Leveraging genetics to optimize rehabilitation outcomes after spinal cord injury: contemporary challenges and future opportunities.
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ABSTRACT:
SUBMITTER: Park A
PROVIDER: S-EPMC10896969 | biostudies-literature | 2024
REPOSITORIES: biostudies-literature
Publications
Leveraging genetics to optimize rehabilitation outcomes after spinal cord injury: contemporary challenges and future opportunities.
Frontiers in genetics 20240213
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Project description:Despite promising basic science discoveries and a surge in clinical trials, the quest for effective treatments that restore neurological function after spinal cord injury lags on. While "failed" in a conventional sense, emerging solutions to longstanding challenges represent promising steps towards a future with effective interventions. In this personal view, we highlight clinical trials implementing new solutions and their impact on the field. Our perspective is that, ultimately, the integration of shared knowledge, adaptive designs, and a deeper understanding of the intricacies of spinal cord injury holds promise of unlocking of major breakthroughs, leading to improved outcomes for people with spinal cord injury.
| S-EPMC11490878 | biostudies-literature
Project description:Dispersal is one of the most important but least understood processes in plant ecology and evolutionary biology. Dispersal of seeds maintains and establishes populations, and pollen and seed dispersal are responsible for gene flow within and among populations. Traditional views of dispersal and gene flow assume models that are governed solely by geographic distance and do not account for variation in dispersal vector behavior in response to heterogenous landscapes. Landscape genetics integrates population genetics with Geographic Information Systems (GIS) to evaluate the effects of landscape features on gene flow patterns (effective dispersal). Surprisingly, relatively few landscape genetic studies have been conducted on plants. Plants present advantages because their populations are stationary, allowing more reliable estimates of the effects of landscape features on effective dispersal rates. On the other hand, plant dispersal is intrinsically complex because it depends on the habitat preferences of the plant and its pollen and seed dispersal vectors. We discuss strategies to assess the separate contributions of pollen and seed movement to effective dispersal and to delineate the effects of plant habitat quality from those of landscape features that affect vector behavior. Preliminary analyses of seed dispersal for three species indicate that isolation by landscape resistance is a better predictor of the rates and patterns of dispersal than geographic distance. Rates of effective dispersal are lower in areas of high plant habitat quality, which may be due to the effects of the shape of the dispersal kernel or to movement behaviors of biotic vectors. Landscape genetic studies in plants have the potential to provide novel insights into the process of gene flow among populations and to improve our understanding of the behavior of biotic and abiotic dispersal vectors in response to heterogeneous landscapes.
| S-EPMC7748010 | biostudies-literature
Project description:Activity-based therapy (ABT) is a therapeutic approach with multiple benefits including promoting neurorecovery and reducing the likelihood of secondary complications in people living with spinal cord injury (SCI). Barriers and facilitators to ABT implementation for SCI rehabilitation have been studied from various perspectives through qualitative research. However, these viewpoints have not been synthesized to identify challenges of and strategies for implementing ABT across the Canadian healthcare system. Thus, the purpose of our study was to examine the current state of ABT in Canadian healthcare settings according to users' perspectives. Our main objectives were to compare barriers and facilitators to ABT implementation across Canadian healthcare settings according to users' perspectives and to identify optimal intervention strategies for ABT delivery across the Canadian healthcare system from acute to community care. We searched Scopus, CINAHL, OvidMedline, and other sources. Eligible articles were qualitative or mixed methods studies exploring ABT for adults with SCI in a Canadian healthcare setting. We analyzed qualitative findings through a thematic synthesis followed by a deductive content analysis. The Mixed Methods Appraisal Tool was used for critical appraisal. Nine articles were included. The thematic synthesis revealed two main themes: (1) factors influencing acceptance and adaptation of ABT across healthcare settings in Canada and (2) proposed solutions. The deductive analysis applied the Behaviour Change Wheel (BCW) to identify limited components of behaviour and appropriate interventions. To address ABT implementation challenges across the Canadian healthcare system, evidence-based interventions should target BCW subcategories of reflective motivation, social opportunity, and physical opportunity.
| S-EPMC11011823 | biostudies-literature
Project description:The rapid growth of the number of protein sequences that can be inferred from sequenced genomes presents challenges for function assignment, because only a small fraction (currently <1%) has been experimentally characterized. Bioinformatics tools are commonly used to predict functions of uncharacterized proteins. Recently, there has been significant progress in using protein structures as an additional source of information to infer aspects of enzyme function, which is the focus of this review. Successful application of these approaches has led to the identification of novel metabolites, enzyme activities, and biochemical pathways. We discuss opportunities to elucidate systematically protein domains of unknown function, orphan enzyme activities, dead-end metabolites, and pathways in secondary metabolism.
