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Journal of Speech, Language, and... Nov 2023The purpose of this scoping review was to (a) summarize methodological characteristics of studies examining vocal characteristics of infants at high risk for... (Review)
Review
PURPOSE
The purpose of this scoping review was to (a) summarize methodological characteristics of studies examining vocal characteristics of infants at high risk for neurological speech motor involvement and (b) report the state of the high-quality evidence on vocal characteristic trends of infants diagnosed or at high risk for cerebral palsy (CP).
METHOD
The PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) extension for scoping reviews was followed for reporting our review. Studies measured prelinguistic vocal characteristics of infants under 24 months with birth risk or genetic conditions known to commonly present with speech motor involvement. Fifty-five studies met criteria for Part 1. Eleven studies met criteria for synthesis in Part 2.
RESULTS
A smaller percentage of studies examined infants with or at risk for CP compared to studies examining genetic conditions such as Down syndrome. The median year of publication was 1999, with a median sample size of nine participants. Most studies were conducted in laboratory settings and used human coding of vocalizations produced during caregiver-child interactions. Substantial methodological differences were noted across all studies. A small number of high-quality studies of infants with or at risk for CP revealed high rates of marginal babbling, low rates of canonical babbling, and limited consonant diversity under 24 months. Mixed findings were noted across studies of general birth risk factors.
CONCLUSIONS
There is limited evidence available to support the early detection of speech motor involvement. Large methodological differences currently impact the ability to synthesize findings across studies. There is a critical need to conduct longitudinal research with larger sample sizes and advanced, modern technologies to detect vocal precursors of speech impairment to support the accurate diagnosis and prognosis of speech development in infants with CP and other clinical populations.
Topics: Humans; Infant; Speech; Speech Disorders; Cerebral Palsy
PubMed: 37850852
DOI: 10.1044/2023_JSLHR-23-00336 -
Neurobiology of Disease Mar 2024Transgenic models of familial Alzheimer's disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (Aβ)-induced pathology.... (Meta-Analysis)
Meta-Analysis Review
Transgenic models of familial Alzheimer's disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (Aβ)-induced pathology. In this meta-analysis, we sought to evaluate levels of phosphorylated tau (p-tau) and explore potential age-related variations in tau hyperphosphorylation, within mouse models of AD. The PubMed and Scopus databases were searched for studies measuring soluble p-tau in 5xFAD, APP/PSEN1, J20 and APP23 mice. Data were extracted and analyzed using standardized procedures. For the 5xFAD model, the search yielded 36 studies eligible for meta-analysis. Levels of p-tau were higher in 5xFAD mice relative to control, a difference that was evident in both the carboxy-terminal (CT) and proline-rich (PR) domains of tau. Age negatively moderated the relationship between genotype and CT phosphorylated tau in studies using hybrid mice, female mice, and preparations from the neocortex. For the APP/PSEN1 model, the search yielded 27 studies. Analysis showed tau hyperphosphorylation in transgenic vs. control animals, evident in both the CT and PR regions of tau. Age positively moderated the relationship between genotype and PR domain phosphorylated tau in the neocortex of APP/PSEN1 mice. A meta-analysis was not performed for the J20 and APP23 models, due to the limited number of studies measuring p-tau levels in these mice (<10 studies). Although tau is hyperphosphorylated in both 5xFAD and APP/PSEN1 mice, the effects of ageing on p-tau are contingent upon the model being examined. These observations emphasize the importance of tailoring model selection to the appropriate disease stage when considering the relationship between Aβ and tau, and suggest that there are optimal intervention points for the administration of both anti-amyloid and anti-tau therapies.
