Ketamine Infusion for Complex Regional Pain Syndrome Treatment: A Narrative Review.

Purpose Of Review: Complex Regional Pain Syndrome (CRPS) is a neuropathic pain disorder characterized by pain disproportionate to the inciting event that is constant for an extended duration. Numerous treatment options for this condition have been explored with unsatisfactory results in many cases. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist typically used as an anesthetic and analgesic, presents a promising potential treatment for CRPS in patients who fail to respond to traditional therapies.

The Role of Glucagon-Like Peptide-1 Agonists in the Treatment of Multiple Sclerosis: A Narrative Review.

Multiple sclerosis (MS) is a chronic, progressive autoimmune disease modulated by autoantibodies that inflame and destroy the myelin sheath encasing neuronal axons, impairing proper axonal conduction and function. Glucagon-like peptide-1 (GLP-1) receptor agonists have been demonstrated to exert anti-inflammatory and neuroprotective effects, making these drugs particularly exciting prospects in the treatment of MS. While the exact mechanism remains unclear, GLP-1 receptor agonists may modulate inflammatory responses by targeting GLP-1 receptors present on immune cells such as macrophages, monocytes, and lymphocytes.

Efficacy and Safety of Intrathecal Morphine for Cesarean Delivery: A Narrative Review.

Purpose Of Review: Pain management is a critical aspect of care during and following a cesarean delivery. Without proper control of pain, individuals can experience poor mobility, increased thromboembolic events, and difficulty caring for the neonate in the postpartum period. There have been multiple methods for pain management for cesarean delivery and intrathecal morphine (ITM) has emerged as a prominent option for post-operative analgesia due to its efficacy, safety, and potential benefits over other treatments.

Advances in long-read single-cell transcriptomics.

Long-read single-cell transcriptomics (scRNA-Seq) is revolutionizing the way we profile heterogeneity in disease. Traditional short-read scRNA-Seq methods are limited in their ability to provide complete transcript coverage, resolve isoforms, and identify novel transcripts. The scRNA-Seq protocols developed for long-read sequencing platforms overcome these limitations by enabling the characterization of full-length transcripts.

Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs.

A major question in developmental and regenerative biology is how organ size and architecture are controlled by progenitor cells. While limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse fetal cartilage is repaired postnatally, via a two-step process.

Stromal Niche Signals That Orchestrate Intestinal Regeneration.

Stromal cell populations have a central role in providing signals that support the maintenance, differentiation, and function of the intestinal epithelium. The behavior and fate of epithelial cells is directed by the spatial organization of stromal cells that either sustain stem and progenitor cell identity or drive differentiation. A combination of single-cell analyses, mouse models, and organoid coculture assays have provided insight into the diversity of signals delivered by stromal cells.

Factors impacting sustained coverage in the context of donor transitions: experience from Sri Lanka.

Although not reliant on donor funding for health, the external assistance that Sri Lanka receives contributes to the improvement of the health system and health outcomes. In this study, we evaluated transition experiences of the expanded programme on immunization (EPI) that received Gavi funding to expand the vaccine portfolio and the Anti-Malaria Campaign (AMC) that received funding from the Global Fund for AIDS, Tuberculosis and Malaria to scale-up interventions to target and achieve malaria elimination. We assessed if EPI and AMC programmes were able to sustain coverage of previously donor-funded interventions post-transition and explain the facilitators and barriers that contribute to this.

Sri Lanka's COVID-19 response and maintaining health services: implications for future pandemics.

This study examines how Sri Lanka, a lower-middle income country, managed its COVID-19 response and maintained health services. It draws on an extensive document review, key informant interviews and a national survey of public experience and opinion to assess what Sri Lanka did, its effectiveness and why.Owing to a strong health system and luck, Sri Lanka stopped the first wave of COVID-19 infections, and it adopted a 'Zero-COVID' approach with the explicit goal of stopping outbreaks.

scPipe: an extended preprocessing pipeline for comprehensive single-cell ATAC-Seq data integration in R/Bioconductor.

scPipe is a flexible R/Bioconductor package originally developed to analyse platform-independent single-cell RNA-Seq data. To expand its preprocessing capability to accommodate new single-cell technologies, we further developed scPipe to handle single-cell ATAC-Seq and multi-modal (RNA-Seq and ATAC-Seq) data. After executing multiple data cleaning steps to remove duplicated reads, low abundance features and cells of poor quality, a object is created that contains a sparse count matrix with features of interest in the rows and cells in the columns.

Benchmarking long-read RNA-sequencing analysis tools using in silico mixtures.

The lack of benchmark data sets with inbuilt ground-truth makes it challenging to compare the performance of existing long-read isoform detection and differential expression analysis workflows. Here, we present a benchmark experiment using two human lung adenocarcinoma cell lines that were each profiled in triplicate together with synthetic, spliced, spike-in RNAs (sequins). Samples were deeply sequenced on both Illumina short-read and Oxford Nanopore Technologies long-read platforms.

Rare Combinational Hemoglobinopathies.

Hemoglobinopathies are genetic defects that result in the abnormal formation and composition of globin chains in the hemoglobin molecule. Sickle cell disease is one of the more common forms of genetic malformation, while Hemoglobin (Hb) Arab, Lepore, Korle-Bu, Kansas, D-Punjab, and Hasharon are uncommon presentations. Herein, we describe the case of a young patient who presented with a low hemoglobin level and was subsequently diagnosed with a rare combination of Hemoglobin Korle-Bu, D-Punjab, and sickle cell trait.

Arginine-rich C9ORF72 ALS proteins stall ribosomes in a manner distinct from a canonical ribosome-associated quality control substrate.

