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Journal of Diabetes and Its... 2014The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to perform a systematic meta-analysis of biomarkers investigated with diabetic retinopathy (DR) in the vitreous, and to explore the molecular pathway interactions of these markers found to be consistently associated with DR. Relevant databases [PubMed and ISI web of science] were searched for all published articles investigating molecular biomarkers of the vitreous associated with DR. Based on set exclusion/inclusion criteria available data from studies with human vitreous samples were extracted and used for our meta-analysis. The interactions of significant biomarkers in DR were investigated via STRING and KEGG pathway analysis. Our meta-analysis of DR identifies eleven biomarkers as potential therapeutic candidates alternate to current anti-VEGF therapy. Four of these are deemed viable therapeutic targets for PDR; ET receptors (ET A and ET B), anti-PDGF-BB, blocking TGF-β using cell therapy and PEDF. The identification of supplementary or synergistic therapeutic candidates to anti VEGF in the treatment of DR may aid in the development of future treatment trials.
Topics: Becaplermin; Biomarkers; Diabetic Retinopathy; Humans; Proto-Oncogene Proteins c-sis; Receptor, Endothelin A; Receptor, Endothelin B; Transforming Growth Factor beta; Vitreous Body
PubMed: 24630762
DOI: 10.1016/j.jdiacomp.2013.09.010 -
Frontiers in Neurology 2021By reviewing the existing clinical studies about visual snow (VS) as a symptom or as part of visual snow syndrome (VSS), we aim at improving our understanding of VSS...
By reviewing the existing clinical studies about visual snow (VS) as a symptom or as part of visual snow syndrome (VSS), we aim at improving our understanding of VSS being a network disorder. Patients with VSS suffer from a continuous visual disturbance resembling the view of a badly tuned analog television (i.e., VS) and other visual, as well as non-visual symptoms. These symptoms can persist over years and often strongly impact the quality of life. The exact prevalence is still unknown, but up to 2.2% of the population could be affected. Presently, there is no established treatment, and the underlying pathophysiology is unknown. In recent years, there have been several approaches to identify the brain areas involved and their interplay to explain the complex presentation. We collected the clinical and paraclinical evidence from the currently published original studies on VS and its syndrome by searching PubMed and Google Scholar for the term visual snow. We included original studies in English or German and excluded all reviews, case reports that did not add new information to the topic of this review, and articles that were not retrievable in PubMed or Google Scholar. We grouped the studies according to the methods that were used. Fifty-three studies were found for this review. In VSS, the clinical spectrum includes additional visual disturbances such as excessive floaters, palinopsia, nyctalopia, photophobia, and entoptic phenomena. There is also an association with other perceptual and affective disorders as well as cognitive symptoms. The studies that have been included in this review demonstrate structural, functional, and metabolic alterations in the primary and/or secondary visual areas of the brain. Beyond that, results indicate a disruption in the pre-cortical visual pathways and large-scale networks including the default mode network and the salience network. The combination of the clinical picture and widespread functional and structural alterations in visual and extra-visual areas indicates that the VSS is a network disorder. The involvement of pre-cortical visual structures and attentional networks might result in an impairment of "filtering" and prioritizing stimuli as top-down process with subsequent excessive activation of the visual cortices when exposed to irrelevant external and internal stimuli. Limitations of the existing literature are that not all authors used the ICHD-3 definition of the VSS. Some were referring to the symptom VS, and in many cases, the control groups were not matched for migraine or migraine aura.
PubMed: 34671311
DOI: 10.3389/fneur.2021.724072 -
Neural Regeneration Research Nov 2023Amblyopia is the most common cause of vision loss in children and can persist into adulthood in the absence of effective intervention. Previous clinical and neuroimaging...