Topics: Mice; Female; Animals; Alzheimer Disease; Phosphorylation; Amyloid beta-Protein Precursor; Mice, Transgenic; tau Proteins; Amyloid beta-Peptides; Disease Models, Animal
PubMed: 38307366
DOI: 10.1016/j.nbd.2024.106427 -
Nutrition Reviews Jul 2023Dietary fatty acids (FAs), primarily n-3 polyunsaturated FAs, have been associated with enrichment of the circulating bioactive lipidome and changes in the enzymatic... (Meta-Analysis)
Meta-Analysis
The effects of fatty acid-based dietary interventions on circulating bioactive lipid levels as intermediate biomarkers of health, cardiovascular disease, and cardiovascular disease risk factors: a systematic review and meta-analysis of randomized clinical trials.
CONTEXT
Dietary fatty acids (FAs), primarily n-3 polyunsaturated FAs, have been associated with enrichment of the circulating bioactive lipidome and changes in the enzymatic precursor lipoprotein-associated phospholipase A2 (Lp-PLA2) mass; however, the magnitude of this effect remains unclear.
OBJECTIVE
The aim of this systematic review and meta-analysis was to evaluate the effect of different dietary FAs on the bioactive lipid profile of healthy participants and those with cardiovascular disease (CVD) and CVD risk factors.
DATA SOURCES
PubMed, SCOPUS and the Cochrane Library databases were searched for relevant articles published between October 2010 and May 2022.
DATA EXTRACTION
Data were screened for relevance and then retrieved in full and evaluated for eligibility by 2 reviewers independently.
DATA ANALYSIS
The net difference in the bioactive lipid mean values between the endpoint and the baseline, and the corresponding SDs or SEs, were used for the qualitative synthesis. For the meta-analysis, a fixed-effects model was used.
RESULTS
Twenty-seven randomized clinical trials (representing >2560 participants) were included. Over 78% of the enrolled participants had ≥1 associated CVD risk factor, whereas <22% were healthy. In the meta-analysis, marine n-3 supplements (dose range, 0.37-1.9 g/d) significantly increased pro-inflammatory lysophosphatidylcholines (lyso-PCs; for lyso-PC(16:0): mean, +0.52 [95% confidence interval (CI), 0.02-1.01] µM; for lyso-PC(18:0): mean, +0.58 [95%CI, 0.09-1.08] µM) in obese participants. Additionally, n-3 supplementation (1-5.56 g/d) decreased plasma Lp-PLA2 mass, a well-known inflammation marker, in healthy (-0.35 [95%CI, -0.59 to -0.10] ng/mL), dyslipidemic (-0.36 [95%CI, -0.47 to -0.25] ng/mL), and stable coronary artery disease participants (-0.52 [95%CI, -0.91 to -0.12] ng/mL).
CONCLUSIONS
Daily n-3 provided as EPA+DHA supplements and consumed from 1 to 6 months reduced plasma Lp-PLA2 mass in healthy participants and those with CVD and CVD risk factors, suggesting an anti-inflammatory effect. However, the saturated lyso-PC response to n-3 was impaired in obese participants.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42021218335.
Topics: Humans; 1-Alkyl-2-acetylglycerophosphocholine Esterase; Biomarkers; Cardiovascular Diseases; Fatty Acids; Obesity; Randomized Controlled Trials as Topic; Lipids
PubMed: 36545749
DOI: 10.1093/nutrit/nuac101 -
Revue Neurologique 2024Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein... (Review)
Review
BACKGROUND
Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein (APP), avoiding the production of amyloid-β peptide (Aβ), one of the pathological hallmarks of Alzheimer's disease (AD).
OBJECTIVE
To investigate ADAM10 from cerebrospinal fluid (CSF) and plasma/serum as a potential biomarker for AD.
METHODS
A systematic review was carried out in the MEDLINE/PubMed, Web of Science, Embase, and Scopus databases using the terms and Boolean operators: "Alzheimer" AND "ADAM10" AND "biomarker". Citation searching was also adopted. The inclusion criteria were original studies of ADAM10 in blood or CSF in patients with AD. The risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The analysis methods were registered in the PROSPERO database (#CRD42021274239).
