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Molecular Neurodegeneration Nov 2022The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely... (Review)
Review
The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer's disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Depressive Disorder, Major; Protein Transport; Nerve Growth Factors
PubMed: 36397124
DOI: 10.1186/s13024-022-00576-2 -
The Cochrane Database of Systematic... Sep 2020In in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection (ICSI), selection of the most competent embryo(s) for transfer is based on morphological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In in vitro fertilisation (IVF) with or without intracytoplasmic sperm injection (ICSI), selection of the most competent embryo(s) for transfer is based on morphological criteria. However, many women do not achieve a pregnancy even after 'good quality' embryo transfer. One of the presumed causes is that such morphologically normal embryos have an abnormal number of chromosomes (aneuploidies). Preimplantation genetic testing for aneuploidies (PGT-A), formerly known as preimplantation genetic screening (PGS), was therefore developed as an alternative method to select embryos for transfer in IVF. In PGT-A, the polar body or one or a few cells of the embryo are obtained by biopsy and tested. Only polar bodies and embryos that show a normal number of chromosomes are transferred. The first generation of PGT-A, using cleavage-stage biopsy and fluorescence in situ hybridisation (FISH) for the genetic analysis, was demonstrated to be ineffective in improving live birth rates. Since then, new PGT-A methodologies have been developed that perform the biopsy procedure at other stages of development and use different methods for genetic analysis. Whether or not PGT-A improves IVF outcomes and is beneficial to patients has remained controversial.
OBJECTIVES
To evaluate the effectiveness and safety of PGT-A in women undergoing an IVF treatment.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group Trials Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and two trials registers in September 2019 and checked the references of appropriate papers.
SELECTION CRITERIA
All randomised controlled trials (RCTs) reporting data on clinical outcomes in participants undergoing IVF with PGT-A versus IVF without PGT-A were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, assessed risk of bias, and extracted study data. The primary outcome was the cumulative live birth rate (cLBR). Secondary outcomes were live birth rate (LBR) after the first embryo transfer, miscarriage rate, ongoing pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, proportion of women reaching an embryo transfer, and mean number of embryos per transfer.
MAIN RESULTS
We included 13 trials involving 2794 women. The quality of the evidence ranged from low to moderate. The main limitations were imprecision, inconsistency, and risk of publication bias. IVF with PGT-A versus IVF without PGT-A with the use of genome-wide analyses Polar body biopsy One trial used polar body biopsy with array comparative genomic hybridisation (aCGH). It is uncertain whether the addition of PGT-A by polar body biopsy increases the cLBR compared to IVF without PGT-A (odds ratio (OR) 1.05, 95% confidence interval (CI) 0.66 to 1.66, 1 RCT, N = 396, low-quality evidence). The evidence suggests that for the observed cLBR of 24% in the control group, the chance of live birth following the results of one IVF cycle with PGT-A is between 17% and 34%. It is uncertain whether the LBR after the first embryo transfer improves with PGT-A by polar body biopsy (OR 1.10, 95% CI 0.68 to 1.79, 1 RCT, N = 396, low-quality evidence). PGT-A with polar body biopsy may reduce miscarriage rate (OR 0.45, 95% CI 0.23 to 0.88, 1 RCT, N = 396, low-quality evidence). No data on ongoing pregnancy rate were available. The effect of PGT-A by polar body biopsy on improving clinical pregnancy rate is uncertain (OR 0.77, 95% CI 0.50 to 1.16, 1 RCT, N = 396, low-quality evidence). Blastocyst stage biopsy One trial used blastocyst stage biopsy with next-generation sequencing. It is uncertain whether IVF with the addition of PGT-A by blastocyst stage biopsy increases cLBR compared to IVF without PGT-A, since no data were available. It is uncertain if LBR after the first embryo transfer improves with PGT-A with blastocyst