Amblyopia is the most common cause of vision loss in children and can persist into adulthood in the absence of effective intervention. Previous clinical and neuroimaging studies have suggested that the neural mechanisms underlying strabismic amblyopia and anisometropic amblyopia may be different. Therefore, we performed a systematic review of magnetic resonance imaging studies investigating brain alterations in patients with these two subtypes of amblyopia; this study is registered with PROSPERO (registration ID: CRD42022349191). We searched three online databases (PubMed, EMBASE, and Web of Science) from inception to April 1, 2022; 39 studies with 633 patients (324 patients with anisometropic amblyopia and 309 patients with strabismic amblyopia) and 580 healthy controls met the inclusion criteria (e.g., case-control designed, peer-reviewed articles) and were included in this review. These studies highlighted that both strabismic amblyopia and anisometropic amblyopia patients showed reduced activation and distorted topological cortical activated maps in the striate and extrastriate cortices during task-based functional magnetic resonance imaging with spatial-frequency stimulus and retinotopic representations, respectively; these may have arisen from abnormal visual experiences. Compensations for amblyopia that are reflected in enhanced spontaneous brain function have been reported in the early visual cortices in the resting state, as well as reduced functional connectivity in the dorsal pathway and structural connections in the ventral pathway in both anisometropic amblyopia and strabismic amblyopia patients. The shared dysfunction of anisometropic amblyopia and strabismic amblyopia patients, relative to controls, is also characterized by reduced spontaneous brain activity in the oculomotor cortex, mainly involving the frontal and parietal eye fields and the cerebellum; this may underlie the neural mechanisms of fixation instability and anomalous saccades in amblyopia. With regards to specific alterations of the two forms of amblyopia, anisometropic amblyopia patients suffer more microstructural impairments in the precortical pathway than strabismic amblyopia patients, as reflected by diffusion tensor imaging, and more significant dysfunction and structural loss in the ventral pathway. Strabismic amblyopia patients experience more attenuation of activation in the extrastriate cortex than in the striate cortex when compared to anisometropic amblyopia patients. Finally, brain structural magnetic resonance imaging alterations tend to be lateralized in the adult anisometropic amblyopia patients, and the patterns of brain alterations are more limited in amblyopic adults than in children. In conclusion, magnetic resonance imaging studies provide important insights into the brain alterations underlying the pathophysiology of amblyopia and demonstrate common and specific alterations in anisometropic amblyopia and strabismic amblyopia patients; these alterations may improve our understanding of the neural mechanisms underlying amblyopia.
PubMed: 37282452
DOI: 10.4103/1673-5374.371349 -
Archivos de La Sociedad Espanola de... Jul 2021Eye oscillations, both nystagmic and non-nystagic, can occur from birth. Most correspond to infantile nystagmus that dubates in the first six months of life, which... (Review)
Review
INTRODUCTION
Eye oscillations, both nystagmic and non-nystagic, can occur from birth. Most correspond to infantile nystagmus that dubates in the first six months of life, which include idiopathic, sensory, latent, or overt latent motor nystagmus. Those associated with neurological diseases or syndromes correspond to approximately 33%, their identification and correct evaluation being important given the potential visual and vital complications.
MATERIAL AND METHODS
We made a systematic review of the literature on supranuclear gaze control mechanisms and the main ocular oscillations with possible neurological implications, both in childhood. With this, we intend to assess if there are already established clinical-anatomical associations, and to propose a protocol on the complementary studies to be carried out in these cases.
RESULTS
There are still anatomical pathways involved in supranuclear gaze control that are not fully clarified and understood. Besides, except in the case of nystagmus in seesaw and upbeat, we did not find anatomical explanations for their pathogenesis. The need for complete neuro-ophthalmological physical examinations and the request for additional tests in children who present ocular oscillations with neurological characteristics are clear.
CONCLUSIONS
Supranuclear gaze control follows a complex neurological network that still needs to be studied better. With a better dissection of the same we could try to understand why the ocular oscillations that we studied have these specific forms of presentation. As for the complementary requests, the request for neuroimaging tests is practically constant, making the others according to the specific case before which we find ourselves.
Topics: Child; Eye Movements; Humans; Nystagmus, Pathologic; Physical Examination; Syndrome
PubMed: 34217474
DOI: 10.1016/j.oftale.2020.09.018 -
EClinicalMedicine Jul 2022Glaucoma and chronic kidney disease (CKD) are prevalent and debilitating conditions, with common pathogenic pathways like oxidative stress and fluid dysregulation. We...
