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Frontiers in Immunology 2022Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently...
Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently treated, therapies for progression are scarce and suboptimal, and biomarkers to predict the disease course are insufficient. Cure or preventive measures for MS require knowledge of core pathological events at the site of the tissue damage. Novelties in systems biology have emerged and paved the way for a more fine-grained understanding of key pathological pathways within the CNS, but they have also raised questions still without answers. Here, we systemically review the power of tissue and single-cell/nucleus CNS omics and discuss major gaps of integration into the clinical practice. Systemic search identified 49 transcriptome and 11 proteome studies of the CNS from 1997 till October 2021. Pioneering molecular discoveries indicate that MS affects the whole brain and all resident cell types. Despite inconsistency of results, studies imply increase in transcripts/proteins of semaphorins, heat shock proteins, myelin proteins, apolipoproteins and HLAs. Different lesions are characterized by distinct astrocytic and microglial polarization, altered oligodendrogenesis, and changes in specific neuronal subtypes. In all white matter lesion types, are highly expressed, and STAT6- and TGFβ-signaling are increased. In the grey matter lesions, TNF-signaling seems to drive cell death, and especially -expressing neurons may be susceptible to neurodegeneration. The vast heterogeneity at both cellular and lesional levels may underlie the clinical heterogeneity of MS, and it may be more complex than the current disease phenotyping in the clinical practice. Systems biology has not solved the mystery of MS, but it has discovered multiple molecules and networks potentially contributing to the pathogenesis. However, these results are mostly descriptive; focused functional studies of the molecular changes may open up for a better interpretation. Guidelines for acceptable quality or awareness of results from low quality data, and standardized computational and biological pipelines may help to overcome limited tissue availability and the "snap shot" problem of omics. These may help in identifying core pathological events and point in directions for focus in clinical prevention.
Topics: Brain; Humans; Multiple Sclerosis; Proteome; Transcriptome; White Matter
PubMed: 35309325
DOI: 10.3389/fimmu.2022.761225 -
Journal of Affective Disorders Mar 2019Hypersomnia is a common problem amongst individuals with Bipolar Disorder (BD). The objective of this meta-analysis is to estimate the frequency of hypersomnia in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypersomnia is a common problem amongst individuals with Bipolar Disorder (BD). The objective of this meta-analysis is to estimate the frequency of hypersomnia in individuals with BD, and identify associated factors METHODS: Our search focused on articles documenting the frequency of hypersomnia among individuals with BD indexed in PubMed database and in the Cochrane Library, following the recommendations from the Meta-Analysis Of Observational Studies in Epidemiology (MOOSE) Group. A meta-analysis of proportion was conducted; funnel plot and Egger's test were used for the assessment of publication bias. Subgroups analyses were performed in order to evaluate possible confounders and associated factors.
RESULTS
We identified 10 studies, which included 1824 patients with BD. The overall estimate of the proportion of BD cases that reported hypersomnia was 29.9% [95% confidence interval (CI): 25.8 - 34.1%, I = 59.2%; p < .05]. The funnel plot and the Egger's test suggest a low risk of publication bias (p = .527). The polarity of mood state, Bipolar Disorder type, use of medication, age, diagnostic criteria and hypersomnia criteria were not significantly related to hypersomnia.
LIMITATIONS
There is a possibility that smaller cross-sectional studies were not included. The high heterogeneity between studies is frequent in meta-analysis of both interventional and observational studies. Hypersomnia was not the primary outcome in some of the included studies.
CONCLUSIONS
To our knowledge, this is the first systematic review and meta-analysis of hypersomnia prevalence in patients with BD. Further studies focused on clinical correlates and implications for health outcomes in BD are warranted.
Topics: Bipolar Disorder; Cross-Sectional Studies; Databases, Factual; Disorders of Excessive Somnolence; Humans; Prevalence; Risk
PubMed: 30611064
DOI: 10.1016/j.jad.2018.12.030 -
Prevalence and clinical features associated with bipolar disorder polypharmacy: a systematic review.Neuropsychiatric Disease and Treatment 2016Uncertainty exists regarding the prevalence and clinical features associated with the practice of polypharmacy in bipolar disorder (BD), warranting a systematic review... (Review)
Review
BACKGROUND
Uncertainty exists regarding the prevalence and clinical features associated with the practice of polypharmacy in bipolar disorder (BD), warranting a systematic review on the matter.
METHODS
Three authors independently searched major electronic databases from inception till September 2015. Articles were included that reported either qualitative or quantitative data about the prevalence and clinical features associated with polypharmacy in adult cases of BD.
