysis suggest that Danish strains contain fewer virulence mechanisms and are more susceptible to antimicrobials compared to strains from other countries, likely due to the relatively low antibiotic usage in Denmark where 70% of hospital antibiotic usage is penicillins. We also identified potential novel AMR determinants to tigecycline through statistical analysis of genomic and phenotypic data. To conclude, we obtained a more comprehensive understanding of the KP strains in Denmark and provided valuable insights for future experiments and strategies to combat AMR in KP.