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Human Cell Jan 2024Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and... (Review)
Review
Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurodegenerative disease of the central nervous system (CNS), characterized by demyelination and axonal loss. It is induced by attack of autoreactive lymphocytes on the myelin sheath and endogenous remyelination failure, eventually leading to accumulation of neurological disability. Disease-modifying agents can successfully address inflammatory relapses, but have low efficacy in progressive forms of MS, and cannot stop the progressive neurodegenerative process. Thus, the stem cell replacement therapy approach, which aims to overcome CNS cell loss and remyelination failure, is considered a promising alternative treatment. Although the mechanisms behind the beneficial effects of stem cell transplantation are not yet fully understood, neurotrophic support, immunomodulation, and cell replacement appear to play an important role, leading to a multifaceted fight against the pathology of the disease. The present systematic review is focusing on the efficacy of stem cells to migrate at the lesion sites of the CNS and develop functional oligodendrocytes remyelinating axons. While most studies confirm the improvement of neurological deficits after the administration of different stem cell types, many critical issues need to be clarified before they can be efficiently introduced into clinical practice.
Topics: Humans; Multiple Sclerosis; Neurodegenerative Diseases; Myelin Sheath; Stem Cells; Oligodendroglia
PubMed: 37985645
DOI: 10.1007/s13577-023-01006-1 -
BMJ (Clinical Research Ed.) Nov 2023To summarize the breadth and quality of evidence supporting commonly recommended early childhood autism interventions and their estimated effects on developmental... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To summarize the breadth and quality of evidence supporting commonly recommended early childhood autism interventions and their estimated effects on developmental outcomes.
DESIGN
Updated systematic review and meta-analysis (autism intervention meta-analysis; Project AIM).
DATA SOURCES
A search was conducted in November 2021 (updating a search done in November 2017) of the following databases and registers: Academic Search Complete, CINAHL Plus with full text, Education Source, Educational Administration Abstracts, ERIC, Medline, ProQuest Dissertations and Theses, PsycINFO, Psychology and Behavioral Sciences Collection, and SocINDEX with full text, , and ClinicalTrials.gov.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Any controlled group study testing the effects of any non-pharmacological intervention on any outcome in young autistic children younger than 8 years.
REVIEW METHODS
Newly identified studies were integrated into the previous dataset and were coded for participant, intervention, and outcome characteristics. Interventions were categorized by type of approach (such as behavioral, developmental, naturalistic developmental behavioral intervention, and technology based), and outcomes were categorized by domain (such as social communication, adaptive behavior, play, and language). Risks of bias were evaluated following guidance from Cochrane. Effects were estimated for all intervention and outcome types with sufficient contributing data, stratified by risk of bias, using robust variance estimation to account for intercorrelation of effects within studies and subgroups.
RESULTS
The search yielded 289 reports of 252 studies, representing 13 304 participants and effects for 3291 outcomes. When contributing effects were restricted to those from randomized controlled trials, significant summary effects were estimated for behavioral interventions on social emotional or challenging behavior outcomes (Hedges' g=0.58, 95% confidence interval 0.11 to 1.06; P=0.02), developmental interventions on social communication (0.28, 0.12 to 0.44; P=0.003); naturalistic developmental behavioral interventions on adaptive behavior (0.23, 0.02 to 0.43; P=0.03), language (0.16, 0.01 to 0.31; P=0.04), play (0.19, 0.02 to 0.36; P=0.03), social communication (0.35, 0.23 to 0.47; P<0.001), and measures of diagnostic characteristics of autism (0.38, 0.17 to 0.59; P=0.002); and technology based interventions on social communication (0.33, 0.02 to 0.64; P=0.04) and social emotional or challenging behavior outcomes (0.57, 0.04 to 1.09; P=0.04). When effects were further restricted to exclude caregiver or teacher report outcomes, significant effects were estimated only for developmental interventions on social communication (0.31, 0.13 to 0.49; P=0.003) and naturalistic developmental behavioral interventions on social communication (0.36, 0.23 to 0.49; P<0.001) and measures of diagnostic characteristics of autism (0.44, 0.20 to 0.68; P=0.002). When effects were then restricted to exclude those at high risk of detection bias, only one significant summary effect was estimated-naturalistic developmental behavioral interventions on measures of diagnostic characteristics of autism (0.30, 0.03 to 0.57; P=0.03). Adverse events were poorly monitored, but possibly common.