RESULTS
The operative definitions of polypharmacy adopted across varying studies varied, with concomitant use of two or more psychotropic medications or use of four or more psychotropic medications at once being the most common and the most reliable, respectively. Regardless of type or current mood episode polarity of BD, prevalence rates up to 85% and 36% were found using the most permissive (two or more medications at once) and the most conservative (four or more) operative definitions for polypharmacy, respectively. Point prevalence prescription rates of one or more antidepressant or antipsychotic as part of a polypharmacy regimen occurred in up to 45% or 80% of the cases, respectively, according to the most permissive definition of polypharmacy. In contrast, lithium prescription rates ranged from 13% to 33% in BD patients receiving polypharmacy according to conservative and permissive definitions, possibly suggesting a reduced need for augmentation of combination strategies for those cases of BD with a favorable lifetime lithium response and/or long-lasting treatment as well as less likelihood of lithium response over the time most severe cases possibly exposed to a more complex polypharmacy overall.
LIMITATIONS
"Apples and oranges" bias; publication bias for most recently introduced compounds.
CONCLUSION
Polypharmacy is common among people with BD across varying type and mood episode phases of illness. Special population, including BD patients at high risk of familial load for suicidal behavior, solicit further research as well as the plausible "protective" role of lithium toward polypharmacy in BD. The PROSPERO registration number is CRD42014015084.
PubMed: 27099503
DOI: 10.2147/NDT.S100846 -
Journal of Oral Pathology & Medicine :... May 2018Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2... (Meta-Analysis)
Meta-Analysis Review
Oral Squamous Cell Carcinoma (OSCC) presents a tumor microenvironment rich in inflammatory cells. Depending on the stimulus, macrophages can polarize in M1 or M2 profile, where M1 acts as proinflammatory and antitumor, and M2 is anti-inflammatory and shows protumor activity. Several studies have shown that macrophages are important to the prognosis of patients with different types of cancer. Our aim was to conduct a systematic review to evaluate the role of macrophages in the prognosis of OSCC patients. A search in the Pubmed, Scopus, and ISI Web of Knowledge database was performed, and it was included only studies that evaluated the importance of macrophages in the prognosis of OSCC patients. From initial 286 articles, 14 fully attended the inclusion criteria. In the majority of the articles, it was evaluated only CD68, a panmacrophage marker, or CD163, a M2 marker. Only one article evaluated the M1 marker, CD11c. Besides, 5 articles analyzed the presence of macrophages in different areas of the tumor. Higher concentrations of CD68 and CD163 were associated with worse survival. In conclusion, macrophages are important to OSCC patients' prognosis; however, it is necessary to address in which tumor region the presence of polarized macrophage is more important to the outcome.
Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Carcinoma, Squamous Cell; Databases, Bibliographic; Disease-Free Survival; Female; Head and Neck Neoplasms; Humans; Macrophages; Male; Middle Aged; Prognosis; Receptors, Cell Surface; Tumor Microenvironment; Young Adult
PubMed: 28940738
DOI: 10.1111/jop.12643 -
Journal of Clinical Pathology Aug 2016Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities.
METHODS
PubMed database was used to identify relevant literature. Primary end point was comparison of positive immunostaining of the biomarkers in chRCC and RO, with extracted data used to calculate OR and 95% CI and statistical I(2) test of heterogeneity for multiple studies.
RESULTS
One hundred and nine manuscripts were available for review. Data extracted were subjected to quantitative meta-analysis. Ten most effective biomarkers (OR of chRCC/RO and CI) are: amylase α1A (n=129, OR=0.001, 95% CI 0.0001 to 0.019); Wnt-5a (n=38, OR=0.0076, 95% CI 0.0004 to 0.015); FXYD2 (n=57, OR=130, 95% CI 14.2 to 1192.3); ankyrin-repeated protein with a proline-rich region (ARPP) (n=25, OR=0.0054, 95% CI 0.0002 to 0.12); cluster of differentiation 63 (CD63) (n=62, diffuse (chRCC) vs apical/polar (RO) stain pattern); transforming growth factor β 1 (TGFβ1) (n=34, membranous (chRCC) vs cytoplasmic (RO)); cytokeratin 7 (CK7) (11 studies, n=448, pooled OR=44.22, 95% CI 22.52 to 86.64, I(2)=15%); S100A1 (4 studies, n=124, pooled OR=0.01, 95% CI 0 to 0.03, I(2)=0%); caveolin-1 (2 studies, n=102, pooled OR=32.95, 95% CI 3.67 to 296.1, I(2)=70%) and claudin-7 (3 studies, n=89, pooled OR=24.7, 95% CI 6.28 to 97.1, I(2)=0%).