RESULTS
Of the 97 records screened, 17 were included. There is strong evidence for lower levels of ADAM10 in platelets of persons with AD compared to cognitively healthy participants. On the other hand, higher levels of ADAM10 were found in plasma. Regarding CSF, controversial results were found with lower and higher levels of ADAM10 in persons with AD compared to healthy older adults. The differences may be due to diverse reasons, including different sample collection and processing and different antibodies, highlighting the importance of standardizing the experiments and choosing the appropriate antibodies for ADAM10 detection.
CONCLUSION
Evidence shows that ADAM10 levels are altered in platelets, plasma, serum, and CSF of individuals with AD. The alteration was evident in all stages of the disease, and therefore, the protein may represent a complementary biomarker for the disease. However, more studies must be performed to establish cut-off values for ADAM10 levels to discriminate AD participants from cognitively unimpaired older adults.
Topics: Humans; Aged; Alzheimer Disease; Cross-Sectional Studies; ADAM10 Protein; Amyloid beta-Peptides; Biomarkers; Amyloid Precursor Protein Secretases; Membrane Proteins
PubMed: 37460331
DOI: 10.1016/j.neurol.2023.04.002 -
European Journal of Surgical Oncology :... Oct 2023Neuroblastoma is a malignant tumour affecting 10.5/1 million children annually. It arises from sympathetic nervous system precursor cells and is most frequently found in... (Review)
Review
Neuroblastoma is a malignant tumour affecting 10.5/1 million children annually. It arises from sympathetic nervous system precursor cells and is most frequently found in the adrenal gland and abdominal paravertebral ganglia. Diarrhoea as a presenting symptom of neuroblastoma is uncommon and usually linked to vasoactive intestinal peptide (VIP) tumour secretion. Even more rarely, postoperative diarrhoea may follow neuroblastoma tumour resection. Published studies generally associate postoperative diarrhoea with subadventitial tumour resection. These findings are however based on a handful of reports. This systematic review therefore aims to analyse the true incidence of postoperative diarrhoea and its morbid correlation with the extent/type of surgical resection. Pubmed/Embase databases were searched according to PRISMA guidelines. Final analysis consisted of 16 studies: N = 779 patients. Postoperative diarrhoea was significantly more common in all patients who underwent subadventitial resection compared to non subadventitial resection, p < 0.001 (OR 25.9, 95% CI 9.3-72.4). 5-year survival rates were equivalent in both groups. Preoperative diarrhoea was rarely reported in studies and always strongly linked to elevated VIP secretion. In the majority of neuroblastoma patients, preoperative diarrhoea ameliorated after gross tumour resection with elevated VIP normalized. The operative technique of subadventitial neuroblastoma resection portends significant risk(s) of post operative diarrhoea not seen in those patients undergoing other classical methods of tumour resection with 5-year survival rates strikingly similar. These findings affirm that subadventitial tumour resection should be avoided when undertaking surgery for neuroblastoma to minimize the risk(s) of persistent postoperative diarrhoea.