| S-EPMC4117707 | biostudies-literature
Project description:Intracranial metastatic disease (IMD) is a prevalent complication of cancer that significantly limits patient survival and quality of life. Over the past half-century, our understanding of the epidemiology and pathogenesis of IMD has improved and enabled the development of surveillance and treatment algorithms based on prognostic factors and tumor biomolecular characteristics. In addition to advances in surgical resection and radiation therapy, the treatment of IMD has evolved to include monoclonal antibodies and small molecule antagonists of tumor-promoting proteins or endogenous immune checkpoint inhibitors. Moreover, improvements in the sensitivity and specificity of imaging as well as the development of new serological assays to detect brain metastases promise to revolutionize IMD diagnosis. In this review, we will explore current treatment principles in patients with IMD, including the emerging role of targeted and immunotherapy in select primary cancers, and discuss potential areas for further investigation.
| S-EPMC8940535 | biostudies-literature
Project description:Enterovirus D68 (EV-D68) is a nonpolio enterovirus associated with severe respiratory illness and acute flaccid myelitis (AFM), a polio-like illness causing paralysis in children. AFM outbreaks have been associated with increased circulation and genetic diversity of EV-D68 since 2014, although the virus was discovered in the 1960s. The mechanisms by which EV-D68 targets the central nervous system are unknown. Since enteroviruses are human pathogens that do not routinely infect other animal species, establishment of a human model of the central nervous system is essential for understanding pathogenesis. Here, we describe two human spinal cord organoid (hSCO)-based models for EV-D68 infection derived from induced, pluripotent stem cell (iPSC) lines. One hSCO model consists primarily of spinal motor neurons, while the another model comprises multiple neuronal cell lineages, including motor neurons, interneurons, and glial cells. These hSCOs can be productively infected with contemporary strains, but not a historic strain, of EV-D68 and produce extracellular virus for at least 2 weeks without appreciable cytopathic effect. By comparison, infection with hSCO with another enterovirus, echovirus 11, causes significant structural destruction and apoptosis. Together, these findings suggest that EV-D68 infection is not the sole mediator of neuronal cell death in the spinal cord in those with AFM and that secondary injury from the immune response likely contributes to pathogenesis. IMPORTANCE AFM is a rare condition that causes significant morbidity in affected children, often contributing to life-long sequelae. It is unknown how EV-D68 causes paralysis in children, and effective therapeutic and preventative strategies are not available. Mice are not native hosts for EV-D68, and thus, existing mouse models use immunosuppressed or neonatal mice, mouse-adapted viruses, or intracranial inoculations. To complement existing models, we report two hSCO models for EV-D68 infection. These three-dimensional, multicellular models comprised human cells and include multiple neural lineages, including motor neurons, interneurons, and glial cells. These new hSCO models for EV-D68 infection will contribute to understanding how EV-D68 damages the human spinal cord, which could lead to new therapeutic and prophylactic strategies for this virus.
| S-EPMC10470749 | biostudies-literature
Project description:Pregnancy is associated with an increased risk of infection related to its associated mechanical and physiological changes. Sepsis remains among the top causes of maternal death worldwide and is associated with substantial maternal morbidity. However, there are sparse data on pregnancy-associated severe sepsis (PASS), related in part to infrequent reports, varying case definitions and methodological approach, small cohort size, and often limited focus on severe sepsis in selected phases of pregnancy outcomes. Available reports vary, but indicate that PASS is a rare but likely increasing complication, and it is more likely to develop with increased maternal age, among minority women, the poor, those lacking health insurance, those with chronic illness or pregnancy-associated complications, and following invasive procedures. Obstetric sites of infection are the most prevalent, but non-obstetric infections often underlie pregnancy-associated severe sepsis, though the source of infection is often not readily apparent during initial care. Women with PASS can have a rapidly fatal course and require heightened clinician vigilance for early diagnosis and timely effective intervention. Nevertheless, available reports raise concerns about prevalent substandard care of these patients, contributing to adverse outcomes. The case fatality of PASS appears lower than that in the general population with severe sepsis, while the long-term outcomes of survivors remain unknown.