CONCLUSION
The available evidence on interventions to support young autistic children has approximately doubled in four years. Some evidence from randomized controlled trials shows that behavioral interventions improve caregiver perception of challenging behavior and child social emotional functioning, and that technology based interventions support proximal improvements in specific social communication and social emotional skills. Evidence also shows that developmental interventions improve social communication in interactions with caregivers, and naturalistic developmental behavioral interventions improve core challenges associated with autism, particularly difficulties with social communication. However, potential benefits of these interventions cannot be weighed against the potential for adverse effects owing to inadequate monitoring and reporting.
Topics: Child; Humans; Child, Preschool; Autistic Disorder; Behavior Therapy; Early Intervention, Educational; Social Skills; Adaptation, Psychological
PubMed: 37963634
DOI: 10.1136/bmj-2023-076733 -
Cureus Oct 2023Cancer is a leading cause of mortality around the world, despite continued advancements in the management of cancer. Recent research efforts have shifted to evaluating... (Review)
Review
Cancer is a leading cause of mortality around the world, despite continued advancements in the management of cancer. Recent research efforts have shifted to evaluating the role that modifiable risk factors play in cancer risk and development, as diet and nutrition have been found to play a significant role in the onset and progression of cancer. As a result, there has been an increasing focus on the impact of dietary modifications on preventing the onset, progression, and reoccurrence of cancer. In this systematic review, data were collected on three common diets, the Mediterranean diet (MD), ketogenic diet (KD), and plant-based diet, to gain insight into the application of these three dietary modification approaches for risk prevention and limitation of cancer burden. Initially, 4,397 articles were identified from three databases (Ovid, Web of Science, and CINHAL). After removing studies based on the exclusion criteria, only 23 studies were eligible to be included in the systematic review of which 15 evaluated the MD, four assessed the ketogenic diet, and four evaluated the plant-based diet. Each article was considered for its methods, procedures, and findings. The findings indicate that dietary interventions may effectively reduce the odds of cancer development and the advancement of diagnosed cancers. With the introduction of the MD, KD, and plant-based diets, significant improvements in lowering cancer development, recurrence-free status, and limiting tumor growth were noted across numerous cancer types. Currently, the MD has been extensively studied in the literature, and amongst the widest variety of cancer types. Additional information and evaluation are required on the ketogenic and plant-based diets to fully understand their impact on the cancer burden across a wider subset of cancers. Clinicians should evaluate and recommend nutritional adaptations to their patients to limit the development of specific cancers and as an adjunctive therapy to traditional pharmacological treatment options for patients with diagnosed cancers.
PubMed: 37937022
DOI: 10.7759/cureus.46639 -
p38 MAPK signaling in chronic obstructive pulmonary disease pathogenesis and inhibitor therapeutics.Cell Communication and Signaling : CCS Nov 2023Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar remodeling.... (Review)
Review
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar remodeling. Although the abnormalities are primarily prompted by chronic exposure to inhaled irritants, maladjusted and self-reinforcing immune responses are significant contributors to the development and progression of the disease. The p38 isoforms are regarded as pivotal hub proteins that regulate immune and inflammatory responses in both healthy and disease states. As a result, their inhibition has been the subject of numerous recent studies exploring their therapeutic potential in COPD.
MAIN BODY
We performed a systematic search based on the PRISMA guidelines to find relevant studies about P38 signaling in COPD patients. We searched the PubMed and Google Scholar databases and used "P38" AND "COPD" Mesh Terms. We applied the following inclusion criteria: (1) human, animal, ex vivo and in vitro studies; (2) original research articles; (3) published in English; and (4) focused on P38 signaling in COPD pathogenesis, progression, or treatment. We screened the titles and abstracts of the retrieved studies and assessed the full texts of the eligible studies for quality and relevance. We extracted the following data from each study: authors, year, country, sample size, study design, cell type, intervention, outcome, and main findings. We classified the studies according to the role of different cells and treatments in P38 signaling in COPD.