CONCLUSIONS
We recommend a panel of IHC biomarkers of amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.
Topics: Adenoma, Oxyphilic; Biomarkers, Tumor; Carcinoma, Renal Cell; Diagnosis, Differential; Humans; Kidney Neoplasms
PubMed: 26951082
DOI: 10.1136/jclinpath-2015-203585 -
Journal of Affective Disorders Jan 2018The DSM-5 mixed features specifier for mood disorders encourages renewed interest in mixed states and led us to pool research findings regarding prevalence of mixed... (Review)
Review
BACKGROUND
The DSM-5 mixed features specifier for mood disorders encourages renewed interest in mixed states and led us to pool research findings regarding prevalence of mixed features in episodes of major depressive (MDD) and bipolar disorders (BD).
METHODS
We systematically searched to July 2017 for reports on mixed symptoms in depressive episodes of MDD and in depression and mania or hypomania in types I and II BD. For primary mood-states and diagnostic groups we compared rates of the presence of mixed symptoms: as defined by DSM-5 (≥3 features opposite to the dominant mood-polarity but not overlapping those of the primary disorder) or as having any ≥3 features of opposite polarity.
RESULTS
We identified 17 reports, from 13 world regions involving 19,198 participants meeting standard diagnostic criteria for an index major depressive or [hypo]manic episode. Prevalence of cases with ≥3 features of opposite polarity averaged 27.8% [CI: 27.2-28.5] overall, and differed significantly between BD and MDD disorders, ranking: BD-depressed (35.2% [33.8-36.5]) = BD-[hypo]manic (35.1% [32.9-37.3]) > MDD-depressed (23.8% [23.0-24.5]).
LIMITATIONS
Available findings were limited to mood disorders with mixed features by particular criteria, with few comparisons to other criteria or to their prognostic or therapeutic implications.
CONCLUSIONS
Prevalence of ≥3 features of opposite polarity ranked: depressive = [hypo]manic episodes of BD > depression in MDD.
Topics: Adult; Antidepressive Agents; Bipolar Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Middle Aged; Prevalence
PubMed: 28922738
DOI: 10.1016/j.jad.2017.09.006 -
Cancers Jul 2021An increased presence of CD206-expressing tumor associated macrophages in solid cancers was proposed to be associated with worse outcomes in multiple types of... (Review)
Review
An increased presence of CD206-expressing tumor associated macrophages in solid cancers was proposed to be associated with worse outcomes in multiple types of malignancies, but contradictory results are published. We performed a reproducible systematic review and meta-analysis to provide increased evidence to confirm or reject this hypothesis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The Embase, Web of Science, and MEDLINE-databases were systematically searched for eligible manuscripts. A total of 27 papers studying the prognostic impact of CD206 in 14 different tumor types were identified. Meta-analyses showed a significant impact on the overall survival (OS) and disease-free survival (DFS). While no significant differences were revealed in progression-free survival (PFS) and disease-specific survival (DSS), a shift towards negative survival was correlated with increased CD206-expresion. As a result of the different tumor types, large heterogeneity was present between the different tumor types. Subgroup analysis of hepatocellular carcinoma and gastric cancers revealed no heterogeneity, associated with a significant negative impact on OS in both groups. The current systematic review displays the increased presence CD206-expressing macrophages as a significant negative prognostic biomarker for both OS and DFS in patients diagnosed with solid cancers. Because a heterogenous group of tumor types was included in the meta-analysis, the results cannot be generalized. These results can, however, be used to further lead follow-up research to validate the specific prognostic value of CD206 in individual tumor types and therapeutic approaches.
PubMed: 34298638
DOI: 10.3390/cancers13143422 -
Osteoarthritis and Cartilage May 2022Early and non-invasive detection of osteoarthritis (OA) is required to enable early treatment and monitoring of interventions. Some of the earliest signs of OA are the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Early and non-invasive detection of osteoarthritis (OA) is required to enable early treatment and monitoring of interventions. Some of the earliest signs of OA are the change in proteoglycan and collagen composition. The aim of this study is to establish the relations between quantitative magnetic resonance imaging (MRI) and biochemical concentration and organization in knee articular cartilage.
METHODS
A preregistered systematic literature review was performed using the databases PubMed and Embase. Papers were included if quantitative MRI and a biochemical assay or polarized light microscopy (PLM) was performed on knee articular cartilage, and a quantified correlation was described. The extracted correlations were pooled using a random effects model.
