Cerebral palsy.

Cerebral palsy is a lifelong physical disability affecting movement and posture. The motor impairments of cerebral palsy result from non-degenerative brain injuries, brain malformations, and genetic variations, arising from multiple risk factors and causal pathways during preconception, pregnancy, birth, or within the first 2 years of life. Over the past decade, substantial progress in diagnosing, preventing, and managing the condition has transformed treatment approaches.

Clinical Evidence of Mesenchymal Stromal Cells for Cerebral Palsy: Scoping Review with Meta-Analysis of Efficacy in Gross Motor Outcomes.

Mesenchymal stromal cells (MSCs) have been under clinical investigation for the treatment of cerebral palsy (CP) for over a decade. However, the field has been limited by study heterogeneity and variable reports of efficacy. We conducted a scoping review of published and registered reports of MSC treatment for CP, with meta-analysis of Gross Motor Function Measure (GMFM) outcomes to summarize research and provide future recommendations.

Cord Blood Treatment for Children With Cerebral Palsy: Individual Participant Data Meta-Analysis.

Context: Umbilical cord blood (UCB) is a novel treatment for cerebral palsy (CP), with trials indicating UCB can improve gross motor function. However, heterogeneity has limited the ability to interpret findings.

Objective: Assess the safety and efficacy of UCB for improving gross motor function in children with CP, including exploring cell dose effect and responder subgroups.

Updates on neonatal cell and novel therapeutics: Proceedings of the Second Neonatal Cell Therapies Symposium (2024).

Cell therapies as treatments for neonatal conditions have attracted significant research and parent interest over the last two decades. Mesenchymal stromal cells, umbilical cord blood cells and neural stem cells translate from lab, to preclinical and into clinical trials, with contributions being made from all over the world. Effective and timely translation involves frequent reflection and consultation from research-adjacent fields (i.

Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic-Ischaemic Brain Injury in Rats.

(1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic-ischaemic (HI)-induced injury.

Acceptability of neural stem cell therapy for cerebral palsy: survey of the Australian cerebral palsy community.

Background: Neural stem cells (NSCs) have the potential to engraft and replace damaged brain tissue, repairing the damaged neonatal brain that causes cerebral palsy (CP). There are procedures that could increase engraftment of NSCs and may be critical for efficacy, but hold notable risks. Before clinical trials progress, it is important to engage with the CP community to understand their opinions.

Proportion of Infant Neurodevelopment Trials Reporting a Null Finding: A Systematic Review.

Context: Discovering new interventions to improve neurodevelopmental outcomes is a priority; however, clinical trials are challenging and methodological issues may impact the interpretation of intervention efficacy.

Objectives: Characterize the proportion of infant neurodevelopment trials reporting a null finding and identify features that may contribute to a null result.

Data Sources: The Cochrane library, Medline, Embase, and CINAHL databases.

Persistent Inflammation in Cerebral Palsy: Pathogenic Mediator or Comorbidity? A Scoping Review.

Research has established inflammation in the pathogenesis of brain injury and the risk of developing cerebral palsy (CP). However, it is unclear if inflammation is solely pathogenic and primarily contributes to the acute phase of injury, or if inflammation persists with consequence in CP and may therefore be considered a comorbidity. We conducted a scoping review to identify studies that analyzed inflammatory biomarkers in CP and discuss the role of inflammation in the pathogenesis of CP and/or as a comorbidity.

Are We Getting It Right? A Scoping Review of Outcomes Reported in Cell Therapy Clinical Studies for Cerebral Palsy.

Cell therapies are an emergent treatment for cerebral palsy (CP) with promising evidence demonstrating efficacy for improving gross motor function. However, families value improvements in a range of domains following intervention and the non-motor symptoms, comorbidities and complications of CP can potentially be targeted by cell therapies. We conducted a scoping review to describe all outcomes that have been reported in cell therapy studies for CP to date, and to examine what instruments were used to capture these.

Rehabilitation Evidence-Based Decision-Making: The READ Model.

Evidence-based practice is the foundation of rehabilitation for maximizing client outcomes. However, an unacceptably high number of ineffective or outdated interventions are still implemented, leading to sub-optimal outcomes for clients. This paper proposes the Rehabilitation Evidence bAsed Decision-Making (READ) Model, a decision-making algorithm for evidence-based decision-making in rehabilitation settings.

Neurodevelopmental Therapy for Cerebral Palsy: A Meta-analysis.

Background And Objective: Bobath therapy, or neurodevelopmental therapy (NDT) is widely practiced despite evidence other interventions are more effective in cerebral palsy (CP). The objective is to determine the efficacy of NDT in children and infants with CP or high risk of CP.

Methods: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Embase, and Medline were searched through March 2021.

LncRNA SFTA1P mediates positive feedback regulation of the Hippo-YAP/TAZ signaling pathway in non-small cell lung cancer.