BACKGROUND
Glaucoma and chronic kidney disease (CKD) are prevalent and debilitating conditions, with common pathogenic pathways like oxidative stress and fluid dysregulation. We evaluated if there is a bidirectional association between them, as previous studies have yielded conflicting results.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase and Cochrane Library from inception until 15 June 2021, including full-length English articles published in peer-reviewed journals reporting on glaucoma and CKD as either exposure or outcome, among participants aged ≥18 years. We pooled overall summary estimates of odds ratios using random-effect meta-analysis and conducted subgroup meta-analyses and univariate meta regression. We assessed risk of bias using the Newcastle-Ottawa Scale (NOS) and quality of evidence using the GRADE framework. Our article is PROSPERO-registered and adherent to both PRISMA and MOOSE guidelines. This review is registered with PROSPERO (CRD42021262846).
FINDINGS
We identified 14 articles comprising of 3 retrospective cohort studies and 12 cross-sectional studies from 2,428 records, including 1,978,254 participants. Risk of bias was low to moderate. Participants with CKD at baseline had higher pooled odds of glaucoma (odds ratio[OR]=1.18, 95% confidence interval[CI]=1.04-1.33, I=66%, N=12) compared to participants without CKD. The association remained significant in subgroups of longitudinal studies, participants with diabetes, East Asian studies and primary open-angle glaucoma. In the reverse direction, participants with glaucoma at baseline had over three-fold higher odds of incident CKD compared to participants without glaucoma after 10-15 years of follow-up in longitudinal studies (OR=3.67, 95% CI=2.16-6.24, I=75%, N=2). All studies adjusted for age and sex, while most studies adjusted for comorbidities such as diabetes and hypertension. Meta-regression identified ethnicity (East Asians vs Non-East Asians) as a significant effect moderator. Associations were robust to trim-and-fill adjustment for publication bias, single-study influence and cumulative meta-analyses.
INTERPRETATION
Our meta-analysis suggests a bidirectional relationship between glaucoma and CKD, particularly among East Asians. Further studies are required to elucidate underlying mechanisms and account for differential association by ethnicity.
FUNDING
Ching-Yu Cheng is supported by Clinician Scientist Award (NMRC/CSA-SI/0012/2017) of the Singapore Ministry of Health's National Medical Research Council.
PubMed: 35747173
DOI: 10.1016/j.eclinm.2022.101498 -
Neuropsychology Review Mar 2023Pediatric survivors of brain tumors and acute lymphoblastic leukemia (ALL) are at risk for long-term deficits in their neuropsychological functioning. Researchers have... (Review)
Review
Pediatric survivors of brain tumors and acute lymphoblastic leukemia (ALL) are at risk for long-term deficits in their neuropsychological functioning. Researchers have begun examining associations between germline single nucleotide polymorphisms (SNPs), which interact with cancer treatment, and neuropsychological outcomes. This review synthesizes the impact of treatment-related toxicity from germline SNPs by neuropsychological domain (i.e., working memory, processing speed, psychological functioning) in pediatric survivors. By focusing on specific neuropsychological domains, this review will examine outcome measurement and critique methodology. Fourteen studies were identified and included in this review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). All studies were published in peer-reviewed journals in English by November 24, 2021. Reviewed studies were not of sufficient quality for a meta-analysis due to varying measurement strategies, gaps in reported descriptive variables, and low power. All neuropsychological domains evaluated in this review had associations with SNPs, except fine motor and visual integration abilities. Only five SNPs had consistent neuropsychological findings in more than one study or cohort. Future research and replication studies should use validated measures of discrete skills that are central to empirically validated models of survivors' long-term outcomes (i.e., attention, working memory, processing speed). Researchers should examine SNPs across pathophysiological pathways to investigate additive genetic risk in pediatric cancer survivors. Two SNPs were identified that confer resiliency in neuropsychological functioning, and future work should investigate resiliency genotypes and their underlying biological mechanisms.