RESULTS
21 papers were identified. The strongest pooled correlation was found for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) vs proteoglycan concentration (r = 0.59). T1ρ relaxation times are inversely correlated to proteoglycan concentration (r = -0.54). A weak correlation between T2 relaxation times and proteoglycans was found (r = -0.38). No correlation between T2 relaxation time and collagen concentration was found (r = -0.02). A heterogeneous set of correlations between T2 relaxation times and PLM were identified, including strong correlations to anisotropy.
CONCLUSION
DGEMRIC measures are significantly correlated to proteoglycan concentration. The needed contrast agent is however a disadvantage; the T1ρ sequence was found as a non-invasive alternative. Remarkably, no correlation was found between T2 relaxation times and collagen concentration. T2 relaxation times is related to organization, rather than concentration of collagen fibers.
PROSPERO ID
CRD42020168337.
Topics: Cartilage, Articular; Collagen; Humans; Knee Joint; Magnetic Resonance Imaging; Osteoarthritis; Osteoarthritis, Knee; Proteoglycans
PubMed: 34826570
DOI: 10.1016/j.joca.2021.10.016 -
Journal of Pain Research 2021Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results.... (Review)
Review
PURPOSE
Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine.
METHODS
In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities.
RESULTS
Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of migraine pain intensity (MD: -1.44; CI: [-2.13, -0.76]) in active vs sham tDCS treated patients. Within active treatment groups, pain intensity and duration were significantly improved from baseline after tDCS treatment (intensity MD: -1.86; CI: [-3.30, -0.43]; duration MD: -4.42; CI: [-8.11, -0.74]) and during a follow-up period (intensity MD: -1.52; CI: [-1.84, -1.20]; duration MD: -1.94; CI: [-3.10, -0.77]). There was a significant reduction of pain intensity by both anodal (MD: -1.74; CI: [-2.80, -0.68]) and cathodal (MD: -1.49; CI: [-1.89, -1.09]) stimulation conditions.
CONCLUSION
tDCS treatment repeated over days for a period of 4 weeks or more is effective in reducing migraine pain intensity and duration of migraine episode. The benefit of tDCS can persist for at least 4 weeks after the completion of last tDCS session. Both anodal and cathodal stimulation are effective for reducing migraine pain intensity.
PubMed: 33953607
DOI: 10.2147/JPR.S295704 -
Journal of Sport and Health Science Mar 2022This systematic review and meta-analysis aimed to evaluate the effect of wearable devices for improving physical activity and health-related outcomes in cancer survivors. (Meta-Analysis)
Meta-Analysis Review
Effect and feasibility of wearable physical activity trackers and pedometers for increasing physical activity and improving health outcomes in cancer survivors: A systematic review and meta-analysis.
PURPOSE
This systematic review and meta-analysis aimed to evaluate the effect of wearable devices for improving physical activity and health-related outcomes in cancer survivors.
METHODS
CINAHL, Cochrane, Ebscohost, MEDLINE, Pubmed, ProQuest Health and Medical Complete, ProQuest Nursing and Allied Health Source, ScienceDirect, and SPORTDiscus databases were searched for randomized controlled trials published before September 1, 2020, that evaluated interventions involving wearable devices in cancer survivors. Standardized mean differences (SMDs) were calculated to assess effects on physical activity and health-related outcomes. Subgroup analyses were conducted to assess whether the effects differed by interventions and cancer characteristics. Risk of bias was assessed using the Cochrane risk of bias tool.
RESULTS
Thirty-five trials were included (breast cancer, n = 15, 43%). Intervention durations ranged between 4 weeks and 1 year. Most trials (n = 25, 71%) involved pedometer-based physical activity interventions. Seven (20%) involved Fitbit-based interventions, and 3 (9%) involved other wearable physical activity trackers (e.g., Polar, Garmin). Compared to usual care, wearable devices had moderate-to-large effects (SMD range 0.54-0.87, p < 0.001) on moderate-intensity physical activity, moderate-to-vigorous-intensity physical activity, total physical activity, and daily steps. Compared to usual care, those in the intervention had higher quality of life, aerobic fitness, physical function, and reduced fatigue (SMD range = 0.18-0.66, all p < 0.05).
CONCLUSION
Wearable physical activity trackers and pedometers are effective tools that increase physical activity and improve health-related outcomes in individuals with cancer. Identifying how these devices can be implemented for longer-term use with other intervention components remains an area for future research.
Topics: Actigraphy; Cancer Survivors; Exercise; Feasibility Studies; Fitness Trackers; Humans; Neoplasms; Outcome Assessment, Health Care; Quality of Life; Wearable Electronic Devices
PubMed: 34314878
DOI: 10.1016/j.jshs.2021.07.008