| S-EPMC4269633 | biostudies-literature
Project description:Spinal cord injury (SCI) has considerable impact on patient physical, mental, and financial health. Secondary SCI is associated with inflammation, vascular destruction, and subsequent permanent damage to the nervous system. Mesenchymal stem cells (MSCs) have anti-inflammatory properties, promoting vascular regeneration and the release neuro-nutrients, and are a promising strategy for the treatment of SCI. Preclinical studies have shown that MSCs promote sensory and motor function recovery in rats. In clinical trials, MSCs have been reported to improve the American Spinal Injury Association (ASIA) sensory and motor scores. However, the effectiveness of MSCs in treating patients with SCI remains controversial. MSCs promote tumorigenesis and ensuring the survival of MSCs in the hostile environment of SCI is challenging. In this article we examine the evidence on the pathophysiological changes occurring after SCI. We then review the underlying mechanisms of MSCs in the treatment of SCI and summarize the potential application of MSCs in clinical practice. Finally, we highlight the challenges surrounding the use of MSCs in the treatment of SCI and discuss future applications.
| S-EPMC9999104 | biostudies-literature
Project description:The field of spinal robotics has witnessed considerable advances, which have primarily focused on enhancing pedicle screw placement. This article critically evaluates the current direction of spinal robotics development, raising concerns about the disproportionate emphasis on pedicle screw placement when existing techniques already yield commendable results. Discussions on various parameters, including quality, cost-effectiveness, and accessibility, highlight the need for a broader perspective in the development of robotics for spinal surgery. Comparative analyses reveal that navigation systems offer cost-effective and time-efficient alternatives to robotics, with similar accuracy levels. Patient demand for robotic interventions is influenced by perceived superiority, warranting careful consideration of public sentiment. This article also underscores the need for future spine surgeons to maintain proficiency in traditional techniques. The influence of industry and key opinion leaders in steering the focus toward pedicle screw placement is discussed, emphasizing the need for a more holistic approach. Accessibility issues and legal considerations in the evolving field of spinal robotics are addressed, and the potential for robotics to enhance various aspects of surgical procedures beyond pedicle screw placement is explored. In conclusion, we advocate for a shift in focus in spinal robotics, emphasizing the untapped potential to streamline common surgical procedures (such as discectomy, laminectomy, and endoscopy), enhance precision, and improve patient outcomes in areas beyond pedicle screw placement. Future advances in spinal robotics have the potential to transform the surgical landscape, benefitting all stakeholders, including patients, surgeons, and hospitals.
| S-EPMC11467282 | biostudies-literature
Project description:Study designSystematic review update.ObjectivesInterventions that aim to optimize spinal cord perfusion are thought to play an important role in minimizing secondary ischemic damage and improving outcomes in patients with acute traumatic spinal cord injuries (SCIs). However, exactly how to optimize spinal cord perfusion and enhance neurologic recovery remains controversial. We performed an update of a recent systematic review (Evaniew et al, J. Neurotrauma 2020) to evaluate the effects of Mean Arterial Pressure (MAP) support or Spinal Cord Perfusion Pressure (SCPP) support on neurological recovery and rates of adverse events among patients with acute traumatic SCI.MethodsWe searched PubMed/MEDLINE, EMBASE and ClinicalTrials.gov for new published reports. Two reviewers independently screened articles, extracted data, and evaluated risk of bias. We implemented the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach to rate confidence in the quality of the evidence.ResultsFrom 569 potentially relevant new citations since 2019, we identified 9 new studies for inclusion, which were combined with 19 studies from a prior review to give a total of 28 studies. According to low or very low quality evidence, the effect of MAP support on neurological recovery is uncertain, and increased SCPP may be associated with improved neurological recovery. Both approaches may involve risks for specific adverse events, but the importance of these adverse events to patients remains unclear. Very low quality evidence failed to yield reliable guidance about particular monitoring techniques, perfusion ranges, pharmacological agents, or durations of treatment.ConclusionsThis update provides an evidence base to support the development of a new clinical practice guideline for the hemodynamic management of patients with acute traumatic SCI. While avoidance of hypotension and maintenance of spinal cord perfusion are important principles in the management of an acute SCI, the literature does not provide high quality evidence in support of a particular protocol. Further prospective, controlled research studies with objective validated outcome assessments are required to examine interventions to optimize spinal cord perfusion in this setting.
| S-EPMC10964891 | biostudies-literature