Topics: Child; Humans; Brain Neoplasms; Cancer Survivors; Genomics; Memory, Short-Term; Neuropsychological Tests; Survivors
PubMed: 35305234
DOI: 10.1007/s11065-022-09539-2 -
Frontiers in Oncology 2024Patients undergoing chemotherapy often encounter troubling and common side effects, notably Chemotherapy-induced nausea and vomiting (CINV). This side effect not only...
BACKGROUND
Patients undergoing chemotherapy often encounter troubling and common side effects, notably Chemotherapy-induced nausea and vomiting (CINV). This side effect not only impairs the patient's quality of life but could also result in the interruption or discontinuation of the chemotherapy treatment. Consequently, research into CINV has consistently remained a focal point in the realm of clinical medicine. In this research domain, bibliometric analysis has not been conducted. The purpose of this study is to deliver a thorough summary of the knowledge framework and key areas of interest in the field of Chemotherapy-induced nausea and vomiting, using bibliometric methods. This approach aims to furnish novel concepts and pathways for investigators working in this area.
METHODS
Publications focusing on Chemotherapy-induced nausea and vomiting, spanning from 2004 to 2023, were identified using the Web of Science Core Collection (WoSCC) database. Tools such as VOSviewer, CiteSpace, and the R package "bibliometrix" were employed for this bibliometric analysis.
RESULTS
This research covers 734 publications from 61 countries, with the United States and China being the primary contributors. There has been a significant rise in the volume of papers published in the most recent decade compared to the one before it, spanning over the past twenty years. However, the annual publication rate in the last ten years has not shown a significant upward trend. The University of Toronto, Merck & Co., Sun Yat-sen University, and Helsinn Healthcare SA emerged as the principal research institutions in this field. Supportive Care in Cancer stands out as the most frequently published and cited journal in this domain. These works are contributed by 3,917 authors, with Rudolph M Navari, Matti Aapro, Shimokawa Mototsugu, and Lee Schwartzberg being among those who have published the most. Paul J. Hesketh is notably the most co-cited author. The primary focus of this research field lies in exploring the mechanisms of CINV and the therapeutic strategies for managing it. Key emerging research hotspots are represented by terms such as "Chemotherapy-induced nausea and vomiting," "nausea," "vomiting," "chemotherapy," and "antiemetics."
CONCLUSION
This represents the inaugural bibliometric study to thoroughly outline the research trends and advancements in the field of CINV. It highlights the latest research frontiers and trending directions, offering valuable insights for scholars engaged in studying CINV.
PubMed: 38720800
DOI: 10.3389/fonc.2024.1377486 -
Molecular Cancer Research : MCR Jun 2021Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated... (Meta-Analysis)
Meta-Analysis
Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated frequency of driver events across multiple studies. Published studies using whole genome, whole exome, targeted gene panel, or individual gene sequencing were identified. Datasets from these studies were collated to summarize mutations, structural variants, and regions of copy-number alteration. Studies using next-generation sequencing were divided into the "main" cohort ( = 173; fresh-frozen samples), "validation" cohort ( = 48; formalin-fixed, paraffin-embedded samples) and a second "validation" cohort comprised 104 tumors sequenced using a targeted panel. Studies assessing mutations in , and were summarized to assess hotspot mutations. Statistical analysis of the main cohort variant data revealed , and as significantly mutated genes. and mutations occurred more commonly in lower anatomy melanomas and in the upper anatomy. , and were commonly affected by chromosomal copy loss, while , and were commonly amplified. Further notable genomic alterations occurring at lower frequencies indicated commonality of signaling networks in tumorigenesis, including MAPK, PI3K, Notch, Wnt/β-catenin, cell cycle, DNA repair, and telomere maintenance pathways. This analysis identified genomic aberrations that provide some insight to the way in which specific pathways may be disrupted. IMPLICATIONS: Our analysis has shown that mucosal melanomas have a diverse range of genomic alterations in several biological pathways. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/6/991/F1.large.jpg.
