Effect of Buspirone on Upper Gastrointestinal Disorders of Gut-Brain Interaction: A Systematic Review and Meta-analysis.

Background/aims: Buspirone shows promise in treating disorders of gut-brain interaction (DGBIs), particularly functional dyspepsia. However, findings have been mixed.

Methods: We systematically searched for prospective studies testing buspirone for any upper gastrointestinal DGBI in 4 databases (Cochrane, PubMed, Scopus, and PsycInfo).

Predictive value of urine microscopy and urine culture in bacteraemic adults without localising urinary features.

Background: Urine microscopy (UM) and urine culture (UC) are used in bacteraemic patients to identify a urinary focus of infection. However, their positive and negative predictive values (PPV and NPV) in patients without localising urinary features are uncertain.

Aims: We aimed to determine the predictive value of UM/UC for diagnosing bacteraemic urinary tract infection (bUTI) in bacteraemic patients without localising urinary features.

Activation of the interleukin-23/Th17 axis in major depression: a systematic review and meta-analysis.

The interleukin-23/Th17 axis is a promising modifiable target for depression. However, its association with depression has not been systematically evaluated. We systematically searched four databases (EMBASE, Web of Science, Pubmed and PsycINFO) for studies comparing patients with major depression and healthy controls for plasma/serum levels of Th17 cells and their canonical cytokines (interleukin-17A [IL-17A], IL-22, granulocyte macrophage colony stimulating factor [GM-CSF]).

Caenorhabditis elegans models for striated muscle disorders caused by missense variants of human LMNA.

Striated muscle laminopathies caused by missense mutations in the nuclear lamin gene LMNA are characterized by cardiac dysfunction and often skeletal muscle defects. Attempts to predict which LMNA variants are pathogenic and to understand their physiological effects lag behind variant discovery. We created Caenorhabditis elegans models for striated muscle laminopathies by introducing pathogenic human LMNA variants and variants of unknown significance at conserved residues within the lmn-1 gene.

A humanized Caenorhabditis elegans model of hereditary spastic paraplegia-associated variants in KLC4.

Hereditary spastic paraplegia (HSP) is a group of degenerative neurological disorders. We identified a variant in human kinesin light chain 4 (KLC4) that is suspected to be associated with autosomal-dominant HSP. How this and other variants relate to pathologies is unknown.

Emerging technologies in personalized medicine.

A variety of technologies are emerging to help clinicians provide patient-specific diagnosis and therapies. This special edition of the Molecular Aspects of Medicine is a collection of mini reviews covering a broad range of topics, from systems to model patient variants and discover therapies (Microphysiological systems with patient derived tissue and CRISPR-humanized animal models), to new modalities in diagnostics and therapeutics (Extracellular Vesicles, RNA therapeutics, microbiome and molecular dynamics).

A humanized model of Hereditary Spastic Paraplegia-associated variants in kinesin light chain KLC4.

Unlabelled: Hereditary spastic paraplegia (HSP) is a group of degenerative neurological disorders. We identified a variant in human kinesin light chain that is suspected to be associated with autosomal dominant HSP. How this and other variants relate to pathologies is unknown.

Clinical variants in expressing human STXBP1 reveal a novel class of pathogenic variants and classify variants of uncertain significance.

Purpose: Modeling disease variants in animals is useful for drug discovery, understanding disease pathology, and classifying variants of uncertain significance (VUS) as pathogenic or benign.

Methods: Using Clustered Regularly Interspaced Short Palindromic Repeats, we performed a Whole-gene Humanized Animal Model procedure to replace the coding sequence of the animal model's ortholog with the coding sequence for the human gene. Next, we used Clustered Regularly Interspaced Short Palindromic Repeats to introduce precise point variants in the Whole-gene Humanized Animal Model-humanized locus from 3 clinical categories (benign, pathogenic, and VUS).

Phenotypic screening models for rapid diagnosis of genetic variants and discovery of personalized therapeutics.

Precision medicine strives for highly individualized treatments for disease under the notion that each individual's unique genetic makeup and environmental exposures imprints upon them not only a disposition to illness, but also an optimal therapeutic approach. In the realm of rare disorders, genetic predisposition is often the predominant mechanism driving disease presentation. For such, mostly, monogenic disorders, a causal gene to phenotype association is likely.

Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics.

With more than 5 million fatalities and close to 300 million reported cases, COVID-19 is the first documented pandemic due to a coronavirus that continues to be a major health challenge. Despite being rapid, uncontrollable, and highly infectious in its spread, it also created incentives for technology development and redefined public health needs and research agendas to fast-track innovations to be translated. Breakthroughs in computational biology peaked during the pandemic with renewed attention to making all cutting-edge technology deliver agents to combat the disease.

The use of CRISPR to generate a whole-gene humanized and the examination of P301L and G272V clinical variants, along with the creation of deletion null alleles of and loci.

To study important genes involved in Frontotemporal Dementia ( , and ), we created deletion alleles in the three orthologous genes ( , , and ). Simultaneously, we replaced the gene with the predicted orthologous human gene, often called whole-gene humanization, which allows direct assessment of conserved gene function, as well as the opportunity to examine consequences of clinical disease-associated patient variations. Each gene was manipulated using a different selection strategy, including a novel strategy using an mutation rescue technique.

Systems to model the personalized aspects of microbiome health and gut dysbiosis.

The human gut microbiome is a complex and dynamic microbial entity that interacts with the environment and other parts of the body including the brain, heart, liver, and immune system. These multisystem interactions are highly conserved from invertebrates to humans, however the complexity and diversity of human microbiota compositions often yield a context that is unique to each individual. Yet commonalities remain across species, where a healthy gut microbiome will be rich in symbiotic commensal biota while an unhealthy gut microbiota will be experiencing abnormal blooms of pathobiont bacteria.

The effects of burning on isotope ratio values in modern bone: Importance of experimental design for forensic applications.

This study examined preservation of isotope ratio values by comparing isotope composition of bones before and after burning. We analyzed common geoprofiling isotope systems (δC, δN, δO, and Sr/Sr) and lesser studied systems (δS and δSr) to evaluate if inferences about diet and residence history were altered by the burning process. We used two burn methods: one to simulate previous academic studies using a muffle furnace and one to more closely resemble a house fire or body disposal attempt using open flame.

Cognitive Impairment in Adult Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Background: People living with inflammatory bowel disease (IBD) are exposed to multiple risk factors for cognitive impairment and frequently report cognitive difficulties. However, the presence of cognitive impairment in IBD has not been systematically reviewed.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a systematic multidatabase search for cross-sectional and longitudinal studies comparing adults with IBD versus healthy controls for domain-specific cognitive function or scores on multidomain cognitive screening tools.

Computed Tomography and Magnetic Resonance Imaging are Similarly Reliable in the Assessment of Glenohumeral Arthritis and Glenoid Version.

Background: The purpose of this study was to compare the intraobserver and interobserver reliability of CT and T2-weighted MRI for evaluation of the severity of glenoid wear, glenohumeral subluxation, and glenoid version.

Methods: Sixty-one shoulders with primary osteoarthritis had CT and MRI scans before shoulder arthroplasty. All slices were blinded and randomized before evaluation.

Platforms for Personalized Polytherapeutics Discovery in COVID-19.

The COVID-19 pandemic entered its third and most intense to date wave of infections in November 2020. This perspective article describes how combination therapies (polytherapeutics) are a needed focus for helping battle the severity of complications from SARS-CoV-2 infection. It outlines the types of systems that are needed for fast and efficient combinatorial assessment of therapeutic candidates.

Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma.

Human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) represents a unique disease entity within head and neck cancer with rising incidence. Previous work has shown that alternative splicing events (ASEs) are prevalent in HPV+ OPSCC, but further validation is needed to understand the regulation of this process and its role in these tumours. In this study, eleven ASEs (, and were selected for validation from 109 previously published candidate ASEs to elucidate the post-transcriptional mechanisms of oncogenesis in HPV+ disease.

Anterior cingulate and medial prefrontal cortex response to systematically controlled tonal dissonance during passive music listening.

Several studies have attempted to investigate how the brain codes emotional value when processing music of contrasting levels of dissonance; however, the lack of control over specific musical structural characteristics (i.e., dynamics, rhythm, melodic contour or instrumental timbre), which are known to affect perceived dissonance, rendered results difficult to interpret.