stage biopsy (OR 0.93, 95% CI 0.69 to 1.27, 1 RCT, N = 661, low-quality evidence). It is uncertain whether PGT-A with blastocyst stage biopsy reduces miscarriage rate (OR 0.89, 95% CI 0.52 to 1.54, 1 RCT, N = 661, low-quality evidence). No data on ongoing pregnancy rate or clinical pregnancy rate were available. IVF with PGT-A versus IVF without PGT-A with the use of FISH for the genetic analysis Eleven trials were included in this comparison. It is uncertain whether IVF with addition of PGT-A increases cLBR (OR 0.59, 95% CI 0.35 to 1.01, 1 RCT, N = 408, low-quality evidence). The evidence suggests that for the observed average cLBR of 29% in the control group, the chance of live birth following the results of one IVF cycle with PGT-A is between 12% and 29%. PGT-A performed with FISH probably reduces live births after the first transfer compared to the control group (OR 0.62, 95% CI 0.43 to 0.91, 10 RCTs, N = 1680, I² = 54%, moderate-quality evidence). The evidence suggests that for the observed average LBR per first transfer of 31% in the control group, the chance of live birth after the first embryo transfer with PGT-A is between 16% and 29%. There is probably little or no difference in miscarriage rate between PGT-A and the control group (OR 1.03, 95%, CI 0.75 to 1.41; 10 RCTs, N = 1680, I² = 16%; moderate-quality evidence). The addition of PGT-A may reduce ongoing pregnancy rate (OR 0.68, 95% CI 0.51 to 0.90, 5 RCTs, N = 1121, I² = 60%, low-quality evidence) and probably reduces clinical pregnancies (OR 0.60, 95% CI 0.45 to 0.81, 5 RCTs, N = 1131; I² = 0%, moderate-quality evidence).
AUTHORS' CONCLUSIONS
There is insufficient good-quality evidence of a difference in cumulative live birth rate, live birth rate after the first embryo transfer, or miscarriage rate between IVF with and IVF without PGT-A as currently performed. No data were available on ongoing pregnancy rates. The effect of PGT-A on clinical pregnancy rate is uncertain. Women need to be aware that it is uncertain whether PGT-A with the use of genome-wide analyses is an effective addition to IVF, especially in view of the invasiveness and costs involved in PGT-A. PGT-A using FISH for the genetic analysis is probably harmful. The currently available evidence is insufficient to support PGT-A in routine clinical practice.
Topics: Abortion, Spontaneous; Aneuploidy; Bias; Biopsy; Birth Rate; Blastocyst; Female; Fertilization in Vitro; Genetic Testing; Humans; Live Birth; Maternal Age; Polar Bodies; Pregnancy; Preimplantation Diagnosis; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 32898291
DOI: 10.1002/14651858.CD005291.pub3 -
International Journal of Molecular... Sep 2023Thyroid hormones play a crucial role in regulating normal development, growth, and metabolic function. However, the controversy surrounding seasonal changes in free... (Review)
Review
A Systematic Review and Meta-Analysis of Free Triiodothyronine (FT3) Levels in Humans Depending on Seasonal Air Temperature Changes: Is the Variation in FT3 Levels Related to Nonshivering Thermogenesis?
Thyroid hormones play a crucial role in regulating normal development, growth, and metabolic function. However, the controversy surrounding seasonal changes in free triiodothyronine (FT3) levels remains unresolved. Therefore, the aim of this study was to conduct a systematic review and meta-analysis of variations in FT3 levels in relation to seasonal air temperatures in the context of current knowledge about its role in nonshivering thermogenesis. Ten eligible articles with a total of 336,755 participants were included in the meta-analysis. The studies were categorized into two groups based on the air temperature: "Cold winter", where the winter temperature fell below 0 °C, and "Warm winter", where the winter temperature was above 0 °C. The analysis revealed that in cold regions, FT3 levels decreased in winter compared to summer (I = 57%, < 0.001), whereas in warm regions, FT3 levels increased during winter (I = 28%, < 0.001). These findings suggest that seasonal variations in FT3 levels are likely to be influenced by the winter temperature. Considering the important role of the FT3 in the nonshivering thermogenesis process, we assume that this observed pattern is probably related to the differences in use of thyroid hormones in the brown adipose tissue during adaptive thermogenesis, which may depend on intensity of cold exposure.