CONCLUSION
While targeting p38 MAPK has demonstrated some therapeutic potential in COPD, its efficacy is limited. Nevertheless, combining p38 MAPK inhibitors with other anti-inflammatory steroids appears to be a promising treatment choice. Clinical trials testing various p38 MAPK inhibitors have produced mixed results, with some showing improvement in lung function and reduction in exacerbations in COPD patients. Despite these mixed results, research on p38 MAPK inhibitors is still a major area of study to develop new and more effective therapies for COPD. As our understanding of COPD evolves, we may gain a better understanding of how to utilize p38 MAPK inhibitors to treat this disease. Video Abstract.
Topics: Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 37919729
DOI: 10.1186/s12964-023-01337-4 -
Frontiers in Bioscience (Landmark... Oct 2023In the past 10 years, significant progress has been made in understanding the pathogenic chain of events that causes Alzheimer's disease (AD). According to the most...
BACKGROUND
In the past 10 years, significant progress has been made in understanding the pathogenic chain of events that causes Alzheimer's disease (AD). According to the most widely accepted concept, the production and aggregation of β-amyloid (Aβ) peptides play a critical role in AD. As a result, therapeutic intervention with these processes is the focus of intense research. The Aβ peptide is cleaved by the α-secretase, β-secretase, and γ-secretase enzymes in a region near the pathogenic amyloid precursor protein (APP) and mutations occurring site.
METHODS
In the current review, a complete picture of the risk factors behind AD has been investigated. Mutations involved in AD progression have also been screened in various studies.
RESULTS
Most of the mutations in the amyloid precursor protein (APP) can lead to the accumulation of APP oligomers in the brain, leading to AD. Several point mutations in APP can cause familial AD (FAD), including the Swedish mutation (K>M670/671N>L) and the A673>V mutation. The pathogenic A673>V mutation and Swedish mutation (M670>K/N671>L) are present in the same region of amyloid precursor protein (). However, the A673>T mutation has been shown to confer protection against AD.
CONCLUSION
More investigations are needed from geographically distinct regions on mutations associated with AD development and applications of nanomedicines for better management of the disease burden in the future. Nanotechnology-produced metal nanoparticles (NPs) have gotten much attention because of their wide range of uses in the medicinal and agricultural industries. Nanomedicine containing potential phytochemicals, including GX-50 and curcumin conjugated with NPs, maybe a potential candidate for treating AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Protein Precursor; Amyloid beta-Peptides; Mutation; Amyloid Precursor Protein Secretases
PubMed: 37919079
DOI: 10.31083/j.fbl2810258 -
Frontiers in Endocrinology 2023Paraneoplastic Cushing's syndrome (PCS) is a rare, but clinically important feature of small cell lung cancer (SCLC) that is associated with even worse prognosis. To...
Paraneoplastic Cushing's syndrome (PCS) is a rare, but clinically important feature of small cell lung cancer (SCLC) that is associated with even worse prognosis. To identify key considerations in comprehensive management of SCLC patients complicated with PCS, we conducted a systematic review of relevant reports on PubMed and Web of Science, focusing on SCLC with PCS cases. The systematic review analyzed 61 reports published between 1985 and 2022 with a total of 157 SCLC patients included. Out of the 157 patients, 132 (84.1%) patients across 58 (95.1%) reports were diagnosed with ectopic Cushing's syndrome. The immunohistochemical (IHC) staining for adrenocorticotropic hormone (ACTH) was performed on 30 (19.1%) patients across 22 (36.1%) reports and demonstrated encouraging performance. For treatment, chemotherapy and ketoconazole were utilized in 50 (81.97%) and 24 (39.34%) reports, respectively. Regarding cause of death, infection and cancer were equally frequent, each being recorded in 17 (27.87%) reports. To conclude, the majority of PCS cases in SCLC patients were caused by ectopic hormone secretion. In order to make a differential diagnosis, it is recommended to utilize IHC staining for a specific hormone such as ACTH or corticotropin-releasing hormone. In the comprehensive treatment of SCLC with PCS patients, effective management of hypercortisolism and potent safeguarding against infection play two crucial roles. Ultimately, further confirmations are required regarding the specificity and accuracy of IHC staining technique as well as the efficacy and safety of immunotherapy in the treatment of SCLC with PCS patients.