PubMed: 37183049
DOI: 10.1016/j.ejso.2023.04.020 -
Carcinogenesis Feb 2024Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have... (Meta-Analysis)
Meta-Analysis
Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69-0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Androgens; Follow-Up Studies; Cohort Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Prospective Studies; Genotype; Organic Anion Transporters; Solute Carrier Organic Anion Transporter Family Member 1B3
PubMed: 37856781
DOI: 10.1093/carcin/bgad075 -
Biomedicines Jan 2024Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with... (Review)
Review
Acute myeloid leukemia (AML) is a diverse group of leukemias characterized by the uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells with chromosomal rearrangements and multiple gene mutations and the impairment of normal hematopoiesis. Current efforts to improve AML outcomes have focused on developing targeted therapies that may allow for improved antileukemic effects while reducing toxicity significantly. Gemtuzumab ozogamicin (GO) is one of the most thoroughly studied molecularly targeted therapies in adults. GO is a monoclonal antibody against CD33 IgG4 linked to the cytotoxic drug calicheamicin DMH. The use of GO as a chemotherapeutic agent is not generalized for all patients who suffer from AML, particularly for those whose health prevents them from using intensive conventional chemotherapy, in which case it can be used on its own, and those who have suffered a first relapse, where its combination with other chemotherapeutic agents is possible. This systematic review aimed to comprehensively evaluate GO, focusing on its molecular structure, mode of action, pharmacokinetics, recommended dosage, resistance mechanisms, and associated toxicities to provide valuable information on the potential benefits and risks associated with its clinical use. A systematic review of eight scientific articles from 2018 to 2023 was conducted using PRISMA analysis. The results showed that GO treatment activates proapoptotic pathways and induces double-strand breaks, initiating DNA repair mechanisms. Cells defective in DNA repair pathways are susceptible to GO cytotoxicity. GO has recommended doses for newly diagnosed CD33+ AML in combination or as a single agent. Depending on the treatment regimen and patient status, GO doses vary for induction, consolidation, and continuation cycles. Multidrug resistance (MDR) involving P-glycoprotein (P-gp) is associated with GO resistance. The overexpression of P-gp reduces GO cytotoxicity; inhibitors of P-gp can restore sensitivity. Mitochondrial pathway activation and survival signaling pathways are linked to GO resistance. Other resistance mechanisms include altered pharmacokinetics, reduced binding ability, and anti-apoptotic mechanisms. GO has limited extramedullary toxicity compared to other AML treatments and may cause hepatic veno-occlusive disease (HVOD). The incidence of hepatic HVOD after GO therapy is higher in patients with high tumor burden. Hematological side effects and hepatotoxicity are prominent, with thrombocytopenia and neutropenia observed. In conclusion, GO's reintroduction in 2017 followed a thorough FDA review considering its altered dose, dosing schedule, and target population. The drug's mechanism involves CD33 targeting and calicheamicin-induced DNA damage, leading to apoptosis and resistance mechanisms, including MDR and survival signaling, which impact treatment outcomes. Despite limited extramedullary toxicity, GO is associated with hematological side effects and hepatotoxicity.
PubMed: 38255313
DOI: 10.3390/biomedicines12010208 -
Leukemia Research Dec 2023We aimed to evaluate the efficacy, safety, and latent toxicity of total body irradiation (TBI)-based conditioning regimens compared to non-TBI regimens for pediatric... (Meta-Analysis)
Meta-Analysis Review
A comprehensive comparison between TBI vs non-TBI-based conditioning regimen in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis.
INTRODUCTION
We aimed to evaluate the efficacy, safety, and latent toxicity of total body irradiation (TBI)-based conditioning regimens compared to non-TBI regimens for pediatric patients (under 18 years old) with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT).
METHODS
A systematic search was performed on MEDLINE, Scopus, WOS, and PMC. Also, a search for grey literature was performed on Google Scholar and relevant articles' references were included. Relevant articles which met the inclusion criteria were retrieved up to October 31th, 2022. CMA version 2 was used for the quantitative synthesis of the data.
RESULTS
Eight studies on efficacy and safety of TBI and non-TBI as a conditioning regimen were analyzed and six comparative studies on late toxicity were investigated. The meta-analysis revealed a hazard ratio (HR) of 1.508 (95% CI 0.96-2.35) for overall survival (OS) in instances of non-TBI conditioning. Also, an HR of 1.503 (95% CI 1.006-2.25) for disease-free- survival (DFS) favoring TBI-based conditioning. Late complications were reported to be significantly higher in the TBI conditioning regimen group than in the non-TBI group.
CONCLUSION
It appears that non-TBI regimens are as effective as TBI regimens in pediatrics with ALL regarding OS. Occurrence of latent toxicity is higher with TBI conditioning regimen. Conversely, TBI-based regimens are superior to non-TBI conditioning regimens regarding DFS. Considering all aspects, non-TBI conditioning regimens can be an alternative treatment option for pediatric ALL undergoing HSCT.
Topics: Humans; Child; Adolescent; Whole-Body Irradiation; Retrospective Studies; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Disease-Free Survival; Progression-Free Survival; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning; Graft vs Host Disease; Cyclophosphamide
PubMed: 37918224
DOI: 10.1016/j.leukres.2023.107416 -
Brain Connectivity May 2024The subventricular zone promotes remyelination through activation differentiation of oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) into mature...