Long non-coding RNAs (lncRNAs) regulate numerous biological processes involved in both development and carcinogenesis. Hippo-YAP/TAZ signaling, a critical pathway responsible for organ size control, is often dysregulated in a variety of cancers. However, the nature and function of YAP/TAZ-regulated lncRNAs during tumorigenesis remain largely unexplored.

Maraviroc Prevents HCC Development by Suppressing Macrophages and the Liver Progenitor Cell Response in a Murine Chronic Liver Disease Model.

Maraviroc (MVC), a CCR5 antagonist, reduces liver fibrosis, injury and tumour burden in mice fed a hepatocarcinogenic diet, suggesting it has potential as a cancer therapeutic. We investigated the effect of MVC on liver progenitor cells (LPCs) and macrophages as both have a role in hepatocarcinogenesis. Mice were fed the hepatocarcinogenic choline-deficient, ethionine-supplemented diet (CDE) ± MVC, and immunohistochemistry, RNA and protein expression were used to determine LPC and macrophage abundance, migration and related molecular mechanisms.

Neural stem cell treatment for perinatal brain injury: A systematic review and meta-analysis of preclinical studies.

Perinatal brain injury can lead to significant neurological and cognitive deficits and currently no therapies can regenerate the damaged brain. Neural stem cells (NSCs) have the potential to engraft and regenerate damaged brain tissue. The aim of this systematic review was to evaluate the preclinical literature to determine whether NSC administration is more effective than controls in decreasing perinatal brain injury.

Is the search for cerebral palsy 'cures' a reasonable and appropriate goal in the 2020s?

In the field of disability research and advocacy, the notion of 'cures' is contentious. Cerebral palsy (CP) is no exception. In this narrative review, we combine perspectives gained during community consultation undertaken for the Australian and New Zealand Cerebral Palsy Strategy, 2020 with those published in the scientific and grey literature to understand whether 'cures for CP' is a reasonable and appropriate goal.

Safety of allogeneic umbilical cord blood infusions for the treatment of neurological conditions: a systematic review of clinical studies.

Background Aims: Umbilical cord blood (UCB) infusion is being investigated as a treatment for a range of neurological conditions, primarily because of its potent immunomodulatory effects mediated via paracrine signaling. Although initial research mainly utilized autologous UCB, allogeneic samples from a sibling or unrelated donor have now become more common. With the use of allogeneic UCB, questions have arisen surrounding the necessity for human leukocyte antigen (HLA) matching, preparative regimens and immunosuppressant drugs.

Education can improve clinician confidence in information sharing and willingness to refer to stem cell clinical trials for cerebral palsy.

To progress stem cell therapies for cerebral palsy, clinicians need to openly engage with patients about emerging evidence and be willing to refer to relevant clinical trials, if and when appropriate. To assess whether education can change clinicians' confidence in information sharing and willingness to refer to relevant clinical trials, an online questionnaire was distributed at a scientific conference before and after a professional workshop on cell therapies for cerebral palsy. Of the 42 participants who completed the survey, 26 self-identified as clinicians.

Positive perception of stem cells for neurological conditions: results from an Australian public forum.

Stem cells offer great hope and promise as a potential treatment for human diseases. The aim of this study was to gain insight into the public perception of stem cells for neurological conditions. A paper-based questionnaire was administered to all attendees of a free, public stem cell forum.

miR-582-5p Is a Tumor Suppressor microRNA Targeting the Hippo-YAP/TAZ Signaling Pathway in Non-Small Cell Lung Cancer.

The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved signaling pathway involved in a broad spectrum of biological processes, including tumorigenesis. Whilst aberrant Hippo-YAP/TAZ signaling is frequently reported in various cancers, the genetic alterations of this pathway are relatively rare, suggesting regulation at the post-transcriptional level. MicroRNAs play key role in tumorigenesis by regulating gene expression post-transcriptionally.

Common and Unique Transcription Signatures of YAP and TAZ in Gastric Cancer Cells.

YAP and its paralog TAZ are the nuclear effectors of the Hippo tumour-suppressor pathway, and function as transcriptional co-activators to control gene expression in response to mechanical cues. To identify both common and unique transcriptional targets of YAP and TAZ in gastric cancer cells, we carried out RNA-sequencing analysis of overexpressed YAP or TAZ in the corresponding paralogous gene-knockouts (KOs), TAZ KO or YAP KO, respectively. Gene Ontology (GO) analysis of the YAP/TAZ-transcriptional targets revealed activation of genes involved in platelet biology and lipoprotein particle formation as targets that are common for both YAP and TAZ.

Loss of ARF/INK4A Promotes Liver Progenitor Cell Transformation Toward Tumorigenicity Supporting Their Role in Hepatocarcinogenesis.

Liver progenitor cells (LPCs) contribute to liver regeneration during chronic damage and are implicated as cells of origin for liver cancers including hepatocellular carcinoma (HCC). The locus, which encodes the tumor suppressors alternate reading frame protein (ARF) and INK4A, was identified as one of the most frequently altered genes in HCC. This study demonstrates that inactivation of enhances tumorigenic transformation of LPCs.