Topics: Humans; Cushing Syndrome; Small Cell Lung Carcinoma; Lung Neoplasms; Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Paraneoplastic Syndromes
PubMed: 37916144
DOI: 10.3389/fendo.2023.1177125 -
Cureus Sep 2023The coronavirus disease 2019 (COVID-19) is associated with prolonged prothrombin time (PT), active partial thromboplastin time (aPTT), and increased D-dimer levels.... (Review)
Review
The coronavirus disease 2019 (COVID-19) is associated with prolonged prothrombin time (PT), active partial thromboplastin time (aPTT), and increased D-dimer levels. Therefore, we aim to investigate if anticoagulants (AC) and antiplatelet (AP) therapy play a role in mitigating COVID-19 and its associated thrombosis along with its effect on the mortality rate, the need for mechanical ventilation, and the risk of hospital admission. Electronic databases were searched from their inception to July 19, 2022. The studies were divided into two groups: Group A (any dose of AC/AP versus no AC/AP) and Group B (therapeutic dose of AC (tAC)/AP versus prophylactic dose of AC (pAC)/AP). Review Manager (RevMan) version 5.4.1 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) was used for all statistical analyses. Adjusted data ratios were extracted from all included studies and pooled using the random effects model. A total of 33 studies were taken for the analysis of two groups (Group A: 285,065 COVID-19-positive patients, Group B: 2,421 COVID-19-positive patients). Overall analysis in Group A showed that the AC/AP group had a low risk of mortality in COVID-19 patients compared to the control group (risk ratio (RR): 0.77, 95% confidence interval (CI): 0.69-0.86). There was no significant difference in the need for mechanical ventilation (RR: 0.80, 95% CI: 0.60-1.08) and hospital admission (RR: 1.12, 95% CI: 0.78-1.59) between the AC/AP and no AC/AP group. Alongside, in Group B, tAC/AP did not demonstrate a significant decrease in mortality as compared to pAC/AP (RR: 0.62, 95% CI: 0.37-1.06). Treatment with AC and AP drugs can significantly decrease the mortality rate in COVID-19-infected patients, while AC also significantly reduces the need for mechanical ventilation.
PubMed: 37872904
DOI: 10.7759/cureus.45749 -
BMC Oral Health Oct 2023People with Intellectual and developmental disabilities (IDDs) experience oral health inequality due to myriad of risk factors and complex needs. Sensory processing... (Meta-Analysis)
Meta-Analysis
Effectiveness of sensory adaptive dental environments to reduce psychophysiology responses of dental anxiety and support positive behaviours in children and young adults with intellectual and developmental disabilities: a systematic review and meta-analyses.
BACKGROUND
People with Intellectual and developmental disabilities (IDDs) experience oral health inequality due to myriad of risk factors and complex needs. Sensory processing difficulties, maladaptive behaviours and dental anxiety contribute to difficulties in receiving preventive and routine dental treatments. This study aimed to systematically review the evidence on the effectiveness of sensory adaptive dental environments (SADE) for children and young adults (up to the ages 24 years) with IDD to address cooperation and dental anxiety.
METHODS
This review was reported according to The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. MEDLINE (Ovid), The Cochrane Library, Embase, Google Scholar, Web of Science and OT Seeker were searched using appropriate terms to identify Randomised Control Trails (RCTs) that matched inclusion criteria. Screening was conducted by two reviewers after de-duplication based on titles and abstracts followed by full text retrieval. Quality of the included studies was assessed using Cochrane Risk of Bias (ROB)-2 for crossover trials and data extracted by two reviewers. The details of the interventions and effectiveness were compared and discussed narratively, and comparable outcomes were included to meta-analyses using R software.
RESULTS
A total of 622 articles were identified and five articles met eligibility for inclusion. Three studies used multi-sensory adaptations and one used single sensory adaptation of music. Narrative synthesis showed some evidence of SADE reducing magnitude and duration, although, questionable for reducing the number of maladaptive behaviours. Two studies demonstrated conflicting evidence of the effect of SADE on cooperation. Three studies demonstrated significant positive impact of SADE on psychophysiological outcomes. Despite an overall tendency to favour SADE, no statistically significant difference of maladaptive behaviours was found between SADE and regular dental environment (RDE) (Standardised mean change (SMC) = 0.51; 95% Confidence Interval (CI) -0.20 to 1.22; p = 0.161). SADE was superior to RDE (SMC -0.66; 95% CI -1.01 to -0.30; p = < 0.001) in reducing psychophysiological responses of dental anxiety.