The subventricular zone promotes remyelination through activation differentiation of oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) into mature oligodendrocytes and thus in the adult brain. In multiple sclerosis (MS) this regenerative capability is halted resulting in neurodegeneration. We aimed to systematically search and synthesize evidence on mechanisms and phenomena associated with subventricular zone (SVZ) dysfunction in MS. Our systematic review was reported according to the PRISMA-ScR statement. MEDLINE, SCOPUS, ProQuest, and Google Scholar were searched using the terms "subventricular zone" and "multiple sclerosis," including English-written and postmortem studies. Twenty studies were included. Thirteen studies on models of experimental autoimmune encephalomyelitis (EAE) reported among others strong stathmin immunoreactivity in the SVZ of EAE models, the role of MOG immunization in neurogenesis impairment, the effect of parenchymal OPCs and NSCs in myelin repair, and the importance of ependymal cells (E1/E2) and ciliated B1 cells in SVZ stem cell signaling. CXCR4 signaling and transcriptional profiles of SVZ microglia, Gli1 pathway, and galactin-3 were also explored. Studies in humans demonstrated microstructural SVZ damage in progressive MS and the persistence of black holes near the SVZ, whereas postmortem confirmed the generation of polysialic acid-neural cell adhesion molecule and NG2-positive progenitors through SVZ activation, SVZ stathmin immunoreactivity, Shh pathway, and Gal-3 upregulation. Oligodendrogenesis defects translate to reduced remyelination, a hallmark of MS that determines its end-phenotype and disease course. The role of inflammation and subsequent SVZ microenvironment disruption is evident in MS pathology.
Topics: Animals; Humans; Cell Differentiation; Encephalomyelitis, Autoimmune, Experimental; Lateral Ventricles; Multiple Sclerosis; Neural Stem Cells; Neurogenesis; Oligodendroglia
PubMed: 38534961
DOI: 10.1089/brain.2023.0081 -
Cytotherapy Sep 2023The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults...
A systematic review on the cost-effectiveness assessment of tisagenlecleucel for refractory or relapsing B-cell acute lymphoblastic leukemia (R/R B-ALL) treatment in children and young adults.
BACKGROUND AIMS
The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We sought to evaluate the cost-effectiveness of tisagenlecleucel compared with conventional salvage therapies in pediatric and young adult patients with R/R B-ALL.
METHODS
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses parameters as registered in International Prospective Register of Systematic Reviews (CRD42021266998). Literature was searched using the MEDLINE databases via PubMed, EMBASE, Lilacs, the Cochrane Central Register of Controlled Trials and Web of Science in January 2022. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts were reviewed.
RESULTS
In total, 5627 publications were identified, from which six eligible studies were selected. The conventional therapies identified were blinatumomab (Blina), clofarabine monotherapy (Clo-M), clofarabine combined with cyclophosphamide and etoposide (Clo-C) and the combination of fludarabine, cytarabine and idarubicin (FLA-IDA). The discounted incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for tisagenlecleucel compared with Clo-C and Blina averages was $38 837 and $25 569, respectively. In relation to the cost of the drug, the average of tisagenlecleucel was approximately 4.3 times, 10.8 times or 4.7 times greater than the Clo-M, Clo-C and Blina, respectively.
CONCLUSIONS
This systematic review highlighted that tisagenlecleucel is a much more expensive therapy than conventional alternatives. However, tisagenlecleucel performed well on the ICER, not exceeding $100 000/QALY. It was also found that the advanced therapy product was more effective than the conventional small molecule and biological drugs, in terms of life years and QALY gained.
Topics: Humans; Young Adult; Child; Clofarabine; Cost-Benefit Analysis; Receptors, Antigen, T-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence
PubMed: 37341664
DOI: 10.1016/j.jcyt.2023.05.011