Hexanucleotide expansion mutations in C9ORF72 are a frequent cause of amyotrophic lateral sclerosis. We previously reported that long arginine-rich dipeptide repeats (DPRs), mimicking abnormal proteins expressed from the hexanucleotide expansion, caused translation stalling when expressed in cell culture models. Whether this stalling provides a mechanism of pathogenicity remains to be determined.

A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells.

MR1 is a highly conserved microbial immune-detection system in mammals. It captures vitamin B-related metabolite antigens from diverse microbes and presents them at the cell surface to stimulate MR1-restricted lymphocytes including mucosal-associated invariant T (MAIT) cells. MR1 presentation and MAIT cell recognition mediate homeostasis through host defense and tissue repair.

Spondylolysis.

Spondylolysis is a bony defect of the pars interarticularis and most often results from repetitive stress. Although spondylolysis is usually asymptomatic, symptomatic spondylolysis is the most common cause of identifiable back pain in children and adolescent athletes. A thorough history and physical exam, as well as appropriate imaging studies are helpful in diagnosis.

A curious case of bacteremia associated with adenocarcinoma.

is a pathogen typically acquired from the consumption of raw seafood or unpasteurized dairy products. Here, we present the unique case of a middle-aged gentleman who presented with back pain, originally thought to be muscle spasms due to poor posture and heavy lifting. Initial radiological imaging showed evidence of a lumbar epidural abscess and lung nodule.

Comprehensive characterization of single-cell full-length isoforms in human and mouse with long-read sequencing.

A modified Chromium 10x droplet-based protocol that subsamples cells for both short-read and long-read (nanopore) sequencing together with a new computational pipeline (FLAMES) is developed to enable isoform discovery, splicing analysis, and mutation detection in single cells. We identify thousands of unannotated isoforms and find conserved functional modules that are enriched for alternative transcript usage in different cell types and species, including ribosome biogenesis and mRNA splicing. Analysis at the transcript level allows data integration with scATAC-seq on individual promoters, improved correlation with protein expression data, and linked mutations known to confer drug resistance to transcriptome heterogeneity.

VALTOCO (Diazepam Nasal Spray) for the Acute Treatment of Intermittent Stereotypic Episodes of Frequent Seizure Activity.

Valtoco is a new FDA-approved nasal spray version of diazepam indicated for the treatment of acute, intermittent, and stereotypic episodes of frequent seizure activity in epilepsy patients six years of age and older. Although IV and rectal diazepam are already used to treat seizure clusters, Valtoco has less variability in plasma concentration compared to rectal diazepam. Furthermore, the intranasal administration of Valtoco is more convenient and less invasive than rectal or IV diazepam, making it ideal for self-administration outside of a hospital setting.

long-read-tools.org: an interactive catalogue of analysis methods for long-read sequencing data.

Background: The data produced by long-read third-generation sequencers have unique characteristics compared to short-read sequencing data, often requiring tailored analysis tools for tasks ranging from quality control to downstream processing. The rapid growth in software that addresses these challenges for different genomics applications is difficult to keep track of, which makes it hard for users to choose the most appropriate tool for their analysis goal and for developers to identify areas of need and existing solutions to benchmark against.

Findings: We describe the implementation of long-read-tools.

Increased Intensity Of PCR Testing Reduced COVID-19 Transmission Within Countries During The First Pandemic Wave.

Experts agree that reverse transcription-polymerase chain reaction (PCR) testing is critical in controlling coronavirus disease 2019 (COVID-19), but decision makers disagree on how much testing is optimal. Controlling for interventions and ecological factors, we used linear regression to quantify testing's impact on COVID-19's average reproduction number, which represents transmissibility, in 173 countries and territories (which account for 99 percent of the world's COVID-19 cases) during March-June 2020. Among interventions, PCR testing had the greatest influence: a tenfold increase in the ratio of tests to new cases reported reduced the average reproduction number by 9 percent across a range of testing levels.

Opportunities and challenges in long-read sequencing data analysis.

Long-read technologies are overcoming early limitations in accuracy and throughput, broadening their application domains in genomics. Dedicated analysis tools that take into account the characteristics of long-read data are thus required, but the fast pace of development of such tools can be overwhelming. To assist in the design and analysis of long-read sequencing projects, we review the current landscape of available tools and present an online interactive database, long-read-tools.

Seq: A High-Performance Language for Bioinformatics.

The scope and scale of biological data are increasing at an exponential rate, as technologies like next-generation sequencing are becoming radically cheaper and more prevalent. Over the last two decades, the cost of sequencing a genome has dropped from $100 million to nearly $100-a factor of over 10-and the amount of data to be analyzed has increased proportionally. Yet, as Moore's Law continues to slow, computational biologists can no longer rely on computing hardware to compensate for the ever-increasing size of biological datasets.

The first introduced malaria case reported from Sri Lanka after elimination: implications for preventing the re-introduction of malaria in recently eliminated countries.

Background: There has been no local transmission of malaria in Sri Lanka for 6 years following elimination of the disease in 2012. Malaria vectors are prevalent in parts of the country, and imported malaria cases continue to be reported. The country is therefore at risk of malaria being re-established.

The evolutionary origin of CIPK16: A gene involved in enhanced salt tolerance.

Calcineurin B-like protein interacting protein kinases (CIPKs) are key regulators of pre-transcriptional and post-translational responses to abiotic stress. Arabidopsis thaliana CIPK16 (AtCIPK16) was identified from a forward genetic screen as a gene that mediates lower shoot salt accumulation and improved salinity tolerance in Arabidopsis and transgenic barley. Here, we aimed to gain an understanding of the evolution of AtCIPK16, and orthologues of CIPK16 in other plant species including barley, by conducting a phylogenetic analysis of terrestrial plant species.