Topics: Biomarkers, Tumor; DNA Copy Number Variations; Genetic Predisposition to Disease; Genomics; Humans; Melanoma; Mutation; Signal Transduction; Skin Neoplasms; Whole Genome Sequencing
PubMed: 33707307
DOI: 10.1158/1541-7786.MCR-20-0839 -
Brain Imaging and Behavior Dec 2022Our primary objective was to assess consistent activation and deactivation among healthy participants and patients reporting vertigo. Our secondary aim was to evaluate... (Review)
Review
Our primary objective was to assess consistent activation and deactivation among healthy participants and patients reporting vertigo. Our secondary aim was to evaluate the influence of the stimulus and the direction of the perception of self-motion We realized a systematic review with an extensive data visualization. We included neuroimaging studies (e.g., functional magnetic resonance imaging [fMRI], positron emission tomography [PET] or near infrared spectroscopy [NIRS]) that have measured functional activity in human adults reporting vertigo and/or dizziness. We included 21 studies (n = 336 participants), ~ 64% male, age ranging from 18 to 80.5 years. The different stimuli used to induce vertigo: caloric stimulation, galvanic stimulation, visual stimulation or vibratory stimulus on neck muscles. We found a consistent activation of the insular cortex, inferior parietal lobule, putamen, cerebellum, anterior cingulate cortex, precentral gyrus, superior temporal gyrus and thalamus. Cortical and subcortical activation seems to have a contralateral pattern to the perception of self-movement. We found a deactivation pattern of structures related to the ventral and third visual pathway. Vertigo is an unpleasant and subjective experience which involves multiple vestibular and non-specific networks with the involvement of a cortico-basal ganglia- cerebellar-thalamic network.
Topics: Adult; Humans; Male; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Female; Magnetic Resonance Imaging; Brain Mapping; Photic Stimulation; Neuroimaging; Vertigo
PubMed: 36242719
DOI: 10.1007/s11682-022-00729-3 -
Frontiers in Neurology 2017Multiple system atrophy (MSA) is a rare, adult-onset, rapidly progressive fatal synucleinopathy that primarily affects oligodendroglial cells in the brain. Patients with... (Review)
Review
BACKGROUND
Multiple system atrophy (MSA) is a rare, adult-onset, rapidly progressive fatal synucleinopathy that primarily affects oligodendroglial cells in the brain. Patients with MSA only rarely have visual complaints, but recent studies of the retina using optical coherence tomography (OCT) showed atrophy of the peripapillary retinal nerve fiber layer (RNFL) and to a lesser extent the macular ganglion cell layer (GCL) complex.
METHODS
We performed a literature review and meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines for studies published before January 2017, identified through PubMed and databases, which reported OCT-related outcomes in patients with MSA and controls. A random-effects model was constructed.
RESULTS
The meta-analysis search strategy yielded 15 articles of which 7 met the inclusion criteria. The pooled difference in the average thickness of the RNFL was -5.48 μm (95% CI, -6.23 to -4.73; < 0.0001), indicating significant thinning in patients with MSA. The pooled results showed significant thinning in all the specific RNFL quadrants, except in the temporal RNFL quadrant, where the thickness in MSA and controls was similar [pooled difference of 1.11 µm (95% CI, -4.03 to 6.26; = 0.67)]. This pattern of retinal damage suggests that MSA patients have preferential loss of retinal ganglion cells projecting to the magnocellular pathway (M-cells), which are mainly located in the peripheral retina and are not essential for visual acuity. Visual acuity, on the other hand, relies mostly on macular ganglion cells projecting to the parvocellular pathway (P-cells) through the temporal portion of the RNFL, which are relatively spared in MSA patients.
CONCLUSION
The retinal damage in patients with MSA differs from that observed in patients with Parkinson disease (PD). Patients with MSA have more relative preservation of temporal sector of the RNFL and less severe atrophy of the macular GCL complex. We hypothesize that in patients with MSA there is predominant damage of large myelinated optic nerve axons like those originating from the M-cells. These large axons may require higher support from oligodendrocytes. Conversely, in patients with PD, P-cells might be more affected.
PubMed: 28596752
DOI: 10.3389/fneur.2017.00206