CONCLUSION
Current evidence suggests that adapting visual, tactile, and auditory aspects of the dental environment in a single or multi-sensory approach demonstrates small positive effects on psychophysiological responses and maladaptive behaviours of dental anxiety for people with IDD.
TRIAL REGISTRATION
The title of this review was registered with PROSPERO (CRD42022322083).
Topics: Child; Humans; Young Adult; Dental Anxiety; Developmental Disabilities; Oral Health; Psychophysiology; Risk Factors
PubMed: 37858057
DOI: 10.1186/s12903-023-03445-6 -
Physical Therapy Feb 2024Technology-based interventions offer many opportunities to enhance neurorehabilitation, with associated research activity gathering pace. Despite this fact, translation...
OBJECTIVE
Technology-based interventions offer many opportunities to enhance neurorehabilitation, with associated research activity gathering pace. Despite this fact, translation for use in clinical practice has lagged research innovation. An overview of the current "state of play" regarding the extent of clinical uptake and factors that might influence use of technologies is required. This scoping review explored the uptake of technologies as neurorehabilitation interventions in clinical practice and factors that are reported to influence their uptake.
METHODS
This systematic scoping review was conducted with narrative synthesis and evidence mapping. Studies of any design reporting uptake or implementation of technology (wearable devices, virtual reality, robotics, and exergaming) for movement neurorehabilitation after stroke and other neurological conditions were sought via a formal search strategy in MEDLINE (Ovid), CINAHL, AMED, and Embase. Full-text screening and data extraction were completed independently by 2 reviewers.
RESULTS
Of 609 studies returned, 25 studies were included after title, abstract, and full-text screening. Studies investigated a range of technologies at various stages of development. Only 4 of the included studies explored the sustained use of technology in practice. The following 5 themes representing experiences of technology use emerged: perceived usefulness, technology design, social interaction, integration with services, and suggested improvements to enhance uptake.
CONCLUSION
Reporting of uptake and use of neurorehabilitation technologies in clinical practice is limited. The synthesis provided comprehensive knowledge of barriers to and facilitators of uptake to be considered in future protocols, including a steep learning curve required to engage with technology, a need for a supportive organizational culture, and a need for user involvement in both design and development.
IMPACT
This scoping review has provided indicators from current evidence of important factors to consider in the planning of research into and clinical implementation of technologies for neurorehabilitation. It serves to support an evidence-based, user-centered platform for improved research on and translation of technologies in neurorehabilitation clinical practice.
Topics: Humans; Neurological Rehabilitation; Health Personnel; Virtual Reality
PubMed: 37856528
DOI: 10.1093/ptj/pzad140 -
Cureus Sep 2023Diabetes mellitus (DM) and thyroid dysfunction are two disorders that are closely related. This systematic review aimed to investigate the effect of levothyroxine... (Review)
Review
Diabetes mellitus (DM) and thyroid dysfunction are two disorders that are closely related. This systematic review aimed to investigate the effect of levothyroxine supplementation on diabetic nephropathy in type 2 diabetic patients with co-existing thyroid dysfunction. We explored medical databases such as PubMed, Medline, Multidisciplinary Digital Publishing Institute (MDPI), and Cochrane Library for relevant medical literature. The papers were screened, and 12 research papers involving 10,371 patients were identified after applying eligibility criteria and quality assessment using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The included papers analyzed the effect of aberrant thyroid profile on kidney disease in diabetic individuals and the role that achieving euthyroid status with levothyroxine supplementation could play in diabetic nephropathy. Reduced free triiodothyronine (FT3) was the most common independent factor associated with diabetic microvascular and macrovascular complications. Levothyroxine (LT4) regimen was more effective than the placebo in lowering urinary albumin excretion rate (UAER), low-density lipoprotein cholesterol, and uric acid and decreasing oxidative stress overall. However, replacement therapy's effect may differ in the short and long terms. Thyroid hormone replacement therapy (THRT) may reduce the risk of diabetic nephropathy and cardiovascular disease (CVD) development in hypothyroid patients, but more randomized trials are needed to confirm the effect of THRT.
PubMed: 37809188
DOI: 10.7759/cureus.44729