PubMed: 37762355
DOI: 10.3390/ijms241814052 -
Clinics in Shoulder and Elbow Jun 2024Radial head arthroplasty allows a high degree of customizability, and implant polarity has emerged as an important variable. The purpose of this meta-analysis was to...
BACKGROUND
Radial head arthroplasty allows a high degree of customizability, and implant polarity has emerged as an important variable. The purpose of this meta-analysis was to evaluate differences in functional and clinical outcomes between patients receiving monopolar and bipolar radial head prosthetic implants.
METHODS
A systematic review and meta-analysis were employed, and 65 articles were identified in three databases. Twelve articles contained non-English or insufficient text and were consequently excluded, and 20 others did not contain sufficient data or follow-up. The remaining 33 articles were qualitatively and quantitatively reviewed.
RESULTS
In total, 33 populations were identified, with 809 unduplicated patients: 565 with monopolar and 244 with bipolar implants. In these respective patients, the mean follow-up was 40.2 and 56.9 months. Average Mayo Elbow Performance Score were 86.7 and 87.4 (P=0.80), respectively; average Disability of the Arm, Shoulder, and Hand scores were 17.9 and 14.7 (P=0.47), and average final flexion/extension arcs were 119.4° and 118.7° (P=0.48). Revision rates were 4.07% and 6.56%, while complication rates were 19.65% and 20.08% in the respective monopolar and bipolar patients. These increased relative risks associated with bipolar implants were not significant.
CONCLUSIONS
Radial head implant polarity does not appear to affect functional outcomes. While bipolar prosthetic design may increase the risks of revision and complications, the increases were not significant. Level of evidence: IV.
PubMed: 38738328
DOI: 10.5397/cise.2023.01088 -
Journal of Assisted Reproduction and... Jul 2018Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation,... (Review)
Review
PURPOSE
Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation, follicles must respond to soluble signals (growth factors and hormones) and physical stresses, including mechanical forces and osmotic shifts. Likewise, mechanical processes are involved in cortical tension and cell polarity in oocytes. Our objective was to examine the contribution and influence of biomechanical signaling in female mammalian gametogenesis.
METHODS
We performed a systematic review to assess and summarize the effects of mechanical signaling and mechanotransduction in oocyte maturation and folliculogenesis and to explore possible clinical applications. The review identified 2568 publications of which 122 met the inclusion criteria.
RESULTS
The integration of mechanical and cell signaling pathways in gametogenesis is complex. Follicular activation or quiescence are influenced by mechanical signaling through the Hippo and Akt pathways involving the yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), phosphatase and tensin homolog deleted from chromosome 10 (PTEN) gene, the mammalian target of rapamycin (mTOR), and forkhead box O3 (FOXO3) gene.
CONCLUSIONS
There is overwhelming evidence that mechanical signaling plays a crucial role in development of the ovary, follicle, and oocyte throughout gametogenesis. Emerging data suggest the complexities of mechanotransduction and the biomechanics of oocytes and follicles are integral to understanding of primary ovarian insufficiency, ovarian aging, polycystic ovary syndrome, and applications of fertility preservation.
Topics: Animals; Female; Humans; Mechanotransduction, Cellular; Oocytes; Oogenesis; Ovarian Follicle; Ovary; Signal Transduction
PubMed: 29691711
DOI: 10.1007/s10815-018-1180-y -
Frontiers in Nutrition 2022Polysaccharides have a variety of biological activities, and in the anti-tumor field, they produce tumor suppressive effects by regulating the polarization of... (Review)
Review
Polysaccharides have a variety of biological activities, and in the anti-tumor field, they produce tumor suppressive effects by regulating the polarization of tumor-associated macrophages (TAMs). In immunotherapy, it has significant activities in modulating cytokines and antibody production. We reviewed them and selected CD24, an immune target, for meta-analysis with colorectal cancer (CRC) to investigate the correlation between CD24 expression and CRC. Correlation of CD24 positive expression with clinical-pathological features: age, sex, Duke's stage, diameter, depth of invasion, degree of differentiation, and lymph node metastasis. It showed that: CD24 expression in CRC was significantly correlated with advanced nuclear grade of CRC, lymph node metastasis, Duke's stage of CRC and age of CRC patients, while there was no significant correlation with gender, tumor diameter and invasion depth. The aim is to clarify the specific mechanism of polysaccharide immune anti-tumor, combined with targeted site-specific anti-solid tumor.
PubMed: 35938128
DOI: 10.3389/fnut.2022.961507 -
Internet Policy Review Mar 2022There has been much concern that social media, in particular YouTube, may facilitate radicalisation and polarisation of online audiences. This systematic review aimed to...
There has been much concern that social media, in particular YouTube, may facilitate radicalisation and polarisation of online audiences. This systematic review aimed to determine whether the YouTube recommender system facilitates pathways to problematic content such as extremist or radicalising material. The review conducted a narrative synthesis of the papers in this area. It assessed the eligibility of 1,187 studies and excluded studies using the PRISMA process for systematic reviews, leaving a final sample of 23 studies. Overall, 14 studies implicated the YouTube recommender system in facilitating problematic content pathways, seven produced mixed results, and two did not implicate the recommender system. The review's findings indicate that the YouTube recommender system could lead users to problematic content. However, due to limited access and an incomplete understanding of the YouTube recommender system, the models built by researchers might not reflect the actual mechanisms underlying the YouTube recommender system and pathways to problematic content.
PubMed: 36466439
DOI: 10.14763/2022.1.1652 -
Journal of Functional Biomaterials May 2023Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes... (Review)
Review
Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon-bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a "snowball" search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon-bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon-bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon-bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials.
PubMed: 37367263
DOI: 10.3390/jfb14060299 -
Neuroscience and Biobehavioral Reviews Sep 2021Transcranial direct current stimulation (tDCS) is widely used to explore the role of various cortical regions for reactive response inhibition. In recent years, tDCS... (Review)
Review
Transcranial direct current stimulation (tDCS) is widely used to explore the role of various cortical regions for reactive response inhibition. In recent years, tDCS studies reported polarity-, time- and stimulation-site dependent effects on response inhibition. Given the large parameter space in which study designs, tDCS procedures and task procedures can differ, it is crucial to systematically explore the existing tDCS literature to increase the current understanding of potential modulatory effects and limitations of different approaches. We performed a systematic review on the modulatory effects of tDCS on response inhibition as measured by the Stop-Signal Task. The final dataset shows a large variation in methodology and heterogeneous effects of tDCS on performance. The most consistent result across studies is a performance enhancement due to anodal tDCS over the right prefrontal cortex. Partially sub-optimal choices in study design, methodology and lacking consistency in reporting procedures may impede valid conclusions and obscured the effects of tDCS on response inhibition in some previous studies. Finally, we outline future directions and areas to improve research.
Topics: Humans; Prefrontal Cortex; Reaction Time; Reactive Inhibition; Research Design; Transcranial Direct Current Stimulation
PubMed: 34271027
DOI: 10.1016/j.neubiorev.2021.07.013 -
BJPsych Open May 2024Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management... (Review)
Review
BACKGROUND
Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder.
AIMS
We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder.
METHOD
The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates.
RESULTS
We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = -3.19, 95% CI: -5.30 to -1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = -1.57, 95% CI: -2.88 to -0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP ( < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP ( < 0.05). No differences were estimated for other variables.
CONCLUSIONS
Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgroups of patients with specific clinical characteristics.
PubMed: 38708573
DOI: 10.1192/bjo.2024.51